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Sample records for high-risk myelodysplastic syndrome

  1. Outcome of acute myeloid leukemia and high-risk myelodysplastic syndrome according to health insurance status.

    Science.gov (United States)

    Al-Ameri, Ali; Anand, Ankit; Abdelfatah, Mohamed; Kanaan, Zeyad; Hammonds, Tracy; Haller, Nairmeen; Cherry, Mohamad

    2014-12-01

    Age, cytogenetic status, and molecular features are the most important prognostic factors in acute myeloid leukemia (AML). This study aimed to analyze the outcomes of patients with AML or high-risk myelodysplastic syndrome (MDS) according to insurance status. A retrospective chart review was performed, covering all patients with AML and high-risk MDS evaluated and treated at Akron General Medical Center between 2002 and 2012. A Cox regression model was analyzed to account for survival over time, adjusted for insurance type, while controlling for patient age at diagnosis and patient risk of mortality. A total of 130 adult patients (age ≥ 18 years) were identified. Insurance information was available for 97 patients enrolled in the study; 3 were excluded because of self-pay status. Cox regression analysis with insurance type as the predictor found that overall survival declines over time and that the rate of decline may be influenced by insurance type (χ(2)(2) = 6.4; P = .044). The likelihood of survival in patients with Medicaid or Medicare without supplemental insurance was .552 (95% CI, .338-.903; P = .018) times the likelihood in patients who had Medicare with supplemental insurance. To explain the difference, variables of age, gender, and risk of mortality were added to the model. Age and risk of mortality were found to be significant predictors of survival. The addition of insurance type to the model did not significantly contribute (χ(2)(3) = 3.83; P = .147). No significant difference in overall survival was observed when patients with AML or high-risk MDS were analyzed according to their health insurance status. The overall survival was low in this study compared with the national average. Early referral to a specialized center or possible clinical trial enrollment may be a good alternative to improve outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Tratamento do paciente com mielodisplasia de alto risco Treatment of myelodysplastic syndrome in high risk patients

    Directory of Open Access Journals (Sweden)

    Evandro M. Fagundes

    2006-09-01

    Full Text Available O tratamento do paciente com mielodisplasia deve ser feito considerando o risco biológico da doença, a idade e as condições clínicas do paciente. De um modo geral, uma doença de alto risco necessitaria de um tratamento mais agressivo. Porém, devido à elevada idade mediana no diagnóstico, a maioria dos pacientes não tolera tratamentos intensivos. O transplante de células-tronco hematopoiéticas é a única opção para aqueles que objetivam a cura da doença. Para aqueles que não podem se submeter a um transplante, as opções incluem o uso de quimioterapia intensiva, agentes hipometilantes, tratamento suportivo e/ou inclusão em estudos clínicos. A quimioterapia intensiva semelhante à utilizada para leucemia mielóide aguda é uma boa opção para pacientes em boas condições clínicas e com menos de 65 anos de idade.To initiate a treatment for myelodysplastic syndrome, the physician should consider the patient's age, status performance and the risk of transformation to acute myeloid leukemia (AML and death. In theory, a high risk disease should be approached with intense treatment however most patients are not healthy enough to receive aggressive treatment with chemotherapy or stem cell transplantation. For those who are not able to receive a transplantation, the treatment options include AML-like chemotherapy, hypomethylating agents, supportive care alone or participation in a clinical trial. AML-like chemotherapy is still a reasonable choice for those patients who are in good clinical conditions and are younger than 65 years of age.

  3. Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities

    DEFF Research Database (Denmark)

    Möllgård, Lars; Saft, Leonie; Treppendahl, Marianne Bach

    2011-01-01

    Background Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ...... hybridization for del(5q31). DESIGN AND METHODS: Twenty-eight patients at diagnosis or with relapsed disease and not eligible for standard therapy (16 with acute myeloid leukemia, 12 with intermediate-risk 2 or high-risk myelodysplastic syndrome) were enrolled in this prospective phase II multicenter trial...... the 16 weeks of trial responded to treatment. Using the International Working Group criteria for acute myeloid leukemia and myelodysplastic syndrome the overall response rate in treated patients with acute myeloid leukemia was 20% (3/15), while that for patients with myelodysplastic syndrome was 36% (4...

  4. Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities

    DEFF Research Database (Denmark)

    Möllgård, Lars; Saft, Leonie; Treppendahl, Marianne Bach

    2011-01-01

    Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ hybridization...

  5. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction ......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

  6. Treatment strategies in patients with AML or high-risk myelodysplastic syndrome relapsed after Allo-SCT.

    Science.gov (United States)

    Sauer, T; Silling, G; Groth, C; Rosenow, F; Krug, U; Görlich, D; Evers, G; Albring, J; Besoke, R; Mesters, R M; Müller-Tidow, C; Kessler, T; Büchner, T; Berdel, W E; Stelljes, M

    2015-04-01

    Non-relapse mortality after Allo-SCT has significantly decreased over the last years. Nevertheless, relapse remains a major cause for post SCT mortality in patients with AML and high-risk myelodysplastic syndrome (MDS). In this retrospective single-center analysis, we have analyzed the treatment outcomes of 108 patients with AML or MDS, who relapsed after Allo-SCT. Seventy of these patients (65%) were treated with salvage therapies containing chemotherapy alone, allogeneic cell-based treatment or the combination of both. Thirty-eight patients (35%) received palliative treatment. Median OS after diagnosis of relapse was 130 days. Compared with patients who received chemotherapy alone, response to salvage therapy was significantly improved in patients treated with a combination of chemo- and allogeneic cell-based therapy (CR rate 57% vs 13%, P=0.002). Among risk factors concerning pretreatment characteristics, disease status before first Allo-SCT, and details of transplantation, only the time interval from Allo-SCT to relapse was an independent predictor of response to salvage therapy and OS. These data confirmed that time to relapse after transplantation is an important prognostic factor. Up to now, only patients eligible for treatment regimens containing allogeneic cell-based interventions achieved relevant response rates.

  7. Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome

    DEFF Research Database (Denmark)

    Grövdal, Michael; Khan, Rasheed; Aggerholm, Anni

    2007-01-01

    was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. EXPERIMENTAL DESIGN: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-beta-d-arabinofuranosylcytosine. Standard.......008), and CDH methylation retained its prognostic value also in the multivariate analysis. Hypermethylation was associated with increased CD34 expression, but not with other known predictive factors for response, such as cytogenetic profile. CONCLUSIONS: We show for the first time a significant effect...

  8. Ibrutinib and Azacitidine for Treatment of Higher Risk Myelodysplastic Syndrome

    Science.gov (United States)

    2018-03-01

    Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts in Transformation; Secondary Myelodysplastic Syndrome

  9. Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome

    Science.gov (United States)

    2018-05-14

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; CD45-Positive Neoplastic Cells Present; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

  10. Impact of baseline cytogenetic findings and cytogenetic response on outcome of high-risk myelodysplastic syndromes and low blast count AML treated with azacitidine.

    Science.gov (United States)

    Sébert, Marie; Komrokji, Rami S; Sekeres, Mikkael A; Prebet, Thomas; Cluzeau, Thomas; Santini, Valeria; Gyan, Emmanuel; Sanna, Alessandro; Ali, Najla HAl; Hobson, Sean; Eclache, Virginie; List, Alan; Fenaux, Pierre; Adès, Lionel

    2017-12-01

    Karyotype according to the revised IPSS is a strong independent prognostic factor for overall survival (OS) in myelodysplastic syndromes (MDS), however established in untreated patients. The prognostic impact of cytogenetics and cytogenetic response (CyR) in MDS patients receiving azacitidine (AZA) remains uncertain. We examined the prognostic value of baseline cytogenetics and CyR for overall response rate (ORR) and OS in 702 AZA-treated higher risk MDS and low blast count acute myeloid leukemia (AML), including 493 (70%) with abnormal karyotype. None of the cytogenetic abnormalities had significant impact on ORR (43.9%) or complete response (15.35%), except 3q abnormalities and complex karyotypes, which were associated with a lower ORR. OS differed significantly across all R-IPSS cytogenetic subgroups (pcytogenetics. CyR was achieved in 32% of the 281 evaluable patients with abnormal cytogenetics, was complete (CCyR) in 71 (25.3%) patients. We found no correlation between hematological response and cytogenetic response and 21% of the patients with CCyR did not achieve morphological response. In the 281 patients, we found no impact of CyR on survival, but when restricting to MDS (ie: <20% marrow blasts) achievement of CCyR was associated with better OS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Donor-Cell Origin High-Risk Myelodysplastic Syndrome Synchronous with an Intracranial Meningioma-Like Tumor, 8 Years after Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    G. Brás

    2017-01-01

    Full Text Available Secondary neoplasias are well known consequences of radiotherapy or chemotherapy for a primary cancer. In this report, we describe two rare secondary neoplasias occurring in the same patient: a meningioma-like intracranial tumor and high-risk myelodysplastic syndrome (MDS of donor-cells origin, both diagnosed simultaneously, 8 years after an allogeneic hematopoietic stem cell transplantation (allo-HSCT for chronic lymphocytic leukemia (CLL. Due to an engraftment failure during the first allo-HSCT of a matched related donor for CLL treatment, the salvage treatment was a second allo-HSCT. At the moment of meningioma-like tumor diagnosis, the patient was pancytopenic due to high-risk MDS, so it was decided to postpone a surgical intervention until hematological improvement. For the high-risk MDS of donor-cells origin the chosen treatment was induction with intensive chemotherapy. Due to refractory disease, the patient was treated with 5-azacitidine and donor-lymphocytes infusion with no response and, finally, a third allo-HSCT of a matched unrelated donor was performed. The patient died 6 months after the third allo-HSCT, in cytogenetic remission but without hematological recovery, due to an intracranial hemorrhage with origin in the meningioma-like tumor.

  12. Immune Mechanisms in Myelodysplastic Syndrome

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    Andreas Glenthøj

    2016-06-01

    Full Text Available Myelodysplastic syndrome (MDS is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive sequencing efforts have revealed a range of mutations characteristic, but not specific, of MDS. Epidemiologically, autoimmune diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients—especially younger low-risk patients with HLA-DR15 tissue type—demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS.

  13. [Marked hemosiderosis in myelodysplastic syndrome].

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    Klinz, C

    1999-01-29

    A 68-year-old man was admitted because of symptoms of lumbar pain. He was known to have chronic anemia with ring sideroblasts and diabetes melitus and to be in heart failure. Three months before he had been given 7 units of red cell concentrate. On admission the outstanding features were brown discoloration of the skin, absent body hair, tachycardia, hepatomegaly and small testicles. He had a normocytic anemia, hyperglycemia and raised transaminases, hypogonadism and vitamin D3 deficiency. The serum levels of iron, transferrin saturation and feritin were markedly elevated. Liver iron content/g dried liver was 4.2 g (by biomagnetometer). Radiology of the lumbar vertebrae showed osteoporosis and sonography confirmed hepatomegaly. The known myelodysplastic syndrome (MDS) had fed to secondary hemosiderosis with heart failure, liver involvement, diabetes mellitus, hypogonadism and osteoporosis. Symptomatic treatment was unsuccessfully complemented by desferoxamine (up to 4 g/12 h) to release iron. But very good iron excretion was then achieved with deferiprone (3 x 1 g/d). The patient later died of the sequelae of hemosiderosis. Even when they have not required transfusions, patients with long-standing MDS should be examined regularly for the possible development of secondary hemosiderosis so that iron-chelating agents can be administered as needed.

  14. Erythroleukemia shares biological features and outcome with myelodysplastic syndromes with excess blasts: a rationale for its inclusion into future classifications of myelodysplastic syndromes.

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    Calvo, Xavier; Arenillas, Leonor; Luño, Elisa; Senent, Leonor; Arnan, Montserrat; Ramos, Fernando; Ardanaz, María Teresa; Pedro, Carme; Tormo, Mar; Montoro, Julia; Díez-Campelo, María; Arrizabalaga, Beatriz; Xicoy, Blanca; Bonanad, Santiago; Jerez, Andrés; Nomdedeu, Benet; Ferrer, Ana; Sanz, Guillermo F; Florensa, Lourdes

    2016-12-01

    Erythroleukemia was considered an acute myeloid leukemia in the 2008 World Health Organization (WHO) classification and is defined by the presence of ≥50% bone marrow erythroblasts, having <20% bone marrow blasts from total nucleated cells but ≥20% bone marrow myeloblasts from nonerythroid cells. Erythroleukemia shares clinicopathologic features with myelodysplastic syndromes, especially with erythroid-predominant myelodysplastic syndromes (≥50% bone marrow erythroblasts). The upcoming WHO revision proposes to eliminate the nonerythroid blast cell count rule and to move erythroleukemia patients into the appropriate myelodysplastic syndrome category on the basis of the absolute blast cell count. We conducted a retrospective study of patients with de novo erythroleukemia and compared their clinico-biological features and outcome with those of de novo myelodysplastic syndromes, focusing on erythroid-predominant myelodysplastic syndromes. Median overall survival of 405 erythroid-predominant myelodysplastic syndromes without excess blasts was significantly longer than that observed in 57 erythroid-predominant refractory anemias with excess blasts-1 and in 59 erythroleukemias, but no significant difference was observed between erythroid-predominant refractory anemias with excess blasts-1 and erythroleukemias. In this subset of patients with ≥50% bone marrow erythroblasts and excess blasts, the presence of a high-risk karyotype defined by the International Prognostic Scoring System or by the Revised International Prognostic Scoring System was the main prognostic factor. In the same way, the survival of 459 refractory anemias with excess blasts-2, independently of having ≥20% bone marrow blasts from nonerythroid cells or not, was almost identical to the observed in 59 erythroleukemias. Interestingly, 11 low-blast count erythroleukemias with 5 to <10% bone marrow blasts from total nucleated cells showed similar survival than the rest of erythroleukemias. Our data

  15. Sequential acquisition of mutations in myelodysplastic syndromes.

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    Makishima, Hideki

    2017-01-01

    Recent progress in next-generation sequencing technologies allows us to discover frequent mutations throughout the coding regions of myelodysplastic syndromes (MDS), potentially providing us with virtually a complete spectrum of driver mutations in this disease. As shown by many study groups these days, such driver mutations are acquired in a gene-specific fashion. For instance, DDX41 mutations are observed in germline cells long before MDS presentation. In blood samples from healthy elderly individuals, somatic DNMT3A and TET2 mutations are detected as age-related clonal hematopoiesis and are believed to be a risk factor for hematological neoplasms. In MDS, mutations of genes such as NRAS and FLT3, designated as Type-1 genes, may be significantly associated with leukemic evolution. Another type (Type-2) of genes, including RUNX1 and GATA2, are related to progression from low-risk to high-risk MDS. Overall, various driver mutations are sequentially acquired in MDS, at a specific time, in either germline cells, normal hematopoietic cells, or clonal MDS cells.

  16. Protein Carbonylation in Patients with Myelodysplastic Syndromes

    Czech Academy of Sciences Publication Activity Database

    Hlaváčková, A.; Štikarová, J.; Kotlín, R.; Chrastinová, L.; Šácha, Pavel; Májek, P.; Čermák, J.; Suttnar, J.; Dyr, J. E.

    2015-01-01

    Roč. 126, č. 23 (2015), s. 5232 ISSN 0006-4971. [Annual Meeting and Exposition of the American Society of Hematology /55./. 07.12.2013-10.12.2013, New Orleans] Institutional support: RVO:61388963 Keywords : protein carbonylation * myelodysplastic syndromes Subject RIV: CE - Biochemistry

  17. Myelodysplastic syndromes: clinical and biological advances

    National Research Council Canada - National Science Library

    Greenberg, Peter L

    2006-01-01

    ..., to a review of recent molecular and cytogenetic discoveries and insights. This book will be a valuable resource for clinicians and researchers who wish to learn more about myelodysplastic syndromes. Peter L. Greenberg is Professor of Medicine at Stanford University Cancer Center, Stanford, and Chief, Hematology Section, VA Palo Alto Health Care Sy...

  18. Myelodysplastic syndromes: histopathology as prognostic factor

    Directory of Open Access Journals (Sweden)

    Romeo Maura

    2001-01-01

    Full Text Available Bone marrow biopsy allows evaluation of cellularity, abnormal localization of immature precursors and fibrosis in myelodysplastic syndrome. It has been considered important to make diagnosis and prognosis of this disorder. The object of this study evaluated the influence of histopathological parameters, such as cellularity, erythroid/myeloid ratio, abnormal localization of immature precursors and marrow fibrosis, on survival of myelodysplastic syndrome patients. Forty-six patients, admitted from April 1985 to June 1998, and diagnosed as being myelodysplastic syndrome according to French-American-British criteria, were selected. There were 20 males and 26 females, with median age of 61 years. Forty-six bone marrow smears and 36 trephine biopsies were reviewed. Mean survival of hypocellular cases was 64.8 months and of hyper and normocellular cases was 31.8 months. Patients with predominance of erythroid hyperplasia had mean survival of 50.8 months, greater than those with predominance of myeloid hyperplasia (20.3 months. There was no statistical difference in survival of patients with or without abnormal localization of immature precursors and with or without marrow fibrosis. Bone marrow biopsy is a useful tool for the identification of parameters that influence prognosis in myelodysplastic syndrome. Hypocellularity and erythroid hyperplasia were correlated with longer survival while myeloid hyperplasia with poorer survival.

  19. IER3 Expression in Childhood Myelodysplastic Syndrome

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    de Vries, Andrica; Zwaan, Christian M.; Danen van Ooschot, Astrid

    Background: Childhood myelodysplastic syndrome (MDS) is a rare disease accounting for less than 5% of all hematological malignancies. In about 50% of the MDS cases an abnormal karyotype is found by conventional karyotyping, of which chromosome 6 is involved in 10%. The immediate-early-response 3...

  20. 5-Fluoro-2'-Deoxycytidine and Tetrahydrouridine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

    Science.gov (United States)

    2015-06-03

    Adult Acute Myeloid Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  1. Peptide Vaccination Against Cancer Testis Antigens in Combination With Azacitidine for Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia

    DEFF Research Database (Denmark)

    Holmberg, S.; Ortved Gang, A.; Svane, I.M.

    2016-01-01

    Myelodysplastic Syndrome (MDS) is a clonal disorder and characterized by increasing bone marrow failure due to accumulation of genetic and epigenetic changes in hematopoietic stem cells. Patients with high-risk disease have a poor prognosis and a high risk of progression to Acute Myeloid Leukemia...

  2. Management of older adults with myelodysplastic syndromes (MDS).

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    Luskin, Marlise R; Abel, Gregory A

    2017-12-28

    The myelodysplastic syndromes (MDS) are a varied group of hematologic neoplasms that lead to bone marrow failure, and also carry a risk of progression to acute myeloid leukemia. Patients with MDS suffer significant impairments to both their quality of life and survival. Age is the dominant risk factor for the development of MDS, with a median age at diagnosis over 70years. Consequently, patients with MDS frequently have concurrent comorbidities and/or frailty which may be coincident or related to the disease itself. Disease characteristics, degree of comorbidity, and presence of frailty all impact prognosis. Treatment of MDS focuses on supportive care, with disease-modifying approaches (chemotherapy and allogeneic hematopoietic cell transplantation) reserved for fit patients with high-risk disease. Care of patients with MDS requires understanding the disease in the context of an older population, and tailoring approaches to both disease risk and patient suitability for therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. IER3 Expression in Childhood Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

    de Vries, Andrica; Zwaan, Christian M.; Danen van Ooschot, Astrid

    Background: Childhood myelodysplastic syndrome (MDS) is a rare disease accounting for less than 5% of all hematological malignancies. In about 50% of the MDS cases an abnormal karyotype is found by conventional karyotyping, of which chromosome 6 is involved in 10%. The immediate-early-response 3...... (IER3) gene, which is located on chromosome 6p21, encodes for a glycoprotein that plays a role in the regulation of apoptosis and cell cycle progression. Recently, it was shown that IER3 gene aberrations frequently occur in adult MDS patients, which are not restricted to patients with chromosome 6...... aberrations and that low IER3 expression was associated with a worse outcome. Therefore, we investigated the frequency and prognostic impact of IER3 expression in childhood MDS. Methods: IER3 mRNA expression was determined by quantitative real-time PCR in 58 childhood MDS patients of which 17 carried...

  4. [Progress of cytogenetic detection in myelodysplastic syndromes].

    Science.gov (United States)

    Zhou, Qing-Bing; Hu, Xiao-Mei; Liu, -Feng; Ma, Rou

    2011-12-01

    In recent years, significant progresses have been got in study on pathogenesis, treatment and prognosis of myelodysplastic syndromes (MDS), especially on use of new technology, that has great importance for cytogenetics of MDS. Recently, the progress of cytogenetic detection in MDS is very remarkable. Based on the metaphase cytogenetics (MC) method, prognostic significance of cytogenetics in MDS was clarified gradually. For example, people have known the prognostic significance of 12 p-, 11 q-, +21, t(11(q23)), although these genetic abnormalities are rare in the MDS. In addition, chromosome mutation emerged in the process of MDS may indicate the poor prognosis. On the other hand, with the use of SNP-A and aCGH in the study of genetics, MDS cytogenetic abnormality detection rate has been further improved and can reach to 78%. At the same time, some of MDS patients with the "normal karyotype" detected by MC have new hidden aberrations through the SNP or CGH detection, and these patients have a poorer prognosis. In this review, the advances of study on cytogenetic detection for MDS based on MC and SNP-A or aCGH methods are summarized.

  5. Lactobacillus in Preventing Infection in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer or Myelodysplastic Syndrome

    Science.gov (United States)

    2017-02-02

    Breast Cancer; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  6. Successful treatment of myelodysplastic syndrome-induced pyoderma gangrenosum.

    Science.gov (United States)

    Koca, E; Duman, A E; Cetiner, D; Buyukasik, Y; Haznedaroglu, I C; Uner, A; Demirhan, B; Kerimoglu, U; Barista, I; Calguneri, M; Ozcebe, O I

    2006-12-01

    We report successful treatment of a refractory myelodysplastic syndrome-associated pyoderma gangrenosum with the combination of thalidomide and interferon-alpha2a in a single patient. A non-healing wound developed on a 40-year-old woman's left thumb after minor trauma. Massive ulcerovegetative lesions developed after reconstruction surgery. Histopathological examination of the bone marrow and cytogenetic studies revealed an atypical myeloproliferative/myelodysplastic syndrome. The skin lesions resolved dramatically after two months of thalidomide and interferon-alpha2a combination therapy and the haematological status improved.

  7. Frequent Chromatin Rearrangements in Myelodysplastic Syndromes - What Stands Behind?

    Czech Academy of Sciences Publication Activity Database

    Pagáčová, Eva; Falk, Martin; Falková, Iva; Lukášová, Emilie; Michalová, K.; Oltová, A.; Raška, I.; Kozubek, Stanislav

    2014-01-01

    Roč. 60, č. 2014 (2014), s. 1-7 ISSN 0015-5500 R&D Projects: GA ČR(CZ) GBP302/12/G157; GA MŠk(CZ) EE2.3.30.0030 Institutional support: RVO:68081707 Keywords : myelodysplastic syndromes * chromosomal rearrangements * chromosome 5 deletions Subject RIV: BO - Biophysics Impact factor: 1.000, year: 2014

  8. Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kim, Sung-Yong; Le Rademacher, Jennifer; Antin, Joseph H; Anderlini, Paolo; Ayas, Mouhab; Battiwalla, Minoo; Carreras, Jeanette; Kurtzberg, Joanne; Nakamura, Ryotaro; Eapen, Mary; Deeg, H Joachim

    2014-12-01

    A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patients with de novo myelodysplastic syndrome. There was no difference in overall survival. There were no significant differences with regard to 5-year probabilities of relapse, non-relapse mortality, relapse-free survival and overall survival; these were 14%, 40%, 46% and 49% for post-aplastic anemia myelodysplastic syndrome, and 20%, 33%, 47% and 49% for de novo myelodysplastic syndrome, respectively. In multivariate analysis, relapse (hazard ratio 0.71; P=0.18), non-relapse mortality (hazard ratio 1.28; P=0.18), relapse-free survival (hazard ratio 0.97; P=0.80) and overall survival (hazard ratio 1.02; P=0.88) of post-aplastic anemia myelodysplastic syndrome were similar to those of patients with de novo myelodysplastic syndrome. Cytogenetic risk was independently associated with overall survival in both groups. Thus, transplant success in patients with post-aplastic anemia myelodysplastic syndrome was similar to that in patients with de novo myelodysplastic syndrome, and cytogenetics was the only significant prognostic factor for post-aplastic anemia myelodysplastic syndrome patients. Copyright© Ferrata Storti Foundation.

  9. Genetic features of myelodysplastic syndrome and aplastic anemia in pediatric and young adult patients

    Science.gov (United States)

    Keel, Siobán B.; Scott, Angela; Sanchez-Bonilla, Marilyn; Ho, Phoenix A.; Gulsuner, Suleyman; Pritchard, Colin C.; Abkowitz, Janis L.; King, Mary-Claire; Walsh, Tom; Shimamura, Akiko

    2016-01-01

    The clinical and histopathological distinctions between inherited versus acquired bone marrow failure and myelodysplastic syndromes are challenging. The identification of inherited bone marrow failure/myelodysplastic syndromes is critical to inform appropriate clinical management. To investigate whether a subset of pediatric and young adults undergoing transplant for aplastic anemia or myelodysplastic syndrome have germline mutations in bone marrow failure/myelodysplastic syndrome genes, we performed a targeted genetic screen of samples obtained between 1990–2012 from children and young adults with aplastic anemia or myelodysplastic syndrome transplanted at the Fred Hutchinson Cancer Research Center. Mutations in inherited bone marrow failure/myelodysplastic syndrome genes were found in 5.1% (5/98) of aplastic anemia patients and 13.6% (15/110) of myelodysplastic syndrome patients. While the majority of mutations were constitutional, a RUNX1 mutation present in the peripheral blood at a 51% variant allele fraction was confirmed to be somatically acquired in one myelodysplastic syndrome patient. This highlights the importance of distinguishing germline versus somatic mutations by sequencing DNA from a second tissue or from parents. Pathological mutations were present in DKC1, MPL, and TP53 among the aplastic anemia cohort, and in FANCA, GATA2, MPL, RTEL1, RUNX1, SBDS, TERT, TINF2, and TP53 among the myelodysplastic syndrome cohort. Family history or physical examination failed to reliably predict the presence of germline mutations. This study shows that while any single specific bone marrow failure/myelodysplastic syndrome genetic disorder is rare, screening for these disorders in aggregate identifies a significant subset of patients with inherited bone marrow failure/myelodysplastic syndrome. PMID:27418648

  10. Acquired Myelodysplasia or Myelodysplastic Syndrome: Clearing the Fog

    Directory of Open Access Journals (Sweden)

    Ethan A. Natelson

    2013-01-01

    Full Text Available Myelodysplastic syndromes (MDS are clonal myeloid disorders characterized by progressive peripheral blood cytopenias associated with ineffective myelopoiesis. They are typically considered neoplasms because of frequent genetic aberrations and patient-limited survival with progression to acute myeloid leukemia (AML or death related to the consequences of bone marrow failure including infection, hemorrhage, and iron overload. A progression to AML has always been recognized among the myeloproliferative disorders (MPD but occurs only rarely among those with essential thrombocythemia (ET. Yet, the World Health Organization (WHO has chosen to apply the designation myeloproliferative neoplasms (MPN, for all MPD but has not similarly recommended that all MDS become the myelodysplastic neoplasms (MDN. This apparent dichotomy may reflect the extremely diverse nature of MDS. Moreover, the term MDS is occasionally inappropriately applied to hematologic disorders associated with acquired morphologic myelodysplastic features which may rather represent potentially reversible hematological responses to immune-mediated factors, nutritional deficiency states, and disordered myelopoietic responses to various pharmaceutical, herbal, or other potentially myelotoxic compounds. We emphasize the clinical settings, and the histopathologic features, of such AMD that should trigger a search for a reversible underlying condition that may be nonneoplastic and not MDS.

  11. [Large vessel vasculitis with myelodysplastic syndrome: A rare association].

    Science.gov (United States)

    Galland, J; Kawski, H; Guichard, J-F; Maurier, F

    2017-07-01

    The vasculitis can be the consequence of malignancy: most often hematologic rather than solid tumors. The association between large vessels vasculitis and myelodysplastic syndrome is rare. A 55-year-old man experienced asthenia, fever, polyarthritis and inflammatory syndrome. Haematological investigations found a type 2 refractory anemia with excess blasts (RAEB-2) with discovery of severe anemia (Hb: 7,8g/dl) and thrombopenia (platelets: 40,000/mm 3 ). Radiological examinations found thoracic aortitis and carotid vasculitis. Treatment in the form of steroids and azacitidine was instituted. The lack of control of both RAEB-2 and vasculitis was responsible for the death of the patient. Myelodysplastic syndrome and large vessels vasculitis is a rare but serious association disease. The lack of efficiency of corticosteroids seems to be common. Prognosis depends on the haematological treatment effectiveness. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  12. Bone marrow MRI in patients with myelodysplastic syndromes

    International Nuclear Information System (INIS)

    Chen Zhao; Guo You; Wang Renfa; Zou Mingli; Liu Wenli; Xia Liming; Wang Chengyuan

    2004-01-01

    Objective: To observe the MR imaging of bone marrow in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and to reveal the rule of bone marrow infiltration and the role of MRI in diagnosing and predicting the prognosis of myelodysplastic syndromes. Methods: Thirty patients received MRI after the diagnosis based on clinic and FAB subtype study, including 16 with MDS and 14 with AML. MR image was obtained by T 1 -weighted spin echo and shot time inversion recovery in pelvis and femur. The examining results of morphology and blood routine were collected at the same time. 30 age-matched volunteers were selected as controls. Results: The MRI appearance was classified into their patterns based on scope of focus. MRI patterns from grade 1 to grade 3 was observed in patients with MDS. All patients with AML distributed in grade 2 to grade 3. The distribution of patterns had no significant difference between MDS and AML (P>0.05). The marrow ratio had significant difference among MDS, AML, and controls (P<0.05). The MRI grade was consistent with the clinic diagnostic indexes. Conclusion: MRI can provide a better understanding of the difference between MDS and AML. MRI can estimate the extent of disease in the marrow as a whole. MRI of bone marrow can provide imaging basis in diagnosis and predicting the prognosis for patients with MDS

  13. Longitudinal Analysis of DNA Methylation in CD34+ Hematopoietic Progenitors in Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

    Wong, Yan Fung; Micklem, Chris N; Taguchi, Masataka

    2014-01-01

    Myelodysplastic syndrome (MDS) is a disorder of hematopoietic stem cells (HSCs) that is often treated with DNA methyltransferase 1 (DNMT1) inhibitors (5-azacytidine [AZA], 5-aza-2'-deoxycytidine), suggesting a role for DNA methylation in disease progression. How DNMT inhibition retards disease...... regulators not expressed within the hematopoietic compartment and was distinct from that observed between healthy hematopoietic cell types. After AZA treatment, we observed only limited DNA demethylation at sites that varied between patients. This suggests that a subset of the stem cell population...... is resistant to AZA and provides a basis for disease relapse. Using gene expression data from patient samples and an in vitro AZA treatment study, we identified differentially methylated genes that can be activated following treatment and that remain silent in the CD34+ stem cell compartment of high-risk MDS...

  14. Increased relative risk of myelodysplastic syndrome in atomic bomb survivors

    International Nuclear Information System (INIS)

    Oda, Kenji; Kimura, Akiro; Matsuo, Tatsuki; Tomonaga, Masao; Kodama, Kazunori; Mabuchi, Kiyohiko

    1998-01-01

    It was investigated what blood disorders except leukemia increased the relative risk with dose dependency in atomic bomb survivors. Subjects were 217 patients of atomic bomb survivors in Hiroshima and Nagasaki, who had blood disorders except leukemia and died between 1950 and 1990. Their medical records were analyzed and their diagnoses were reevaluated. Sixteen cases were diagnosed as the aplastic anemia and 12 as the myelodysplastic syndrome (MDS). In the aplastic anemia, there was no correlation between the exposure dose and the mortality. In MDS, the excess relative risk (ERR)/bone marrow exposure dose of 1 Sv was very high (13.0). These results supports the hypothesis that MDS would be broken out by the clonal abnormality of the hematopoietic stem cell and radiation exposure could cause the appearance of the abnormal stem cell clone. (K.H.)

  15. Increased relative risk of myelodysplastic syndrome in atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Oda, Kenji [Hiroshima City Hospital (Japan); Kimura, Akiro; Matsuo, Tatsuki; Tomonaga, Masao; Kodama, Kazunori; Mabuchi, Kiyohiko

    1998-12-01

    It was investigated what blood disorders except leukemia increased the relative risk with dose dependency in atomic bomb survivors. Subjects were 217 patients of atomic bomb survivors in Hiroshima and Nagasaki, who had blood disorders except leukemia and died between 1950 and 1990. Their medical records were analyzed and their diagnoses were reevaluated. Sixteen cases were diagnosed as the aplastic anemia and 12 as the myelodysplastic syndrome (MDS). In the aplastic anemia, there was no correlation between the exposure dose and the mortality. In MDS, the excess relative risk (ERR)/bone marrow exposure dose of 1 Sv was very high (13.0). These results supports the hypothesis that MDS would be broken out by the clonal abnormality of the hematopoietic stem cell and radiation exposure could cause the appearance of the abnormal stem cell clone. (K.H.)

  16. Causes of death in 2877 patients with myelodysplastic syndromes.

    Science.gov (United States)

    Nachtkamp, Kathrin; Stark, Romina; Strupp, Corinna; Kündgen, Andrea; Giagounidis, Aristoteles; Aul, Carlo; Hildebrandt, Barbara; Haas, Rainer; Gattermann, Norbert; Germing, Ulrich

    2016-05-01

    Patients with myelodysplastic syndromes face a poor prognosis. The exact causes of death have not been described properly in the past. We performed a retrospective analysis of causes of death using data of 3792 patients in the Düsseldorf registry who have been followed up for a median time of 21 months. Medical files as well as death certificates were screened and primary care physicians were contacted. Death after AML evolution, infection, and bleeding was considered to be clearly disease-related. Further categories of causes of death were heart failure, other possibly disease-related reasons, such as hemochromatosis, disease-independent reasons as well as cases with unclear causes of death. Median age at the time of diagnosis was 71 years. At the time of analysis, 2877 patients (75.9 %) had deceased. In 1212 cases (42.1 %), the exact cause of death could not be ascertained. From 1665 patients with a clearly documented cause of death, 1388 patients (83.4 %) succumbed directly disease-related (AML (46.6 %), infection (27.0 %), bleeding (9.8 %)), whereas 277 patients (16.6 %) died for reasons not directly related with myelodysplastic syndromes (MDS), including 132 patients with cardiac failure, 77 non-disease-related reasons, 23 patients with solid tumors, and 45 patients with possibly disease-related causes like hemochromatosis. Correlation with IPSS, IPSS-R, and WPSS categories showed a proportional increase of disease-related causes of death with increasing IPSS/IPSS-R/WPSS risk category. Likewise, therapy-related MDS were associated with a higher percentage of disease-related causes of death than primary MDS. This reflects the increasing influence of the underlying disease on the cause of death with increasing aggressiveness of the disease.

  17. Myelodysplastic syndromes in Chernobyl clean-up workers.

    Science.gov (United States)

    Gluzman, Daniil F; Sklyarenko, Lilia M; Koval, Stella V; Rodionova, Nataliia K; Zavelevich, Michael P; Ivanivskaya, Tetiana S; Poludnenko, Liudmyla Yu; Ukrainskaya, Nataliia I

    2015-10-01

    The studies of the recent decades posed the question of the association between radiation exposure and myelodysplastic syndromes (MDS). This association has been proved in secondary MDS originating upon exposure to chemotherapeutics and/or radiation therapy. The long-term study in Japanese atomic (A)-bomb survivors demonstrated the significant linear dose-response for MDS confirming the link between radiation exposure and this form of hematopoietic malignancies. All these findings provide the strong basis for studying MDS in the persons exposed to radiation following the Chernobyl disaster, especially those in the cohort of Chernobyl clean-up workers of 1986-1987. The data on MDS among Chernobyl clean-up workers (1986-1987) diagnosed in 1996-2012 at the reference laboratory of RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology are summarized. MDS cases were diagnosed in 23 persons (21 males and 2 females) having been exposed to radiation as clean-up workers of 1986-1987. Refractory anemia (RA) has been detected in 13, refractory anemia with ring sideroblasts (RARS)-in 2, and refractory anemia with excess blasts (RAEB)-in 8 patients. The median age of those MDS patients was 62.0 years. In addition, 5 cases of chronic myelomonocytic leukemia (CMML) were recorded in the group of Chernobyl clean-up workers with the median time of 14.8 years from 1986-1987 to diagnosis. The association between radiation exposure and MDS is discussed. The suggested life-long risk for myelodysplastic syndromes among A-bomb survivors in Japan highlights the importance of the continuing follow-up studies in the affected populations in the post-Chernobyl period.

  18. Aberrant Methylation-Mediated Suppression of APAF1 in Myelodysplastic Syndrome.

    Science.gov (United States)

    Zaker, Farhad; Nasiri, Nahid; Amirizadeh, Naser; Razavi, Seyed Mohsen; Yaghmaie, Marjan; Teimoori-Toolabi, Ladan; Maleki, Ali; Bakhshayesh, Masoumeh

    2017-04-01

    Background: Myelodysplastic syndromes (MDSs) include a diverse group of clonal bone marrow disorders characterized by ineffective hematopoiesis and pancytopenia. It was found that down regulation of APAF1, a putative tumor suppressor gene (TSG), leads to resistance to chemotherapy and disease development in some cancers. In this study, we investigated the relation of APAF1 methylation status with its expression and clinicopathological factors in myelodysplastic syndrome (MDS) patients. Materials and Methods: Methylation Sensitive-High Resolution Melting Curve Analysis (MS-HRM) was employed in studying the methylation of CpG islands in the APAF1promoter region in MDS. Gene expression was analyzed by using real time RT-PCR. Results: 42.6% of patient samples were methylated in promoter region of APAF1analyzed, while methylation of the gene was not seen in controls (P<0.05). Methylation of APAF1was significantly associated with the suppression of its mRNA expression (P=0.00). The methylation status of APAF1in advanced-stage MDS patients (80%) was significantly higher than that of the early-stage MDS patients (28.2%) (P=0.001). The difference in frequency of hypermethylatedAPAF1 gene was significant between good (37.5%) and poor (85.71%) cytogenetic risk groups (P=0.043). In addition, a higher frequency of APAF1hypermethylation was observed in higher-risk MDS group (69.2%) compared to lower-risk MDS group (34.14%) (P=0.026). Conclusion: Our study indicated that APAF1hypermethylation in MDS was associated to high-risk disease classified according to the IPSS, WHO and cytogenetic risk.

  19. The biology of myelodysplastic syndromes: unity despite heterogeneity

    Directory of Open Access Journals (Sweden)

    Azra Raza

    2010-06-01

    Full Text Available Myelodysplastic syndromes (MDS traditionally have been grouped together as a disease entity based on clinical phenomena seen in association. Despite the similarities, there is great heterogeneity among the syndromes. Recent insights have shown, however, that there exists a biologically cohesive theme that unifies and thereby validates the conceptual interconnectedness. The first suggestion that such a relationship existed where biology could directly explain the observed cytopenias was the finding of excessive premature apoptosis of hematopoietic cells in MDS marrows. This apoptosis was mediated by paracrine as well as autocrine factors implicating both the seed and the soil in the pathology of the disease. Pro-inflammatory cytokines in the marrow microenvironment were mainly the paracrine mediators of apoptosis, but how the clonal cells committed suicide because of autocrine stimulation had remained a mystery for more than a decade. It has been shown now that deregulation of ribosome biogenesis can initiate a stress response in the cell through the p53 signaling pathway. Congenital anemias had been associated with mutations in ribosomal protein genes. The surprise came with the investigation of 5q- syndrome patients where haplo-insufficiency of the ribosomal protein gene RPS14 was found to be the cause of this MDS subtype. Similar ribosomal deregulation was shown to be present in all varieties of MDS patients, serving as another unifying characteristic. In addition to these findings, there are other DNA-related abnormalities such as uniparental disomy, mutations in the TET2 gene, and epigenetic phenomena that are associated with and occur across all types of MDS. This paper summarizes the themes unifying this heterogeneous group of diseases.

  20. The role of magnetic resonance imaging in the evaluation of transfusional iron overload in myelodysplastic syndromes.

    Science.gov (United States)

    Petrou, Emmanouil; Mavrogeni, Sophie; Karali, Vasiliki; Kolovou, Genovefa; Kyrtsonis, Marie-Christine; Sfikakis, Petros P; Panayiotidis, Panayiotis

    2015-01-01

    Myelodysplastic syndromes represent a group of heterogeneous hematopoietic neoplasms derived from an abnormal multipotent progenitor cell, characterized by a hyperproliferative bone marrow, dysplasia of the cellular hemopoietic elements and ineffective erythropoiesis. Anemia is a common finding in myelodysplastic syndrome patients, and blood transfusions are the only therapeutic option in approximately 40% of cases. The most serious side effect of regular blood transfusion is iron overload. Currently, cardiovascular magnetic resonance using T2 is routinely used to identify patients with myocardial iron overload and to guide chelation therapy, tailored to prevent iron toxicity in the heart. This is a major validated non-invasive measure of myocardial iron overloading and is superior to surrogates such as serum ferritin, liver iron, ventricular ejection fraction and tissue Doppler parameters. The indication for iron chelation therapy in myelodysplastic syndrome patients is currently controversial. However, cardiovascular magnetic resonance may offer an excellent non-invasive, diagnostic tool for iron overload assessment in myelodysplastic syndromes. Further studies are needed to establish the precise indications of chelation therapy and the clinical implications of this treatment on survival in myelodysplastic syndromes. Copyright © 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

  1. MR imaging findings of the femoral marrow in myelodysplastic syndrome

    International Nuclear Information System (INIS)

    Tanaka, Osamu; Takagi, Shojiro; Matsuura, Katsuhiko; Ichikawa, Tamaki; Kobayashi, Yasuyuki; Nagai, Jun

    1995-01-01

    MR imaging of the femoral marrow was performed in 30 patients with myelodysplastic syndrome (MDS), 11 cases of which evolved to acute myeloid leukemia (AML). The MRI appearance was classified into five patterns: fatty marrow; faint signal; nodular pattern; heterogeneous infiltration; and diffuse infiltration. For each type of MDS, MRI patterns of the femoral marrow were evaluated and compared with those in normal subjects as well as in patients with aplastic anemia. Signal intensity alteration, a low signal on T1-weighted SE image and a high signal on STIR image, began in the proximal femoral marrow almost symmetrically in patients with MDS. The area of abnormal signal intensity tended to gradually extend towards the distal portion of the femur as the disease progressed. MRI patterns of the femoral marrow correlated with marrow cellularity, and diffuse marrow infiltration was noted in patients with a more advanced type of MDS or with severe anemia. There were limitations to making an accurate diagnosis of the MDS type on the basis of the MRI pattern. Progression of the MRI appearance in the course of MDS was thought to be a sign suggesting evolution to AML. It was difficult to differentiate hypoplastic MDS from aplastic anemia, although the nodular pattern was commonly seen in the latter disease. (author)

  2. MR imaging findings of the femoral marrow in myelodysplastic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Osamu; Takagi, Shojiro; Matsuura, Katsuhiko; Ichikawa, Tamaki; Kobayashi, Yasuyuki; Nagai, Jun [Jichi Medical School, Minamikawachi, Tochigi (Japan)

    1995-10-01

    MR imaging of the femoral marrow was performed in 30 patients with myelodysplastic syndrome (MDS), 11 cases of which evolved to acute myeloid leukemia (AML). The MRI appearance was classified into five patterns: fatty marrow; faint signal; nodular pattern; heterogeneous infiltration; and diffuse infiltration. For each type of MDS, MRI patterns of the femoral marrow were evaluated and compared with those in normal subjects as well as in patients with aplastic anemia. Signal intensity alteration, a low signal on T1-weighted SE image and a high signal on STIR image, began in the proximal femoral marrow almost symmetrically in patients with MDS. The area of abnormal signal intensity tended to gradually extend towards the distal portion of the femur as the disease progressed. MRI patterns of the femoral marrow correlated with marrow cellularity, and diffuse marrow infiltration was noted in patients with a more advanced type of MDS or with severe anemia. There were limitations to making an accurate diagnosis of the MDS type on the basis of the MRI pattern. Progression of the MRI appearance in the course of MDS was thought to be a sign suggesting evolution to AML. It was difficult to differentiate hypoplastic MDS from aplastic anemia, although the nodular pattern was commonly seen in the latter disease. (author).

  3. Distinct neutrophil subpopulations phenotype by flow cytometry in myelodysplastic syndromes.

    Science.gov (United States)

    Vikentiou, Myrofora; Psarra, Katerina; Kapsimali, Violetta; Liapis, Konstantinos; Michael, Michalis; Tsionos, Konstantinos; Lianidou, Evi; Papasteriades, Chryssa

    2009-03-01

    The cardinal feature of myelodysplastic syndromes (MDS) is dysplasia involving one or more myeloid cell lineages. In the present study, we used 4-color flow cytometric analysis to investigate dysgranulopoiesis in bone marrow specimens from 65 patients with MDS. The antigen expression patterns of total neutrophil granulocytes (TNG) and of the two distinct neutrophil granulocytic subpopulations (NGSs), NGS-1 (dimmer CD45 expression) and NGS-2 (stronger CD45 expression) identified on the side scatter (SS) vs. CD45-intensity plot, were studied. The neutrophil granulocytes from patients with MDS showed characteristic antigen expression aberrancies which were more pronounced in NGS-2 subpopulation. Studying separately the NGS-2 subpopulation with the CD16/MPO/LF combination, the low CD16(+)/MPO(+) and low CD16(+)/LF(+) percentages seemed to discriminate between lower-risk and higher-risk patients with MDS in most occasions. Furthermore, a detailed assessment of the NGS-1 and NGS-2 immunophenotypic patterns revealed early dysplastic changes, not otherwise observed by standard TNG analysis, especially in cases of lower-risk MDS.

  4. Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes

    Directory of Open Access Journals (Sweden)

    Marianna Guida

    2014-01-01

    Full Text Available A role for intracellular ROS production has been recently implicated in the pathogenesis and progression of a wide variety of neoplasias. ROS sources, such as NAD(PH oxidase (Nox complexes, are frequently activated in AML (acute myeloid leukemia blasts and strongly contribute to their proliferation, survival, and drug resistance. Myelodysplastic syndromes (MDS comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop AML. The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is the genomic instability. NADPH oxidases are now recognized to have specific subcellular localizations, this targeting to specific compartments for localized ROS production. Local Nox-dependent ROS production in the nucleus may contribute to the regulation of redox-dependent cell growth, differentiation, senescence, DNA damage, and apoptosis. We observed that Nox1, 2, and 4 isoforms and p22phox and Rac1 subunits are expressed in MDS/AML cell lines and MDS samples, also in the nuclear fractions. Interestingly, Nox4 interacts with ERK and Akt1 within nuclear speckle domain, suggesting that Nox4 could be involved in regulating gene expression and splicing factor activity. These data contribute to the elucidation of the molecular mechanisms used by nuclear ROS to drive MDS evolution to AML.

  5. The third International Congress on Myeloproliferative and Myelodysplastic Syndromes.

    Science.gov (United States)

    Silver, R T; Bennett, J M; Goldman, J M; Spivak, J L; Tefferi, A

    2007-01-01

    This meeting was convened by Richard T. Silver and co-chaired by Jerry L. Spivak. It was held from 27 to 29 October 2005 in Washington, DC. Thirty-one invited speakers from seven different countries participated in the conference, which was attended by more than 300 individuals from 23 countries. As in previous years, a clinical symposium for patients, held the day before the symposium, was sponsored by the Cancer Research and Treatment Fund, Inc., New York, NY 10021. This meeting report provides a summary of the five sessions prepared and highlighted by one of the session chairs. In addition to the formal presentations on the biology, clinical aspects and management of these diverse marrow stem cell disorders, there was considerable interest generated because of the availability of several new agents that have been recently approved. A special luncheon satellite symposium was devoted to the dramatic changes in the therapeutic options for the myelodysplastic syndromes, sponsored by MGI Pharma, Inc. The keynote address was presented by Dr. George Q. Daley from Harvard Medical School and the Children's Hospital Medical Center. He reviewed the molecular steps in the formation of the Philadelphia chromosome and some of the newly described mutations leading to resistance to chemotherapy (see Section 4).

  6. Iron overload in patients with myelodysplastic syndromes: An updated overview.

    Science.gov (United States)

    Moukalled, Nour M; El Rassi, Fuad A; Temraz, Sally N; Taher, Ali T

    2018-06-15

    Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by a broad clinical spectrum related to ineffective hematopoiesis leading to unilineage or multilineage cytopenias, with a high propensity for transformation to acute myeloid leukemia. Iron overload has been recently identified as one of the important conditions complicating the management of these diverse disorders. The accumulation of iron is mainly related to chronic transfusions; however, evidence suggests a possible role for ineffective erythropoiesis and increased intestinal absorption of iron, related to altered hepcidin and growth differentiation factor-15 levels in the development of hemosiderosis in patients with MDS. In addition to its suggested role in the exacerbation of ineffective erythropoiesis, multiple reports have identified a prognostic implication for the development of iron overload in patients with MDS, with an improvement in overall survival after the initiation of iron chelation therapy. This review includes a detailed discussion of iron overload in patients with MDS whether they are undergoing supportive therapy or curative hematopoietic stem cell transplantation, with a focus on the mechanism, diagnosis, and effect on survival as well as the optimal management of this highly variable complication. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

  7. Myelodysplastic syndromes and the role of iron overload.

    Science.gov (United States)

    Harvey, R Donald

    2010-04-01

    The epidemiology of myelodysplastic syndromes (MDS) and iron overload, recent clinical findings that highlight the importance of actively managing iron overload, and recommendations for initiating and maintaining iron chelation therapy (ICT) are summarized. MDS are a variety of hematological disorders with differing time courses. Disease morbidities are primarily due to cytopenias and evolution to acute myeloid leukemia. Iron overload is a serious complication in patients with MDS due to the long-term use of red blood cell transfusions in patients with symptomatic anemia. Clinical consequences of iron overload include end-organ damage and dysfunction, an increased frequency of transplant-related complications, and reduced survival rates. To prevent these complications, recommendations for initiating and maintaining ICT should be followed by clinicians caring for patients with MDS and iron overload. As current therapeutic options for patients with MDS do not always reduce the transfusion burden, many patients will still need long-term transfusion therapy. Strategies for the management of iron overload in MDS should be considered early in the disease course and in appropriate patients in order to prevent negative clinical outcomes associated with excessive iron accumulation.

  8. Myelodysplastic Syndromes (MDS) and autoimmune disorders (AD): cause or consequence?

    Science.gov (United States)

    Braun, Thorsten; Fenaux, Pierre

    2013-12-01

    Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) are frequently associated with clinical manifestations of autoimmune disorders (AD) and inflammatory response of the immune system. AD accompanying MDS and CMML include vasculitis, seronegative polyarthritis and neutrophilic dermatosis. Rare AD including relapsing polychondritis is strongly associated with MDS as in a high proportion of those patients MDS is diagnosed during disease course. Antinuclear antibodies (ANA) are frequently found among MDS patients without clinical manifestation of AD. In a subset of patients, MDS and resulting cytopenias appear to be the consequence of auto reactive immunologic activity and may respond to immunosuppressive treatment (IST). Increased release of inflammatory cytokines like tumor necrosis factor-(TNF)-α and interferon (IF)-γ triggers apoptosis of myeloid precursor cells leading to cytopenias. Impaired function of immune cells including cytotoxic, regulatory (Treg), helper (Th17) T cells and NK cells also appears to predict response to IST, outcome and occurrence of AD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Differential diagnosis of myelodysplastic syndrome and aplastic anemia using MRI

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Seung Eun; Park, Jung Mi; Lee, Jae Mun; Kim, Ki Tae; Kim, Dong Wook; Kim, Chun Choo; Kim, Chun Yul; Shinn, Kyung Sub [Catholic University Medical College, Seoul (Korea, Republic of)

    1995-04-15

    To assess the patterns of myelodysplastic syndrome (MDS) and aplastic anemia (AA) on MRI of the spinal bone marrow and to find the differential points between the two groups. Fourteen patients with MDS (n=7) and AA (n=7) were studied using magnetic resonance imaging. Sagittal images from the lower thoracic and lumbar vertebral marrow were evaluated on T1-weighted and STIR images. Five distinct patterns of signal intensity of the T1-weighted and STIR images were classified. T1 and T2 relaxation times and T1 marrow/fat signal intensity ratio were measured and analyzed (t-test). The cellularity of bone marrow was evaluated on histologic slides. MDS showed homogeneously low signal intensity on T1WI and high signal intensity on STIR image, indicating hypercellular marrow, whereas AA showed relative high signal intensity on T1WI and low signal intensity on STIR image, representing fatty marrow. T1 and T2 relaxation time (T1 for MDS=750.26 msec {+-} 177.50, T1 for AA=413.21 msec {+-} 167.39 ({rho} < 0.000), T2 for MDS=91.86 msec {+-} 14.16, T2 for AA=81.44 msec {+-} 15.31 ({rho} < 0.001) and T1 marrow/fat signal intensity ratio (0.22 {+-} 0.048 in MDS, 0.30 {+-} 0.083 in AA ({rho} < 0.000) revealed statistically significant difference between the two groups. Although the marrow aspiration and needle biopsy are mandatory in hematologic disease for diagnosis, there are limited in assessing the change of total marrow mass. Therefore MRI of bone marrow might be useful in distinguishing MDS from AA because of its ability of representation of total marrow mass.

  10. The Differencies in Adult and Pediatric Myelodysplastic Syndrome: A Review

    Directory of Open Access Journals (Sweden)

    Vasekova P

    2016-08-01

    Full Text Available Myelodysplastic syndrome (MDS represent very heterogenous group of clonal stem cell bone marrow disorders with ineffective haematopoesis leading to cytopenias in peripheral blood and increased risk of blastic transformation and evolution of acute myeloid leukemia. MDS is a disease of older age mostly, in children it seems to be very rare. There are several significant morphological, cytogenetic and prognostic differencies of the disease in adults and in children. Adult MDS patients most commonly manifest with symptoms of anemia, bleeding and infection are uncommon. In childhood, MDS manifests predominantly by neutropenia and thrombocytopenia. In addition, some pediatric MDS patients present also with constitutional disease’s signs and symptoms. Early and correct diagnosis in both age groups is essential for the choice of appropriate therapy and also for next life of patients. However, the diagnosis of MDS is challenging, complex and requiring close correlation of clinical symptoms, laboratory parameters and standardized examination of BM biopsies. The authors present an overview focused on biology of MDS in adults and children, on the differences in the incidence, clinical presentation and treatment. They summarize the possibilities and limits of histopathological diagnosis and differential diagnosis of the disease in different age groups. A major problem in the morphological diagnosis of MDS remains the determination, whether the myelodysplasia is due to clonal disorder. It might result also from some other factors, as significant dysplasia can also occur in reactive conditions, and vice versa, only discrete dysplasia is sometimes observed in MDS patients. Although histomorphological and immunohistochemical analysis of BM biopsy is invasive and time-consuming examination, it has its value in the diagnosis, differential diagnosis and evaluation of therapeutic effect.

  11. Therapy with recombinant human erythropoietin in patients with myelodysplastic syndromes.

    Science.gov (United States)

    Stone, R M; Bernstein, S H; Demetri, G; Facklam, D P; Arthur, K; Andersen, J; Aster, J C; Kufe, D

    1994-10-01

    We conducted a Phase I-II trial of recombinant human erythropoietin-beta (rhEPO) in patients with myelodysplastic syndrome (MDS). Patients with anemia and pathologically confirmed MDS were eligible for the study. Treatment consisted of rhEPO by subcutaneous injection thrice weekly for 6 weeks at one of three dose levels (100 U/kg (three patients), 200 U/kg (three patients) and 400 U/kg (14 patients)). Ferrous sulfate (325 mg po tid) was also administered if the transferrin saturation was below 30% (two patients). Patients were monitored with weekly CBC, white cell differential, and reticulocyte counts. Bone marrow examinations were performed at the conclusion of the treatment period and after a 2 week washout period. Patients who responded to therapy were continued on rhEPO at the same dose for 6 additional months. Response criteria included: 50% reduction in transfusion requirements compared with the 6 week pre-study period; doubling of reticulocyte count that was maintained on two determinations at least 1 week apart; or an increase in hemoglobin by at least 1.2 gm/dl without transfusions. Pre-treatment factors potentially predictive of response were analyzed by univariate analysis and in a multivariate fashion by classification and regression trees. Seven of the twenty patients sustained an untransfused rise in serum hemoglobin > or = 1.2 gm/dl. Four of the sixteen patients (including three of seven patients experiencing a rise in serum hemoglobin) who were transfusion-dependent prior to the study achieved a reduction or elimination of their transfusion requirements. Five of thirteen patients who received rhEPO during the extension phase had a continued response. A low baseline erythropoietin level (< 50 mU/ml) was the best predictor of hemoglobin response when controlling for other variables. rhEPO has a role in the treatment of certain patients with MDS, particularly in those whose endogenous serum erythropoietin levels are not markedly elevated.

  12. Mechanisms of resistance to decitabine in the myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Taichun Qin

    Full Text Available The DNA methylation inhibitor 5-aza-2'-deoxycytidine (DAC is approved for the treatment of myelodysplastic syndromes (MDS, but resistance to DAC develops during treatment and mechanisms of resistance remain unknown. Therefore, we investigated mechanisms of primary and secondary resistance to DAC in MDS.We performed Quantitative Real-Time PCR to examine expression of genes related to DAC metabolism prior to therapy in 32 responders and non-responders with MDS as well as 14 patients who achieved a complete remission and subsequently relapsed while on therapy (secondary resistance. We then performed quantitative methylation analyses by bisulfite pyrosequencing of 10 genes as well as Methylated CpG Island Amplification Microarray (MCAM analysis of global methylation in secondary resistance.Most genes showed no differences by response, but the CDA/DCK ratio was 3 fold higher in non-responders than responders (P<.05, suggesting that this could be a mechanism of primary resistance. There were no significant differences at relapse in DAC metabolism genes, and no DCK mutations were detected. Global methylation measured by the LINE1 assay was lower at relapse than at diagnosis (P<.05. On average, the methylation of 10 genes was lower at relapse (16.1% compared to diagnosis (18.1% (P<.05. MCAM analysis showed decreased methylation of an average of 4.5% (range 0.6%-9.7% of the genes at relapse. By contrast, new cytogenetic changes were found in 20% of patients.Pharmacological mechanisms are involved in primary resistance to DAC, whereas hypomethylation does not prevent a relapse for patients with DAC treatment.

  13. Differential diagnosis of myelodysplastic syndrome and aplastic anemia using MRI

    International Nuclear Information System (INIS)

    Jung, Seung Eun; Park, Jung Mi; Lee, Jae Mun; Kim, Ki Tae; Kim, Dong Wook; Kim, Chun Choo; Kim, Chun Yul; Shinn, Kyung Sub

    1995-01-01

    To assess the patterns of myelodysplastic syndrome (MDS) and aplastic anemia (AA) on MRI of the spinal bone marrow and to find the differential points between the two groups. Fourteen patients with MDS (n=7) and AA (n=7) were studied using magnetic resonance imaging. Sagittal images from the lower thoracic and lumbar vertebral marrow were evaluated on T1-weighted and STIR images. Five distinct patterns of signal intensity of the T1-weighted and STIR images were classified. T1 and T2 relaxation times and T1 marrow/fat signal intensity ratio were measured and analyzed (t-test). The cellularity of bone marrow was evaluated on histologic slides. MDS showed homogeneously low signal intensity on T1WI and high signal intensity on STIR image, indicating hypercellular marrow, whereas AA showed relative high signal intensity on T1WI and low signal intensity on STIR image, representing fatty marrow. T1 and T2 relaxation time (T1 for MDS=750.26 msec ± 177.50, T1 for AA=413.21 msec ± 167.39 (ρ < 0.000), T2 for MDS=91.86 msec ± 14.16, T2 for AA=81.44 msec ± 15.31 (ρ < 0.001) and T1 marrow/fat signal intensity ratio (0.22 ± 0.048 in MDS, 0.30 ± 0.083 in AA (ρ < 0.000) revealed statistically significant difference between the two groups. Although the marrow aspiration and needle biopsy are mandatory in hematologic disease for diagnosis, there are limited in assessing the change of total marrow mass. Therefore MRI of bone marrow might be useful in distinguishing MDS from AA because of its ability of representation of total marrow mass

  14. Current State of the Art: Management of Higher Risk Myelodysplastic Syndromes.

    Science.gov (United States)

    Komrokji, Rami S

    2016-08-01

    The higher risk myelodysplastic syndrome (MDS) patients, defined by the International Prognostic Scoring System (IPSS) as intermediate-2 or high-risk groups, compromise a third of MDS patients who have an expected survival of less than 1.5 years. Our ability to better define higher risk MDS improved with the proposal of new clinical risk models such as the revised IPSS and by integration of molecular data, including somatic gene mutations. Allogeneic hematopoietic stem-cell transplantation (AHSCT) remains the only curative option. In higher risk MDS patients, proceeding early with AHSCT is associated with maximum survival gain. The decision to pursue AHSCT is individualized according to disease risk, comorbidities, and functional status. The role of therapy before AHSCT remains controversial, and the role of post-AHSCT maintenance is evolving. Hypomethylating agents are the only medications that alter the natural history of the disease. Azacitidine is the only drug reported to improve overall survival in higher risk MDS patients. Appropriate use and assessment of response is key for assuring patients benefit of such limited options. Treatment after failure of hypomethylating agents is an unmet need. The role of detectable somatic gene mutations in prognosis and tailoring therapy continue to emerge. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Should elderly patients with higher-risk myelodysplastic syndromes undergo allogeneic hematopoietic stem cell transplantation?

    Science.gov (United States)

    Zeidan, Amer M; Gore, Steven D

    2013-10-01

    Myelodysplastic syndromes (MDS) include a group of hematopoietic malignancies characterized by dysplastic changes, ineffective hematopoiesis and variable risk of leukemic progression. At diagnosis, 86% of MDS patients are ≥60 years. Azacitidine, the only drug that prolongs life in high-risk (HR)-MDS patients, adds a median of only 9.5 months to life. Allogeneic stem cell transplantation (alloSCT) remains the only potentially curative approach. Despite recent improvements including use of reduced intensity conditioning (RIC) that decrease transplant-related mortality, alloSCT continues to be used rarely in elderly MDS. There is paucity of data regarding outcomes of RIC alloSCT in elderly MDS patients, especially in direct comparison with azanucleosides. In this paper, the authors discuss the recent Markov decision analysis by Koreth et al. in which investigators demonstrated superior survival of patients with HR-MDS aged 60-70 years who underwent RIC alloSCT in comparison with those who were treated with azanucleosides.

  16. Treatment-related Myelodysplastic Syndrome in a Child With Acute Myeloid Leukemia and TPMT Heterozygosity

    DEFF Research Database (Denmark)

    Stensman, Lars M; Kjeldsen, Eigil; Nersting, Jacob

    2015-01-01

    INTRODUCTION: We describe a patient diagnosed with acute myeloid leukemia (AML) and low activity of thiopurine methyltransferase (TPMT) who developed secondary myelodysplastic syndrome after treatment. OBSERVATION: A 10-year-old boy presented with AML-M2 with t(8;21)(q22;q22) and genotyping...

  17. Oxidative DNA damage in bone marrow cells of patients with low-risk myelodysplastic syndrome

    Czech Academy of Sciences Publication Activity Database

    Novotná, Božena; Bagryantseva, Yana; Šišková, M.; Neuwirtová, R.

    2009-01-01

    Roč. 33, č. 2 (2009), s. 340-343 ISSN 0145-2126 R&D Projects: GA MZd NR8265 Institutional research plan: CEZ:AV0Z50390512 Keywords : Myelodysplastic syndrome * Refractory anemia * Oxidative DNA damage Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.358, year: 2009

  18. New recurrent deletions in the PPARgamma and TP53 genes are associated with childhood myelodysplastic syndrome

    DEFF Research Database (Denmark)

    Silveira, Cássia G T; Oliveira, Fábio M; Valera, Elvis T

    2009-01-01

    Myelodysplastic syndrome (MDS) is a rare hematological malignancy in children. It was performed FISH analysis in 19 pediatric MDS patients to investigate deletions involving the PPARgamma and TP53 genes. Significant losses in the PPARgamma gene and deletions in the tumor suppressor gene TP53 were...

  19. Dynamic alterations of bone marrow cytokine landscape of myelodysplastic syndromes patients treated with 5-azacytidine

    Czech Academy of Sciences Publication Activity Database

    Moudrá, Alena; Hubáčková, Soňa; Machalová, Veronika; Vančurová, Markéta; Bartek, Jiří; Reiniš, Milan; Hodný, Zdeněk; Jonasova, A.

    2016-01-01

    Roč. 5, č. 10 (2016), č. článku e1183860. ISSN 2162-402X R&D Projects: GA MZd NT14174 Institutional support: RVO:68378050 Keywords : 5-azacyatidine * bone marrow plasma * cytokines * DNA damage * inflammation * myelodysplastic syndromes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.719, year: 2016

  20. The second international congress on myeloproliferative and myelodysplastic syndromes.

    Science.gov (United States)

    Silver, R T; Bennett, J M; Deininger, M; Feldman, E; Rafii, S; Silverstein, R L; Solberg, L A; Spivak, J L

    2004-09-01

    This meeting was convened by Richard T. Silver, M.D. and co-chaired by Jerry L. Spivak, M.D. It was held from 16 to 18 October 2003 in New York City, New York, USA. Thirty-nine invited speakers from nine different countries participated in the conference. There were more than 350 attendees. There were formal presentations and discussions on biology, clinical aspects, and management of patients with these diverse bone marrow stem cell disorders linked by a variable progression to acute myeloid leukemia. Of considerable interest, a clinical symposium exclusively for patients was held the day preceding the meeting at which John Bennett, Tiziano Barbui, Richard Silver, Jerry Spivak, and Ayalew Tefferi spoke on various topics pertaining to these diseases. This proved to be highly informative to the patients who reported that they enjoyed the program immensely. This was sponsored by the Cancer Research & Treatment Fund, Inc. Representatives of the Myelodysplasia Foundation were also present. This meeting report provides a summary of five different sections prepared by one or more of the session chairs. The keynote address was given by Shahin Rafii (Cornell Medical Center). Most appropriately, this talk focused on the expression and activation of angiogenic factors which play a crucial role in the progression of both myeloproliferative disorders and myelodysplastic syndromes (MDS). Among the known factors, vascular endothelial growth tyrosine kinase receptors (VEGF-R1, R2, and R3) support proliferation, survival, and mobility. Rafii's team has demonstrated that these receptors are expressed on subsets of primary hematopoietic cells as well as leukemic cells. Some leukemic cells express both VEGF-A and VEGF-R2, resulting in the generation of an autocrine loop that supports survival and within the osteoblastic zone translocating these cells to the vascular enriched niche for receipt of molecular instructions required for proliferation and differentiation. A pathologic

  1. Risk stratification in myelodysplastic syndromes: is there a role for gene expression profiling?

    Science.gov (United States)

    Zeidan, Amer M; Prebet, Thomas; Saad Aldin, Ehab; Gore, Steven David

    2014-04-01

    Evaluation of: Pellagatti A, Benner A, Mills KI et al. Identification of gene expression-based prognostic markers in the hematopoietic stem cells of patients with myelodysplastic syndromes. J. Clin. Oncol. 31(28), 3557-3564 (2013). Patients with myelodysplastic syndromes (MDS) exhibit wide heterogeneity in clinical outcomes making accurate risk-stratification an integral part of the risk-adaptive management paradigm. Current prognostic schemes for MDS rely on clinicopathological parameters. Despite the increasing knowledge of the genetic landscape of MDS and the prognostic impact of many newly discovered molecular aberrations, none to date has been incorporated formally into the major risk models. Efforts are ongoing to use data generated from genome-wide high-throughput techniques to improve the 'individualized' outcome prediction for patients. We here discuss an important paper in which gene expression profiling (GEP) technology was applied to marrow CD34(+) cells from 125 MDS patients to generate and validate a standardized GEP-based prognostic signature.

  2. Precision Medicine in Myelodysplastic Syndromes and Leukemias: Lessons from Sequential Mutations.

    Science.gov (United States)

    Nazha, Aziz; Sekeres, Mikkael A

    2017-01-14

    Precision medicine can be simply defined as the identification of personalized treatment that matches patient-specific clinical and genomic characteristics. Since the completion of the Human Genome Project in 2003, significant advances have been made in our understanding of the genetic makeup of diseases, especially cancers. The identification of somatic mutations that can drive cancer has led to the development of therapies that specifically target the abnormal proteins derived from these mutations. This has led to a paradigm shift in our treatment methodology. Although some success has been achieved in targeting some genetic abnormalities, several challenges and limitations exist when applying precision-medicine concepts in leukemia and myelodysplastic syndromes. We review the current understanding of genomics in myelodysplastic syndromes (MDS) and leukemias and the limitations of precision-medicine concepts in MDS.

  3. Usefulness of spinal magnetic resonance imaging in patients with myelodysplastic syndromes

    International Nuclear Information System (INIS)

    Kwiatkowska-Pamuła, Anna; Ziółko, Ewa; Muc-Wierzgoń, Małgorzata; Nowakowska-Zajdel, Ewa; Podwińska, Ewa; Adamczyk, Tomasz

    2013-01-01

    Myelodysplastic syndrome is a rare, chronic hematological disease characterized by heterogeneous clinical presentations. Subtypes of myelodysplastic syndrome are characterized by different survival times and ability to transform into acute myeloid leukemia. The objective of the study included the assessment of the relationship between the images obtained by magnetic resonance scans of lumbar spine and the clinical symptoms of the disease in patients diagnosed with myelodysplastic syndrome, as well as the assessment of the correlation of the images with the phase of transformation into acute myeloid leukemia. The study-related tests were carried out in Specialist Hospital No. 1 in Bytom between 2006 and 2011 and involved 53 patients aged 55÷77, divided into groups according to the diagnosed subtype of myelodysplastic syndrome. The study also included the prognosis of overall survival and time to transformation into AML on the basis of valid classifications. The spinal magnetic resonance scans were obtained from medical documentation. The analysis included images obtained using T1- and T2-weighted sequences in sagittal, transverse and frontal planes in all patients, images obtained using the STIR sequence from 21 patients as well as 40 images obtained after contrast administration. The statistical analysis of the results was carried out using STATISTICA software. The obtained results demonstrated that the magnetic resonance scans revealed statistically significant changes in the images of bone marrow in vertebral body scans; with a decrease in the intensity of MRI signals correlated with the RAEB subtype, particularly with transformation into acute myeloid leukemia as well as with the high IPSS risk score with regard to the time of survival and transformation into acute myeloid leukemia. The research-related test results indicate the importance of magnetic resonance imaging in diagnostics and the assessment of the disease dynamics

  4. Rescue of TET2 Haploinsufficiency in Myelodysplastic Syndrome Patients Using Turbo Cosubstrate

    Science.gov (United States)

    2017-07-01

    prevalent in a number of myeloid malignancies such as MDS-myeloproliferative neoplasms (MDS-MPN) and acute myeloid leukemia derived from MDS and MDS...Myelodysplastic syndromes (MDS), MDS-myeloproliferative neoplasms (MDS-MPN), Acute myeloid leukemia (AML), 5-methylcytosine (5mC), Mutation...normal initially, with age, develop diverse myeloid malignancies similar to humans. The objective in this project is to develop effective strategies

  5. Outcome of patients treated for myelodysplastic syndromes with 5q deletion after failure of lenalidomide therapy

    OpenAIRE

    Prebet, Thomas; Cluzeau, Thomas; Park, Sophie; Sekeres, Mikkael A.; Germing, Ulrich; Ades, Lionel; Platzbecker, Uwe; Gotze, Katharina; Vey, Norbert; Oliva, Esther; Sugrue, Mary M.; Bally, Cecile; Kelaidi, Charikleia; Al Ali, Najla; Fenaux, Pierre

    2017-01-01

    While lenalidomide (LEN) is the standard of care for the lower-risk myelodysplastic syndromes (MDS) patients with deletion 5q, 35% will not respond to or do not tolerate the drug. Moreover, most of the patients will lose their response after a few years. Defining the outcome of patients with LEN failure and determining the impact of subsequent therapies is therefore important to develop alternative strategies. Based on an international collaboration, we were able to compile a total of 392 pat...

  6. Outcome of patients treated for myelodysplastic syndromes without deletion 5q after failure of lenalidomide therapy

    OpenAIRE

    Prebet, Thomas; Toma, Andrea; Cluzeau, Thomas; Sekeres, Mikkael A.; Vey, Norbert; Park, Sophie; Al Ali, Najla; Sugrue, Marie M.; Komrokji, Rami; Fenaux, Pierre; Gore, Steven D.

    2017-01-01

    Anemia is a key survival prognostic factor in lower-risk myelodysplastic syndromes (MDS). Lenalidomide (LEN) can correct anemia in 25% of MDS patients without deletion 5q (del5q). As this therapy will inevitably fail, understanding the outcome of these patients will facilitate development of subsequent treatment strategies. To answer this question, an international retrospective study focused on LEN-treated lower-risk, non-del5q, MDS patients was performed. We analyzed the overall survival af...

  7. First report of anti-TIF1γ dermatomyositis in a patient with myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    B. Palterer

    2017-08-01

    Full Text Available Inflammatory myopathies as para-neoplastic phenomena were first described by Sterz in 1916. Recently, myositis specific autoantibodies were described in cancer-associated myositis. Anti-transcription intermediary factor 1 gamma (anti-TIF1γ antibodies have been found in both young adults affected by juvenile dermatomyositis and in elderly patients with cancer-associated myositis. In this regard, we report herein the first case of anti-TIF1γ dermatomyositis secondary to a myelodysplastic syndrome.

  8. Cost of transfusion-dependent myelodysplastic syndrome (MDS) from a German payer?s perspective

    OpenAIRE

    2010-01-01

    Abstract No curative treatment exists for patients with myelodysplastic syndrome (MDS) besides allogeneic stem cell transplantation. Hence, palliative treatment is provided for a life time accruing high health care cost. As no study in cost of MDS exists in Germany, the objective of this study was to assess and analyze costs of transfusion-dependent low/intermediate-1-risk MDS in Germany from a payers? perspective. From seven centers, 116 low/intermediate-1-risk transfusion-depende...

  9. SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

    Science.gov (United States)

    2013-01-10

    Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  10. Reproducibility of the World Health Organization 2008 criteria for myelodysplastic syndromes.

    Science.gov (United States)

    Senent, Leonor; Arenillas, Leonor; Luño, Elisa; Ruiz, Juan C; Sanz, Guillermo; Florensa, Lourdes

    2013-04-01

    The reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is uncertain and its assessment was the major aim of this study. The different peripheral blood and bone marrow variables required for an adequate morphological classification were blindly evaluated by four cytomorphologists in samples from 50 patients with myelodysplastic syndromes. The degree of agreement among observers was calculated using intraclass correlation coefficient and the generalized kappa statistic for multiple raters. The degree of agreement for the percentages of blasts in bone marrow and peripheral blood, ring sideroblasts in bone marrow, and erythroid, granulocytic and megakaryocytic dysplastic cells was strong (P<0.001 in all instances). After stratifying the percentages according to the categories required for the assignment of World Health Organization subtypes, the degree of agreement was not statistically significant for cases with 5-9% blasts in bone marrow (P=0.07), 0.1-1% blasts in peripheral blood (P=0.47), or percentage of erythroid dysplastic cells (P=0.49). Finally, the interobserver concordance for World Health Organization-defined subtypes showed a moderate overall agreement (P<0.001), the reproducibility being lower for cases with refractory anemia with excess of blasts type 1 (P=0.05) and refractory anemia with ring sideroblasts (P=0.09). In conclusion, the reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is acceptable but the defining criteria for blast cells and features of erythroid dysplasia need to be refined.

  11. Recombinant EphB4-HSA Fusion Protein and Azacitidine or Decitabine for Relapsed or Refractory Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia Patients Previously Treated With a Hypomethylating Agent

    Science.gov (United States)

    2017-08-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Recurrent Adult Acute Myeloid Leukemia

  12. Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7.

    Science.gov (United States)

    Pastor, Victor B; Sahoo, Sushree S; Boklan, Jessica; Schwabe, Georg C; Saribeyoglu, Ebru; Strahm, Brigitte; Lebrecht, Dirk; Voss, Matthias; Bryceson, Yenan T; Erlacher, Miriam; Ehninger, Gerhard; Niewisch, Marena; Schlegelberger, Brigitte; Baumann, Irith; Achermann, John C; Shimamura, Akiko; Hochrein, Jochen; Tedgård, Ulf; Nilsson, Lars; Hasle, Henrik; Boerries, Melanie; Busch, Hauke; Niemeyer, Charlotte M; Wlodarski, Marcin W

    2018-03-01

    Familial myelodysplastic syndromes arise from haploinsufficiency of genes involved in hematopoiesis and are primarily associated with early-onset disease. Here we describe a familial syndrome in seven patients from four unrelated pedigrees presenting with myelodysplastic syndrome and loss of chromosome 7/7q. Their median age at diagnosis was 2.1 years (range, 1-42). All patients presented with thrombocytopenia with or without additional cytopenias and a hypocellular marrow without an increase of blasts. Genomic studies identified constitutional mutations (p.H880Q, p.R986H, p.R986C and p.V1512M) in the SAMD9L gene on 7q21, with decreased allele frequency in hematopoiesis. The non-random loss of mutated SAMD9L alleles was attained via monosomy 7, deletion 7q, UPD7q, or acquired truncating SAMD9L variants p.R1188X and p.S1317RfsX21. Incomplete penetrance was noted in 30% (3/10) of mutation carriers. Long-term observation revealed divergent outcomes with either progression to leukemia and/or accumulation of driver mutations (n=2), persistent monosomy 7 (n=4), and transient monosomy 7 followed by spontaneous recovery with SAMD9L -wildtype UPD7q (n=2). Dysmorphic features or neurological symptoms were absent in our patients, pointing to the notion that myelodysplasia with monosomy 7 can be a sole manifestation of SAMD9L disease. Collectively, our results define a new subtype of familial myelodysplastic syndrome and provide an explanation for the phenomenon of transient monosomy 7. Registered at: www.clinicaltrials.gov; #NCT00047268 . Copyright© 2018 Ferrata Storti Foundation.

  13. Inversion of chromosome 7q22 and q36 as a sole abnormality presenting in myelodysplastic syndrome: a case report.

    Science.gov (United States)

    Kaneko, Hiroto; Shimura, Kazuho; Kuwahara, Saeko; Ohshiro, Muneo; Tsutsumi, Yasuhiko; Iwai, Toshiki; Horiike, Shigeo; Yokota, Shouhei; Ohkawara, Yasuo; Taniwaki, Masafumi

    2014-08-05

    Deletions of chromosome 7 are often detected in myelodysplastic syndrome. The most commonly deleted segments are clustered at band 7q22. A critical gene is therefore suggested to be located in this region. We report a patient with myelodysplastic syndrome whose marrow cells carried an inversion of 7q22 and q36 as a sole karyotypic abnormality. How this extremely rare chromosomal aberration contributes to the pathogenesis of myelodysplastic syndrome should be clarified by accumulating clinical data of such cases. A 74-year-old Japanese man presented with pancytopenia incidentally detected by routine medical check-up. His complete blood cell counts revealed that his white blood cells had decreased to 2100/mm3, neutrophils 940/mm3, red blood cells 320×104/mm3, hemoglobin 11.1g/dL, hematocrit 33.1%, and platelets 12.6×104/mm3. Bone marrow examination showed normal cellularity with nucleated cells of 9.4×104/mm3. The proportion of blasts was 4%. A morphological examination showed only basophilic stippling of erythroblasts which was seen as dysplasia. According to World Health Organization classification, the diagnosis was myelodysplastic syndrome-u. Karyotypic analysis showed 46,XY,inv(7)(q22q36) in all of 20 metaphases examined. Additional analysis revealed the karyotype of his lymphocytes was 46,XY. He is asymptomatic and cytopenia has slowly progressed. To the best of our knowledge, this karyotype from a clinical sample of de novo malignancies has never been documented although the identical karyotype from secondary myelodysplastic syndrome was reported. Despite the extremely low frequency, inversion of 7q22 appears to play a crucial role for myelodysplastic syndrome in this patient.

  14. [Characteristic and function of peripheral blood mononuclear cells-induced macrophages in patients with myelodysplastic syndrome].

    Science.gov (United States)

    Han, Y; Wang, H Q; Fu, R; Qu, W; Ruan, E B; Wang, X M; Wang, G J; Wu, Y H; Liu, H; Song, J; Guan, J; Xing, L M; Li, L J; Jiang, H J; Liu, H; Wang, Y H; Liu, C Y; Zhang, W; Shao, Z H

    2017-08-14

    Objective: To explore characteristic and function of peripheral blood mononuclear cells (PBMNC) -induced macrophages in patients with myelodysplastic syndrome (MDS) to couple with its progression. Methods: A total of 24 MDS patients (11 low-risk patients and 13 high-risk group patients) referred to Department of Hematology of Tianjin Medical University General Hospital and normal controls were enrolled from September 2014 to December 2015. PBMNC was stimulated with GM-CSF to transform to macrophages. The morphology of macrophages was observed by microscope. The quantity of macrophages, CD206 and SIRPα on surface of macrophages were detected by flow cytometry. The phagocytic function of macrophages was analyzed by fluorescence microscopy and flow cytometry. Results: The morphology of macrophages from MDS patients was abnormal. The percentage of transformed macrophages was (5.17±3.47) % in patients with MDS, which was lower than that in controls significantly[ (66.18±13.43) %, t =3.529, P =0.001]. The expression of CD206 on macrophages from MDS patients was significantly lower than that of controls[ (9.73±2.59) % vs (51.15±10.82) %, t =4.551, P patients was significantly lower than that of controls [ (0.51±0.09) % vs (0.77±0.06) %, t =2.102, P =0.043]. The phagocytic index and the percentage of phagocytic of macrophages from MDS patients were significantly lower than those of macrophages from normal controls[0.45±0.08 vs 0.92±0.07, t =-6.253, P =0.008; (23.69±3.22) % vs (42.75±2.13) %, t =-6.982, P =0.006 respectively]by flow cytometry. The phagocytic index of MDS patients was significantly lower than that of controls (0.24±0.04 vs 0.48±0.96, t =3.464, P =0.001) by fluorescence microscopy. Conclusion: The quantity, recognization receptors and phagocytosis of PBMNC-induced macrophages decreased in MDS patients.

  15. Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes

    DEFF Research Database (Denmark)

    Musto, Pellegrino; Lanza, Francesco; Balleari, Enrico

    2005-01-01

    Thirty-seven anaemic subjects with low-to-intermediate risk myelodysplastic syndrome (MDS) received the highly glycosylated, long-acting erythropoiesis-stimulating molecule darbepoetin-alpha (DPO) at the single, weekly dose of 150 microg s.c. for at least 12 weeks. Fifteen patients (40.5%) achieved......, no excess of blasts and hypoplastic bone marrow. This study suggests that DPO, at the dose and schedule used, can be safely given in low-intermediate risk MDS and may be effective in a significant proportion of these patients....

  16. Simultaneous Presentation of Giant Cell Arteritis and Myelodysplastic Syndrome in an Elderly Japanese Man.

    Science.gov (United States)

    Senjo, Hajime; Higuchi, Takakazu; Morimoto, Masaya; Koyamada, Ryosuke; Yanaoka, Chisun; Okada, Sadamu

    2018-05-18

    An 81-year-old Japanese man presented with constitutional symptoms and anemia and was diagnosed with giant cell arteritis (GCA) and myelodysplastic syndrome (MDS) simultaneously. His symptoms and anemia improved promptly with steroids; however, the MDS rapidly progressed to overt leukemia. While MDS patients are at an increased risk of autoimmune diseases, an association with GCA has rarely been reported. This case illustrates the importance of considering GCA as a cause of anemia in elderly patients if MDS is already diagnosed, even in countries where the prevalence of GCA is very low. The simultaneous development of GCA and MDS suggests a common pathogenetic link between these two diseases.

  17. Acquired Elliptocytosis as a Manifestation of Myelodysplastic Syndrome with Ring Sideroblasts and Multilineage Dysplasia

    Directory of Open Access Journals (Sweden)

    Jacob D. Kjelland

    2017-01-01

    Full Text Available Acquired elliptocytosis is a known but rarely described abnormality in the myelodysplastic syndromes (MDS. Here we report the case of an elderly male who was admitted to the hospital with chest pain, dyspnea, and fatigue and was found to be anemic with an elliptocytosis that had only recently been noted on peripheral smears of his blood. After bone marrow biopsy he was diagnosed with MDS with ring sideroblasts and multilineage dysplasia and acquired elliptocytosis. Here we report a rare case of acquired elliptocytosis cooccurring with MDS with ring sideroblasts and multilineage dysplasia.

  18. Impact of azacitidine on red blood cell alloimmunisation in myelodysplastic syndrome.

    Science.gov (United States)

    Ortiz, Sebastián; Orero, Maria T; Javier, Karla; Villegas, Carolina; Luna, Irene; Pérez, Pedro; Roig, Mónica; López, María; Costa, Sofía; Carbonell, Félix; Collado, Rosa; Ivars, David; Linares, Mariano

    2017-09-01

    The incidence of alloimmunisation in myelodysplastic syndromes (MDS) during the era of supportive treatment ranges from 9 to 56%. However, it is unknown if the widespread use of hypomethylating agents has changed the risk of immunisation. The aim of this study is to evaluate the impact of azacitidine (AZA) therapy on red blood cell (RBC) alloimmunisation in transfused patients with MDS, myelodysplastic syndromes/myeloproliferative syndromes (MDS/MPS) and secondary acute myeloid leukaemia (AML). We have analysed retrospectively all patients with MDS, MDS/MPS and secondary AML from MDS, who received their first transfusion in our hospital between January 1995 and December 2014. We have assessed the impact of age, sex, RBC and platelets units transfused, and AZA treatment on developing alloantibodies. In our study, the number of RBC units transfused increased the risk of developing alloantibodies. However aging and the treatment with AZA were associated with a lower rate of alloimmunisation. Patients with MDS, MDS/MPS and secondary AML who received treatment with AZA developed RBC antibodies at a lower rate than control group. We suggest that aging and immunosuppression due to AZA therapy could develop an immunological tolerance with a weak response to allotransfusions.

  19. Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.

    Science.gov (United States)

    Arenillas, Leonor; Mallo, Mar; Ramos, Fernando; Guinta, Kathryn; Barragán, Eva; Lumbreras, Eva; Larráyoz, María-José; De Paz, Raquel; Tormo, Mar; Abáigar, María; Pedro, Carme; Cervera, José; Such, Esperanza; José Calasanz, María; Díez-Campelo, María; Sanz, Guillermo F; Hernández, Jesús María; Luño, Elisa; Saumell, Sílvia; Maciejewski, Jaroslaw; Florensa, Lourdes; Solé, Francesc

    2013-12-01

    Cytogenetic aberrations identified by metaphase cytogenetics (MC) have diagnostic, prognostic, and therapeutic implications in myelodysplastic syndromes (MDS). However, in some MDS patients MC study is unsuccesful. Single nucleotide polymorphism array (SNP-A) based karyotyping could be helpful in these cases. We performed SNP-A in 62 samples from bone marrow or peripheral blood of primary MDS with an unsuccessful MC study. SNP-A analysis enabled the detection of aberrations in 31 (50%) patients. We used the copy number alteration information to apply the International Prognostic Scoring System (IPSS) and we observed differences in survival between the low/intermediate-1 and intermediate-2/high risk patients. We also saw differences in survival between very low/low/intermediate and the high/very high patients when we applied the revised IPSS (IPSS-R). In conclusion, SNP-A can be used successfully in PB samples and the identification of CNA by SNP-A improve the diagnostic and prognostic evaluation of this group of MDS patients. Copyright © 2013 Wiley Periodicals, Inc.

  20. PAS positivity of erythroid precursor cells is associated with a poor prognosis in newly diagnosed myelodysplastic syndrome patients.

    Science.gov (United States)

    Masuda, Kenta; Shiga, Shuichi; Kawabata, Hiroshi; Takaori-Kondo, Akifumi; Ichiyama, Satoshi; Kamikubo, Yasuhiko

    2018-07-01

    Myelodysplastic syndrome (MDS) is a group of clonal stem cell disorders characterized by hematopoietic insufficiency. The accurate risk stratification of patients with MDS is essential for selection of appropriate therapies. We herein conducted a retrospective cohort study to examine the prognostic value of periodic acid-Schiff (PAS) reaction-positive erythroblasts in MDS patients. We examined the PAS positivity of the bone marrow erythroblasts of 144 patients newly diagnosed with MDS; 26 (18.1%) of them had PAS-positive erythroblasts, whereas 118 (81.9%) did not. The PAS-positive group showed significantly poorer karyotypes as defined in the revised International Prognostic Scoring System (IPSS-R) and higher scores in age-adjusted IPSS-R (IPSS-RA) than the PAS-negative group. Overall survival (OS) and leukemia-free survival (LFS) were also significantly shorter in the PAS-positive group than in the PAS-negative group. Similar results were obtained when only high- and very high risk groups were analyzed using IPSS-RA. This retrospective study suggested that the PAS positivity of erythroblasts is an additional prognostic factor combined with other risk scores for OS and LFS in MDS, and our results may contribute to improved clinical decision-making and rapid risk stratification.

  1. Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study

    DEFF Research Database (Denmark)

    Gattermann, Norbert; Finelli, Carlo; Porta, Matteo Della

    2010-01-01

    The prospective 1-year EPIC study enrolled 341 patients with myelodysplastic syndromes (MDS); although baseline iron burden was >2500ng/mL, approximately 50% were chelation-naïve. Overall median serum ferritin decreased significantly at 1 year (p=0.002). Decreases occurred irrespective of whether...

  2. Phenotypic characterization of aberrant stem and progenitor cell populations in myelodysplastic syndromes.

    Science.gov (United States)

    Ostendorf, Benjamin N; Flenner, Eva; Flörcken, Anne; Westermann, Jörg

    2018-01-01

    Recent reports have revealed myelodysplastic syndromes (MDS) to arise from cancer stem cells phenotypically similar to physiological hematopoietic stem cells. Myelodysplastic hematopoiesis maintains a hierarchical organization, but the proportion of several hematopoietic compartments is skewed and multiple surface markers are aberrantly expressed. These aberrant antigen expression patterns hold diagnostic and therapeutic promise. However, eradication of MDS requires targeting of early myelodysplasia propagating stem cells. This warrants an exact assessment of the differentiation stage at which aberrant expression occurs in transformed hematopoiesis. Here, we report results on the prospective and extensive dissection of the hematopoietic hierarchy in 20 patients with either low-risk MDS or MDS with excess blasts and compare it to hematopoiesis in patients with non-malignancy-associated cytopenia or B cell lymphoma without bone marrow infiltration. We found patients with MDS with excess blasts to exhibit characteristic expansions of specific immature progenitor compartments. We also identified the aberrant expression of several markers including ALDH, CLL-1, CD44, and CD47 to be specific features of hematopoiesis in MDS with excess blasts. We show that amongst these, aberrant CLL-1 expression manifested at the early uncommitted hematopoietic stem cell level, suggesting a potential role as a therapeutic target.

  3. Phenotypic characterization of aberrant stem and progenitor cell populations in myelodysplastic syndromes.

    Directory of Open Access Journals (Sweden)

    Benjamin N Ostendorf

    Full Text Available Recent reports have revealed myelodysplastic syndromes (MDS to arise from cancer stem cells phenotypically similar to physiological hematopoietic stem cells. Myelodysplastic hematopoiesis maintains a hierarchical organization, but the proportion of several hematopoietic compartments is skewed and multiple surface markers are aberrantly expressed. These aberrant antigen expression patterns hold diagnostic and therapeutic promise. However, eradication of MDS requires targeting of early myelodysplasia propagating stem cells. This warrants an exact assessment of the differentiation stage at which aberrant expression occurs in transformed hematopoiesis. Here, we report results on the prospective and extensive dissection of the hematopoietic hierarchy in 20 patients with either low-risk MDS or MDS with excess blasts and compare it to hematopoiesis in patients with non-malignancy-associated cytopenia or B cell lymphoma without bone marrow infiltration. We found patients with MDS with excess blasts to exhibit characteristic expansions of specific immature progenitor compartments. We also identified the aberrant expression of several markers including ALDH, CLL-1, CD44, and CD47 to be specific features of hematopoiesis in MDS with excess blasts. We show that amongst these, aberrant CLL-1 expression manifested at the early uncommitted hematopoietic stem cell level, suggesting a potential role as a therapeutic target.

  4. The Role of mDia1 in the Aberrant Innate Immune Signaling in del(5q) Myelodysplastic Syndromes

    Science.gov (United States)

    2017-10-01

    chromosome 5q (del(5q)). There are two common deleted regions (CDRs) identified on 5q: a distal locus that is often deleted in 5q- syndrome with good ...chromosome 5q being the most common . Our recently published work demonstrated that loss of mDia1, a protein with its encoding genes located at chromosome 5...is the most common cytogenetic abnormality in patients with myelodysplastic syndromes (MDS). We discovered in 2014 that CD14 was aberrantly

  5. Tumor suppressor microRNAs are downregulated in myelodysplastic syndrome with spliceosome mutations

    DEFF Research Database (Denmark)

    Aslan, Derya; Garde, Christian; Nygaard, Mette Katrine

    2016-01-01

    Spliceosome mutations are frequently observed in patients with myelodysplastic syndromes (MDS). However, it is largely unknown how these mutations contribute to the disease. MicroRNAs (miRNAs) are small noncoding RNAs, which have been implicated in most human cancers due to their role in post...... the most downregulated miRNAs were several tumor-suppressor miRNAs, including several let-7 family members, miR-423, and miR-103a. Finally, we observed that the predicted targets of the most downregulated miRNAs were involved in apoptosis, hematopoiesis, and acute myeloid leukemia among other cancer......- and metabolic pathways. Our data indicate that spliceosome mutations may play an important role in MDS pathophysiology by affecting the expression of tumor suppressor miRNA genes involved in the development and progression of MDS....

  6. Two cases of therapy-related myelodysplastic syndrome after concurrent oral cancer chemoradiotherapy

    International Nuclear Information System (INIS)

    Doi, Katsuyuki; Asano, Takanori; Kinoshita, Takashi

    2010-01-01

    Therapy-related myelodysplastic syndrome (t-MDS) and therapy-related leukemia (TRL) are reported increasingly often, and we report two cases of T-MDS after concurrent chemoradiotherapy (CCRT) with oral cancer. Patients underwent CCRT with cisplatin (CDDP) or carboplatin (CBDCA). The interval between primary CCRT and t-MDS was 11 months in 1 case and 14 years in the other. Chromosomal analysis indicated abnormal karyotypes. Platinum has a relatively lower t-MDS risk than alkylating agents or topoisomerase II inhibitors, but our experience supports concurrent use of radiotherapy with platinum affects the risk of t-MDS. If pancytopenia is detected after CCRT, bone marrow and cytogenetic examinations should be conducted to rule out t-MDS. (author)

  7. Characterization and prognostic implication of 17 chromosome abnormalities in myelodysplastic syndrome.

    Science.gov (United States)

    Sánchez-Castro, Judit; Marco-Betés, Víctor; Gómez-Arbonés, Xavier; Arenillas, Leonor; Valcarcel, David; Vallespí, Teresa; Costa, Dolors; Nomdedeu, Benet; Jimenez, María José; Granada, Isabel; Grau, Javier; Ardanaz, María T; de la Serna, Javier; Carbonell, Félix; Cervera, José; Sierra, Adriana; Luño, Elisa; Cervero, Carlos J; Falantes, José; Calasanz, María J; González-Porrás, José R; Bailén, Alicia; Amigo, M Luz; Sanz, Guillermo; Solé, Francesc

    2013-07-01

    The prognosis of chromosome 17 (chr17) abnormalities in patients with primary myelodysplastic syndrome (MDS) remains unclear. The revised International Prognostic Scoring System (IPSS-R) includes these abnormalities within the intermediate cytogenetic risk group. This study assessed the impact on overall survival (OS) and risk of acute myeloid leukemia transformation (AMLt) of chr17 abnormalities in 88 patients with primary MDS. We have compared this group with 1346 patients with primary MDS and abnormal karyotype without chr17 involved. The alterations of chr17 should be considered within group of poor prognosis. The different types of alterations of chromosome 17 behave different prognosis. The study confirms the intermediate prognostic impact of the i(17q), as stated in IPSS-R. The results of the study, however, provide valuable new information on the prognostic impact of alterations of chromosome 17 in complex karyotypes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Proposal for refining the definition of dysgranulopoiesis in acute myeloid leukemia and myelodysplastic syndromes.

    Science.gov (United States)

    Goasguen, Jean E; Bennett, John M; Bain, Barbara J; Brunning, Richard; Vallespi, Maria-Teresa; Tomonaga, Masao; Zini, Gina; Renault, Alain

    2014-04-01

    Studies of morphology of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) refer to the definitions produced by the French-American-British (FAB) group and by the World Health Organization expert group. To clarify some points regarding the dysgranulopoiesis that are still unclear we analyzed a series of 98 neutrophils from MDS patients with regard to granularity, nuclear segmentation, the appearance of the chromatin, the presence of giant neutrophils, and the presence of nuclear chromatin extensions. We found that cells with at least 2/3 reduction of the content of granules, Pelger-like neutrophils, dysplastic non-Pelger cells, neutrophils with abnormal clumping of the chromatin, and macropolycytes could be recognized as dysplastic and included in the 10% count recommended by these two classifications. In addition, we suggest that neutrophils with more than 4 nuclear projections could be recognized as a relevant dysplastic feature. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. 657del5 mutation of the NBS1 gene in myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    Bunjevacki Vera

    2014-01-01

    Full Text Available Myelodysplastic syndromes (MDS are clonal hematologic stem cell disorders with an as yet unknown molecular pathology. Genetic instability has been proposed as a cause of MDS. Mutations in the NBS1 gene, whose product nibrin (p95 is involved in DNA damage repair and cell-cycle control, might be associated with an elevated predisposition to the development of MDS. The aim of the study was to examine truncating 5 bp deletion (657del5, the most frequent NBS1 gene mutation in Slavic populations, in MDS patients. Among 71 MDS patients, we found one case that was heterozygous for the NBS1 657del5 mutation. To the best of our knowledge, this is the first report of a NBS1 mutation in MDS. [Projekat Ministarstva nauke Republike Srbije, br. 175091

  10. Prognostic factors in de novo myelodysplastic syndrome in young and middle-aged people

    Directory of Open Access Journals (Sweden)

    Наталья Николаевна Климкович

    2015-01-01

    Full Text Available We spent multivariate analysis of clinical and laboratory parameters for the prediction of de-novo myelodysplastic syndromes (MDS patients aged 18-60 years. The results of clinical application of prognostic systems in MDS show that there is a large variability within individual risk groups, especially at low-risk MDS. So now hematologists conduct research aimed at identifying additional adverse risk MDS. This is done so that patients with low-risk MDS embodiments and unfavorable prognosis could benefit from early therapeutic intervention, and not only be clinician monitored until disease progression. We found that additional adverse risk factors for the development of MDS are the expression of CD95 in bone marrow ≤40 % and FLT3≥60 %. The expression level of CD95 in bone marrow cells≤40 % and FLT3≥60 % can be considered as a prognostic marker progression of MDS and time start specific therapy

  11. Impact of Nagasaki atomic bomb exposure on myelodysplastic syndrome patients who are treated with azacitidine.

    Science.gov (United States)

    Jo, Tatsuro; Horio, Kensuke; Shigematsu, Kazuto

    2015-05-01

    High-dose radiation exposure greatly increases the risk of myelodysplastic syndromes (MDS), however the clinical characteristics of MDS among atomic bomb survivors have not been thoroughly investigated to date. We designed this study to identify these characteristics. We retrospectively evaluated data from 13 atomic bomb survivors with MDS and 15 elderly patients with de novo MDS who were diagnosed between April 2011 and April 2013 at the Nagasaki Genbaku Hospital. All patients were treated with azacitidine (AZA; a hypomethylating agent) and overall survival rates were estimated. No clear difference was observed in the clinical response to AZA between the two groups. However, atomic bomb survivors had a survival disadvantage, independent of their karyotype. Minute genetic alterations caused by exposure to atomic radiation can adversely affect the response to AZA, even 66 years after the exposure. Further studies are required to clarify the mechanisms underlying this phenomenon. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Comparison of childhood myelodysplastic syndrome, AML FAB M6 or M7, CCG 2891: report from the Children's Oncology Group.

    Science.gov (United States)

    Barnard, Dorothy R; Alonzo, Todd A; Gerbing, Robert B; Lange, Beverly; Woods, William G

    2007-07-01

    Myelodysplastic syndromes (MDS), acute erythroleukemia (FAB M6), and acute megakaryocytic leukemia (FAB M7) have overlapping features. Children without Down syndrome or acute promyelocytic leukemia who were newly diagnosed with primary myelodysplastic syndrome or acute myeloid leukemia (AML) M6 or M7 were compared to children with de novo AML M0-M5. All children were entered on the Children's Cancer Group therapeutic research study CCG 2891. The presentation and outcomes of the 132 children diagnosed with MDS (60 children), AML FAB M6 (19 children), or AML FAB M7 (53 children) were similar. Children with AML FAB M7 were diagnosed at a significantly younger age (P = 0.001). Children with MDS, M6, or M7 had significantly lower white blood cell (WBC) counts (P = 0.001), lower peripheral blast counts (P M6 and AML M7 resemble MDS in presentation, poor induction success rates, and outcomes.

  13. Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country

    Directory of Open Access Journals (Sweden)

    E.D.R.P. Velloso

    2013-01-01

    Full Text Available Myelodysplastic syndromes (MDS and juvenile myelomonocytic leukemia (JMML are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED. We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome. Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

  14. Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country.

    Science.gov (United States)

    Velloso, E D R P; Chauffaille, M L; Peliçario, L M; Tanizawa, R S S; Toledo, S R C; Gaiolla, R D; Lopes, L F

    2013-01-01

    Myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED). We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome). Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

  15. Cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC in myelodysplastic syndrome (MDS

    Directory of Open Access Journals (Sweden)

    Myrna Candelaria-Hernández

    2017-06-01

    Full Text Available ABSTRACTIntroductionMyelodysplastic syndrome (MDS comprises a group of clonal hematological disorders, characterized by ineffective hematopoiesis and progressive bone marrow failure. It increases the risk of transformation to acute myeloid leukemia (AML. Therapeutic benefit should include overall survival increase (OS, hematological improvement, transfusion dependence and time to progression to AML decrease.ObjectiveAssess, from a Mexican health-care perspective, the cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC plus best supportive care (BSC for the treatment of adult patients with intermediate-2 and high-risk MDS, who are not eligible for hematopoietic stem-cell transplantation. We developed a cost-effectiveness survival analysis model of three stages: MDS, AML, and death. OS and costs are extrapolated beyond three-year time horizon. Discount rate of 5% was applied. To estimate the model cycle probability transition to mortality state, survival curves were constructed for each treatment arm using individual patient-level data from Study AZA-001. Unitary costs are from public price list, and profiles for the management of MDS and AML were collected separately using a structured questionnaire. Probabilistic sensitivity analyses (PSA were conducted by simultaneously sampling from estimated probability distributions of model parameters.ResultsOverall survival was projected to increase by 72.26 weeks with azacitidine. Incremental expected total costs for azacitidine compared to LDC was MXN$68,045. However, the cost of the drug therapy was lower with azacitidine. The incremental cost-effectiveness ratio (ICER for azacitidine compared to LDC was MXN$48,932 per life-year gained (LYG. PSA showed that azacitidine was a highly cost-effective option in 96.49% of the simulated cases in MXN$180,000/LYG willingness-to-pay.ConclusionsCompared with LDC, azacitidine represents a cost-effective treatment alternative in patients

  16. Meeting report: Vienna 2008 Workshop of the German–Austrian Working Group for Studying Prognostic Factors in Myelodysplastic Syndromes

    OpenAIRE

    Valent , Peter; Hofmann , Wolf-Karsten; Büsche , Guntram; Sotlar , Karl; Horny , Hans-Peter; Haase , Detlef; Haferlach , Torsten; Kern , Wolfgang; Bettelheim , Peter; Baumgartner , Christian; Sperr , Wolfgang R.; Nösslinger , Thomas; Wimazal , Friedrich; Giagounidis , Aristoteles A.; Lübbert , Michael

    2009-01-01

    Abstract Criteria, scoring systems, and treatment algorithms for myelodysplastic syndromes (MDS) have been updated repeatedly in recent years. This apparently results from increased awareness and early recognition of the disease, an increasing number of new diagnostic and prognostic markers and tools, and new therapeutic options that may change the course and thus prognosis in MDS. To address these challenges and to create useful new diagnostic and prognostic parameters and scores,...

  17. FOXP1 and TP63 involvement in the progression of myelodysplastic syndrome with 5q- and additional cytogenetic abnormalities

    International Nuclear Information System (INIS)

    L’Abbate, Alberto; Tagliafico, Enrico; Minoia, Carla; De Tullio, Giacoma; Guarini, Attilio; Testoni, Nicoletta; Agostinelli, Claudio; Storlazzi, Clelia Tiziana; Lo Cunsolo, Crocifissa; Macrì, Ettore; Iuzzolino, Paolo; Mecucci, Cristina; Doglioni, Claudio; Coco, Michelina; Muscarella, Lucia Anna; Salati, Simona

    2014-01-01

    The progression of low-risk del(5q) myelodysplastic syndrome to acute myeloid leukemia is increased when associated with mutations of TP53, or with additional chromosomal abnormalities. However, to date the prognostic impact and molecular consequences of these rearrangements were poorly investigated. Single additional alterations to del(5q) by balanced chromosome rearrangements were rarely found in myelodysplasia. In particular, balanced alterations involving TP63 and FOXP1 genes were never reported in the literature. Here we report on a 79-year woman with an aggressive form of myelodysplastic syndrome with del(5q), no TP53 mutation, and a novel complex rearrangement of chromosome 3 in bone marrow cells. Our results revealed that the FOXP1 and TP63 genes were both relocated along chromosome 3. Strikingly, immunohistochemistry analysis showed altered protein levels, disclosing that this rearrangement triggered the expression of FOXP1 and TP63 genes. FOXP1 was also found activated in other patients with myelodysplasia and acute myeloid leukemia, showing that it is an important, recurrent event. We document an apparent role of FOXP1 and TP63, up to now poorly documented, in the progression of MDS in our patient who is lacking mutations in the TP53 tumor suppressor gene normally associated with poor outcome in myelodysplastic syndrome with 5q-. Finally, our results may suggest a possible broader role of FOXP1 in the pathogenesis and progression of myelodysplasia and acute myeloid leukemia

  18. An Unexpected Innocent Complication Associated with Azacitidine Treatment of Myelodysplastic Syndrome: Erythema Annulare Centrifugum

    Directory of Open Access Journals (Sweden)

    Esra Turan Erkek

    2016-03-01

    Full Text Available Skin lesions accompanying hematological malignancies can be formed due to either direct tumor infiltration of the skin or indirect effects. Indirectly developing lesions may be a component of paraneoplastic syndrome. Erythema annulare centrifugum (EAC is considered to be a hypersensitivity reaction developed against various antigens associated with infections, drugs, and endocrine diseases. EAC, rarely seen in neoplastic diseases, has been reported in lymphoma, leukemia, histiocytosis, and prostate cancer. Here we report EAC in a patient using a hypomethylating agent, azacitidine. A 69-year-old female patient was admitted to our polyclinic with weakness and ecchymosis in her legs existing for 3 months. She was considered as having refractory anemia with excess blasts-2 according to myelodysplastic syndrome (MDS classification [1]. Because there was only hyperdiploidy in conventional cytogenetic examination, she was classified in group intermediate-2 of the International Prognostic Scoring System. She had a history of radical mastectomy and adjuvant chemoradiotherapy for breast cancer 3 years ago. She said that variously sized round and oval erythematous, itching, painless lesions had formed in the abdominal region on the 4th day of azacitidine usage (75 mg/m2/day, 7 days, s.c. (Figure 1 and 2. There were no concomitant complaints or physical examination findings except fatigue. After azacitidine was stopped, a skin biopsy was taken. In the biopsy, mild perivascular inflammatory infiltration accompanying vascular ectasia in the papillary dermis was detected. The possibility of paraneoplastic syndrome was excluded due to the disappearance of all lesions by 1 week after cessation of treatment. During the second course of azacitidine, the lesions reoccurred on the second day. Subsequently to the second course, the patient died of sepsis, which developed after pneumonia.

  19. Awareness and prevalence of metabolic syndrome among high-risk ...

    African Journals Online (AJOL)

    MetS) in high-risk individuals attending 30 internal medicine clinics in Amman, Jordan, and also to evaluate the various factors associated with increased risk of MetS among them. Methods: This retrospective cross-sectional study was carried out ...

  20. Significant association between polymorphism of the erythropoietin gene promoter and myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    O'Brien Susan

    2010-11-01

    Full Text Available Abstract Background Myelodysplastic syndrome (MDS may be induced by certain mutagenic environmental or chemotherapeutic toxins; however, the role of susceptibility genes remains unclear. The G/G genotype of the single-nucleotide polymorphism (SNP rs1617640 in the erythropoietin (EPO promoter has been shown to be associated with decreased EPO expression. We examined the association of rs1617640 genotype with MDS. Methods We genotyped the EPO rS1617640 SNP in 189 patients with MDS, 257 with acute myeloid leukemia (AML, 106 with acute lymphoblastic leukemia, 97 with chronic lymphocytic leukemia, 353 with chronic myeloid leukemia, and 95 healthy controls. Results The G/G genotype was significantly more common in MDS patients (47/187; 25.1% than in controls (6/95; 6.3% or in patients with other leukemias (101/813; 12.4% (all P P = 0.03. Time to neutrophils recovery after therapy was significantly longer in MDS patients with the G/G genotype (P = 0.02. Conclusions These findings suggest a strong association between the rs1617640 G/G genotype and MDS. Further studies are warranted to investigate the utility of screening for this marker in individuals exposed to environmental toxins or chemotherapy.

  1. Therapy related myelodysplastic syndrome: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Smita Sonawane

    2011-01-01

    Full Text Available Therapy related myeloid neoplasm is directly related to previous cytotoxic chemotherapy or radiation therapy. We present a 47-year-old lady who developed therapy related myelodysplastic syndrome (MDS 2.5 years after she received four cycles of chemotherapy and local radiation therapy for carcinoma breast. She presented with bicytopenia with trilineage dyspoiesis in the peripheral blood, bone marrow aspirate and biopsy. Fluorescent in-situ hybridization studies did not reveal any of the common abnormalities associated with MDS. A diagnosis of therapy related MDS was rendered. Different studies have shown that patients treated with alkylating agents and ionizing radiation present as MDS with a latent period of 3-10 years. Our patient developed MDS within 2.5 years of starting chemotherapy and radiotherapy and did not reveal any of the conventional cytogenetic abnormalities. It highlights the importance of simple tests like a complete blood count and peripheral blood smear examination in follow-up of the patients treated with chemotherapy.

  2. BCOR and BCORL1 mutations in myelodysplastic syndromes and related disorders.

    Science.gov (United States)

    Damm, Frederik; Chesnais, Virginie; Nagata, Yasunobu; Yoshida, Kenichi; Scourzic, Laurianne; Okuno, Yusuke; Itzykson, Raphael; Sanada, Masashi; Shiraishi, Yuichi; Gelsi-Boyer, Véronique; Renneville, Aline; Miyano, Satoru; Mori, Hiraku; Shih, Lee-Yung; Park, Sophie; Dreyfus, François; Guerci-Bresler, Agnes; Solary, Eric; Rose, Christian; Cheze, Stéphane; Prébet, Thomas; Vey, Norbert; Legentil, Marion; Duffourd, Yannis; de Botton, Stéphane; Preudhomme, Claude; Birnbaum, Daniel; Bernard, Olivier A; Ogawa, Seishi; Fontenay, Michaela; Kosmider, Olivier

    2013-10-31

    Patients with low-risk myelodysplastic syndromes (MDS) that rapidly progress to acute myeloid leukemia (AML) remain a challenge in disease management. Using whole-exome sequencing of an MDS patient, we identified a somatic mutation in the BCOR gene also mutated in AML. Sequencing of BCOR and related BCORL1 genes in a cohort of 354 MDS patients identified 4.2% and 0.8% of mutations respectively. BCOR mutations were associated with RUNX1 (P = .002) and DNMT3A mutations (P = .015). BCOR is also mutated in chronic myelomonocytic leukemia patients (7.4%) and BCORL1 in AML patients with myelodysplasia-related changes (9.1%). Using deep sequencing, we show that BCOR mutations arise after mutations affecting genes involved in splicing machinery or epigenetic regulation. In univariate analysis, BCOR mutations were associated with poor prognosis in MDS (overall survival [OS]: P = .013; cumulative incidence of AML transformation: P = .005). Multivariate analysis including age, International Prognostic Scoring System, transfusion dependency, and mutational status confirmed a significant inferior OS to patients with a BCOR mutation (hazard ratio, 3.3; 95% confidence interval, 1.4-8.1; P = .008). These data suggest that BCOR mutations define the clinical course rather than disease initiation. Despite infrequent mutations, BCOR analyses should be considered in risk stratification.

  3. Emerging roles of the spliceosomal machinery in myelodysplastic syndromes and other hematological disorders.

    Science.gov (United States)

    Visconte, V; Makishima, H; Maciejewski, J P; Tiu, R V

    2012-12-01

    In humans, the majority of all protein-coding transcripts contain introns that are removed by mRNA splicing carried out by spliceosomes. Mutations in the spliceosome machinery have recently been identified using whole-exome/genome technologies in myelodysplastic syndromes (MDS) and in other hematological disorders. Alterations in splicing factor 3 subunit b1 (SF3b1) were the first spliceosomal mutations described, immediately followed by identification of other splicing factor mutations, including U2 small nuclear RNA auxillary factor 1 (U2AF1) and serine arginine-rich splicing factor 2 (SRSF2). SF3b1/U2AF1/SRSF2 mutations occur at varying frequencies in different disease subtypes, each contributing to differences in survival outcomes. However, the exact functional consequences of these spliceosomal mutations in the pathogenesis of MDS and other hematological malignancies remain largely unknown and subject to intense investigation. For SF3b1, a gain of function mutation may offer the promise of new targeted therapies for diseases that carry this molecular abnormality that can potentially lead to cure. This review aims to provide a comprehensive overview of the emerging role of the spliceosome machinery in the biology of MDS/hematological disorders with an emphasis on the functional consequences of mutations, their clinical significance, and perspectives on how they may influence our understanding and management of diseases affected by these mutations.

  4. Emerging roles of the spliceosomal machinery in myelodysplastic syndromes and other hematologic disorders

    Science.gov (United States)

    Visconte, V; Makishima, H; Maciejewski, JP; Tiu, RV

    2013-01-01

    In humans, the majority of all protein-coding transcripts contain introns that are removed by mRNA splicing carried out by spliceosomes. Mutations in the spliceosome machinery have recently been identified using whole exome/genome technologies in myelodysplastic syndromes (MDS) and in other hematologic disorders. Alterations in Splicing Factor 3 Subunit b1 (SF3b1) were the first spliceosomal mutations described, immediately followed by identification of other splicing factor mutations, including U2 Small Nuclear RNA Auxillary Factor 1 (U2AF1) and Serine Arginine Rich Splicing Factor 2 (SRSF2). SF3b1/U2AF1/SRSF2 mutations occur at varying frequencies in different disease subtypes, each contributing to differences in survival outcomes. However, the exact functional consequences of these spliceosomal mutations in the pathogenesis of MDS and other hematologic malignancies remain largely unknown and subject to intense investigation. For SF3b1, a gain of function mutation may offer the promise of new targeted therapies for diseases that carry this molecular abnormality that can potentially lead to cure. This review aims to provide a comprehensive overview of the emerging role of the spliceosome machinery in the biology of MDS/hematologic disorders with an emphasis on the functional consequences of mutations, their clinical significance, and perspectives on how they may influence our understanding and management of diseases affected by these mutations. PMID:22678168

  5. Outcomes for Patients with Chronic Lymphocytic Leukemia (CLL) and Acute Leukemia or Myelodysplastic Syndrome

    Science.gov (United States)

    Tambaro, Francesco Paolo; Garcia-Manero, Guillermo; O’Brien, Susan M.; Faderl, Stefan H.; Ferrajoli, Alessandra; Burger, Jan A.; Pierce, Sherry; Wang, Xuemei; Do, Kim-Anh; Kantarjian, Hagop M.; Keating, Michael J.; Wierda, William G.

    2016-01-01

    Acute leukemia (AL) and myelodysplastic syndrome (MDS) are uncommon in CLL. We retrospectively identified 95 patients with CLL also diagnosed with AL (n=38) or MDS (n=57), either concurrently (n=5) or subsequent (n=90) to CLL diagnosis and report their outcomes. Median number of CLL treatments prior to AL and MDS was 2(0–9) and 1(0–8), respectively; the most common regimen was purine analogue combined with alkylating agent±CD20 mAb. Twelve had no prior CLL treatment. Among 38 with AL, 33 had AML, 3 had ALL (1Ph+), 1 had biphenotypic, and 1 had extramedullary (bladder) AML. Unfavorable AML karyotype was noted in 26, intermediate-risk in 7. There was no association between survival from AL and number of prior CLL regimens or karyotype. Expression of CD7 on blasts was associated with shorter survival. Among MDS cases, all IPSS were represented; karyotype was unfavorable in 36, intermediate in 6, and favorable in 12 patients; 10 experienced transformation to AML. Shorter survival from MDS correlated with higher-risk IPSS, poor-risk karyotype, and increased number of prior CLL treatments. Overall, outcomes for patients with CLL subsequently diagnosed with AL or MDS were poor; AL/MDS occurred without prior CLL treatment. Effective therapies for these patients are desperately needed. PMID:26290497

  6. Trisomy 8, a Cytogenetic Abnormality in Myelodysplastic Syndromes, Is Constitutional or Not?

    Science.gov (United States)

    Saumell, Sílvia; Solé, Francesc; Arenillas, Leonor; Montoro, Julia; Valcárcel, David; Pedro, Carme; Sanzo, Carmen; Luño, Elisa; Giménez, Teresa; Arnan, Montserrat; Pomares, Helena; De Paz, Raquel; Arrizabalaga, Beatriz; Jerez, Andrés; Martínez, Ana B; Sánchez-Castro, Judith; Rodríguez-Gambarte, Juan D; Raya, José M; Ríos, Eduardo; Rodríguez-Rivera, María; Espinet, Blanca; Florensa, Lourdes

    2015-01-01

    Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS) in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8) can be found as a constitutional mosaicism (cT8M). We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional cytogenetics (CC) and on granulocytes, CD3+ lymphocytes and oral mucosa cells by fluorescence in situ hybridization (FISH). In peripheral blood CC, +8 was seen in 4/32 patients. By FISH, only one patient with chronic myelomonocytic leukemia showed +8 in all cell samples and was interpreted as a cT8M. In our series +8 was acquired in all MDS. Probably, once discarded cT8M by FISH from CD3+ lymphocytes and non-hematological cells, +8 should be considered with enough evidence to MDS.

  7. Incidence of extramedullary relapse after haploidentical SCT for advanced AML/myelodysplastic syndrome.

    Science.gov (United States)

    Yoshihara, S; Ikegame, K; Kaida, K; Taniguchi, K; Kato, R; Inoue, T; Fujioka, T; Tamaki, H; Okada, M; Soma, T; Ogawa, H

    2012-05-01

    Extramedullary (EM) relapse of leukemia after allo-SCT in patients with AML/myelodysplastic syndrome has been increasingly reported. The reduced effectiveness of the GVL effect in EM sites, as compared with BM, has been suggested to underlie this problem. We retrospectively analyzed the pattern of relapse after haploidentical SCT (haplo-SCT), performed as the first or second SCT. Among 38 patients who received haplo-SCT as their first SCT, the cumulative incidences of BM and EM relapse at 3 years were 40.5 and 10.9%, respectively. Among 19 patients who received haplo-SCT as their second SCT, the cumulative incidences of BM and EM relapse were 30.9 and 31.9%, respectively. Moreover, most of the patients who underwent repeat haplo-SCT for the treatment of EM relapse had further EM relapse at other sites. Post-relapse survival did not differ significantly with different patterns of relapse. The frequent occurrence of EM relapse after haplo-SCT, particularly when performed as a second SCT, suggests that the potent GVL effect elicited by an HLA disparity also occurs preferentially in BM. Our findings emphasize the need for a treatment strategy for EM relapse that recognizes the reduced susceptibility of EM relapse to the GVL effect.

  8. Clinical consequences of iron overload in patients with myelodysplastic syndromes: the case for iron chelation therapy.

    Science.gov (United States)

    Shammo, Jamile M; Komrokji, Rami S

    2018-06-14

    Patients with myelodysplastic syndromes (MDS) are at increased risk of iron overload due to ineffective erythropoiesis and chronic transfusion therapy. The clinical consequences of iron overload include cardiac and/or hepatic failure, endocrinopathies, and infection risk. Areas covered: Iron chelation therapy (ICT) can help remove excess iron and ultimately reduce the clinical consequences of iron overload. The authors reviewed recent (last five years) English-language articles from PubMed on the topic of iron overload-related complications and the use of ICT (primarily deferasirox) to improve outcomes in patients with MDS. Expert Commentary: While a benefit of ICT has been more firmly established in other transfusion-dependent conditions such as thalassemia, its role in reducing iron overload in MDS remains controversial due to the lack of prospective controlled data demonstrating a survival benefit. Orally administered chelation agents (e.g., deferasirox), are now available, and observational and/or retrospective data support a survival benefit of using ICT in MDS. The placebo-controlled TELESTO trial (NCT00940602) is currently examining the use of deferasirox in MDS patients with iron overload, and is evaluating specifically whether use of ICT to alleviate iron overload can also reduce iron overload-related complications in MDS and improve survival.

  9. Impact of iron overload and potential benefit from iron chelation in low-risk myelodysplastic syndrome.

    Science.gov (United States)

    Shenoy, Niraj; Vallumsetla, Nishanth; Rachmilewitz, Eliezer; Verma, Amit; Ginzburg, Yelena

    2014-08-07

    Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal bone marrow disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and potential for malignant transformation. Lower/intermediate-risk MDSs are associated with longer survival and high red blood cell (RBC) transfusion requirements resulting in secondary iron overload. Recent data suggest that markers of iron overload portend a relatively poor prognosis, and retrospective analysis demonstrates that iron chelation therapy is associated with prolonged survival in transfusion-dependent MDS patients. New data provide concrete evidence of iron's adverse effects on erythroid precursors in vitro and in vivo. Renewed interest in the iron field was heralded by the discovery of hepcidin, the main serum peptide hormone negative regulator of body iron. Evidence from β-thalassemia suggests that regulation of hepcidin by erythropoiesis dominates regulation by iron. Because iron overload develops in some MDS patients who do not require RBC transfusions, the suppressive effect of ineffective erythropoiesis on hepcidin may also play a role in iron overload. We anticipate that additional novel tools for measuring iron overload and a molecular-mechanism-driven description of MDS subtypes will provide a deeper understanding of how iron metabolism and erythropoiesis intersect in MDSs and improve clinical management of this patient population. © 2014 by The American Society of Hematology.

  10. Clinical implications of somatic mutations in aplastic anemia and myelodysplastic syndrome in genomic age.

    Science.gov (United States)

    Maciejewski, Jaroslaw P; Balasubramanian, Suresh K

    2017-12-08

    Recent technological advances in genomics have led to the discovery of new somatic mutations and have brought deeper insights into clonal diversity. This discovery has changed not only the understanding of disease mechanisms but also the diagnostics and clinical management of bone marrow failure. The clinical applications of genomics include enhancement of current prognostic schemas, prediction of sensitivity or refractoriness to treatments, and conceptualization and selective application of targeted therapies. However, beyond these traditional clinical aspects, complex hierarchical clonal architecture has been uncovered and linked to the current concepts of leukemogenesis and stem cell biology. Detection of clonal mutations, otherwise typical of myelodysplastic syndrome, in the course of aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria has led to new pathogenic concepts in these conditions and created a new link between AA and its clonal complications, such as post-AA and paroxysmal nocturnal hemoglobinuria. Distinctions among founder vs subclonal mutations, types of clonal evolution (linear or branching), and biological features of individual mutations (sweeping, persistent, or vanishing) will allow for better predictions of the biologic impact they impart in individual cases. As clonal markers, mutations can be used for monitoring clonal dynamics of the stem cell compartment during physiologic aging, disease processes, and leukemic evolution. © 2016 by The American Society of Hematology. All rights reserved.

  11. Trisomy 8, a Cytogenetic Abnormality in Myelodysplastic Syndromes, Is Constitutional or Not?

    Directory of Open Access Journals (Sweden)

    Sílvia Saumell

    Full Text Available Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8 can be found as a constitutional mosaicism (cT8M. We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional cytogenetics (CC and on granulocytes, CD3+ lymphocytes and oral mucosa cells by fluorescence in situ hybridization (FISH. In peripheral blood CC, +8 was seen in 4/32 patients. By FISH, only one patient with chronic myelomonocytic leukemia showed +8 in all cell samples and was interpreted as a cT8M. In our series +8 was acquired in all MDS. Probably, once discarded cT8M by FISH from CD3+ lymphocytes and non-hematological cells, +8 should be considered with enough evidence to MDS.

  12. SPAG6 regulates cell apoptosis through the TRAIL signal pathway in myelodysplastic syndromes.

    Science.gov (United States)

    Li, Xinxin; Yang, Bihui; Wang, Li; Chen, Liping; Luo, Xiaohua; Liu, Lin

    2017-05-01

    Myelodysplastic syndromes (MDSs) are a group of malignant clone hematopoietic stem-cell diseases, and the evolution and progression of MDS depend on the abnormal apoptosis of bone marrow cells. Our previous studies have indicated that sperm-associated antigen 6 (SPAG6), located in the uniparental disomy regions of myeloid cells, is overexpressed in patients with MDS as compared to controls, and SPAG6 can inhibit apoptosis of SKM-1. However, the concrete mechanism is still unclear. In the present study, it was found that the TNF-related apoptosis-inducing ligand (TRAIL)signal pathway was activated when the expression of SPAG6 was inhibited by SPAG6-shRNA lentivirus in SKM-1 cells. Additionally, the results of flow cytometry, Cell Counting Kit-8 assay and western blot analysis implied that the TRAIL signal pathway could be inhibited by a high expression of SPAG6. However, SPAG6 cannot influence the expression of TRAIL death receptors, except for FADD. Additionally the interaction between FADD and TRAIL death receptors also increased in SKM-1 cells infected with SPAG6-shRNA lentivirus. Thus, our study demonstrates that SPAG6 may regulate apoptosis in SKM-1 through the TRAIL signal pathway, indicating that SPAG6 could be a potential therapeutic target.

  13. Distinct mutation profile and prognostic relevance in patients with hypoplastic myelodysplastic syndromes (h-MDS).

    Science.gov (United States)

    Yao, Chi-Yuan; Hou, Hsin-An; Lin, Tzung-Yi; Lin, Chien-Chin; Chou, Wen-Chien; Tseng, Mei-Hsuan; Chiang, Ying-Chieh; Liu, Ming-Chih; Liu, Chia-Wen; Kuo, Yuan-Yeh; Wu, Shang-Ju; Liao, Xiu-Wen; Lin, Chien-Ting; Ko, Bor-Shen; Chen, Chien-Yuan; Hsu, Szu-Chun; Li, Chi-Cheng; Huang, Shang-Yi; Yao, Ming; Tang, Jih-Luh; Tsay, Woei; Liu, Chieh-Yu; Tien, Hwei-Fang

    2016-09-27

    Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies. Although most MDS patients have normal or increased BM cellularity (NH-MDS), some have hypocellular BM (h-MDS). The reports concerning the differences in genetic alterations between h-MDS and NH-MDS patients are limited. In this study, 369 MDS patients diagnosed according to the WHO 2008 criteria were recruited. h-MDS patients had lower PB white blood cell and blast counts, and lower BM blast percentages, than those with NH-MDS. h-MDS was closely associated with lower-risk MDS, defined by the International Prognostic Scoring System (IPSS) and revised IPSS (IPSS-R). IPSS-R could properly predict the prognosis in h-MDS (PMDS patients. The h-MDS patients had lower incidences of RUNX1, ASXL1, DNMT3A, EZH2 and TP53 mutations than NH-MDS patients. The cumulated incidence of acute leukemic transformation at 5 years was 19.3% for h-MDS and 40.4% for NH-MDS patients (P= 0.001). Further, the patients with h-MDS had longer overall survival (OS) than those with NH-MDS (P= 0.001), and BM hypocellularity remains an independent favorable prognostic factor for OS irrespective of age, IPSS-R, and gene mutations. Our findings provide evidence that h-MDS indeed represent a distinct clinico-biological subgroup of MDS and can predict better leukemia-free survival and OS.

  14. Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions.

    Science.gov (United States)

    Valent, Peter; Orazi, Attilio; Steensma, David P; Ebert, Benjamin L; Haase, Detlef; Malcovati, Luca; van de Loosdrecht, Arjan A; Haferlach, Torsten; Westers, Theresia M; Wells, Denise A; Giagounidis, Aristoteles; Loken, Michael; Orfao, Alberto; Lübbert, Michael; Ganser, Arnold; Hofmann, Wolf-Karsten; Ogata, Kiyoyuki; Schanz, Julie; Béné, Marie C; Hoermann, Gregor; Sperr, Wolfgang R; Sotlar, Karl; Bettelheim, Peter; Stauder, Reinhard; Pfeilstöcker, Michael; Horny, Hans-Peter; Germing, Ulrich; Greenberg, Peter; Bennett, John M

    2017-09-26

    Myelodysplastic syndromes (MDS) comprise a heterogeneous group of myeloid neoplasms characterized by peripheral cytopenia, dysplasia, and a variable clinical course with about 30% risk to transform to secondary acute myeloid leukemia (AML). In the past 15 years, diagnostic evaluations, prognostication, and treatment of MDS have improved substantially. However, with the discovery of molecular markers and advent of novel targeted therapies, new challenges have emerged in the complex field of MDS. For example, MDS-related molecular lesions may be detectable in healthy individuals and increase in prevalence with age. Other patients exhibit persistent cytopenia of unknown etiology without dysplasia. Although these conditions are potential pre-phases of MDS they may also transform into other bone marrow neoplasms. Recently identified molecular, cytogenetic, and flow-based parameters may add in the delineation and prognostication of these conditions. However, no generally accepted integrated classification and no related criteria are as yet available. In an attempt to address this challenge, an international consensus group discussed these issues in a working conference in July 2016. The outcomes of this conference are summarized in the present article which includes criteria and a proposal for the classification of pre-MDS conditions as well as updated minimal diagnostic criteria of MDS. Moreover, we propose diagnostic standards to delineate between ´normal´, pre-MDS, and MDS. These standards and criteria should facilitate diagnostic and prognostic evaluations in clinical studies as well as in clinical practice.

  15. Potential Relationship between Inadequate Response to DNA Damage and Development of Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Ting Zhou

    2015-01-01

    Full Text Available Hematopoietic stem cells (HSCs are responsible for the continuous regeneration of all types of blood cells, including themselves. To ensure the functional and genomic integrity of blood tissue, a network of regulatory pathways tightly controls the proliferative status of HSCs. Nevertheless, normal HSC aging is associated with a noticeable decline in regenerative potential and possible changes in other functions. Myelodysplastic syndrome (MDS is an age-associated hematopoietic malignancy, characterized by abnormal blood cell maturation and a high propensity for leukemic transformation. It is furthermore thought to originate in a HSC and to be associated with the accrual of multiple genetic and epigenetic aberrations. This raises the question whether MDS is, in part, related to an inability to adequately cope with DNA damage. Here we discuss the various components of the cellular response to DNA damage. For each component, we evaluate related studies that may shed light on a potential relationship between MDS development and aberrant DNA damage response/repair.

  16. Abrupt evolution of Philadelphia chromosome-positive acute myeloid leukemia in myelodysplastic syndrome.

    Science.gov (United States)

    Fukunaga, Akiko; Sakoda, Hiroto; Iwamoto, Yoshihiro; Inano, Shojiro; Sueki, Yuki; Yanagida, Soshi; Arima, Nobuyoshi

    2013-03-01

    Myelodysplastic syndrome (MDS) is a clonal disorder arising from an alteration in multipotent stem cells, which lose the ability of normal proliferation and differentiation. Disease progression occurs in approximately 30% MDS cases. Specific chromosomal alterations seem responsible for each step in the evolution of acute myeloid leukemia (AML). Multiple genetic aberrations occur during the clonal evolution of MDS; however, few studies report the presence of the Philadelphia (Ph) chromosome. We report a rare case of Ph-positive AML, which evolved during the course of low-risk MDS. The patient, a 76-year-old man with mild leukocytopenia, was diagnosed with MDS, refractory neutropenia (RN). After 1.5 yr, his peripheral blood and bone marrow were suddenly occupied by immature basophils and myeloblasts, indicating the onset of AML. A bone marrow smear showed multilineage dysplasia, consistent with MDS evolution. Chromosomal analysis showed an additional t(9;22)(q34;q11) translocation. Because progression occurred concurrently with emergence of the Ph chromosome, we diagnosed this case as Ph-positive AML with basophilia arising from the clonal evolution of MDS. The patient was initially treated with nilotinib. A hematological response was soon achieved with disappearance of the Ph chromosome in the bone marrow. Emergence of Ph-positive AML in the course of low-risk MDS has rarely been reported. We report this case as a rare clinical course of MDS. © 2012 John Wiley & Sons A/S.

  17. Endothelial Progenitor Cell Dysfunction in Myelodysplastic Syndromes: Possible Contribution of a Defective Vascular Niche to Myelodysplasia

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    Luciana Teofili

    2015-05-01

    Full Text Available We set a model to replicate the vascular bone marrow niche by using endothelial colony forming cells (ECFCs, and we used it to explore the vascular niche function in patients with low-risk myelodysplastic syndromes (MDS. Overall, we investigated 56 patients and we observed higher levels of ECFCs in MDS than in healthy controls; moreover, MDS ECFCs were found variably hypermethylated for p15INK4b DAPK1, CDH1, or SOCS1. MDS ECFCs exhibited a marked adhesive capacity to normal mononuclear cells. When normal CD34+ cells were co-cultured with MDS ECFCs, they generated significant lower amounts of CD11b+ and CD41+ cells than in co-culture with normal ECFCs. At gene expression profile, several genes involved in cell adhesion were upregulated in MDS ECFCs, while several members of the Wingless and int (Wnt pathways were underexpressed. Furthermore, at miRNA expression profile, MDS ECFCs hypo-expressed various miRNAs involved in Wnt pathway regulation. The addition of Wnt3A reduced the expression of intercellular cell adhesion molecule-1 on MDS ECFCs and restored the defective expression of markers of differentiation. Overall, our data demonstrate that in low-risk MDS, ECFCs exhibit various primary abnormalities, including putative MDS signatures, and suggest the possible contribution of the vascular niche dysfunction to myelodysplasia.

  18. New polymorphisms of Xeroderma Pigmentosum DNA repair genes in myelodysplastic syndrome.

    Science.gov (United States)

    Santiago, Sabrina Pinheiro; Junior, Howard Lopes Ribeiro; de Sousa, Juliana Cordeiro; de Paula Borges, Daniela; de Oliveira, Roberta Taiane Germano; Farias, Izabelle Rocha; Costa, Marília Braga; Maia, Allan Rodrigo Soares; da Nóbrega Ito, Mayumi; Magalhães, Silvia Maria Meira; Pinheiro, Ronald Feitosa

    2017-07-01

    The association between Xeroderma Pigmentosum DNA repair genes (XPA rs1800975, XPC rs2228000, XPD rs1799793 and XPF rs1800067) polymorphisms and myelodysplastic syndrome (MDS) have not been reported. To assess the functional role between these polymorphisms and MDS, we evaluated 189 samples stratified in two groups: 95 bone marrow samples from MDS patients and 94 from healthy elderly volunteers used as controls. Genotypes for all polymorphisms were identified in DNA samples in an allelic discrimination experiment by real-time polymerase chain reaction (qPCR). We also studied the mRNA expression of XPA and XPC genes to evaluate if its polymorphisms were functional in 53 RNAm MDS patients by qPCR methodologies. To the rs2228000 polymorphism, the CT and TT polymorphic genotype were associated with increased odds ratio (OR) of more profound cytopenia (hemoglobin and neutrophils count). To the rs1799793 polymorphism, we found that the GG homozygous wild-type genotype was associated with a decreased chance of developing MDS. We observed low expression of XPA in younger patients, in hypoplastic MDS and patients with abnormal karyotype when presented AG or AA polymorphic genotypes. We also found that there was a statistically significant interaction between the presence of micromegakaryocyte on down regulation of XPC regarding the CT heterozygous genotype of the rs1800975 polymorphism. Our results suggest that new functional polymorphisms of Xeroderma Pigmentosum DNA repair genes in MDS are related to its pathogenesis and prognosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome.

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    Mariane de Montalembert

    Full Text Available The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS. In patients with sickle cell anemia (SCA, iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15% patients with thalassemia, none with SCA, and 4 (16% with MDS. The liver iron content (LIC ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29. Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001. Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001. Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation.

  20. Myelodysplastic syndromes: advantages of a combined cytogenetic and molecular diagnostic workup.

    Science.gov (United States)

    Ciabatti, Elena; Valetto, Angelo; Bertini, Veronica; Ferreri, Maria Immacolata; Guazzelli, Alice; Grassi, Susanna; Guerrini, Francesca; Petrini, Iacopo; Metelli, Maria Rita; Caligo, Maria Adelaide; Rossi, Simona; Galimberti, Sara

    2017-10-03

    In this study we present a new diagnostic workup for the myelodysplastic syndromes (MDS) including FISH, aCGH, and somatic mutation assays in addition to the conventional cytogenetics (CC). We analyzed 61 patients by CC, FISH for chromosome 5, 7, 8 and PDGFR rearrangements, aCGH, and PCR for ASXL1, EZH2, TP53, TET2, RUNX1, DNMT3A, SF3B1 somatic mutations. Moreover, we quantified WT1 and RPS14 gene expression levels, in order to find their possible adjunctive value and their possible clinical impact. CC analysis showed 32% of patients with at least one aberration. FISH analysis detected chromosomal aberrations in 24% of patients and recovered 5 cases (13.5%) at normal karyotype (two 5q- syndromes, one del(7) case, two cases with PDGFR rearrangement). The aGCH detected 10 "new" unbalanced cases in respect of the CC, including one with alteration of the ETV6 gene. After mutational analysis, 33 patients (54%) presented at least one mutation and represented the only marker of clonality in 36% of all patients. The statistical analysis confirmed the prognostic role of CC either on overall or on progression-free-survival. In addition, deletions detected by aCGH and WT1 over-expression negatively conditioned survival. In conclusion, our work showed that 1) the addition of FISH (at least for chr. 5 and 7) can improve the definition of the risk score; 2) mutational analysis, especially for the TP53 and SF3B1, could better define the type of MDS and represent a "clinical warning"; 3) the aCGH use could be probably applied to selected cases (with suboptimal response or failure).

  1. Allogeneic hematopoietic stem cell transplant in adult patients with myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes.

    Science.gov (United States)

    Sharma, Prashant; Shinde, Shivani S; Damlaj, Moussab; Hefazi Rorghabeh, Mehrdad; Hashmi, Shahrukh K; Litzow, Mark R; Hogan, William J; Gangat, Naseema; Elliott, Michelle A; Al-Kali, Aref; Tefferi, Ayalew; Patnaik, Mrinal M

    2017-04-01

    MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasm) overlap syndromes are myeloid malignancies for which allogeneic hematopoietic stem cell transplant (allo-HSCT) is potentially curative. We describe transplant outcomes of 43 patients - 35 with chronic myelomonocytic leukemia, CMML (of which 17 had blast transformation, BT) and eight with MDS/MPN-unclassifiable (MDS/MPN,U). At median follow-up of 21 months, overall survival (OS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 55%, 29%, and 25% respectively in CMML without BT and 47%, 40%, and 34% respectively in CMML with BT. Higher HSCT-comorbidity index (HSCT-CI >3 versus ≤3; p = 0.015) and splenomegaly (p = 0.006) predicted worse OS in CMML without BT. In CMML with BT, engraftment failure (p = 0.006) and higher HSCT-CI (p = 0.03) were associated with inferior OS, while HSCT within 1-year of diagnosis was associated with improved OS (p = 0.045). In MDS/MPN,U, at median follow-up of 15 months, OS, CIR, and NRM were 62%, 30%, and 14%, respectively.

  2. High risk of metabolic syndrome among black South African women ...

    African Journals Online (AJOL)

    Background: There is an increased prevalence of metabolic syndrome (MetS) in individuals with severe mental illness (SMI) globally. The prevalence of MetS is higher in black women compared to black men from South Africa. Aim: To compare the prevalence of MetS between black South African men and women with SMI ...

  3. Connect MDS/AML: design of the myelodysplastic syndromes and acute myeloid leukemia disease registry, a prospective observational cohort study.

    Science.gov (United States)

    Steensma, David P; Abedi, Medrdad; Bejar, Rafael; Cogle, Christopher R; Foucar, Kathryn; Garcia-Manero, Guillermo; George, Tracy I; Grinblatt, David; Komrokji, Rami; Ma, Xiaomei; Maciejewski, Jaroslaw; Pollyea, Daniel A; Savona, Michael R; Scott, Bart; Sekeres, Mikkael A; Thompson, Michael A; Swern, Arlene S; Nifenecker, Melissa; Sugrue, Mary M; Erba, Harry

    2016-08-19

    Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are myeloid neoplasms in which outgrowth of neoplastic clones disrupts normal hematopoiesis. Some patients with unexplained persistent cytopenias may not meet minimal diagnostic criteria for MDS but an alternate diagnosis is not apparent; the term idiopathic cytopenia of undetermined significance (ICUS) has been used to describe this state. MDS and AML occur primarily in older patients who are often treated outside the clinical trial setting. Consequently, our understanding of the patterns of diagnostic evaluation, management, and outcomes of these patients is limited. Furthermore, there are few natural history studies of ICUS. To better understand how patients who have MDS, ICUS, or AML are managed in the routine clinical setting, the Connect MDS/AML Disease Registry, a multicenter, prospective, observational cohort study of patients newly diagnosed with these conditions has been initiated. The Connect MDS/AML Disease Registry will capture diagnosis, risk assessment, treatment, and outcomes data for approximately 1500 newly diagnosed patients from approximately 150 community and academic sites in the United States in 4 cohorts: (1) lower-risk MDS (International Prognostic Scoring System [IPSS] low and intermediate-1 risk), with and without del(5q); (2) higher-risk MDS (IPSS intermediate-2 and high risk); (3) ICUS; and (4) AML in patients aged ≥ 55 years (excluding acute promyelocytic leukemia). Diagnosis will be confirmed by central review. Baseline patient characteristics, diagnostic patterns, treatment patterns, clinical outcomes, health economics outcomes, and patient-reported health-related quality of life will be entered into an electronic data capture system at enrollment and quarterly for 8 years. A tissue substudy to explore the relationship between karyotypes, molecular markers, and clinical outcomes will be conducted, and is optional for patients. The Connect MDS/AML Disease

  4. High Frequency of AML1/RUNX1 Point Mutations in Radiation-Associated Myelodysplastic Syndrome Around Semipalatinsk Nuclear Test Site

    OpenAIRE

    Dinara, ZHARLYGANOVA; Hironori, HARADA; Yuka, HARADA; Sergey, SHINKAREV; Zhaxybay, ZHUMADILOV; Aigul, ZHUNUSOVA; Naylya J., TCHAIZHUNUSOVA; Kazbek N., APSALIKOV; Vadim, KEMAIKIN; Kassym, ZHUMADILOV; Noriyuki, KAWANO; Akiro, KIMURA; Masaharu, HOSHI; Department of Radiation Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University; Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University

    2008-01-01

    It is known that bone marrow is a sensitive organ to ionizing radiation, and many patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) have been diagnosed in radiation-treated cases and atomic bomb survivors in Hiroshima and Nagasaki. The AML1/RUNX1 gene has been known to be frequently mutated in MDS/AML patients among atomic bomb survivors and radiation therapy-related MDS/AML patients. In this study, we investigated the AML1 mutations in radiation-exposed patients wi...

  5. In vivo measurements of the T1 relaxation processes in the bone marrow in patients with myelodysplastic syndrome

    International Nuclear Information System (INIS)

    Jensen, K.E.; Nielsen, H.; Thomsen, C.; Soerensen, P.G.; Karle, H.; Christoffersen, P.; Henriksen, O.; Hvidovre Hospital, Copenhagen; Hvidovre Hospital, Copenhagen

    1989-01-01

    Nine patients with myelodysplastic syndrome (MDS) were examined with magnetic resonance imaging and in vivo T1 relaxation time measurements of the vertebral bone marrow in a 1.5 tesla whole body scanner. Two patients underwent transformation to acute myeloid leukemia and were evaluated at follow-up examinations. At the time of diagnosis the T1 relaxation times of the vertebral bone marrow were significantly prolonged compared with normal values. The T1 relaxation times of the vertebral bone marrow in patients with MDS showed significantly lower values compared with patients with acute leukemia and did not differ from patients with polycythemia vera. (orig.)

  6. Hypermethylation of the VTRNA1-3 Promoter is Associated with Poor Outcome in Lower Risk Myelodysplastic Syndrome Patients

    DEFF Research Database (Denmark)

    Helbo, Alexandra Søgaard; Treppendahl, Marianne; Aslan, Derya

    2015-01-01

    Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders. MDS is frequently associated with deletions on chromosome 5q as well as aberrant DNA methylation patterns including hypermethylation of key tumor suppressors. We have previously shown that hypermethylation...... causes reactivation these genes. In normal hematopoiesis, we find that vault RNAs (vtRNAs) show differential methylation between various hematopoietic cell populations, indicating that allele-specific methylation events may occur during hematopoiesis. In addition, we show that VTRNA1-3 promoter...... hypermethylation is frequent in lower risk MDS patients and is associated with a decreased overall survival....

  7. Azacitidine in Lower-Risk Myelodysplastic Syndromes: A Meta-Analysis of Data from Prospective Studies.

    Science.gov (United States)

    Komrokji, Rami; Swern, Arlene S; Grinblatt, David; Lyons, Roger M; Tobiasson, Magnus; Silverman, Lewis R; Sayar, Hamid; Vij, Ravi; Fliss, Albert; Tu, Nora; Sugrue, Mary M

    2018-02-01

    After erythropoiesis-stimulating agent (ESA) failure, lenalidomide and hypomethylating agents are the only remaining treatment options for most patients with lower-risk myelodysplastic syndromes (LR-MDS). Optimal choice of these agents as front-line therapy in non-del(5q) LR-MDS is unclear. Because azacitidine clinical data mainly describe experience in higher-risk MDS, we performed a meta-analysis of patient-level data to evaluate azacitidine in patients with red blood cell (RBC) transfusion-dependent LR-MDS. We searched English-language articles for prospective phase II and III azacitidine clinical trials and patient registries published between 2000 and 2015, and Embase abstracts from 2015 conferences. Patient-level data from identified relevant studies were provided by investigators. Meta-analyses followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Efficacy endpoints were RBC transfusion independence (TI) and Clinical Benefit (RBC-TI, erythroid response, and complete or partial remission, per International Working Group 2006 criteria for MDS). Data for 233 patients from 6 clinical studies and 1 registry study met criteria for inclusion in analyses. Overall, 90.3% of patients had non-del(5q) LR-MDS. Pooled estimates from random-effects models of RBC-TI and Clinical Benefit were 38.9% and 81.1%, respectively; for the ESA-refractory subgroup, they were 40.5% and 77.3%; and for patients with isolated anemia, they were 41.9% and 82.5%. In multivariate analyses, planned use of ≥6 azacitidine treatment cycles was significantly predictive of response. Azacitidine effects in these patients, most with non-del(5q) LR-MDS, were promising and generally similar to those reported for lenalidomide in similar patients. The choice of initial therapy is important because most patients eventually stop responding to front-line therapy and alternatives are limited. Lower-risk myelodysplastic syndromes (LR-MDS) are primarily characterized by

  8. Detection of paroxysmal nocturnal hemoglobinuria clones in patients with myelodysplastic syndromes and related bone marrow diseases, with emphasis on diagnostic pitfalls and caveats.

    Science.gov (United States)

    Wang, Sa A; Pozdnyakova, Olga; Jorgensen, Jeffrey L; Medeiros, L Jeffrey; Stachurski, Dariusz; Anderson, Mary; Raza, Azra; Woda, Bruce A

    2009-01-01

    The presence of paroxysmal nocturnal hemoglobinuria clones in the setting of aplastic anemia or myelodysplastic syndrome has been shown to have prognostic and therapeutic implications. However, the status of paroxysmal nocturnal hemoglobinuria clones in various categories of myelodysplastic syndrome and in other bone marrow disorders is not well-studied. By using multiparameter flow cytometry immunophenotypic analysis with antibodies specific for four glycosylphosphatidylinositol-anchored proteins (CD55, CD59, CD16, CD66b) and performing an aerolysin lysis confirmatory test in representative cases, we assessed the paroxysmal nocturnal hemoglobinuria-phenotype granulocytes in 110 patients with myelodysplastic syndrome, 15 with myelodysplastic/myeloproliferative disease, 5 with idiopathic myelofibrosis and 6 with acute myeloid leukemia. Paroxysmal nocturnal hemoglobinuria-phenotype granulocytes were detected in nine patients with low grade myelodysplastic syndrome who showed clinicopathological features of bone marrow failure, similar to aplastic anemia. All paroxysmal nocturnal hemoglobinuria-positive cases demonstrated loss of the four glycosylphosphatidylinositol-anchored proteins, with CD16(-)CD66b(-) clones being larger than those of CD55(-)CD59(-) (p<0.05). Altered glycosylphosphatidylinositol-anchored protein expression secondary to granulocytic hypogranulation, immaturity, and/or immunophenotypic abnormalities was present in a substantial number of cases and diagnostically challenging. These results show that routine screening for paroxysmal nocturnal hemoglobinuria clones in patients with an intrinsic bone marrow disease who show no clinical evidence of hemolysis has an appreciable yield in patients with low grade myelodysplastic syndromes. The recognition of diagnostic caveats and pitfalls associated with the underlying intrinsic bone marrow disease is essential in interpreting paroxysmal nocturnal hemoglobinuria testing correctly. In our experience, the CD

  9. Aging- and Senescence-associated Changes of Mesenchymal Stromal Cells in Myelodysplastic Syndromes.

    Science.gov (United States)

    Mattiucci, Domenico; Maurizi, Giulia; Leoni, Pietro; Poloni, Antonella

    2018-01-01

    Hematopoietic stem and progenitor cells reside within the bone marrow (BM) microenvironment. By a well-balanced interplay between self-renewal and differentiation, they ensure a lifelong supply of mature blood cells. Physiologically, multiple different cell types contribute to the regulation of stem and progenitor cells in the BM microenvironment by cell-extrinsic and cell-intrinsic mechanisms. During the last decades, mesenchymal stromal cells (MSCs) have been identified as one of the main cellular components of the BM microenvironment holding an indispensable role for normal hematopoiesis. During aging, MSCs diminish their functional and regenerative capacities and in some cases encounter replicative senescence, promoting inflammation and cancer progression. It is now evident that alterations in specific stromal cells that comprise the BM microenvironment can contribute to hematologic malignancies, and there is growing interest regarding the contribution of MSCs to the pathogenesis of myelodysplastic syndromes (MDSs), a clonal hematological disorder, occurring mostly in the elderly, characterized by ineffective hematopoiesis and increased tendency to acute myeloid leukemia evolution. The pathogenesis of MDS has been associated with specific genetic and epigenetic events occurring both in hematopoietic stem cells (HSCs) and in the whole BM microenvironment with an aberrant cross talk between hematopoietic elements and stromal compartment. This review highlights the role of MSCs in MDS showing functional and molecular alterations such as altered cell-cycle regulation with impaired proliferative potential, dysregulated cytokine secretion, and an abnormal gene expression profile. Here, the current knowledge of impaired functional properties of both aged MSCs and MSCs in MDS have been described with a special focus on inflammation and senescence induced changes in the BM microenvironment. Furthermore, a better understanding of aberrant BM microenvironment could

  10. Impairment of FOS mRNA stabilization following translation arrest in granulocytes from myelodysplastic syndrome patients.

    Science.gov (United States)

    Feng, Xiaomin; Shikama, Yayoi; Shichishima, Tsutomu; Noji, Hideyoshi; Ikeda, Kazuhiko; Ogawa, Kazuei; Kimura, Hideo; Takeishi, Yasuchika; Kimura, Junko

    2013-01-01

    Although quantitative and qualitative granulocyte defects have been described in myelodysplastic syndromes (MDS), the underlying molecular basis of granulocyte dysfunction in MDS is largely unknown. We recently found that FOS mRNA elevation under translation-inhibiting stimuli was significantly smaller in granulocytes from MDS patients than in healthy individuals. The aim of this study is to clarify the cause of the impaired FOS induction in MDS. We first examined the mechanisms of FOS mRNA elevation using granulocytes from healthy donors cultured with the translation inhibitor emetine. Emetine increased both transcription and mRNA stability of FOS. p38 MAPK inhibition abolished the emetine-induced increase of FOS transcription but did not affect FOS mRNA stabilization. The binding of an AU-rich element (ARE)-binding protein HuR to FOS mRNA containing an ARE in 3'UTR was increased by emetine, and the knockdown of HuR reduced the FOS mRNA stabilizing effect of emetine. We next compared the emetine-induced transcription and mRNA stabilization of FOS between MDS patients and healthy controls. Increased rates of FOS transcription by emetine were similar in MDS and controls. In the absence of emetine, FOS mRNA decayed to nearly 17% of initial levels in 45 min in both groups. In the presence of emetine, however, 76.7±19.8% of FOS mRNA remained after 45 min in healthy controls, versus 37.9±25.5% in MDS (Pknowledge, this is the first report demonstrating attenuation of stress-induced FOS mRNA stabilization in MDS granulocytes.

  11. The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts

    International Nuclear Information System (INIS)

    Kang, Min-Gu; Kim, Hye-Ran; Seo, Bo-Young; Lee, Jun Hyung; Choi, Seok-Yong; Kim, Soo-Hyun; Shin, Jong-Hee; Suh, Soon-Pal; Ahn, Jae-Sook; Shin, Myung-Geun

    2015-01-01

    Mutations in genes that are part of the splicing machinery for myelodysplastic syndromes (MDS), including MDS without ring sideroblasts (RS), have been widely investigated. The effects of these mutations on clinical outcomes have been diverse and contrasting. We examined a cohort of 129 de novo MDS patients, who did not harbor RS, for mutations affecting three spliceosomal genes (SF3B1, U2AF1, and SRSF2). The mutation rates of SF3B1, U2AF1, and SRSF2 were 7.0 %, 7.8 %, and 10.1 %, respectively. Compared with previously reported results, these rates were relatively infrequent. The SRSF2 mutation strongly correlated with old age (P < 0.001), while the mutation status of SF3B1 did not affect overall survival (OS), progression-free survival (PFS), or acute myeloid leukemia (AML) transformation. In contrast, MDS patients with mutations in U2AF1 or SRSF2 exhibited inferior PFS. The U2AF1 mutation was associated with inferior OS in low-risk MDS patients (P = 0.035). The SRSF2 mutation was somewhat associated with AML transformation (P = 0.083). Our findings suggest that the frequencies of the SF3B1, U2AF1, and SRSF2 splicing gene mutations in MDS without RS were relatively low. We also demonstrated that the U2AF1 and SRSF2 mutations were associated with an unfavorable prognostic impact in MDS patients without RS. The online version of this article (doi:10.1186/s12885-015-1493-5) contains supplementary material, which is available to authorized users

  12. Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations.

    Science.gov (United States)

    Mallo, Mar; Del Rey, Mónica; Ibáñez, Mariam; Calasanz, M José; Arenillas, Leonor; Larráyoz, M José; Pedro, Carmen; Jerez, Andrés; Maciejewski, Jaroslaw; Costa, Dolors; Nomdedeu, Meritxell; Diez-Campelo, María; Lumbreras, Eva; González-Martínez, Teresa; Marugán, Isabel; Such, Esperanza; Cervera, José; Cigudosa, Juan C; Alvarez, Sara; Florensa, Lourdes; Hernández, Jesús M; Solé, Francesc

    2013-07-01

    Lenalidomide is an effective drug in low-risk myelodysplastic syndromes (MDS) with isolated del(5q), although not all patients respond. Studies have suggested a role for TP53 mutations and karyotype complexity in disease progression and outcome. In order to assess the impact of complex karyotypes on treatment response and disease progression in 52 lenalidomide-treated patients with del(5q) MDS, conventional G-banding cytogenetics (CC), single nucleotide polymorphism array (SNP-A), and genomic sequencing methods were used. SNP-A analysis (with control sample, lymphocytes CD3+, in 30 cases) revealed 5q losses in all cases. Other recurrent abnormalities were infrequent and were not associated with lenalidomide responsiveness. Low karyotype complexity (by CC) and a high baseline platelet count (>280 × 10(9) /l) were associated with the achievement of haematological response (P = 0·020, P = 0·013 respectively). Unmutated TP53 status showed a tendency for haematological response (P = 0·061). Complete cytogenetic response was not observed in any of the mutated TP53 cases. By multivariate analysis, the most important predictor for lenalidomide treatment failure was a platelet count <280 × 10(9) /l (Odds Ratio = 6·17, P = 0·040). This study reveals the importance of a low baseline platelet count, karyotypic complexity and TP53 mutational status for response to lenalidomide treatment. It supports the molecular study of TP53 in MDS patients treated with lenalidomide. © 2013 John Wiley & Sons Ltd.

  13. Considering Bone Marrow Blasts From Nonerythroid Cellularity Improves the Prognostic Evaluation of Myelodysplastic Syndromes.

    Science.gov (United States)

    Arenillas, Leonor; Calvo, Xavier; Luño, Elisa; Senent, Leonor; Alonso, Esther; Ramos, Fernando; Ardanaz, María Teresa; Pedro, Carme; Tormo, Mar; Marco, Víctor; Montoro, Julia; Díez-Campelo, María; Brunet, Salut; Arrizabalaga, Beatriz; Xicoy, Blanca; Andreu, Rafael; Bonanad, Santiago; Jerez, Andrés; Nomdedeu, Benet; Ferrer, Ana; Sanz, Guillermo F; Florensa, Lourdes

    2016-09-20

    WHO classification of myeloid malignancies is based mainly on the percentage of bone marrow (BM) blasts. This is considered from total nucleated cells (TNCs), unless there is erythroid-hyperplasia (erythroblasts ≥ 50%), calculated from nonerythroid cells (NECs). In these instances, when BM blasts are ≥ 20%, the disorder is classified as erythroleukemia, and when BM blasts are < 20%, as myelodysplastic syndrome (MDS). In the latter, the percentage of blasts is considered from TNCs. We assessed the percentage of BM blasts from TNCs and NECs in 3,692 patients with MDS from the Grupo Español de Síndromes Mielodisplásicos, 465 patients with erythroid hyperplasia (MDS-E) and 3,227 patients without erythroid hyperplasia. We evaluated the relevance of both quantifications on classification and prognostication. By enumerating blasts systematically from NECs, 22% of patients with MDS-E and 12% with MDS from the whole series diagnosed within WHO categories with < 5% BM blasts, were reclassified into higher-risk categories and showed a poorer overall survival than did those who remained in initial categories (P = .006 and P = .001, respectively). Following WHO recommendations, refractory anemia with excess blasts (RAEB)-2 diagnosis is not possible in MDS-E, as patients with 10% to < 20% BM blasts from TNCs fulfill erythroleukemia criteria; however, by considering blasts from NECs, 72 patients were recoded as RAEB-2 and showed an inferior overall survival than did patients with RAEB-1 without erythroid hyperplasia. Recalculating the International Prognostic Scoring System by enumerating blasts from NECs in MDS-E and in the overall MDS population reclassified approximately 9% of lower-risk patients into higher-risk categories, which indicated the survival expected for higher-risk patients. Regardless of the presence of erythroid hyperplasia, calculating the percentage of BM blasts from NECs improves prognostic assessment of MDS. This fact should be considered in future

  14. Lenalidomide induces lipid raft assembly to enhance erythropoietin receptor signaling in myelodysplastic syndrome progenitors.

    Science.gov (United States)

    McGraw, Kathy L; Basiorka, Ashley A; Johnson, Joseph O; Clark, Justine; Caceres, Gisela; Padron, Eric; Heaton, Ruth; Ozawa, Yukiyasu; Wei, Sheng; Sokol, Lubomir; List, Alan F

    2014-01-01

    Anemia remains the principal management challenge for patients with lower risk Myelodysplastic Syndromes (MDS). Despite appropriate cytokine production and cellular receptor display, erythropoietin receptor (EpoR) signaling is impaired. We reported that EpoR signaling is dependent upon receptor localization within lipid raft microdomains, and that disruption of raft integrity abolishes signaling capacity. Here, we show that MDS erythroid progenitors display markedly diminished raft assembly and smaller raft aggregates compared to normal controls (p = 0.005, raft number; p = 0.023, raft size). Because lenalidomide triggers raft coalescence in T-lymphocytes promoting immune synapse formation, we assessed effects of lenalidomide on raft assembly in MDS erythroid precursors and UT7 cells. Lenalidomide treatment rapidly induced lipid raft formation accompanied by EpoR recruitment into raft fractions together with STAT5, JAK2, and Lyn kinase. The JAK2 phosphatase, CD45, a key negative regulator of EpoR signaling, was displaced from raft fractions. Lenalidomide treatment prior to Epo stimulation enhanced both JAK2 and STAT5 phosphorylation in UT7 and primary MDS erythroid progenitors, accompanied by increased STAT5 DNA binding in UT7 cells, and increased erythroid colony forming capacity in both UT7 and primary cells. Raft induction was associated with F-actin polymerization, which was blocked by Rho kinase inhibition. These data indicate that deficient raft integrity impairs EpoR signaling, and provides a novel strategy to enhance EpoR signal fidelity in non-del(5q) MDS.

  15. Polymorphisms of Interlukin-1β rs16944 confer susceptibility to myelodysplastic syndromes.

    Science.gov (United States)

    Yin, Congcong; He, Na; Li, Peng; Zhang, Chen; Yu, Jie; Hua, Mingqiang; Ji, Chunyan; Ma, Daoxin

    2016-11-15

    Genetic factors have been shown to be associated with Myelodysplastic syndromes (MDS) susceptibility. In recent years, the role of inflammation in the promotion of tumor growth is supported by a broad range of experimental and clinical evidence. But the relationship between polymorphisms in NOD-like receptor protein 3 (NLRP3) inflammasome and MDS is rarely reported. Thus, we conducted a case-control study, and genotyped five single nucleotide polymorphisms (SNPs) (NLRP3, IL-1β, IL-18, CARD8, and NF-κB) in MDS patients and healthy controls. The association of different genotypes with patient characteristics was analyzed. Comparing MDS patients with controls, GG genotype of IL-1β (rs16944) was observed to be associated with a significantly increased risk of MDS 78/166 (48.8%) vs 26/96 (27.0%), OR=2.1, CI (1.0-4.4). No significant association was identified regarding the rest of investigated polymorphisms and MDS susceptibility. Complex karyotypes were more frequent in patients with GG genotype of IL-1β (rs16944). Patients with IL-1β polymorphisms (rs16944) GG and GA had lower hemoglobin than those without. Patients with IL-1β polymorphisms (rs16944) GG had higher IPSS scores than those without IL-1β polymorphisms. In conclusion, our present data shows that the IL-1β polymorphisms (rs16944) GG were frequently occurred in MDS. IL-1β (rs16944) GG genotype might serve as a novel biomarker and potential targets for MDS. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Chromosomal instability and the abrogated G2/M arrest in x-irradiated myelodysplastic syndrome cells

    International Nuclear Information System (INIS)

    Ban, S.; Sudo, H.; Saegusa, K.; Sagara, M.; Imai, T.; Kimura, A.

    2003-01-01

    A preliminary epidemiological study demonstrated that myelodysplastic syndrome (MDS) has an excess relative risk per sievert of 13 in atomic bomb survivors in Hiroshima. MDS is the only other radiogenic blood disease apart from leukemia. Clinically, MDS involves dysplastic hematopoiesis and an increased risk of leukemic transformation. Because it is uncertain whether MDS pathogenesis affects lymphoid progenitor cells as well as myeloid progenitor cells, we investigated the karyotypes of bone marrow cells and the micronucleus (MN) frequency in peripheral T lymphocytes of twenty- three atomic bomb survivors with MDS and five normal individuals. Aneuploidy was observed in 10 of 23 patients. Chromosome aberrations were observed in 3 of 12 patients with mild symptoms, and six of 11 patients of severe symptoms. The spontaneous- and X-ray-induced-MN frequencies were significantly higher in MDS patients than in normal individuals. Interestingly, radiation sensitivity increased along with the severity of MDS clinical subtypes. Because many of the patients in this study had not been exposed to chemo- or radiation- therapy, their unusual radiosensitivity may be related to their chromosomal or genomic instability. Immortalized lymphoid cell lines were established from B-lymphocytes infected with Epstein-Barr virus in vitro. The abrogation of radiation-induced-G2/M arrest was observed in 10 of 12 MDS-B lymphoid cell lines, but not in the normal B lymphoid cell lines. Our data suggest that the control of chromosomal stability is impaired in pluripotent stem cells of MDS patients, and that the abrogated G2/M arrest may be involved in the pathophysiology of disease progression and the high radiation sensitivity of patients

  17. Clinical Features and Outcomes of 666 Cases with Therapy-Related Myelodysplastic Syndrome (t-MDS).

    Science.gov (United States)

    El-Fattah, Mohamed Abd

    2018-01-01

    Therapy-related myelodysplastic syndrome (t-MDS) is a serious complication of chemoradiotherapy for primary diseases. This cohort was aimed to determine the clinical features and outcomes of t-MDS in comparison with de novo MDS. I retrieved data of 666 cases with t-MDS, and 29,703 cases with de novo MDS diagnosed between 2001 and 2012 from the database of U.S. National Cancer Institute. Survival curves were estimated, and Cox proportional hazards model was constructed. Compared with patients with de novo MDS, patients with t-MDS tended to be young (median age; 65 vs. 76 years, p  MDS than de novo MDS (17.2 months and 22% vs. 31 months and 32%, respectively, p  MDS cases, with a median follow-up of 16 months (range 1-143 months), 521 cases (78.2%) had died. Of which, 78 (15%) cases had died from acute myeloid leukemia, and 66 (12.7%) cases had died from solid cancers. Of the total 66 cases died from solid cancers; 19 cases (28.8%) died from cancer of lung/bronchus, 11 cases (16.7%) breast cancers, and 10 cases (15.2%) ovarian cancer. In a multivariate analysis adjusted for clinical features, calendar period and radiotherapy, the hazard of mortality was significantly low in de novo MDS compared with t-MDS (hazard ratio 0.59; p  MDS is a distinct entity of MDS in terms of clinical characteristics and prognosis.

  18. Impact of socioeconomic status on disease phenotype, genomic landscape and outcomes in myelodysplastic syndromes.

    Science.gov (United States)

    Mastaglio, Francesca; Bedair, Khaled; Papaemmanuil, Elli; Groves, Michael J; Hyslop, Ann; Keenan, Norene; Hothersall, Eleanor J; Campbell, Peter J; Bowen, David T; Tauro, Sudhir

    2016-07-01

    Genetic and epigenetic alterations contribute to the biological and clinical characteristics of myelodysplastic syndromes (MDS), but a role for socioeconomic environment remains unclear. Here, socioeconomic status (SES) for 283 MDS patients was estimated using the Scottish Index of Multiple Deprivation tool. Indices were assigned to quintile categorical indicators ranked from SES1 (lowest) to SES5 (highest). Clinicopathological features and outcomes between SES quintiles containing 15%, 20%, 19%, 30% and 16% of patients were compared. Prognostic scores identified lower-risk MDS in 82% of patients, with higher-risk disease in 18%. SES quintiles did not associate with age, gender, cytogenetics, International Prognostic scores or, in sub-analysis (n = 95), driver mutations. The odds ratio of a diagnosis of refractory anaemia was greater than other MDS sub-types in SES5 (OR 1·9, P = 0·024). Most patients (91%) exclusively received supportive care. SES did not associate with leukaemic transformation or cause of death. Cox regression models confirmed male gender (P < 0·05), disease-risk (P < 0·0001) and age (P < 0·01) as independent predictors of leukaemia-free survival, with leukaemic transformation an additional determinant of overall survival (P = 0·07). Thus, if access to healthcare is equitable, SES does not determine disease biology or survival in MDS patients receiving supportive treatment; additional studies are required to determine whether outcomes following disease-modifying therapies are influenced by SES. © 2016 John Wiley & Sons Ltd.

  19. Myelodysplastic syndrome and pancytopenia responding to treatment of hyperthyroidism: Peripheral blood and bone marrow analysis before and after antihormonal treatment

    Directory of Open Access Journals (Sweden)

    Akoum Riad

    2007-01-01

    Full Text Available Hematological disorders, especially single lineage abnormalities, have been described in hyperthyroidism. Pancytopenia has been reported, without myelodysplastic syndrome or megaloblastic anemia. We studied the peripheral blood smear and the bone marrow aspiration and biopsy of a 65-year-old lady, who presented with pancytopenia and thyrotoxicosis due to multinodular goiter. She denied ingesting any toxic medication. At diagnosis: WBC: 2500 /ul, platelets count: 58.000/ul, hemoglobin level: 6.5 g/dl. The bone marrow was moderately hyper cellular with moderate myelofibrosis and arrested hematopoiesis. The TSH level was: 0.02 mIU/l (N: 0.25-4, the fT3: 18 pmol/l (N: 4-10, the routine serum immunologic tests were negative. After treatment with single agent neomercazole (carbimazole, complete recovery of the blood cell counts was obtained within one month. The bone marrow aspiration, performed three months after starting therapy, showed normal hematopoiesis. The thyroid function tests returned to normal and no autoimmune reaction was detected on routine serum testing. Persistent response was observed six months later under medical treatment. The patient has refused surgical treatment. Reversible myelodysplastic syndrome may also be part of the changes in blood picture of patients with hyperthyroidism, probably due to direct toxic mechanism.

  20. Developments in the treatment of transfusion-dependent anemia in patients with myelodysplastic syndromes: epidemiology, etiology, genetics, and targeted therapies

    Directory of Open Access Journals (Sweden)

    Raza A

    2014-07-01

    Full Text Available Azra Raza, Nicholas Iverson, Abdullah M AliThe MDS Center, Columbia University, New York, NY, USAAbstract: Myelodysplastic syndromes are malignant hematopoietic stem cell disorders that present with variable cytopenias and predominantly affect the elderly. Treatment options are limited, with allogeneic transplant being the only potentially curative strategy. Recent mutational profiling studies have led to cataloguing of driver and passenger mutations most commonly affecting the epigenetic regulators and genes involved in RNA splicing. Despite improved understanding of the disease biology, these emerging molecular insights have not led to identification of novel therapeutic strategies. Although several drugs approved in the last decade improve the cytopenias, the relief is temporary, most likely due to the sequential activation of clones. Future advances depend upon identification of signaling pathways in dominant clones and targeting these with agents that might be known but need to be matched to suit the needs of individual patients in a longitudinal, dynamic fashion. Myelodysplastic syndromes are ideally suited for the development of such personalized medicine.Keywords: cancer, epigenetics, iron, MDS, myelodysplasia, splicing

  1. WHO-defined 'myelodysplastic syndrome with isolated del(5q)' in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations.

    Science.gov (United States)

    Patnaik, M M; Lasho, T L; Finke, C M; Gangat, N; Caramazza, D; Holtan, S G; Pardanani, A; Knudson, R A; Ketterling, R P; Chen, D; Hoyer, J D; Hanson, C A; Tefferi, A

    2010-07-01

    The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with 'myelodysplastic syndrome with isolated del(5q)' (median age 74 years; 60 females). In all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age >or=70 years (P=0.01), transfusion need at diagnosis (P=0.04) and dysgranulopoiesis (P=0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or >or=2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, respectively. Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), isocitrate dehydrogenase 1 (IDH1) and IDH2 mutational analysis was performed on archived bone marrows in 78 patients; JAK2V617F and MPLW515L mutations were shown in five (6.4%) and three (3.8%) patients, respectively, and did not seem to affect phenotype or prognosis. IDH mutations were not detected. Survival was not affected by serum ferritin and there were no instances of death directly related to iron overload. The current study is unique in its strict adherence to WHO criteria for selecting study patients and providing information on long-term survival, practical prognostic factors, baseline risk of leukemic transformation and the prevalence of JAK2, MPL and IDH mutations.

  2. Lenalidomide for the Treatment of Low- or Intermediate-1-Risk Myelodysplastic Syndromes Associated with Deletion 5q Cytogenetic Abnormality: An Evidence Review of the NICE Submission from Celgene

    NARCIS (Netherlands)

    H.M. Blommestein (Hedwig); N. Armstrong (Nigel); S. Ryder; S. Deshpande (Sohan); G. Worthy (Gill); C. Noake; R. Riemsma (Rob); J. Kleijnen (Jos); J.L. Severens (Hans); M.J. Al (Maiwenn)

    2016-01-01

    textabstractThe National Institute for Health and Care Excellence (NICE) invited the manufacturer of lenalidomide (Celgene) to submit evidence of the clinical and cost effectiveness of the drug for treating adults with myelodysplastic syndromes (MDS) associated with deletion 5q cytogenetic

  3. In vivo measurements of the T1 relaxation processes in the bone marrow in patients with myelodysplastic syndrome. A magnetic resonance imaging study

    DEFF Research Database (Denmark)

    Jensen, K E; Nielsen, H; Thomsen, C

    1989-01-01

    Nine patients with myelodysplastic syndrome (MDS) were examined with magnetic resonance imaging and in vivo T1 relaxation time measurements of the vertebral bone marrow in a 1.5 tesla whole body scanner. Two patients underwent transformation to acute myeloid leukemia and were evaluated at follow-...... not differ from patients with polycythemia vera....

  4. Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2013-01-09

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Melanoma; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer

  5. Aberrations of chromosome 8 in myelodysplastic syndromes: Clinical and biological significance

    Directory of Open Access Journals (Sweden)

    Marisavljević Dragomir

    2006-01-01

    Full Text Available Introduction: Rearrangements of any single chromosome in human karyotype have been reported in patients with pMDS. Objective: To examine the role of aberrations of chromosome 8 in pathogenesis, clinical presentation and progression of myelodysplastic syndromes. Method: Cytogenetic analysis of bone marrow cells was carried out by direct method and by means of 24- and/or 48-hour unstimulated cell culture. Chromosomes were obtained by modified method of HG-bands. Results: On presentation, 109 out of 271 successfully karyotyped patients (40,2% had abnormal karyotypes. Among them, 22 patients (10.9% had aberrations of chromosome 8. Ten patients had trisomy 8 as "simple" aberration whilst additional three cases had trisomy 8 included in "complex" karyotypes (≥3 chromosomes. Cases with constitutional trisomy 8 mosaicism (CT8M were excluded using the chromosome analyses of PHA-stimulated blood cultures. On the contrary, monosomy (seven patients or deletion of chromosome 8 (two patients were exclusively found in "complex" karyotypes. During prolonged cytogenetic follow-up, trisomy 8 was not recorded in evolving karyotypes. In contrast, trisomy 8 disappeared in two cases during subsequent cytogenetic studies, i.e. 23 and 72 months from diagnosis, accompanied in one patient with complete hematological remission. No difference regarding age, sex, cytopenia, blood and marrow blast count or response to treatment was found between patients with trisomy 8 as the sole aberration compared to those with normal cytogenetics. Median survival of patients with trisomy 8 as the sole aberration was 27 months, as compared to 32 months in patients with normal cytogenetics (p=0.468, whilst median survival of patients with aberrations of chromosome 8 included in "complex" karyotypes was only 4 months. Conclusion: Aberrations of chromosome 8 are common in patients with pMDS. The presence of a clone with trisomy 8 is not always the sign of disease progression or poor

  6. Mayo Alliance Prognostic Model for Myelodysplastic Syndromes: Integration of Genetic and Clinical Information.

    Science.gov (United States)

    Tefferi, Ayalew; Gangat, Naseema; Mudireddy, Mythri; Lasho, Terra L; Finke, Christy; Begna, Kebede H; Elliott, Michelle A; Al-Kali, Aref; Litzow, Mark R; Hook, C Christopher; Wolanskyj, Alexandra P; Hogan, William J; Patnaik, Mrinal M; Pardanani, Animesh; Zblewski, Darci L; He, Rong; Viswanatha, David; Hanson, Curtis A; Ketterling, Rhett P; Tang, Jih-Luh; Chou, Wen-Chien; Lin, Chien-Chin; Tsai, Cheng-Hong; Tien, Hwei-Fang; Hou, Hsin-An

    2018-06-01

    To develop a new risk model for primary myelodysplastic syndromes (MDS) that integrates information on mutations, karyotype, and clinical variables. Patients with World Health Organization-defined primary MDS seen at Mayo Clinic (MC) from December 28, 1994, through December 19, 2017, constituted the core study group. The National Taiwan University Hospital (NTUH) provided the validation cohort. Model performance, compared with the revised International Prognostic Scoring System, was assessed by Akaike information criterion and area under the curve estimates. The study group consisted of 685 molecularly annotated patients from MC (357) and NTUH (328). Multivariate analysis of the MC cohort identified monosomal karyotype (hazard ratio [HR], 5.2; 95% CI, 3.1-8.6), "non-MK abnormalities other than single/double del(5q)" (HR, 1.8; 95% CI, 1.3-2.6), RUNX1 (HR, 2.0; 95% CI, 1.2-3.1) and ASXL1 (HR, 1.7; 95% CI, 1.2-2.3) mutations, absence of SF3B1 mutations (HR, 1.6; 95% CI, 1.1-2.4), age greater than 70 years (HR, 2.2; 95% CI, 1.6-3.1), hemoglobin level less than 8 g/dL in women or less than 9 g/dL in men (HR, 2.3; 95% CI, 1.7-3.1), platelet count less than 75 × 10 9 /L (HR, 1.5; 95% CI, 1.1-2.1), and 10% or more bone marrow blasts (HR, 1.7; 95% CI, 1.1-2.8) as predictors of inferior overall survival. Based on HR-weighted risk scores, a 4-tiered Mayo alliance prognostic model for MDS was devised: low (89 patients), intermediate-1 (104), intermediate-2 (95), and high (69); respective median survivals (5-year overall survival rates) were 85 (73%), 42 (34%), 22 (7%), and 9 months (0%). The Mayo alliance model was subsequently validated by using the external NTUH cohort and, compared with the revised International Prognostic Scoring System, displayed favorable Akaike information criterion (1865 vs 1943) and area under the curve (0.87 vs 0.76) values. We propose a simple and contemporary risk model for MDS that is based on a limited set of genetic and clinical variables

  7. A genome-wide association study by ImmunoChip reveals potential modifiers in myelodysplastic syndromes.

    Science.gov (United States)

    Danjou, Fabrice; Fozza, Claudio; Zoledziewska, Magdalena; Mulas, Antonella; Corda, Giovanna; Contini, Salvatore; Dore, Fausto; Galleu, Antonio; Di Tucci, Anna Angela; Caocci, Giovanni; Gaviano, Eleonora; Latte, Giancarlo; Gabbas, Attilio; Casula, Paolo; Delogu, Lucia Gemma; La Nasa, Giorgio; Angelucci, Emanuele; Cucca, Francesco; Longinotti, Maurizio

    2016-11-01

    Because different findings suggest that an immune dysregulation plays a role in the pathogenesis of myelodysplastic syndrome (MDS), we analyzed a large cohort of patients from a homogeneous Sardinian population using ImmunoChip, a genotyping array exploring 147,954 single-nucleotide polymorphisms (SNPs) localized in genomic regions displaying some degree of association with immune-mediated diseases or pathways. The population studied included 133 cases and 3,894 controls, and a total of 153,978 autosomal markers and 971 non-autosomal markers were genotyped. After association analysis, only one variant passed the genome-wide significance threshold: rs71325459 (p = 1.16 × 10 -12 ), which is situated on chromosome 20. The variant is in high linkage disequilibrium with rs35640778, an untested missense variant situated in the RTEL1 gene, an interesting candidate that encodes for an ATP-dependent DNA helicase implicated in telomere-length regulation, DNA repair, and maintenance of genomic stability. The second most associated signal is composed of five variants that fall slightly below the genome-wide significance threshold but point out another interesting gene candidate. These SNPs, with p values between 2.53 × 10 -6 and 3.34 × 10 -6 , are situated in the methylene tetrahydrofolate reductase (MTHFR) gene. The most associated of these variants, rs1537514, presents an increased frequency of the derived C allele in cases, with 11.4% versus 4.4% in controls. MTHFR is the rate-limiting enzyme in the methyl cycle and genetic variations in this gene have been strongly associated with the risk of neoplastic diseases. The current understanding of the MDS biology, which is based on the hypothesis of the sequential development of multiple subclonal molecular lesions, fits very well with the demonstration of a possible role for RTEL1 and MTHFR gene polymorphisms, both of which are related to a variable risk of genomic instability. Copyright © 2016 ISEH - International

  8. Primary myelodysplastic syndrome with complex chromosomal rearrangements in a patient with Klinefelter's syndrome.

    OpenAIRE

    Abidi, S M; Griffiths, M; Oscier, D G; Mufti, G J; Hamblin, T J

    1986-01-01

    A patient with Klinefelter's syndrome and diabetes mellitus was diagnosed as having myelodysplasia. Cytogenetic analysis of the peripheral blood and the bone marrow cells confirmed the presence of a constitutional 47,XXY chromosome complement. In addition, complex karyotypic abnormalities were present.

  9. Síndromes mielodisplásicas e mielodisplásicas/mieloproliferativas Myelodysplastic syndromes and diseases with myelodysplastic and myeloproliferative features

    Directory of Open Access Journals (Sweden)

    José Vassallo

    2009-08-01

    Full Text Available As síndromes mielodisplásicas (SMD representam um grupo heterogêneo de doenças hematológicas caracterizadas por hematopoese ineficaz e risco aumentado de evolução para leucemia mieloide aguda. Neste artigo educativo são apresentados aspectos gerais da sua fisiopatologia, diagnóstico, apresentação histopatológica e seu papel no diagnóstico diferencial, classificação e estratificação prognóstica. Ressalta-se a importância da avaliação clínica e laboratorial, que inclui avaliação do sangue periférico e medula óssea: morfologia - aspirado medular e biópsia óssea -, citogenética, imunofenotipagem, além de dados evolutivos. O diagnóstico definitivo, em especial nos casos de baixo risco, deve considerar a exclusão de causas não clonais que podem, através de alterações dismielopoéticas reativas, simular a mielodisplasia, tais como infecções virais, principalmente pelo HIV. A nova classificação revisada da Organização Mundial da Saúde (OMS-2008 é apresentada e discutida.Myelodysplastic syndromes (MDS represent a heterogeneous group of hematologic disorders characterized by ineffective hematopoiesis and an increased risk of developing acute myeloid leukemia. In this educational article the general aspects of the physiopathology, diagnosis, and histopathological features of MDS and their role in differential diagnosis, classification and prognostic categorization are presented. The importance of clinical and laboratory evaluations, including peripheral blood and bone marrow analyses, including morphology - aspirate and core biopsy, cytogenetics, immunophenotype and careful serial follow-up is emphasized. Definite diagnosis of MDS, especially in low-risk subtypes, should consider the exclusion of disorders with reactive bone marrow alterations, such as viral infections for example HIV. The new revised World Health Organization (WHO-2008 classification is presented and discussed.

  10. Increasing the effectiveness of hematopoiesis in myelodysplastic syndromes: erythropoiesis-stimulating agents and transforming growth factor-β superfamily inhibitors.

    Science.gov (United States)

    Mies, Anna; Platzbecker, Uwe

    2017-07-01

    Patients with lower-risk myelodysplastic syndromes (MDS) are mainly affected by chronic anemia and fatigue. Treatment strategies aim to improve anemia and quality of life, as well as iron overload due to red blood cell transfusion support. To promote proliferation and differentiation of erythropoiesis, erythropoiesis-stimulating agents (ESAs) such as erythropoietin (EPO) and mimetics are applied as first-line therapy in a large fraction of lower-risk MDS patients. In general, ESAs yield favorable responses in about half of the patients, although responses are often short-lived. In fact, many ESA-refractory patients harbor defects in late-stage erythropoiesis downstream of EPO action. Novel transforming growth factor (TGF)-β superfamily inhibitors sotatercept and luspatercept represent a promising approach to alleviate anemia by stimulating erythroid differentiation. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Cytogenetic evidence of metastatic myxoid liposarcoma and therapy-related myelodysplastic syndrome in a bone marrow biopsy.

    Science.gov (United States)

    Rossi, Sabrina; Canal, Fabio; Licci, Stefano; Zanatta, Lucia; Laurino, Licia; Gottardi, Michele; Gherlinzoni, Filippo; Dei Tos, Angelo Paolo

    2009-07-01

    Myxoid liposarcoma exhibits a peculiar clinical behavior, with a tendency to spread to serosal membranes, distant soft tissues, and bones, even in the absence of lung metastases. Therapy-related hematological neoplasms are well-known side effects of cytotoxic chemotherapy. We describe an exceptional case of metastatic myxoid liposarcoma of the spine associated with therapy-related refractory anemia with excess of blasts in a 37-year-old woman who underwent multi-agent chemotherapy for a myxoid liposarcoma of the left thigh. Microscopic examination of the bone marrow biopsy revealed dysplastic features, with abnormal localization of immature precursors and micromegakaryocytes, and islands of undifferentiated oval small/medium-size cells, suggestive of acute myeloid leukemia arising in the setting of a myelodysplastic syndrome. Immunohistochemistry was not discriminant. Cytogenetic analyses of bone marrow aspirate disclosed the presence of 2 different rearrangements, subsequently confirmed by fluorescent in situ hybridization and was crucial in making the correct diagnosis.

  12. Diagnosis, management and response criteria of iron overload in myelodysplastic syndromes (MDS): updated recommendations of the Austrian MDS platform.

    Science.gov (United States)

    Valent, Peter; Stauder, Reinhard; Theurl, Igor; Geissler, Klaus; Sliwa, Thamer; Sperr, Wolfgang R; Bettelheim, Peter; Sill, Heinz; Pfeilstöcker, Michael

    2018-02-01

    Despite the availability of effective iron chelators, transfusion-related morbidity is still a challenge in chronically transfused patients with myelodysplastic syndromes (MDS). In these patients, transfusion-induced iron overload may lead to organ dysfunction or even organ failure. In addition, iron overload is associated with reduced overall survival in MDS. Areas covered: During the past 10 years, various guidelines for the management of MDS patients with iron overload have been proposed. In the present article, we provide our updated recommendations for the diagnosis, prevention and therapy of iron overload in MDS. In addition, we propose refined treatment response criteria. As in 2006 and 2007, recommendations were discussed and formulated by participants of our Austrian MDS platform in a series of meetings in 2016 and 2017. Expert commentary: Our updated recommendations should support early recognition of iron overload, optimal patient management and the measurement of clinical responses to chelation treatment in daily practice.

  13. Severe atypical herpes zoster as an initial symptom of fatal myelodysplastic syndrome with refractory anemia and blast excess (RAEB II

    Directory of Open Access Journals (Sweden)

    Wollina U

    2017-05-01

    Full Text Available Uwe Wollina,1 Gesina Hansel,1 Anja Baunacke,1 Georgi Tchernev2 1Department of Dermatology and Allergology, Academic Teaching Hospital Dresden-Friedrichstadt, Dresden, Germany; 2Department of Dermatology and Dermatologic Surgery, Medical Institute of Ministry of Interior (MVR, Sofia, Bulgaria Abstract: Herpes zoster is a common disease caused due to varicella zoster virus (VZV infection with increasing incidence by age. If the patient has a severe, extended, or treatment-recalcitrant course of herpes zoster, this must be a red flag to search for underlying pathologies. Here, we report about a 64-year-old male patient with diabetes, who came to our emergency department because of general malaise, fever, chills, and a pronounced nuchal and facial swelling on the left side. Based on herpetiform-grouped vesicles and yellowish crusts, an impetiginized facial herpes zoster was diagnosed, and combined antiviral and antibiotic treatment was initiated. He was HIV negative. Despite intensified treatment, his situation worsened. We observed blasts in peripheral blood, but bone marrow biopsy was initially denied. Some days later after deterioration of his disease, he accepted further diagnostics. A myelodysplastic syndrome with blast excess (refractory anemia and blast excess II, RAEB II could be confirmed. The following translocations were detected: t(2;12(p13; q13 and t(6;9(p22;q34. REAB II has an unfortunate prognosis. Cytoreductive treatment was initiated by the hemato-oncologist. Unfortunately, the patient deceased due to septic shock. Keywords: herpes zoster, varicella zoster virus, myelodysplastic syndrome, sepsis, emergency

  14. Síndromes mielodisplásicas: protocolo de exclusão Myelodysplastic syndrome: diagnostic protocol

    Directory of Open Access Journals (Sweden)

    Silvia Maria M. Magalhães

    2004-12-01

    Full Text Available As síndromes mielodisplásicas (SMD são doenças hematológicas clonais com apresentação heterogênea que resultam em insuficiência medular progressiva e evolução para leucemia aguda. A anemia é um achado comum na apresentação. Nos pacientes idosos, a anemia não é atribuída ao processo normal de senescência, portanto, uma etiologia pode ser identificada na maioria dos casos. A presença de citopenias associadas a alterações displásticas medulares podem também ser devidas a condições não clonais secundárias e reversíveis. Alterações citogenéticas são observadas numa proporção de pacientes portadores de SMD contribuindo para o diagnóstico diferencial e prognóstico. A avaliação laboratorial para demonstração de clonalidade não está rotineiramente disponível. O diagnóstico de SMD é, portanto, um diagnóstico de exclusão, por vezes firmado após um período mínimo de seguimento. Considerando a teoria de múltiplas etapas proposta para a patogênese, os pacientes considerados de baixo grau, com alterações displásticas mínimas, podem apresentar dificuldade no diagnóstico. A deficiência de vitamina B12 e/ou folato, a exposição recente a metais pesados, terapia citotóxica ou fatores de crescimento devem ser considerados fatores de exclusão absolutos. O etilismo, doenças inflamatórias crônicas, auto-imunes, insuficiência hepática ou renal, disfunções hormonais e infecções virais, incluindo SIDA, devem ser descartados ou interpretados com cautela. Algumas doenças da célula-tronco pluripotencial devem também ser consideradas no diagnóstico diferencial. A exclusão de hemoglobinúria paroxística noturna e anemia aplástica pode ser difícil em casos de SMD hipocelular. Em resumo, a presença de alterações displásticas, por si, não estabelece o diagnóstico de SMD e um protocolo de exclusão deve ser rotineiramente realizado.Myelodysplastic syndromes are clonal hematological diseases with

  15. Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

    Science.gov (United States)

    2017-03-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  16. Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases

    International Nuclear Information System (INIS)

    Michels, S.D.; McKenna, R.W.; Arthur, D.C.; Brunning, R.D.

    1985-01-01

    This study consists of 65 patients (pts) who developed a myelodysplastic syndrome (MDS) (39 pts) or acute myeloid leukemia (AML) (26 pts) following chemotherapy and/or radiotherapy; the interval from the onset of therapy to bone marrow abnormality ranged from 11 to 192 months (median, 58). Thirty-three patients had been previously treated for lymphoproliferative diseases, 29 for carcinoma, and three for a nonneoplastic disorder. Approximately 30% of the cases presenting in the MDS phase evolved to AML in one to 12 months (median, 3.5). The AML in 49% of the cases was not readily classified according to French-American-British (FAB) criteria; the primary difficulty in classification related to the involvement of multiple cell lines. Among the cases that could be classified, all FAB types were represented except for M1; M2 was the most frequent type. Clonal chromosome abnormalities were found in marrow specimens from 22 of 24 (92%) patients studied with G banding; 11 had abnormalities of chromosomes 5 and/or 7. The median survival for all patients was four months with no significant difference between those treated and not treated with antileukemic therapy. The median survival was three months for the patients presenting with AML, six months for the patients with AML following an MDS, and four months for the patients with an MDS that did not evolve to AML. The findings in the present study suggest that there are three stages of therapy-related panmyelosis: (1) pancytopenia with associated myelodysplastic changes, (2) a frank MDS, and (3) overt AML. Many patients will present in the stage of overt AML that differs from de novo AML primarily by the high incidence of trilineage involvement, difficulty in classification, frequent cytogenetic abnormalities, and poor response to antileukemic therapy

  17. Síndrome mielodisplásica na infância Myelodysplastic syndromes in childhood

    Directory of Open Access Journals (Sweden)

    Luiz F. Lopes

    2006-09-01

    ,7%. Quanto à evolução clínica dos pacientes encontramos: óbito em 54,8% dos casos, remissão espontânea em 5,4% e 16,1% encontrava-se em tratamento conservador. Infecções em pacientes com SMD e naqueles que sofreram transformação leucêmica foram as causas mais freqüentes de óbito (58,8%. Propomos também neste artigo uma abordagem de diagnóstico em genética e biologia molecular voltada para os casos infantis assim como uma revisão de literatura sobre transplante de medula óssea para os casos pediátricos, além de outros aspectos que diferem da abordagem feita para pacientes adultos.The Brazilian Cooperative Study Group on Pediatric Myelodysplastic Syndromes (GCB-SMD-PED started in January 1997 with the goal of studying under 18-year-old patients with MDS or suspected MDS from all over the country. Some primary or secondary disorders are incorrectly called MDS. Because of this the GCB-SMD-PED is a referral group in the country to review and also to give diagnostic support (morphology, genetics, etc.. Some groups still use the FAB classification but two new classifications for pediatric cases have been published: one from the Sick Children's Hospital, University of Toronto, Canada the "CCC Classification" (category, cytology and cytogenetic, and the WHO pediatric classification by Hasle et al. Our proposal here is to present data from the 173 pediatric cases which were referred to the GCB-SMD-PED from 15 states (41 centers. From 1983 to 1997, 51 pediatric cases were registered as retrospective cases and from January 1998 to February 2003, 122 prospective cases were registered. From these 173 cases, 93 where confirmed as MDS. In 36.5% of them there was a transformation into acute leukemia with 82.3% as AML and 17.7% as ALL. The follow up showed that 54.8% died, 5.4% had spontaneous remission and 16.1% were in treatment with no chemotherapy (just transfusion or conservative approach. Infections were the primary cause of death (58.8%. Additionally, in this

  18. Additional Treatments for High-Risk Obstetric Antiphospholipid Syndrome: a Comprehensive Review.

    Science.gov (United States)

    Ruffatti, Amelia; Hoxha, Ariela; Favaro, Maria; Tonello, Marta; Colpo, Anna; Cucchini, Umberto; Banzato, Alessandra; Pengo, Vittorio

    2017-08-01

    Most investigators currently advocate prophylactic-dose heparin plus low-dose aspirin as the preferred treatment of otherwise healthy women with obstetric antiphospholipid syndrome, whilst women with a history of vascular thrombosis alone or associated with pregnancy morbidity are usually treated with therapeutic heparin doses in association with low-dose aspirin in an attempt to prevent both thrombosis and pregnancy morbidity. However, the protocols outlined above fail in about 20 % of pregnant women with antiphospholipid syndrome. Identifying risk factors associated with pregnancy failure when conventional therapies are utilized is an important step in establishing guidelines to manage these high-risk patients. Some clinical and laboratory risk factors have been found to be related to maternal-foetal complications in pregnant women on conventional therapy. However, the most efficacious treatments to administer to high-risk antiphospholipid syndrome women in addition to conventional therapy in order to avoid pregnancy complications are as yet unestablished. This is a comprehensive review on this topic and an invitation to participate in a multicentre study in order to identify the best additional treatments to be used in this subset of antiphospholipid syndrome patients.

  19. Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes.

    Science.gov (United States)

    Svobodova, Karla; Zemanova, Zuzana; Lhotska, Halka; Novakova, Milena; Podskalska, Lucie; Belickova, Monika; Brezinova, Jana; Sarova, Iveta; Izakova, Silvia; Lizcova, Libuse; Berkova, Adela; Siskova, Magda; Jonasova, Anna; Cermak, Jaroslav; Michalova, Kyra

    2016-03-01

    Complex karyotypes are seen in approximately 20% of patients with myelodysplastic syndromes (MDS) and are associated with a high risk of transformation to acute myeloid leukemia and poor outcomes in patients. Copy number neutral loss of heterozygosity (CN-LOH, i.e., both copies of a chromosomal pair or their parts originate from one parent) might contribute to increased genomic instability in the bone-marrow cells of patients with MDS. The pathological potential of CN-LOH, which arises as a clonal aberration in a proportion of somatic cells, consists of tumor suppressor gene and oncogene homozygous mutations. The aim of our study was to evaluate the frequency of CN-LOH at 17p in bone-marrow cells of newly diagnosed MDS patients with complex chromosomal aberrations and to assess its correlation with mutations in the TP53 gene (17p13.1). CN-LOH was detected in 40 chromosomal regions in 21 (29%) of 72 patients analyzed. The changes in 27 of the 40 regions identified were sporadic. The most common finding was CN-LOH of the short arm of chromosome 17, which was detected in 13 (18%) of 72 patients. A mutational analysis confirmed the homozygous mutation of TP53 in all CN-LOH 17p patients, among which two frameshift mutations are not registered in the International Agency for Research on Cancer TP53 Database. CN-LOH 17p correlated with aggressive disease (median overall survival 4 months) and was strongly associated with a complex karyotype in the cohort studied, which might cause rapid disease progression in high-risk MDS. No other CN-LOH region previously recorded in MDS or AML patients (1p, 4q, 7q, 11q, 13q, 19q, 21q) was detected in our cohort of patients with complex karyotype examined at the diagnosis of MDS. The LOH region appeared to be balanced (i.e., with no DNA copy number change) when examined with conventional and molecular cytogenetic methods. Therefore, a microarray that detects single-nucleotide polymorphisms is an ideal method with which to identify and

  20. [Rapid prenatal genetic diagnosis of a fetus with a high risk for Morquio A syndrome].

    Science.gov (United States)

    Guo, Yi-bin; Ai, Yang; Zhao, Yan; Tang, Jia; Jiang, Wei-ying; Du, Min-lian; Ma, Hua-mei; Zhong, Yan-fang

    2012-04-01

    To provide rapid and accurate prenatal genetic diagnosis for a fetus with high risk of Morquio A syndrome. Based on ascertained etiology of the proband and genotypes of the parents, particular mutations of the GALNS gene were screened at 10th gestational week with amplification refractory mutation system (ARMS), denaturing high performance liquid chromatography (DHPLC), and direct DNA sequencing. DHPLC screening has identified abnormal double peaks in the PCR products of exons 1 and 10, whilst only a single peak was detected in normal controls. Amplification of ARMS specific primers derived a specific product for the fetus's gene, whilst no similar product was detected in normal controls. Sequencing of PCR products confirmed that exons 1 and 10 of the GALNS gene from the fetus contained a heterozygous paternal c.106-111 del (p.L36-L37 del) deletion and a heterozygous maternal c.1097 T>C (p.L366P) missense mutation, which resulted in a compound heterozygote status. The fetus was diagnosed with Morquio A syndrome and a genotype similar to the proband. Termination of the pregnancy was recommended. Combined ARMS, DHPLC and DNA sequencing are effective for rapid and accurate prenatal diagnosis for fetus with a high risk for Morquio A syndrome. Such methods are particularly suitable for early diagnosis when pathogenesis is clear. Furthermore, combined ARMS and DHPLC are suitable for rapid processing of large numbers of samples for the identification of new mutations.

  1. Oral Ezatiostat HCl (TLK199) and Myelodysplastic syndrome: a case report of sustained hematologic response following an abbreviated exposure.

    Science.gov (United States)

    Quddus, Fahd; Clima, Jessica; Seedham, Helen; Sajjad, Ghulam; Galili, Naomi; Raza, Azra

    2010-04-23

    Treatment options for patients with lower risk non-del(5q) myelodysplastic syndromes (MDS) who fail erythroid stimulating agents are restricted to one of the hypomethylating drugs with an expected response rate of approximately 50%. Ezatiostat HCl, an agent with the potential for producing multi-lineage responses in this population is currently in clinical investigation phase. This case report describes a 77 year old male who received less than two cycles of therapy with ezatiostat HCl which had to be aborted due to intolerable side effects, but which produced a sustained normalization of all three blood counts. This trilineage response has now lasted for more than a year. Interestingly, the patient began with a del(5q) abnormality and responded briefly to lenalidomide. Upon relapse of the anemia, a bone marrow showed the disappearance of the del(5q) but the appearance of a new clonal abnormality t(2;3). Given that the patient had a complete cytogenetic response to a truncated exposure to lenalidomide followed by a trilineage response to an even briefer course of ezatiostat HCl suggests a potential role for ezatiostat HCl in del(5q) patients who relapse following lenalidomide.

  2. Fluorescence in situ hybridization of TP53 for the detection of chromosome 17 abnormalities in myelodysplastic syndromes.

    Science.gov (United States)

    Sánchez-Castro, Judit; Marco-Betés, Víctor; Gómez-Arbonés, Xavier; García-Cerecedo, Tomás; López, Ricard; Talavera, Elisabeth; Fernández-Ruiz, Sara; Ademà, Vera; Marugan, Isabel; Luño, Elisa; Sanzo, Carmen; Vallespí, Teresa; Arenillas, Leonor; Marco Buades, Josefa; Batlle, Ana; Buño, Ismael; Martín Ramos, María Luisa; Blázquez Rios, Beatriz; Collado Nieto, Rosa; Vargas, Ma Teresa; González Martínez, Teresa; Sanz, Guillermo; Solé, Francesc

    2015-01-01

    Conventional G-banding cytogenetics (CC) detects chromosome 17 (chr17) abnormalities in 2% of patients with de novo myelodysplastic syndromes (MDS). We used CC and fluorescence in situ hybridization (FISH) (LSI p53/17p13.1) to assess deletion of 17p in 531 patients with de novo MDS from the Spanish Group of Hematological Cytogenetics. FISH detected - 17 or 17p abnormalities in 13 cases (2.6%) in whom no 17p abnormalities were revealed by CC: 0.9% of patients with a normal karyotype, 0% in non-informative cytogenetics, 50% of patients with a chr17 abnormality without loss of 17p and 4.7% of cases with an abnormal karyotype not involving chr17. Our results suggest that applying FISH of 17p13 to identify the number of copies of the TP53 gene could be beneficial in patients with a complex karyotype. We recommend using FISH of 17p13 in young patients with a normal karyotype or non-informative cytogenetics, and always in isolated del(17p).

  3. Prognostic value of trisomy 8 as a single anomaly and the influence of additional cytogenetic aberrations in primary myelodysplastic syndromes.

    Science.gov (United States)

    Saumell, Sílvia; Florensa, Lourdes; Luño, Elisa; Sanzo, Carmen; Cañizo, Consuelo; Hernández, Jesus M; Cervera, José; Gallart, Miguel A; Carbonell, Félix; Collado, Rosa; Arenillas, Leonor; Pedro, Carme; Bargay, Joan; Nomdedeu, Benet; Xicoy, Blanca; Vallespí, Teresa; Raya, José M; Belloch, Luis; Sanz, Guillermo F; Solé, Francesc

    2012-11-01

    Trisomy 8 is the most common chromosomal gain in myelodysplastic syndromes (MDS), however, little is known about the features of MDS with isolated trisomy 8 and the influence of additional cytogenetic aberrations. We determined the characteristics and prognostic factors of 72 patients with trisomy 8 as a single anomaly and analysed also the impact of other aberrations added to trisomy 8 in another 62 patients. According to our study, MDS with isolated trisomy 8 was more frequent in men, with more than one cytopenia in most patients (62%) and having about 4% bone marrow blasts. The multivariate analysis demonstrated that platelet count and percentage bone marrow blasts had the strongest impact on overall survival (OS). The median OS for isolated trisomy 8, trisomy 8 plus one aberration (tr8 + 1), plus two (tr8 + 2) and plus three or more aberrations (tr8 + ≥3) was 34·3, 40, 23·4 and 5·8 months, respectively (P < 0·001). Trisomy 8 confers a poorer prognosis than a normal karyotype in MDS patients with ≥5% bone marrow blasts. This study supports the view that MDS with isolated trisomy 8 should be included in the intermediate cytogenetic risk group. © 2012 Blackwell Publishing Ltd.

  4. Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome

    International Nuclear Information System (INIS)

    Chen, T-C; Hou, H-A; Chou, W-C; Tang, J-L; Kuo, Y-Y; Chen, C-Y; Tseng, M-H; Huang, C-F; Lai, Y-J; Chiang, Y-C; Lee, F-Y; Liu, M-C; Liu, C-W; Liu, C-Y; Yao, M; Huang, S-Y; Ko, B-S; Hsu, S-C; Wu, S-J; Tsay, W; Chen, Y-C; Tien, H-F

    2014-01-01

    Recently, mutations of the additional sex comb-like 1 (ASXL1) gene were identified in patients with myelodysplastic syndrome (MDS), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, ASXL1 mutations were identified in 106 (22.7%) of the 466 patients with primary MDS based on the French-American-British (FAB) classification and 62 (17.1%) of the 362 patients based on the World Health Organization (WHO) classification. ASXL1 mutation was closely associated with trisomy 8 and mutations of RUNX1, EZH2, IDH, NRAS, JAK2, SETBP1 and SRSF2, but was negatively associated with SF3B1 mutation. Most ASXL1-mutated patients (85%) had concurrent other gene mutations at diagnosis. ASXL1 mutation was an independent poor prognostic factor for survival. Sequential studies showed that the original ASXL1 mutation remained unchanged at disease progression in all 32 ASXL1-mutated patients but were frequently accompanied with acquisition of mutations of other genes, including RUNX1, NRAS, KRAS, SF3B1, SETBP1 and chromosomal evolution. On the other side, among the 80 ASXL1-wild patients, only one acquired ASXL1 mutation at leukemia transformation. In conclusion, ASXL1 mutations in association with other genetic alterations may have a role in the development of MDS but contribute little to disease progression

  5. Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome.

    Science.gov (United States)

    Zheng, Qing-Qing; Zhao, You-Shan; Guo, Juan; Zhao, Si-da; Song, Lu-Xi; Fei, Cheng-Ming; Zhang, Zheng; Li, Xiao; Chang, Chun-Kang

    2017-07-01

    Erythroid apoptosis increases significantly in myelodysplastic syndrome (MDS) patients with iron overload, but the underlying mechanism is not fully clear. In this study, we aim to explore the effect of HIF-1a/ROS on erythroid apoptosis in MDS patients with iron overload. We found that iron overload injured cellular functions through up-regulating ROS levels in MDS/AML cells, including inhibited cell viability, increased cell apoptosis and blocked cell cycle at G0/G1 phase. Interestingly, overexpression of hypoxia inducible factor-1a (HIF-1a), which was under-expressed in iron overload models, reduced ROS levels and attenuated cell damage caused by iron overload in MDS/AML cells. And gene knockdown of HIF-1a got the similar results as iron overload in MDS/AML cells. Furthermore, iron overload caused high erythroid apoptosis was closely related with ROS in MDS patients. Importantly, the HIF-1a protein levels of erythrocytes elevated obviously after incubation with desferrioxamine (DFO) from MDS patients with iron overload, accompanied by ROS levels inhibited and erythroid apoptosis reduced. Taken together, our findings determine that the HIF-1a/ROS signaling pathway plays a key role in promoting erythroid apoptosis in MDS patients with iron overload. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Impaired Expression of Focal Adhesion Kinase in Mesenchymal Stromal Cells from Low-Risk Myelodysplastic Syndrome Patients

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    Yuenv Wu

    2017-08-01

    Full Text Available The pathogenic role of mesenchymal stromal cells (MSCs in myelodysplastic syndromes (MDS development and progression has been investigated by numerous studies, yet, it remains controversial in some aspects (1, 2. In the present study, we found distinct features of MSCs from low-risk (LR-MDS stromal microenvironment as compared to those from healthy subjects. At the molecular level, focal adhesion kinase, a key tyrosine kinase in control of cell proliferation, survival, and adhesion process, was found profoundly suppressed in expression and activation in LR-MDS MSC. At a functional level, LR-MDS MSCs showed impaired growth and clonogenic capacity, which were independent of cellular senescence and apoptosis. The pro-adipogenic differentiation and attenuated osteogenic capacity along with reduced SDF-1 expression could be involved in creating an unfavorable microenvironment for hematopoiesis. In conclusion, our experiments support the theory that the stromal microenvironment is fundamentally altered in LR-MDS, and these preliminary data offer a new perspective on LR-MDS pathophysiology.

  7. Quantitative Detection of ID4 Gene Aberrant Methylation in the Differentiation of Myelodysplastic Syndrome from Aplastic Anemia

    Directory of Open Access Journals (Sweden)

    Mian-Yang Li

    2015-01-01

    Full Text Available Background: The diagnosis of myelodysplastic syndrome (MDS, especially hypoplastic MDS, and MDS with low blast counts or normal karyotype may be problematic. This study characterized ID4 gene methylation in patients with MDS and aplastic anemia (AA. Methods: The methylation status of ID4 was analyzed by bisulfite sequencing polymerase chain reaction (PCR and quantitative real-time methylation-specific PCR (MethyLight PCR in 100 patients with MDS and 31 patients with AA. Results: The MDS group had a higher ID4 gene methylation positivity rate (22.22% and higher methylation levels (0.21 [0-3.79] than the AA group (P < 0.05. Furthermore, there were significant differences between the hypoplastic MDS and AA groups, the MDS with low blast count and the AA groups, and the MDS with normal karyotype and the AA groups. The combination of genetic and epigenetic markers was used in much more patients with MDS (62.5% [35/56] than the use of genetic markers only (51.79% [29/56]. Conclusions: These results showed that the detection of ID4 methylation positivity rates and levels could be a useful biomarker for MDS diagnosis.

  8. A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome.

    Science.gov (United States)

    Kirschbaum, Mark; Gojo, Ivana; Goldberg, Stuart L; Bredeson, Christopher; Kujawski, Lisa A; Yang, Allen; Marks, Peter; Frankel, Paul; Sun, Xing; Tosolini, Alessandra; Eid, Joseph E; Lubiniecki, Gregory M; Issa, Jean-Pierre

    2014-10-01

    Patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) may respond to treatment with epigenetic-modifying agents. Histone deacetylase inhibitors may synergize with hypomethylating agents. This phase 1 dose-escalation study was designed to determine the maximum tolerated dose, recommended phase 2 dose, safety and tolerability of vorinostat plus decitabine in patients with relapsed/refractory AML, newly-diagnosed AML, or intermediate- to high-grade MDS. Thirty-four patients received concurrent therapy with decitabine plus vorinostat and 37 received sequential therapy with decitabine followed by vorinostat. Twenty-nine patients had relapsed/refractory AML, 31 had untreated AML and 11 had MDS. The target maximum administered dose (MAD) of decitabine 20 mg/m(2) daily for 5 d plus vorinostat 400 mg/d for 14 d was achieved for concurrent and sequential schedules, with one dose-limiting toxicity (Grade 3 QTc prolongation) reported in the sequential arm. Common toxicities were haematological and gastrointestinal. Responses were observed more frequently at the MAD on the concurrent schedule compared with the sequential schedule in untreated AML (46% vs. 14%), relapsed/refractory AML (15% vs. 0%) and MDS (60% vs. 0%). Decitabine plus vorinostat given concurrently or sequentially appears to be safe and well-tolerated. Concurrent therapy shows promising clinical activity in AML or MDS, warranting further investigation. © 2014 John Wiley & Sons Ltd.

  9. MR imaging of the bone marrow in myeloid leukemia and myelodysplastic syndrome. Comparison of the lumbar spine and femur

    International Nuclear Information System (INIS)

    Tanaka, Osamu; Kobayashi, Yasuyuki; Ichikawa, Tamaki; Matsuura, Katsuhiko; Nagai, Jun; Takagi, Shojiro

    1995-01-01

    MR imaging of the lumber spine and the femur was performed with T1-weighted SE sequence and comparison of the MRI findings of the lumber vertebral body and the femoral marrow was made in 15 patients with acute myeloid leukemia (AML), 5 chronic myelogenous leukemia (CML), and 9 myelodysplastic syndrome (MDS). The MRI appearance of the bone marrow was classified into four patterns: 1) fatty marrow; 2) faint signal; 3) heterogeneous infiltration; and 4) diffuse infiltration. The MRI of the lumber vertebral body showed a diffuse marrow infiltration pattern in over the half of the cases of AML and MDS. On the MRI of the femoral marrow, the signal intensity alteration, a low signal on T1-weighted SE image, began in the proximal femurs almost symmetrically. The abnormal low signal intensity area tended to gradually extend towards the distal portion of the femoral marrow with progression of the disease in the patients with AML and MDS. M2 type of AML tended to be demonstrated as a faint signal pattern, which was significantly different from the other types of AML. In all the cases of CML, a diffuse cellular infiltration pattern was noted with total replacement of the fatty marrow on both lumbar spinal and femoral MRI, and the femoral marrow involvement was more downwardly extended than AML. We concluded that MRI of the femoral marrow was more efficient than that of the lumbar spine in the assessment of myeloid leukemia and MDS. (author)

  10. Effectiveness of 2-hour Troponin in High-risk Patients With Suspected Acute Coronary Syndrome.

    Science.gov (United States)

    Bove, Joseph; Hochman, Steven; Miller, Jacob; Artim, Stephen

    2017-06-01

    Research has shown the safety and effectiveness of drawing a standard troponin level at presentation and again at 2 hours in only low-risk patients. Because high-sensitivity troponins are not currently approved in the United States, we studied the utility of a standard troponin that is presently in use. Our goal was to determine if 2-hour standard troponin would be safe and effective in the evaluation of a high-risk cohort of patients never studied previously. We conducted a single-center prospective observational study of adult patients presenting to the emergency department with signs and symptoms suggestive of acute coronary syndrome. Patients were defined as high risk if the attending physician planned to admit or transfer the patient to the observation unit. History, Electrocardiography, Age, Risk factors, Troponin scores were calculated on all patients to provide verification that the individuals were high risk. The primary outcome was a composite of 30-day myocardial infarction, death, cardiac arrest with return of spontaneous circulation, or dysrhythmia. The secondary outcome was 30-day revascularization. We included a total of 122 patients with an average follow-up of 112 days (minimum 30 days). A total of 86% of cases had History, Electrocardiography, Age, Risk factors, Troponin scores ≥4. The primary outcome was met in 22 (18%) patients, and the secondary outcome occurred in 7 (5.7%) patients. The negative predictive value of negative 2-hour troponins along with no significant delta troponin rise was 98.7%. Discharging patients thought to be high risk who have negative troponins at 0 and 2 hours and no delta troponin rise appears safe. No deaths occurred in follow-up. Larger studies are warranted.

  11. Chemotherapy versus Hypomethylating Agents for the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome after Allogeneic Stem Cell Transplant.

    Science.gov (United States)

    Motabi, Ibraheem H; Ghobadi, Armin; Liu, Jingxia; Schroeder, Mark; Abboud, Camille N; Cashen, Amanda F; Stockler-Goldstein, Keith E; Uy, Geoffrey L; Vij, Ravi; Westervelt, Peter; DiPersio, John F

    2016-07-01

    Allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). For patients with relapsed disease after transplantation, intensive chemotherapy followed by donor lymphocyte infusion (DLI) or a second allo-SCT may result in a durable response in some patients. High-intensity chemotherapy and less aggressive therapy with hypomethylating agents (HAs) with and without DLI are often used for relapse after allo-SCT. Here we compared the treatment outcomes of intensive chemotherapy with that of HAs in relapsed AML and MDS after allo-SCT. Patients who had received a second SCT within 90 days of the relapse date were excluded. The primary endpoints were overall response rate (ORR) and overall survival (OS). Secondary endpoints were complete remission (CR) rate and progression-free survival (PFS). One hundred patients were included: 73 patients received chemotherapy and 27 patients received an HA. Fifty-six percent of patients in the chemotherapy group and 33% of patients in the HA group received at least 1 DLI after treatment. Treatment with chemotherapy resulted in a higher ORR (51% versus 19%, P = .004) and a higher CR rate (40% versus 7%, P = .002). The median OS (6 versus 3.9 months, P = .01) and PFS (4.9 versus 3.8 months, P = .02) were longer in the chemotherapy group. Similar benefit of chemotherapy over HAs was maintained in all treatment outcomes after controlling for the use of DLI. The use of chemotherapy followed by DLI offered the greatest benefit (ORR, 68%; CR, 59%, 1-year OS, 44%; and median OS, 9.8 months). In conclusion, in our hands, with limited numbers, the use of more conventional salvage chemotherapy, with DLI when possible, for the treatment of relapsed AML and MDS after allo-SCT is associated with better outcomes than nonchemotherapy (HA) options. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier

  12. In vivo measurements of the T1 relaxation processes in the bone marrow in patients with myelodysplastic syndrome. A magnetic resonance imaging study

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    Jensen, K.E.; Nielsen, H.; Thomsen, C.; Soerensen, P.G.; Karle, H.; Christoffersen, P.; Henriksen, O. (Hvidovre Hospital, Copenhagen (Denmark). Dept. of Magnetic Resonance; Hvidovre Hospital, Copenhagen (Denmark). Dept. of Hematology; Hvidovre Hospital, Copenhagen (Denmark). Dept. of Pathology)

    Nine patients with myelodysplastic syndrome (MDS) were examined with magnetic resonance imaging and in vivo T1 relaxation time measurements of the vertebral bone marrow in a 1.5 tesla whole body scanner. Two patients underwent transformation to acute myeloid leukemia and were evaluated at follow-up examinations. At the time of diagnosis the T1 relaxation times of the vertebral bone marrow were significantly prolonged compared with normal values. The T1 relaxation times of the vertebral bone marrow in patients with MDS showed significantly lower values compared with patients with acute leukemia and did not differ from patients with polycythemia vera. (orig.).

  13. An exploratory phase 2 study of investigational Aurora A kinase inhibitor alisertib (MLN8237 in acute myelogenous leukemia and myelodysplastic syndromes

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    Stuart L. Goldberg

    2014-01-01

    Full Text Available Alisertib (MLN8237 is an investigational, oral, selective, Aurora A kinase (AAK inhibitor. In this phase 2 trial, 57 patients with acute myeloid leukemia (AML or high-grade myelodysplastic syndrome received alisertib 50 mg BID for 7 days in 21-day cycles. Responses in 6/35 AML patients (17% response rate with an additional 49% stable disease, 34% transfusion independence included 1 complete response lasting >1 year. No responses were observed in MDS patients. Adverse events >30% included diarrhea, fatigue, nausea, febrile neutropenia, and stomatitis. Results suggest modest activity in AML, supporting further research to better understand how AAK inhibition may induce leukemic cell senescence.

  14. A sequential erythropoietin and GM-CSF schedule offers clinical benefits in the treatment of anaemia in myelodysplastic syndromes.

    Science.gov (United States)

    Bernell, P; Stenke, L; Wallvik, J; Hippe, E; Hast, R

    1996-08-01

    In order to reduce anaemia in patients with myelodysplastic syndromes (MDS) a stepwise treatment protocol including erythropoietin (EP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) was designed. Thirty-seven MDS patients (stages I-III) with symptomatic anaemia were first given EPO 10,000 U s.c. 3 times weekly for 6 weeks. Those not responding, i.e. increased their haemoglobin levels > 15 g/l, proceeded into the second phase of the study where GM-CSF (200 micrograms/d. s.c. on weeks 1-6) was combined with EPO (10,000 U s.c. 3 times weekly on weeks 5-14). Following the initial EPO treatment phase, 14 of the 37 patients (38%) responded with increased haemoglobin levels. Responders were significantly different from non-responders in that their pre-treatment values of s-EPO, s-LDH and bone marrow blast cell counts were lower, their baseline haemoglobin levels higher and their transfusion dependency less pronounced. Eighteen of the 23 non-responders proceeded into the second phase, 13 of those were evaluable having completed the entire schedule. Three of the 13 initially EPO resistant patients (23%) responded to the GM-CSF/EPO combination with increased haemoglobin levels, suggesting a positive synergy between the two cytokines. Thus, the overall response rate to the present protocol was 46% (17 of 37 cases), but only a limited subset of the patients did clearly benefit from the combined GM-CSF/EPO administration. Therefore, we believe this step-wise approach to multiple growth factor treatment in MDS, starting with EPO alone and reserving the combination for refractory cases, has considerable advantages, taking into account both medical and socio-economical aspects.

  15. Hematopoietic stem cell transplantation in children and young adults with secondary myelodysplastic syndrome and acute myelogenous leukemia after aplastic anemia.

    Science.gov (United States)

    Yoshimi, Ayami; Strahm, Brigitte; Baumann, Irith; Furlan, Ingrid; Schwarz, Stephan; Teigler-Schlegel, Andrea; Walther, Joachim-Ulrich; Schlegelberger, Brigitte; Göhring, Gudrun; Nöllke, Peter; Führer, Monika; Niemeyer, Charlotte M

    2014-03-01

    Secondary myelodysplastic syndrome and acute myelogenous leukemia (sMDS/sAML) are the most serious secondary events occurring after immunosuppressive therapy in patients with aplastic anemia. Here we evaluate the outcome of hematopoietic stem cell transplantation (HSCT) in 17 children and young adults with sMDS/sAML after childhood aplastic anemia. The median interval between the diagnosis of aplastic anemia and the development of sMDS/sAML was 2.9 years (range, 1.2 to 13.0 years). At a median age of 13.1 years (range, 4.4 to 26.7 years), patients underwent HSCT with bone marrow (n = 6) or peripheral blood stem cell (n = 11) grafts from HLA-matched sibling donors (n = 2), mismatched family donors (n = 2), or unrelated donors (n = 13). Monosomy 7 was detected in 13 patients. The preparative regimen consisted of busulfan, cyclophosphamide, and melphalan in 11 patients and other agents in 6 patients. All patients achieved neutrophil engraftment. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and that of chronic GVHD was 70%. Relapse occurred in 1 patient. The major cause of death was transplant-related complication (n = 9). Overall survival and event-free survival at 5 years after HSCT were both 41%. In summary, this study indicates that HSCT is a curative therapy for some patients with sMDS/sAML after aplastic anemia. Future efforts should focus on reducing transplantation-related mortality. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  16. Fatores prognósticos nas síndromes mielodisplásicas Prognostic factors for myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Alexandre G. Apa

    2006-09-01

    Full Text Available As síndromes mielodisplásicas compreendem um conjunto heterogêneo de doenças hematopoéticas que se caracterizam por hematopoese ineficaz e se apresentam geralmente com citopenias no sangue periférico, medula óssea hipercelular e displasia na diferenciação celular. Vários fatores clínicos e laboratoriais foram analisados como prognósticos. O objetivo dessa revisão é analisar os sistemas prognósticos avaliando sobrevida global e abordagem terapêutica. A avaliação do sistema WPSS, que alia grupos de riscos citogenéticos e a presença ou não de dependência transfusional define cinco grupos de riscos com diferença estatística em termos de sobrevida global e risco de transformação leucêmica. A proposta formulada é a avaliação do sistema WPSS como sistema prognóstico capaz de substituir o IPSS a fim de melhor definir os grupos de risco e diferentes abordagens terapêuticas.The myelodysplastic syndromes represent a heterogeneous group of haematopoietic disorders characterized by ineffective haematopoiesis, peripheral cytopenias, hypercellular bone marrow and dysplastic haematopoiesis. Several laboratory and clinical features have been analysed as prognostic factors. The aim of this review is to evaluate the prognostic scoring systems focusing on overall survival and therapeutic approach. The WPSS evaluation includes both cytogenetic risk groups and transfusional necessities. It has five well-defined risk groups with statistical divergences related to overall survival and leukemic transformation risk. Our proposal is to evaluate the WPSS as a prognostic scoring system able to replace the IPSS, in order to establish a better definition of the risk groups and the different therapeutic approaches.

  17. Therapy-related myelodysplastic syndrome after successful treatment of acute promyelocytic leukemia: case report and literature review

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    Cîrstea Mihaela

    2017-04-01

    Full Text Available In the 2016 revision of the World Health Organization classification the term therapy-related myeloid neoplasia (t-MN defines a subgroup of acute myeloid leukemia (AML comprising patients who develop myelodysplastic syndrome (MDS-t or acute myeloid leukemia (AML-t after treatment with cytotoxic and/or radiation therapy for various malignancies or autoimmune disorders. We report the case of a 36 year old patient with t-MN (t-MDS after achieving complete remission (CR of a PML-RARA positive acute promyelocytic leukemia (APL at 32 months after diagnosis. Initially classified as low risk APL and treated according to the AIDA protocol - induction and 3 consolidation cycles - the patient achieved a complete molecular response in September 2013 and started maintenance therapy. On follow-up PML-RARA transcript remained negative. In January 2016 leukopenia and thrombocytopenia developed and a peripheral blood smear revealed hypogranular and agranular neutrophils. Immunophenotyping in the bone marrow aspirate identified undifferentiated blast cells that did not express cytoplasmic myeloperoxidase. The cytogenetic study showed normal karyotype. The molecular biology tests not identified PMLRARA transcript. A diagnosis of t-MDS (AREB-2 - WHO 2008 was established. Treatment of AML was started with 2 “3+7” regimens and 1 MEC cycle. Two months from diagnosis, while in CR, an allogeneic HSCT from an unrelated HLA compatible donor was performed after myeloablative regimen. An unfavorable clinical evolution was followed by death on day 9 after transplantation. The occurrence of t-MNs during CR of APL represents a particular problem in terms of follow-up and differential diagnosis of relapse and constitutes a dramatic complication for a disease with a favorable prognosis.

  18. Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone marrow microenvironment of patients with myelodysplastic syndromes

    International Nuclear Information System (INIS)

    Xiong, H.; Yang, X.Y.; Han, J.; Wang, Q.; Zou, Z.L.

    2015-01-01

    The purpose of this study was to explore cytokine expression patterns and cytogenetic abnormalities of mesenchymal stem cells (MSCs) from the bone marrow microenvironment of Chinese patients with myelodysplastic syndromes (MDS). Bone marrow samples were obtained from 30 cases of MDS (MDS group) and 30 healthy donors (control group). The expression pattern of cytokines was detected by customized protein array. The karyotypes of MSCs were analyzed using fluorescence in situ hybridization. Compared with the control group, leukemia inhibitory factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and transforming growth factor-β in the MDS group were significantly downregulated (P<0.05), while interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and programmed death ligand (B7-H1) were significantly upregulated (P<0.05). For chromosome abnormality analysis, the detection rate of abnormal karyotypes (+8, -8, -20, 20q-, -Y, -7, 5q-) was 30% in the MDS group and 0% in the control group. In conclusion, the up- and downregulated expression of these cytokines might play a key role in the pathogenesis of MDS. Among them, SCF and SDF-1 may play roles in the apoptosis of HSCs in MDS; and IFN-γ, TNF-α, and B7-H1 may be associated with apoptosis of bone marrow cells in MDS. In addition, the abnormal karyotypes might be actively involved in the pathogenesis of MDS. Further studies are required to determine the role of abnormal karyotypes in the occurrence and development of MDS

  19. Flow cytometry in the diagnosis of myelodysplastic syndromes (MDS) and the value of myeloid nuclear differentiation antigen (MNDA).

    Science.gov (United States)

    Bellos, Frauke; Kern, Wolfgang

    2014-09-25

    Background: Confirming diagnosis of myelodysplastic syndromes (MDS) is often challenging. Standard diagnostic methods are cytomorphology (CM) and cytogenetics (CG). Multiparameter flow cytometry (MFC) is upcoming in MDS diagnostic work up, comparability and investigator experience are critical. Myeloid nuclear differentiation antigen (MNDA) in myelomonocytic cells might be expressed more weakly in patients with MDS. The analysis of MNDA may thus improve diagnostic capabilities of MFC in MDS. Methods: Staining methods and antibody combinations for MFC in MDS are outlined, giving details for interpretation of results in regard to dyspoiesis. MFC results are correlated with CM and CG and with survival data. Use of myeloid nuclear differentiation antigen (MNDA) in MDS diagnostics was evaluated in 239 patients with MDS, AML, other cytopenic conditions and in 30 negative controls. Results: Strong correlation between findings in CM and MFC was found; MFC results correlated well with those of CG. Patients with higher grades of dysplasia in MFC had shorter overall survival. Percentages of granulocytes and monocytes with diminished MNDA expression (%dimG, %dimM) were higher in patients with MDS and AML. Mean fluorescence intensity (MFI) of MNDA in monocytes was lower in MDS and AML. Cut-off values for %dimG (12%) and %dimM (22%) as well as for MFI in monocytes (72) were defined discriminating between MDS and non-MDS. Conclusion: MFC adds significant information on dyspoiesis in the diagnostic work up for MDS and provides prognostic information. MNDA expression can be assessed by MFC and may facilitate evaluation of dyspoiesis when added to MDS MFC panels. © 2014 Clinical Cytometry Society. Copyright © 2014 Clinical Cytometry Society.

  20. Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone marrow microenvironment of patients with myelodysplastic syndromes

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    Xiong, H.; Yang, X.Y.; Han, J.; Wang, Q.; Zou, Z.L. [Department of Hematology, Shanghai Clinical Research Center, Chinese Academy of Sciences, Shanghai Xuhui District Central Hospital, Shanghai (China)

    2015-01-20

    The purpose of this study was to explore cytokine expression patterns and cytogenetic abnormalities of mesenchymal stem cells (MSCs) from the bone marrow microenvironment of Chinese patients with myelodysplastic syndromes (MDS). Bone marrow samples were obtained from 30 cases of MDS (MDS group) and 30 healthy donors (control group). The expression pattern of cytokines was detected by customized protein array. The karyotypes of MSCs were analyzed using fluorescence in situ hybridization. Compared with the control group, leukemia inhibitory factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and transforming growth factor-β in the MDS group were significantly downregulated (P<0.05), while interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and programmed death ligand (B7-H1) were significantly upregulated (P<0.05). For chromosome abnormality analysis, the detection rate of abnormal karyotypes (+8, -8, -20, 20q-, -Y, -7, 5q-) was 30% in the MDS group and 0% in the control group. In conclusion, the up- and downregulated expression of these cytokines might play a key role in the pathogenesis of MDS. Among them, SCF and SDF-1 may play roles in the apoptosis of HSCs in MDS; and IFN-γ, TNF-α, and B7-H1 may be associated with apoptosis of bone marrow cells in MDS. In addition, the abnormal karyotypes might be actively involved in the pathogenesis of MDS. Further studies are required to determine the role of abnormal karyotypes in the occurrence and development of MDS.

  1. TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis.

    Science.gov (United States)

    Kulasekararaj, Austin G; Smith, Alexander E; Mian, Syed A; Mohamedali, Azim M; Krishnamurthy, Pramila; Lea, Nicholas C; Gäken, Joop; Pennaneach, Coralie; Ireland, Robin; Czepulkowski, Barbara; Pomplun, Sabine; Marsh, Judith C; Mufti, Ghulam J

    2013-03-01

    This study aimed to determine the incidence/prognostic impact of TP53 mutation in 318 myelodysplastic syndrome (MDS) patients, and to correlate the changes to cytogenetics, single nucleotide polymorphism array karyotyping and clinical outcome. The median age was 65 years (17-89 years) and median follow-up was 45 months [95% confidence interval (CI) 27-62 months]. TP53 mutations occurred in 30 (9.4%) patients, exclusively in isolated del5q (19%) and complex karyotype (CK) with -5/5q-(72%), correlated with International Prognostic Scoring System intermediate-2/high, TP53 protein expression, higher blast count and leukaemic progression. Patients with mutant TP53 had a paucity of mutations in other genes implicated in myeloid malignancies. Median overall survival of patients with TP53 mutation was shorter than wild-type (9 versus 66 months, P disappearance of the mutant clone or emergence of new clones, suggesting an early occurrence of TP53 mutations. A reduction in mutant clone correlated with response to 5-azacitidine, however clones increased in non-responders and persisted at relapse. The adverse impact of TP53 persists after adjustment for cytogenetic risk and is of practical importance in evaluating prognosis. The relatively common occurrence of these mutations in two different prognostic spectrums of MDS, i.e. isolated 5q- and CK with -5/5q-, possibly implies two different mechanistic roles for TP53 protein. © 2013 Crown copyright. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.

  2. Annotating function to differentially expressed LincRNAs in myelodysplastic syndrome using a network-based method.

    Science.gov (United States)

    Liu, Keqin; Beck, Dominik; Thoms, Julie A I; Liu, Liang; Zhao, Weiling; Pimanda, John E; Zhou, Xiaobo

    2017-09-01

    Long non-coding RNAs (lncRNAs) have been implicated in the regulation of diverse biological functions. The number of newly identified lncRNAs has increased dramatically in recent years but their expression and function have not yet been described from most diseases. To elucidate lncRNA function in human disease, we have developed a novel network based method (NLCFA) integrating correlations between lncRNA, protein coding genes and noncoding miRNAs. We have also integrated target gene associations and protein-protein interactions and designed our model to provide information on the combined influence of mRNAs, lncRNAs and miRNAs on cellular signal transduction networks. We have generated lncRNA expression profiles from the CD34+ haematopoietic stem and progenitor cells (HSPCs) from patients with Myelodysplastic syndromes (MDS) and healthy donors. We report, for the first time, aberrantly expressed lncRNAs in MDS and further prioritize biologically relevant lncRNAs using the NLCFA. Taken together, our data suggests that aberrant levels of specific lncRNAs are intimately involved in network modules that control multiple cancer-associated signalling pathways and cellular processes. Importantly, our method can be applied to prioritize aberrantly expressed lncRNAs for functional validation in other diseases and biological contexts. The method is implemented in R language and Matlab. xizhou@wakehealth.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  3. Diretrizes para diagnóstico morfológico em síndromes mielodisplásicas Guidelines for morphological diagnosis of myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Lígia Niero-Melo

    2006-09-01

    Full Text Available As síndromes mielodisplásicas são reconhecidas como doenças que se originam nas células-tronco da medula óssea e que requerem avaliação sistemática e criteriosa de sangue periférico e medula óssea para seu correto diagnóstico. O objetivo deste relato é estabelecer os critérios morfológicos (cito-histológicos como parâmetros para o diagnóstico de SMD em amostras de sangue periférico e medula óssea, com especial direcionamento aos hematologistas e patologistas clínicos que exercem a hematologia laboratorial na sua rotina de trabalho. Os principais achados morfológicos são listados no final deste relato, na forma de "check-list", objetivando a sistematização sobre estes achados.Myelodysplastic syndromes require both thorougly and systematic blood smear and bone marrow examinations. The main goal of this report is to establish criteria of the morphological ( cyto-histological features, as parameters for the diagnosis of myelodysplastic syndromes ( MDS from peripheral blood smears and bone marrow samples, with especial address to hematology and pathology practitioners. The main features are listed ( checklist at the end of this report, in order to synthesize them.

  4. WHO-defined ‘myelodysplastic syndrome with isolated del(5q)' in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations

    Science.gov (United States)

    Patnaik, M M; Lasho, T L; Finke, C M; Gangat, N; Caramazza, D; Holtan, S G; Pardanani, A; Knudson, R A; Ketterling, R P; Chen, D; Hoyer, J D; Hanson, C A; Tefferi, A

    2010-01-01

    The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with ‘myelodysplastic syndrome with isolated del(5q)' (median age 74 years; 60 females). In all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age ⩾70 years (P=0.01), transfusion need at diagnosis (P=0.04) and dysgranulopoiesis (P=0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or ⩾2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, respectively. Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), isocitrate dehydrogenase 1 (IDH1) and IDH2 mutational analysis was performed on archived bone marrows in 78 patients; JAK2V617F and MPLW515L mutations were shown in five (6.4%) and three (3.8%) patients, respectively, and did not seem to affect phenotype or prognosis. IDH mutations were not detected. Survival was not affected by serum ferritin and there were no instances of death directly related to iron overload. The current study is unique in its strict adherence to WHO criteria for selecting study patients and providing information on long-term survival, practical prognostic factors, baseline risk of leukemic transformation and the prevalence of JAK2, MPL and IDH mutations. PMID:20485371

  5. Cytogenetic as an Important Tool for Diagnosis and Prognosis for Patients with Hypocellular Primary Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Daiane Corrêa de Souza

    2014-01-01

    Full Text Available We analyzed cytogenetically 105 patients with hypocellular primary MDS and their clinical implications. The main chromosomal abnormalities found were del(5q/−5, del(6q/+6, del(7q/−7, del(11q, and del(17p. Pediatric patients had a higher frequency of abnormal karyotypes compared with adult patients (P < 0,05. From our patients, 18% showed evolution of the disease. The chromosomal abnormalities presented in the diagnosis of patients who evolved to AML included numerical (−7, +8 and structural del(6q, del(7q, i(7q, t(7;9, i(9q, and del(11q abnormalities and complex karyotypes. Although the frequency of evolution from hypocellular MDS to AML is low, our results suggest that some chromosomal alterations may play a critical role during this process. We applied the IPSS in our patients because this score system has been proved to be useful for predicting evolution of disease. When we considered the patients according to group 1 (intermediate-1 and group 2 (intermediate-2 and high risk, we showed that group 2 had a high association with respect to the frequency of abnormal karyotypes (P < 0,0001, evolution of disease (P < 0,0001, and mortality (P < 0,001. In fact, the cytogenetic analysis for patients with hypocellular primary MDS is an important tool for diagnosis, prognosis, in clinical decision-making and in follow-up.

  6. Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome. Conceptual chances

    International Nuclear Information System (INIS)

    Buchmann, I.; Helisch, A.; Bartenstein, P.; Meyer, R.G.; Herr, W.

    2005-01-01

    The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term disease-free survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myelblative conditioning before SCT. This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand. (orig.)

  7. Outcome of Allogeneic Stem Cell Transplantation for Patients Transformed to Myelodysplastic Syndrome or Leukemia from Severe Aplastic Anemia: A Report from the MDS Subcommittee of the Chronic Malignancies Working Party and the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation

    NARCIS (Netherlands)

    Hussein, A.A.; Halkes, C.M.; Socie, G.; Tichelli, A.; Borne, P.A. von dem; Schaap, M.N.; Foa, R.; Ganser, A.; Dufour, C.; Bacigalupo, A.; Locasciulli, A.; Aljurf, M.; Peters, C.; Robin, M.; Biezen, A.A. van; Volin, L.; Witte, T.J. de; Marsh, J.; Passweg, J.R.; Kroger, N.; et al.,

    2014-01-01

    One hundred and forty patients who had undergone hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) transformation after treatment of severe aplastic anemia (SAA) were identified in the European Group for Blood and Marrow

  8. Patients with a high risk for obstructive sleep apnea syndrome: postoperative respiratory complications.

    Science.gov (United States)

    Pereira, H; Xará, D; Mendonça, J; Santos, A; Abelha, F J

    2013-01-01

    STOP-BANG score (snore; tired; observed apnea; arterial pressure; body mass index; age; neck circumference and gender) can predict the risk of a patient having Obstructive Syndrome Apnea (OSA). The aim of this study was to evaluate the incidence STOP-BANG score≥3, in surgical patients admitted to the Post-Anesthesia Care Unit (PACU). Observational, prospective study conducted in a post-anesthesia care unit (PACU) during three weeks (2011). The study population consisted of adult patients after noncardiac and non-neurological surgery. Patients were classified as high risk of OSA (HR-OSA) if STOP-BANG score≥3 and Low-risk of OSA (LR-OSA) if STOP-BANG score<3 (LR-OSA). Patient demographics, intraoperative and postoperative data were collected. Patient characteristics were compared using Mann-Whitney U-test, t-test for independent groups, and chi-square or Fisher's exact test. A total of 357 patients were admitted to PACU; 340 met the inclusion criteria. 179 (52%) were considered HR-OSA. These patients were older, more likely to be masculine, had higher BMI, higher ASA physical status, higher incidence of ischemic heart disease, heart failure, hypertension, dyslipidemia and underwent more frequently insulin treatment for diabetes. These patients had more frequently mild/moderated hypoxia in the PACU (9% vs. 3%, p=0.012) and had a higher incidence of residual neuromuscular blockade (NMB) (20% vs. 16%, p=0.035). Patients with HR-OSA had a longer hospital stay. Patients with HR-OSA had an important incidence among patients scheduled for surgery in our hospital. These patients had more co-morbidities and were more prone to post-operative complications. Copyright © 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  9. Transplante de célula-tronco hematopoética para síndrome mielodisplásica Bone marrow transplantation in myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Daniel G. Tabak

    2010-05-01

    Full Text Available As síndromes mielodisplásicas (SMD constituem um grupo de doenças hematológicas caracterizadas por citopenias crônicas, associadas a uma maturação celular anormal. A melhor forma de classificação atual destas patologias é o International Prognostic Scoring System (IPSS, que se baseia no grau de citopenia, número de mieloblastos na medula óssea e alterações citogenéticas. Há quatro estágios: baixo risco, riscos intermediário-1 e 2 e alto risco. Um grupo destes pacientes pode ser curado com o transplante de células-tronco hematopoéticas (TCTH. Esta forma de tratamento pode ser considerada para pacientes com idade inferior a 60 anos, que possuam um doador familiar HLA-idêntico. A opção por esta modalidade terapêutica depende de alguns critérios, que incluem o IPSS, o risco de progressão de doença, o risco de infecção e o estado geral do paciente. O TCTH autólogo pode ser considerado em pacientes que alcancem uma remissão completa citogenética e que não disponham de doador HLAidêntico. Em pacientes não candidatos ao TCTH mieloablativo, uma possibilidade é o transplante com regimes de intensidade reduzida. Estudos recentes têm demonstrado resultados favoráveis com esta opção terapêutica, pois, apesar do alto rico de recaída, as taxas de mortalidade associada ao procedimento são menores. Os pacientes com SMD devem ser dispostos em ensaios clínicos que considerem as comorbidades, DECH e riscos de recaída.The myelodysplastic syndrome (MDS encompasses a series of hematological conditions characterized by chronic cytopenias with abnormal cellular maturation. Based on the cytopenias, number of blast cells in bone marrow and cytogenetic abnormalities, MDS may be best classified by the International Prognostic Scoring System (IPSS in four groups: low risk, intermediate 1, intermediate 2 risks and high risk. A subset of patients can be cured following allogeneic hematopoietic stem cell transplantation (SCT. This

  10. Progressive transfusion and growth factor independence with adjuvant sertraline in low risk myelodysplastic syndrome treated with an erythropoiesis stimulating agent and granulocyte-colony stimulating factor

    Directory of Open Access Journals (Sweden)

    Kirtan Nautiyal

    2015-01-01

    Full Text Available Refractoriness to growth factor therapy is commonly associated with inferior outcome in patients with low-risk myelodysplastic syndrome (LR-MDS who require treatment for cytopenias. However, the mechanisms leading to refractoriness are unknown. Here we describe a clinically depressed 74-year-old male with refractory cytopenia with multilineage dysplasia (RCMD and documented growth factor refractory anemia after erythropoeisis stimulating agent (ESA therapy, who attained transfusion and growth factor independence after the addition of sertraline to his medication regimen. Our case demonstrates hematological improvement-erythroid (HI-E in growth factor refractory, low risk MDS and highlights a potential mechanistic link between common inflammatory diseases and LR-MDS.

  11. Miliary tuberculosis with no pulmonary involvement in myelodysplastic syndromes: a curable, yet rarely diagnosed, disease: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Krambovitis Elias

    2008-03-01

    Full Text Available Abstract Background Although tuberculosis is not uncommon among patients with myelodysplastic syndrome (MDS, only a few reports of such patients suffering from miliary tuberculosis (MT exist. MT often presents as a fever of unknown origin and it is a curable disease, yet fatal if left untreated. Case presentation We report a case of MT with no clinical or laboratory indications of pulmonary involvement in a patient with MDS, and review the relevant literature. Mycobacterium tuberculosis was isolated from the liquid culture of a bone marrow aspirate. Conclusion Even if the initial diagnostic investigation for a fever of obscure etiology is negative, MT should not be excluded from the differential diagnosis list. Since it is a curable disease, persistent and vigorous diagnostic efforts are warranted. In suspected cases, mycobacterial blood cultures should be collected as soon as possible after hospital admission and early bone marrow aspirate with mycobacterial cultures is advocated.

  12. Histiocytoid Sweet Syndrome Diagnosed with Concurrent Myelodysplastic Syndrome with t(1;3) on Bone Marrow Examination

    Science.gov (United States)

    2017-10-08

    Affairs (59 MDW/PA) for review and then forward you a final letter of approval or disapproval. g, Once your manuscript, poster or presentation has been...CHANGES: [gj NO 0 YES If yes. give date. 29. COMMENTS [gJ APPROVED D DISAPPROVED The poster presentation is approved. 30. PRINTED NAME. RANK/GRADE...FROM: 59 MDW/SGVU SUBJECT: Professional Presentation Approval 27 JULY 2017 1. Your paper, entitled Histiocytoid Sweet Syndrome Diagnosed with

  13. Dopamine in high-risk populations: A comparison of subjects with 22q11.2 deletion syndrome and subjects at ultra high-risk for psychosis.

    Science.gov (United States)

    Vingerhoets, Claudia; Bloemen, Oswald J N; Boot, Erik; Bakker, Geor; de Koning, Mariken B; da Silva Alves, Fabiana; Booij, Jan; van Amelsvoort, Thérèse A M J

    2018-02-28

    Striatal dopamine (DA) dysfunction has been consistently reported in psychotic disorders. Differences and similarities in the pathogenesis between populations at clinical and genetic risk for developing psychosis are yet to be established. Here we explored markers of dopamine (DA) function in subjects meeting clinically ultra-high risk criteria for psychosis (UHR) and in subjects with 22q11.2 deletion syndrome (22q11DS), a genetic condition associated with significant risk for developing psychotic disorders. Single Photon Emission Computed Tomography (SPECT) with 123 I-labelled iodobenzamide ([ 123 I]IBZM) was used to measure striatal DA D 2/3 receptor binding potential (D 2 R BP ND ). Also, peripheral DAergic markers were assessed in serum and urine (plasma prolactin (pPRL), plasma homovanillic acid (pHVA) and urine DA(uDA)). No significant difference in striatal D 2 R BP ND was found between UHR and 22q11DS subjects. Compared to UHR subjects, pPRL and pHVA were lower and uDA levels were higher in the 22q11DS subjects. However, after correcting for age and gender, only pPRL as significantly lower in the 22q11DS patients. These results may suggest that there are differences in DAergic markers between subjects with UHR and with 22q11DS that may reflect differences in the pathways to psychosis. However, bigger samples are needed to replicate these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Myelodysplastic Syndromes (MDS)

    Science.gov (United States)

    ... talk about donating their baby's cord blood College football player stays true to his commitment Be the ... appointment, the transplant doctor will: Review your medical history Talk with you about your treatment options Discuss ...

  15. Pathophysiology and management of thrombocytopenia in bone marrow failure: possible clinical applications of TPO receptor agonists in aplastic anemia and myelodysplastic syndromes

    Science.gov (United States)

    Desmond, Ronan; Dunbar, Cynthia E.; Young, Neal S.

    2014-01-01

    Aplastic anemia is a bone marrow failure syndrome that causes pancytopenia and can lead to life-threatening complications. Bone marrow transplantation remains the standard of care for younger patients and those with a good performance status but many patients may not have a suitable donor. Immunosuppressive therapy is able to resolve cytopenias in a majority of patients with aplastic anemia but relapses are not uncommon and some patients remain refractory to this approach. Patients may require frequent blood and platelet transfusion support which is expensive and inconvenient. Life-threatening bleeding complications still occur despite prophylactic platelet transfusion. Thrombopoietin (TPO) mimetics, such as romiplostim and eltrombopag, were developed to treat patients with refractory immune thrombocytopenia but are now being investigated for the treatment of bone marrow failure syndromes. TPO is the main regulator for platelet production and its receptor (c-Mpl) is present on megakaryocytes and hematopoietic stem cells. Trilineage hematopoietic responses were observed in a recent clinical trial using eltrombopag in patients with severe aplastic anemia refractory to immunosuppression suggesting that these agents can provide a new therapeutic option for enhancing blood production. In this review, we discuss these recent results and ongoing investigation of TPO mimetics for aplastic anemia and other bone marrow failure states like myelodysplastic syndromes. Clonal evolution or progression to acute myeloid leukemia remains a concern when using these drugs in bone marrow failure and patients should only be treated in the setting of a clinical trial. PMID:23690288

  16. Patients with a high risk for obstructive sleep apnea syndrome: Postoperative respiratory complications

    Directory of Open Access Journals (Sweden)

    H. Pereira

    2013-07-01

    Full Text Available Background: STOP-BANG score (snore; tired; observed apnea; arterial pressure; body mass index; age; neck circumference and gender can predict the risk of a patient having Obstructive Syndrome Apnea (OSA. The aim of this study was to evaluate the incidence STOP-BANG score ≥ 3, in surgical patients admitted to the Post-Anesthesia Care Unit (PACU. Methods: Observational, prospective study conducted in a post-anesthesia care unit (PACU during three weeks (2011. The study population consisted of adult patients after noncardiac and non-neurological surgery. Patients were classified as high risk of OSA (HR-OSA if STOP-BANG score ≥ 3 and Low-risk of OSA (LR-OSA if STOP-BANG score  3, em pacientes cirúrgicos internados na Unidade de Cuidados Pós-Anestésica (UCPA. Métodos: Estudo observacional e prospectivo conduzido numa UCPA, durante três semanas (2011. A população de estudo consistiu em doentes adultos após cirurgia não cardíaca e não neurológica. Os doentes foram considerados com alto risco de SAOS (AR-SAOS se tinham um score de STOP-BANG ≥3 e de baixo risco de SAOS (BR-SAOS se tinham score de STOP-BANG <3. Foram avaliados dados demográficos dos doentes e colhidas variáveis intraoperatórias e pós-operatórias. As características dos doentes foram comparadas através do teste de Mann-Whitney, teste t, qui-quadrado ou teste exato de Fisher. Resultados: Um total de 357 doentes foram admitidos de UCPA e 340 preencheram os critérios de inclusão. Cento e setenta e nove (52% tinham AR-SAOS. Estes doentes eram mais velhos, tinham maior probabilidade de serem do sexo masculino, tinham um Índice Massa Corporal superior, tiveram uma classificação maior no estado físico American Society Anesthesiologists, uma maior incidência de doença cardíaca isquémica, insuficiência cardíaca, hipertensão, dislipidemia e eram mais frequentemente doentes

  17. Adverse respiratory events after general anesthesia in patients at high risk of obstructive sleep apnea syndrome.

    Science.gov (United States)

    Xará, Daniela; Mendonça, Júlia; Pereira, Helder; Santos, Alice; Abelha, Fernando José

    2015-01-01

    Patients with STOP-BANG score >3 have a high risk of Obstructive sleep apnea. The aim of this study was to evaluate early postoperative respiratory complications in adults with STOP-BANG score >3 after general anesthesia. This is a prospective double cohort study matching 59 pairs of adult patients with STOP-BANG score >3 (high risk of obstructive sleep apnea) and patients with STOP-BANG score <3 (low risk of obstructive sleep apnea), similar with respect to gender, age and type of surgery, admitted after elective surgery in the Post-Anaesthesia Care Unit in May 2011. Primary outcome was the development of adverse respiratory events. Demographics data, perioperative variables, and postoperative length of stay in the Post-Anesthesia Care Unit and in hospital were recorded. The Mann-Whitney test, the chi-square test and the Fisher exact test were used for comparisons. Subjects in both pairs of study subjects had a median age of 56 years, including 25% males, and 59% were submitted to intra-abdominal surgery. High risk of obstructive sleep apnea patients had a higher median body mass index (31 versus 24kg/m(2), p<0.001) and had more frequently co-morbidities, including hypertension (58% versus 24%, p<0.001), dyslipidemia (46% versus 17%, p<0.001) and insulin-treated diabetes mellitus (17% versus 2%, p=0.004). These patients were submitted more frequently to bariatric surgery (20% versus 2%, p=0.002). Patients with high risk of obstructive sleep apnea had more frequently adverse respiratory events (39% versus 10%, p<0.001), mild to moderate desaturation (15% versus 0%, p=0.001) and inability to breathe deeply (34% versus 9%, p=0.001). After general anesthesia high risk of obstructive sleep apnea patients had an increased incidence of postoperative respiratory complications. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  18. [Adverse respiratory events after general anesthesia in patients at high risk of obstructive sleep apnea syndrome].

    Science.gov (United States)

    Xará, Daniela; Mendonça, Júlia; Pereira, Helder; Santos, Alice; Abelha, Fernando José

    2015-01-01

    Patients with STOP-BANG score >3 have a high risk of Obstructive sleep apnea. The aim of this study was to evaluate early postoperative respiratory complications in adults with STOP-BANG score >3 after general anesthesia. This is a prospective double cohort study matching 59 pairs of adult patients with STOP-BANG score >3 (high risk of obstructive sleep apnea) and patients with STOP-BANG score <3 (low risk of obstructive sleep apnea), similar with respect to gender, age and type of surgery, admitted after elective surgery in the Post-Anaesthesia Care Unit in May 2011. Primary outcome was the development of adverse respiratory events. Demographics data, perioperative variables, and postoperative length of stay in the Post-Anesthesia Care Unit and in hospital were recorded. The Mann-Whitney test, the chi-square test and the Fisher exact test were used for comparisons. Subjects in both pairs of study subjects had a median age of 56 years, including 25% males, and 59% were submitted to intra-abdominal surgery. High risk of obstructive sleep apnea patients had a higher median body mass index (31 versus 24kg/m(2), p<0.001) and had more frequently co-morbidities, including hypertension (58% versus 24%, p<0.001), dyslipidemia (46% versus 17%, p<0.001) and insulin-treated diabetes mellitus (17% versus 2%, p=0.004). These patients were submitted more frequently to bariatric surgery (20% versus 2%, p=0.002). Patients with high risk of obstructive sleep apnea had more frequently adverse respiratory events (39% versus 10%, p<0.001), mild to moderate desaturation (15% versus 0%, p=0.001) and inability to breathe deeply (34% versus 9%, p=0.001). After general anesthesia high risk of obstructive sleep apnea patients had an increased incidence of postoperative respiratory complications. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  19. Consistent high clinical pregnancy rates and low ovarian hyperstimulation syndrome rates in high-risk patients after GnRH agonist triggering and modified luteal support

    DEFF Research Database (Denmark)

    Iliodromiti, Stamatina; Blockeel, Christophe; Tremellen, Kelton P

    2013-01-01

    Are clinical pregnancy rates satisfactory and the incidence of OHSS low after GnRH agonist trigger and modified intensive luteal support in patients with a high risk of ovarian hyperstimulation syndrome (OHSS)?......Are clinical pregnancy rates satisfactory and the incidence of OHSS low after GnRH agonist trigger and modified intensive luteal support in patients with a high risk of ovarian hyperstimulation syndrome (OHSS)?...

  20. Williams Syndrome and Anesthesia for Non-cardiac Surgery: High Risk Can Be Mitigated with Appropriate Planning.

    Science.gov (United States)

    Brown, Morgan L; Nasr, Viviane G; Toohey, Rebecca; DiNardo, James A

    2018-03-23

    Patients with Williams syndrome are considered at high risk for anesthesia-related adverse events. At our institution, all William syndrome patients undergoing cardiac surgical, cardiac catheterization/interventional procedures, and cardiac imaging studies are cared for by cardiac anesthesiologists. All William syndrome patients undergoing non-cardiac surgical, interventional, or imaging studies are cared for by main operating room pediatric anesthesiologists with consultative input from a cardiac anesthesiologist. We reviewed our experience with 75 patients undergoing 202 separate anesthetics for 95 non-cardiac procedures and 107 cardiac procedures from 2012 to 2016. The mean age was 7.5 ± 7.0 years and the mean weight was 22.3 ± 17.0 kg. One hundred and eighty-seven patients had a general anesthetic (92.6%). Medications used included etomidate in 26.2%, propofol in 37.6%, isoflurane in 47.5%, and sevoflurane in 68.3%. Vasopressors and inotropes were required including calcium (22.8%), dopamine (10.4%), norepinephrine (17.3%), phenylephrine (35.1%), vasopressin (0.5%), and ephedrine (5.4%). The median length of stay after anesthesia was 2.8 days (range 0-32). No adverse events occurred in 89.6% of anesthetics. There were two cases of cardiac arrest, one of which required extracorporeal life support for resuscitation. Of the non-cardiac surgical procedures, 95.7% did not have a cardiovascular adverse event. Patients with Williams syndrome are at high risk for anesthesia, especially when undergoing cardiac procedures. The risk can be mitigated with appropriate planning and adherence to the hemodynamic goals for non-cardiac surgical procedures.

  1. Evaluating the use of cell phone messaging for community Ebola syndromic surveillance in high risked settings in Southern Sierra Leone.

    Science.gov (United States)

    Jia, Kangbai; Mohamed, Koroma

    2015-09-01

    Most underdeveloped countries do not meet core disease outbreak surveillance because of the lack of human resources, laboratory and infrastructural facilities. The use of cell phone technology for disease outbreak syndromic surveillance is a new phenomenon in Sierra Leone despite its successes in other developing countries like Sri Lanka. In this study we set to evaluate the effectiveness of using cell phone technology for Ebola hemorrhagic fever syndromic surveillance in a high risked community in Sierra Leone. This study evaluated the effectiveness of using cell phone messaging (text and calls) for community Ebola hemorrhagic fever syndromic surveillance in high risked community in southern Sierra Leone. All cell phone syndromic surveillance data used for this study was reported as cell phone alert messages-texts and voice calls; by the Moyamba District Health Management Team for both Ebola hemorrhagic fever suspect and mortalities. We conducted a longitudinal data analysis of the monthly cumulative confirmed Ebola hemorrhagic fever cases and mortalities collected by both the traditional sentinel and community cell phone syndromic surveillance from August 2014 to October 2014. A total of 129 and 49 Ebola hemorrhagic fever suspect and confirmed cases respectively were recorded using the community Ebola syndromic surveillance cell phone alert system by the Moyamba District Health Management Team in October 2014. The average number of Ebola hemorrhagic fever suspects and confirmed cases for October 2014 were 4.16 (Std.dev 3.76) and 1.58 (Std.dev 1.43) respectively. Thirty-four percent (n=76) of the community Ebola syndromic surveillance cell phone alerts that were followed-up within 24 hours reported Ebola hemorrhagic fever suspect cases while 65.92% (n=147) reported mortality. Our study suggests some form of underreporting by the traditional sentinel Ebola hemorrhagic fever disease surveillance system in Moyamba District southern Sierra Leone for August

  2. Metabolic syndrome in family practice in Jordan: a study of high-risk groups.

    Science.gov (United States)

    Yasein, N; Masa'd, D

    2011-12-01

    This study assessed the prevalence of the metabolic syndrome, and its components, as defined by Adult Treatment Panel III criteria in Jordanian patients attending a family practice clinic for management of cardiovascular risk factors. The sample was 730 randomly selected patients aged > or = 25 years. The prevalence of metabolic syndrome was 37.4% (31.7% in men; 41.0% in women). The prevalence increased with age in the total sample and in both sexes. High waist circumference showed the highest prevalence in the total sample (61.6%). Among females it ranked as the first criterion (73.5%). High serum triglyceride level showed the highest prevalence in males (50.2%). Differences between the sexes were significant. Family practitioners should be alerted to the importance of multiple risk factors in the metabolic syndrome.

  3. Associations between neurodevelopmental genes, neuroanatomy, and ultra high risk symptoms of psychosis in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Thompson, Carlie A; Karelis, Jason; Middleton, Frank A; Gentile, Karen; Coman, Ioana L; Radoeva, Petya D; Mehta, Rashi; Fremont, Wanda P; Antshel, Kevin M; Faraone, Stephen V; Kates, Wendy R

    2017-04-01

    22q11.2 deletion syndrome is a neurogenetic disorder resulting in the deletion of over 40 genes. Up to 40% of individuals with 22q11.2DS develop schizophrenia, though little is known about the underlying mechanisms. We hypothesized that allelic variation in functional polymorphisms in seven genes unique to the deleted region would affect lobar brain volumes, which would predict risk for psychosis in youth with 22q11.2DS. Participants included 56 individuals (30 males) with 22q11.2DS. Anatomic MR images were collected and processed using Freesurfer. Participants were genotyped for 10 SNPs in the COMT, DGCR8, GNB1L, PIK4CA, PRODH, RTN4R, and ZDHHC8 genes. All subjects were assessed for ultra high risk symptoms of psychosis. Allelic variation of the rs701428 SNP of RTN4R was significantly associated with volumetric differences in gray matter of the lingual gyrus and cuneus of the occipital lobe. Moreover, occipital gray matter volumes were robustly associated with ultra high risk symptoms of psychosis in the presence of the G allele of rs701428. Our results suggest that RTN4R, a relatively under-studied gene at the 22q11 locus, constitutes a susceptibility gene for psychosis in individuals with this syndrome through its alteration of the architecture of the brain. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. A rare variant in MYH6 is associated with high risk of sick sinus syndrome

    DEFF Research Database (Denmark)

    Holm, Hilma; Gudbjartsson, Daniel F; Sulem, Patrick

    2011-01-01

    Through complementary application of SNP genotyping, whole-genome sequencing and imputation in 38,384 Icelanders, we have discovered a previously unidentified sick sinus syndrome susceptibility gene, MYH6, encoding the alpha heavy chain subunit of cardiac myosin. A missense variant in this gene, ...

  5. High risk of rhabdomyolysis and acute kidney injury after traumatic limb compartment syndrome.

    Science.gov (United States)

    Tsai, Wei-Hsuan; Huang, Shih-Tsai; Liu, Wen-Chung; Chen, Lee-Wei; Yang, Kuo-Chung; Hsu, Kuei-Chang; Lin, Cheng-Ta; Ho, Yen-Yi

    2015-05-01

    Rhabdomyolysis often occurs after traumatic compartment syndrome, and high morbidity and mortality have been reported with the acute kidney injury that develops subsequently. We focused on the risk factors for rhabdomyolysis and acute kidney injury in patients with traumatic compartment syndrome. We also analyzed the relation between renal function and rhabdomyolysis in these patients. A retrospective chart review was conducted from January 2006 to March 2012. Inpatients with traumatic compartment syndrome were included. We evaluated patients' demographics, history of illicit drugs use or alcohol consumption, mechanism of injury, symptoms, serum creatine kinase levels, and kidney function. A total of 52 patients with a mean age of 40.9 years were included; 23 patients had rhabdomyolysis (44.2%), of which 9 patients developed acute kidney injury (39.1%). Significant predictive factors for rhabdomyolysis were history of illicit drugs or alcohol use (P=0.039; odds ratio, 5.91) and ischemic injury (P=0.005). We found a moderate correlation between serum creatine kinase levels and serum creatinine levels (R=0.57; PRhabdomyolysis was a predisposing factor for acute kidney injury (P=0.011; odds ratio, 8.68). Four patients with rhabdomyolysis required a short period of renal replacement therapy. A high percentage of patients with traumatic compartment syndrome developed rhabdomyolysis (44.2%). Patients with rhabdomyolysis had a higher possibility of developing acute kidney injury (39.1%), and rhabdomyolysis was correlated to renal function. Early diagnosis, frequent monitoring, and aggressive treatment are suggested once compartment syndrome is suspected. The overall prognosis is good with early diagnosis and proper treatment.

  6. BCR CDR3 length distributions differ between blood and spleen and between old and young patients, and TCR distributions can be used to detect myelodysplastic syndrome

    International Nuclear Information System (INIS)

    Pickman, Yishai; Mehr, Ramit; Dunn-Walters, Deborah

    2013-01-01

    Complementarity-determining region 3 (CDR3) is the most hyper-variable region in B cell receptor (BCR) and T cell receptor (TCR) genes, and the most critical structure in antigen recognition and thereby in determining the fates of developing and responding lymphocytes. There are millions of different TCR Vβ chain or BCR heavy chain CDR3 sequences in human blood. Even now, when high-throughput sequencing becomes widely used, CDR3 length distributions (also called spectratypes) are still a much quicker and cheaper method of assessing repertoire diversity. However, distribution complexity and the large amount of information per sample (e.g. 32 distributions of the TCRα chain, and 24 of TCRβ) calls for the use of machine learning tools for full exploration. We have examined the ability of supervised machine learning, which uses computational models to find hidden patterns in predefined biological groups, to analyze CDR3 length distributions from various sources, and distinguish between experimental groups. We found that (a) splenic BCR CDR3 length distributions are characterized by low standard deviations and few local maxima, compared to peripheral blood distributions; (b) healthy elderly people's BCR CDR3 length distributions can be distinguished from those of the young; and (c) a machine learning model based on TCR CDR3 distribution features can detect myelodysplastic syndrome with approximately 93% accuracy. Overall, we demonstrate that using supervised machine learning methods can contribute to our understanding of lymphocyte repertoire diversity. (paper)

  7. Transformation of myelodysplastic syndrome to acute myeloid leukemia: a case with whole-body 2- (18F) fluoro-2-deoxy-D-glucose positron emission tomography

    International Nuclear Information System (INIS)

    Liu, Fang; Cao, Qinghua

    2011-01-01

    The case reported here was that of an old woman characterized by pancytopenia, chromosome clonal abnormality, fluctuation of the percent of blast cells at 20%, and negative evidence of malignancy in whole-body 2-( 18 F) fluoro-2-deoxy-D-glucose positron emission tomography ( 18 F-FDG PET). After about 10 months, the blast cells accounted for about 25%, the morphology of which was similar to that of previous ones, and 18 F-FDG PET demonstrated diffusing increased uptake in the right upper leg and lymph nodes and patchy high uptake of bone marrow. 2-( 18 F)-fluoro-2-deoxyglucose can reflect extramedullary infiltration and bone marrow cellularity of the whole body, compared with invasive, regional biopsies and aspirations. The value of 2-( 18 F)-fluoro-2-deoxyglucose or 3'-deoxy-3'-( 18 F)-fluorothymidine positron emission tomography as an indicator in predicting the transformation of myelodysplastic syndrome to acute myeloid leukemia needs to be explored in the future. (author)

  8. Pilot study of combination transcriptional modulation therapy with sodium phenylbutyrate and 5-azacytidine in patients with acute myeloid leukemia or myelodysplastic syndrome.

    Science.gov (United States)

    Maslak, P; Chanel, S; Camacho, L H; Soignet, S; Pandolfi, P P; Guernah, I; Warrell, R; Nimer, S

    2006-02-01

    Epigenetic mechanisms underlying tumorigenesis have recently received much attention as potential therapeutic targets of human cancer. We designed a pilot study to target DNA methylation and histone deacetylation through the sequential administration of 5-azacytidine followed by sodium phenylbutyrate (PB) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Ten evaluable patients (eight AML, two MDS) were treated with seven consecutive daily subcutaneous injections of 5-azacytidine at 75 mg/m2 followed by 5 days of sodium PB given intravenously at a dose of 200 mg/kg. Five patients (50%) were able to achieve a beneficial clinical response (partial remission or stable disease). One patient with MDS proceeded to allogeneic stem cell transplantation and is alive without evidence of disease 39 months later. The combination regimen was well tolerated with common toxicities of injection site skin reaction (90% of the patients) from 5-azacytidine, and somnolence/fatigue from the sodium PB infusion (80% of the patients). Correlative laboratory studies demonstrated the consistent reacetylation of histone H4, although no relationship with the clinical response could be demonstrated. Results from this pilot study demonstrate that a combination approach targeting different mechanisms of transcriptional modulation is clinically feasible with acceptable toxicity and measurable biologic and clinical outcomes.

  9. Evaluation of renal uptake on [sup 111]InCl[sub 3] bone marrow scintigraphy in patients with aplastic anemia and myelodysplastic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Koizumi, Mitsuru; Goto, Masafumi; Nomura, Toshiharu; Watari, Tsutomu; Saito, Kenji (Dokkyo Univ. School of Medicine, Mibu, Tochigi (Japan))

    1993-04-01

    High renal uptake on bone marrow scan with indium-111 chloride is often shown in patients with bone marrow abnormality. We evaluated the renal uptake on bone marrow scan in 27 cases of aplastic anemia, 20 cases of myelodysplastic syndrome (MDS) and 10 cases of other diseases. The high renal uptake was observed in patients not only with aplastic anemia but also with MDS. The renal uptake correlated with blood transfusion units, unsaturated iron binding capacity (UIBC), blood pool imaging and bone marrow uptake. The renal uptake correlated with UIBC better than with the blood transfusion units. Following mechanism of the renal uptake is proposed that frequent blood transfusion makes low UIBC, and the low UIBC causes the failure to chelate indium with transferrin. The fast blood clearance of un-chelated indium via kidneys is followed. Hypoplastic bone marrow may also play an important role for the high renal uptake because all patients with the high renal uptake could not be explained by above mentioned mechanism. Caution should be paid to the scans with the high renal uptake because both aplastic anemia and MDS patients show the high renal uptake. (author).

  10. Therapy-Related Myelodysplastic Syndrome Following Treatment for Childhood Acute Lymphoblastic Leukemia: Outcome of Patients Registered in the EWOG-MDS 98/06 Studies

    DEFF Research Database (Denmark)

    Strahm, Birgitte; Amann, Roland; De Moerloose, Barbara

    Objective: Therapy-related myelodysplastic syndrome (tMDS) following treatment of childhood acute lymphoblastic leukemia (ALL) is one of the most frequently observed secondary malignancies in survivors of childhood cancer. Allogeneic stem cell transplantation (SCT) is the only curative treatment....... This analysis was performed to asses the outcome of patients with tMDS following treatment for childhood ALL reported to the EWOG-MDS study group. Patients and Transplant Procedure: Forty-three patients (19 male/24 female) were diagnosed with tMDS between August 1989 and August 2009. The median age at diagnosis...... was 8.9 yrs (3.4–20.5). The median interval from diagnosis of ALL to the diagnosis of tMDS was 3.3 yrs (1.7–7.0). Five patients did not receive SCT and died due to progressive disease at a median of 5.6 mo after diagnosis. Thirty-eight patients were transplanted. One patient was excluded from...

  11. Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study.

    Science.gov (United States)

    Swords, Ronan T; Erba, Harry P; DeAngelo, Daniel J; Bixby, Dale L; Altman, Jessica K; Maris, Michael; Hua, Zhaowei; Blakemore, Stephen J; Faessel, Hélène; Sedarati, Farhad; Dezube, Bruce J; Giles, Francis J; Medeiros, Bruno C

    2015-05-01

    This trial was conducted to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the first in class NEDD8-activating enzyme (NAE) inhibitor, pevonedistat, and to investigate pevonedistat pharmacokinetics and pharmacodynamics in patients with acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Pevonedistat was administered via a 60-min intravenous infusion on days 1, 3 and 5 (schedule A, n = 27), or days 1, 4, 8 and 11 (schedule B, n = 26) every 21-days. Dose escalation proceeded using a standard '3 + 3' design. Responses were assessed according to published guidelines. The MTD for schedules A and B were 59 and 83 mg/m(2) , respectively. On schedule A, hepatotoxicity was dose limiting. Multi-organ failure (MOF) was dose limiting on schedule B. The overall complete (CR) and partial (PR) response rate in patients treated at or below the MTD was 17% (4/23, 2 CRs, 2 PRs) for schedule A and 10% (2/19, 2 PRs) for schedule B. Pevonedistat plasma concentrations peaked after infusion followed by elimination in a biphasic pattern. Pharmacodynamic studies of biological correlates of NAE inhibition demonstrated target-specific activity of pevonedistat. In conclusion, administration of the first-in-class agent, pevonedistat, was feasible in patients with MDS and AML and modest clinical activity was observed. © 2015 John Wiley & Sons Ltd.

  12. Pesticide exposure as a risk factor for myelodysplastic syndromes: a meta-analysis based on 1,942 cases and 5,359 controls.

    Directory of Open Access Journals (Sweden)

    Jie Jin

    Full Text Available Pesticide exposure has been linked to increased risk of cancer at several sites, but its association with risk of myelodysplastic syndromes (MDS is still unclear. A meta-analysis of studies published through April, 2014 was performed to investigate the association of pesticide exposure with the risk of MDS.Studies were identified by searching the Web of Science, Cochrane Library and PubMed databases. Summary odds ratios (ORs with corresponding 95% confidence intervals (CIs were calculated using random- or fixed-effect models.This meta-analysis included 11 case-control studies, all of which demonstrated a correlation between pesticide exposure and a statistically significant increased risk of MDS (OR=1.95, 95% CI 1.23-3.09. In subgroup analyses, patients with pesticide exposure had increased risk of developing MDS if they were living in the Europe or Asia and had refractory anemia (RA or RA with ringed sideroblasts (RARS. Moreover, in the analysis by specific pesticides, increased risk was associated with exposure to insecticides (OR=1.71, 95% CI 1.22-2.40 but not exposure to herbicides or fungicides.This meta-analysis supports the hypothesis that exposure to pesticides increases the risk of developing MDS. Further prospective cohort studies are warranted to verify the association and guide clinical practice in MDS prevention.

  13. Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group.

    Science.gov (United States)

    Remacha, A F; Arrizabalaga, B; Villegas, A; Manteiga, R; Calvo, T; Julià, A; Fernández Fuertes, I; González, F A; Font, L; Juncà, J; del Arco, A; Malcorra, J J; Equiza, E P; de Mendiguren, B P; Romero, M

    1999-12-01

    Anemia leading to transfusion is probably the most important problem in patients with myelodysplastic syndromes (MDS). Human recombinant erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (G-CSF) have been used to treat patients with anemia of MDS, but fewer than 50% respond. The aim of this work was to evaluate the benefit of rHuEpo +/- G-CSF treatment and to isolate the response predictive variables in a group of selected patients with MDS. A non-randomized multicenter trial was carried out in 32 patients with MDS. The inclusion criteria were age >= 18 years, refractory anemia (RA) or refractory anemia with ringed sideroblasts, Hb +1 (77% of cases responded). In contrast, when this score was <= 1 only 15 % of the cases responded. Use of the Scandinavian-American response score is to be recommended in a patient-oriented approach to treating MDS cases with the Epo and G-CSF. Treatment with rHuEpo and G-CSF is safe, its main drawback being its cost. However, a long-term study evaluating the regimen's cost-benefit ratio is warranted.

  14. Evaluation of renal uptake on 111InCl3 bone marrow scintigraphy in patients with aplastic anemia and myelodysplastic syndrome

    International Nuclear Information System (INIS)

    Koizumi, Mitsuru; Goto, Masafumi; Nomura, Toshiharu; Watari, Tsutomu; Saito, Kenji

    1993-01-01

    High renal uptake on bone marrow scan with indium-111 chloride is often shown in patients with bone marrow abnormality. We evaluated the renal uptake on bone marrow scan in 27 cases of aplastic anemia, 20 cases of myelodysplastic syndrome (MDS) and 10 cases of other diseases. The high renal uptake was observed in patients not only with aplastic anemia but also with MDS. The renal uptake correlated with blood transfusion units, unsaturated iron binding capacity (UIBC), blood pool imaging and bone marrow uptake. The renal uptake correlated with UIBC better than with the blood transfusion units. Following mechanism of the renal uptake is proposed that frequent blood transfusion makes low UIBC, and the low UIBC causes the failure to chelate indium with transferrin. The fast blood clearance of un-chelated indium via kidneys is followed. Hypoplastic bone marrow may also play an important role for the high renal uptake because all patients with the high renal uptake could not be explained by above mentioned mechanism. Caution should be paid to the scans with the high renal uptake because both aplastic anemia and MDS patients show the high renal uptake. (author)

  15. BCR CDR3 length distributions differ between blood and spleen and between old and young patients, and TCR distributions can be used to detect myelodysplastic syndrome

    Science.gov (United States)

    Pickman, Yishai; Dunn-Walters, Deborah; Mehr, Ramit

    2013-10-01

    Complementarity-determining region 3 (CDR3) is the most hyper-variable region in B cell receptor (BCR) and T cell receptor (TCR) genes, and the most critical structure in antigen recognition and thereby in determining the fates of developing and responding lymphocytes. There are millions of different TCR Vβ chain or BCR heavy chain CDR3 sequences in human blood. Even now, when high-throughput sequencing becomes widely used, CDR3 length distributions (also called spectratypes) are still a much quicker and cheaper method of assessing repertoire diversity. However, distribution complexity and the large amount of information per sample (e.g. 32 distributions of the TCRα chain, and 24 of TCRβ) calls for the use of machine learning tools for full exploration. We have examined the ability of supervised machine learning, which uses computational models to find hidden patterns in predefined biological groups, to analyze CDR3 length distributions from various sources, and distinguish between experimental groups. We found that (a) splenic BCR CDR3 length distributions are characterized by low standard deviations and few local maxima, compared to peripheral blood distributions; (b) healthy elderly people's BCR CDR3 length distributions can be distinguished from those of the young; and (c) a machine learning model based on TCR CDR3 distribution features can detect myelodysplastic syndrome with approximately 93% accuracy. Overall, we demonstrate that using supervised machine learning methods can contribute to our understanding of lymphocyte repertoire diversity.

  16. Delayed globin synthesis leads to excess heme and the macrocytic anemia of Diamond Blackfan anemia and del(5q) myelodysplastic syndrome.

    Science.gov (United States)

    Yang, Zhantao; Keel, Siobán B; Shimamura, Akiko; Liu, Li; Gerds, Aaron T; Li, Henry Y; Wood, Brent L; Scott, Bart L; Abkowitz, Janis L

    2016-05-11

    Diamond Blackfan anemia (DBA) and myelodysplastic syndrome (MDS) with isolated del(5q) are severe macrocytic anemias; although both are associated with impaired ribosome assembly, why the anemia occurs is not known. We cultured marrow cells from DBA (n = 3) and del(5q) MDS (n = 6) patients and determined how heme (a toxic chemical) and globin (a protein) are coordinated. We show that globin translation initiates slowly, whereas heme synthesis proceeds normally. This results in insufficient globin protein, excess heme and excess reactive oxygen species in early erythroid precursors, and CFU-E (colony-forming unit-erythroid)/proerythroblast cell death. The cells that can more rapidly and effectively export heme or can slow heme synthesis preferentially survive and appropriately mature. Consistent with these observations, treatment with 10 μM succinylacetone, a specific inhibitor of heme synthesis, improved the erythroid cell output of DBA and del(5q) MDS marrow cultures by 68 to 95% (P = 0.03 to 0.05), whereas the erythroid cell output of concurrent control marrow cultures decreased by 4 to 13%. Our studies demonstrate that erythropoiesis fails when heme exceeds globin. Our data further suggest that therapies that decrease heme synthesis (or facilitate heme export) could improve the red blood cell production of persons with DBA, del(5q) MDS, and perhaps other macrocytic anemias. Copyright © 2016, American Association for the Advancement of Science.

  17. Multi-color CD34⁺ progenitor-focused flow cytometric assay in evaluation of myelodysplastic syndromes in patients with post cancer therapy cytopenia.

    Science.gov (United States)

    Tang, Guilin; Jorgensen, L Jeffrey; Zhou, Yi; Hu, Ying; Kersh, Marian; Garcia-Manero, Guillermo; Medeiros, L Jeffrey; Wang, Sa A

    2012-08-01

    Bone marrow assessment for myelodysplastic syndrome (MDS) in a patient who develops cytopenia(s) following cancer therapy is challenging. With recent advances in multi-color flow cytometry immunophenotypic analysis, a CD34(+) progenitor-focused 7-color assay was developed and tested in this clinical setting. This assay was first performed in 73 MDS patients and 53 non-MDS patients (developmental set). A number of immunophenotypic changes were differentially observed in these two groups. Based on the sensitivity, specificity and reproducibility, a core panel of markers was selected for final assessment that included increased total CD34(+) myeloblasts; decreased stage I hematogones; altered CD45/side scatter; altered expression of CD13, CD33, CD34, CD38, CD117, and CD123; aberrant expression of lymphoid or mature myelomonocytic antigens on CD34(+) myeloblasts; and several marked alterations in maturing myelomonocytic cells. The data were translated into a simplified scoring system which was then used in 120 patients with cytopenia(s) secondary to cancer therapy over a 2-year period (validation set). With a median follow-up of 11 months, this assay demonstrated 89% sensitivity, 94% specificity, and 92% accuracy in establishing or excluding a diagnosis of MDS. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. A phase 1/2 study of rigosertib in patients with myelodysplastic syndromes (MDS) and MDS progressed to acute myeloid leukemia.

    Science.gov (United States)

    Navada, Shyamala C; Fruchtman, Steven M; Odchimar-Reissig, Rosalie; Demakos, Erin P; Petrone, Michael E; Zbyszewski, Patrick S; Holland, James F; Silverman, Lewis R

    2018-01-01

    This Phase 1/2, dose-escalating study of rigosertib enrolled 22 patients with higher-risk myelodysplastic syndromes (MDS) (n=9) and acute myeloid leukemia (AML; n=13) who had relapsed or were refractory to standard therapy and for whom no second-line therapies were approved. Patients received 3- to 7-day continuous intravenous infusions of rigosertib, an inhibitor of Ras-effector pathways that interacts with the Ras-binding domains, common to several signaling proteins including Raf and PI3 kinase. Rigosertib was administered at doses of 650-1700mg/m 2 /day in 14-day cycles. Initial dose escalation followed a Fibonacci scheme, followed by recommended phase 2 dose confirmation in an expanded cohort. Rigosertib was well tolerated for up to 23 cycles, with no treatment-related deaths and 18% of patients with related serious adverse events (AEs). Common AEs were fatigue, diarrhea, pyrexia, dyspnea, insomnia, and anemia. Rigosertib exhibited biologic activity, with reduction or stabilization of bone marrow blasts and improved peripheral blood counts in a subset of patients. Ten of 19 evaluable patients (53%) demonstrated bone marrow/peripheral blood responses (n=4 MDS, n=1 AML) or stable disease (n=3 MDS, n=2 AML). Median survival was 15.7 and 2.0 months for responders and non-responders, respectively. Additional studies of rigosertib are ongoing in higher-risk MDS (NCT00854646). Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. A review of therapy-related myelodysplastic syndromes and acute myeloid leukaemia (t-MDS/AML) in Irish patients: a single centre experience.

    Science.gov (United States)

    Maung, Su W; Burke, Cathie; Hayde, Jennifer; Walshe, Janice; McDermott, Ray; Desmond, Ronan; McHugh, Johnny; Enright, Helen

    2017-07-01

    To demonstrate the incidence, characteristics, treatment and outcomes of patients with therapy-related myelodysplastic syndromes and therapy-related acute myeloid leukaemia (t-MDS/AML) in a tertiary referral centre. Patients meeting the diagnostic criteria for t-MDS/AML from 2003 to 2014 were reviewed to analyse their diagnostic features, details of antecedent disorder and treatment, approach to management and survival. 39 patients who developed t-MDS/AML were identified with incidence of 8.7%. Median age and gender distribution were similar to de novo MDS but t-MDS/AML patients had greater degree of cytopenia and adverse karyotypes. Time to development of t-MDS/AML was shortest for patients with antecedent haematological malignancy compared to solid tumours and autoimmune disorders (46, 85 and 109 months). Patients with prior acute leukaemia had the shortest latency and poor overall survival. Treatment options included best supportive care (56%), Azacitidine (31%) or intensive chemotherapy/allogeneic transplant (13%). Median OS of all patients was 14 months. Survival declined markedly after two years and 5-year OS was 13.8%. Longer survival was associated with blast count MDS/AML patients showed unique characteristics which influenced their treatment and outcomes. IPSS-R may be useful in risk-adapted treatment approaches and can predict outcomes. Survival remains poor but improved outcomes were seen with allogeneic transplantation. Azacitidine may be effective in patients unfit for intensive therapies.

  20. Myelodysplastic Syndrome, Unclassifiable (MDS-U) With 1% Blasts Is a Distinct Subgroup of MDS-U With a Poor Prognosis.

    Science.gov (United States)

    Margolskee, Elizabeth; Hasserjian, Robert P; Hassane, Duane; Tam, Wayne; Mathew, Susan; Ok, Chi Young; Wang, Sa A; Oak, Jean; Arber, Daniel A; Orazi, Attilio

    2017-07-01

    Three situations qualify as myelodysplastic syndrome, unclassifiable (MDS-U): (1) refractory cytopenia with dysplasia and 1% blasts in peripheral blood (BL), (2) pancytopenia with unilineage dysplasia (Pan), and (3) persistent cytopenia, less than 5% bone marrow blasts, and less than 10% dysplastic cells and presence of MDS-defining cytogenetic abnormalities (CG). We compared the clinicopathologic features and mutational profiles for these three groups. MDS-U cases were reviewed at four major academic institutions. Targeted next-generation sequencing for genes implicated in myeloid neoplasms was performed in a subset of cases. Twenty-seven patients were identified (six MDS-U BL, 13 MDS-U Pan, and eight MDS-U CG). Clonal cytogenetic abnormalities were found in six of six, seven of 13, and eight of eight cases in MDS-U BL, Pan, and CG, respectively (P > .05). Overall, four of six patients with MDS-U BL progressed to acute myeloid leukemia; no MDS-U Pan or CG patients did. The rates of progression-free survival and mortality (overall survival) were significantly higher in MDS-U BL compared with Pan and CG (P MDS-U BL is a distinct subset of MDS-U with a poor prognosis, while MDS-U Pan and CG are relatively indolent. Evaluation of peripheral blood smears in patients with MDS is essential for accurate classification and prognosis. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  1. Inspecting Targeted Deep Sequencing of Whole Genome Amplified DNA Versus Fresh DNA for Somatic Mutation Detection: A Genetic Study in Myelodysplastic Syndrome Patients.

    Science.gov (United States)

    Palomo, Laura; Fuster-Tormo, Francisco; Alvira, Daniel; Ademà, Vera; Armengol, María Pilar; Gómez-Marzo, Paula; de Haro, Nuri; Mallo, Mar; Xicoy, Blanca; Zamora, Lurdes; Solé, Francesc

    2017-08-01

    Whole genome amplification (WGA) has become an invaluable method for preserving limited samples of precious stock material and has been used during the past years as an alternative tool to increase the amount of DNA before library preparation for next-generation sequencing. Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders characterized by presenting somatic mutations in several myeloid-related genes. In this work, targeted deep sequencing has been performed on four paired fresh DNA and WGA DNA samples from bone marrow of MDS patients, to assess the feasibility of using WGA DNA for detecting somatic mutations. The results of this study highlighted that, in general, the sequencing and alignment statistics of fresh DNA and WGA DNA samples were similar. However, after variant calling and when considering variants detected at all frequencies, there was a high level of discordance between fresh DNA and WGA DNA (overall, a higher number of variants was detected in WGA DNA). After proper filtering, a total of three somatic mutations were detected in the cohort. All somatic mutations detected in fresh DNA were also identified in WGA DNA and validated by whole exome sequencing.

  2. Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Asou, Hiroya; Matsui, Hirotaka; Ozaki, Yuko; Nagamachi, Akiko; Nakamura, Megumi; Aki, Daisuke [Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553 (Japan); Inaba, Toshiya, E-mail: tinaba@hiroshima-u.ac.jp [Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553 (Japan)

    2009-05-29

    Monosomy 7 and interstitial deletions in the long arm of chromosome 7 (-7/7q-) is a common nonrandom chromosomal abnormality found frequently in myeloid disorders including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and juvenile myelomonocytic leukemia (JMML). Using a short probe-based microarray comparative genomic hybridization (mCGH) technology, we identified a common microdeletion cluster in 7q21.3 subband, which is adjacent to 'hot deletion region' thus far identified by conventional methods. This common microdeletion cluster contains three poorly characterized genes; Samd9, Samd9L, and a putative gene LOC253012, which we named Miki. Gene copy number assessment of three genes by real-time PCR revealed heterozygous deletion of these three genes in adult patients with AML and MDS at high frequency, in addition to JMML patients. Miki locates to mitotic spindles and centrosomes and downregulation of Miki by RNA interference induced abnormalities in mitosis and nuclear morphology, similar to myelodysplasia. In addition, a recent report indicated Samd9 as a tumor suppressor. These findings indicate the usefulness of the short probe-based CGH to detect microdeletions. The three genes located to 7q21.3 would be candidates for myeloid tumor-suppressor genes on 7q.

  3. Hybrid endovascular treatment of an aortic root and thoracoabdominal aneurysm in a high-risk patient with Marfan syndrome.

    Science.gov (United States)

    Gelpi, Guido; Mazzaccaro, Daniela; Romagnoni, Claudia; Contino, Monica; Antona, Carlo

    2013-05-01

    This report describes the hybrid endovascular treatment of an aortic root dilatation and a thoracoabdominal aneurysm in a high-risk patient with Marfan syndrome. A 50-year-old male, in hemodialysis for polycystic kidney and polycystic liver, was referred to our department for aortic root dilatation of 5 cm and a 6.3-cm thoracoabdominal aneurysm . He already underwent surgical repair of abdominal aortic aneurysm 10 years ago, complicated by pseudoaneurysm of the proximal anastomosis that had been treated in another center, with an endoprosthesis. The patient underwent aortic root replacement, aortic valve sparing operation, and rerouting of the superior mesenteric artery and celiac trunk to the ascending aorta. The thoracoabdominal aneurysm was excluded with an endoprosthesis few days after the surgical step. The 12-month computed tomography scan confirmed the complete exclusion of the thoracoabdominal aneurysm.

  4. A high-risk patient with long-QT syndrome with no response to cardioselective beta-blockers.

    Science.gov (United States)

    Toyota, Naoki; Miyazaki, Aya; Sakaguchi, Heima; Shimizu, Wataru; Ohuchi, Hideo

    2015-09-01

    We present a case of a high-risk 19-year-old female with long-QT syndrome (LQTS) with compound mutations. She had a history of aborted cardiac arrest and syncope and had received treatment with propranolol for 15 years. However, because she developed adult-onset asthma we tried to switch propranolol, a nonselective beta-blocker, to beta-1-cardioselective agents, bisoprolol and metoprolol. These resulted in both a markedly prolonged corrected QT interval and the development of LQTS-associated arrhythmias. Eventually, propranolol was reinitiated at a higher dose with the addition of verapamil, and she has had no further cardiac or asthmatic events for 5 years.

  5. High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2010-08-05

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With T(15;17)(q22;q12); Adult Acute Myeloid Leukemia With T(16;16)(p13;q22); Adult Acute Myeloid Leukemia With T(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Burkitt Lymphoma; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Childhood Acute Promyelocytic Leukemia (M3); Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; De Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-Cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent

  6. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter-methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre-induction, in CR and 6, 12...... and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13.5 months, >24 months in 17% of the patients, and 18-30.5 months in the four patients with trisomy 8. CR duration was not associated......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

  7. High-Risk Coronary Plaques Complicated with Acute Coronary Syndrome in Young Patients

    Directory of Open Access Journals (Sweden)

    Opincariu Diana

    2017-06-01

    Full Text Available Coronary computed tomography angiography (CCTA has evolved notably over the last decade, gaining an increased amount of temporo-spatial resolution in combination with decreased radiation exposure. The importance of CCTA is emerging especially in vulnerable and young patients who might not have developed a viable collateral vascular network to sustain the circulation to an infarction area during a major adverse coronary event. There are a few well-known markers by which a vulnerable plaque can be assessed and that can predict the subsequent events of sudden myocardial ischemia, such as an increased positive remodeling index (cut-off >1.4, low-attenuation plaque (cut-off 0.7, and napkin-ring sign (NRS. This manuscript presents a series of 3 clinical cases of young patients experiencing symptoms and signs of myocardial ischemia who underwent CCTA in order to assess the composition and functional characteristics of atherosclerotic plaques and their repercussion in developing an acute coronary syndrome.

  8. Ethical, Legal, and Clinical Considerations when Disclosing a High-Risk Syndrome for Psychosis.

    Science.gov (United States)

    Mittal, Vijay A; Dean, Derek J; Mittal, Jyoti; Saks, Elyn R

    2015-10-01

    There are complex considerations when planning to disclose an attenuated psychosis syndrome (APS) diagnosis. In this review, we evaluate ethical, legal, and clinical perspectives as well as caveats related to full, non- and partial disclosure strategies, discuss societal implications, and provide clinical suggestions. Each of the disclosure strategies is associated with benefits as well as costs/considerations. Full disclosure promotes autonomy, allows for the clearest psychoeducation about additional risk factors, helps to clarify and/or correct previous diagnoses/treatments, facilitates early intervention and bolsters communication between providers but there are important considerations involving heritability, comorbidity, culture, and stigma. Non-disclosure advances nonmaleficence by limiting stigma and stress (which may inadvertently exacerbate the condition), and confusion (related to the rapidly evolving diagnosis) in a sensitive developmental period but is complicated by varying patient preferences and the possibility that, as new treatments without adverse effects become available, the risk with false positives no longer justifies the accompanying loss of autonomy. Partial disclosure balances ethical considerations by focusing on symptoms instead of labels, but evidence that laypersons may interpret this information as a pseudo-diagnosis and that symptoms alone also contribute to stigma limits the efficacy of this approach. In addition, there are notable societal considerations relating to disclosure involving conservatorship, the reach of insurance companies, and discrimination. We advocate a hybrid approach to disclosure and recommend future research aimed at understanding the effects of stigma on clinical course and a renewed focus on those help-seeking cases that do not transition but remain clinically relevant. © 2015 John Wiley & Sons Ltd.

  9. High risk of metabolic syndrome among black South African women with severe mental illness

    Directory of Open Access Journals (Sweden)

    Shamima Saloojee

    2017-04-01

    Full Text Available Background: There is an increased prevalence of metabolic syndrome (MetS in individuals with severe mental illness (SMI globally. The prevalence of MetS is higher in black women compared to black men from South Africa. Aim: To compare the prevalence of MetS between black South African men and women with SMI taking antipsychotic medication. Further, this prevalence was compared to the prevalence in a matched control group of black South African men and women without SMI. Setting: A general hospital psychiatric unit. Methods: A cross-sectional study was undertaken to compare the prevalence of MetS in a group of multi-ethnic participants with SMI treated with antipsychotic medication and a matched control group without SMI, applying the 2009 Joint Interim Statement (JIS criteria. Here, we included only the black African participants to compare MetS prevalence between men and women. Results: There were 232 participants in the group with SMI (male 155 and female 77 and without SMI (male 156 and female 76. The prevalence of MetS was more than three times higher in women with SMI compared to men with SMI (37.7% vs. 10.3%, p < 0.001. There was no significant difference in the prevalence of MetS in men or women between the groups with and without SMI. In multivariate logistic regression analysis, female gender (odds ratio [OR] 7.66, advancing age (OR 1.08 and longer duration of illness (OR = 1.15 were significant risk factors for MetS in SMI. Conclusion: In black South Africans with SMI on antipsychotic medication, there is a higher prevalence and risk for MetS in women compared to men.

  10. High risk of post-infectious irritable bowel syndrome in patients with Clostridium difficile infection.

    Science.gov (United States)

    Wadhwa, A; Al Nahhas, M F; Dierkhising, R A; Patel, R; Kashyap, P; Pardi, D S; Khanna, S; Grover, M

    2016-09-01

    Infectious enteritis is a commonly identified risk factor for irritable bowel syndrome (IBS). The incidence of Clostridium difficile infection (CDI) is on the rise. However, there is limited information on post-infectious IBS (PI-IBS) development following CDI and the host- and infection-related risk factors are not known. To determine the incidence and risk factors for PI-IBS following CDI. A total of 684 cases of CDI identified from September 2012 to November 2013 were surveyed. Participants completed the Rome III IBS questionnaire and details on the CDI episode. Predictive modelling was done using logistic regression to evaluate risk factors for PI-IBS development. A total of 315 CDI cases responded (46% response rate) and 205 were at-risk (no pre-CDI IBS) for PI-IBS development. A total of 52/205 (25%) met the Rome III criteria for IBS ≥6 months following CDI. IBS-mixed was most common followed by IBS-diarrhoea. In comparison to those without subsequent PI-IBS, greater percentage of PI-IBS patients had CDI symptoms >7 days, nausea, vomiting, abdominal pain during CDI, anxiety and a higher BMI. Using logistic regression, CDI symptoms >7 days [Odds ratio (OR): 2.96, P = 0.01], current anxiety (OR: 1.33, P < 0.0001) and a higher BMI (OR: 1.08, P = 0.004) were independently associated with PI-IBS development; blood in the stool during CDI was protective (OR: 0.44, P = 0.06). In this cohort study, new-onset IBS is common after CDI. Longer CDI duration, current anxiety and higher BMI are associated with the diagnosis of C. difficile PI-IBS. This chronic sequela should be considered during active management and follow-up of patients with CDI. © 2016 John Wiley & Sons Ltd.

  11. Depletion of cytotoxic T-cells does not protect NUP98-HOXD13 mice from myelodysplastic syndrome but reveals a modest tumor immunosurveillance effect.

    Directory of Open Access Journals (Sweden)

    Sheryl M Gough

    Full Text Available Myelodysplastic syndrome (MDS and aplastic anemia (AA patients both present with symptoms of bone marrow failure. In many AA patients, these features are thought to result from an oligoclonal expansion of cytotoxic T-cells that destroy haematopoietic stem or progenitor cells. This notion is supported by the observation that AA patients respond to immunosuppressive therapy. A fraction of MDS patients also respond well to immunosuppressive therapy suggesting a similar role for cytotoxic T-cells in the etiology of MDS, however the role of cytotoxic T-cells in MDS remains unclear. Mice that express a NUP98-HOXD13 (NHD13 transgene develop a MDS that closely mimics the human condition in terms of dysplasia, ineffective hematopoiesis, and transformation to acute myeloid leukemia (AML. We followed a cohort of NHD13 mice lacking the Rag1 protein (NHD13/Rag1KO to determine if the absence of lymphocytes might 1 delay the onset and/or diminish the severity of the MDS, or 2 effect malignant transformation and survival of the NHD13 mice. No difference was seen in the onset or severity of MDS between the NHD13 and NHD13/Rag1KO mice. However, NHD13/Rag1KO mice had decreased survival and showed a trend toward increased incidence of transformation to AML compared to the NHD13 mice, suggesting protection from AML transformation by a modest immuno-surveillance effect. In the absence of functional Tcrb signaling in the NHD13/Rag1KO T-cell tumors, Pak7 was identified as a potential Tcrb surrogate survival signal.

  12. Multidimensional assessment of patient condition and mutational analysis in peripheral blood, as tools to improve outcome prediction in myelodysplastic syndromes: A prospective study of the Spanish MDS group.

    Science.gov (United States)

    Ramos, Fernando; Robledo, Cristina; Pereira, Arturo; Pedro, Carmen; Benito, Rocío; de Paz, Raquel; Del Rey, Mónica; Insunza, Andrés; Tormo, Mar; Díez-Campelo, María; Xicoy, Blanca; Salido, Eduardo; Sánchez-Del-Real, Javier; Arenillas, Leonor; Florensa, Lourdes; Luño, Elisa; Del Cañizo, Consuelo; Sanz, Guillermo F; María Hernández-Rivas, Jesús

    2017-09-01

    The International Prognostic Scoring System and its revised form (IPSS-R) are the most widely used indices for prognostic assessment of patients with myelodysplastic syndromes (MDS), but can only partially account for the observed variation in patient outcomes. This study aimed to evaluate the relative contribution of patient condition and mutational status in peripheral blood when added to the IPSS-R, for estimating overall survival and the risk of leukemic transformation in patients with MDS. A prospective cohort (2006-2015) of 200 consecutive patients with MDS were included in the study series and categorized according to the IPSS-R. Patients were further stratified according to patient condition (assessed using the multidimensional Lee index for older adults) and genetic mutations (peripheral blood samples screened using next-generation sequencing). The change in likelihood-ratio was tested in Cox models after adding individual covariates. The addition of the Lee index to the IPSS-R significantly improved prediction of overall survival [hazard ratio (HR) 3.02, 95% confidence interval (CI) 1.96-4.66, P < 0.001), and mutational analysis significantly improved prediction of leukemic evolution (HR 2.64, 1.56-4.46, P < 0.001). Non-leukemic death was strongly linked to patient condition (HR 2.71, 1.72-4.25, P < 0.001), but not to IPSS-R score (P = 0.35) or mutational status (P = 0.75). Adjustment for exposure to disease-modifying therapy, evaluated as a time-dependent covariate, had no effect on the proposed model's predictive ability. In conclusion, patient condition, assessed by the multidimensional Lee index and patient mutational status can improve the prediction of clinical outcomes of patients with MDS already stratified by IPSS-R. © 2017 Wiley Periodicals, Inc.

  13. Azacitidine in the 'real-world': an evaluation of 1101 higher-risk myelodysplastic syndrome/low blast count acute myeloid leukaemia patients in Ontario, Canada.

    Science.gov (United States)

    Mozessohn, Lee; Cheung, Matthew C; Fallahpour, Saber; Gill, Tripat; Maloul, Asmaa; Zhang, Liying; Lau, Olivia; Buckstein, Rena

    2018-06-01

    The outcome of myelodysplastic syndrome (MDS) patients with uniformly higher-risk disease treated with azacitidine (AZA) in the 'real-world' remains largely unknown. We evaluated 1101 consecutive higher-risk MDS patients (International Prognostic Scoring System intermediate-2/high) and low-blast count acute myeloid leukaemia (AML; 21-30% blasts) patients treated in Ontario, Canada. By dosing schedule, 24·7% received AZA for seven consecutive days, 12·4% for six consecutive days and 62·9% by 5-2-2. Overall, median number of cycles was 6 (range 1-67) and 8 (range 6-14) when restricted to the 692 (63%) patients who received at least 4 cycles. The actuarial median survival was 11·6 months [95% confidence interval (CI) 10·7-12·4) for the entire cohort and 18·0 months (landmark analysis; 95% CI 16·6-19·1 months) for those receiving at least 4 cycles. There was no difference in overall survival (OS) between the 3 dosing schedules (P = 0·87). In our large 'real-world' evaluation of AZA in higher-risk MDS/low-blast count AML, we demonstrated a lower than expected OS. Reassuringly, survival did not differ by dosing schedules. The OS was higher in the 2/3 of patients who received at least 4 cycles of treatment, reinforcing the necessity of sustained administration until therapeutic benefits are realised. This represents the largest 'real-world' evaluation of AZA in higher-risk MDS/low-blast count AML. © 2018 John Wiley & Sons Ltd.

  14. Myelodysplastic syndromes and acute myeloid leukemia in cats infected with feline leukemia virus clone33 containing a unique long terminal repeat.

    Science.gov (United States)

    Hisasue, Masaharu; Nagashima, Naho; Nishigaki, Kazuo; Fukuzawa, Isao; Ura, Shigeyoshi; Katae, Hiromi; Tsuchiya, Ryo; Yamada, Takatsugu; Hasegawa, Atsuhiko; Tsujimoto, Hajime

    2009-03-01

    Feline leukemia virus (FeLV) clone33 was obtained from a domestic cat with acute myeloid leukemia (AML). The long terminal repeat (LTR) of this virus, like the LTRs present in FeLV from other cats with AML, differs from the LTRs of other known FeLV in that it has 3 tandem direct 47-bp repeats in the upstream region of the enhancer (URE). Here, we injected cats with FeLV clone33 and found 41% developed myelodysplastic syndromes (MDS) characterized by peripheral blood cytopenias and dysplastic changes in the bone marrow. Some of the cats with MDS eventually developed AML. The bone marrow of the majority of cats with FeLV clone33 induced MDS produced fewer erythroid and myeloid colonies upon being cultured with erythropoietin or granulocyte-macrophage colony-stimulating factor (GM-SCF) than bone marrow from normal control cats. Furthermore, the bone marrow of some of the cats expressed high-levels of the apoptosis-related genes TNF-alpha and survivin. Analysis of the proviral sequences obtained from 13 cats with naturally occurring MDS reveal they also bear the characteristic URE repeats seen in the LTR of FeLV clone33 and other proviruses from cats with AML. Deletions and mutations within the enhancer elements are frequently observed in naturally occurring MDS as well as AML. These results suggest that FeLV variants that bear URE repeats in their LTR strongly associate with the induction of both MDS and AML in cats.

  15. Simultaneous analysis of the expression of 14 genes with individual prognostic value in myelodysplastic syndrome patients at diagnosis: WT1 detection in peripheral blood adversely affects survival.

    Science.gov (United States)

    Santamaría, Carlos; Ramos, Fernando; Puig, Noemi; Barragán, Eva; de Paz, Raquel; Pedro, Carme; Insunza, Andrés; Tormo, Mar; Del Cañizo, Consuelo; Diez-Campelo, María; Xicoy, Blanca; Salido, Eduardo; Sánchez del Real, Javier; Hernández, Montserrat; Chillón, Carmen; Sanz, Guillermo F; García-Sanz, Ramón; San Miguel, Jesús F; González, Marcos

    2012-12-01

    Several studies have evaluated the prognostic value of the individual expression of certain genes in patients with myelodysplastic syndromes (MDS). However, none of them includes their simultaneous analysis by quantitative polymerase chain reaction (PCR). We evaluated relative expression levels of 14 molecular markers in 193 peripheral blood samples from untreated MDS patients using real-time PCR. Detectable WT1 expression levels, low TET2, and low IER3 gene expression were the only markers showing in univariate analysis a poor prognostic value for all treatment-free (TFS), progression-free (PFS), and overall survival (OS). In multivariate analysis, molecular parameters associated with a shorter TFS were: WT1 detection (p = 0.014), low TET2 (p = 0.002), and low IER3 expression (p = 0.025). WT1 detection (p = 0.006) and low TET2 (p = 0.006) expression were associated with a shorter PFS when multivariate analysis was carried out by including only molecular markers. Molecular values with an independent value in OS were: WT1 detection (p = 0.003), high EVI1 expression (p = 0.001), and undetectatable p15-CDKN2B (p = 0.037). WT1 expressers were associated with adverse clinical-biological features, high IPSS and WPSS scoring, and unfavorable molecular expression profile. In summary, detectable WT1 expression levels, and low TET2 and low IER3 expression in peripheral blood showed a strong association with adverse prognosis in MDS patients at diagnosis. However, WT1 was the only molecular marker displaying an independent prognostic value in both OS and TFS.

  16. A pilot study on the usefulness of peripheral blood flow cytometry for the diagnosis of lower risk myelodysplastic syndromes: the "MDS thermometer".

    Science.gov (United States)

    Aires, Ana; Teixeira, Maria Dos Anjos; Lau, Catarina; Moreira, Cláudia; Spínola, Ana; Mota, Alexandra; Freitas, Inês; Coutinho, Jorge; Lima, Margarida

    2018-01-01

    Immunophenotypic analysis of the bone marrow (BM) cells has proven to be helpful in the diagnosis of Myelodysplastic Syndromes (MDS). However, the usefulness of flow cytometry (FCM) for the detection of myelodysplasia in the peripheral blood (PB) still needs to be investigated. The aim of this pilot study was to evaluate the value of FCM-based PB neutrophil and monocyte immunophenotyping for the diagnosis of lower risk MDS (LR-MDS). We evaluated by 8-color FCM the expression of multiple cell surface molecules (CD10, CD11b, CD11c, CD13, CD14, CD15, CD16, CD34, CD45, CD56, CD64 and HLA-DR) in PB neutrophils and monocytes from a series of 14 adult LR-MDS patients versus 14 normal individuals. Peripheral blood neutrophils from patients with LR-MDS frequently had low forward scatter (FSC) and side scatter (SSC) values and low levels of CD11b, CD11c, CD10, CD16, CD13 and CD45 expression, in that order, as compared to normal neutrophils. In addition, patients with LR-MDS commonly display a higher fraction of CD14 + CD56 + and a lower fraction of CD14 + CD16 + monocytes in the PB. Based on these results, we proposed an immunophenotyping score based on which PB samples from patients with LR-MDS could be distinguished from normal PB samples with a sensitivity 93% and a specificity of 100%. In addition, we used this score to construct the MDS Thermometer, a screening tool for detection and monitoring of MDS in the PB in clinical practice. Peripheral blood neutrophil and monocyte immunophenotyping provide useful information for the diagnosis of LR-MDS, as a complement to cytomorphology. If validated by subsequent studies in larger series of MDS patients and extended to non-MDS patients with cytopenias, our findings may improve the diagnostic assessment and avoid invasive procedures in selected groups of MDS patients.

  17. Clinical and biological significance of isolated Y chromosome loss in myelodysplastic syndromes and chronic myelomonocytic leukemia. A report from the Spanish MDS Group.

    Science.gov (United States)

    Nomdedeu, Meritxell; Pereira, Arturo; Calvo, Xavier; Colomer, Joan; Sole, Francesc; Arias, Amparo; Gomez, Candida; Luño, Elisa; Cervera, Jose; Arnan, Montserrat; Pomares, Helena; Ramos, Fernando; Oiartzabal, Itziar; Espinet, Blanca; Pedro, Carme; Arrizabalaga, Beatriz; Blanco, María Laura; Tormo, Mar; Hernandez-Rivas, Jesus Maria; Díez-Campelo, María; Ortega, Margarita; Valcárcel, David; Cedena, Maria-Teresa; Collado, Rosa; Grau, Javier; Granada, Isabel; Sanz, Guillermo; Campo, Elias; Esteve, Jordi; Costa, Dolors

    2017-12-01

    Isolate loss of chromosome Y (-Y) in myelodysplastic syndromes (MDS) is associated to a better outcome but it is also well described as an age-related phenomenon. In this study we aimed to analyze the prognostic impact of -Y in the context of the IPSS-R cytogenetic classification, evaluate the clinical significance of the percentage of metaphases with isolated -Y, and test whether finding -Y may predispose to over-diagnose MDS in patients with borderline morphological features. We evaluated 3581 male patients from the Spanish MDS Registry with a diagnosis of MDS or chronic myelomonocytic leukemia (CMML). -Y was identified in 177 patients (4.9%). Compared with the 2246 male patients with normal karyotype, -Y group showed a reduced risk of leukemic transformation that did not translate into a survival advantage. The overall survival and the risk of leukemic transformation were not influenced by the percentage of metaphases with -Y. The -Y group was not enriched in patients with minor morphologic traits of dysplasia, suggesting that the better outcome in the -Y group cannot be explained by enrichment in cases misdiagnosed as MDS. In conclusion, our results support the current recommendation of classifying patients with -Y within the very good risk category of the IPSS-R for MDS and rule out a selection bias as a possible explanation of this better outcome. An analysis of the molecular basis of MDS with isolated -Y would be of interest as it may provide a biological basis of protection against progression to acute leukemia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Iron overload in lower international prognostic scoring system risk patients with myelodysplastic syndrome receiving red blood cell transfusions: Relation to infections and possible benefit of iron chelation therapy.

    Science.gov (United States)

    Wong, Colleen A C; Wong, Shannon A Y; Leitch, Heather A

    2018-04-01

    An increased incidence of infections and infectious mortality has been reported in myelodysplastic syndromes (MDS) patients receiving red blood cell (RBC) transfusions. We examined incidence of infections requiring antibiotics, antifungal or antiviral medications in transfused lower International Prognostic Scoring System (IPSS) risk MDS patients and whether this differed with iron chelation therapy (ICT). 138 transfused MDS patients were lower IPSS risk. 59 received ICT; median duration was 13 months. There was no significant difference between groups in neutrophil count at first RBC transfusion or first infection. Infections included: bacterial, n = 88; viral; fungal; and mycobacterial; n = 2 each. In ICT and non-ICT patients, respectively, infections were (number [%]): patients, 23 (40.0%) and 22 (27.8%); episodes (median [range]), 2 (1-6) and 2 (1-5); hospitalizations, 16 (27.1%) and 8 (10.1%); and deaths, 0 (0%) and 1 (1.3%), p = NS for all. Median overall survival (OS) from first RBC transfusion was superior in ICT patients, p = 0.01, and remained significant in a multivariate analysis (MVA), p = 0.003. Median time to first infection (TTI) was 27 and 7.8 months, respectively, p < 0.0001, and ICT remained significant for TTI in an MVA, p = 0.02, hazard ratio 0.3. For ICT patients with blast count <5%, TTI was significantly superior (p = 0.004). In this retrospective analysis, for lower IPSS risk MDS patients receiving RBC transfusions, though number and type of infections were similar between groups and despite similar neutrophil counts, time to first infection was significantly longer in ICT patients (p < 0.0001). These results should be confirmed in larger, prospective analyses. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Cytogenetic abnormalities in a series of 1,029 patients with primary myelodysplastic syndromes: a report from the US with a focus on some undefined single chromosomal abnormalities.

    Science.gov (United States)

    Pozdnyakova, Olga; Miron, Patricia M; Tang, Guilin; Walter, Otto; Raza, Azra; Woda, Bruce; Wang, Sa A

    2008-12-15

    Conventional karyotype has an established role in myelodysplastic syndrome (MDS) and is included in the International Prognostic Scoring System (IPSS) for patient risk stratification and treatment selection. Although some chromosomal abnormalities have been well characterized, the significance of several miscellaneous, infrequent, single chromosomal abnormalities remains to be defined. In addition, the emerging therapeutic agents may change the natural course of disease in patients with MDS and the cytogenetic impact on risk stratification. Clinicopathologic data were retrieved on 1029 patients who had a diagnosis of primary MDS and had available cytogenetic data (karyotype) on file. Cytogenetic abnormalities were identified in 458 patients (45%) and occurred most frequently in patients who had refractory anemia with excess blasts (62%). Overall, the 3 cytogenetic risk groups defined by the IPSS -- good, intermediate, and poor -- effectively stratified the patients' overall survival (OS) (64 months, 31 months, and 12 months, respectively; P < .001). With the exception of gain of chromosome 8, single cytogenetic abnormalities within the intermediate group were extremely infrequent in the series but demonstrated variable OS ranging from 10 months for patients who had isochromosome (17q) to 69 months for patients who had deletion of 12p [del(12p)], suggesting different prognostic significance. In the poor cytogenetic risk group, patients with isolated del(7q) and derivative (1;7)(q10;p10) had a significantly better median OS than patients who had either loss of chromosome 7 or a complex karyotype (P < .05). The current data generated from a large cohort of patients with primary MDS indicated that some specific cytogenetic abnormalities carry different risk than their IPSS cytogenetic risk-group assignment, especially in the new treatment era. Because of the extreme low frequency, additional combined studies are needed to better categorize some rare single cytogenetic

  20. Investigation of 305 patients with myelodysplastic syndromes and 20q deletion for associated cytogenetic and molecular genetic lesions and their prognostic impact.

    Science.gov (United States)

    Bacher, Ulrike; Haferlach, Torsten; Schnittger, Susanne; Zenger, Melanie; Meggendorfer, Manja; Jeromin, Sabine; Roller, Andreas; Grossmann, Vera; Krauth, Maria-Theresa; Alpermann, Tamara; Kern, Wolfgang; Haferlach, Claudia

    2014-03-01

    In patients with myelodysplastic syndromes (MDS), sole 20q deletion [del(20q)] is a recurrent favourable abnormality. We studied additional molecular and cytogenetic lesions and their prognostic impact in 305 MDS patients with del(20q) (229 males/76 females; 29-90 years). All patients were investigated by cytomorphology and chromosome banding analysis (CBA), subsets by fluorescence in situ hybridization, molecular mutation screening, and array comparative genomic hybridization (aCGH). By aCGH (n = 30), the minimal common deleted region (CDR) was flanked by PTPRT (20q13·11) and EYA2 (20q13·12). 210 (68·9%) patients had 'early MDS' without blast increase, 95 (31·1%) 'advanced' MDS with blast increase (5-19%). Additional chromosomal abnormalities (ACAs) were detected in 88/305 (28·9%) patients. Patients with advanced MDS more frequently had ACAs (P = 0·003) and had a higher mean number of ACAs (P = 0·020) and of molecular mutations (P = 0·060). Spliceosome mutations were frequent (U2AF1: n = 31/155; 20·0%; SRSF2: n = 31/159; 19·5%; SF3B1mut: n = 8/159; 5·0%). ASXL1mut (25/153; 16·3%) were associated with advanced MDS (P = 0·001). Presence of ≥3 ACAs (P = 0·003) and ASXL1mut (P = 0·002) were associated with worse 2-year survival. In conclusion, the cytogenetic subgroup of MDS with del(20q) has a good prognosis but may be further subclassified by additional cytogenetic and molecular lesions. U2AF1mut is overrepresented in MDS with del(20q), and ASXL1mut is prognostically adverse. © 2013 John Wiley & Sons Ltd.

  1. Report on outcomes of hypomethylating therapy for analyzing prognostic value of Revised International Prognostic Scoring System for patients with lower-risk myelodysplastic syndromes.

    Science.gov (United States)

    Lee, Yoo Jin; Park, Sung Woo; Lee, In Hee; Ahn, Jae Sook; Kim, Hyeoung Joon; Chung, Joo Seop; Shin, Ho Jin; Lee, Won Sik; Lee, Sang Min; Joo, Young Don; Kim, Hawk; Lee, Ho Sup; Kim, Yang Soo; Cho, Yoon Young; Moon, Joon Ho; Sohn, Sang Kyun

    2016-10-01

    The outcomes for patients with lower-risk myelodysplastic syndromes (LR-MDS) by the International Prognostic Scoring System (IPSS) vary widely. For more precise prognostication, this study evaluates the prognostic value of revised IPSS with the response to hypomethylating therapy (HMT). Using the Korean MDS Working Party database, treatment outcomes for 236 patients with HMT were retrospectively evaluated. The patients were then reclassified into very low/low (VL/L), intermediate (INT), and high (H) risk groups according to IPSS-R. According to the HMT response, the 3-year overall survival (OS) did not differ between the response group (37.9 ± 9.1 %) and the stable group (52.9 ± 6.6 %, p = 0. 782). When reclassifying according to IPSS-R, 42 patients (20.8 %) were reclassified into the H risk group. Most of them did not have benefit from continued HMT and progressed to secondary failure. The median OS was 59.0 months (range, 40.0-77.9 months) for the VL/L risk group, 31 months (range, 22.7-439.3 months) for the INT risk group, and 20.0 months (range, 15.9-24.1 months) for the H risk group (p risk group according to IPSS-R (HR = 3.054, p risk according to IPSS-R (HR = 4.912, p = 0.003), and transformation to AML (HR = 2.158, p = 0.002). If IPSS-R reclassifies LR-MDS patients as H risk, these patients should be considered for early allo-HCT, regardless of the current benefits from HMT.

  2. [Distribution of abnormal cell clone with deletion of chromosome 20q in marrow cell lineages and apoptosis cells in myelodysplastic syndrome].

    Science.gov (United States)

    Qin, Ling; Wang, Chun; Qin, You-Wen; Xie, Kuang-Cheng; Yan, Shi-Ke; Gao, Yan-Rong; Wang, Xiao-Rui; Zhao, Chu-Xian

    2008-06-01

    This study was aimed to investigate the distribution of abnormal clone in marrow cell lineages and apoptosis cells in myelodysplastic syndrome (MDS) with deletion of chromosome 20q. Monoclonal antibodies recognizing myeloid precursors (CD15), erythroid precursors (GPA), T cells (CD3(+)CD56(-)CD16(-)), B cells (CD19), NK cells (CD3(-)CD56(+)CD16(+)) were used to sort bone marrow cells in a MDS patient with del (20q) by fluorescence activated cell sorting (FACS). Annexin V-FITC and PI were used to sort bone marrow Annexin V(+)PI(-) and Annexin V(-)PI(-) cells by FACS. The sorted positive cells were detected by interphase dual-color fluorescence in situ hybridization (D-FISH) using a LSI D20S108 probe (Spectrum Orange) and a Telvysion TM 20p probe (Spectrum Green). FACS and FISH analysis were also performed on the samples from 4 cases with normal karyotype. The results showed that the proportions of MDS clone in the myeloid and erythroid precursors were 70.50% and 93.33% respectively, in the RAEB-1 patient with del (20q) and were obviously higher than that in control group (5.39% and 6.17%). The proportions of abnormal clone in T, B and NK cells were 3.23%, 4.32% and 5.77% respectively and were less than that in control group (5.76%, 4.85%, 6.36%). The percentage of apoptotic cells in the bone marrow nucleated cells was 16.09%. The proportions of MDS clone in Annexin V(+)PI(-) and Annexin V(-)PI(-) cells were 32.48% and 70.11%, respectively. It is concluded that most myeloid and erythroid precursors are originated from the abnormal clone in MDS with del (20q). A little part of apoptotic cells are derived from the abnormal clone.

  3. Cortical morphology development in patients with 22q11.2 deletion syndrome at ultra-high risk of psychosis.

    Science.gov (United States)

    Padula, Maria Carmela; Schaer, Marie; Armando, Marco; Sandini, Corrado; Zöller, Daniela; Scariati, Elisa; Schneider, Maude; Eliez, Stephan

    2018-01-17

    Patients with 22q11.2 deletion syndrome (22q11DS) present a high risk of developing psychosis. While clinical and cognitive predictors for the conversion towards a full-blown psychotic disorder are well defined and largely used in practice, neural biomarkers do not yet exist. However, a number of investigations indicated an association between abnormalities in cortical morphology and higher symptoms severities in patients with 22q11DS. Nevertheless, few studies included homogeneous groups of patients differing in their psychotic symptoms profile. In this study, we included 22 patients meeting the criteria for an ultra-high-risk (UHR) psychotic state and 22 age-, gender- and IQ-matched non-UHR patients. Measures of cortical morphology, including cortical thickness, volume, surface area and gyrification, were compared between the two groups using mass-univariate and multivariate comparisons. Furthermore, the development of these measures was tested in the two groups using a mixed-model approach. Our results showed differences in cortical volume and surface area in UHR patients compared with non-UHR. In particular, we found a positive association between surface area and the rate of change of global functioning, suggesting that higher surface area is predictive of improved functioning with age. We also observed accelerated cortical thinning during adolescence in UHR patients with 22q11DS. These results, although preliminary, suggest that alterations in cortical volume and surface area as well as altered development of cortical thickness may be associated to a greater probability to develop psychosis in 22q11DS.

  4. Magnitude and consequences of undertreatment of high-risk patients with non-ST segment elevation acute coronary syndromes: insights from the DESCARTES Registry.

    Science.gov (United States)

    Heras, M; Bueno, H; Bardají, A; Fernández-Ortiz, A; Martí, H; Marrugat, J

    2006-11-01

    To analyse intensity of treatment of high-risk patients with non-ST elevation acute coronary syndromes (NSTEACS) included in the DESCARTES (Descripción del Estado de los Sindromes Coronarios Agudos en un Registro Temporal Español) registry. Patients with NSTEACS (n = 1877) admitted to 45 randomly selected Spanish hospitals in April and May 2002 were studied. Patients with ST segment depression and troponin rise were considered high risk (n = 478) and were compared with non-high risk patients (n = 1399). 46.9% of high-risk patients versus 39.5% of non-high-risk patients underwent angiography (p = 0.005), 23.2% versus 18.8% (p = 0.038) underwent percutaneous revascularisation, and 24.9% versus 7.4% (p or = 4, 2-3 and or = 4 (OR 2.87, 95% CI 1.27 to 6.52, p = 0.012). Class I recommended treatments were underused in high-risk patients in the DESCARTES registry. This undertreatment was an independent predictor of death of patients with an acute coronary syndrome.

  5. The Jervell and Lange-Nielsen syndrome; atrial pacing combined with ß-blocker therapy, a favorable approach in young high-risk patients with long QT syndrome?

    Science.gov (United States)

    Früh, Andreas; Siem, Geir; Holmström, Henrik; Døhlen, Gaute; Haugaa, Kristina H

    2016-11-01

    Patients with Jervell and Lange-Nielsen syndrome (JLNS) exhibit severe phenotypes that are characterized by congenital deafness, very long QT intervals, and high risk of life-threatening arrhythmias. Current treatment strategies include high doses of beta-blocker medication, left cardiac sympathetic denervation, and ICD placement, which is challenging in young children. The purpose of this study was to evaluate the safety and effect of pacing in addition to beta-blocker treatment in children with JLNS. All genetically confirmed patients with JLNS born since 1999 in Norway were included in the study. Data on history of long QT syndrome-related symptoms, QT interval, and beta-blocker and pacemaker treatment were recorded. A total of 9 patients with QT intervals ranging from 510 to 660 ms were identified. Eight patients developed long QT syndrome-related symptoms, and 1 patient died before diagnosis. The survivors received beta-blocker medication. Seven patients also received a pacemaker; 1 had a ventricular lead and 6 had atrial leads. The patient with the ventricular lead died during follow-up. The 6 patients with atrial leads survived without events at a mean follow-up of 6.9 years after pacemaker implantation. Two patients received prophylactic upgrade to a 2-chamber ICD. No arrhythmic events occurred in 6 very young JLNS patients who received atrial pacing in combination with increased doses of beta-blockers during 7-year follow-up. If confirmed in additional patients, this treatment strategy may prevent life-threatening arrhythmias in this high-risk patient group and may act as a bridge to insertion of a 2-chamber ICD when left cardiac sympathetic denervation is not available. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Increased incidence of myelodysplastic syndrome and acute myeloid leukemia following breast cancer treatment with radiation alone or combined with chemotherapy: a registry cohort analysis 1990-2005

    International Nuclear Information System (INIS)

    Kaplan, Henry G; Malmgren, Judith A; Atwood, Mary K

    2011-01-01

    Our objective was to measure myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) risk associated with radiation and/or chemotherapy breast cancer (BC) treatment. Our study cohort was composed of BC patients diagnosed from 1990 to 2005 and followed up for blood disorders, mean length of follow up = 7.17 years, range 2-18 years. 5790 TNM stage 0-III patients treated with surgery alone, radiation and/or chemotherapy were included. Patients without surgery (n = 111), with stem cell transplantation (n = 98), unknown or non-standard chemotherapy regimens (n = 94), lost to follow up (n = 66) or 'cancer status unknown' (n = 67) were excluded. Rates observed at our community based cancer care institution were compared to SEER incidence data for rate ratio (RR) calculations. 17 cases of MDS/AML (10 MDS/7 AML) occurred during the follow up period, crude rate .29% (95% CI = .17, .47), SEER comparison RR = 3.94 (95% CI = 2.34, 6.15). The RR of MDS in patients age < 65 comparing our cohort incidence to SEER incidence data was 10.88 (95% CI = 3.84, 24.03) and the RR of AML in patients age < 65 was 5.32 (95% CI = 1.31, 14.04). No significant increased risk of MDS or AML was observed in women ≥ 65 or the surgery/chemotherapy-only group. A RR of 3.32 (95% CI = 1.42, 6.45) was observed in the surgery/radiation-only group and a RR of 6.32 (95% CI = 3.03, 11.45) in the surgery/radiation/chemotherapy group. 3 out of 10 MDS cases died of disease at an average 3.8 months post diagnosis and five of seven AML cases died at an average 9 months post diagnosis. An elevated rate of MDS and AML was observed among breast cancer patients < 65, those treated with radiation and those treated with radiation and chemotherapy compared to available population incidence data. Although a small number of patients are affected, leukemia risk associated with treatment and younger age is significant

  7. Síndromes mielodisplásticas: diagnóstico de exclusão Myelodysplastic syndromes: diagnosis by exclusion

    Directory of Open Access Journals (Sweden)

    Silvia M. M. Magalhães

    2006-09-01

    Full Text Available As síndromes mielodisplásticas são comuns nos indivíduos com idade superior a 60 anos e se apresentam laboratorialmente com macrocitose isolada, anemia, citopenias isoladas ou combinadas e alterações morfológicas na medula óssea. O diagnóstico depende da exclusão de causas não clonais e reversíveis. Especialmente nas fases mais precoces da doença, na ausência de excesso de blastos, sideroblastos em anel ou alteração citogenética clonal, o diagnóstico requer um protocolo de exclusão. A exposição recente a agentes tóxicos ou drogas citostáticas, a deficiência de vitamina B12 e ácido fólico e o uso recente de fatores de crescimento são considerados fatores de exclusão absolutos. O etilismo, a anemia da doença crônica, distúrbios metabólicos, hormonais, auto-imunes e infecções virais devem ser excluídos ou interpretados com cautela. Outras doenças da célula-tronco hematopoética devem ser consideradas, sobretudo na SMD hipocelular. Em alguns casos, um período mínimo de seis meses de seguimento é necessário.Myelodysplastic syndromes are common in elderly people. Laboratory presentation includes isolated macrocytosis, anemia, isolated or combined cytopenias and dysplastic bone marrow. Diagnosis depends on exclusion of non-clonal and reversible disorders. Especially in lowest grade of the disease, with no blast excess, no ringed sideroblasts, no clonal cytogenetic abnormalities the diagnosis requires an exclusion protocol. Recent exposure to toxin, cytotoxic drugs or growth factor therapy and vitamin B12 or folate deficiency are considered absolute exclusion factors precluding the definite diagnosis. Alcohol abuse, chronic inflammatory states, auto-immune disorders, metabolic dysfunctions, hormonal disorders and viral infections must all be ruled out or interpreted with caution. Some diseases of the pluripotential stem cell must also be considered especially in hypocellular MDS. Moreover, in some cases a 6-month

  8. Using peripheral blood circulating DNAs to detect CpG global methylation status and genetic mutations in patients with myelodysplastic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Iriyama, Chisako [Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Tomita, Akihiro, E-mail: atomita@med.nagoya-u.ac.jp [Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Hoshino, Hideaki; Adachi-Shirahata, Mizuho [Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Furukawa-Hibi, Yoko; Yamada, Kiyofumi [Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Nagoya (Japan); Kiyoi, Hitoshi; Naoe, Tomoki [Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya (Japan)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer Circulating DNAs (CDs) can be used to detect genetic/epigenetic abnormalities in MDS. Black-Right-Pointing-Pointer Epigenetic changes can be detected more sensitively when using plasma DNA than PBMNC. Black-Right-Pointing-Pointer Mutation ratio in CDs may reflect the ratio in stem cell population in bone marrow. Black-Right-Pointing-Pointer Using CDs can be a safer alternate strategy compared to bone marrow aspiration. -- Abstract: Myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder. Several genetic/epigenetic abnormalities are deeply associated with the pathogenesis of MDS. Although bone marrow (BM) aspiration is a common strategy to obtain MDS cells for evaluating their genetic/epigenetic abnormalities, BM aspiration is difficult to perform repeatedly to obtain serial samples because of pain and safety concerns. Here, we report that circulating cell-free DNAs from plasma and serum of patients with MDS can be used to detect genetic/epigenetic abnormalities. The plasma DNA concentration was found to be relatively high in patients with higher blast cell counts in BM, and accumulation of DNA fragments from mono-/di-nucleosomes was confirmed. Using serial peripheral blood (PB) samples from patients treated with hypomethylating agents, global methylation analysis using bisulfite pyrosequencing was performed at the specific CpG sites of the LINE-1 promoter. The results confirmed a decrease of the methylation percentage after treatment with azacitidine (days 3-9) using DNAs from plasma, serum, and PB mono-nuclear cells (PBMNC). Plasma DNA tends to show more rapid change at days 3 and 6 compared with serum DNA and PBMNC. Furthermore, the TET2 gene mutation in DNAs from plasma, serum, and BM cells was quantitated by pyrosequencing analysis. The existence ratio of mutated genes in plasma and serum DNA showed almost equivalent level with that in the CD34+/38- stem cell population in BM. These data suggest that genetic

  9. HFE gene mutation and oxidative damage biomarkers in patients with myelodysplastic syndromes and its relation to transfusional iron overload: an observational cross-sectional study.

    Science.gov (United States)

    De Souza, Geane Felix; Ribeiro, Howard Lopes; De Sousa, Juliana Cordeiro; Heredia, Fabíola Fernandes; De Freitas, Rivelilson Mendes; Martins, Manoel Ricardo Alves; Gonçalves, Romélia Pinheiro; Pinheiro, Ronald Feitosa; Magalhães, Silvia Maria Meira

    2015-04-03

    A relation between transfusional IOL (iron overload), HFE status and oxidative damage was evaluated. An observational cross-sectional study involving 87 healthy individuals and 78 patients with myelodysplastic syndromes (MDS) with and without IOL, seen at University Hospital of the Federal University of Ceará, Brazil, between May 2010 and September 2011. IOL was defined using repeated measures of serum ferritin ≥1000 ng/mL. Variations in the HFE gene were investigated using PCR/restriction fragment length polymorphism (RFLP). The biomarkers of oxidative stress (plasmatic malonaldehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD)) were determined by spectrophotometry. The HFE gene variations were identified in 24 patients (30.77%) and 5 volunteers (5.74%). The H63D variant was observed in 35% and the C282Y variant as heterozygous in 5% of patients with MDS with IOL. One patient showed double heterozygous variant (C282Y/H63D) and serum ferritin of 11,649 ng/mL. In patients without IOL, the H63D variant was detected in 29.34%. Serum MDA levels were highest in patients with MDS with IOL, with a significant difference when compared with patients without IOL and healthy volunteers, pointing to the relationship between IOL and oxidative stress. The GPx and SOD were also significantly higher in these patients, indicating that lipid peroxidation increase was followed by an increase in antioxidant capacity. Higher ferritin levels were observed in patients with HFE gene variation. 95.7% of patients with MDS with the presence of HFE gene variations had received more of 20 transfusions. We observed a significant increase in MDA levels in patients with MDS and IOL, suggesting an increased lipid peroxidation in these patients. The accumulation of MDA alters the organisation of membrane phospholipids, contributing to the process of cellular degeneration. Results show that excess iron intensifies the process of cell damage through oxidative stress

  10. Using peripheral blood circulating DNAs to detect CpG global methylation status and genetic mutations in patients with myelodysplastic syndrome

    International Nuclear Information System (INIS)

    Iriyama, Chisako; Tomita, Akihiro; Hoshino, Hideaki; Adachi-Shirahata, Mizuho; Furukawa-Hibi, Yoko; Yamada, Kiyofumi; Kiyoi, Hitoshi; Naoe, Tomoki

    2012-01-01

    Highlights: ► Circulating DNAs (CDs) can be used to detect genetic/epigenetic abnormalities in MDS. ► Epigenetic changes can be detected more sensitively when using plasma DNA than PBMNC. ► Mutation ratio in CDs may reflect the ratio in stem cell population in bone marrow. ► Using CDs can be a safer alternate strategy compared to bone marrow aspiration. -- Abstract: Myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder. Several genetic/epigenetic abnormalities are deeply associated with the pathogenesis of MDS. Although bone marrow (BM) aspiration is a common strategy to obtain MDS cells for evaluating their genetic/epigenetic abnormalities, BM aspiration is difficult to perform repeatedly to obtain serial samples because of pain and safety concerns. Here, we report that circulating cell-free DNAs from plasma and serum of patients with MDS can be used to detect genetic/epigenetic abnormalities. The plasma DNA concentration was found to be relatively high in patients with higher blast cell counts in BM, and accumulation of DNA fragments from mono-/di-nucleosomes was confirmed. Using serial peripheral blood (PB) samples from patients treated with hypomethylating agents, global methylation analysis using bisulfite pyrosequencing was performed at the specific CpG sites of the LINE-1 promoter. The results confirmed a decrease of the methylation percentage after treatment with azacitidine (days 3–9) using DNAs from plasma, serum, and PB mono-nuclear cells (PBMNC). Plasma DNA tends to show more rapid change at days 3 and 6 compared with serum DNA and PBMNC. Furthermore, the TET2 gene mutation in DNAs from plasma, serum, and BM cells was quantitated by pyrosequencing analysis. The existence ratio of mutated genes in plasma and serum DNA showed almost equivalent level with that in the CD34+/38- stem cell population in BM. These data suggest that genetic/epigenetic analyses using PB circulating DNA can be a safer and painless alternative to using BM

  11. Red Blood Cell Transfusion Dependency and Hyperferritinemia Are Associated with Impaired Survival in Patients Diagnosed with Myelodysplastic Syndromes: Results from the First Polish MDS-PALG Registry.

    Science.gov (United States)

    Waszczuk-Gajda, Anna; Mądry, Krzysztof; Machowicz, Rafał; Drozd-Sokołowska, Joanna; Stella-Hołowiecka, Beata; Mital, Andrzej; Obara, Agata; Szmigielska-Kapłon, Anna; Sikorska, Anna; Subocz, Edyta; Jędrzejczak, Wiesław W; Dwilewicz-Trojaczek, Jadwiga

    2016-01-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis, cytopenias and a risk of progression to acute myeloid leukemia (AML). Anemia is the most frequent cytopenia diagnosed in patients with MDS. Regular RBC transfusions are the only treatment option for about 40% of patients. Transfusion-dependent patients develop secondary iron overload. The influence of serum ferritin (SF) concentration on survival and acute myeloid leukemia transformation in MDS patients remains controversial. The data for the Central European population is scarce and so far there is no description for Poland. The aim of this study was to perform a retrospective analysis of the relationship of SF concentration with red blood cell transfusion dependency, survival and transformation to acute myeloid leukemia. We retrospectively evaluated the data of the 819 MDS patients (58% male; median age 70 years) included in the MDS Registry of the MDS Section of the Polish Adult Leukemia Group (PALG). Analyses were performed on 190 patients diagnosed with MDS, maximal 6 months before inclusion to the registry in order to avoid selection bias (a shorter survival of higher risk MDS patients). Patients with hyperferritinemia higher than 1000 ng/L vs. patients with SF concentration lower than 1000 ng/L had a median survival of 320 days vs. 568 days, respectively (p log-rank = 0.014). The following factors were found to significantly worsen survival: RBC-transfusion dependence (p = 0.0033; HR 2.67L), platelet transfusion dependence (p = 0.0071; HR 3.321), hemoglobin concentration lower than 10 g/dL (p = 0.0036; HR 2.97), SF concentration higher than 1000 ng/L (p = 0.0023; HR = 2.94), platelet count lower than 10 G/L (p = 0.0081 HR = 5.04), acute leukemia transformation (p = 0.0081; HR 1.968). Taking into account the relatively low number of patients in previous studies exploring hyperferritinemia in MDS, the results of the first Polish

  12. Restless legs syndrome after high-risk TIA and minor stroke: association with reduced quality of life.

    Science.gov (United States)

    Boulos, Mark I; Wan, Anthony; Black, Sandra E; Lim, Andrew S; Swartz, Richard H; Murray, Brian J

    2017-09-01

    Restless legs syndrome (RLS) is a movement disorder that is associated with poor quality of life and depressive symptoms in the general population. Emerging evidence suggests that RLS is closely associated with cerebrovascular disease. We assessed the effect of RLS on quality of life after stroke and transient ischemic attack (TIA). In this single-center prospective study, we recruited patients within 14 days of high-risk TIA or minor stroke. Patients were diagnosed with RLS using a questionnaire based on the 2003 International RLS Study Group criteria, and diagnoses were confirmed by a sleep neurologist. Follow-up assessments were conducted within 2-6 months of recruitment. The outcome of quality of life was measured using the Stroke-specific Quality of Life (SS-QoL). Of the 94 patients recruited into the study, 23 (24.4%) were diagnosed with RLS: 11 were newly diagnosed with RLS and 12 had RLS preceding the index stroke/TIA. There were no significant differences in baseline characteristics between those with or without RLS. Median SS-QoL in patients with RLS was lower at baseline (p = 0.008) and at follow-up (p = 0.002). RLS patients had more depressive symptoms at follow-up (p = 0.007). Ordinal logistic regression demonstrated that RLS was negatively associated with quality of life at baseline (OR = 0.28; p = 0.010) and at follow-up (OR = 0.14; p = 0.029), independent of functional outcome and depressive symptoms. RLS is common after stroke or TIA and negatively affects the quality of life. Screening for RLS after cerebrovascular events may be warranted, and future research should assess whether treatment of RLS can improve post-stroke quality of life. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Case reports of the use of immunoadsorption or plasma exchange in high-risk pregnancies of women with antiphospholipid syndrome.

    Science.gov (United States)

    Bortolati, Maria; Marson, Piero; Chiarelli, Silvia; Tison, Tiziana; Facchinetti, Myriam; Gervasi, Maria Teresa; De Silvestro, Giustina; Ruffatti, Amelia

    2009-04-01

    Conventional treatment of antiphospholipid syndrome (APS) pregnancies with aspirin and/or heparin is sometimes unable to counteract maternal and/or fetal complications. In this article we report the cases of two patients who were unresponsive to conventional treatment for APS during their first pregnancy, and who were treated in the following pregnancy with plasma exchange and immunoadsorption respectively, in addition to conventional therapy. Both patients had a history of thrombotic events, a previous pregnancy loss at the 11th week of gestation and the same antiphospholipid antibody profile (lupus anticoagulant activity and high titers of immunoglobulin G (IgG) anti-beta2 glycoprotein I and IgG anticardiolipin antibodies). Patient 1 was treated from the fourth week of her second pregnancy with weekly plasma exchange. Due to fetal growth restriction and oligohydramnios in the 26th week she delivered, by cesarean section, a healthy female infant weighing 730 g who survived. Patient 2 was treated from the seventh week of her second pregnancy with twice a week protein A immunoadsorption. The pregnancy proceeded normally until the 36th week, when, due to slight intrauterine growth restriction, she delivered a healthy baby girl weighing 2375 g by cesarean section. Anti-beta2 glycoprotein I antibody trends were similar during both types of treatment. On the basis of our findings obtained from only two cases it is impossible to define the best aphaeretic treatment of APS high risk pregnancies. Nevertheless, as a whole these data suggest better disease control using the immunoadsorption technique as compared to plasma exchange, despite their apparently similar anti-beta2 glycoprotein I antibody removal capabilities.

  14. Disrupted pregnancies? How doctors, sonographers and pregnant couples negotiate high risk for Down’s syndrome – a qualitative study

    DEFF Research Database (Denmark)

    Lou, Stina; Hvidman, Lone; Petersen, Olav Bjørn

    2012-01-01

    that 90–95% of the high-risk couples carry a foetus with normal chromosomes. How do these couples frame the disruption caused by the high risk category? Are they able to return to a ‘normal’ pregnancy or does the disruption cause subsequent worry? In the presentation, we will reflect on this important...

  15. French registry of acute leukemia and myelodysplastic syndromes. Age distribution and hemogram analysis of the 4496 cases recorded during 1982-1983 and classified according to FAB criteria. Groupe Francais de Morphologie Hematologique

    International Nuclear Information System (INIS)

    Anon.

    1987-01-01

    During 1982 and 1983, 4496 new cases were recorded in the French Registry of acute leukemia and myelodysplastic syndromes by the French Group of Hematologic Morphology. This cooperative group associated members of 37 university centers spread throughout France; these centers handle the overwhelming majority of acute leukemias diagnoses. The cases were all classified according to FAB guidelines. Two thousand four hundred ninety-nine cases of acute myeloid leukemia were recorded, with similar total recruitment and distribution by cytologic subclass for both years. Hemogram data analysis revealed significant differences between different classes for certain parameters, particularly leukocytosis. A greater proportion of the acute myelogenous leukemias (AMLs) secondary to chemotherapy and/or radiotherapy (n = 145) were unclassifiable according to the French-American-British (FAB) system than the de novo AMLs (n = 1954). Eight hundred twenty cases of myelodysplastic syndromes were analyzed. Their frequency was underestimated due to optional reporting during the first year and the less favorable position of the university centers for recruiting these syndromes. The characteristics of the hemograms were established for acquired idiopathic sideroblastic anemia (n = 107), refractory anemia with excess blasts (RAEB) (n = 329), chronic myelomonocytic leukemia (n = 129) and RAEB in transformation (n = 65). Analysis of the 1177 acute lymphoblastic leukemias (ALLs) recorded showed good stability from one year to the next in terms of numbers of cases and distribution in the subclasses L1, L2, and L3. The distribution among these three subclasses by age also was determined. For L1 and L2 the hemogram data were examined separately for adults and children. The study of 74 cases of type L3 ALL enabled us to detail the hematologic presentation of this rare form of leukemia

  16. [The Design Requirements for an E-Health Management Platform: Addressing the Needs of Adolescent Girls at High Risk of Metabolic Syndrome].

    Science.gov (United States)

    Su, Mei-Chen; Chen, Wen-Chin; Liu, Chieh-Yu; Jou, Hei-Jen; Hsiao, Ya-Chu; Tsao, Lee-Ing

    2015-10-01

    The rising prevalence of metabolic syndrome among adolescents has not been effectively addressed by current campus-based health promotions. Using the Internet in these promotions may help health professionals achieve better healthcare management. The purpose of the present study was to explore the design requirements of an e-health management platform from the subjective perspective of adolescent girls who were at a high risk of metabolic syndrome. The findings may provide a reference for designing nursing interventions that more effectively promote healthly lifestyle habits to adolescents. This qualitative study employed a snowball approach and used a semi-structured interview guide to collect data. A total of 20 Taiwanese adolescent females who were at a high risk of metabolic syndrome, aged 16-20 years, able to speak Mandarin or Taiwanese, and willing to participate and to have their sessions tape-recorded were enrolled as participants and engaged individually in in-depth interviews. The constant comparative method was used to inductively analyze the interview data. Five main themes related to the e-health management platform emerged from the data. These themes included: an attractive and user-friendly website interface, access to reliable information and resources, provision of tailored health information, access to peer support, and self-monitoring and learning tools. The findings highlight the key design needs of an e-Health management platform from the perspective of adolescent girls who are at a high risk of metabolic syndrome. The identified themes may be addressed in future revisions / developments of these platforms in order to better address the needs of this vulnerable population and to effectively reduce the incidence of metabolic syndrome. The authors hope that the results of the present study may be used to provide better healthcare and support for adolescent girls with metabolic syndrome.

  17. Diagnostic and Prognostic Significance of DSM-5 Attenuated Psychosis Syndrome in Services for Individuals at Ultra High Risk for Psychosis.

    Science.gov (United States)

    Fusar-Poli, Paolo; De Micheli, Andrea; Cappucciati, Marco; Rutigliano, Grazia; Davies, Cathy; Ramella-Cravaro, Valentina; Oliver, Dominic; Bonoldi, Ilaria; Rocchetti, Matteo; Gavaghan, Lauren; Patel, Rashmi; McGuire, Philip

    2018-02-15

    The diagnostic and prognostic significance of the DSM-5-defined Attenuated Psychosis Syndrome (DSM-5-APS) in individuals undergoing an ultra high risk (UHR) clinical assessment for suspicion of psychosis risk is unknown. Prospective cohort study including all consecutive help-seeking individuals undergoing both a DSM-5-APS and a Comprehensive Assessment of At Risk Mental States (CAARMS 12/2006) assessment for psychosis risk at the Outreach and Support in South London (OASIS) UHR service (March 2013-April 2014). The diagnostic significance of DSM-5-APS was assessed with percent overall agreement, prevalence bias adjusted kappa, Bowker's test, Stuart-Maxwell test, residual analysis; the prognostic significance with Cox regression, Kaplan-Meier failure function, time-dependent area under the curve (AUC) and net benefits analysis. The impact of specific revisions of the DSM-5-APS was further tested. In 203 help-seeking individuals undergoing UHR assessment, the agreement between the DSM-5-APS and the CAARMS 12/2006 was only moderate (kappa 0.59). Among 142 nonpsychotic cases, those meeting DSM-5-APS criteria had a 5-fold probability (HR = 5.379) of developing psychosis compared to those not meeting DSM-5-APS criteria, with a 21-month cumulative risk of psychosis of 28.17% vs 6.49%, respectively. The DSM-5-APS prognostic accuracy was acceptable (AUC 0.76 at 24 months) and similar to the CAARMS 12/2006. The DSM-5-APS designation may be clinically useful to guide the provision of indicated interventions within a 7%-35% (2-year) range of psychosis risk. The removal of the criterion E or C of the DSM-5-APS may improve its prognostic performance and transdiagnostic value. The DSM-5-APS designation may be clinically useful in individuals accessing clinical services for psychosis prevention. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

  18. Treatment Options for Myelodysplastic Syndromes

    Science.gov (United States)

    ... special light. Certain factors affect prognosis and treatment options. The prognosis (chance of recovery) and treatment options ... age and general health of the patient. Treatment Option Overview Key Points There are different types of ...

  19. Treatment Option Overview (Myelodysplastic Syndromes)

    Science.gov (United States)

    ... special light. Certain factors affect prognosis and treatment options. The prognosis (chance of recovery) and treatment options ... age and general health of the patient. Treatment Option Overview Key Points There are different types of ...

  20. Immune Mechanisms in Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

    Glenthøj, Andreas; Ørskov, Andreas Due; Hansen, Jakob Werner

    2016-01-01

    diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients......-especially younger low-risk patients with HLA-DR15 tissue type-demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune...... mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS....

  1. Aplastic Anemia and Myelodysplastic Syndromes

    Science.gov (United States)

    ... when it is safe to eat in a restaurant. When dining out, stem cell transplant recipients should ... Process Research Training & Career Development Funded Grants & Grant History Research Resources Research at NIDDK Technology Advancement & Transfer ...

  2. High-risk Long QT Syndrome Mutations in the Kv7.1 (KCNQ1) Pore Disrupt the Molecular Basis for Rapid K+ Permeation

    Science.gov (United States)

    Burgess, Don E.; Bartos, Daniel C.; Reloj, Allison R.; Campbell, Kenneth S.; Johnson, Jonathan N.; Tester, David J.; Ackerman, Michael J.; Fressart, Véronique; Denjoy, Isabelle; Guicheney, Pascale; Moss, Arthur J.; Ohno, Seiko; Horie, Minoru; Delisle, Brian P.

    2012-01-01

    Type 1 long QT syndrome (LQT1) syndrome is caused by loss-of-function mutations in the KCNQ1, which encodes the K+ channel (Kv7.1) that underlies the slowly activating delayed rectifier K+ current in the heart. Intragenic risk stratification suggests LQT1 mutations that disrupt conserved amino acid residues in the pore are an independent risk factor for LQT1-related cardiac events. The purpose of this study is to determine possible molecular mechanisms that underlie the loss-of-function for these high-risk mutations. Extensive genotype-phenotype analyses of LQT1 patients showed that T322M-, T322A-, or G325R-Kv7.1 confer a high risk for LQT1-related cardiac events. Heterologous expression of these mutations with KCNE1 revealed they generated non-functional channels and caused dominant negative suppression of WT-Kv7.1 current. Molecular dynamic simulations (MDS) of analogous mutations in KcsA (T85M-, T85A-, and G88R-KcsA) demonstrated that they disrupted the symmetrical distribution of the carbonyl oxygen atoms in the selectivity filter, which upset the balance between the strong attractive and K+-K+ repulsive forces required for rapid K+ permeation. We conclude high-risk LQT1 mutations in the pore likely disrupt the architectural and physical properties of the K+ channel selectivity filter. PMID:23092362

  3. Metabolic syndrome and the development of vascular disease and type 2 diabetes in high-risk patients

    NARCIS (Netherlands)

    Wassink, A.M.J.

    2009-01-01

    Abdominal obesity and its associated insulin resistance play a key role in the clustering of vascular risk factors, known as Metabolic Syndrome. Subjects with Metabolic Syndrome are at increased risk for the development of both type 2 diabetes and cardiovascular disease. Type 2 diabetes and

  4. An exercise trial targeting African-American women with metabolic syndrome and at high risk for breast cancer: Rationale, design, and methods.

    Science.gov (United States)

    Dash, Chiranjeev; Makambi, Kepher; Wallington, Sherrie F; Sheppard, Vanessa; Taylor, Teletia R; Hicks, Jennifer S; Adams-Campbell, Lucile L

    2015-07-01

    Metabolic syndrome and obesity are known risk factors for breast cancers. Exercise interventions can potentially modify circulating biomarkers of breast cancer risk but evidence in African-Americans and women with metabolic syndrome is lacking. The Focused Intervention on Exercise to Reduce CancEr (FIERCE) trial is a prospective, 6-month, 3-arm, randomized controlled trial to examine the effect of exercise on obesity, metabolic syndrome components, and breast cancer biomarkers among African-American women at high risk of breast cancer. Two hundred-forty inactive women with metabolic syndrome and absolute risk of breast cancer ≥ 1.40 will be randomized to one of the three trial arms: 1) a supervised, facility-based exercise arm; 2) a home-based exercise arm; and 3) a control group that maintains physical activity levels through the course of the trial. Assessments will be conducted at baseline, 3 months, and 6 months. The primary outcome variables are anthropometric indicators of obesity, metabolic syndrome components, and inflammatory, insulin-pathway, and hormonal biomarkers of breast cancer risk. The FIERCE trial will provide evidence on whether a short-term exercise intervention might be effective in reducing breast cancer risk among African-American women with comorbidities and high breast cancer risk--a group traditionally under-represented in non-therapeutic breast cancer trials. NCT02103140. Copyright © 2015. Published by Elsevier Inc.

  5. High-risk long QT syndrome mutations in the Kv7.1 (KCNQ1) pore disrupt the molecular basis for rapid K(+) permeation.

    Science.gov (United States)

    Burgess, Don E; Bartos, Daniel C; Reloj, Allison R; Campbell, Kenneth S; Johnson, Jonathan N; Tester, David J; Ackerman, Michael J; Fressart, Véronique; Denjoy, Isabelle; Guicheney, Pascale; Moss, Arthur J; Ohno, Seiko; Horie, Minoru; Delisle, Brian P

    2012-11-13

    Type 1 long QT syndrome (LQT1) is caused by loss-of-function mutations in the KCNQ1 gene, which encodes the K(+) channel (Kv7.1) that underlies the slowly activating delayed rectifier K(+) current in the heart. Intragenic risk stratification suggests LQT1 mutations that disrupt conserved amino acid residues in the pore are an independent risk factor for LQT1-related cardiac events. The purpose of this study is to determine possible molecular mechanisms that underlie the loss of function for these high-risk mutations. Extensive genotype-phenotype analyses of LQT1 patients showed that T322M-, T322A-, or G325R-Kv7.1 confers a high risk for LQT1-related cardiac events. Heterologous expression of these mutations with KCNE1 revealed they generated nonfunctional channels and caused dominant negative suppression of WT-Kv7.1 current. Molecular dynamics simulations of analogous mutations in KcsA (T85M-, T85A-, and G88R-KcsA) demonstrated that they disrupted the symmetrical distribution of the carbonyl oxygen atoms in the selectivity filter, which upset the balance between the strong attractive and K(+)-K(+) repulsive forces required for rapid K(+) permeation. We conclude high-risk LQT1 mutations in the pore likely disrupt the architectural and physical properties of the K(+) channel selectivity filter.

  6. Management of mediastinal syndromes in pediatrics: a new challenge of ultrasound guidance to avoid high-risk general anesthesia.

    Science.gov (United States)

    Sola, Chrystelle; Choquet, Olivier; Prodhomme, Olivier; Capdevila, Xavier; Dadure, Christophe

    2014-05-01

    Adverse events associated with anesthetic management of anterior mediastinal masses in pediatrics are common. To avoid an extremely hazardous general anesthesia, the use of real-time ultrasonography offers an effective alternative in high-risk cases. We report the anesthetic management including a light sedation and ultrasound guidance for regional anesthesia, surgical node biopsy, and placement of a central venous line in two children with an anterior symptomatic mediastinal mass. For pediatric patients with clinical and/or radiologic signs of airway compression, ultrasound guidance provides safety technical assistance to avoid general anesthesia and should be performed for the initial diagnostic and therapeutic procedures. © 2013 John Wiley & Sons Ltd.

  7. Can We Predict Psychosis Outside the Clinical High-Risk State? A Systematic Review of Non-Psychotic Risk Syndromes for Mental Disorders

    Science.gov (United States)

    Lee, Tae Young; Lee, Junhee; Kim, Minah; Choe, Eugenie

    2018-01-01

    Abstract Recent evidence has suggested that psychosis could develop not only in people at clinical high risk for psychosis (CHR-P) but also in those with clinical risk syndromes for emergent nonpsychotic mental disorders. The proportion of people with these clinical risk syndromes who will develop psychosis rather than to other nonpsychotic mental disorders is undetermined. Electronic databases were searched for studies reporting on clinical risk syndromes for the development of emergent nonpsychotic mental disorders. Incidence of emerging psychotic and nonpsychotic mental disorders defined on the ICD or DSM. Of a total of 9 studies relating to 3006 nonpsychotic at-risk individuals were included. Within prospective studies (n = 4, sample = 1051), the pooled incidence of new psychotic disorders across these clinical risk syndromes was of 12.9 per 1000 person-years (95% CI: 4.3 to 38.6) and that of nonpsychotic disorders (n = 3, sample = 538) was of 43.5 per 1000 person-years (95% CI: 30.9 to 61.3). Psychotic disorders may emerge outside the CHR-P paradigm, from clinical risk syndromes for incident nonpsychotic disorders, albeit at lower rates than in the CHR-P group. The clinical risk syndromes for emerging nonpsychotic disorders may exhibit a pluripotential risk of developing several types of mental disorders compared with CHR-P. If substantiated by future research, the current findings suggest that it may be useful to move beyond the current strategy of identifying individuals meeting CHR-P criteria only. PMID:29438561

  8. The role of T2*-weighted gradient echo in the diagnosis of tumefactive intrahepatic extramedullary hematopoiesis in myelodysplastic syndrome and diffuse hepatic iron overload: a case report and review of the literature.

    Science.gov (United States)

    Belay, Abel A; Bellizzi, Andrew M; Stolpen, Alan H

    2018-01-15

    Extramedullary hematopoiesis is the proliferation of hematopoietic cells outside bone marrow secondary to marrow hematopoiesis failure. Extramedullary hematopoiesis rarely presents as a mass-forming hepatic lesion; in this case, imaging-based differentiation from primary and metastatic hepatic neoplasms is difficult, often leading to biopsy for definitive diagnosis. We report a case of tumefactive hepatic extramedullary hematopoiesis in the setting of myelodysplastic syndrome with concurrent hepatic iron overload, and the role of T2*-weighted gradient-echo magnetic resonance imaging in differentiating extramedullary hematopoiesis from primary and metastatic hepatic lesions. To the best of our knowledge, T2*-weighted gradient-echo evaluation of extramedullary hematopoiesis in the setting of diffuse hepatic hemochromatosis has not been previously described. A 52-year-old white man with myelodysplastic syndrome and marrow fibrosis was found to have a 4 cm hepatic lesion on ultrasound during workup for bone marrow transplantation. Magnetic resonance imaging revealed diffuse hepatic iron overload and non-visualization of the lesion on T2* gradient-echo sequence suggesting the presence of iron deposition within the lesion similar to that in background hepatic parenchyma. Subsequent ultrasound-guided biopsy of the lesion revealed extramedullary hematopoiesis. Six months later, while still being evaluated for bone marrow transplant, our patient was found to have poor pulmonary function tests. Follow-up computed tomography angiogram showed a mass within his right main pulmonary artery. Bronchoscopic biopsy of this mass once again revealed extramedullary hematopoiesis. He received radiation therapy to his chest. However, 2 weeks later, he developed mediastinal hematoma and died shortly afterward, secondary to respiratory arrest. Mass-forming extramedullary hematopoiesis is rare; however, our report emphasizes that it needs to be considered in the initial differential

  9. Lettuce Allergy Is a Lipid Transfer Syndrome-Related Food Allergy With a High Risk of Severe Reactions.

    Science.gov (United States)

    Muñoz-García, E; Luengo-Sánchez, O; Moreno-Pérez, N; Cuesta-Herranz, J; Pastor-Vargas, C; Cardona, V

    Lipid transfer protein (LTP) sensitization is the most common cause of food allergy in the Mediterranean area, with peach allergy acting as the primary sensitizer in most cases. Lettuce has been described as a common offending food in patients with LTP syndrome. The aim of the study was to investigate the frequency and clinical expression of LTP syndrome in a sample of lettuceallergic patients. We determined specific IgE to Pru p 3 and lettuce in a sample of 30 patients with a diagnosis of lettuce allergy. Symptoms elicited by other LTP-containing plant-derived foods and the presence of cofactors were assessed. The clinical symptoms of lettuce allergy were frequently severe, with 18 of the 30 patients experiencing anaphylaxis. All the patients had allergic reactions to other plant foods. Cofactors were involved in the clinical reactions of 13 of the 30 patients. Sensitization to pollens was found in 90% of patients. Lettuce allergy is found not as an isolated condition but in the context of LTP syndrome and it is characterized by severe reactions and frequent cofactor association.

  10. [Constitutional mismatch repair deficiency syndrome].

    Science.gov (United States)

    Jongmans, Marjolijn C; Gidding, Corrie E; Loeffen, Jan; Wesseling, Pieter; Mensenkamp, Arjen; Hoogerbrugge, Nicoline

    2015-01-01

    Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. An 8-year-old girl was diagnosed with CMMR-D syndrome after she developed a brain tumour at the age of 4 and a T-cell non-Hodgkin lymphoma at the age of 6. She had multiple hyperpigmented skin lesions and died of myelodysplastic syndrome at the age of 11. In children with cancer CMMR-D syndrome can be recognized particularly if there are multiple primary malignancies and skin hyperpigmentations and hypopigmentations. The parents of these children are at high risk for colorectal and endometrial cancer (Lynch syndrome), amongst others.

  11. How can we identify low- and high-risk patients among unselected patients with possible acute coronary syndrome?

    DEFF Research Database (Denmark)

    Nielsen, Kirsten Melgaard; Færgeman, Ole; Larsen, Mogens Lytken

    2007-01-01

    Objective Prognosis among patients admitted with possible acute coronary syndrome (ACS) may differ from that of patients with definite ACS. The aim of this study was to identify risk factors for mortality among unselected patients and to use the statistical model to identify patients at low or high...... mortality risk. Methods From April 1, 2000, to March 31, 2002, we identified all consecutive patients aged 30 to 69 years admitted to the 2 coronary care units covering the municipality of Aarhus, Denmark (population, 138 290). ACS was considered a possible diagnosis if the physician at admission (1) had...

  12. Constitutional t(5;7)(q11;p15) rearranged to acquire monosomy 7q and trisomy 1q in a patient with myelodysplastic syndrome transforming to acute myelocytic leukemia.

    Science.gov (United States)

    Ganly, Peter; McDonald, Margaret; Spearing, Ruth; Morris, Christine M

    2004-03-01

    We report the case of a 61-year-old woman who presented with a myelodysplastic syndrome (MDS) and a t(5;7)(q11.2;p15) in her bone marrow cells. Subsequent analysis of phytohemagglutinin-stimulated peripheral blood lymphocytes and cultured skin fibroblasts showed that the translocation was constitutional. Disruption of chromosome bands 5q11.2 and 7p15 has been described recurrently in MDS and acute myelocytic leukemia (AML) and, although the age of onset was not earlier than usual, it is nonetheless possible that genes interrupted by this translocation may been a predisposing factor for her condition. With progression to AML, a further rearrangement of the constitutional der(7)t(5;7) occurred, involving chromosome arm 1q. Fluorescence in situ hybridization (FISH) with whole-chromosome paints showed that the result of the second rearrangement, a t(1;7)(q32.1;q32), was observed, leading to trisomy of the segment 1q32.1 approximately qter and monosomy of the segment 7q32.1 approximately qter. The acquired imbalances, particularly loss of 7q, are commonly associated with MDS/AML and a poor prognosis; however, this patient remained in remission after treatment for more than two years before AML relapse, perhaps because the affected regions fall outside of the critical regions of imbalance.

  13. Health-Related Quality of Life, Treatment Satisfaction, Adherence and Persistence in β-Thalassemia and Myelodysplastic Syndrome Patients with Iron Overload Receiving Deferasirox: Results from the EPIC Clinical Trial

    Directory of Open Access Journals (Sweden)

    John Porter

    2012-01-01

    Full Text Available Treatment of iron overload using deferoxamine (DFO is associated with significant deficits in patients' health-related quality of life (HRQOL and low treatment satisfaction. The current article presents patient-reported HRQOL, satisfaction, adherence, and persistence data from β-thalassemia (n=274 and myelodysplastic syndrome (MDS patients (n=168 patients participating in the Evaluation of Patients' Iron Chelation with Exjade (EPIC study (NCT00171821; a large-scale 1-year, phase IIIb study investigating the efficacy and safety of the once-daily oral iron chelator, deferasirox. HRQOL and satisfaction, adherence, and persistence to iron chelation therapy (ICT data were collected at baseline and end of study using the Medical Outcomes Short-Form 36-item Health Survey (SF-36v2 and the Satisfaction with ICT Questionnaire (SICT. Compared to age-matched norms, β-thalassemia and MDS patients reported lower SF-36 domain scores at baseline. Low levels of treatment satisfaction, adherence, and persistence were also observed. HRQOL improved following treatment with deferasirox, particularly among β-thalassemia patients. Furthermore, patients reported high levels of satisfaction with deferasirox at end of study and greater ICT adherence, and persistence. Findings suggest deferasirox improves HRQOL, treatment satisfaction, adherence, and persistence with ICT in β-thalassemia and MDS patients. Improving such outcomes is an important long-term goal for patients with iron overload.

  14. Mammalian-target of rapamycin inhibition with temsirolimus in myelodysplastic syndromes (MDS) patients is associated with considerable toxicity: results of the temsirolimus pilot trial by the German MDS Study Group (D-MDS).

    Science.gov (United States)

    Wermke, Martin; Schuster, Claudia; Nolte, Florian; Al-Ali, Haifa-Kathrin; Kiewe, Philipp; Schönefeldt, Claudia; Jakob, Christiane; von Bonin, Malte; Hentschel, Leopold; Klut, Ina-Maria; Ehninger, Gerhard; Bornhäuser, Martin; Baretton, Gustavo; Germing, Ulrich; Herbst, Regina; Haase, Detelef; Hofmann, Wolf K; Platzbecker, Uwe

    2016-12-01

    The mammalian-target of rapamycin (also termed mechanistic target of rapamycin, mTOR) pathway integrates various pro-proliferative and anti-apoptotic stimuli and is involved in regulatory T-cell (TREG) development. As these processes contribute to the pathogenesis of myelodysplastic syndromes (MDS), we hypothesized that mTOR modulation with temsirolimus (TEM) might show activity in MDS. This prospective multicentre trial enrolled lower and higher risk MDS patients, provided that they were transfusion-dependent/neutropenic or relapsed/refractory to 5-azacitidine, respectively. All patients received TEM at a weekly dose of 25 mg. Of the 9 lower- and 11 higher-risk patients included, only 4 (20%) reached the response assessment after 4 months of treatment and showed stable disease without haematological improvement. The remaining patients discontinued TEM prematurely due to adverse events. Median overall survival (OS) was not reached in the lower-risk group and 296 days in the higher-risk group. We observed a significant decline of bone marrow (BM) vascularisation (P = 0·006) but were unable to demonstrate a significant impact of TEM on the balance between TREG and pro-inflammatory T-helper-cell subsets within the peripheral blood or BM. We conclude that mTOR-modulation with TEM at a dose of 25 mg per week is accompanied by considerable toxicity and has no beneficial effects in elderly MDS patients. © 2016 John Wiley & Sons Ltd.

  15. Comparison of clinical outcomes and prognostic utility of risk stratification tools in patients with therapy-related vs de novo myelodysplastic syndromes: a report on behalf of the MDS Clinical Research Consortium.

    Science.gov (United States)

    Zeidan, A M; Al Ali, N; Barnard, J; Padron, E; Lancet, J E; Sekeres, M A; Steensma, D P; DeZern, A; Roboz, G; Jabbour, E; Garcia-Manero, G; List, A; Komrokji, R

    2017-06-01

    While therapy-related (t)-myelodysplastic syndromes (MDS) have worse outcomes than de novo MDS (d-MDS), some t-MDS patients have an indolent course. Most MDS prognostic models excluded t-MDS patients during development. The performances of the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), MD Anderson Global Prognostic System (MPSS), WHO Prognostic Scoring System (WPSS) and t-MDS Prognostic System (TPSS) were compared among patients with t-MDS. Akaike information criteria (AIC) assessed the relative goodness of fit of the models. We identified 370 t-MDS patients (19%) among 1950 MDS patients. Prior therapy included chemotherapy alone (48%), chemoradiation (31%), and radiation alone in 21%. Median survival for t-MDS patients was significantly shorter than for d-MDS (19 vs 46 months, PMDS (PMDS had a significantly higher hazard of death relative to d-MDS in every risk model, and had inferior survival compared to patients with d-MDS within all risk group categories. AIC Scores (lower is better) were 2316 (MPSS), 2343 (TPSS), 2343 (IPSS-R), 2361 (WPSS) and 2364 (IPSS). In conclusion, subsets of t-MDS patients with varying clinical outcomes can be identified using conventional risk stratification models. The MPSS, TPSS and IPSS-R provide the best predictive power.

  16. Translocations (5;17) and (7;17) in patients with de novo or therapy-related myelodysplastic syndromes or acute nonlymphocytic leukemia. A possible association with acquired pseudo-Pelger-Hut anomaly and small vacuolated granulocytes

    International Nuclear Information System (INIS)

    La, J.L.Z.; Zandecki, M.; Fenaux, P.; Le Baron, F.; Bauters, F.; Cosson, A.; Deminatti, M.

    1990-01-01

    Twelve patients [two with de novo myelodysplastic syndrome (MDS), four with secondary MDS, five with de novo acute nonlymphocytic leukemia (ANLL), one with secondary ANLL] showed a 17p deletion resulting from translocations involving 17p: t(5;17)(p11;p11) in four cases, t(7;17)(p11;p11) in six cases, complex (5;17)(q23;p12) translocation with dicentric chromosome in one case, and t(17;?)(p11-12;?) in the remaining patient. All these structural anomalies were observed in hypodiploid clones associated with total or partial monosomy of chromosomes 5 and 7 (12 cases), monosomy 12 (five cases), monosomy 3 (four cases), and monosomy 4 (three cases). Median survival was only 3.3 months (range 3 days to 8 months). Striking features were observed in bone marrow mature granulocytes: all but one case had a pseudo-Pelger-Hut anomaly in a significant number of granulocytes, and eight patients had granulocytes with reduced size and clear cytoplasmic vacuoles. Careful cytological review of 51 patients with MDS or ANLL and various cytogenetic anomalies was performed for comparison: vacuolated granulocytes were a very uncommon finding. On the other hand, eight patients had a pseudo-Pelger-Hut anomaly, which correlated significantly with total monosomy 17 in these patients. A possible correlation between cytological anomalies and cytogenetic data is discussed, and the role of 17p in the nuclear segmentation of granulocytes is stressed

  17. Apheresis and intravenous immunoglobulins used in addition to conventional therapy to treat high-risk pregnant antiphospholipid antibody syndrome patients. A prospective study.

    Science.gov (United States)

    Ruffatti, Amelia; Favaro, Maria; Hoxha, Ariela; Zambon, Alessandra; Marson, Piero; Del Ross, Teresa; Calligaro, Antonia; Tonello, Marta; Nardelli, Giovanni B

    2016-06-01

    Pregnant women with triple antibody positive antiphospholipid syndrome (APS) who have had thrombosis or a history of early, severe pregnancy complications are generally considered at high risk of pregnancy loss. The objectives of this study were to investigate the efficacy and safety of a relatively new treatment protocol used in addition to conventional therapy in high-risk pregnant patients affected with primary APS. The study's two inclusion criteria were: (1) the presence of triple antiphospholipid positivity, (2) previous thrombosis and/or a history of one or more early, severe pregnancy complications. Eighteen pregnancies occurring between 2002 and 2015 in 14 APS patients, (mean age 34.8±3.6 SD) were monitored. All 14 (100%) patients had triple antiphospholipid positivity. In addition, six of them (42.8%) had a history of thrombosis, four (28.6%) had one or more previous early and severe pregnancy complications, and four (30.8%) met both clinical study criteria. The study protocol included weekly plasmapheresis or immunoadsorption and fortnightly 1g/kg intravenous immunoglobulins. Seventeen of the pregnancies (94.4%) produced live neonates, all born between the 26th and 37th weeks of gestation (mean 33.1±3.5 SD). One female (5.5%), born prematurely at 24 weeks, died of sepsis a week after birth. There were two cases (11.1%) of severe pregnancy complications. No treatment side effects were registered. Given the high live birth rate and the safety associated to it, the study protocol described here could be taken into consideration by medical teams treating high-risk APS pregnant patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Preventive role of exercise training in autonomic, hemodynamic, and metabolic parameters in rats under high risk of metabolic syndrome development.

    Science.gov (United States)

    Moraes-Silva, Ivana Cinthya; Mostarda, Cristiano; Moreira, Edson Dias; Silva, Kleiton Augusto Santos; dos Santos, Fernando; de Angelis, Kátia; Farah, Vera de Moura Azevedo; Irigoyen, Maria Claudia

    2013-03-15

    High fructose consumption contributes to metabolic syndrome incidence, whereas exercise training promotes several beneficial adaptations. In this study, we demonstrated the preventive role of exercise training in the metabolic syndrome derangements in a rat model. Wistar rats receiving fructose overload in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) or kept sedentary (F) for 10 wk. Control rats treated with normal water were also submitted to exercise training (CT) or sedentarism (C). Metabolic evaluations consisted of the Lee index and glycemia and insulin tolerance test (kITT). Blood pressure (BP) was directly measured, whereas heart rate (HR) and BP variabilities were evaluated in time and frequency domains. Renal sympathetic nerve activity was also recorded. F rats presented significant alterations compared with all the other groups in insulin resistance (in mg · dl(-1) · min(-1): F: 3.4 ± 0.2; C: 4.7 ± 0.2; CT: 5.0 ± 0.5 FT: 4.6 ± 0.4), mean BP (in mmHG: F: 117 ± 2; C: 100 ± 2; CT: 98 ± 2; FT: 105 ± 2), and Lee index (in g/mm: F = 0.31 ± 0.001; C = 0.29 ± 0.001; CT = 0.27 ± 0.002; FT = 0.28 ± 0.002), confirming the metabolic syndrome diagnosis. Exercise training blunted all these derangements. Additionally, FS group presented autonomic dysfunction in relation to the others, as seen by an ≈ 50% decrease in baroreflex sensitivity and 24% in HR variability, and increases in sympathovagal balance (140%) and in renal sympathetic nerve activity (45%). These impairments were not observed in FT group, as well as in C and CT. Correlation analysis showed that both Lee index and kITT were associated with vagal impairment caused by fructose. Therefore, exercise training plays a preventive role in both autonomic and hemodynamic alterations related to the excessive fructose consumption.

  19. Managing myelodysplastic symptoms in elderly patients

    Directory of Open Access Journals (Sweden)

    R Ria

    2009-10-01

    Full Text Available R Ria, M Moschetta, A Reale, G Mangialardi, A Castrovilli, A Vacca, F DammaccoDepartment of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, ItalyAbstract: Most patients with myelodysplastic syndromes (MDS are elderly (median age range 65 to 70 years; as a consequence, the incidence and prevalence of these diseases are rising as the population ages. Physicians are often uncertain about how to identify patients who may benefit from specific treatment strategies. The International Prognostic Scoring System is a widely used tool to assess the risk of transformation to leukemia and to guide treatment decisions, but it fails to take into account many aspects of treating elderly patients, including comorbid illnesses, secondary causes of MDS, prior therapy for MDS, and other age-related health, functional, cognitive, and social problems that affect the outcome and managing of myelodysplastic symptoms. Patients with low-risk disease traditionally have been given only best supportive care, but evidence is increasing that treatment with novel non-conventional drugs such as lenalidomide or methyltransferase inhibitors may influence the natural history of the disease and should be used in conjunction with supportive-care measures. Supportive care of these patients could also be improved in order to enhance their quality of life and functional performance. Elderly patients commonly have multiple medical problems and use medications to deal with these. In addition, they are more likely to have more than one health care provider. These factors all increase the risk of drug interactions and the consequent treatment of toxicities. Manifestations of common toxicities or illnesses may be more subtle in the elderly, owing to age-associated functional deficits in multiple organ systems. Particularly important to the elderly MDS patient is the age-related decline in normal bone

  20. Enoxaparin injection for the treatment of high-risk patients with non-ST elevation acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Caroline Schmidt-Lucke

    2007-05-01

    Full Text Available Caroline Schmidt-Lucke, Heinz-Peter SchultheissCharité Medical University Berlin, Campus Benjamin Franklin, Dept. of Cardiology and Pulmology, GermanyAbstract: Non-ST elevation acute coronary syndrome (NSTE-ACS refers to a cardiovascular disorder characterized by intracoronary thrombus formation on a disrupted atherosclerotic plaque with partial or transient occlusion. Generation of thrombin resulting from exposure of collagen leads to activation of platelets and conversion of fibrinogen to fibrin, thus forming a platelet-rich thrombus. The main therapeutic objective is to protect the patient from thrombotic complications, independent of the choice of antithrombotic agents. The management of NSTE myocardial infarction (MI is constantly evolving. For primarily conservative strategy, enoxaparin has been proven superior to unfractioned heparin (UFH. With early invasive strategy providing better clinical outcome compared with conservative strategy, the effectiveness of enoxaparin in reducing death and MI rates is now being reconsidered in the era of poly-pharmacotherapy, early percutaneous coronary interventions and drug eluting stents. Bleeding complications can be minimized by avoiding cross-over from UFH to enoxaparin or vice versa, or by reducing the dosage of enoxaparin. We review the studies of enoxaparin and discuss its current role in the contemporary treatment of NSTE-ACS.Keywords: low-molecular weight heparin, NSTEMI, treatment

  1. Prenatal diagnosis of 17q12 deletion syndrome: from fetal hyperechogenic kidneys to high risk for autism.

    Science.gov (United States)

    Gilboa, Yinon; Perlman, Sharon; Pode-Shakked, Naomi; Pode-Shakked, Ben; Shrim, Alon; Azaria-Lahav, Einat; Dekel, Benjamin; Yonath, Hagith; Berkenstadt, Michal; Achiron, Reuven

    2016-11-01

    The linkage between 17q12 microdeletions, renal anomalies, and higher risk for neurodevelopmental disorders is well described in the literature. The current study presents prenatal diagnosis of normal-sized fetal hyperechogenic kidneys leading to the diagnosis of 17q12 deletion syndrome and autism spectrum disorder. Over a period of 9 years in a single referral center, seven fetuses were diagnosed with hyperechogenic renal parenchyma and were followed up prospectively. Amniocentesis for molecular diagnosis was performed in all cases, and subsequently, five fetuses were found to harbor a 17q12 deletion by chromosomal microarray analysis. Postnatal evaluation was carried out by a developmental neurologist. Five of the seven fetuses had molecular diagnosis of 17q12 deletion. One patient elected termination of pregnancy. On long-term follow-up, all of the four children showed symptoms consistent with neurodevelopmental disorders. The two fetuses with no deletion have a normal follow-up with regression of the renal hyperechogenicity. We report a strikingly high correlation between prenatal hyperechogenic kidneys, 17q12 microdeletion, and autism spectrum disorder with the advantage of optimal prenatal counseling as well as early diagnosis and intervention. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

  2. A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial.

    Science.gov (United States)

    Abbara, Ali; Clarke, Sophie; Islam, Rumana; Prague, Julia K; Comninos, Alexander N; Narayanaswamy, Shakunthala; Papadopoulou, Deborah; Roberts, Rachel; Izzi-Engbeaya, Chioma; Ratnasabapathy, Risheka; Nesbitt, Alexander; Vimalesvaran, Sunitha; Salim, Rehan; Lavery, Stuart A; Bloom, Stephen R; Huson, Les; Trew, Geoffrey H; Dhillo, Waljit S

    2017-09-01

    Can increasing the duration of LH-exposure with a second dose of kisspeptin-54 improve oocyte maturation in women at high risk of ovarian hyperstimulation syndrome (OHSS)? A second dose of kisspeptin-54 at 10 h following the first improves oocyte yield in women at high risk of OHSS. Kisspeptin acts at the hypothalamus to stimulate the release of an endogenous pool of GnRH from the hypothalamus. We have previously reported that a single dose of kisspeptin-54 results in an LH-surge of ~12-14 h duration, which safely triggers oocyte maturation in women at high risk of OHSS. Phase-2 randomized placebo-controlled trial of 62 women at high risk of OHSS recruited between August 2015 and May 2016. Following controlled ovarian stimulation, all patients (n = 62) received a subcutaneous injection of kisspeptin-54 (9.6 nmol/kg) 36 h prior to oocyte retrieval. Patients were randomized 1:1 to receive either a second dose of kisspeptin-54 (D; Double, n = 31), or saline (S; Single, n = 31) 10 h thereafter. Patients, embryologists, and IVF clinicians remained blinded to the dosing allocation. Study participants: Sixty-two women aged 18-34 years at high risk of OHSS (antral follicle count ≥23 or anti-Mullerian hormone level ≥40 pmol/L). Setting: Single centre study carried out at Hammersmith Hospital IVF unit, London, UK. Primary outcome: Proportion of patients achieving an oocyte yield (percentage of mature oocytes retrieved from follicles ≥14 mm on morning of first kisspeptin-54 trigger administration) of at least 60%. Secondary outcomes: Reproductive hormone levels, implantation rate and OHSS occurrence. A second dose of kisspeptin-54 at 10 h following the first induced further LH-secretion at 4 h after administration. A higher proportion of patients achieved an oocyte yield ≥60% following a second dose of kisspeptin-54 (Single: 14/31, 45%, Double: 21/31, 71%; absolute difference +26%, CI 2-50%, P = 0.042). Patients receiving two doses of kisspeptin-54 had a variable LH

  3. Prevalence of high-risk alleles in the LOXL1 gene and its association with pseudoexfoliation syndrome and exfoliation glaucoma in a Latin American population.

    Science.gov (United States)

    Jaimes, Martha; Rivera-Parra, David; Miranda-Duarte, Antonio; Valdés, Gerardo; Zenteno, Juan Carlos

    2012-03-01

    Pseudoexfoliation syndrome (XFS) is a major risk factor for exfoliation glaucoma (XFG). A significant association exists between XFG and several SNPs in the lysyl oxidase-like 1 (LOXL1) gene. The purpose of this study was to report the results of the first association study between LOXL1 polymorphisms and XFS and/or XFG in a Latin American population. Genotypes of three high-risk SNPs of LOXL1 (rs1048661, rs3825942, and rs2165241) were analyzed by direct sequencing. A case-control study was conducted with 102 unrelated XFS/XFG Mexican patients (42 XFS/60 XFG) as well as 97 control subjects. Allele frequencies, Hardy-Weinberg equilibrium, and haplotype association analysis were assessed with the Haplo View software. The T allele of the intronic SNP rs2165241 was more frequent in XFS/XFG patients than in controls (OR [95% CI] = 2.41 [1.59-3.64]; p = 0.00001). The G allele of rs3825942 was found in a higher frequency in XFS/XFG than in controls (100% vs 95% respectively, p = 0.0019). No significant association between XFS and the rs1048661 (R141L) SNP was observed. The TGT haplotype was observed in a higher frequency in patients than in controls (p = 0.025), and produced the highest risk in our study (OR [95% CI] = 3.20 [1.09-9.39]; p = 0.025). This is the first study associating LOXL1 gene polymorphism and XFS/XFG in Latin America. LOXL1 variants are associated with an elevated risk for XFS/XFG in the Mexican population. A higher risk was conferred by the T allele of the intronic rs2165241 SNP rather than by the worldwide "high-risk" G allele of rs3825942.

  4. Identification of High-Risk Plaques Destined to Cause Acute Coronary Syndrome Using Coronary Computed Tomographic Angiography and Computational Fluid Dynamics.

    Science.gov (United States)

    Lee, Joo Myung; Choi, Gilwoo; Koo, Bon-Kwon; Hwang, Doyeon; Park, Jonghanne; Zhang, Jinlong; Kim, Kyung-Jin; Tong, Yaliang; Kim, Hyun Jin; Grady, Leo; Doh, Joon-Hyung; Nam, Chang-Wook; Shin, Eun-Seok; Cho, Young-Seok; Choi, Su-Yeon; Chun, Eun Ju; Choi, Jin-Ho; Nørgaard, Bjarne L; Christiansen, Evald H; Niemen, Koen; Otake, Hiromasa; Penicka, Martin; de Bruyne, Bernard; Kubo, Takashi; Akasaka, Takashi; Narula, Jagat; Douglas, Pamela S; Taylor, Charles A; Kim, Hyo-Soo

    2018-03-14

    We investigated the utility of noninvasive hemodynamic assessment in the identification of high-risk plaques that caused subsequent acute coronary syndrome (ACS). ACS is a critical event that impacts the prognosis of patients with coronary artery disease. However, the role of hemodynamic factors in the development of ACS is not well-known. Seventy-two patients with clearly documented ACS and available coronary computed tomographic angiography (CTA) acquired between 1 month and 2 years before the development of ACS were included. In 66 culprit and 150 nonculprit lesions as a case-control design, the presence of adverse plaque characteristics (APC) was assessed and hemodynamic parameters (fractional flow reserve derived by coronary computed tomographic angiography [FFR CT ], change in FFR CT across the lesion [△FFR CT ], wall shear stress [WSS], and axial plaque stress) were analyzed using computational fluid dynamics. The best cut-off values for FFR CT , △FFR CT , WSS, and axial plaque stress were used to define the presence of adverse hemodynamic characteristics (AHC). The incremental discriminant and reclassification abilities for ACS prediction were compared among 3 models (model 1: percent diameter stenosis [%DS] and lesion length, model 2: model 1 + APC, and model 3: model 2 + AHC). The culprit lesions showed higher %DS (55.5 ± 15.4% vs. 43.1 ± 15.0%; p stress than nonculprit lesions (all p values statistic [c-index] 0.789 vs. 0.747; p = 0.014) and reclassification abilities (category-free net reclassification index 0.287; p = 0.047; relative integrated discrimination improvement 0.368; p < 0.001) than model 2. Lesions with both APC and AHC showed significantly higher risk of the culprit for subsequent ACS than those with no APC/AHC (hazard ratio: 11.75; 95% confidence interval: 2.85 to 48.51; p = 0.001) and with either APC or AHC (hazard ratio: 3.22; 95% confidence interval: 1.86 to 5.55; p < 0.001). Noninvasive hemodynamic assessment enhanced

  5. Agentes imunossupressores, talidomida e ácido valpróico nas síndromes mielodisplásicas Immunosuppressive agents, thalidomide and valproate acid in myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Elvira R. P. Velloso

    2006-09-01

    Full Text Available Agentes imunossupressores, como a globulina antitimocítica (GAL ou antilinfocítica (GAL e a ciclosporina A têm mostrado eficácia nas SMD, particularmente nos subtipos Anemias refratária (AR e nas SMD com fenótipo HLA-DR15, independente do grau de celularidade medular. Outras drogas disponíveis em nosso meio, de baixo custo, como a talidomida podem ser utilizada em pacientes refratários, e o ácido valpróico está sendo utilizado em ensaios clínicos. A quantificação da resposta a drogas deve utilizar os critérios de resposta do International Working Group (IWG. É proposto um fluxograma para uso de fatores de crescimento, agentes imunossupressores e talidomida em pacientes com SMD, de baixo risco, não candidatos a transplante de medula óssea (TMO.Patients with refractory anemia subtypes and HLA-DR15 with any degree of marrow cellularity have good responses to immunosuppressive agents, such as antithymocyte globulin, antilymphocyte globulin and cyclosporine A. Other cheaper drugs available in Brazil, including thalidomide may be useful in refractory patients. Valproate acid has started to be used in clinical trials. Response to treatment should be reported using the criteria proposed by the International Working Group. The use of growth factors, immunosuppressive agents and thalidomide in low risk patients with myelodysplastic syndromes who are not candidates for hematopoietic stem cell transplantation is suggested at the end of this publication.

  6. Comparison of allogeneic stem cell transplantation and non-transplant approaches in elderly patients with advanced myelodysplastic syndrome: optimal statistical approaches and a critical appraisal of clinical results using non-randomized data.

    Directory of Open Access Journals (Sweden)

    Ronald Brand

    Full Text Available Allogeneic stem cell transplantation (ASCT from related or unrelated donors may cure patients with myelodysplastic syndromes (MDS, a heterogeneous group of clonal stem cell disorders. We analysed 384 elderly patients (55-69 years with advanced MDS who received either ASCT (n=247 and were reported to The European Group for Blood and Marrow Transplantation (EBMT or a non -transplant approach (n=137 reported to the Düsseldorf registry. Besides an attempt to answer the question of "comparison", the purpose of this work is to explain the difficulties in comparing a non-transplant with a transplant cohort, when death before transplant is likely but unknown and the selection of patients for transplant is based on assumptions. It shows which methods are almost always biased and that even the most sophisticated approaches crucially rely on clinical assumptions. Using the most appropriate model for our data, we derive an overall univariate non-significant survival disadvantage for the transplant cohort (HR: 1.29, p = 0.11. We show that such an "average" hazard ratio is however misleading due to non-proportionality of the hazards reflecting early treatment related mortality, the occurring of which is logically correlated with the interval between diagnosis and transplant creating a disproportional drop in the (reconstructed survival curve of the transplanted patients. Also in multivariate analysis (correcting for age > 60 (HR: 1.4, p = 0.02 and abnormal cytogenetics (HR: 1.46, p = 0.01, transplantation seems to be worse (HR: 1.39, p = 0.05 but only in the (incorrect but commonly applied model without time varying covariates. The long term (time depending hazard ratio is shown to be virtually 1 and overall survival is virtually identical in both groups. Nonetheless no conclusion can be reached from a clinical point of view without assumptions which are by their very nature untestable unless all patients would be followed from diagnosis.

  7. Randomized Phase II Study of Azacitidine Alone or in Combination With Lenalidomide or With Vorinostat in Higher-Risk Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia: North American Intergroup Study SWOG S1117.

    Science.gov (United States)

    Sekeres, Mikkael A; Othus, Megan; List, Alan F; Odenike, Olatoyosi; Stone, Richard M; Gore, Steven D; Litzow, Mark R; Buckstein, Rena; Fang, Min; Roulston, Diane; Bloomfield, Clara D; Moseley, Anna; Nazha, Aziz; Zhang, Yanming; Velasco, Mario R; Gaur, Rakesh; Atallah, Ehab; Attar, Eyal C; Cook, Elina K; Cull, Alyssa H; Rauh, Michael J; Appelbaum, Frederick R; Erba, Harry P

    2017-08-20

    Purpose Azacitidine is standard, first-line therapy in higher-risk myelodysplastic syndromes (MDS). Whether azacitidine-based combinations with lenalidomide or vorinostat produce superior overall response rates (ORRs) to azacitidine is not known. Patients and Methods North American Intergroup Study S1117 is a phase II/III trial that randomly assigned patients with higher-risk MDS and chronic myelomonocytic leukemia (CMML) 1:1:1 to azacitidine (75 mg/m 2 /day on days 1 to 7 of a 28-day cycle); azacitidine plus lenalidomide (10 mg/day on days 1 to 21); or azacitidine plus vorinostat (300 mg twice daily on days 3 to 9). The primary phase II end point was improved ORR. Results Of 277 patients from 90 centers, 92 received azacitidine, 93 received azacitidine plus lenalidomide, and 92 received azacitidine plus vorinostat. Median age was 70 years (range, 28 to 93 years), 85 patients (31%) were female, and 53 patients (19%) had CMML. Serious adverse events were similar across arms, although combination-arm patients were more likely to undergo nonprotocol-defined dose modifications ( P vorinostat ( P = .16 v azacitidine). For patients with CMML, ORR was higher for azacitidine plus lenalidomide versus azacitidine (68% v 28%, P = .02) but similar for all arms across cytogenetic subgroups, as was remission duration and overall survival. ORR was higher with mutations in DNMT3A and lower for SRSF2, whereas ORR duration improved with fewer mutations. Lenalidomide dose reduction was associated with worse overall survival (hazard ratio, 1.30; P = .05). Conclusion Patients with higher-risk MDS treated with azacitidine-based combinations had similar ORR to azacitidine monotherapy, although patients with CMML benefitted from azacitidine plus lenalidomide. The efficacy of combination regimens may have been affected by dose modifications.

  8. Defibrotide for Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease Prophylaxis in High-Risk Adult Patients: A Single-Center Experience Study.

    Science.gov (United States)

    Picod, Adrien; Bonnin, Agnès; Battipaglia, Giorgia; Giannotti, Federica; Ruggeri, Annalisa; Brissot, Eolia; Malard, Florent; Médiavilla, Clémence; Belhocine, Ramdane; Vekhoff, Anne; Gueye, Mor Sény; Lapusan, Simona; Adaeva, Rosa; Isnard, Françoise; Legrand, Ollivier; Baylatry, Minh-Tam; Joly, Anne-Christine; Labopin, Myriam; Duléry, Rémy; Mohty, Mohamad

    2018-03-01

    Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a serious complication after hematopoietic stem cell transplantation (HSCT). SOS/VOD usually occurs within 3 weeks of HSCT, but the 2016 European Society for Blood and Marrow Transplantation diagnosis criteria have been revised to include late forms. Prophylactic use of defibrotide is recommended in the pediatric setting, but its value remains uncertain in the adult population. We report here a single-center series of 63 adult patients considered at high risk for SOS/VOD who received defibrotide prophylaxis in combination with ursodeoxycholic acid between May 2012 and August 2016. The median duration of defibrotide therapy was 23 days. Bleeding occurred in 14 patients (21.5%). Defibrotide prophylaxis was discontinued in 7 patients (10.8%): 4 cases (6.3%) due to bleeding and 3 cases (4.6%) because of the need for antithrombotic therapy. Overall, SOS/VOD occurred in 4 cases (6.3%) within 21 days after HSCT (days 13 and 14) in 2 cases and late-onset SOS/VOD (days 57 and 58) in the other 2 cases. SOS/VOD was moderate in 1 case, very severe in 3 cases, with 2 deaths related to SOS/VOD. Cumulative incidence of grades II to IV acute graft-versus-host disease and transplant-associated thrombotic microangiopathy were 22.2% and 3.2%, respectively. With a median follow-up of 31 months (range, 10.7 to 60.3), the rates of 2-year overall survival, progression-free survival, incidence of relapse, and nonrelapse mortality were 56.5%, 49%, 28.7%, and 22.3%, respectively. In our experience defibrotide prophylaxis is associated with a low incidence of SOS/VOD after allogeneic HSCT in a high-risk adult population with an acceptable safety profile. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  9. Efficacy and safety of rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome: Rationale and design of the Trial on Rivaroxaban in AntiPhospholipid Syndrome (TRAPS) trial.

    Science.gov (United States)

    Pengo, V; Banzato, A; Bison, E; Zoppellaro, G; Padayattil Jose, S; Denas, G

    2016-03-01

    New oral anticoagulants may simplify long-term therapy in conditions requiring anticoagulation. Rivaroxaban is a direct factor Xa inhibitor that has been extensively studied and is now approved for the prevention and therapy of a number of thromboembolic conditions. This is a multicentre, randomized, open-label, study that will evaluate if Rivaroxaban 20 mg od (or 15 mg od in patients with moderate renal insufficiency) is non-inferior to warfarin (INR target 2.5), for the prevention of thromboembolic events, major bleeding and death in high risk (triple positive) patients with antiphospholipid syndrome. Secondary endpoints will assess the incidence of any individual component of the composite end point. An external adjudication committee will evaluate all suspected outcome events. This will be a unique trial, as it will enrol the biggest homogenous cohort of high risk APS individuals. The methods and the study design should be appropriate to achieve study results that are both scientifically valid and relevant to clinical practice. © The Author(s) 2015.

  10. Azacitidine front-line in 339 patients with myelodysplastic syndromes and acute myeloid leukaemia: comparison of French-American-British and World Health Organization classifications

    Directory of Open Access Journals (Sweden)

    Lisa Pleyer

    2016-04-01

    Full Text Available Abstract Background The MDS-IWG and NCCN currently endorse both FAB and WHO classifications of MDS and AML, thus allowing patients with 20–30 % bone marrow blasts (AML20–30, formerly MDS-RAEB-t to be categorised and treated as either MDS or AML. In addition, an artificial distinction between AML20–30 and AML30+ was made by regulatory agencies by initially restricting approval of azacitidine to AML20–30. Thus, uncertainty prevails regarding the diagnosis, prognosis and optimal treatment timing and strategy for patients with AML20–30. Here, we aim to provide clarification for patients treated with azacitidine front-line. Methods The Austrian Azacitidine Registry is a multicentre database (ClinicalTrials.gov: NCT01595295. For this analysis, we selected 339 patients treated with azacitidine front-line. According to the WHO classification 53, 96 and 190 patients had MDS-RAEB-I, MDS-RAEB-II and AML (AML20–30: n = 79; AML30+: n = 111, respectively. According to the FAB classification, 131, 101 and 111 patients had MDS-RAEB, MDS-RAEB-t and AML, respectively. Results The median ages of patients with MDS and AML were 72 (range 37–87 and 77 (range 23–93 years, respectively. Overall, 80 % of classifiable patients (≤30 % bone marrow blasts had intermediate-2 or high-risk IPSS scores. Most other baseline, treatment and response characteristics were similar between patients diagnosed with MDS or AML. WHO-classified patients with AML20–30 had significantly worse OS than patients with MDS-RAEB-II (13.1 vs 18.9 months; p = 0.010, but similar OS to patients with AML30+ (10.9 vs 13.1 months; p = 0.238. AML patients that showed MDS-related features did not have worse outcomes compared with patients who did not (13.2 vs 8.9 months; p = 0.104. FAB-classified patients with MDS-RAEB-t had similar survival to patients with AML30+ (12.8 vs 10.9 months; p = 0.376, but significantly worse OS than patients with MDS-RAEB (10

  11. High-Risk List

    Science.gov (United States)

    2017-01-01

    economy. The World Bank has said that “corruption creates an unfavorable business environment by undermining the operation efficiency of firms and... Bank Began as ‘Ponzi Scheme,’” 11/27/2012. 64 Independent Joint Anti-Corruption Monitoring and Evaluation Committee, Unfinished Business : The Follow...HIGH RISK AREA 7: Oversight 51 HIGH-RISK AREA 8: Strategy and Planning 55 CONCLUSION HIGH RISK LIST I JANUARY 11, 2017 2 EXECUTIVE SUMMARY

  12. A predictive model to identify patients with suspected acute coronary syndromes at high risk of cardiac arrest or in-hospital mortality: An IMMEDIATE Trial sub-study

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    Madhab Ray

    2015-12-01

    Conclusions: The multivariable predictive model developed identified patients with very early ACS at high risk of cardiac arrest or death. Using this model could assist treating those with greatest potential benefit from GIK.

  13. Tratamento de suporte e quelação de ferro em pacientes com síndromes mielodisplásicas Supportive care, tranfusion and chelation therapy for patients with myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Elizabeth X. Souto

    2006-09-01

    Full Text Available As síndromes mielodisplásicas (SMD são um grupo heterogêneo de distúrbios hematológicos que ocorrem mais freqüentemente em pacientes idosos e que cursa, na maioria dos casos, com anemia crônica dependente de transfusão de hemoderivados. Conseqüentemente, muitos destes pacientes passam a apresentar sobrecarga de ferro, que pode levar a danos teciduais graves. Ambas as terapias, transfusional e de quelação de ferro, quando indicadas, são importantes para manter a sobrevida e a qualidade de vida destes pacientes. A terapia de quelação de ferro está indicada especialmente nos subtipos de SMD com melhor prognóstico e sobrevida longa o suficiente para o desenvolvimento de sobrecarga de ferro com relevância clínica. A terapia de quelação de ferro apresenta algumas limitações relacionadas à necessidade de longo tempo de infusão da deferoxamina, da dificuldade de adesão pelo paciente, bem como da aquisição da bomba de infusão. O uso da deferiprona, que é um quelante oral de ferro, está contra-indicado neste grupo de pacientes, pelo risco de neutropenia e agranulocitose. O deferasirox é um novo quelante oral de ferro em estudo e que poderá, no futuro, ser uma opção adequada para os pacientes com SMD e sobrecarga de ferro. Novos estudos em pacientes com síndromes mielodisplásicas são necessários para melhor estabelecer critérios de diagnóstico da sobrecarga de ferro, bem com da terapia de quelação neste grupo.Myelodysplastic syndromes (MDSs are a heterogeneous group of hematological disorders which are more common in the elderly and related to chronic anemia dependent on blood transfusions. Consequently, many of these patients develop iron overload which may lead to severe injury to tissues. Transfusions and chelation therapy, when indicated, are important for survival and to maintain the quality of life. Chelation therapy is indicated especially for MDS subtypes with a better prognosis and a sufficiently long

  14. Allogeneic hematopoietic stem cell transplantation for primary myelodysplastic syndrome Transplante alogênico de células progenitoras hematopoiéticas para síndrome mielodisplásica primária

    Directory of Open Access Journals (Sweden)

    Carlos R. Medeiros

    2004-01-01

    Full Text Available Characteristics and outcomes of 52 patients with myelodysplastic syndrome (MDS who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT were analyzed. Median age was 30 years (range 2-61 years and median time from diagnosis to allo-HSCT was 10 months (range 1-161 months. Thirty-six patients had advanced MDS or acute myeloid leukemia following MDS at transplant. Conditioning with busulfan and cyclophosphamide was administered to 73% of patients, and the median value of graft dose was 2.595 x 10(8 of total nucleated cells/kg. Overall survival and disease free survival at 4 years were 36% and 33%, respectively. Nineteen patients were alive, with a median follow-up of 3.8 years. Twelve patients relapsed and only one is alive, after donor lymphocyte infusion. Interval II occurred in 19 patients. Donor type (identical related versus non-related/partially matched related influenced the incidence of acute GVHD (P = 0.03. Eleven patients developed chronic GVHD and previous acute GVHD was a risk factor (P = 0.03. Thirty-three patients died, 22 (67% secondary to transplant-related complications. Patients with MDS should undergo allo-HSCT earlier, mainly if they have a compatible donor and are young.Características e resultados de 52 pacientes com síndrome mielodisplásica (MDS submetidos a transplante alogênico de células progenitoras hematopoiéticas (TCPH foram analisados. A idade mediana foi de 30 anos (variação de 2-61 anos e o tempo mediano entre o diagnóstico e transplante foi de dez meses (variação de 1-161 meses. Trinta e seis pacientes tinham MDS avançada ou leucemia mielóide aguda secundária a MDS ao transplante. O condicionamento com busulfano e ciclo­fosfamida foi recebido por 73% dos pacientes, e a dose celular mediana do enxerto foi de 2.56 x 10(8 células nucleadas/kg. A sobrevida global e a sobrevida livre de doença aos quatro anos foi de 36% e 33%, respectivamente. Dezenove pacientes estavam vivos, com um

  15. Anesthetic Management of Mitochondrial Encephalopathy With Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome) in a High-Risk Pregnancy: A Case Report.

    Science.gov (United States)

    Bell, Josh D; Higgie, Kushlin; Joshi, Mital; Rucker, Joshua; Farzi, Sahar; Siddiqui, Naveed

    2017-07-15

    MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like symptoms) is a rare and complex mitochondrial disorder. We present the in-hospital course of a 36-year-old gravida 2, para 0 with MELAS syndrome and severe preeclampsia, complicated by hyponatremia, hyperkalemia, and diabetes. A retained placenta with postpartum hemorrhage required urgent instrumental delivery under spinal anesthesia, transfusion, and intensive care unit admission for pulmonary edema, effusions, and atelectasis. Postpartum endometritis and sepsis also were encountered. This is to our knowledge the first case report of obstetric complications in MELAS syndrome and highlights the salient metabolic sequelae of this syndrome.

  16. Asthma and risk of myelodysplastic syndromes

    DEFF Research Database (Denmark)

    Frederiksen, Henrik; Farkas, Dóra Körmendiné; Horváth-Puhó, Erzsébet

    2017-01-01

    /CMML among asthma patients overall was 1.6 (95% CI: 1.3-2.0) with little variation across subgroups. CONCLUSIONS: Asthma may be a risk factor for the development of MDS/CMML.British Journal of Cancer advance online publication, 29 November 2016; doi:10.1038/bjc.2016.389 www.bjcancer.com....

  17. Innate Immunity Dysregulation in Myelodysplastic Syndromes

    Science.gov (United States)

    2013-10-01

    by the Regional Ministry of Education of Castilla-la Mancha, Spain, supported by the European Social Fund (ESF). We are thankful for the efforts...consistent with previous reports that aber rant activation of innate immune signals in MDS, including overcxpression of several TLRs (36) and loss...281: 1652- 1659. 14. Loiarro M, Set te C , Gallo G. Ciacc.i A, Fa nto N, et al. (2005) Peptide- media ted interference of T JR domain dimeri7.ation

  18. Innate Immunity Dysregulation in Myelodysplastic Syndromes

    Science.gov (United States)

    2014-10-01

    motif-ligand (CXCL), C-C motif ligand (CCL), World Health Organization (WHO), French-American-British classification (FAB), macrophage inflammatory...constitutive NF-κB 5 signaling provides malignant cells, which overpopulate BM in late stages of MDS, with a survival 6 advantage. 7 There is also...20 survival advantage and contribute to the aberrant proliferation of the clone, which at this point 21 overpopulates the BM. (9) This switch in the

  19. Iron overload in myelodysplastic syndromes (MDS).

    Science.gov (United States)

    Gattermann, Norbert

    2018-01-01

    Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

  20. Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death

    DEFF Research Database (Denmark)

    Bezzina, Connie; Barc, Julien; Mizusawa, Yuka

    2013-01-01

    Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases. Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) a...

  1. Conditioning with Treosulfan and Fludarabine Followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies

    Science.gov (United States)

    Nemecek, Eneida R.; Guthrie, Katherine A.; Sorror, Mohamed L.; Wood, Brent L.; Doney, Kristine C.; Hilger, Ralf A.; Scott, Bart L.; Kovacsovics, Tibor J.; Maziarz, Richard T.; Woolfrey, Ann E.; Bedalov, Antonio; Sanders, Jean E.; Pagel, John M.; Sickle, Eileen J.; Witherspoon, Robert; Flowers, Mary E.; Appelbaum, Frederick R.; Deeg, H. Joachim

    2010-01-01

    In this prospective study 60 patients of median age 46 (range 5–60) years, with acute myeloid leukemia (AML; n=44), acute lymphoblastic leukemia (ALL; n=3), or myelodysplastic syndrome (MDS; n=13) were conditioned for allogeneic hematopoietic cell transplantation with a treosulfan/fludarabine combination. Most patients were considered at high risk for relapse or non-relapse mortality (NRM). Patients received intravenous treosulfan, 12 g/m2/day (n=5) or 14 g/m2/day (n=55) on days -6 to -4, and fludarabine (30 mg/m2/day) on days -6 to -2, followed by infusion of marrow (n=7) or peripheral blood stem cells (n=53) from HLA-identical siblings (n=30) or unrelated donors (n=30). All patients engrafted. NRM was 5% at day 100, and 8% at 2 years. With a median follow-up of 22 months, the 2-year relapse-free survival for all patients was 58% and 88% for patients without high risk cytogenetics. The 2-year cumulative incidence of relapse was 33% (15% for patients with MDS, 34% for AML in first remission, 50% for AML or ALL beyond first remission and 63% for AML in refractory relapse). Thus, a treosulfan/fludarabine regimen was well tolerated and yielded encouraging survival and disease control with minimal NRM. Further trials are warranted to compare treosulfan/fludarabine to other widely used regimens, and to study the impact of using this regimen in more narrowly defined groups of patients. PMID:20685259

  2. Mortality in high-risk patients with bleeding Mallory-Weiss syndrome is similar to that of peptic ulcer bleeding. Results of a prospective database study.

    Science.gov (United States)

    Ljubičić, Neven; Budimir, Ivan; Pavić, Tajana; Bišćanin, Alen; Puljiz, Zeljko; Bratanić, Andre; Troskot, Branko; Zekanović, Dražen

    2014-04-01

    The aim of this study was to identify the predictive factors influencing mortality in patients with bleeding Mallory-Weiss syndrome in comparison with peptic ulcer bleeding. Between January 2005 and December 2009, 281 patients with endoscopically confirmed Mallory-Weiss syndrome and 1530 patients with peptic ulcer bleeding were consecutively evaluated. The 30-day mortality and clinical outcome were related to the patients' demographic data, endoscopic, and clinical characteristics. The one-year cumulative incidence for bleeding Mallory-Weiss syndrome was 7.3 cases/100,000 people and for peptic ulcer bleeding 40.4 cases/100,000 people. The age-standardized incidence for both bleeding Mallory-Weiss syndrome and peptic ulcer bleeding remained unchanged during the observational five-year period. The majority of patients with bleeding Mallory-Weiss syndrome were male patients with significant overall comorbidities (ASA class 3-4). Overall 30-day mortality rate was 5.3% for patients with bleeding Mallory-Weiss syndrome and 4.6% for patients with peptic ulcer bleeding (p = 0.578). In both patients with bleeding Mallory-Weiss syndrome and peptic ulcer bleeding, mortality was significantly higher in patients over 65 years of age and those with significant overall comorbidities (ASA class 3-4). The incidence of bleeding Mallory-Weiss syndrome and peptic ulcer bleeding has not changed over a five-year observational period. The overall 30-day mortality was almost equal for both bleeding Mallory-Weiss syndrome and peptic ulcer bleeding and was positively correlated to older age and underlying comorbid illnesses.

  3. Impact of abciximab in elderly patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention: an observational registry study

    DEFF Research Database (Denmark)

    Iversen, Allan Z; Galatius, Soeren; Haahr-Pedersen, Sune Ammentorp

    2011-01-01

    BACKGROUND: An increasing proportion of patients with acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI) are classified as elderly (aged =70 years). The glycoprotein IIb/IIIa inhibitor abciximab is known to reduce adverse outcomes in patients aged

  4. Survey of expert opinions and related recommendations regarding bridging therapy using hypomethylating agents followed by allogeneic transplantation for high-risk MDS.

    Science.gov (United States)

    Sohn, Sang Kyun; Moon, Joon Ho

    2015-08-01

    According to current guidelines on therapeutic strategies for myelodysplastic syndrome (MDS), cytoreductive therapies before allogeneic stem cell transplantation (SCT) are not widely recommended for patients with high-risk MDS or refractory anemia with excess blasts (RAEB) who are eligible for allogeneic SCT because of controversial evidence on the role of such therapies. Yet, while treatment with hypomethylating agents (HMAs) has a critical limitation in eradicating MDS clones, the use of HMA treatment as a bridge to allogeneic SCT has become a focus with the hope of improving the SCT outcome based on the chance of achieving complete remission or reducing the blast percentage safely and effectively before allogeneic SCT. However, a consensus needs to be established on the use of HMAs as a bridging therapy for high-risk MDS or RAEB. Thus, the Korean AML/MDS working party group surveyed 34 Korean MDS experts on their bridging therapies for high-risk MDS. Accordingly, this paper presents the survey questionnaire and resulting data, along with a summary of the consensus and related recommendations regarding strategies using HMA treatment and allogeneic SCT based on reported studies and the current survey results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Early versus delayed invasive strategy for intermediate- and high-risk acute coronary syndromes managed without P2Y12 receptor inhibitor pretreatment: Design and rationale of the EARLY randomized trial.

    Science.gov (United States)

    Lemesle, Gilles; Laine, Marc; Pankert, Mathieu; Puymirat, Etienne; Cuisset, Thomas; Boueri, Ziad; Maillard, Luc; Armero, Sébastien; Cayla, Guillaume; Bali, Laurent; Motreff, Pascal; Peyre, Jean-Pascal; Paganelli, Franck; Kerbaul, François; Roch, Antoine; Michelet, Pierre; Baumstarck, Karine; Bonello, Laurent

    2018-01-01

    According to recent literature, pretreatment with a P2Y 12 ADP receptor antagonist before coronary angiography appears no longer suitable in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) due to an unfavorable risk-benefit ratio. Optimal delay of the invasive strategy in this specific context is unknown. We hypothesize that without P2Y 12 ADP receptor antagonist pretreatment, a very early invasive strategy may be beneficial. The EARLY trial (Early or Delayed Revascularization for Intermediate- and High-Risk Non-ST-Segment Elevation Acute Coronary Syndromes?) is a prospective, multicenter, randomized, controlled, open-label, 2-parallel-group study that plans to enroll 740 patients. Patients are eligible if the diagnosis of intermediate- or high-risk NSTE-ACS is made and an invasive strategy intended. Patients are randomized in a 1:1 ratio. In the control group, a delayed strategy is adopted, with the coronary angiography taking place between 12 and 72 hours after randomization. In the experimental group, a very early invasive strategy is performed within 2 hours. A loading dose of a P2Y 12 ADP receptor antagonist is given at the time of intervention in both groups. Recruitment began in September 2016 (n = 558 patients as of October 2017). The primary endpoint is the composite of cardiovascular death and recurrent ischemic events at 1 month. The EARLY trial aims to demonstrate the superiority of a very early invasive strategy compared with a delayed strategy in intermediate- and high-risk NSTE-ACS patients managed without P2Y 12 ADP receptor antagonist pretreatment. © 2018 Wiley Periodicals, Inc.

  6. [Detecting high risk pregnancy].

    Science.gov (United States)

    Doret, Muriel; Gaucherand, Pascal

    2009-12-20

    Antenatal care is aiming to reduce maternal land foetal mortality and morbidity. Maternal and foetal mortality can be due to different causes. Their knowledge allows identifying pregnancy (high risk pregnancy) with factors associated with an increased risk for maternal and/or foetal mortality and serious morbidity. Identification of high risk pregnancies and initiation of appropriate treatment and/or surveillance should improve maternal and/or foetal outcome. New risk factors are continuously described thanks to improvement in antenatal care and development in biology and cytopathology, increasing complexity in identifying high risk pregnancies. Level of risk can change all over the pregnancy. Ideally, it should be evaluated prior to the pregnancy and at each antenatal visit. Clinical examination is able to screen for intra-uterin growth restriction, pre-eclampsia, threatened for preterm labour; ultrasounds help in the diagnosis of foetal morphological anomalies, foetal chromosomal anomalies, placenta praevia and abnormal foetal growth; biological exams are used to screen for pre-eclampsia, gestational diabetes, trisomy 21 (for which screening method just changed), rhesus immunisation, seroconversion for toxoplasmosis or rubeola, unknown infectious disease (syphilis, hepatitis B, VIH). During pregnancy, most of the preventive strategies have to be initiated during the first trimester or even before conception. Prevention for neural-tube defects, neonatal hypocalcemia and listeriosis should be performed for all women. On the opposite, some measures are concerning only women with risk factors such as prevention for toxoplasmosis, rhesus immunization (which recently changed), tobacco complications and pre-eclampsia and intra-uterine growth factor restriction.

  7. Point-of-care heart-type fatty acid binding protein versus high-sensitivity troponin T testing in emergency patients at high risk for acute coronary syndrome.

    Science.gov (United States)

    Kellens, Sebastiaan; Verbrugge, Frederik H; Vanmechelen, Maxime; Grieten, Lars; Van Lierde, Johan; Dens, Joseph; Vrolix, Mathias; Vandervoort, Pieter

    2016-04-01

    High-sensitivity cardiac troponin testing is used to detect myocardial damage in patients with acute chest pain. Heart-type fatty acid binding protein (H-FABP) may be an alternative, available as point-of-care test. Patients (n=203) referred by general practitioners for suspected acute coronary syndrome or presenting with typical chest pain and one major cardiovascular risk factor at the emergency department were prospectively included in a single-centre cohort study. High-sensitivity cardiac troponin T (hs-TnT) and point-of-care H-FABP testing were concomitantly performed at admission and after 6h. Maximal hs-TnT levels above the 99th percentile were observed in 152 patients (75%) with 127 (63%) fulfilling criteria for myocardial infarction. Upon admission, hs-TnT and H-FABP were associated with an area under the curve (95% CI) of 0.83 (0.77-0.89) and 0.79 (0.73-0.85), respectively, to predict myocardial infarction, which increased to 0.93 (0.90-0.97) and 0.88 (0.84-0.93), respectively, after 6h. The diagnostic accuracy for non-ST-segment elevation myocardial infarction was somewhat lower with an area under the curve (95% CI) of 0.80 (0.72-0.87), 0.90 (0.84-0.96), 0.73 (0.64-0.81) and 0.77 (0.67-0.86), respectively. When assessment was performed within 3h of chest pain onset, diagnostic accuracy of H-FABP versus hs-TnT was similar. Each standard deviation increase in admission H-FABP was associated with a 68% relative risk increase of all-cause mortality (p-value=0.027) during 666 ± 155 days of follow-up. Point-of-care H-FABP testing has lower diagnostic accuracy compared with hs-TnT assessment in patients with high pre-test acute coronary syndrome probability, but might be of interest when assessment is possible early after chest pain onset. © The European Society of Cardiology 2015.

  8. Safety of open ventral hernia repair in high-risk patients with metabolic syndrome: a multi-institutional analysis of 39,118 cases.

    Science.gov (United States)

    Zavlin, Dmitry; Jubbal, Kevin T; Van Eps, Jeffrey L; Bass, Barbara L; Ellsworth, Warren A; Echo, Anthony; Friedman, Jeffrey D; Dunkin, Brian J

    2018-02-01

    Metabolic syndrome (MetS) entails the simultaneous presence of a constellation of dangerous risk factors including obesity, diabetes, hypertension, and dyslipidemia. The prevalence of MetS in Western society continues to rise and implies an elevated risk for surgical complications and/or poor surgical outcomes within the affected population. To assess the risks and outcomes of multi-morbid patients with MetS undergoing open ventral hernia repair. Multi-institutional case-control study in the United States. The American College of Surgeons National Surgical Quality Improvement Program database was sampled for patients undergoing initial open ventral hernia repair from 2012 through 2014 and then stratified into 2 cohorts based on the presence or absence of MetS. Statistical analyses were performed to evaluate preoperative co-morbidities, intraoperative details, and postoperative morbidity and mortality to identify risk factors for adverse outcomes. Mean age (61.0 versus 56.0 yr, Phigh operative risk in a population that is generally prone to obesity and its associated diseases. Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  9. Haematopoietic transplants combining a single unrelated cord blood unit and mobilized haematopoietic stem cells from an adult HLA-mismatched third party donor. Comparable results to transplants from HLA-identical related donors in adults with acute leukaemia and myelodysplastic syndromes.

    Science.gov (United States)

    Sebrango, Ana; Vicuña, Isabel; de Laiglesia, Almudena; Millán, Isabel; Bautista, Guiomar; Martín-Donaire, Trinidad; Regidor, Carmen; Cabrera, Rafael; Fernandez, Manuel N

    2010-06-01

    We describe results of the strategy, developed by our group, of co-infusion of mobilized haematopoietic stem cells as a support for single-unit unrelated cord blood transplant (dual CB/TPD-MHSC transplants) for treatment of haematological malignancies in adults, and a comparative analysis of results obtained using this strategy and transplants performed with mobilized haematopoietic stem cells from related HLA-identical donors (RTD) for treatment of adults with acute leukaemia and myelodysplastic syndromes. Our data show that the dual CB/TPD-MHSC transplant strategy results in periods of post-transplant neutropenia, final rates of full donor chimerism and transplant-related mortality rates comparable to those of the RTD. Final survival outcomes are comparable in adults transplanted because of acute leukaemia, with different incidences of the complications that most influence these: a higher incidence of infections related to late recovery of protective immunity dependent on T cell functions, and a lower incidence of serious acute graft-versus-host disease and relapses. Recent advances in cord blood transplant techniques allow allogeneic haematopoietic stem cell transplantation (HSCT) to be a viable option for almost every patient who may benefit from this therapeutic approach. Development of innovative strategies to improve the post-transplant recovery of T cells function is currently the main challenge to further improving the possibilities of unrelated cord blood transplantation. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults.

    Science.gov (United States)

    Savona, Michael R; Malcovati, Luca; Komrokji, Rami; Tiu, Ramon V; Mughal, Tariq I; Orazi, Attilio; Kiladjian, Jean-Jacques; Padron, Eric; Solary, Eric; Tibes, Raoul; Itzykson, Raphael; Cazzola, Mario; Mesa, Ruben; Maciejewski, Jaroslaw; Fenaux, Pierre; Garcia-Manero, Guillermo; Gerds, Aaron; Sanz, Guillermo; Niemeyer, Charlotte M; Cervantes, Francisco; Germing, Ulrich; Cross, Nicholas C P; List, Alan F

    2015-03-19

    Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) are hematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes and myeloproliferative neoplasms. There are currently no standard treatment recommendations for most adult patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic end points and standardized response criteria for clinical trials. The dual dysplastic and proliferative features in these stem cell malignancies define their uniqueness and challenges. We propose response assessment guidelines to harmonize future clinical trials with the principal objective of establishing suitable treatment algorithms. An international panel comprising laboratory and clinical experts in MDS/MPN was established involving 3 independent academic MDS/MPN workshops (March 2013, December 2013, and June 2014). These recommendations are the result of this collaborative project sponsored by the MDS Foundation. © 2015 by The American Society of Hematology.

  11. Single or Double Donor Umbilical Cord Blood Transplant in Treating Patients With High-Risk Hematologic Malignancies

    Science.gov (United States)

    2016-07-13

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory

  12. Timing of intervention in high-risk non-ST-elevation acute coronary syndromes in PCI versus non-PCI centres : Sub-group analysis of the ELISA-3 trial.

    Science.gov (United States)

    Badings, E A; Remkes, W S; Dambrink, J-H E; The, S H K; Van Wijngaarden, J; Tjeerdsma, G; Rasoul, S; Timmer, J R; van der Wielen, M L J; Lok, D J A; van 't Hof, A W J

    2016-03-01

    To compare the effect of timing of intervention in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in percutaneous coronary intervention (PCI) versus non-PCI centres. A post-hoc sub-analysis was performed of the ELISA III trial, a randomised multicentre trial investigating outcome of early ( 48 h) angiography and revascularisation in 542 patients with high-risk NSTE-ACS. 90 patients were randomised in non-PCI centres and tended to benefit more from an early invasive strategy than patients included in the PCI centre (relative risk 0.23 vs. 0.85 [p for interaction = 0.089] for incidence of the combined primary endpoint of death, reinfarction and recurrent ischaemia after 30 days of follow-up). This was largely driven by reduction in recurrent ischaemia. In non-PCI centres, patients randomised to the late group had a 4 and 7 day longer period until PCI or coronary artery bypass grafting, respectively. This difference was less pronounced in the PCI centre. This post-hoc analysis from the ELISA-3 trial suggests that NSTE-ACS patients initially hospitalised in non-PCI centres show the largest benefit from early angiography and revascularisation, associated with a shorter waiting time to revascularisation. Improved patient logistics and transfer between non-PCI and PCI centres might therefore result in better clinical outcome.

  13. A randomized comparison of novel bioresorbable polymer sirolimus-eluting stent and durable polymer everolimus-eluting stent in patients with acute coronary syndromes: The CENTURY II high risk ACS substudy

    International Nuclear Information System (INIS)

    Jiménez, Victor A.; Iñiguez, Andrés; Baz, José A.; Valdés, Mariano; Ortiz, Alberto; Vuilliomenet, André; Mainar, Vicente; Dudek, Dariusz; Banai, Shmuel; Tüller, David; Bonnet, Jean-Louis; De Miguel, Antonio; Bastos, Guillermo; Wijns, William; Saito, Shigeru

    2016-01-01

    Background: To investigate clinical outcomes of percutaneous coronary intervention using a sirolimus-eluting stent with bioresorbable polymer, Ultimaster (BP-SES) compared with a permanent polymer everolimus-eluting stent, Xience (PP-EES) in patients with high risk (ST-segment elevation and non-ST-segment elevation myocardial infarction) acute coronary syndromes (ACS) enrolled in the CENTURY II trial. Methods: CENTURY II is a prospective, multicenter, randomized, single blind, controlled trial comparing BP-SES and PP-EES, with primary endpoint of target lesion failure (TLF) at 9 month post-stent implantation. Out of 1123 patients enrolled in CENTURY II trial, 264 high risk ACS patients were included in this subgroup analysis, and the clinical outcomes including target lesion failure (TLF), target vessel failure (TVF), cardiac death, myocardial infarction, and stent thrombosis were evaluated at 24 months. Results: The baseline clinical, angiographic and procedural characteristics were similar between two groups. At 24 months, TLF occurred in 6.3% of patients receiving a BP-SES and 6.5% of patients receiving a PP-EES (P = 0.95); TVF was 6.3% in patients receiving a BP-SES and 9.4% in patients receiving a PP-EES (P = 0.36). There were no significant differences in cardiac death, myocardial infarction and stent thrombosis rate. Conclusions: BP-SES achieved similar safety and efficacy outcomes as PP-EES in this ACS subgroup of CENTURY II study, at 24-month follow-up. This finding is hypothesis-generating and needs to be confirmed in larger trials with longer follow-up. - Highlights: • This study reported the 24-month clinical outcomes of new-generation BP-SES compared with PP-EES in ACS subgroup from CENTURY II study. • This is a pre-specified subgroup analysis of a large randomized, prospective, multicenter clinical trial. • The BP-SES showed good and comparable clinical performance as PP-EES at 24 months. • This substudy has a relatively small sample size and

  14. A randomized comparison of novel bioresorbable polymer sirolimus-eluting stent and durable polymer everolimus-eluting stent in patients with acute coronary syndromes: The CENTURY II high risk ACS substudy

    Energy Technology Data Exchange (ETDEWEB)

    Jiménez, Victor A., E-mail: victor.alfonso.jimenez.diaz@sergas.es [Interventional Cardiology Unit, Cardiology Department, Hospital Alvaro Cunqueiro, University Hospital of Vigo, Vigo (Spain); Iñiguez, Andrés; Baz, José A. [Interventional Cardiology Unit, Cardiology Department, Hospital Alvaro Cunqueiro, University Hospital of Vigo, Vigo (Spain); Valdés, Mariano [Hospital Universitario V. Arrixaca, Murcia (Spain); Ortiz, Alberto [Interventional Cardiology Unit, Cardiology Department, Hospital Alvaro Cunqueiro, University Hospital of Vigo, Vigo (Spain); Vuilliomenet, André [Kantonsspital Aarau, Aarau (Switzerland); Mainar, Vicente [Department of Cardiology, University General Hospital of Alicante, Alicante (Spain); Dudek, Dariusz [Department of Interventional Cardiology, Jagiellonian University Medical College, Krakow (Poland); Banai, Shmuel [Tel Aviv Sourasky Medical Centre, Tel Aviv (Israel); Tüller, David [Department of Cardiology, Stadtspital Triemli, Zürich (Switzerland); Bonnet, Jean-Louis [Department of Cardiology, Hospital La Timone, Marseille (France); De Miguel, Antonio; Bastos, Guillermo [Interventional Cardiology Unit, Cardiology Department, Hospital Alvaro Cunqueiro, University Hospital of Vigo, Vigo (Spain); Wijns, William [Cardiovascular Center Aalst, OLV Hospital, Aalst (Belgium); Saito, Shigeru [Department of Cardiology and Catheterization Laboratory, Shonan Kamakura General Hospital, Kamakura (Japan)

    2016-09-15

    Background: To investigate clinical outcomes of percutaneous coronary intervention using a sirolimus-eluting stent with bioresorbable polymer, Ultimaster (BP-SES) compared with a permanent polymer everolimus-eluting stent, Xience (PP-EES) in patients with high risk (ST-segment elevation and non-ST-segment elevation myocardial infarction) acute coronary syndromes (ACS) enrolled in the CENTURY II trial. Methods: CENTURY II is a prospective, multicenter, randomized, single blind, controlled trial comparing BP-SES and PP-EES, with primary endpoint of target lesion failure (TLF) at 9 month post-stent implantation. Out of 1123 patients enrolled in CENTURY II trial, 264 high risk ACS patients were included in this subgroup analysis, and the clinical outcomes including target lesion failure (TLF), target vessel failure (TVF), cardiac death, myocardial infarction, and stent thrombosis were evaluated at 24 months. Results: The baseline clinical, angiographic and procedural characteristics were similar between two groups. At 24 months, TLF occurred in 6.3% of patients receiving a BP-SES and 6.5% of patients receiving a PP-EES (P = 0.95); TVF was 6.3% in patients receiving a BP-SES and 9.4% in patients receiving a PP-EES (P = 0.36). There were no significant differences in cardiac death, myocardial infarction and stent thrombosis rate. Conclusions: BP-SES achieved similar safety and efficacy outcomes as PP-EES in this ACS subgroup of CENTURY II study, at 24-month follow-up. This finding is hypothesis-generating and needs to be confirmed in larger trials with longer follow-up. - Highlights: • This study reported the 24-month clinical outcomes of new-generation BP-SES compared with PP-EES in ACS subgroup from CENTURY II study. • This is a pre-specified subgroup analysis of a large randomized, prospective, multicenter clinical trial. • The BP-SES showed good and comparable clinical performance as PP-EES at 24 months. • This substudy has a relatively small sample size and

  15. Temporary reversal by topotecan of marked insulin resistance in a patient with myelodysplastic syndrome: case report and possible mechanism for tumor necrosis factor alpha (TNF-alpha)-induced insulin resistance.

    Science.gov (United States)

    Huntington, M O; Krell, K E; Armour , W E; Liljenquist, J E

    2001-06-01

    Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity of the insulin receptor. We report here a remarkable degree of insulin resistance in a patient with adult respiratory distress syndrome and myelodysplasia.

  16. The prognostic value of monosomal karyotype (MK) in higher-risk patients with myelodysplastic syndromes treated with 5-Azacitidine. A retrospective analysis of the Hellenic (Greek) MDS Study Group.

    Science.gov (United States)

    Papageorgiou, Sotirios G; Vasilatou, Diamantina; Kontos, Christos K; Kotsianidis, Ioannis; Symeonidis, Argiris; Galanopoulos, Athanasios G; Hatzimichael, Eleftheria; Megalakaki, Aekaterini; Poulakidas, Elias; Diamantopoulos, Panagiotis; Vassilakopoulos, Theodoros; Zikos, Panagiotis; Papadaki, Helen; Mparmparousi, Despoina; Bouronikou, Eleni; Panayiotidis, Panayiotis; Viniou, Nora-Athina; Pappa, Vassiliki

    2018-04-16

    In this study, we investigated the incidence and prognostic impact of monosomal karyotype (MK) in 405 higher-risk MDS patients treated with 5-AZA. The MK was present in 66 out of 405 (16.3%) patients, most of whom had complex karyotype (CK). MK was strongly associated with CK and the cytogenetic risk defined according to IPSS-R, as well as with high-risk disease, according to IPSS (P=0.029), IPSS-R (PMDS treated with 5-AZA. Furthermore, we showed that in MDS with high or very-high IPSS-R risk score, MK can further distinguish patients with worse outcome. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  17. Allogeneic bone marrow transplantation with conditioning regimen to total body irradiation + thiotepa + melphalan for 35 patients with high-risk leukemia

    International Nuclear Information System (INIS)

    Yumura-Yagi, Keiko; Inoue, Masami; Okamura, Takayuki

    1997-01-01

    Thirty-five children with high-risk leukemia received an allogeneic bone marrow transplantation (BMT) following a pre-conditioning regimen consisting of total body irradiation, thiotepa and melphalan. Twenty-one patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 acute undifferentiated leukemia, 2 acute mixed lineage leukemia, 2 myelodysplastic syndrome and 2 juvenile chronic myeloid leukemia. Sixteen patients received BMT while in complete remission (CR), but 19 were not in CR. Eighteen patients received transplants from HLA-matched related donors, 15 from unrelated donors and 2 from HLA-mismatched related donors. Cyclosporin±methotrexate was used for graft-versus-host disease (GVHD) prophylaxis in the BMTs from related donors and tacrolimus±prednisolone in the BMTs from unrelated donors. Transplant-related death occurred in 12 patients; 5 acute GVHD, 4 infections (3 fungal infections, 1 Cytomegalovirus pneumonia), 1 intracranial haemorrhage and 2 chronic GVHD. Relapses were observed in 6 patients (69, 168, 175, 222, 275 and 609 days post BMT). Event-free survival rate at 2 years is 38.1% in CR patients and 36.9% in nonCR patients. (author)

  18. Sustained trilineage recovery and disappearance of abnormal chromosome clone in a patient with myelodysplastic syndrome following combination therapy with cytokines (granulocyte colony-stimulating factor and erythropoietin) and high-dose methylprednisolone.

    Science.gov (United States)

    Imai, Y; Fukuoka, T; Nakatani, A; Ohsaka, A; Takahashi, A

    1996-04-01

    We report a case of hypoplastic myelodyplastic syndrome (MDS) (refractory anemia (RA)) in which sustained trilineage haematological response and persistent disappearance of an abnormal chromosome clone were achieved after treatment with combination therapy of cytokines (granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Epo)) and methylprednisolone (mPSL) pulse dose. The patient's haematological recovery was rapid and maintained even after cessation of the therapy. In addition, the predominant chromosome clone 13q- in bone marrow cells disappeared in the fourth week. The patient's improved bone marrow haemopoiesis and disappearance of the abnormal chromosome has continued to the present, 13 months after treatment. The occurrence of both trilineage response and abnormal chromosome disappearance in MDS patients treated with cytokine(s) or steroids is rare. Combination therapy might therefore be advantageous in MDS.

  19. Design and rationale of the QUAZAR Lower-Risk MDS (AZA-MDS-003) trial: a randomized phase 3 study of CC-486 (oral azacitidine) plus best supportive care vs placebo plus best supportive care in patients with IPSS lower-risk myelodysplastic syndromes and poor prognosis due to red blood cell transfusion-dependent anemia and thrombocytopenia.

    Science.gov (United States)

    Garcia-Manero, Guillermo; Almeida, Antonio; Giagounidis, Aristoteles; Platzbecker, Uwe; Garcia, Regina; Voso, Maria Teresa; Larsen, Stephen R; Valcarcel, David; Silverman, Lewis R; Skikne, Barry; Santini, Valeria

    2016-01-01

    CC-486 is an oral formulation of the epigenetic modifier azacitidine. In an expanded phase 1 trial, CC-486 demonstrated clinical and biological activity in patients with International Prognostic Scoring System (IPSS) lower-risk (low- and intermediate-1-risk) myelodysplastic syndromes (MDS) with poor prognostic features including anemia and/or thrombocytopenia who may have required red blood cell or platelet transfusions. The overall response rate was 40 %, including hematologic improvement in 28 % of patients and RBC transfusion independence sustained for 56 days in 47 % of patients with baseline transfusion dependence. Based on the results of this study, the randomized, placebo-controlled phase 3 QUAZAR Lower-Risk MDS trial (AZA-MDS-003) was initiated. The design and rationale for this trial comparing CC-486 with placebo for the treatment of patients with IPSS lower-risk MDS with poor prognostic features are described. Patients must have IPSS lower-risk MDS with red blood cell (RBC) transfusion-dependent anemia and thrombocytopenia. Eligible patients are randomized 1:1 to receive 300 mg of CC-486 or placebo once daily for the first 21 days of 28-day treatment cycles. Disease status assessments occur at the end of cycle 6 and patients may continue to receive treatment unless there is evidence of progressive disease, lack of efficacy, or unacceptable toxicity. The primary endpoint is RBC transfusion independence for ≥ 84 days, assessed according to International Working Group 2006 criteria. Secondary endpoints include overall survival, hematologic response including platelet response and erythroid response, RBC transfusion independence for ≥ 56 days, duration of RBC transfusion independence, time to RBC transfusion independence, rate of acute myeloid leukemia (AML) progression, time to AML progression, clinically significant bleeding events, safety, health-related quality of life, and healthcare resource utilization. This study will provide data

  20. An Overview. High Risk Series.

    Science.gov (United States)

    General Accounting Office, Washington, DC.

    This report provides an overview of efforts undertaken by the U.S. General Accounting Office (GAO) in 1990 to review and report on federal program areas its work identified as high risk because of vulnerabilities to waste, fraud, abuse, and mismanagement. It reviews the current status of efforts to address these concerns. The six categories of…

  1. Cost-effectiveness of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infections among high-risk neutropenic patients in Spain

    Directory of Open Access Journals (Sweden)

    Grau Santiago

    2012-04-01

    Full Text Available Abstract Background We evaluated the cost-effectiveness of posaconazole compared with standard azole therapy (SAT; fluconazole or itraconazole for the prevention of invasive fungal infections (IFI and the reduction of overall mortality in high-risk neutropenic patients with acute myelogenous leukaemia (AML or myelodysplastic syndromes (MDS. The perspective was that of the Spanish National Health Service (NHS. Methods A decision-analytic model, based on a randomised phase III trial, was used to predict IFI avoided, life-years saved (LYS, total costs, and incremental cost-effectiveness ratio (ICER; incremental cost per LYS over patients' lifetime horizon. Data for the analyses included life expectancy, procedures, and costs associated with IFI and the drugs (in euros at November 2009 values which were obtained from the published literature and opinions of an expert committee. A probabilistic sensitivity analysis (PAS was performed. Results Posaconazole was associated with fewer IFI (0.05 versus 0.11, increased LYS (2.52 versus 2.43, and significantly lower costs excluding costs of the underlying condition (€6,121 versus €7,928 per patient relative to SAT. There is an 85% probability that posaconazole is a cost-saving strategy compared to SAT and a 97% probability that the ICER for posaconazole relative to SAT is below the cost per LYS threshold of €30,000 currently accepted in Spain. Conclusions Posaconazole is a cost-saving prophylactic strategy (lower costs and greater efficacy compared with fluconazole or itraconazole in high-risk neutropenic patients.

  2. Clinical high risk for psychosis

    DEFF Research Database (Denmark)

    van der Steen, Y; Gimpel-Drees, J; Lataster, T

    2017-01-01

    OBJECTIVE: The aim of this study was to assess associations between momentary stress and both affective and psychotic symptoms in everyday life of individuals at clinical high risk (CHR), compared to chronic psychotic patients and healthy controls, in search for evidence of early stress...... and 26 healthy controls. RESULTS: Multilevel models showed significantly larger associations between negative affect (NA) and activity-related stress for CHR patients than for psychotic patients (P = 0.008) and for CHR compared to controls (P

  3. Nuances of Morphology in Myelodysplastic Diseases in the Age of Molecular Diagnostics.

    Science.gov (United States)

    Shaver, Aaron C; Seegmiller, Adam C

    2017-10-01

    Morphologic dysplasia is an important factor in diagnosis of myelodysplastic syndrome (MDS). However, the role of dysplasia is changing as new molecular genetic and genomic technologies take a more prominent place in diagnosis. This review discusses the role of morphology in the diagnosis of MDS and its interactions with cytogenetic and molecular testing. Recent changes in diagnostic criteria have attempted to standardize approaches to morphologic diagnosis of MDS, recognizing significant inter-observer variability in assessment of dysplasia. Definitive correlates between cytogenetic/molecular and morphologic findings have been described in only a small set of cases. However, these genetic and morphologic tools do play a complementary role in the diagnosis of both MDS and other myeloid neoplasms. Diagnosis of MDS requires a multi-factorial approach, utilizing both traditional morphologic as well as newer molecular genetic techniques. Understanding these tools, and the interplay between them, is crucial in the modern diagnosis of myeloid neoplasms.

  4. Suspected myelodysplastic/myeloproliferative neoplasm in a feline leukemia virus-negative cat.

    Science.gov (United States)

    Weeden, Amy L; Taylor, Kyle R; Terrell, Scott P; Gallagher, Alexander E; Wamsley, Heather L

    2016-12-01

    A 10-year-old castrated Domestic Short-Haired cat was presented to a primary care veterinarian for a wellness examination and laboratory examination for monitoring of diabetes mellitus. The CBC revealed marked thrombocytosis, leukopenia and macrocytic, normochromic anemia. The cat tested negative for FeLV and feline immunodeficiency virus, but was positive for Mycoplasma haemominutum by PCR. Hematologic abnormalities were not responsive to therapy, so a repeat CBC and a bone marrow aspiration for cytology were performed. Additional blood smear findings included anisocytosis with megaloblastic erythroid precursors, large platelets, eosinophilic myelocytes and metamyelocytes, and rare unidentified blasts. The bone marrow smear was highly cellular, and the cytologic pattern was consistent with myelodysplastic syndrome with an erythroid predominance. At that time, 15% blasts were present. The cat was treated with a vitamin K 2 analog, doxycycline, and prednisolone, but without a clinical response. Within 3 months, euthanasia was elected due to declining quality of life, and a necropsy was performed. Postmortem bone marrow smears were highly cellular and dominated by monomorphic blasts of unknown line of origin (52%), persistent marked erythroid and megakaryocytic dysplasia, and ineffective erythropoiesis and granulopoiesis. Immunohistochemical, immunocytochemical, and cytochemical stains resulted in a diagnosis of acute myeloid leukemia of unclassified type. Additional histologic findings included mixed hepatitis with trematode infestation and lymphoplasmacytic interstitial nephritis with fibrosis. The marked thrombocytosis with myelodysplastic syndrome and the FeLV-negative status of this cat were unusual. The difficulty in classifying the myelodysplasia and subsequent leukemia highlights a need for further reporting and characterization of these types of disease. © 2016 American Society for Veterinary Clinical Pathology.

  5. Myelodysplastic/ Myeloproliferative Neoplasms Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are treated with chemotherapy or other drugs, stem cell transplant, supportive care, and targeted therapy. They include chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and atypical chronic myeloid leukemia (aCML). Learn about the clinical features and treatment options for these leukemias.

  6. Complementation of Myelodysplastic Syndrome Clones with Lentivirus Expression Libraries

    Science.gov (United States)

    2013-01-01

    Description HRAS Homo sapiens v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS), transcript 1 CDC25C Homo sapiens cell division cycle 25...homolog C (CDC25C), transcript variant 1 MYC Homo sapiens v-myc myeloctomatosis viral oncogene homolog (avian) (MYC) MAP3K7 Homo sapiens mitogen...activated protein kinase kinase kinase 7 (MAP3K7) MAP3K8 Homo sapiens mitogen-activated protein kinase kinase kinase 8 (MAP3K8) SF3B1 Homo sapiens

  7. Hematopoietic growth factors for the treatment of myelodysplastic syndromes

    DEFF Research Database (Denmark)

    Hansen, P B; Penkowa, M; Johnsen, H E

    1998-01-01

    with milder forms of MDS combined with low prestudy endogenous S-Epo levels. The possible synergistic effect of combining rhEpo with rhG-CSF or rhGM-CSF has been studied with erythropoietic response rates of about 40%. The safety of the cytokine administration seems acceptable with no significant stimulation...... of leukemic myelopoiesis and subsequent progression into overt acute myeloid leukemia. In conclusion, combinations of hematopoietic growth factors may be of clinical benefit in some patients with MDS. However, due to the cost and unpredictable clinical outcome there is a need for extended laboratory research...

  8. Iron overload and chelation therapy in myelodysplastic syndromes.

    Science.gov (United States)

    Temraz, Sally; Santini, Valeria; Musallam, Khaled; Taher, Ali

    2014-07-01

    Iron overload remains a concern in MDS patients especially those requiring recurrent blood transfusions. The consequence of iron overload may be more relevant in patients with low and intermediate-1 risk MDS who may survive long enough to experience such manifestations. It is a matter of debate whether this overload has time to yield organ damage, but it is quite evident that cellular damage and DNA genotoxic effect are induced. Iron overload may play a critical role in exacerbating pre-existing morbidity or even unmask silent ones. Under these circumstances, iron chelation therapy could play an integral role in the management of these patients. This review entails an in depth analysis of iron overload in MDS patients; its pathophysiology, effect on survival, associated risks and diagnostic options. It also discusses management options in relation to chelation therapy used in MDS patients and the impact it has on survival, hematologic response and organ function. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Regulation and Function of TIFAB in Myelodysplastic Syndrome

    Science.gov (United States)

    2014-08-01

    observation that del(5q) results in inappropriate activation of TRAF6 provides a strong rationale to study the contribution of TIFAB to deregulation of the...rationale to study the contribution of TIFAB to deregulation of the TRAF6 pathway in MDS. BODY Task 1. Plasmid constructs and validation...2011 Lecturer, Ulm University, Germany 2005-2010 Postdoctoral Fellow Research Focus: Identification and functional analysis of genetic and molecular

  10. Novel Therapeutic Approaches Targeting MDSC in Myelodysplastic Syndrome

    Science.gov (United States)

    2017-09-01

    mechanisms involved in the initiation of stem cell malignancies is critical for development of effective strategies for prevention and treatment...IL10); hematopoietic stem and progenitor cells (HSPC) 3. ACCOMPLISHMENTS What were the major goals of the project? The major goals of the project...pathway can cause reactive oxygen species (ROS)-induced genomic instability but BI 836858 reduced both ROS and the levels of double strand breaks and

  11. Loss of RhoB expression enhances the myelodysplastic phenotype of mammalian diaphanous-related Formin mDia1 knockout mice.

    Directory of Open Access Journals (Sweden)

    Aaron D DeWard

    Full Text Available Myelodysplastic syndrome (MDS is characterized by ineffective hematopoiesis and hyperplastic bone marrow. Complete loss or interstitial deletions of the long arm of chromosome 5 occur frequently in MDS. One candidate tumor suppressor on 5q is the mammalian Diaphanous (mDia-related formin mDia1, encoded by DIAPH1 (5q31.3. mDia-family formins act as effectors for Rho-family small GTP-binding proteins including RhoB, which has also been shown to possess tumor suppressor activity. Mice lacking the Drf1 gene that encodes mDia1 develop age-dependent myelodysplastic features. We crossed mDia1 and RhoB knockout mice to test whether the additional loss of RhoB expression would compound the myelodysplastic phenotype. Drf1(-/-RhoB(-/- mice are fertile and develop normally. Relative to age-matched Drf1(-/-RhoB(+/- mice, the age of myelodysplasia onset was earlier in Drf1(-/-RhoB(-/- animals--including abnormally shaped erythrocytes, splenomegaly, and extramedullary hematopoiesis. In addition, we observed a statistically significant increase in the number of activated monocytes/macrophages in both the spleen and bone marrow of Drf1(-/-RhoB(-/- mice relative to Drf1(-/-RhoB(+/- mice. These data suggest a role for RhoB-regulated mDia1 in the regulation of hematopoietic progenitor cells.

  12. The Psychosis High-Risk State

    Science.gov (United States)

    Fusar-Poli, Paolo; Borgwardt, Stefan; Bechdolf, Andreas; Addington, Jean; Riecher-Rössler, Anita; Schultze-Lutter, Frauke; Keshavan, Matcheri; Wood, Stephen; Ruhrmann, Stephan; Seidman, Larry J.; Valmaggia, Lucia; Cannon, Tyrone; Velthorst, Eva; De Haan, Lieuwe; Cornblatt, Barbara; Bonoldi, Ilaria; Birchwood, Max; McGlashan, Thomas; Carpenter, William; McGorry, Patrick; Klosterkötter, Joachim; McGuire, Philip; Yung, Alison

    2014-01-01

    Context During the past 2 decades, a major transition in the clinical characterization of psychotic disorders has occurred. The construct of a clinical high-risk (HR) state for psychosis has evolved to capture the prepsychotic phase, describing people presenting with potentially prodromal symptoms. The importance of this HR state has been increasingly recognized to such an extent that a new syndrome is being considered as a diagnostic category in the DSM-5. Objective To reframe the HR state in a comprehensive state-of-the-art review on the progress that has been made while also recognizing the challenges that remain. Data Sources Available HR research of the past 20 years from PubMed, books, meetings, abstracts, and international conferences. Study Selection and Data Extraction Critical review of HR studies addressing historical development, inclusion criteria, epidemiologic research, transition criteria, outcomes, clinical and functional characteristics, neurocognition, neuroimaging, predictors of psychosis development, treatment trials, socioeconomic aspects, nosography, and future challenges in the field. Data Synthesis Relevant articles retrieved in the literature search were discussed by a large group of leading worldwide experts in the field. The core results are presented after consensus and are summarized in illustrative tables and figures. Conclusions The relatively new field of HR research in psychosis is exciting. It has the potential to shed light on the development of major psychotic disorders and to alter their course. It also provides a rationale for service provision to those in need of help who could not previously access it and the possibility of changing trajectories for those with vulnerability to psychotic illnesses. PMID:23165428

  13. Resuscitation of newborn in high risk deliveries

    International Nuclear Information System (INIS)

    Yousaf, U.F.; Hayat, S.

    2015-01-01

    High risk deliveries are usually associated with increased neonatal mortality and morbidity. Neonatal resuscitation can appreciably affect the outcome in these types of deliveries. Presence of personnel trained in basic neonatal resuscitation at the time of delivery can play an important role in reducing perinatal complications in neonates at risk. The study was carried out to evaluate the effects of newborn resuscitation on neonatal outcome in high risk deliveries. Methods: This descriptive case series was carried out at the Department of Obstetrics and Gynecology, Jinnah Hospital, Lahore. Ninety consecutive high risk deliveries were included and attended by paediatricians trained in newborn resuscitation. Babies delivered by elective Caesarean section, normal spontaneous vaginal deliveries and still births were excluded. Neonatal resuscitation was performed in babies who failed to initiate breathing in the first minute after birth. Data was analyzed using SPSS-16.0. Results: A total of 90 high risk deliveries were included in the study. Emergency caesarean section was the mode of delivery in 94.4% (n=85) cases and spontaneous vaginal delivery in 5.6% (n=5). Preterm pregnancy was the major high risk factor. Newborn resuscitation was required in 37.8% (n=34) of all high risk deliveries (p=0.013). All the new-borns who required resuscitation survived. Conclusion: New-born resuscitation is required in high risk pregnancies and personnel trained in newborn resuscitation should be available at the time of delivery. (author)

  14. The obstetric antiphospholipid syndrome

    NARCIS (Netherlands)

    Derksen, R. H. W. M.; de Grootb, Ph. G.

    The association of persistent presence of circulating antiphospholipid antibodies and thromboembolic events, (recurrent) pregnancy loss or both is termed antiphospholipid syndrome. Pregnancies in women with the syndrome should be regarded as at high-risk for complications. Optimal management

  15. [A model list of high risk drugs].

    Science.gov (United States)

    Cotrina Luque, J; Guerrero Aznar, M D; Alvarez del Vayo Benito, C; Jimenez Mesa, E; Guzman Laura, K P; Fernández Fernández, L

    2013-12-01

    «High-risk drugs» are those that have a very high «risk» of causing death or serious injury if an error occurs during its use. The Institute for Safe Medication Practices (ISMP) has prepared a high-risk drugs list applicable to the general population (with no differences between the pediatric and adult population). Thus, there is a lack of information for the pediatric population. The main objective of this work is to develop a high-risk drug list adapted to the neonatal or pediatric population as a reference model for the pediatric hospital health workforce. We made a literature search in May 2012 to identify any published lists or references in relation to pediatric and/or neonatal high-risk drugs. A total of 15 studies were found, from which 9 were selected. A model list was developed mainly based on the ISMP one, adding strongly perceived pediatric risk drugs and removing those where the pediatric use was anecdotal. There is no published list that suits pediatric risk management. The list of pediatric and neonatal high-risk drugs presented here could be a «reference list of high-risk drugs » for pediatric hospitals. Using this list and training will help to prevent medication errors in each drug supply chain (prescribing, transcribing, dispensing and administration). Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  16. Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group.

    Science.gov (United States)

    Lübbert, Michael; Suciu, Stefan; Hagemeijer, Anne; Rüter, Björn; Platzbecker, Uwe; Giagounidis, Aristoteles; Selleslag, Dominik; Labar, Boris; Germing, Ulrich; Salih, Helmut R; Muus, Petra; Pflüger, Karl-Heinz; Schaefer, Hans-Eckart; Bogatyreva, Lioudmila; Aul, Carlo; de Witte, Theo; Ganser, Arnold; Becker, Heiko; Huls, Gerwin; van der Helm, Lieke; Vellenga, Edo; Baron, Frédéric; Marie, Jean-Pierre; Wijermans, Pierre W

    2016-01-01

    In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lübbert et al., Haematologica 97:393-401, 2012). We now analyzed 206 myelodysplastic syndrome (MDS) patients (88 % of 233 patients randomized in the EORTC/GMDSSG phase III trial 06011, 61 of them with RAEBt, i.e. AML by WHO) with cytogenetics informative for MK status.. Endpoints are the following: complete/partial (CR/PR) and overall response rate (ORR) and progression-free (PFS) and overall survival (OS). Cytogenetic subgroups are the following: 63 cytogenetically normal (CN) patients, 143 with cytogenetic abnormalities, 73 of them MK-negative (MK-), and 70 MK-positive (MK+). These MK+ patients could be divided into 17 with a single autosomal monosomy (MK1) and 53 with at least two monosomies (MK2+). ORR with DAC in CN patients: 36.1 %, in MK- patients: 16.7 %, in MK+ patients: 43.6 % (MK1: 44.4 %, MK2+ 43.3 %). PFS was prolonged by DAC compared to best supportive care (BSC) in the CN (hazard ratio (HR) 0.55, 99 % confidence interval (CI), 0.26; 1.15, p = 0.03) and MK2+ (HR 0.50; 99 % CI, 0.23; 1.06, p = 0.016) but not in the MK-, MK+, and MK1 subgroups. OS was not improved by DAC in any subgroup. In conclusion, we demonstrate for the first time in a randomized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC.

  17. High-Risk Series: An Update

    Science.gov (United States)

    2015-02-01

    the Medicare Trustees, the Office of the Actuary , and the Congressional Budget Office have raised concerns about whether some of the Medicare... actuarially sound. For more information, see the National Flood Insurance Program section of this High-Risk report. Among other things, the report...and mathematics (STEM) functional community. In addition to the efforts of the Working Group, the President’s Fiscal Year 2013 budget—released in

  18. The syndromic child and anaesthesia

    African Journals Online (AJOL)

    fourth and sixth arches give rise to the larynx and trachea, and ... Keywords: anaesthesia, syndrome, atlantoaxial joint, branchial arches, Down's syndrome, 22q11 deletion .... which causes proximal weakness and a high risk of malignant.

  19. High risk process control system assessment methodology

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Venetia [Pontificia Universidade Catolica do Rio de Janeiro (PUC-Rio), RJ (Brazil); Zamberlan, Maria Cristina [National Institute of Tehnology (INT), Rio de Janeiro, RJ (Brazil). Human Reliability and Ergonomics Research Group for the Oil, Gas and Energy Sector

    2009-07-01

    The evolution of ergonomics methodology has become necessary due to the dynamics imposed by the work environment, by the increase of the need of human cooperation and by the high interaction between various sections within a company. In the last 25 years, as of studies made in the high risk process control, we have developed a methodology to evaluate these situations that focus on the assessment of activities and human cooperation, the assessment of context, the assessment of the impact of work of other sectors in the final activity of the operator, as well as the modeling of existing risks. (author)

  20. The high-risk plaque initiative

    DEFF Research Database (Denmark)

    Falk, Erling; Sillesen, Henrik; Muntendam, Pieter

    2011-01-01

    The High-Risk Plaque (HRP) Initiative is a research and development effort to advance the understanding, recognition, and management of asymptomatic individuals at risk for a near-term atherothrombotic event such as myocardial infarction or stroke. Clinical studies using the newest technologies...... have been initiated, including the BioImage Study in which novel approaches are tested in a typical health plan population. Asymptomatic at-risk individuals were enrolled, including a survey-only group (n = 865), a group undergoing traditional risk factor scoring (n = 718), and a group in which all...

  1. Laser prostatectomy in high-risk patients

    International Nuclear Information System (INIS)

    Tayib, Abdulmalik M.

    2008-01-01

    Objective was to evaluate the short-term tolerability and outcome of high power green light potassium titanyl phosphate laser prostatectomy in high-risk patients with symptomatic benign prostatic hyperplasia. Eleven high risk operative patients were included in this study at the International Medical Center, Jeddah, Kingdom of Saudi Arabia, between January and September 2007. Patients enrolled in this study underwent preoperative and postoperative, cardiac and anesthesia evaluation. Clinical presentations, ultrasound of urinary tract and preoperative laboratory investigation were recorded. All patients underwent high power green light laser prostatectomy using the green light photo vaporization system with setting of 120 watts. The intraoperative and postoperative complications and follow-up were recorded. The patient's age varied between 65-82 years with a mean age of 75.3+-8.6 years old. Seven patients presented with refractory acute urinary retention and 4 patients presented with severe lower urinary tract symptoms. The average prostate volume was 61.22 cc. All patients had uneventful intra- and postoperative course, without the intensive care. The average blood loss was insignificant and only one of the patients required blood transfusion. Foley catheters were removed one day after the procedure. All patients voided satisfactorily after removal of catheter and 8 patients complained of urgency. High power green light laser prostatectomy is a safe and effective method of treating symptomatic benign prostatic hyperplasia in patients with high operative risk. (author)

  2. New information on high risk breast screening

    International Nuclear Information System (INIS)

    Riedl, C.C.; Ponhold, L.; Gruber, R.; Pinker, K.; Helbich, T.H.

    2010-01-01

    Women with an elevated risk for breast cancer require intensified screening beginning at an early age. Such high risk screening differs considerably from screening in the general population. After an expert has evaluated the exact risk a breast MRI examination should be offered at least once a year and beginning latest at the age of 30 depending on the patients risk category. Complementary mammograms should not be performed before the age of 35. An additional ultrasound examination is no longer recommended. To ensure a high sensitivity and specificity high risk screening should be performed only at a nationally or regionally approved and audited service. Adequate knowledge about the phenotypical characteristics of familial breast cancer is essential. Besides the common malignant phenotypes, benign morphologies (round or oval shape and smooth margins) as well as a low prevalence of calcifications have been described. Using MRI benign contrast media kinetics as well as non-solid lesions with focal, regional and segmental enhancement can often be visualized. (orig.) [de

  3. Prescription of the High Risk Narcotics and Trading or Illicit Purchasing of High Risk Narcotics

    Directory of Open Access Journals (Sweden)

    Nicoleta-Elena Buzatu

    2012-05-01

    Full Text Available The present essay will analyze the offence of prescribing high risk narcotics and trading or illicit purchasing of high risk narcotics, as it was regulated - together with other offences - by Law no 143 of July 26, 2000 on preventing and fighting against the traffic and illicit consumption of narcotics. The same law defines the meaning of such a phrase “substances which are under national control” by mentioning the fact that they are the narcotics and their precursors listed in Annexes I-IV of the law. The analysis of the offence of prescribing the high risk narcotics and trading or illicit purchasing of high risk narcotics is following the already known structure mentioned in the doctrine and which consists of: object and subjects of the offence, its constituent content: the objective side with its material element, the immediate consequence and causality connections; the subjective side of the offence, as well as forms and modalities of these offences, and the applicable sanctions, of course.

  4. People at High Risk of Developing Flu-Related Complications

    Science.gov (United States)

    ... Influenza Types Seasonal Avian Swine Variant Pandemic Other People at High Risk of Developing Flu–Related Complications ... related complications if they get sick with influenza. People at High Risk for Developing Flu-Related Complications ...

  5. Imaging Frontostriatal Function in Ultra-High-Risk, Early, and Chronic Schizophrenia During Executive Processing

    Science.gov (United States)

    Morey, Rajendra A.; Inan, Seniha; Mitchell, Teresa V.; Perkins, Diana O.; Lieberman, Jeffrey A.; Belger, Aysenil

    2009-01-01

    Context Individuals experiencing prodromal symptoms of schizophrenia (ultra-high-risk group) demonstrate impaired performance on tasks of executive function, attention, and working memory. The neurobiological underpinnings of such executive deficits in ultra-high-risk individuals remains unclear. Objective We assessed frontal and striatal functions during a visual oddball continuous performance task, in ultra-high-risk, early, and chronic schizophrenic patients with the use of functional magnetic resonance imaging. Design Cross-sectional case-control design. Setting Community; outpatient clinic. Patients Fifty-two individuals (control, n = 16; ultra-high risk, n = 10; early, n = 15; chronic, n = 11) from a referred clinical sample and age- and sex-matched control volunteers underwent scanning. Main Outcome Measures Percentage of active voxels and percentage signal change calculated for the anterior cingulate gyrus (ACG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), basal ganglia, and thalamus. Performance on the visual oddball task was measured with percentage of hits and d′ (a measure based on the hit rate and the false-alarm rate). Results The ultra-high-risk group showed significantly smaller differential activation between task-relevant and task-irrelevant stimuli in the frontal regions (ACG, IFG, MFG) than the control group. Frontostriatal activation associated with target stimuli in the early and chronic groups was significantly lower than the control group, while the ultra-high-risk group showed a trend toward the early group. Conclusions Our findings suggest that prefrontal function begins to decline before the onset of syndromally defined illness and hence may represent a vulnerability marker in assessing the risk of developing psychotic disorders among ultra-high-risk individuals. PMID:15753238

  6. Preliminary psychometric properties of the brief Negative Symptom Scale in youth at Clinical High-Risk for psychosis.

    Science.gov (United States)

    Strauss, Gregory P; Chapman, Hannah C

    2018-03-01

    Preliminary psychometric properties of an adapted version of the Brief Negative Symptom Scale (BNSS) are reported in youth at Clinical High-Risk for psychosis (CHR). Participants included 29 CHR youth who met criteria for a prodromal syndrome on the Structured Interview for Prodromal Syndromes (SIPS). The adapted BNSS demonstrated excellent internal consistency, convergent validity, and discriminant validity, suggesting that the BNSS has utility for assessing negative symptoms in a CHR population. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. 2017 Taiwan lipid guidelines for high risk patients

    Directory of Open Access Journals (Sweden)

    Yi-Heng Li

    2017-04-01

    lowering therapies, adjunctive treatment with mipomersen, lomitapide, or PCSK9 inhibitors become necessary to further reduce LDL-C in patients with FH. Overall, these recommendations are to help the health care professionals in Taiwan to treat hyperlipidemia with current scientific evidences. We hope the prescription rate of lipid lowering drugs and control rate of hyperlipidemia in high risk patients could be increased by implementation of the clinical guidelines. The major purpose is to improve clinical outcomes of these high risk patients through the control of hyperlipidemia.

  8. [Targeting high-risk drugs to optimize clinical pharmacists' intervention].

    Science.gov (United States)

    Mouterde, Anne-Laure; Bourdelin, Magali; Maison, Ophélie; Coursier, Sandra; Bontemps, Hervé

    2016-12-01

    By the Order of 6 April 2011, the pharmacist must validate all the prescriptions containing "high-risk drugs" or those of "patients at risk". To optimize this clinical pharmacy activity, we identified high-risk drugs. A list of high-risk drugs has been established using literature, pharmacists' interventions (PI) performed in our hospital and a survey sent to hospital pharmacists. In a prospective study (analysis of 100 prescriptions for each high-risk drug selected), we have identified the most relevant to target. We obtained a statistically significant PI rate (P<0.05) for digoxin, oral anticoagulants direct, oral methotrexate and colchicine. This method of targeted pharmaceutical validation based on high-risk drugs is relevant to detect patients with high risk of medicine-related illness. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  9. Neurocognitive performance of a community-based sample of young people at putative ultra high risk for psychosis: support for the processing speed hypothesis.

    LENUS (Irish Health Repository)

    Kelleher, Ian

    2013-01-01

    A wide variety of neurocognitive deficits have been reported for help-seeking individuals who are at clinical or ultra high risk for psychosis based on fulfilling set criteria for prodromal syndromes\\/at risk mental states. We wished to extend this research by conducting the first population-based assessment of prodromal syndromes and associated neurocognition.

  10. Continuous glucose monitoring system and new era of early diagnosis of diabetes in high risk groups

    Directory of Open Access Journals (Sweden)

    Ashraf Soliman

    2014-01-01

    Full Text Available Continuous glucose monitoring (CGM systems are an emerging technology that allows frequent glucose measurements to monitor glucose trends in real time. Their use as a diagnostic tool is still developing and appears to be promising. Combining intermittent glucose self-monitoring (SGM and CGM combines the benefits of both. Significant improvement in the treatment modalities that may prevent the progress of prediabetes to diabetes have been achieved recently and dictates screening of high risk patients for early diagnosis and management of glycemic abnormalities. The use of CGMS in the diagnosis of early dysglycemia (prediabetes especially in high risk patients appears to be an attractive approach. In this review we searched the literature to investigate the value of using CGMS as a diagnostic tool compared to other known tools, namely oral glucose tolerance test (OGTT and measurement of glycated hemoglobin (HbA1C in high risk groups. Those categories of patients include adolescents and adults with obesity especially those with family history of type 2 diabetes mellitus, polycystic ovary syndrome (PCO, gestational diabetes, cystic fibrosis, thalassemia major, acute coronary syndrome (ACS, and after renal transplantation. It appears that the ability of the CGMS for frequently monitoring (every 5 min glucose changes during real-life settings for 3 to 5 days stretches the chance to detect more glycemic abnormalities during basal and postprandial conditions compared to other short-timed methods.

  11. High risk for obstructive sleep apnea in patients with acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Carla Renata Silva Andrechuk

    2015-10-01

    Full Text Available Objectives: to stratify the risk for obstructive sleep apnea in patients with acute myocardial infarction, treated at a public, tertiary, teaching hospital of the state of São Paulo, Brazil, and to identify related sociodemographic and clinical factors.Method: cross-sectional analytical study with 113 patients (mean age 59.57 years, 70.8% male. A specific questionnaire was used for the sociodemographic and clinical characterization and the Berlin Questionnaire for the stratification of the risk of obstructive sleep apnea syndrome.Results: the prevalence of high risk was 60.2% and the outcome of clinical worsening during hospitalization was more frequent among these patients. The factors related to high risk were body mass index over 30 kg/m2, arterial hypertension and waist circumference indicative of cardiovascular risk, while older age (60 years and over constituted a protective factor.Conclusion: considering the high prevalence of obstructive sleep apnea and its relation to clinical worsening, it is suggested that nurses should monitor, in their clinical practice, people at high risk for this syndrome, guiding control measures of modifiable factors and aiming to prevent the associated complications, including worsening of cardiovascular diseases.

  12. Impact Of Mutation-derived Antigens In Immune Recognition Of Hematological Malignancies, Specifically Myeloid Dysplastic Syndromes (MDS)

    DEFF Research Database (Denmark)

    Saini, Sunil Kumar; Dorfmüller, S.; Bjerregaard, Anne-Mette

    2016-01-01

    Mutation-derived neoepitopes have been suggested as a major component for immune recognition of solid tumors with a high mutational load, e.g. Melanoma and Non-Small-Cell Lung Cancer (NSCLC). Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms characterized by increasing...

  13. Classificações morfológicas das síndromes mielodisplásicas: da classificação Franco-Americana-Britânica (FAB à classificação da Organização Mundial da Saúde (OMS Morphologic classifications of myelodysplastic syndromes: from FAB to WHO

    Directory of Open Access Journals (Sweden)

    Teresa C. Bortolheiro

    2006-09-01

    Full Text Available A classificação inicial das síndromes mielodisplásicas (SMD foi realizada em 1976, pelo grupo FAB, e era baseada em parâmetros morfológicos observados no sangue periférico e na medula óssea. A classificação FAB foi revisada em 1982 e utilizada nos últimos 25 anos como guia para melhor compreensão desse heterogêneo grupo de doenças. Em 2001, a OMS publicou uma nova classificação, com modificações significativas nos diversos subgrupos da FAB, com o intuito de agrupar melhor subtipos com comportamento clínico semelhante. A mudança mais importante foi a diminuição do número mínimo de blastos para o diagnóstico de LMA de 30% para 20%, causando o desaparecimento do subtipo AREB-T. Esta é também a mudança mais polêmica, havendo inúmeras publicações discutindo as evidentes diferenças clínicas e biológicas entre SMD e LMA, sendo unânime a opinião de que apenas o número de blastos é insuficiente para a escolha da terapêutica. Outro ponto importante foi a diferenciação de grupos com displasia em única e em múltiplas linhagens, que mostra ter grande importância para o prognóstico. Diversos estudos têm sido publicados, comparando as classificações FAB e OMS, reconhecendo a grande contribuição da classificação FAB para a melhor compreensão das SMD, bem como suas falhas e tentando validar as mudanças propostas pela classificação da OMS e identificar pontos passíveis de modificação.The initial classification of the myelodisplastic syndromes (MDS was compiled in 1976 by the FAB group and was based on morphological parameters observed in the peripheral blood and in the bone marrow. The FAB classification was revised in 1982 and has been used in the last 25 years as a guide for a better understanding of this heterogeneous group of diseases. In 2001, the WHO published a new classification with significant modifications in the diverse subgroups of FAB with the intention of obtaining a better grouping of the

  14. Natriuretic peptides: prediction of cardiovascular disease in the general population and high risk populations

    DEFF Research Database (Denmark)

    Hildebrandt, Per

    2009-01-01

    (General Practitioner) setting as in the acute setting. Supporting this use is a very strong prognostic value of the natriuretic peptides. This has been shown in as well heart failure as acute coronary syndromes, but also in the general population and in high-risk groups as patients with diabetes......, hypertension and coronary artery disease. This has of course raised interest for the use of the natriuretic peptides as a risk marker and for screening for heart failure with reduced systolic function in these populations. In symptomatic persons and in high risk populations, the natriuretic peptides have...... demonstrated a high sensitivity for ruling out the disease, if the right decision limits are choosen. Thus the number of normal echocardiographies can be reduced. More recently, the use in screening asymptomatic persons for left ventricular systolic dysfunction has gained more interest. In the unselected...

  15. Alcohol consumption and high risk sexual behaviour among female ...

    African Journals Online (AJOL)

    Alcohol consumption has been associated with high risk sexual behaviour among key populations such as female sex workers. We explored the drivers of alcohol consumption and its relationship to high risk sexual behaviour. Participants were drawn from a cohort of 1 027 women selected from 'hot spots' in the suburbs of ...

  16. Correlation between high-risk pregnancy and developmental delay ...

    African Journals Online (AJOL)

    Background: The future development of children is considered more than ever now due to the advances in medical knowledge and thus the increase in survival rates of high-risk infants. This study investigated the correlation between high-risk pregnancy and developmental delay in children aged 4- 60 months. Methods: ...

  17. Drug response prediction in high-risk multiple myeloma

    DEFF Research Database (Denmark)

    Vangsted, A J; Helm-Petersen, S; Cowland, J B

    2018-01-01

    from high-risk patients by GEP70 at diagnosis from Total Therapy 2 and 3A to predict the response by the DRP score of drugs used in the treatment of myeloma patients. The DRP score stratified patients further. High-risk myeloma with a predicted sensitivity to melphalan by the DRP score had a prolonged...

  18. Elevated level of serum triglyceride among high risk stress bank ...

    African Journals Online (AJOL)

    The objective of this study was to estimate lipid profile among high risk stress bank employees' correlated with heart disorders in Riyadh, Saudi Arabia. A total of 129 patients with high risk stress employees were involved in this study, which were divided into 69 males and 60 females between the age of 25 to 55 years.

  19. Resveratrol Suppresses Growth and Migration of Myelodysplastic Cells by Inhibiting the Expression of Elevated Cyclin D1 (CCND1).

    Science.gov (United States)

    Zhou, Wei; Xu, Shilin; Ying, Yi; Zhou, Ruiqing; Chen, Xiaowei

    2017-11-01

    Myelodysplastic syndromes (MDS) are a group of heterogeneous diseases characterized by poorly formed blood cells. We wanted to elucidate the underlying molecular mechanism to better determine pathogenesis, prognosis, diagnosis, and treatment for patients with MDS. We compared gene expression levels between normal and MDS tissue samples by immunohistochemical analysis. We studied the proliferation, survival, and migration of MDS cells using the EDU assay, colony formation, and transwell assays. We assessed the apoptotic rate and cell cycle status using flow cytometry and Hoechst staining. Finally, we evaluated RNA and protein expressions using polymerase chain reaction and Western blots, respectively. We found that resveratrol suppressed SKM-1 (an advanced MDS cell line) proliferation in a dose-dependent manner. Consistent with this finding, the EDU and colony formation assays also showed that resveratrol inhibited SKM-1 growth. Moreover, flow cytometry and Hoechst 33258 staining demonstrated that resveratrol induced apoptosis and a change in cell cycle status in SKM-1 cells, while the transwell assay showed that resveratrol reduced the migratory ability of SKM-1 cells. Resveratrol also decreased the expression of CCND1 (a gene that encodes the cyclin D1 protein) and increased expressions of KMT2A [lysine (K)-specific methyltransferase 2A] and caspase-3, suggesting that resveratrol exerts its effect by regulating CCND1 in SKM-1 cells. In addition, a combination of resveratrol and the PI3K/AKT inhibitor LY294002 exhibited a stronger inhibitory effect on the SKM-1 cells, compared with resveratrol alone. Our study proved that resveratrol suppresses SKM-1 growth and migration by inhibiting CCND1 expression. This finding provides novel insights into the pathogenesis of MDS and might help develop new diagnosis and treatment for patients with MDS.

  20. Disturbed functional connectivity of cortical activation during semantic discrimination in patients with schizophrenia and subjects at genetic high-risk.

    Science.gov (United States)

    Li, Xiaobo; Branch, Craig A; Nierenberg, Jay; Delisi, Lynn E

    2010-03-01

    Schizophrenia has a strong genetic component that is relevant to the understanding of the pathophysiology of the syndrome. Thus, recent investigations have shifted from studies of diagnosed patients with schizophrenia to examining their unaffected relatives. Previous studies found that during language processing, relatives thought to be at genetic high-risk for the disorder exhibit aberrant functional activation in regions of language processing, specifically in the left inferior frontal gyrus (Broca's area). However, functional connectivity among the regions involved in language pathways is not well understood. In this study, we examined the functional connectivity between a seed located in Broca's area and the remainder of the brain during a visual lexical decision task, in 20 schizophrenia patients, 21 subjects at genetic high risk for the disorder and 21 healthy controls. Both the high-risk subjects and patients showed significantly reduced activation correlations between seed and regions related to visual language processing. Compared to the high-risk subjects, the schizophrenia patients showed even fewer regions that were correlated with the seed regions. These results suggest that there is aberrant functional connectivity within cortical language circuitry in high-risk subjects and patients with schizophrenia. Broca's area, which is one of the important regions for language processing in healthy controls, had a significantly reduced role in the high-risk subjects and patients with schizophrenia. Our findings are consistent with the existence of an underlying biological disturbance that begins in genetically at risk individuals and progresses to a greater extent in those who eventually develop schizophrenia.

  1. Radical prostatectomy for high-risk prostate cancer.

    Science.gov (United States)

    Yossepowitch, Ofer; Eastham, James A

    2008-06-01

    Consensus recommendations for the identification and treatment of men whose apparent organ confined prostate cancer has high risk features are lacking. Despite ongoing refinements in surgical technique and improvements in morbidity and functional outcomes, the tradition of steering high-risk patients away from radical prostatectomy (RP) remains steadfast. We performed a medical literature search in English using MEDLINE/PubMed that addressed high risk prostate cancer. We analyzed the literature with respect to the historical evolution of this concept, current risk stratification schemes and treatment guidelines and related short and long term outcomes following RP. Contemporary evidence suggest that patients classified with high-risk prostate cancer by commonly used definitions do not have a uniformly poor prognosis after RP. Many cancers categorized clinically as high risk are actually pathologically confined to the prostate, and most men with such cancers who undergo RP are alive and free of additional therapy long after surgery. RP in the high-risk setting appears to be associated with a similar morbidity as in lower-risk patients. Men with clinically localized high-risk prostate cancer should not be categorically disqualified from local definitive therapy with RP. With careful attention to surgical technique, cancer control rates should improve further, and adverse effects on quality of life after RP should continue to decrease.

  2. The Very High Risk Prostate Cancer – a Contemporary Update

    Science.gov (United States)

    Mano, Roy; Eastham, James; Yossepowitch, Ofer

    2017-01-01

    Background Treatment of high-risk prostate cancer has evolved considerably over the past two decades, yet patients with very high-risk features may still experience poor outcome despite aggressive therapy. We review the contemporary literature focusing on current definitions, role of modern imaging and treatment alternatives in very high-risk prostate cancer. Methods We searched the MEDLINE database for all clinical trials or practice guidelines published in English between 2000 – 2016 with the following search terms: ‘prostatic neoplasms’ (MeSH Terms) AND (‘high risk’ (keyword) OR ‘locally advanced’ (keyword) OR ‘node positive’ (keyword)). Abstracts pertaining to very high-risk prostate cancer were evaluated and 40 pertinent studies served as the basis for this review. Results The term ‘very’ high-risk prostate cancer remains ill defined. The EAU and NCCN guidelines provide the only available definitions, categorizing those with clinical stage T3-4 or minimal nodal involvement as very-high risk irrespective of PSA level or biopsy Gleason score. Modern imaging with mpMRI and PET-PSMA scans plays a role in pretreatment assessment. Local definitive therapy by external beam radiation combined with androgen deprivation is supported by several randomized clinical trials whereas the role of surgery in the very high-risk setting combined with adjuvant radiation/ androgen deprivation therapy is emerging. Growing evidence suggest neoadjuvant taxane based chemotherapy in the context of a multimodal approach may be beneficial. Conclusions Men with very high-risk tumors may benefit from local definitive treatment in the setting of a multimodal regimen, offering local control and possibly cure in well selected patients. Further studies are necessary to better characterize the ‘very’ high-risk category and determine the optimal therapy for the individual patient. PMID:27618950

  3. 2017 Taiwan lipid guidelines for high risk patients.

    Science.gov (United States)

    Li, Yi-Heng; Ueng, Kwo-Chang; Jeng, Jiann-Shing; Charng, Min-Ji; Lin, Tsung-Hsien; Chien, Kuo-Liong; Wang, Chih-Yuan; Chao, Ting-Hsing; Liu, Ping-Yen; Su, Cheng-Huang; Chien, Shih-Chieh; Liou, Chia-Wei; Tang, Sung-Chun; Lee, Chun-Chuan; Yu, Tse-Ya; Chen, Jaw-Wen; Wu, Chau-Chung; Yeh, Hung-I

    2017-04-01

    statin to consolidate the CV protection in CKD patients. Mutations in LDL receptor, apolipoprotein B and PCSK9 genes are the common causes of FH. Diagnosis of FH usually depends on family history, clinical history of premature CAD, physical findings of xanthoma or corneal arcus and high levels of LDL-C. In addition to conventional lipid lowering therapies, adjunctive treatment with mipomersen, lomitapide, or PCSK9 inhibitors become necessary to further reduce LDL-C in patients with FH. Overall, these recommendations are to help the health care professionals in Taiwan to treat hyperlipidemia with current scientific evidences. We hope the prescription rate of lipid lowering drugs and control rate of hyperlipidemia in high risk patients could be increased by implementation of the clinical guidelines. The major purpose is to improve clinical outcomes of these high risk patients through the control of hyperlipidemia. Copyright © 2016. Published by Elsevier B.V.

  4. Sensation seeking in males involved in recreational high risk sports

    OpenAIRE

    M Guszkowska; A Bołdak

    2010-01-01

    The study examined sensation seeking intensity level in males involved in recreational high risk sports and investigated whether its level depends on type of sport practised. Additionally, in case of parachutists, sport experience of study participants were scrutinised with regard to its possible impact on the level of sensation seeking.The research involved 217 males aged 17 to 45, practising recreational high risk sports, namely: parachuting (n=98); wakeboarding (n=30); snowboarding (n=30);...

  5. A social work study high-risk behavior among teenagers

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Iravani

    2012-01-01

    Full Text Available Teenagers are believed the people who are supposed to build the world's future. High-risk behaviors such as addiction to drugs, smoking cigarettes, sex, etc. could significantly hurts teenagers and there must be some supporting programs to reduce these issues as much as possible. This paper performs an empirical investigation to study the different factors influencing high- risk behavior among teenagers who live in a city of Esfahan, Iran. The proposed study designs a questionnaire and distribute between two groups of female and male teenagers. The results indicate that while there is a meaningful relationship between high-risk behaviors and average high school marks among male students there is no meaningful relationship between high-risk behaviors and high school grades among female students. The results also indicate that there is a meaningful difference between gender and high-risk behavior. The season of birth for female and male students is another important factor for having high-risk behaviors. While the order of birth plays an important role among male students, the order of birth is not an important factor among female teenagers. Finally, the results indicate that teenagers' parental financial affordability plays a vital role on both female and male teenagers.

  6. Chromosomal instability in acute myelocytic leukemia and myelodysplastic syndrome patients among atomic bomb survivors

    International Nuclear Information System (INIS)

    Nakanishi, Mitsue; Tanaka, Kimio; Shintani, Takahiro; Takahashi, Tomoko; Kamada, Nanao

    1999-01-01

    To clarify the mechanism of leukemogenesis in atomic bomb survivors, leukemic cells were investigated using fluorescence in situ hybridization (FISH) analysis on the basis of conventional G-banding in patients with a history of radiation exposure and also in de novo patients. Conventional G-banding showed higher incidences (p<0.005) of structural and numerical abnormalities without any specific types of chromosome aberrations in the group exposed to a dose of more than one Gy, compared to the non-exposed group. FISH analysis revealed significantly higher incidences (P<0.05) of subclones with monosomy 7 and deletion of the 20q13.2 region, which were not found in conventional cytogenetic analysis in the exposed group (more than one Gy) compared to the non-exposed controls. Furthermore, segmental jumping translocation (SJT) of the c-MYC gene region was observed only in the exposed group. These chromosomal instability suggested that the leukemic cells from the heavily exposed patients contained persistent cellular genetic instability which may strongly influence the development of leukemia in people exposed to radiation. (author)

  7. DNA instability in low-risk myelodysplastic syndromes: refractory anemia with or without ring sideroblasts.

    Czech Academy of Sciences Publication Activity Database

    Novotná, Božena; Neuwirtová, R.; Šišková, M.; Bagryantseva, Yana

    2008-01-01

    Roč. 17, č. 14 (2008), s. 2144-2149 ISSN 0964-6906 R&D Projects: GA MZd NR8265 Institutional research plan: CEZ:AV0Z50390512 Keywords : Anemia * DNA Subject RIV: FD - Oncology ; Hematology Impact factor: 7.249, year: 2008

  8. The Role of U2AF1 Mutations in the Pathogenesis of Myelodysplastic Syndromes

    Science.gov (United States)

    2016-12-01

    splicing contribute to disease patho mutation in the spliceosome gene U2AF1 and observed hemat also occur in patients with MDS or acute myeloid...Method for Combining Non-Independent, One-Sided Tests of Significance. Biometrics 31, 987–992. Buschbeck, M., Uribesalgo, I., Wibowo, I., Rué, P

  9. Recurrent spleen enlargement during cyclic granulocyte-macrophage colony-stimulating factor therapy for myelodysplastic syndrome

    International Nuclear Information System (INIS)

    Delmer, A.; Karmochkine, M.; Cadiou, M.; Gerhartz, H.; Zittoun, R.

    1990-01-01

    A 65-year-old woman with refractory anemia with excess of blasts received sequential courses of granulocyte-macrophage colony-stimulating factor therapy (GM-CSF) and low-dose cytosine arabinoside. Each course of GM-CSF induced a rapid and tremendous increase in leukocyte count as well as in spleen size, 111-indium chloride scanning suggested a myeloid metaplasia of the spleen. This observation suggests that in some patients the granulopoietic response to the myeloid growth factor stimulation may be predominant in the spleen

  10. Dynamic alterations of bone marrow cytokine landscape of myelodysplastic syndromes patients treated with 5-azacytidine

    Czech Academy of Sciences Publication Activity Database

    Moudra, A.; Hubackova, Sona; Machalova, V.; Vančurová, M.; Bartek, J.; Reinis, M.; Hodny, Z.; Jonasova, A.

    2016-01-01

    Roč. 5, č. 10 (2016), č. článku e1183860. ISSN 2162-402X Institutional support: RVO:86652036 Keywords : 5-azacytidine * DNA damage * cytokines * bone marrow plasma Subject RIV: FD - Oncology ; Hematology Impact factor: 7.719, year: 2016

  11. Red Blood Cell Transfusion Independence Following the Initiation of Iron Chelation Therapy in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Maha A. Badawi

    2010-01-01

    Full Text Available Iron chelation therapy is often used to treat iron overload in patients requiring transfusion of red blood cells (RBC. A 76-year-old man with MDS type refractory cytopenia with multilineage dysplasia, intermediate-1 IPSS risk, was referred when he became transfusion dependent. He declined infusional chelation but subsequently accepted oral therapy. Following the initiation of chelation, RBC transfusion requirement ceased and he remained transfusion independent over 40 months later. Over the same time course, ferritin levels decreased but did not normalize. There have been eighteen other MDS patients reported showing improvement in hemoglobin level with iron chelation; nine became transfusion independent, nine had decreased transfusion requirements, and some showed improved trilineage myelopoiesis. The clinical features of these patients are summarized and possible mechanisms for such an effect of iron chelation on cytopenias are discussed.

  12. Rhino cerebral mucormycosis in a patient with a myelodysplastic syndrome: Disease course as studied by CT

    International Nuclear Information System (INIS)

    Martin, M.T.; Marcos, F.; Villanueva, J.M.; Vicente, L.

    1996-01-01

    A case of richinocerebral mucormycosis is reported a patient with refractory sideroblastic anemia assessed by means of serial CT; the disorder initially mimicked bacterial rhino sinusitis, coursing later with sinonasal necrosis, orbital involvement and, finally, cerebral involvement. The CT findings are compared with those described in the literature. (Author) 8 refs

  13. Effectiveness of Palivizumab in Preventing RSV Hospitalization in High Risk Children: A Real-World Perspective

    Directory of Open Access Journals (Sweden)

    Nusrat Homaira

    2014-01-01

    Full Text Available Infection with respiratory syncytial virus (RSV is one of the major causes globally of childhood respiratory morbidity and hospitalization. Palivizumab, a humanized monoclonal antibody, has been recommended for high risk infants to prevent severe RSV-associated respiratory illness. This recommendation is based on evidence of efficacy when used under clinical trial conditions. However the real-world effectiveness of palivizumab outside of clinical trials among different patient populations is not well established. We performed a systematic review focusing on postlicensure observational studies of the protective effect of palivizumab prophylaxis for reducing RSV-associated hospitalizations in infants and children at high risk of severe infection. We searched studies published in English between 1 January 1999 and August 2013 and identified 420 articles, of which 20 met the inclusion criteria. This review supports the recommended use of palivizumab for reducing RSV-associated hospitalization rates in premature infants born at gestational age < 33 weeks and in children with chronic lung and heart diseases. Data are limited to allow commenting on the protective effect of palivizumab among other high risk children, including those with Down syndrome, cystic fibrosis, and haematological malignancy, indicating further research is warranted in these groups.

  14. Development of a high risk pancreatic screening clinic using 3.0 T MRI.

    Science.gov (United States)

    Barnes, Chad A; Krzywda, Elizabeth; Lahiff, Shannon; McDowell, Dena; Christians, Kathleen K; Knechtges, Paul; Tolat, Parag; Hohenwalter, Mark; Dua, Kulwinder; Khan, Abdul H; Evans, Douglas B; Geurts, Jennifer; Tsai, Susan

    2018-01-01

    Selective screening for pancreatic cancer (PC) has been proposed. We describe the establishment of a comprehensive multidisciplinary screening program using 3.0 T MRI. Criteria for screening included the presence of PC in: ≥ 2 first degree relatives (FDR), 1 FDR and 1 s degree relative (SDR), ≥ 3 any degree relatives (ADR), or any known hereditary cancer syndrome with increased PC risk. Imaging with 3.0 T MRI was performed routinely and endoscopic ultrasound was used selectively. Screening was completed in 75 patients (pts). Hereditary cancer syndromes were present in 42 (56%) of the 75 pts: BRCA2 (18), ATM (8), BRCA1 (6), CDKN2A (4), PALB2 (3), Lynch (2), and Peutz-Jeghers (1). A family history of PC was present in ≥ 2 FDR in 12 (16%) pts, 1 FDR and 1 SDR in 5 (7) pts, and ≥ 3 ADR in 16 (21%) pts. Of the 65 pts who received screening MRI, 28 (43%) pts had pancreatic cystic lesions identified, including 1 (1%) patient in whom a cholangiocarcinoma was diagnosed as well. No patient underwent surgical resection. Using a 3.0 T MRI to screen patients at high risk for developing PC identified radiographic abnormalities in 43% of patients, which were stable on subsequent surveillance. Specific guidelines for the frequency of surveillance and indications for surgery remain areas of active investigation as the global experience with high risk screening continues to mature.

  15. Finding the High-Risk Patient in Primary Prevention Is Not as Easy as a Conventional Risk Score!

    Science.gov (United States)

    Ambrose, John A; Acharya, Tushar; Roberts, Micah J

    2016-12-01

    Patients with coronary artery disease or its equivalent are an appropriate target for guideline-directed therapy. However, finding and treating the individuals at risk for myocardial infarction or sudden death in primary prevention has been problematic. Most initial cardiovascular events are acute syndromes, and only a minority of these occurs in those deemed high risk by contemporary algorithms. Even newer noninvasive modalities cannot detect a majority of those at risk. Furthermore, accurate and early detection of high risk/vulnerability does not guarantee event prevention. Until new tools can be identified, one should consider a few simplistic solutions. In addition to a greater emphasis on lifestyle, earlier use of statins than currently recommended and a direct assault on tobacco could go a long way in reducing acute syndromes and cardiovascular mortality. To achieve the tobacco goal, the medical community would have to be directly and communally engaged. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. How to Identify High-Risk APS Patients: Clinical Utility and Predictive Values of Validated Scores.

    Science.gov (United States)

    Oku, Kenji; Amengual, Olga; Yasuda, Shinsuke; Atsumi, Tatsuya

    2017-08-01

    Antiphospholipid syndrome (APS) is a clinical disorder characterised by thrombosis and/or pregnancy morbidity in the persistence of antiphospholipid (aPL) antibodies that are pathogenic and have pro-coagulant activities. Thrombosis in APS tends to recur and require prophylaxis; however, the stereotypical treatment for APS patients is inadequate and stratification of the thrombotic risks is important as aPL are prevalently observed in various diseases or elderly population. It is previously known that the multiple positive aPL or high titre aPL correlate to thrombotic events. To progress the stratification of thrombotic risks in APS patients and to quantitatively analyse those risks, antiphospholipid score (aPL-S) and the Global Anti-phospholipid Syndrome Score (GAPSS) were defined. These scores were raised from the large patient cohort data and either aPL profile classified in detail (aPL-S) or simplified aPL profile with classical thrombotic risk factors (GAPSS) was put into a scoring system. Both the aPL-S and GAPSS have shown a degree of accuracy in identifying high-risk APS patients, especially those at a high risk of thrombosis. However, there are several areas requiring improvement, or at least that clinicians should be aware of, before these instruments are applied in clinical practice. One such issue is standardisation of the aPL tests, including general testing of phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT). Additionally, clinicians may need to be aware of the patient's medical history, particularly with respect to the incidence of SLE, which influences the cutoff value for identifying high-risk patients.

  17. Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Vinayak Muralidhar

    2016-02-01

    Full Text Available Purpose : Recent retrospective data suggest that brachytherapy (BT boost may confer a cancer-specific survival benefit in radiation-managed high-risk prostate cancer. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4 + 4 = 8, PSA 20 ng/ml. Material and methods: We identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aN0M0 intermediate- to high-risk prostate cancer diagnosed 2004-2011 treated with external beam radiation therapy (EBRT only or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM after EBRT + BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors. Results : EBRT + BT was not associated with an improvement in 5-year PCSM compared to EBRT alone among patients with favorable high-risk disease (1.6% vs. 1.8%; adjusted hazard ratio [AHR]: 0.56; 95% confidence interval [CI]: 0.21-1.52, p = 0.258, and intermediate-risk disease (0.8% vs. 1.0%, AHR: 0.83, 95% CI: 0.59-1.16, p = 0.270. Others with high-risk disease had significantly lower 5-year PCSM when treated with EBRT + BT compared with EBRT alone (3.9% vs. 5.3%; AHR: 0.73; 95% CI: 0.55-0.95; p = 0.022. Conclusions : Brachytherapy boost is associated with a decreased rate of PCSM in some men with high-risk prostate cancer but not among patients with favorable high-risk disease. Our results suggest that the recently-defined “favorable high-risk” category may be used to personalize therapy for men with high-risk disease.

  18. Physical activity barriers and motivators among high-risk employees.

    Science.gov (United States)

    Paguntalan, John C; Gregoski, Mathew

    2016-11-22

    Worksite wellness programs offer an ideal setting to target high-risk sedentary workers to improve health status. Lack of physical activity is associated with increased risk for coronary heart disease and mortality. Despite the risks, the number of sedentary workers is increasing. This study examined the perceived barriers and motivators for physical activity among employees at high-risk for coronary heart disease. A purposive sample of 24 high-risk workers participating in a wellness program in rural South Carolina were enrolled in the study. Qualitative data was obtained through semi-structured face-to-face interviews. Grounded theory was used to analyze qualitative data, and identify overarching themes. Physical limitations due to pain and weakness, lack of motivation, and lack of time emerged as the main barriers to physical activity. Family relationships were reported as the strongest motivator along with social support and potential health benefits. Findings highlight the unique experience of high-risk workers with physical activity. The findingsunderscore the need to design and implement effective interventions specifically designed to meet the needs of high-risk employees.

  19. Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from the National Institutes of Health--National Heart, Lung, and Blood Institute sponsored Women's Ischemia Syndrome Evaluation.

    Science.gov (United States)

    Shaw, Leslee J; Bairey Merz, C Noel; Azziz, Ricardo; Stanczyk, Frank Z; Sopko, George; Braunstein, Glenn D; Kelsey, Sheryl F; Kip, Kevin E; Cooper-Dehoff, Rhonda M; Johnson, B Delia; Vaccarino, Viola; Reis, Steven E; Bittner, Vera; Hodgson, T Keta; Rogers, William; Pepine, Carl J

    2008-04-01

    Women with polycystic ovary syndrome (PCOS) have a greater clustering of cardiac risk factors. However, the link between PCOS and cardiovascular (CV) disease is incompletely described. The aim of this analysis was to evaluate the risk of CV events in 390 postmenopausal women enrolled in the National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS. A total of 104 women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia. Hyperandrogenemia was defined as the top quartile of androstenedione (> or = 701 pg/ml), testosterone (> or = 30.9 ng/dl), or free testosterone (> or = 4.5 pg/ml). Cox proportional hazard model was fit to estimate CV death or myocardial infarction (n = 55). Women with clinical features of PCOS were more often diabetic (P < 0.0001), obese (P = 0.005), had the metabolic syndrome (P < 0.0001), and had more angiographic coronary artery disease (CAD) (P = 0.04) compared to women without clinical features of PCOS. Cumulative 5-yr CV event-free survival was 78.9% for women with clinical features of PCOS (n = 104) vs. 88.7% for women without clinical features of PCOS (n = 286) (P = 0.006). PCOS remained a significant predictor (P < 0.01) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD as covariates. Among postmenopausal women evaluated for suspected ischemia, clinical features of PCOS are associated with more angiographic CAD and worsening CV event-free survival. Identification of postmenopausal women with clinical features of PCOS may provide an opportunity for risk factor intervention for the prevention of CAD and CV events.

  20. Postmenopausal Women with a History of Irregular Menses and Elevated Androgen Measurements at High Risk for Worsening Cardiovascular Event-Free Survival: Results from the National Institutes of Health—National Heart, Lung, and Blood Institute Sponsored Women’s Ischemia Syndrome Evaluation

    Science.gov (United States)

    Shaw, Leslee J.; Bairey Merz, C. Noel; Azziz, Ricardo; Stanczyk, Frank Z.; Sopko, George; Braunstein, Glenn D.; Kelsey, Sheryl F.; Kip, Kevin E.; Cooper-DeHoff, Rhonda M.; Johnson, B. Delia; Vaccarino, Viola; Reis, Steven E.; Bittner, Vera; Hodgson, T. Keta; Rogers, William; Pepine, Carl J.

    2008-01-01

    Background: Women with polycystic ovary syndrome (PCOS) have a greater clustering of cardiac risk factors. However, the link between PCOS and cardiovascular (CV) disease is incompletely described. Objective: The aim of this analysis was to evaluate the risk of CV events in 390 postmenopausal women enrolled in the National Institutes of Health–National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women’s Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS. Methods: A total of 104 women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia. Hyperandrogenemia was defined as the top quartile of androstenedione (≥701 pg/ml), testosterone (≥30.9 ng/dl), or free testosterone (≥4.5 pg/ml). Cox proportional hazard model was fit to estimate CV death or myocardial infarction (n = 55). Results: Women with clinical features of PCOS were more often diabetic (P < 0.0001), obese (P = 0.005), had the metabolic syndrome (P < 0.0001), and had more angiographic coronary artery disease (CAD) (P = 0.04) compared to women without clinical features of PCOS. Cumulative 5-yr CV event-free survival was 78.9% for women with clinical features of PCOS (n = 104) vs. 88.7% for women without clinical features of PCOS (n = 286) (P = 0.006). PCOS remained a significant predictor (P < 0.01) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD as covariates. Conclusion: Among postmenopausal women evaluated for suspected ischemia, clinical features of PCOS are associated with more angiographic CAD and worsening CV event-free survival. Identification of postmenopausal women with clinical features of PCOS may provide an opportunity for risk factor intervention for the prevention of CAD and CV events. PMID:18182456

  1. Radical prostatectomy in clinically localized high-risk prostate cancer

    DEFF Research Database (Denmark)

    Røder, Martin Andreas; Berg, Kasper Drimer; Christensen, Ib Jarle

    2013-01-01

    ) is regarded as primary therapy by others. This study examined the outcome for high-risk localized PCa patients treated with RP. Material and methods. Of 1300 patients who underwent RP, 231 were identified as high-risk. Patients were followed for biochemical recurrence (BCR) (defined as prostate-specific......Abstract Objective. The optimal therapeutic strategy for high-risk localized prostate cancer (PCa) is controversial. Supported by randomized trials, the combination of external beam radiation therapy (EBRT) and endocrine therapy (ET) is advocated by many, while radical prostatectomy (RP...... antigen ≥ 0.2 ng/ml), metastatic disease and survival. Excluding node-positive patients, none of the patients received adjuvant therapy before BCR was confirmed. Univariate and multivariate analysis was performed with Kaplan-Meier and Cox proportional hazard models. Results. Median follow-up was 4.4 years...

  2. The high-risk HPV infection and urinary system tumor

    Directory of Open Access Journals (Sweden)

    Yang Wenyan

    2018-04-01

    Full Text Available HPV is classified into high-risk and low-risk types depending on its probability of leading to tumorigenesis. Many studies have shown that HPV infection, especially the infection caused by the high-risk type, is always related to prostate cancer, bladder cancer, penile cancer, testicular cancer, and other urinary system tumors. However, previous studies differed in sexual openness and racial genetic susceptibility of the study object, sample size, and experimental methods. Hence, the correlation between high-risk HPV infection and urinary system tumors remains controversial. The early open reading frame of the HPV genome is composed of E1–E7, among which E6 and E7 are the key transfer proteins. The combination of these proteins with oncogene and anti-oncogene may be one of the mechanisms leading to tumorigenesis.

  3. Psychological characteristics in high-risk MSM in China

    Directory of Open Access Journals (Sweden)

    Chen Guanzhi

    2012-01-01

    Full Text Available Abstract Background Men who have sex with men (MSM have become a high-risk group of HIV infection in China. To date, little is known regarding the behavioral, social and psychological characteristics in Chinese MSM, which makes the implementation of preventive and therapeutic strategies for this high-risk subpopulation of people extremely difficult. Methods A total of 714 questionnaires were retrieved from the database of a Chinese government-sponsored National Key Research Project titled "Risk Analysis and Strategic Prevention of HIV Transmission from MSM to the General Population in China". The respondents were categorized into a high-risk group and a control group. Their behavioral, social and psychological characteristics were comparatively analyzed. Results Of the 714 MSM analyzed, 59 (8.26% had high-risk homosexual behaviors. This sub-group of MSM had a higher in-marriage rate, a higher monthly income, heavier alcohol consumption and more serious problems with sexual abuse in childhood, intentional suicide attempts and mistaken assumption on condom's role in protecting HIV infection, as compared with the control group (P P > 0.05. A vast majority of the individuals in both behavior categories expressed support of legally protected gay clubs as well as gay marriage legislation in China. There was a strong correlation between high-risk behaviors and sexual abuse in childhood, alcohol drinking, income level and a mistaken belief in perfect HIV protection through the use of condoms. Conclusions MSM with and without high-risk homosexual behaviors have different social and psychological characteristics, which should be taken into account when implementing behavioral and therapeutic interventions aimed at preventing HIV/AIDS transmission among MSM as well as from MSM to the general population in China.

  4. Management of Skin Cancer in the High-Risk Patient.

    Science.gov (United States)

    Behan, James W; Sutton, Adam; Wysong, Ashley

    2016-12-01

    Skin cancer is the most common of human cancers and outnumbers all other types of cancer combined in the USA by over threefold. The majority of non-melanoma skin cancers are easily treated with surgery or locally destructive techniques performed under local anesthesia in the cost-effective outpatient setting. However, there is a subset of "high-risk" cases that prove challenging in terms of morbidity, mortality, adjuvant treatment required, as well as overall cost to the health care system. In our opinion, the term "high risk" when applied to skin cancer can mean one of three things: a high-risk tumor with aggressive histologic and/or clinical features with an elevated risk for local recurrence or regional/distant metastasis, a high-risk patient with the ongoing development of multiple skin cancers, and a high-risk patient based on immunosuppression. We have recently proposed classifying NMSC as a chronic disease in a certain subset of patients. Although no consensus definition exists for a chronic disease in medicine, there are three components that are present in most definitions: duration of at least 1 year, need for ongoing medical care, and functional impairment and/or alteration of activities of daily living (ADLs) and quality of life (QOL). Immunosuppression can refer to exogenous (organ or stem cell transplant patients,) or endogenous (HIV, leukemia, lymphoma, genodermatoses with DNA mismatch repair problems or other immunosuppression) causes. These patients are at risk for high-risk tumors and/or the development of multiple tumors.

  5. Telomerase activation by genomic rearrangements in high-risk neuroblastoma

    Science.gov (United States)

    Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L.; Sand, Frederik; Heuckmann, Johannes M.; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Glöckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R.; Savelyeva, Larissa; Watkins, Simon C.; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H.; Herrmann, Carl; O’Sullivan, Roderick J.; Westermann, Frank; Thomas, Roman K.; Fischer, Matthias

    2016-01-01

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system1. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive2–4. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type1,2,5. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours. PMID:26466568

  6. The effectiveness and cost effectiveness of dark chocolate consumption as prevention therapy in people at high risk of cardiovascular disease: best case scenario analysis using a Markov model

    OpenAIRE

    Zomer, Ella; Owen, Alice; Magliano, Dianna J; Liew, Danny; Reid, Christopher M

    2012-01-01

    Objective To model the long term effectiveness and cost effectiveness of daily dark chocolate consumption in a population with metabolic syndrome at high risk of cardiovascular disease. Design Best case scenario analysis using a Markov model. Setting Australian Diabetes, Obesity and Lifestyle study. Participants 2013 people with hypertension who met the criteria for metabolic syndrome, with no history of cardiovascular disease and not receiving antihypertensive therapy. Main outcome measures ...

  7. Dronedarone in high-risk permanent atrial fibrillation

    DEFF Research Database (Denmark)

    Connolly, Stuart J; Camm, A John; Halperin, Jonathan L

    2011-01-01

    Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events...... in high-risk permanent atrial fibrillation....

  8. Diagnosis and Management of High Risk Group for Gastric Cancer

    Science.gov (United States)

    Yoon, Hyuk; Kim, Nayoung

    2015-01-01

    Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval. PMID:25547086

  9. Sensation seeking in males involved in recreational high risk sports

    Directory of Open Access Journals (Sweden)

    M Guszkowska

    2010-09-01

    Full Text Available The study examined sensation seeking intensity level in males involved in recreational high risk sports and investigated whether its level depends on type of sport practised. Additionally, in case of parachutists, sport experience of study participants were scrutinised with regard to its possible impact on the level of sensation seeking.The research involved 217 males aged 17 to 45, practising recreational high risk sports, namely: parachuting (n=98; wakeboarding (n=30; snowboarding (n=30; scuba diving (n=22; alpinism (n=20; paragliding (n=17. The control group included 54 men not involved in sports. Polish version of Sensation Seeking Scale (SSS-IV of Zuckerman was applied.Results show, that high risk sports males are featured by stronger need of sensations in comparison to control group and this concerned all but one aspect of sensation seeking variable. The only exception was the need of intellectual stimulation. Except from the thrill and adventure seeking dimension, type of sport may also be an important determinant of sensation seeking. Men practising snowboard and wakeboard presented stronger need for sensations, especially in the dimension of experience seeking, disinhibition and boredom susceptibility. Sport experience (number of jumps in parachuting did not differentiate the level of sensation seeking among investigated parachutists. Population of sport high risk male takers was not homogeneous, and therefore in future research one should analyse specific sports (or events in a certain sport separately.

  10. Detection of Patients at High Risk of Medication Errors

    DEFF Research Database (Denmark)

    Sædder, Eva Aggerholm; Lisby, Marianne; Nielsen, Lars Peter

    2016-01-01

    Medication errors (MEs) are preventable and can result in patient harm and increased expenses in the healthcare system in terms of hospitalization, prolonged hospitalizations and even death. We aimed to develop a screening tool to detect acutely admitted patients at low or high risk of MEs...

  11. Alcohol-Related Problems And High Risk Sexual Behaviour In ...

    African Journals Online (AJOL)

    There was a significant association between alcohol-related problems and risky sexual behavior. Alcohol-related problems are fairly common in people already infected with HIV/AIDS and are associated with high-risk sexual behavior. Thus, screening and treatment should be part of an effective HIV intervention program.

  12. Original Research Identifying patients at high risk for obstructive ...

    African Journals Online (AJOL)

    determine the factors associated with high risk for obstructive sleep apnoea and use it to identify patients at risk for the condition in ... mainstay of management is CPAP in addition to behavioral ..... the present study has some potential limitations which ... consequences of obstructive sleep apnea and short sleep duration.

  13. Postmastectomy irradiation in high-risk breast cancer patients

    International Nuclear Information System (INIS)

    Overgaard, M.; Juul Christensen, J.; Johansen, H.; Nybo-Rasmussen, A.; Brincker, H.; Kooy, P. van der; Frederiksen, P.L.; Laursen, F.; Panduro, J.; Soerensen, N.E.; Gadeberg, C.C.; Hjelm-Hansen, M.; Overgaard, J.; West Andersen, K.; Zedeler, K.

    1988-01-01

    All pre- and postmenopausal high-risk breast cancer patients in the protocols DBCG 77 of the Danish Breast Cancer Cooperative Group received postmastectomy irradiation before randomization to either adjuvant systemic therapy or no such treatment. The actuarial loco-regional recurrence rate at 9 years was 6-17%, with the lowest rate in patients who also received additional adjuvant chemotherapy or tamoxifen. In a subsequent study (DBCG 82) the role of postmastectomy irradiation together with systemic treatment was evaluated in high-risk patients. Pre- and menopausal patients were randomized to postmastectomy irradiation+CMF (cyclophosphamide, methotrexate, 5-fluorouracil), CMF alone or CMF+TAM (tamoxifen). Postmenopausal patients were randomized to postmastectomy irradiation+TAM, TAM or CMF+TAM. At 4 years the loco-regional recurrence rate was significantly lower in the irradiated patients (5-7% vs. 23-33%). Further, disease-free survival was significantly improved in both pre- and postmenopausal irradiated patients compared with those who had only systemic treatment. At present, there are no significant differences between survival in the treatment groups. Thus, adjuvant systemic treatment alone (chemotherapy and/or tamoxifen) did not prevent loco-regional recurrences in high-risk patients after mastectomy and axillary lymph node sampling. However, a longer observation time is necessary to evaluate the consequence of primary optimal loco-regional tumour control in high-risk breast cancer patients with respect to survival. (orig.)

  14. Staying Alive! Training High-Risk Teams for Self Correction

    Science.gov (United States)

    Slack, Kelley; Noe, Raymond; Weaver, Sallie

    2011-01-01

    Research examining teams working in high-risk operations has been lacking. The present symposium showcases research on team training that helps to optimize team performance in environments characterized by life or death situations arising spontaneously after long periods of mundane activity by pulling experts from diverse areas of industry: space flight, health care, and medical simulation.

  15. Patients at High-Risk for Surgical Site Infection.

    Science.gov (United States)

    Mueck, Krislynn M; Kao, Lillian S

    Surgical site infections (SSIs) are a significant healthcare quality issue, resulting in increased morbidity, disability, length of stay, resource utilization, and costs. Identification of high-risk patients may improve pre-operative counseling, inform resource utilization, and allow modifications in peri-operative management to optimize outcomes. Review of the pertinent English-language literature. High-risk surgical patients may be identified on the basis of individual risk factors or combinations of factors. In particular, statistical models and risk calculators may be useful in predicting infectious risks, both in general and for SSIs. These models differ in the number of variables; inclusion of pre-operative, intra-operative, or post-operative variables; ease of calculation; and specificity for particular procedures. Furthermore, the models differ in their accuracy in stratifying risk. Biomarkers may be a promising way to identify patients at high risk of infectious complications. Although multiple strategies exist for identifying surgical patients at high risk for SSIs, no one strategy is superior for all patients. Further efforts are necessary to determine if risk stratification in combination with risk modification can reduce SSIs in these patient populations.

  16. Incidence of infective endocarditis among patients considered at high risk

    DEFF Research Database (Denmark)

    Østergaard, Lauge; Valeur, Nana; Ihlemann, Nikolaj

    2018-01-01

    Aims: Patients with prior infective endocarditis (IE), a prosthetic heart valve, or a cyanotic congenital heart disease (CHD) are considered to be at high risk of IE by guidelines. However, knowledge is sparse on the relative risk of IE between these three groups and compared controls. Methods...

  17. Update on the Management of High-Risk Penetrating Keratoplasty.

    Science.gov (United States)

    Jabbehdari, Sayena; Rafii, Alireza Baradaran; Yazdanpanah, Ghasem; Hamrah, Pedram; Holland, Edward J; Djalilian, Ali R

    2017-03-01

    In this article, we review the indications and latest management of high-risk penetrating keratoplasty. Despite the immune-privilege status of the cornea, immune-mediated graft rejection still remains the leading cause of corneal graft failure. This is particularly a problem in the high-risk graft recipients, namely patients with previous graft failure due to rejection and those with inflamed and vascularized corneal beds. A number of strategies including both local and systemic immunosuppression are currently used to increase the success rate of high-risk corneal grafts. Moreover, in cases of limbal stem cell deficiency, limbal stem cells transplantation is employed. Corticosteroids are still the top medication for prevention and treatment in cases of corneal graft rejection. Single and combined administration of immunosuppressive agents e.g. tacrolimus, cyclosporine and mycophenolate are promising adjunctive therapies for prolonging graft survival. In the future, cellular and molecular therapies should allow us to achieve immunologic tolerance even in high-risk grafts.

  18. Monitoring paneer for Listeria monocytogenes - A high risk food ...

    African Journals Online (AJOL)

    A multiplex polymerase chain reaction (PCR) assay was developed and applied to spiked and natural paneer samples to detect Listeria monocytogenes, a high risk food pathogen. The sensitivity of the assay on L. monocytogenes spiked paneer samples was 104 cells prior to enrichment, was improved to 103 cells after 4 h ...

  19. An assessment of high risk sexual behaviour and HIV transmission ...

    African Journals Online (AJOL)

    An assessment of high risk sexual behaviour and HIV transmission among migrant oil workers in the Niger Delta area of Nigeria. ... questionnaires to evaluate key high – risk sexual behavioral parameters such as multiplicity of sexual partners, bisexuality (closet homosexuality), high grade sexual behaviour and lesbianism.

  20. High-risk PCI: how to define it today?

    Science.gov (United States)

    DE Marzo, Vincenzo; D'Amario, Domenico; Galli, Mattia; Vergallo, Rocco; Porto, Italo

    2018-04-11

    Before the percutaneous spread, the mortality rate of patients with coronary heart disease not suitable for cardiac surgery was markedly high. This limit has been progressively exceeded with the advent of minimally invasive approaches, which, although was initially intended exclusively for low risk patients, was then employed in complex patients often too compromised to undergo cardiac surgery. Given to the rising of high-risk population, due to an increase of patients with multiple chronic conditions linked to the best care offered, we are witnessing an expansion of the high-risk percutaneous coronary interventions (PCI) population. Despite defining what high-risk is remains still unclear, all proposed definitions of high-risk PCI combine features related to three clinical areas: 1) patient risk factors and comorbidities (incorporating those which preclude surgical or percutaneous revascularization such as diabetes, COPD, CKD, lung disease, frailty, advanced age); 2) location of the disease and complexity of coronary anatomy (including multi-vessel disease, left main disease, CTO, bifurcations); 3) hemodynamic clinical status (ventricular dysfunction, concomitant valvular disease or unstable characteristics). Since cardiologists have ascertained the encouraging results in terms of efficacy and rewards compared to the low-risks patients, the important role of treating high-risk patients is becoming more and more relevant to the point that current guidelines have now changed the appropriateness of percutaneous interventions indications. Considering the complexity in managing higher-risk patients with coronary artery disease, the next step to ensure the best care for this type of patients is to create a team-based model of cooperation in order to properly establish the right treatment for the right patient.

  1. The hematopoietic system of the acute radiation syndrome reconvalescents in post-accidental period

    International Nuclear Information System (INIS)

    Klimenko, V.; Dyagil, I.; Yukhimuk, L.; Bilko, N.; Bebeshko, V.; Klimenko, S.; Oberenko, O.

    1996-01-01

    The state of hemopoietic system has been studied since 1986 up to now in 145 patients who had acute radiation sickness after the Chernobyl accident. We studied clinical, morpho functional, histological, ultrastructural, biophysical, cultural, cytochemical indexes of the hematopoietic elements. The connection between hemopoietic microenvironment and hemopoiesis state was put up. The realization of the hematological disorders as myelodysplastic syndrome testified the most important problem in future

  2. High-risk diagnosis, social stress, and parent-child relationships: A moderation model.

    Science.gov (United States)

    Bentley, Eryn; Millman, Zachary B; Thompson, Elizabeth; Demro, Caroline; Kline, Emily; Pitts, Steven C; DeVylder, Jordan E; Smith, Melissa Edmondson; Reeves, Gloria; Schiffman, Jason

    2016-07-01

    Stress is related to symptom severity among youth at clinical high-risk (CHR) for psychosis, although this relation may be influenced by protective factors. We explored whether the association of CHR diagnosis with social stress is moderated by the quality of parent-child relationships in a sample of 96 (36 CHR; 60 help-seeking controls) adolescents and young adults receiving mental health services. We examined self-reported social stress and parent-child relationships as measured by the Behavior Assessment System for Children, Second Edition (BASC-2), and determined CHR status from the clinician-administered Structured Interview for Psychosis-Risk Syndrome (SIPS). The social stress subscale, part of the clinical domain of the BASC-2, assesses feelings of stress and tension in personal relationships and the relations with parents subscale, part of the adaptive domain of the BASC-2, assesses perceptions of importance in family and quality of parent-child relationship. There was a modest direct relation between risk diagnosis and social stress. Among those at CHR, however, there was a significant relation between parent-child relationships and social stress (b=-0.73, t[92]=-3.77, psocial stress for those at risk for psychosis. Findings provide additional evidence to suggest that interventions that simultaneously target both social stress and parent-child relationships might be relevant for adolescents and young adults at clinical high-risk for psychosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Projection of human immunodeficiency virus among high-risk groups in Malaysia.

    Science.gov (United States)

    Mondal, Md Nazrul Islam; Shitan, Mahendran

    2013-01-01

    Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) presents a serious healthcare threat to young individuals in Malaysia and worldwide. This study aimed to identify trends in HIV-related risk behaviors among recognized high-risk groups and to estimate HIV transmission up to the year 2015. Data and necessary information were obtained from the Ministry of Health Malaysia, published reports from the World Health Organization and United Nations Program on HIV/AIDS, and other articles. The Estimation and Projection Package was used to estimate HIV transmission. The results of the present study revealed that within the high-risk groups, intravenous drug users (IDUs) had the highest prevalence rate of HIV transmission, followed by patients with sexually transmitted infections (STIs), female sex workers (SWs), and men who have sex with men (MSM). Within these at-risk populations, patients with STIs have the highest prevalence of HIV, followed by IDUs, MSM, and SWs. If the transmission rate continues to increase, the situation will worsen; therefore, there is an urgent need for a comprehensive prevention program to control HIV transmission in Malaysia.

  4. Applying the lessons of high risk industries to health care.

    Science.gov (United States)

    Hudson, P

    2003-12-01

    High risk industries such as commercial aviation and the oil and gas industry have achieved exemplary safety performance. This paper reviews how they have managed to do that. The primary reasons are the positive attitudes towards safety and the operation of effective formal safety management systems. The safety culture provides an important explanation of why such organisations perform well. An evolutionary model of safety culture is provided in which there is a range of cultures from the pathological through the reactive to the calculative. Later, the proactive culture can evolve towards the generative organisation, an alternative description of the high reliability organisation. The current status of health care is reviewed, arguing that it has a much higher level of accidents and has a reactive culture, lagging behind both high risk industries studied in both attitude and systematic management of patient risks.

  5. High risk pregnancy in the workplace. Influencing positive outcomes.

    Science.gov (United States)

    Cannon, R B; Schmidt, J V; Cambardella, B; Browne, S E

    2000-09-01

    Childbearing employees are well served by the occupational health nurse who promotes optimal preconceptual and pregnancy health practices, uses community resources, and maintains current knowledge about high risk pregnancy prevention and care. These broad goals of care can lead to decreased absenteeism, healthier and happier employees, and more positive outcomes of pregnancy. For employees with high risk pregnancies, the role of the occupational health nurse includes, but is not limited to, facilitating awareness with the employer, making suggestions for adjusting working conditions, making frequent assessments of the employee's needs, and communicating with prenatal health care providers. Occupational health nurses should never underestimate their role and potential influence on the mother, and on her significant other, for a positive outcome of her pregnancy.

  6. Physical performance following acute high-risk abdominal surgery

    DEFF Research Database (Denmark)

    Jønsson, Line Rokkedal; Ingelsrud, Lina Holm; Tengberg, Line Toft

    2018-01-01

    BACKGROUND: Acute high-risk abdominal (AHA) surgery is associated with high mortality, multiple postoperative complications and prolonged hospital stay. Further development of strategies for enhanced recovery programs following AHA surgery is needed. The aim of this study was to describe physical...... are primarily fatigue and abdominal pain. Further studies investigating strategies for early mobilization and barriers to mobilization in the immediate postoperative period after AHA surgery are needed.......BACKGROUND: Acute high-risk abdominal (AHA) surgery is associated with high mortality, multiple postoperative complications and prolonged hospital stay. Further development of strategies for enhanced recovery programs following AHA surgery is needed. The aim of this study was to describe physical...... performance and barriers to independent mobilization among patients who received AHA surgery (postoperative days [POD] 1-7). METHODS: Patients undergoing AHA surgery were consecutively enrolled from a university hospital in Denmark. In the first postoperative week, all patients were evaluated daily...

  7. High risk factors in patient with carcinoma esophagus

    International Nuclear Information System (INIS)

    Afridi, S.P.; Khan, A.; Waheed, I.

    2000-01-01

    This study was conducted to identify the presence of high risk factors in carcinoma esophagus from February, 1992 to August, 1995 at Surgical unit 1, Jinnah Postgraduate Medical Centre (JPMC), Karachi. In all 37 patients, 22 males and 15 females, were included in the study through outpatient department, surgical emergency and those referred from other cities of the country. All patients were cachectic. Diagnosis was made by detailed history, examination and laboratory investigations. Diagnosis was confirmed on barium swallow and endoscopic biopsy. Highest number of patients were in their 6th decade of life. History of snuff inhalation and opium was present in 2.7% cases each. Lower 3rd of the esophagus was affected in 62.16% middle third in 21.62% and upper third in 16.21% cases. Smoking, pan chewing, naswar eating and snuff inhalation were identified as high risk factors among patients of carcinoma esophagus. (author)

  8. Screening for breast cancer in a high-risk series

    International Nuclear Information System (INIS)

    Woodard, E.D.; Hempelmann, L.H.; Janus, J.; Logan, W.; Dean, P.

    1982-01-01

    A unique cohort of women at increased risk of breast cancer because of prior X-ray treatment of acute mastitis and their selected high-risk siblings were offered periodic breast cancer screening including physical examination of the breasts, mammography, and thermography. Twelve breast cancers were detected when fewer than four would have been expected based on age-specific breast cancer detection rates from the National Cancer institute/American Cancer Society Breast Cancer Demonstration Detection Projects. Mammograpy was positive in all cases but physical examination was positive in only three cases. Thermography was an unreliable indicator of disease. Given the concern over radiation-induced risk, use of low-dose technique and of criteria for participation that select women at high risk of breast cancer will maximize the benefit/risk ratio for mammography screening

  9. Quality assurance system for sitting high risk facilities

    International Nuclear Information System (INIS)

    Rodriguez, Aymee; Peralta, Jose L.; Fernandez, Manuel

    1999-01-01

    The paper shows how we have conceived and designed the quality assurance system for the site selection process of an area for sitting the facility of high risk in correspondence with the approved methodology. The results obtained in the implementation of the system have permitted the satisfactory performance of each one the expected stage, defining the most favorable sectors in order to continue the studies of the repository site for the disposal of low and intermedium. (author)

  10. Predicting reattendance at a high-risk breast cancer clinic.

    Science.gov (United States)

    Ormseth, Sarah R; Wellisch, David K; Aréchiga, Adam E; Draper, Taylor L

    2015-10-01

    The research about follow-up patterns of women attending high-risk breast-cancer clinics is sparse. This study sought to profile daughters of breast-cancer patients who are likely to return versus those unlikely to return for follow-up care in a high-risk clinic. Our investigation included 131 patients attending the UCLA Revlon Breast Center High Risk Clinic. Predictor variables included age, computed breast-cancer risk, participants' perceived personal risk, clinically significant depressive symptomatology (CES-D score ≥ 16), current level of anxiety (State-Trait Anxiety Inventory), and survival status of participants' mothers (survived or passed away from breast cancer). A greater likelihood of reattendance was associated with older age (adjusted odds ratio [AOR] = 1.07, p = 0.004), computed breast-cancer risk (AOR = 1.10, p = 0.017), absence of depressive symptomatology (AOR = 0.25, p = 0.009), past psychiatric diagnosis (AOR = 3.14, p = 0.029), and maternal loss to breast cancer (AOR = 2.59, p = 0.034). Also, an interaction was found between mother's survival and perceived risk (p = 0.019), such that reattendance was associated with higher perceived risk among participants whose mothers survived (AOR = 1.04, p = 0.002), but not those whose mothers died (AOR = 0.99, p = 0.685). Furthermore, a nonlinear inverted "U" relationship was observed between state anxiety and reattendance (p = 0.037); participants with moderate anxiety were more likely to reattend than those with low or high anxiety levels. Demographic, medical, and psychosocial factors were found to be independently associated with reattendance to a high-risk breast-cancer clinic. Explication of the profiles of women who may or may not reattend may serve to inform the development and implementation of interventions to increase the likelihood of follow-up care.

  11. Optimizing the Management of High-Risk, Localized Prostate Cancer

    OpenAIRE

    Sundi, Debasish; Jeong, Byong Chang; Lee, Seung Bae; Han, Misop

    2012-01-01

    Prostate cancer has a high prevalence and a rising incidence in many parts of the world. Although many screen-detected prostate cancers may be indolent, prostate cancer remains a major contributor to mortality in men. Therefore, the appropriate diagnosis and treatment of localized prostate cancer with lethal potential are of great importance. High-risk, localized prostate cancer has multiple definitions. Treatment options that should be individualized to each patient include observation, radi...

  12. Monitoring of newborns at high risk for brain injury

    OpenAIRE

    Pisani, Francesco; Spagnoli, Carlotta

    2016-01-01

    Due to the increasing number of surviving preterm newborns and to the recognition of therapeutic hypothermia as the current gold standard in newborns with hypoxic-ischaemic encephalopathy, there has been a growing interest in the implementation of brain monitoring tools in newborns at high risk for neurological disorders. Among the most frequent neurological conditions and presentations in the neonatal period, neonatal seizures and neonatal status epilepticus, paroxysmal non-epileptic motor p...

  13. Improving Asthma Communication in High-Risk Children

    OpenAIRE

    Butz, Arlene M.; Walker, Jennifer; Land, Cassia Lewis; Vibbert, Carrie; Winkelstein, Marilyn

    2007-01-01

    Few child asthma studies address the specific content and techniques needed to enhance child communication during asthma preventive care visits. This study examined the content of child and parent communications regarding their asthma management during a medical encounter with their primary care provider (PCP). The majority of parents and children required prompting to communicate symptom information to the PCP during the clinic visit. Some high-risk families may require an asthma advocate to...

  14. Improving antenatal risk assessment in women exposed to high risks.

    Science.gov (United States)

    Perry, Natasha; Newman, Louise K; Hunter, Mick; Dunlop, Adrian

    2015-01-01

    Antenatal substance use and related psychosocial risk factors are known to increase the likelihood of child protection involvement; less is known about the predictive nature of maternal reflective functioning (RF) in this population. This preliminary study assessed psychosocial and psychological risk factors for a group of substance dependent women exposed to high risks in pregnancy, and their impact on child protection involvement. Pregnant women on opiate substitution treatment (n = 11) and a comparison group (n = 15) were recruited during their third trimester to complete measures of RF (Pregnancy Interview), childhood trauma, mental health and psychosocial assessments. At postnatal follow-up, RF was reassessed (Parent Development Interview - Revised Short Version) and mother-infant dyads were videotaped to assess emotional availability (EA). Child protection services were contacted to determine if any concerns had been raised for infant safety. Significant between-group differences were observed for demographics, psychosocial factors, trauma and mental health symptoms. Unexpectedly, no significant differences were found for RF or EA between groups. Eight women in the 'exposed to high risks' group became involved with child protection services. Reflective functioning was not significantly associated with psychosocial risk factors, and therefore did not mediate the outcome of child protection involvement. Women 'exposed to high risks' were equally able to generate a model of their own and their infants' mental states and should not be seen within a deficit perspective. Further research is required to better understand the range of risk factors that predict child protection involvement in high risk groups. © The Author(s) 2013.

  15. Risk perception in women with high-risk pregnancies

    OpenAIRE

    Lee, S.

    2014-01-01

    Risk perception in women with high risk pregnancies affects the decisions they make about antenatal care and so may therefore influence the wellbeing of mother and baby. This article addresses the factors which influence women when making risk assessments and how these assessments may differ from those of healthcare professionals.\\ud \\ud Women use multiple sources of information to determine their risk status including advice from professionals, from other trusted sources, and their own intui...

  16. High risk bladder cancer: current management and survival

    Directory of Open Access Journals (Sweden)

    Anna M. Leliveld

    2011-04-01

    Full Text Available PURPOSE: To evaluate the pattern of care in patients with high risk non muscle invasive bladder cancer (NMIBC in the Comprehensive Cancer Center North-Netherlands (CCCN and to assess factors associated with the choice of treatment, recurrence and progression free survival rates. MATERIALS AND METHODS: Retrospective analysis of 412 patients with newly diagnosed high risk NMIBC. Clinical, demographic and follow-up data were obtained from the CCCN Cancer Registry and a detailed medical record review. Uni and multivariate analysis was performed to identify factors related to choice of treatment and 5 year recurrence and progression free survival. RESULTS: 74/412 (18% patients with high risk NMIBC underwent a transurethral resection (TUR as single treatment. Adjuvant treatment after TUR was performed in 90.7% of the patients treated in teaching hospitals versus 71.8 % in non-teaching hospitals (p 80 years OR 0.1 p = 0.001 and treatment in non-teaching hospitals (OR 0.25; p < 0.001 were associated with less adjuvant treatment after TUR. Tumor recurrence occurred in 191/392 (49% and progression in 84 /392 (21.4% patients. The mean 5-years progression free survival was 71.6% (95% CI 65.5-76.8. CONCLUSION: In this pattern of care study in high risk NMIBC, 18% of the patients were treated with TUR as single treatment. Age and treatment in non-teaching hospitals were associated with less adjuvant treatment after TUR. None of the variables sex, age, comorbidity, hospital type, stage and year of treatment was associated with 5 year recurrence or progression rates.

  17. Tamoxifen for women at high risk of breast cancer

    OpenAIRE

    Nazarali, Safia A; Narod, Steven A

    2014-01-01

    Safia A Nazarali, Steven A Narod Women's College Research Institute, Women's College Hospital, and The University of Toronto, Toronto, Ontario, Canada Abstract: Tamoxifen has been used as a treatment for women who have been diagnosed with breast cancer for roughly four decades and has been approved as chemoprevention for over ten years. Although tamoxifen has been proven to be beneficial in preventing breast cancer in high-risk women, its use has not been widely embraced. To ...

  18. The clinical profile of high-risk mentally disordered offenders.

    Science.gov (United States)

    Yiend, Jenny; Freestone, Mark; Vazquez-Montes, Maria; Holland, Josephine; Burns, Tom

    2013-07-01

    High-risk mentally disordered offenders present a diverse array of clinical characteristics. To contain and effectively treat this heterogeneous population requires a full understanding of the group's clinical profile. This study aimed to identify and validate clusters of clinically coherent profiles within one high-risk mentally disordered population in the UK. Latent class analysis (a statistical technique to identify clustering of variance from a set of categorical variables) was applied to 174 cases using clinical diagnostic information to identify the most parsimonious model of best fit. Validity analyses were performed. Three identified classes were a 'delinquent' group (n = 119) characterised by poor educational history, strong criminal careers and high recidivism risk; a 'primary psychopathy' group (n = 38) characterised by good educational profiles and homicide offences and an 'expressive psychopathy' group (n = 17) presenting the lowest risk and characterised by more special educational needs and sexual offences. Individuals classed as high-risk mentally disordered offenders can be loosely segregated into three discrete subtypes: 'delinquent', 'psychopathic' or 'expressive psychopathic', respectively. These groups represent different levels of risk to society and reflect differing treatment needs.

  19. Postoperative chemoradiotherapy in high risk locally advanced gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Song, Sang Hyuk; Chie, Eui Kyu; Kim, Kyu Bo; Lee, Hyuk Joon; Yang, Han Kwang; Han, Sae Won; Oh, Do Youn; Im, Seok Ah; Bang, Yung Jue; Ha, Sung W. [Seoul National University College of Medicine, Seoul(Korea, Republic of)

    2012-12-15

    To evaluate treatment outcome of patients with high risk locally advanced gastric cancer after postoperative chemoradiotherapy. Between May 2003 and May 2012, thirteen patients who underwent postoperative chemoradiotherapy for gastric cancer with resection margin involvement or adjacent structure invasion were retrospectively analyzed. Concurrent chemotherapy was administered in 10 patients. Median dose of radiation was 50.4 Gy (range, 45 to 55.8 Gy). The median follow-up duration for surviving patients was 48 months (range, 5 to 108 months). The 5-year overall survival rate was 42% and the 5-year disease-free survival rate was 28%. Major pattern of failure was peritoneal seeding with 46%. Loco-regional recurrence was reported in only one patient. Grade 2 or higher gastrointestinal toxicity occurred in 54% of the patients. However, there was only one patient with higher than grade 3 toxicity. Despite reported suggested role of adjuvant radiotherapy with combination chemotherapy in gastric cancer, only very small portion of the patients underwent the treatment. Results from this study show that postoperative chemoradiotherapy provided excellent locoregional control with acceptable and manageable treatment related toxicity in patients with high risk locally advanced gastric cancer. Thus, postoperative chemoradiotherapy may improve treatment result in terms of locoregional control in these high risk patients. However, as these findings are based on small series, validation with larger cohort is suggested.

  20. Screening for Hypoglycemia in Exclusively Breastfed High-risk Neonates.

    Science.gov (United States)

    Singh, Princy; Upadhyay, Amit; Sreenivas, Vishnubhatla; Jaiswal, Vijay; Saxena, Pranjali

    2017-06-15

    To determine incidence of hypoglycemia in exclusively breastfed, high-risk but healthy newborns, and risk factors for its development. This observational study enrolled 407 exclusively breastfed high-risk (low birth weight newborns (1800-2499 g), late preterms, small-for-gestation, large-for-gestation and infant of diabetic mother), who did not require admission to neonatal intensive care unit and were kept in postnatal wards with mother. Hypoglycemia was defined as blood glucose £46 mg/dL (2.6 mmol/L). Blood glucose was monitored till 48 hours of life. 27% of the screened newborns developed hypoglycemia in first 48 hours. 31 (7.6%) developed recurrent (>2) episodes, 28 (6.8%) had moderate (<37mg/dL) while 8 (1.9%) developed symptomatic hypoglycemia. With increase in birthweight, risk of hypoglycemia reduced significantly (P=0.003). Hypoglycemia was observed more frequently in first 2 hours as compared to next 48 hours (P=0.0001). Low birth- weight, preterm gestation and male gender was significantly associated with increased risk of hypoglycemia. Healthy, high-risk exclusively breastfed newborns in postnatal wards need close monitoring for hypoglycemia in first 24 hrs of life.

  1. InSAR deformation monitoring of high risk landslides

    Science.gov (United States)

    Singhroy, V.; Li, J.

    2013-05-01

    During the past year there were at least twenty five media reports of landslides and seismic activities some fatal, occurring in various areas in Canada. These high risk geohazards sites requires high resolution monitoring both spatially and temporally for mitigation purposes, since they are near populated areas and energy, transportation and communication corridors. High resolution air photos, lidar and satellite images are quite common in areas where the landslides can be fatal. Radar interferometry (InSAR) techniques using images from several radar satellites are increasingly being used in slope stability assessment. This presentation provides examples of using high-resolution (1-3m) frequent revisits InSAR techniques from RADARSAT 2 and TerraSAR X to monitor several types of high-risk landslides affecting transportation and energy corridors and populated areas. We have analyses over 200 high resolution InSAR images over a three year period on geologically different landslides. The high-resolution InSAR images are effective in characterizing differential motion within these low velocity landslides. The low velocity landslides become high risk during the active wet spring periods. The wet soils are poor coherent targets and corner reflectors provide an effective means of InSAR monitoring the slope activities.

  2. Genetic predisposition syndromes: when should they be considered in the work-up of MDS?

    Science.gov (United States)

    Babushok, Daria V; Bessler, Monica

    2015-03-01

    Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by cytopenias, ineffective hematopoiesis, myelodysplasia, and an increased risk of acute myeloid leukemia (AML). While sporadic MDS is primarily a disease of the elderly, MDS in children and young and middle-aged adults is frequently associated with underlying genetic predisposition syndromes. In addition to the classic hereditary bone marrow failure syndromes (BMFS) such as Fanconi Anemia and Dyskeratosis Congenita, in recent years there has been an increased awareness of non-syndromic familial MDS/AML predisposition syndromes such as those caused by mutations in GATA2, RUNX1, CEBPA, and SRP72 genes. Here, we will discuss the importance of recognizing an underlying genetic predisposition syndrome a patient with MDS, will review clinical scenarios when genetic predisposition should be considered, and will provide a practical overview of the common BMFS and familial MDS/AML syndromes which may be encountered in adult patients with MDS. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies

    Science.gov (United States)

    2017-12-03

    Sickle Cell Disease; Transfusion Dependent Alpha- or Beta- Thalassemia; Diamond Blackfan Anemia; Paroxysmal Nocturnal Hemoglobinuria; Glanzmann Thrombasthenia; Severe Congenital Neutropenia; Shwachman-Diamond Syndrome; Non-Malignant Hematologic Disorders

  4. RECENT ADVANCES IN THE 5Q- SYNDROME

    Directory of Open Access Journals (Sweden)

    Andrea Pellagatti

    2015-05-01

    Full Text Available The 5q- syndrome is the most distinct of the myelodysplastic syndromes (MDS and patients with this disorder have a deletion of chromosome 5q [del(5q] as the sole karyotypic abnormality. Several genes mapping to the commonly deleted region of the 5q- syndrome have been implicated in disease pathogenesis in recent years. Haploinsufficiency of the ribosomal gene RPS14 has been shown to cause the erythroid defect in the 5q- syndrome. Loss of the microRNA genes miR-145 and miR-146a has been associated with the thrombocytosis observed in 5q- syndrome patients. Haploinsufficiency of CSNK1A1 leads to hematopoietic stem cell expansion in mice and may play a role in the initial clonal expansion in patients with 5q- syndrome. Moreover, a subset of patients harbor mutation of the remaining CSNK1A1 allele. Mouse models of the 5q- syndrome, which recapitulate the key features of the human disease, indicate that a p53-dependent mechanism underlies the pathophysiology of this disorder. Importantly, activation of p53 has been demonstrated in the human 5q- syndrome. Recurrent TP53 mutations have been associated with an increased risk of disease evolution and with decreased response to the drug lenalidomide in del(5q MDS patients. Potential new therapeutic agents for del(5q MDS include the translation enhancer L-leucine.

  5. Adverse pregnancy outcomes in deliveries prior to, at and beyond 39 weeks; low- and high-risk women.

    Science.gov (United States)

    Moussa, Hind N; Hosseini Nasab, Susan; Amro, Farah H; Hoayek, Jennifer; Haidar, Ziad A; Blackwell, Sean C; Sibai, Baha M

    2017-07-18

    Hypertensive disorders are associated with maternal and neonatal complications. Though they are more common in women with history of prior preeclampsia, they can occur in uncomplicated pregnancies. To determine the proportion of adverse pregnancy outcomes in deliveries prior to or at ≥39 weeks, in uncomplicated singleton nulliparous women (low-risk), as well as women with history of preeclampsia in a prior gestation (high-risk). This was a secondary analysis from the multicenter trials of low dose aspirin for preeclampsia prevention in low and high-risk pregnancies. The proportion of adverse pregnancy outcomes including hypertensive disorders in pregnancy, small for gestational age, placental abruption, neonatal intensive critical unit admission, and respiratory distress syndrome were evaluated in the two groups. Adverse pregnancy outcomes were stratified by gestational age at delivery (39 weeks and ≥39 weeks). Descriptive statistics were performed, and results reported as percentages. Three thousand twenty-one pregnancies were included in the low risk group, and 600 in the high risk one. In the low risk group 362 (12%) had hypertensive disorders, with 58% occurring at ≥39 weeks. In the low risk group, the rate of small for gestational age was of 5.9%, placental abruption 0.4%, neonatal intensive care unit admission 9%, and respiratory distress syndrome 3.5%. Sixty percent of all small for gestational age, 31% of all placenta abruptions, 44% of all neonatal intensive care unit admissions and 33% of respiratory distress syndrome cases, occurred at ≥39 weeks in the low risk group. In contrast in the high risk group, 197 (33%) patients developed a hypertensive disorder, with 35.5% occurring at ≥39 weeks. The overall rate of small for gestational age was 9.2%, abruption 2%, neonatal intensive care unit admission 15.5%, and respiratory distress syndrome 5%. In this group, 24% of all small for gestational age, 8.3% of all placental abruptions, 16% of all

  6. Specialized surveillance for individuals at high risk for melanoma: a cost analysis of a high-risk clinic.

    Science.gov (United States)

    Watts, Caroline G; Cust, Anne E; Menzies, Scott W; Coates, Elliot; Mann, Graham J; Morton, Rachael L

    2015-02-01

    Regular surveillance of individuals at high risk for cutaneous melanoma improves early detection and reduces unnecessary excisions; however, a cost analysis of this specialized service has not been undertaken. To determine the mean cost per patient of surveillance in a high-risk clinic from the health service and societal perspectives. We used a bottom-up microcosting method to measure resource use in a consecutive sample of 102 patients treated in a high-risk hospital-based clinic in Australia during a 12-month period. Surveillance and treatment of melanoma. All surveillance and treatment procedures were identified through direct observation, review of medical records, and interviews with staff and were valued using scheduled fees from the Australian government. Societal costs included transportation and loss of productivity. The mean number of clinic visits per year was 2.7 (95% CI, 2.5-2.8) for surveillance and 3.8 (95% CI, 3.4-4.1) for patients requiring surgical excisions. The mean annual cost per patient to the health system was A $882 (95% CI, A $783-$982) (US $599 [95% CI, US $532-$665]); the cost discounted across 20 years was A $11,546 (95% CI, A $10,263-$12,829) (US $7839 [95% CI, US $6969-$8710]). The mean annual societal cost per patient (excluding health system costs) was A $972 (95% CI, A $899-$1045) (US $660 [95% CI, US $611-$710]); the cost discounted across 20 years was A $12,721 (95% CI, A $12,554-$14,463) (US $8637 [95% CI, US $8523-$9820]). Diagnosis of melanoma or nonmelanoma skin cancer and frequent excisions for benign lesions in a relatively small number of patients was responsible for positively skewed health system costs. Microcosting techniques provide an accurate cost estimate for the provision of a specialized service. The high societal cost reflects the time that patients are willing to invest to attend the high-risk clinic. This alternative model of care for a high-risk population has relevance for decision making about health policy.

  7. Fetal programming and early identification of newborns at high risk of free radical-mediated diseases.

    Science.gov (United States)

    Perrone, Serafina; Santacroce, Antonino; Picardi, Anna; Buonocore, Giuseppe

    2016-05-08

    Nowadays metabolic syndrome represents a real outbreak affecting society. Paradoxically, pediatricians must feel involved in fighting this condition because of the latest evidences of developmental origins of adult diseases. Fetal programming occurs when the normal fetal development is disrupted by an abnormal insult applied to a critical point in intrauterine life. Placenta assumes a pivotal role in programming the fetal experience in utero due to the adaptive changes in structure and function. Pregnancy complications such as diabetes, intrauterine growth restriction, pre-eclampsia, and hypoxia are associated with placental dysfunction and programming. Many experimental studies have been conducted to explain the phenotypic consequences of fetal-placental perturbations that predispose to the genesis of metabolic syndrome, obesity, diabetes, hyperinsulinemia, hypertension, and cardiovascular disease in adulthood. In recent years, elucidating the mechanisms involved in such kind of process has become the challenge of scientific research. Oxidative stress may be the general underlying mechanism that links altered placental function to fetal programming. Maternal diabetes, prenatal hypoxic/ischaemic events, inflammatory/infective insults are specific triggers for an acute increase in free radicals generation. Early identification of fetuses and newborns at high risk of oxidative damage may be crucial to decrease infant and adult morbidity.

  8. Teamwork in high-risk environments analogous to space

    Science.gov (United States)

    Kanki, Barbara G.

    1990-01-01

    Mountaineering expeditions combine a number of factors which make them potentially good analogs to the planetary exploration facet of long-duration space missions. A study of mountain climbing teams was conducted in order to evaluate the usefulness of the environment as a space analog and to specifically identify the factors and issues surrounding teamwork and 'successful' team performance in two mountaineering environments. This paper focuses on social/organizational factors, including team size and structure, leadership styles and authority structure which were found in the sample of 22 climb teams (122 individuals). The second major issue discussed is the construction of a valid performance measure in this high-risk environment.

  9. Relationship between PLAP and high-risk pregnancy

    International Nuclear Information System (INIS)

    Yu Huixin; Xiao Weihong; Cao Guoxian; Li Weiyi; Shen Bo

    2001-01-01

    PLAP was isolated and purified from human placenta and the antiserum was obtained by immunizing the rabbits. A radioimmunoassay of PLAP (PLAP RIA) was established by labelling the antigen using the chloramine-T method. Its sensitivity was 1.54 μg/L, the recovery rate was between 96.7% and 105.2%, the intra- and inter-assay CV were 8.94% and 9.43%, respectively, the antiserum provided a linear response from 2 to 1000 μg/L. The assay has no cross-reactivity with liver AP. Serum level of PLAP were measured by PLAP RIA in 649 cases of normal pregnancy and 164 cases of high-risk pregnancy. The results indicated that the PLAP level increased proportionally with the advance of gestational age (r = 0.9843). In 33 cases of pregnancy induced hypertension and 21 cases of intrauterine fetal growth retardation, the PLAP were at significantly low level. In 7 cases of neonatal asphyxia and 26 cases of fetal distress, the PLAP level in the mother's serum were also low. In 53 cases of intrahepatic cholestasis of pregnancy, the PLAP level were similar to those of normal pregnancy. This study illustrated that PLAP RIA can play an important role in evaluation of placental function and fetal prognosis for cases of high-risk pregnancy

  10. Oral health status of women with high-risk pregnancies.

    Science.gov (United States)

    Merglova, Vlasta; Hecova, Hana; Stehlikova, Jaroslava; Chaloupka, Pavel

    2012-12-01

    The aim of this study was to investigate the oral health status of women with high-risk pregnancies. A case-control study of 142 pregnant women was conducted. The case group included 81 pregnant women with high-risk pregnancies, while 61 women with normal pregnancies served as controls. The following variables were recorded for each woman: age, general health status, DMF, CPITN, and PBI index, amounts of Streptococcus mutans in the saliva and dental treatment needs. The Mann-Whitney test, Kruskal-Wallis test, t-test and chi-squared test were used for statistical analyses. Statistically significant differences were detected between the PBI indices and dental treatment needs of the two groups. Out of the entire study cohort, 77% of the women in the case group and 52% of the women in the control group required dental treatment. In this study, women with complications during pregnancy had severe gingivitis and needed more frequent dental treatment than those in the control group.

  11. Personality differences in high risk sports amateurs and instructors.

    Science.gov (United States)

    Watson, Alison E; Pulford, Briony D

    2004-08-01

    This study investigated the personality differences of 21 amateurs and 20 instructors who participated in the high risk sports of skydiving, hang-gliding, paragliding, scuba diving, microlighting, and rock climbing, versus those who did not. 38 men and 28 women (M age=32.6 yr., SD= 10.0) were assessed using the Eysenck Personality Questionnaire-Revised, the General Health Questionnaire, the Generalised Self-efficacy Scale, and a Type A/B personality measure. Instructors and Amateurs scored significantly higher on Extroversion and lower on Neuroticism than Nonparticipants; however, they differed from each other on the General Health Questionnaire and Type A/B personality scores. Amateurs scored significantly higher on Psychoticism and Self-efficacy than Instructors and Nonparticipants. In conclusion, these test scores suggest that people who are attracted to high risk sports tend to be at the extroverted and emotionally stable end of the scale, with a tendency to exhibit Type A characteristics; however, Instructors' scores on Psychoticism and Self-efficacy are more akin to those of Nonparticipants.

  12. High-Risk Stress Fractures: Diagnosis and Management.

    Science.gov (United States)

    McInnis, Kelly C; Ramey, Lindsay N

    2016-03-01

    Stress fractures are common overuse injuries in athletes. They occur during periods of increased training without adequate rest, disrupting normal bone reparative mechanisms. There are a host of intrinsic and extrinsic factors, including biochemical and biomechanical, that put athletes at risk. In most stress fractures, the diagnosis is primarily clinical, with imaging indicated at times, and management focused on symptom-free relative rest with advancement of activity as tolerated. Overall, stress fractures in athletes have an excellent prognosis for return to sport, with little risk of complication. There is a subset of injuries that have a greater risk of fracture progression, delayed healing, and nonunion and are generally more challenging to treat with nonoperative care. Specific locations of high-risk stress fracture include the femoral neck (tension side), patella, anterior tibia, medial malleolus, talus, tarsal navicular, proximal fifth metatarsal, and great toe sesamoids. These sites share a characteristic region of high tensile load and low blood flow. High-risk stress fractures require a more aggressive approach to evaluation, with imaging often necessary, to confirm early and accurate diagnosis and initiate immediate treatment. Treatment consists of nonweight-bearing immobilization, often with a prolonged period away from sport, and a more methodic and careful reintroduction to athletic activity. These stress fractures may require surgical intervention. A high index of suspicion is essential to avoid delayed diagnosis and optimize outcomes in this subset of stress fractures. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  13. Relationship between PLAP and high-risk pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Huixin, Yu; Weihong, Xiao; Guoxian, Cao; Weiyi, Li; Bo, Shen [Jiangsu Inst. of Nuclear Medicine, Wuxi (China). National Key Laboratory of Nuclear Medicine

    2001-04-01

    PLAP was isolated and purified from human placenta and the antiserum was obtained by immunizing the rabbits. A radioimmunoassay of PLAP (PLAP RIA) was established by labelling the antigen using the chloramine-T method. Its sensitivity was 1.54 {mu}g/L, the recovery rate was between 96.7% and 105.2%, the intra- and inter-assay CV were 8.94% and 9.43%, respectively, the antiserum provided a linear response from 2 to 1000 {mu}g/L. The assay has no cross-reactivity with liver AP. Serum level of PLAP were measured by PLAP RIA in 649 cases of normal pregnancy and 164 cases of high-risk pregnancy. The results indicated that the PLAP level increased proportionally with the advance of gestational age (r = 0.9843). In 33 cases of pregnancy induced hypertension and 21 cases of intrauterine fetal growth retardation, the PLAP were at significantly low level. In 7 cases of neonatal asphyxia and 26 cases of fetal distress, the PLAP level in the mother's serum were also low. In 53 cases of intrahepatic cholestasis of pregnancy, the PLAP level were similar to those of normal pregnancy. This study illustrated that PLAP RIA can play an important role in evaluation of placental function and fetal prognosis for cases of high-risk pregnancy.

  14. Breast cancer in high-risk Afrikaner families: Is BRCAfounder ...

    African Journals Online (AJOL)

    Breast cancer is the most common form of cancer in women worldwide. Altogether 6 224 cases were reported in South Africa (SA) in 2009.[1] Up to 10% of breast cancer cases are attributable to germline mutations in cancer susceptibility genes, leading to hereditary syndromes.[2] The most well described of these cancer.

  15. Characterizing and Reaching High-Risk Drinkers Using Audience Segmentation

    Science.gov (United States)

    Moss, Howard B.; Kirby, Susan D.; Donodeo, Fred

    2010-01-01

    Background Market or audience segmentation is widely used in social marketing efforts to help planners identify segments of a population to target for tailored program interventions. Market-based segments are typically defined by behaviors, attitudes, knowledge, opinions, or lifestyles. They are more helpful to health communication and marketing planning than epidemiologically-defined groups because market-based segments are similar in respect to how they behave or might react to marketing and communication efforts. However, market segmentation has rarely been used in alcohol research. As an illustration of its utility, we employed commercial data that describes the sociodemographic characteristics of high-risk drinkers as an audience segment; where they tend to live, lifestyles, interests, consumer behaviors, alcohol consumption behaviors, other health-related behaviors, and cultural values. Such information can be extremely valuable in targeting and planning public health campaigns, targeted mailings, prevention interventions and research efforts. Methods We describe the results of a segmentation analysis of those individuals who self-report consuming five or more drinks per drinking episode at least twice in the last 30-days. The study used the proprietary PRIZM™ audience segmentation database merged with Center for Disease Control and Prevention's (CDC) Behavioral Risk Factor Surveillance System (BRFSS) database. The top ten of the 66 PRIZM™ audience segments for this risky drinking pattern are described. For five of these segments we provide additional in-depth details about consumer behavior and the estimates of the market areas where these risky drinkers reside. Results The top ten audience segments (PRIZM clusters) most likely to engage in high-risk drinking are described. The cluster with the highest concentration of binge drinking behavior is referred to as the “Cyber Millenials.” This cluster is characterized as “the nation's tech-savvy singles

  16. Characterizing and reaching high-risk drinkers using audience segmentation.

    Science.gov (United States)

    Moss, Howard B; Kirby, Susan D; Donodeo, Fred

    2009-08-01

    Market or audience segmentation is widely used in social marketing efforts to help planners identify segments of a population to target for tailored program interventions. Market-based segments are typically defined by behaviors, attitudes, knowledge, opinions, or lifestyles. They are more helpful to health communication and marketing planning than epidemiologically defined groups because market-based segments are similar in respect to how they behave or might react to marketing and communication efforts. However, market segmentation has rarely been used in alcohol research. As an illustration of its utility, we employed commercial data that describes the sociodemographic characteristics of high-risk drinkers as an audience segment, including where they tend to live, lifestyles, interests, consumer behaviors, alcohol consumption behaviors, other health-related behaviors, and cultural values. Such information can be extremely valuable in targeting and planning public health campaigns, targeted mailings, prevention interventions, and research efforts. We described the results of a segmentation analysis of those individuals who self-reported to consume 5 or more drinks per drinking episode at least twice in the last 30 days. The study used the proprietary PRIZM (Claritas, Inc., San Diego, CA) audience segmentation database merged with the Center for Disease Control and Prevention's (CDC) Behavioral Risk Factor Surveillance System (BRFSS) database. The top 10 of the 66 PRIZM audience segments for this risky drinking pattern are described. For five of these segments we provided additional in-depth details about consumer behavior and the estimates of the market areas where these risky drinkers resided. The top 10 audience segments (PRIZM clusters) most likely to engage in high-risk drinking are described. The cluster with the highest concentration of binge-drinking behavior is referred to as the "Cyber Millenials." This cluster is characterized as "the nation's tech

  17. An International MDS/MPN Working Group’s perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic/myeloproliferative neoplasms

    Science.gov (United States)

    Mughal, Tariq I.; Cross, Nicholas C.P.; Padron, Eric; Tiu, Ramon V.; Savona, Michael; Malcovati, Luca; Tibes, Raoul; Komrokji, Rami S.; Kiladjian, Jean-Jacques; Garcia-Manero, Guillermo; Orazi, Attilio; Mesa, Ruben; Maciejewski, Jaroslaw P.; Fenaux, Pierre; Itzykson, Raphael; Mufti, Ghulam; Solary, Eric; List, Alan F.

    2015-01-01

    In the 2008 WHO classification, chronic myeloid malignancies that share both myelodysplastic and myeloproliferative features define the myelodysplastic/myeloproliferative group, which includes chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical chronic myeloid leukemia, refractory anemia with ring sideroblasts and thrombocytosis, and myelodysplastic/myeloproliferative unclassified. With the notable exception of refractory anemia with ring sideroblasts and thrombocytosis, there is much overlap among the various subtypes at the molecular and clinical levels, and a better definition of these entities, an understanding of their biology and an identification of subtype-specific molecular or cellular markers are needed. To address some of these challenges, a panel comprised of laboratory and clinical experts in myelodysplastic/myeloproliferative was established, and four independent academic MDS/MPN workshops were held on: 9th March 2013, in Miami, Florida, USA; 6th December 2013, in New Orleans, Louisiana, USA; 13th June 2014 in Milan, Italy; and 5th December 2014 in San Francisco, USA. During these meetings, the current understanding of these malignancies and matters of biology, diagnosis and management were discussed. This perspective and the recommendations on molecular pathogenesis, diagnosis and clinical characterization for adult onset myelodysplastic/myeloproliferative is the result of a collaborative project endorsed and supported by the MDS Foundation. PMID:26341525

  18. High risk pregnancy referrals adequacy in the Basic Health Services of Sobral, Ceará, Brazil

    Directory of Open Access Journals (Sweden)

    José Juvenal Linhares

    2009-03-01

    Full Text Available Objective: To describe the appropriateness of referrals of high-risk pregnancies in the basic healthcare network of Sobral, in Ceará, Brazil. Methods: A descriptive quantitative study. The medical files of 173 pregnant patients referred to the high-risk outpatient clinic of Centro de Especialidades Médicas of Sobral, during the period from July 2006 to April 2007, were analyzed. Variables analyzed were correctness of the referrals, professionals who made them, causes and origins of the referrals, and age bracket of the patients referred. The referrals were divided into “appropriate” and “inappropriate”, according to the classification of risk established by the technical manual of the Ministry of Health. Rresults: Of the 173 cases, 102 (59% were considered appropriate/correct, and 71 (41% referrals were considered inappropriate/incorrect. The referrals were divided according to the professional class of the referring individuals: physicians or nurses. Of the 173 referrals, 49 (28.3% were made by physicians, and 124 (71.7% by nurses. Of the 49 patients referred by physicians, 39 (79.6% were considered correct. Of the 124 referrals made by nurses, 63 (50.8% were considered incorrect, revealing a significant difference between the groups (p < 0.00001. The most common causes of referrals of pregnant patients were hypertensive syndromes (23.6%, physiological modifications of pregnancy (22.6%, prolonged pregnancy (15.1%, and diabetes (12.3%. Cconclusions: There was a low rate of appropriate/correct referrals. There is a need for training in the basic healthcare network for quality prenatal care, with special emphasis on referring nurses.

  19. Prediction of diabetes based on baseline metabolic characteristics in individuals at high risk.

    Science.gov (United States)

    Defronzo, Ralph A; Tripathy, Devjit; Schwenke, Dawn C; Banerji, Maryann; Bray, George A; Buchanan, Thomas A; Clement, Stephen C; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Ratner, Robert E; Stentz, Frankie B; Musi, Nicolas; Reaven, Peter D; Gastaldelli, Amalia

    2013-11-01

    Individuals with impaired glucose tolerance (IGT) are at high risk for developing type 2 diabetes mellitus (T2DM). We examined which characteristics at baseline predicted the development of T2DM versus maintenance of IGT or conversion to normal glucose tolerance. We studied 228 subjects at high risk with IGT who received treatment with placebo in ACT NOW and who underwent baseline anthropometric measures and oral glucose tolerance test (OGTT) at baseline and after a mean follow-up of 2.4 years. In a univariate analysis, 45 of 228 (19.7%) IGT individuals developed diabetes. After adjusting for age, sex, and center, increased fasting plasma glucose, 2-h plasma glucose, G0-120 during OGTT, HbA1c, adipocyte insulin resistance index, ln fasting plasma insulin, and ln I0-120, as well as family history of diabetes and presence of metabolic syndrome, were associated with increased risk of diabetes. At baseline, higher insulin secretion (ln [I0-120/G0-120]) during the OGTT was associated with decreased risk of diabetes. Higher β-cell function (insulin secretion/insulin resistance or disposition index; ln [I0-120/G0-120 × Matsuda index of insulin sensitivity]; odds ratio 0.11; P < 0.0001) was the variable most closely associated with reduced risk of diabetes. In a stepwise multiple-variable analysis, only HbA1c and β-cell function (ln insulin secretion/insulin resistance index) predicted the development of diabetes (r = 0.49; P < 0.0001).

  20. Cyberbullying in those at clinical high risk for psychosis.

    Science.gov (United States)

    Magaud, Emilie; Nyman, Karissa; Addington, Jean

    2013-11-01

    Several studies suggest an association between experiences of childhood trauma including bullying and the development of psychotic symptoms. The use of communications technology has created a new media for bullying called 'cyberbullying'. Research has demonstrated associations between traditional bullying and cyberbullying. Negative effects of cyberbullying appear similar in nature and severity to the reported effects of traditional bullying. Our aim was to examine the prevalence and correlates of cyberbullying in those at clinical high risk (CHR) for psychosis. Fifty young people at CHR for psychosis were administered the Childhood Trauma Questionnaire with added questions about cyberbullying. Cyberbullying was reported in 38% of the sample. Those who experienced cyberbullying also reported experiencing previous trauma. It is possible that cyberbullying may be a problem for those at CHR of psychosis, and due to the vulnerable nature of these young people may have longitudinal implications. © 2013 Wiley Publishing Asia Pty Ltd.

  1. Early detection of psychosis: finding those at clinical high risk.

    Science.gov (United States)

    Addington, Jean; Epstein, Irvin; Reynolds, Andrea; Furimsky, Ivana; Rudy, Laura; Mancini, Barbara; McMillan, Simone; Kirsopp, Diane; Zipursky, Robert B

    2008-08-01

    In early detection work, recruiting individuals who meet the prodromal criteria is difficult. The aim of this paper was to describe the development of a research clinic for individuals who appear to be at risk of developing a psychosis and the process for educating the community and obtaining referrals. The outcome of all referrals to the clinic over a 4-year period was examined. Following an ongoing education campaign that was over inclusive in order to aid recruitment, approximately 27% of all referrals met the criteria for being at clinical high risk of psychosis. We are seeing only a small proportion of those in the community who eventually go on to develop a psychotic illness. This raises two important issues, namely how to remedy the situation, and second, the impact of this on current research in terms of sampling bias and generalizability of research findings. © 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Asia Pty Ltd.

  2. Recommendations of activity restriction in high-risk pregnancy scenarios

    DEFF Research Database (Denmark)

    Bendix, Jane; Hegaard, Hanne Kristine; Bergholt, Thomas

    2015-01-01

    activity restriction more often than obstetricians in five of the nine scenarios, in women with preterm premature rupture of membranes, preterm labour, cervical ripening, total placenta praevia, and intrauterine growth restriction, whereas no differences were found in the remaining scenarios. Compared...... to the obstetricians, the midwives also reported that they expected the recommendation to be more effective. Most midwives and obstetricians reported that they thought strict activity restriction was associated with severe or moderate adverse effect, and recommended antithrombotic prophylaxis. Conclusions: Danish...... obstetricians and midwives prescribe activity restriction in most high-risk pregnancies. The degree of activity restriction and the presumed effect vary between clinicians. This may reflect different attitudes and lack of guidelines based on clinical studies of a possible benefit of activity restriction....

  3. Condom availability in high risk places and condom use

    DEFF Research Database (Denmark)

    Sandøy, Ingvild Fossgard; Blystad, Astrid; Shayo, Elizabeth H.

    2012-01-01

    study findings indicate that substantial further efforts should be made to secure that condoms are easily accessible in places where sexual relationships are initiated. Although condom distribution in drinking places has been pinpointed in the HIV/AIDS prevention strategies of all the three countries......Background A number of studies from countries with severe HIV epidemics have found gaps in condom availability, even in places where there is a substantial potential for HIV transmission. Although reported condom use has increased in many African countries, there are often big differences...... in the availability of condoms in places where people meet new sexual partners in these three African districts. Considering that previous studies have found that improved condom availability and accessibility in high risk places have a potential to increase condom use among people with multiple partners, the present...

  4. [Prevention of the refeeding syndrome].

    Science.gov (United States)

    Martínez Núñez, Maria E; Hernández Muniesa, B

    2010-01-01

    The refeeding syndrome can be defined as the metabolic alterations developed by the rapid nutrition repletion (oral, enteral as well as parenteral feeding) of severaly malnourished patients. Refeeding syndrome is a potentially fatal clinical condition and it is often underdiagnosed on non-specialized nutrition units. The most important key for its prevention is to identify patients at high risk for developing refeeding syndrome, before nutrition repletion. The present case describes the steps to prevent the refeeding syndrome as well as the clinical recommendations to restart nutrition support.

  5. Bullous Variant of Sweet’s Syndrome after Herpes Zoster Virus Infection

    OpenAIRE

    Yuichiro Endo; Miki Tanioka; Hideaki Tanizaki; Minako Mori; Hiroshi Kawabata; Yoshiki Miyachi

    2011-01-01

    Aim: Cutaneous manifestations of Sweet’s syndrome (SS) are typically painful plaque-forming erythematous papules, while bullae are quite uncommon. We present a case of bullous variant of SS in acute myeloid leukaemia. In this case, herpes infection of the left mandible had preceded the development of SS. Case Report: A 75-year-old male with myelodysplastic syndrome first presented with herpes zoster virus infection-like bullae and erosive plaques on the left side of the face and neck. Treatme...

  6. High-Risk Driving Behaviors among Adolescent Binge-Drinkers

    Science.gov (United States)

    Marcotte, Thomas D.; Bekman, Nicole M.; Meyer, Rachel A.; Brown, Sandra A.

    2013-01-01

    Background Binge drinking is common among adolescents. Alcohol use, and binge-drinking in particular, has been associated with neurocognitive deficits as well as risk-taking behaviors, which may contribute to negative driving outcomes among adolescents even while sober. Objectives To examine differences in self-reported driving behaviors between adolescent binge-drinkers and a matched sample of controls, including (a) compliance with graduated licensing laws, (b) high risk driving behaviors, and (c) driving outcomes (crashes, traffic tickets). Methods The present study examined driving behaviors and outcomes in adolescent recent binge drinkers (n=21) and demographically and driving history matched controls (n=17), ages 16-18. Results Binge drinkers more frequently violated graduated licensing laws (e.g., driving late at night), and engaged in more “high risk” driving behaviors, such as speeding and using a cell-phone while driving. Binge drinkers had more traffic tickets, crashes and “near crashes” than the control group. In a multivariate analysis, binge drinker status and speeding were the most robust predictors of a crash. Conclusion Binge drinking teens consistently engage in more dangerous driving behaviors and experience more frequent crashes and traffic tickets. They are also less compliant with preventative restrictions placed on youth while they are learning critical safe driving skills. Scientific Significance These findings highlight a need to examine the contribution of underlying traits (such as sensation seeking) and binge-related cognitive changes to these high-risk driving behaviors, which may assist researchers in establishing alternative prevention and policy efforts targeting this population. PMID:22324748

  7. [High risk factors of upper gastrointestinal bleeding after neurosurgical procedures].

    Science.gov (United States)

    Zheng, Kang; Wu, Gang; Cheng, Neng-neng; Yao, Cheng-jun; Zhou, Liang-fu

    2005-12-21

    To analyze high risk factors of postoperative upper gastrointestinal (GI) bleeding after neurosurgery so as to give guidance for prevention of GI bleeding. A questionnaire was developed to investigate the medical records of 1500 patients who were hospitalized and underwent neurosurgical operations in 1997. Logistic regression analysis was made. 1430 valid questionnaires were obtained. Postoperative upper GI bleeding occurred in 75 patients (5.24%). The incidence of upper GI bleeding were 6.64% (54/813) in the male patients and 3.40% (21/617) in the female persons (P = 0.007); 9.88% (41/415) in those aged > 50 and 3.35% in those aged hematoma, intraventricular hemorrhage, subdural hematoma, and extradural hematoma were 15.7%, 10.0%, 6.00%, and 2.94% respectively (P = 0.02). The incidence of upper GI bleeding of the patients with tumors of fourth ventricle of cerebrum, brainstem, cerebral hemisphere, and sellar hypothalamus were 15.79% (3/19), 7.89%, 5.71%, and 3.74% respectively. In the emergent cases, the incidence of upper GI bleeding was higher in those with hypertension. The incidence of upper GI bleeding was 5.46% in the patients undergoing adrenocortical hormone treatment, significantly higher than that in those who did not receive such treatment (2.13%). Patients who are at high risk of developing postoperative upper GI bleeding including that: age greater than 50 years; male; Glasgow Coma Score less than 10 pre and post operation; The lesion was located in brain stem and forth ventricle; Hypertensive cerebral hemorrhage; Intracerebral and intraventricular hemorrhagic brain trauma; Postoperative pneumonia, brain edema, encephalic high pressure, pyogenic infection of the central nervous system and other postoperative complications. The mortality of patients with postoperative upper GI bleeding was evidently higher than that of the patients without postoperative upper GI bleeding.

  8. Variation in readmission expenditures after high-risk surgery.

    Science.gov (United States)

    Jacobs, Bruce L; He, Chang; Li, Benjamin Y; Helfand, Alex; Krishnan, Naveen; Borza, Tudor; Ghaferi, Amir A; Hollenbeck, Brent K; Helm, Jonathan E; Lavieri, Mariel S; Skolarus, Ted A

    2017-06-01

    The Hospital Readmissions Reduction Program reduces payments to hospitals with excess readmissions for three common medical conditions and recently extended its readmission program to surgical patients. We sought to investigate readmission intensity as measured by readmission cost for high-risk surgeries and examine predictors of higher readmission costs. We used the Healthcare Cost and Utilization Project's State Inpatient Database to perform a retrospective cohort study of patients undergoing major chest (aortic valve replacement, coronary artery bypass grafting, lung resection) and major abdominal (abdominal aortic aneurysm repair [open approach], cystectomy, esophagectomy, pancreatectomy) surgery in 2009 and 2010. We fit a multivariable logistic regression model with generalized estimation equations to examine patient and index admission factors associated with readmission costs. The 30-d readmission rate was 16% for major chest and 22% for major abdominal surgery (P readmission costs for both chest (odds ratio [OR]: 1.99; 95% confidence interval [CI]: 1.60-2.48) and abdominal surgeries (OR: 1.86; 95% CI: 1.24-2.78). Comorbidities, length of stay, and receipt of blood or imaging was associated with higher readmission costs for chest surgery patients. Readmission >3 wk after discharge was associated with lower costs among abdominal surgery patients. Readmissions after high-risk surgery are common, affecting about one in six patients. Predictors of higher readmission costs differ among major chest and abdominal surgeries. Better identifying patients susceptible to higher readmission costs may inform future interventions to either reduce the intensity of these readmissions or eliminate them altogether. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. High-risk sexual behavior among drug-using men.

    Science.gov (United States)

    Seidman, S N; Sterk-Elifson, C; Aral, S O

    1994-01-01

    Drug-using men are at high risk for acquisition and transmission of STD, presumably due to the risky behaviors practiced in environments of drug use. To study behaviors associated with STD transmission among drug-using men. Drug outreach workers distributed vouchers to self-identified drug-using men in urban Atlanta. Vouchers could be redeemed for cash at a storefront clinic where subjects provided urine for a urethritis screening test (leukocyte esterase test) and a drug screen, and were interviewed. Of 382 voucher recipients, 252 (66%) came to the clinic. Subjects were predominantly black (92%), homeless (70%), and aged 20 to 40 (88%). All used illicit drugs; none were currently receiving drug abuse treatment. Urine drug screen confirmed recent cocaine use in 63%, and recent opiate use in 4%. Three-fourths reported a history of STD, mostly gonorrhea. In the preceding 3 months, 14% had not had sex, 80% had sex exclusively with women, 4% had sex with both men and women, and 2% had sex exclusively with men. Of the heterosexually active men, 29% had 5 or more recent partners. Compared to other heterosexually active men, these men were more likely to always use alcohol or crack before having sex (prevalence ratio [PR] = 2.0, 95% CI = 1.3-2.5) and to drink alcohol every day (PR = 2.0, 95% CI = 1.2-3.3). Daily crack use was associated with choosing partners at elevated STD risk; daily alcohol use with having more partners. Positive drug screen for cocaine was associated with self-reported crack use. Urethritis, detected in 16%, was not correlated with behavior. A substantial number of drug-using men practice high-risk sexual behavior and should be targeted for intervention. Monetary and other incentives should be considered for recruitment. Further study is needed to clarify the relationship between sexual behavior, cocaine use, and STD.

  10. Pre-Irradiation Chemotherapy in High Risk Medulloblastoma

    International Nuclear Information System (INIS)

    Abd-El-Aal, H.

    2006-01-01

    Rationale: The present study evaluates the effect of pre-irradiation chemotherapy in pediatric patients with high risk medulloblastoma. Twenty-four (24) pediatric patients attended the pediatric unit of Kasr-EI-Aini Center of Radiation Oncology and Nuclear Medicine (NEMROCK) from January 2000 to January 2003. Patients and Methods: Our patients were 13 boys and II girls aged 3-12 years with a median of 6.5 years. According to Chang staging system 6 cases had T2, 14 cases had T3 A and 4 cases had T3 B, 20 cases were M0, 3 cases were M I and I case was M2. All patients were treated by initial surgery, 2 cycles of pre-irradiation chemotherapy followed by craniospinal radiation then by 4 cycles of post-radiation chemotherapy. Results: Fifteen out of the 20 patients with M0 had objective response (10CR + 5PR) and no one had disease progression after pre-irradiation chemotherapy. Among 4 patients with M0 disease, 2 patients had PR and 2 had S.D. There was no disease progression among patients who received pre-irradiation chemotherapy. The 3-year overall survival and 3-year progression-free survival; (PFS) were 50% and 51 %, respectively, Myelosuppression was the main toxic effect observed during pre-irradiation chemotherapy; however, there was no delay or interruption of craniospinal irradiation. Conclusion: Pre-irradiation chemotherapy is effective in high risk medulloblastoma and is associated with acceptable side effects. The delay in craniospinal irradiation (CSI) for about 5 weeks to receive 2 courses of chemotherapy will not significantly increase disease progression. Multiple cycles of post-irradiation chemotherapy can be given safely after C51. A larger number of patients and longer follow-up is needed to confirm the results

  11. Multiparameter flow cytometry reveals myelodysplasia-related aberrant antigen expression in myelodysplastic/myeloproliferative neoplasms.

    Science.gov (United States)

    Kern, Wolfgang; Bacher, Ulrike; Schnittger, Susanne; Alpermann, Tamara; Haferlach, Claudia; Haferlach, Torsten

    2013-05-01

    Within the myelodysplastic/myeloproliferative neoplasm (MDS/MPN) category of the WHO (2008), only chronic myelomonocytic leukemia was so far evaluated by multiparameter flow cytometry (MFC). To investigate the potential of MFC for MDS/MPNs, unclassifiable (MDS/MPNu), and refractory anemia associated with ring sideroblasts and marked thrombocytosis (RARS-T), we studied 91 patients with these entities (60 males/31 females; 35.3-87.4 years) for MDS-related aberrant immunophenotypes (≥ 2 different cell lineages with ≥ 3 aberrantly expressed antigens). Data were correlated with cytomorphology and cytogenetics. MFC identified MDS-related immunophenotypes in 54/91 (59.3%) of patients. Patients with or without MDS-related immunophenotype did not differ significantly by demographic characteristics, blood values, or median overall survival. MDS-related immunophenotype cases showed a higher number of aberrantly expressed antigens (mean ± SD, 4.9 ± 2.4 vs. 2.0 ± 1.4; P MPNu and RARS-T. MFC therefore may be helpful to separate cases into more "MDS-like" or "MPN-like" subgroups. Copyright © 2012 International Clinical Cytometry Society.

  12. Symptom assessment in early psychosis: The use of well-established rating scales in clinical high-risk and recent-onset populations

    OpenAIRE

    Fulford, Daniel; Pearson, Rahel; Stuart, Barbara K.; Fisher, Melissa; Mathalon, Daniel H.; Vinogradov, Sophia; Loewy, Rachel L.

    2014-01-01

    Symptom assessment in early psychosis research typically relies on scales validated in chronic schizophrenia samples. Our goal was to inform investigators who are selecting symptom scales for early psychosis research. We described measure characteristics, baseline scores, and scale inter-relationships in clinical high-risk (CHR) and recent-onset psychotic disorder (RO) samples using the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Scale for the Assessment of Positive ...

  13. High risk pregnancies and factors associated with neonatal death.

    Science.gov (United States)

    Demitto, Marcela de Oliveira; Gravena, Angela Andréia França; Dell'Agnolo, Cátia Millene; Antunes, Marcos Benatti; Pelloso, Sandra Marisa

    2017-04-03

    To identify the factors associated with intra-hospital neonatal mortality based on the individual characteristics of at-risk pregnant mothers, delivery and newborns. This was a cross-sectional epidemiological study of live newborns delivered by women attended at the high-risk outpatient unit of a philanthropic hospital in Maringá, Paraná, Brazil between September 2012 and September 2013. Six hundred and eighty-eight women participated in the study. The neonatal mortality coefficient found was 17.7/1,000 live births, most in the early neonatal phase. Premature labor, fetal malformation and multiple gestations were associated with neonatal death. Premature, very low birth weight newborns and those with an Apgar score of less than seven, five minutes after birth were at high risk of death. Identifying risk factors can help plan actions to consolidate the perinatal network. Specific programs should be incentivized in other countries, in the search for significant perinatal results such as reducing neonatal mortality. Identificar os fatores associados à mortalidade neonatal intra-hospitalar com base nas características individuais de gestantes de risco, do parto e do recém-nascido. Estudo epidemiológico do tipo transversal, realizado com crianças nascidas vivas de partos hospitalares de mulheres acompanhadas pelo ambulatório de alto risco de um hospital filantrópico de Maringá, Paraná, Brasil, no período de setembro de 2012 a setembro de 2013.RESULTADOS Fizeram parte da pesquisa 688 mulheres. O coeficiente de mortalidade neonatal foi de 17,7 óbitos/1.000 nascidos vivos, sendo sua maioria no período neonatal precoce. Trabalho de parto prematuro, malformação fetal e gestação múltipla foram as intercorrências associadas ao óbito neonatal. Recém-nascidos prematuros, com muito baixo peso ao nascer e Índice de Apgar menor que sete no quinto minuto de vida apresentaram risco elevado de morte. A identificação de fatores de risco pode auxiliar no

  14. From the lab - Predicting Autism in High-Risk Infants | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... High-Risk Infants Follow us Photo: iStock Predicting Autism in High-Risk Infants AN NIH-SUPPORTED STUDY ... high-risk, 6-month-old infants will develop autism spectrum disorder by age 2. Such a tool ...

  15. Fractional laser-mediated photodynamic therapy of high-risk basal cell carcinomas

    DEFF Research Database (Denmark)

    Haak, C S; Togsverd-Bo, K; Thaysen-Petersen, D

    2015-01-01

    efficacy and safety of AFXL-mediated PDT (AFXL-PDT) compared with conventional PDT of high-risk nBCC. METHODS: Patients with histologically verified facial nBCC (n = 32) defined as high-risk tumours were included; diameter > 15 mm, tumours located in high-risk zones, or on severely sun-damaged skin...

  16. Pressure ulcer prevention in high-risk postoperative cardiovascular patients.

    Science.gov (United States)

    Jackson, Melissa; McKenney, Teresa; Drumm, Jennifer; Merrick, Brian; LeMaster, Tamara; VanGilder, Catherine

    2011-08-01

    Little has been published about how to prevent pressure ulcers in severely debilitated, immobile patients in intensive care units. To present a possible prevention strategy for postoperative cardiovascular surgery patients at high risk for development of pressure ulcers. Staff chose to implement air fluidized therapy beds, which provide maximal immersion and envelopment as a measure for preventing pressure ulcers in patients who (1) required vasopressors for at least 24 hours and (2) required mechanical ventilation for at least 24 hours postoperatively. Only 1 of 27 patients had a pressure ulcer develop while on the air fluidized therapy bed (February 2008 through August 2008), and that ulcer was only a stage I ulcer, compared with 40 ulcers in 25 patients before the intervention. Patients spent a mean of 7.9 days on the mattress, and the cost of bed rental was approximately $18000, which was similar to the cost of treatment of 1 pressure ulcer in stage III or IV (about $40000) and was considered cost-effective.

  17. INSTRUMENTS OF HIGH RISK SEXUAL BEHAVIOR ASSESSMENT: A SYSTEMATIC REVIEW.

    Science.gov (United States)

    Mirzaei, Mojtaba; Ahmadi, Khodabakhsh; Saadat, Seyed-Hassan; Ramezani, Mohammad Arash

    2016-02-01

    Sexual behavior is a complex activity affecting all aspects of human's life. Risky sexual behaviors impose negative outcomes on family, relationships and health. Unsafe sex is the second most leading cause of disability adjusted life years worldwide. Valid and reliable tools for assessment of risky sexual behaviors are necessary for implementing preventive measures. we searched Medline and the Cochrane Library of Systematic Reviews, with the keywords of "risky sexual behavior assessment", "sexual risk assessment", "high risk sexual behavior", "sexual risk taking". By reviewing references of the articles, some complementary studies were added. Assessment can be performed by questionnaire or non-questionnaire instruments. Questionnaires vary depending on their target population, evaluation of risky sexual behavior as a whole or focusing on an associated risk factor. In order to avoid usual biases in self reports, objective biomarker assessment of unprotected sex are employed. These markers include prostate specific antigen, chromosome Y DNA and Seminogelin. Risky sexual behavior can be assessed by various subjective and objective methods. While self-reports are more feasible, objective methods offer a higher degree of reliability. Further studies for finding more feasible methods of using biomarkers are recommended.

  18. High risk HPV testing following treatment for cervical intraepithelial neoplasia.

    Science.gov (United States)

    Molloy, M; Comer, R; Rogers, P; Dowling, M; Meskell, P; Asbury, K; O'Leary, M

    2016-11-01

    To determine the results of combined cytology and high-risk human papilloma virus (HR HPV) tests at 6 and 18 months postcolposcopy treatment at one Irish colposcopy centre. All women who attended the centre's colposcopy smear clinic for a co-test 6 months (initial test) posttreatment were included in the audit (n = 251). The results revealed negative HR HPV for 79 % (n = 198) of women tested 6 months after treatment and positive results for 21 % (n = 53). HR HPV testing was more sensitive than cytology and led to early detection of residual disease. No women with negative HR HPV had high-grade cytology. HR HPV is more sensitive than cytology for detection of persistent CIN. However, 19 women with positive HR HPV had normal colposcopy with no persistent CIN detected. A national cost-benefit analysis is recommended to determine the value of the second co-test.

  19. Patients who reattend after head injury: a high risk group.

    Science.gov (United States)

    Voss, M.; Knottenbelt, J. D.; Peden, M. M.

    1995-01-01

    OBJECTIVE--To assess risk factors for important neurosurgical effects in patients who reattend after head injury. DESIGN--Retrospective study. SUBJECTS--606 patients who reattended a trauma unit after minor head injury. MAIN OUTCOME MEASURES--Intracranial abnormality detected on computed tomography or the need for neurosurgical intervention. RESULTS--Five patients died: two from unrelated causes and three from raised intracranial pressure. On multiple regression analysis the only significant predictor for both abnormality on computed tomography (14.4% of reattenders) and the need for operation (5% of reattenders) was vault fracture seen on the skull radiograph (P personality change, and seizures were significantly associated only with abnormality on computed tomography. Headache, dizziness, nausea, and vomiting were common in reattenders but were found to have no independent significance. CONCLUSIONS--All patients who reattend after head injury should undergo computed tomography as at least 14% of scans can be expected to yield positive results. Where this facility is not available patients with predictors for operation should be urgently referred for neurosurgical opinion. Other patients can be readmitted and need referral only if symptoms persist despite symptomatic treatment or there is neurological deterioration while under observation. These patients are a high risk group and should be treated seriously. PMID:8520273

  20. High-risk bladder cancer: improving outcomes with perioperative chemotherapy

    Directory of Open Access Journals (Sweden)

    Daniel Y.C. Heng

    2011-12-01

    Full Text Available Despite treatment with radical cystectomy and pelvic lymph node dissection, muscle invasive bladder cancer has a relapse rate of 50%. Patients can develop regionally advanced or metastatic disease that ultimately leads to death. The addition of neoadjuvant or adjuvant chemotherapy to reduce the risk of relapse and death has been extensively studied over the past two decades. Two contemporary trials coupled with a recent meta-analysis evaluating neoadjuvant chemotherapy demonstrated a modest but real improvement in overall survival. This has made neoadjuvant chemotherapy a standard of care. Clinical trials evaluating adjuvant chemotherapy in patients with high-risk disease have been plagued with statistical flaws and have, therefore, been unable to define the survival impact of this approach. It is hoped that ongoing adjuvant trials that are powered to detect small but meaningful clinical differences will clarify the benefit of chemotherapy after cystectomy. Since there are theoretical advantages and disadvantages to each of these approaches, both are widely used in North America. The evidence behind each approach and potential future developments in this field will be described.

  1. Characteristics of violence among high-risk adolescent girls.

    Science.gov (United States)

    Secor-Turner, Molly; Garwick, Ann; Sieving, Renee; Seppelt, Ann

    2014-01-01

    Recent evidence demonstrates increasing rates of involvement with violence among adolescent girls. The objective of this study was to describe the types and sources of violence experienced within social contexts of adolescent girls at high risk for pregnancy. Qualitative data for this analysis are drawn from intervention summary reports of 116 girls participating in Prime Time, a youth development intervention for adolescent girls. Descriptive content analysis techniques were used to identify types and sources of violence experienced by girls within their daily contexts. Types of violence included physical fighting, witnessing violence, physical abuse, gang-related violence, verbal fighting, verbal abuse, and sexual abuse. Sources of violence included family, peers and friends, romantic partners, community violence, and self-perpetrated violence. Many girls in this study experienced violence in multiple contexts. It is imperative that efforts to assess and prevent violence among adolescent girls include paying attention to the social contexts in which these adolescents live. Copyright © 2014 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.

  2. The genetic landscape of high-risk neuroblastoma.

    Science.gov (United States)

    Pugh, Trevor J; Morozova, Olena; Attiyeh, Edward F; Asgharzadeh, Shahab; Wei, Jun S; Auclair, Daniel; Carter, Scott L; Cibulskis, Kristian; Hanna, Megan; Kiezun, Adam; Kim, Jaegil; Lawrence, Michael S; Lichenstein, Lee; McKenna, Aaron; Pedamallu, Chandra Sekhar; Ramos, Alex H; Shefler, Erica; Sivachenko, Andrey; Sougnez, Carrie; Stewart, Chip; Ally, Adrian; Birol, Inanc; Chiu, Readman; Corbett, Richard D; Hirst, Martin; Jackman, Shaun D; Kamoh, Baljit; Khodabakshi, Alireza Hadj; Krzywinski, Martin; Lo, Allan; Moore, Richard A; Mungall, Karen L; Qian, Jenny; Tam, Angela; Thiessen, Nina; Zhao, Yongjun; Cole, Kristina A; Diamond, Maura; Diskin, Sharon J; Mosse, Yael P; Wood, Andrew C; Ji, Lingyun; Sposto, Richard; Badgett, Thomas; London, Wendy B; Moyer, Yvonne; Gastier-Foster, Julie M; Smith, Malcolm A; Guidry Auvil, Jaime M; Gerhard, Daniela S; Hogarty, Michael D; Jones, Steven J M; Lander, Eric S; Gabriel, Stacey B; Getz, Gad; Seeger, Robert C; Khan, Javed; Marra, Marco A; Meyerson, Matthew; Maris, John M

    2013-03-01

    Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 affected individuals (cases) using a combination of whole-exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per Mb (0.48 nonsilent) and notably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, and an additional 7.1% had focal deletions), MYCN (1.7%, causing a recurrent p.Pro44Leu alteration) and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1 and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies that rely on frequently altered oncogenic drivers.

  3. The genetic landscape of high-risk neuroblastoma

    Science.gov (United States)

    Pugh, Trevor J.; Morozova, Olena; Attiyeh, Edward F.; Asgharzadeh, Shahab; Wei, Jun S.; Auclair, Daniel; Carter, Scott L.; Cibulskis, Kristian; Hanna, Megan; Kiezun, Adam; Kim, Jaegil; Lawrence, Michael S.; Lichenstein, Lee; McKenna, Aaron; Pedamallu, Chandra Sekhar; Ramos, Alex H.; Shefler, Erica; Sivachenko, Andrey; Sougnez, Carrie; Stewart, Chip; Ally, Adrian; Birol, Inanc; Chiu, Readman; Corbett, Richard D.; Hirst, Martin; Jackman, Shaun D.; Kamoh, Baljit; Khodabakshi, Alireza Hadj; Krzywinski, Martin; Lo, Allan; Moore, Richard A.; Mungall, Karen L.; Qian, Jenny; Tam, Angela; Thiessen, Nina; Zhao, Yongjun; Cole, Kristina A.; Diamond, Maura; Diskin, Sharon J.; Mosse, Yael P.; Wood, Andrew C.; Ji, Lingyun; Sposto, Richard; Badgett, Thomas; London, Wendy B.; Moyer, Yvonne; Gastier-Foster, Julie M.; Smith, Malcolm A.; Auvil, Jaime M. Guidry; Gerhard, Daniela S.; Hogarty, Michael D.; Jones, Steven J. M.; Lander, Eric S.; Gabriel, Stacey B.; Getz, Gad; Seeger, Robert C.; Khan, Javed; Marra, Marco A.; Meyerson, Matthew; Maris, John M.

    2013-01-01

    Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%1. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 cases using a combination of whole exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per megabase (0.48 non-silent), and remarkably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, an additional 7.1% had focal deletions), MYCN (1.7%, a recurrent p.Pro44Leu alteration), and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1, and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies reliant upon frequently altered oncogenic drivers. PMID:23334666

  4. Prediabetes: a high-risk state for diabetes development.

    Science.gov (United States)

    Tabák, Adam G; Herder, Christian; Rathmann, Wolfgang; Brunner, Eric J; Kivimäki, Mika

    2012-06-16

    Prediabetes (intermediate hyperglycaemia) is a high-risk state for diabetes that is defined by glycaemic variables that are higher than normal, but lower than diabetes thresholds. 5-10% of people per year with prediabetes will progress to diabetes, with the same proportion converting back to normoglycaemia. Prevalence of prediabetes is increasing worldwide and experts have projected that more than 470 million people will have prediabetes by 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction-abnormalities that start before glucose changes are detectable. Observational evidence shows associations between prediabetes and early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores using non-invasive measures and blood-based metabolic traits, in addition to glycaemic values, could optimise estimation of diabetes risk. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention, with evidence of a 40-70% relative-risk reduction. Accumulating data also show potential benefits from pharmacotherapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Prediabetes: A high-risk state for developing diabetes

    Science.gov (United States)

    Tabák, Adam G.; Herder, Christian; Rathmann, Wolfgang; Brunner, Eric J.; Kivimäki, Mika

    2013-01-01

    Summary Prediabetes (or “intermediate hyperglycaemia”), based on glycaemic parameters above normal but below diabetes thresholds is a high risk state for diabetes with an annualized conversion rate of 5%–10%; with similar proportion converting back to normoglycaemia. The prevalence of prediabetes is increasing worldwide and it is projected that >470 million people will have prediabetes in 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction, abnormalities that start before glucose changes are detectable. Observational evidence shows associations of prediabetes with early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores could optimize the estimation of diabetes risk using non-invasive parameters and blood-based metabolic traits in addition to glycaemic values. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention with evidence of a 40%–70% relative risk reduction. Accumulating data also suggests potential benefits from pharmacotherapy. PMID:22683128

  6. [Preservation of high risk fungal cultures of Histoplasma and Cryptococcus].

    Science.gov (United States)

    Fernández Andreu, C Carlos Manuel; Díaz Suárez, Luis Alberto; Ilnait Zaragozi, María Teresa; Aragonés López, Carlos; Martínez Machín, Gerardo; Perurena Lancha, Mayda R

    2012-01-01

    culture collections are responsible for providing the microbial resources for development of biological sciences. Storage in distilled water is one of the easiest and least expensive method for long-term fungal preservation. to evaluate the usefulness of this preservation method in fungal culture of Histoplasma and Cryptococcus. the preservation condition of the highest biological risk species from Histoplasma y Cryptococcus genera, included in the fungal culture collection of "Pedro Kouri" Institute of Tropical Medicine in Havana, was evaluated in this study. One hundred and two strains stored in distilled water, 92% of which had been preserved for more than 10 years, were analyzed. the percentages of recovered strains from H. capsulatum, C. neoformans and C. gattii were 64.3%; 79.1% and 100% respectively. This method of preservation proved to be satisfactory for fungal culture in labs with limited financial resources. A web-based database with interesting information about the collection was made. The importance of strict compliance with the biosafety measures in these collections, particularly with high risk pathogens. preservation of fungal cultures in distilled water is a very useful method for laboratories with limited resources. Culture collections should be assumed as an essential activity in order to solve increasing challenges in the development of biomedical sciences.

  7. Protecting military personnel from high risk dietary supplements.

    Science.gov (United States)

    Deuster, Patricia A; Lieberman, Harris R

    2016-01-01

    It is legal tomarketmost naturally occurring substances as dietary supplements in the USA without manufacturers demonstrating they are safe or effective, and an endless variety of ingredients, from esoteric botanicals to unapproved pharmaceuticals, can be found in dietary supplements. Use of certain supplements can pose a risk, but since a robust reporting systemdoes not exist in the USA it is difficult to know which are problematic and the number of adverse events (AE) resulting from their use. Certain populations, includingmilitary personnel, aremore likely to use dietary supplements than the general population. Approximately 70% of military personnel take dietary supplements while about 50% of civilians do. Service members prefer supplements purported to enhance physical performance such as supposedly natural stimulants, protein and amino acids, and combination products. Since some of thesemay be problematic, Servicemembers are probably at higher risk of injury than the general population. Ten percent of military populations appear to be taking potentially risky supplements, and the US Department of Defense (DoD) has taken variousmeasures to protect uniformed personnel including education, policy changes, and restricting sales. Actions taken include launching Operation Supplement Safety (OPSS), introducing a High Risk Supplement list, educating health care professionals on reporting AE thatmight be associated with dietary supplements, recommending policy for reporting AE, and developing an online AE reporting system. OPSS is a DoD-wide effort to educate service members, leaders, health care providers, military families, and retirees on how to safely select supplements

  8. High risk of postpartum relapses in neuromyelitis optica spectrum disorder.

    Science.gov (United States)

    Klawiter, Eric C; Bove, Riley; Elsone, Liene; Alvarez, Enrique; Borisow, Nadja; Cortez, Melissa; Mateen, Farrah; Mealy, Maureen A; Sorum, Jaime; Mutch, Kerry; Tobyne, Sean M; Ruprecht, Klemens; Buckle, Guy; Levy, Michael; Wingerchuk, Dean; Paul, Friedemann; Cross, Anne H; Jacobs, Anu; Chitnis, Tanuja; Weinshenker, Brian

    2017-11-28

    To study the effect of pregnancy on the frequency of neuromyelitis optica spectrum disorder (NMOSD) relapse and evaluate rates of pregnancy-related complications in an international multicenter setting. We administered a standardized survey to 217 women with NMOSD from 7 medical centers and reviewed their medical records. We compared the annualized relapse rate (ARR) during a baseline period 2 years prior to a participant's first pregnancy to that during pregnancy and to the 9 months postpartum. We also assessed pregnancy-related complications. There were 46 informative pregnancies following symptom onset in 31 women with NMOSD. Compared to baseline (0.17), ARR was increased both during pregnancy (0.44; p = 0.035) and during the postpartum period (0.69; p = 0.009). The highest ARR occurred during the first 3 months postpartum (ARR 1.33). A total of 8 of 76 (10.5%) with onset of NMOSD prior to age 40 experienced their initial symptom during the 3 months postpartum, 2.9 times higher than expected. The postpartum period is a particularly high-risk time for initial presentation of NMOSD. In contrast to published observations in multiple sclerosis, in neuromyelitis optica, relapse rate during pregnancy was also increased, although to a lesser extent than after delivery. © 2017 American Academy of Neurology.

  9. Morbidity in extreme low birth weight newborns hospitalized in a high risk public maternity

    Directory of Open Access Journals (Sweden)

    Derijulie Siqueira Sousa

    Full Text Available Abstract Objectives: to determine the prevalence of the most common morbidities in extremely low birth weight (ELBW infants hospitalized in a newborn intensive care unit (NICU and to evaluate the influence of these morbidities through the length of in-hospital stay. Methods: observational, longitudinal, prospective and analytical study in a high risk reference maternity NICU from Sergipe, realized with 158 ELBW infants admitted between March 2014 and April 2015. The analysis of the hospitalization time was realized through the Kaplan-Meier method. Results: the average weight of premature was 785,2g ± 138,2g. The gestational age vary from 22 to 35 weeks and the average was 26,8 weeks. Of those admitted at NICU, sixty three (39,9% were discharged and 95 (60,1% died. The time of hospitalization was influenced for morbidities as: patent ductus arteriosus (PDA, intraventricular hemorrhage and sepsis. Acute respiratory distress syndrome was the most common complication (157 - 99,4%. The incidence of persistent arterial duct, intraventricular hemorrhage, sepsis, hypothermia, hypoglycemia and retinopathy of prematurity was 39,2%, 17,1%, 32,3%,50,3%, 52,3% e 16,6% respectively. Conclusions: the morbidities from respiratory tract, cardiac, neurological and infectious were the most prevalent, whilst PDA, intraventricular hemorrhage and sepsis were the morbidities that significantly influenced the time of hospitalization.

  10. Personal protective equipment and improving compliance among healthcare workers in high-risk settings.

    Science.gov (United States)

    Honda, Hitoshi; Iwata, Kentaro

    2016-08-01

    Personal protective equipment (PPE) protects healthcare workers (HCWs) from infection by highly virulent pathogens via exposure to body fluids and respiratory droplets. Given the recent outbreaks of contagious infectious diseases worldwide, including Ebola virus and Middle Eastern respiratory syndrome, there is urgent need for further research to determine optimal PPE use in high-risk settings. This review intends to provide a general understanding of PPE and to provide guidelines for appropriate use based on current evidence. Although previous studies have focused on the efficacy of PPE in preventing transmission of pathogens, recent studies have examined the dangers to HCWs during removal of PPE when risk of contamination is highest. Access to adequate PPE supplies is crucial to preventing transmission of pathogens, especially in resource-limited settings. Adherence to appropriate PPE use is a challenge due to inadequate education on its usage, technical difficulties, and tolerability of PPE in the workplace. Future projects aim at ameliorating this situation, including redesigning PPE which is crucial to improving the safety of HCWs. PPE remains the most important strategy for protecting HCW from potentially fatal pathogens. Further research into optimal PPE design and use to improve the safety of HCWs is urgently needed.

  11. Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

    DEFF Research Database (Denmark)

    Craddock, Charles; Labopin, Myriam; Robin, Marie

    2016-01-01

    Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic...... syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients...... conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required....

  12. Infant Development in Fragile X Syndrome: Cross-Syndrome Comparisons

    Science.gov (United States)

    Roberts, Jane E.; McCary, Lindsay M.; Shinkareva, Svetlana V.; Bailey, Donald B., Jr.

    2016-01-01

    This study examined the developmental profile of male infants with fragile X syndrome (FXS) and its divergence from typical development and development of infants at high risk for autism associated with familial recurrence (ASIBs). Participants included 174 boys ranging in age from 5 to 28 months. Cross-sectional profiles on the Mullen Scales of…

  13. Serotonin syndrome

    Science.gov (United States)

    Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome ... brain area. For example, you can develop this syndrome if you take migraine medicines called triptans together ...

  14. Results of brachytherapy boost in high risk breast cancer patients

    International Nuclear Information System (INIS)

    Battermann, J.J.

    1996-01-01

    Introduction: in breast conserving therapy the role of brachytherapy as a boost after whole breast irradiation is not clear. The series from the Netherlands Cancer Institute show a very high local control rate, but the question could be raised whether all these patients need a brachy boost. Therefore, it was decided at our institute, to deliver a brachy boost only to high risk patients, viz. patients with incomplete resection margins and/or extensive in situ cancer (ECI). Materials and methods: in the period 1988 through 1993 a total of 148 patients with 151 breast tumours received a boost on the tumour bed using brachytherapy. Age varied from 25 till 74 years, with a mean age of 52.3 years. Incomplete resection margins were found in 60 patients, ECI in 31 and both in 49 patients. In the majority of patients, the ECI component was not completely removed. T-stage was unknown in 9 patients. T1 in 83, T2 in 49 and T3 in 10. Nodal status was N0 in 119 and N1 in 33 patients. Infiltrating duct carcinoma was the most common histology. No infiltrating growth was found in 6 patients, but one patient presented a positive node. The interval period between day of operation and day of brachytherapy implantation was between 3 and 4 months in 62%. The mean interval between completion of beam irradiation and day of implantation was 18 days, while 12 patients received their brachytherapy previous to the beam irradiation. External irradiation was with two tangential fields and a total dose of 50 Gy in 25 fractions over 6 weeks (9 fractions in two weeks). The number of needles in two planes. Most patients were implanted under local anaesthesia. Dose rate in 97 patients was 51 - 60 cGy/h. Results: follow-up for patients alive varied from 2 years till 7 years with a mean follow-up period of 4 years. One hundred and twenty five patients are alive, including 6 patients with manifest metastases. Local recurrence was encountered in 8 patients (interval 14 - 60 months, mean 30 months), with

  15. HPV vaccine acceptability in high-risk Greek men.

    Science.gov (United States)

    Hoefer, Lea; Tsikis, Savas; Bethimoutis, George; Nicolaidou, Electra; Paparizos, Vassilios; Antoniou, Christina; Kanelleas, Antonios; Chardalias, Leonidas; Stavropoulos, Georgios-Emmanouil; Schneider, John; Charnot-Katsikas, Angella

    2018-01-02

    HPV is associated with malignancy in men, yet there is a lack of data on HPV knowledge, vaccine acceptability, and factors affecting vaccine acceptability in Greek men. This study aims to identify determinants of knowledge and willingness to vaccinate against HPV among high-risk Greek men. Men (n = 298) between the ages of 18 and 55 were enrolled from the STI and HIV clinics at "Andreas Syggros" Hospital in Athens, Greece from July-October 2015. Participants completed a survey on demographics, economic factors, sexual history, HPV knowledge, and vaccine acceptability. The majority of participants were younger than 40 (76.6%) and unmarried (84.6%). Our sample was 31.2% MSM (men who have sex with men), and 20.1% were HIV-positive. Most participants (>90%) were aware that HPV is highly prevalent in both men and women; however, fewer identified that HPV causes cancers in both sexes (68%) and that vaccination protects men and women (67%). Amongst participants, 76.7% were willing to vaccinate themselves against HPV, 71.4% an adolescent son, and 69.3% an adolescent daughter. HIV-positive men were more likely to be willing to vaccinate themselves (OR 2.83, p = .015), a son (OR 3.3, p = .015) or a daughter (3.01, p = .020). Higher income levels were associated with increased willingness to vaccinate oneself (OR 1.32, p = .027), a son (1.33, p = .032) or daughter (1.34, p = .027). Although there is a HPV knowledge gap, HPV vaccine acceptability is high despite lack of vaccine promotion to Greek men. Future studies should include lower-risk men to adequately inform public health efforts.

  16. High-Risk Sexual Behavior at Social Venues in Madagascar

    Science.gov (United States)

    KHAN, MARIA R.; RASOLOFOMANANA, JUSTIN R.; McCLAMROCH, KRISTI J.; RALISIMALALA, ANDRIAMAMPIANINA; ZAFIMANJAKA, MAURICE G.; BEHETS, FRIEDA; WEIR, SHARON S.

    2018-01-01

    Background Persistent high levels of sexually transmitted infection (STI) in Madagascar indicate current prevention strategies are inadequate. STI/HIV prevention based in social venues may play an important role in reaching individuals at risk of infection. We identified venues where people meet sexual partners and measured the need and potential for venue-based prevention. Methods Interviews were conducted in 7 Madagascar towns with 1) community informants to identify social venues, 2) individuals socializing at a sample of venues to assess sexual behavior among venue patrons, and 3) venue representatives to assess the potential for venue-based intervention. Results Community informants identified numerous venues (range: 67–211 venues, depending on the town); streets, bars, and hotels were most commonly reported. Among 2982 individuals socializing at venues, 78% of men and 74% of women reported new sexual partnership or sex trade for money, goods, or services in the past 4 weeks and 19% of men and 18% of women reported symptoms suggestive of STI in the past 4 weeks. STI symptom levels were disproportionately high among respondents reporting either sex trade or new sexual partnership in the past 4 weeks. Twenty-eight percent of men and 41% of women reported condom use during the last sex act with a new partner. Although 24% to 45% of venues had hosted STI/HIV interventions, interventions were deemed possible at 73% to 90% venues according to 644 interviews with venue representatives. Conclusions Venue-based intervention is possible and would reach a spectrum of populations vulnerable to STI/HIV including sex workers, their clients, and other high-risk populations. PMID:18496471

  17. Meckel Gruber Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    Celal Devecioglu

    2004-01-01

    Full Text Available Meckel-Gruber syndrome is an autosomal recessive disordercharacterized by a combination of renal cysts and variably associatedfeatures including developmental anomalies of the central nervous system(typically encephalocele, hepatic ductal dysplasia and cysts, andpolydactyly. n this cases AFP levels are increases. Alternative names areMeckel Syndrome, Dysencephalia Splanchnocystica, Gruber Syndrome andMeckel – Gruber Syndrome. This study is presented to draw attention to theMeckel Gruber Syndrome which seen rarely, have high risk of reccurenceand antenathal determination of AFP levels and early diagnosis byultrasonographic screening can be confident.

  18. Dopamine in high-risk populations: A comparison of subjects with 22q11.2 deletion syndrome and subjects at ultra high-risk for psychosis

    NARCIS (Netherlands)

    Vingerhoets, Claudia; Bloemen, Oswald J. N.; Boot, Erik; Bakker, Geor; de Koning, Mariken B.; da Silva Alves, Fabiana; Booij, Jan; van Amelsvoort, Thérèse A. M. J.

    2018-01-01

    Striatal dopamine (DA) dysfunction has been consistently reported in psychotic disorders. Differences and similarities in the pathogenesis between populations at clinical and genetic risk for developing psychosis are yet to be established. Here we explored markers of dopamine (DA) function in

  19. Indsigter og udfordringer i danske Lynch-syndrom-familier

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Timshel, Susanne; Nilbert, Mef

    2008-01-01

    identified 88 unique mutations in 164 Danish families delineated as Lynch syndrome families. Predictive genetic diagnostics enables the identification of high risk individuals, who are offered participation in surveillance programmes that effectively reduce morbidity and mortality in colorectal cancer....

  20. Risk of suicide in high risk pregnancy: an exploratory study.

    Science.gov (United States)

    Benute, Gláucia Rosana Guerra; Nomura, Roseli Mieko Yamamoto; Jorge, Vanessa Marques Ferreira; Nonnenmacher, Daniele; Fráguas Junior, Renério; Lucia, Mara Cristina Souza de; Zugaib, Marcelo

    2011-01-01

    To identify the risk of suicidal behavior in high-risk pregnant women at a public hospital in São Paulo. We conducted a semi-structured interview with each of the participants (n = 268) through a previously prepared questionnaire. Risk of suicidal behavior was assessed by the Portuguese version of PRIME-MD. The mean age of patients was 29 years (SD = 0.507) and gestation period was 30 weeks (SD = 0.556). Of the total sample, specific risk of suicide was found in 5% (n = 14). Of these, 85% have a stable relationship (married or cohabitating), the pregnancy was planned in 50% of cases, and 71% have no religion or professional activities. The correlation of risk of suicide with data from marital status, planned birth, age, education, professional practice, risk of prematurity, and religion showed that having a religion is statistically significant (p = 0.012). There were no positive associations for any of the other selected variables when compared with the risk of suicide. By correlating the risk of suicide with other characteristic symptoms of major depression, there was statistical significance in the sample with regard to insomnia or hypersomnia (p = 0.003), fatigue or loss of energy (p = 0.001), decreased or increased appetite (p = 0.005), less interest in daily activities (p = 0.000), depressed mood (p = 0.000), feelings of worthlessness or guilt (p = 0.000), decreased concentration (p = 0.002), and agitation or psychomotor retardation (p = 0.002). We found that religion can be a protective factor against suicidal behavior. Besides providing a social support network needed by women during pregnancy, religion supports belief in life after death and in a loving God, giving purpose to life and self esteem and providing models for coping with crises. The results show the importance of prevention and early diagnosis of suicidal behavior, since suicide is an attempt to move from one sphere to another by force, seeking to solve what seems impossible.

  1. Family studies to find rare high risk variants in migraine.

    Science.gov (United States)

    Hansen, Rikke Dyhr; Christensen, Anne Francke; Olesen, Jes

    2017-12-01

    variants (less than five), while other studies found several possible variants. Not all of them were genome wide significant. Four studies performed follow-up analyses in unrelated cases and controls and calculated odds ratios that supported an association between detected variants and risk of disease. Studies of 11 diseases identified rare variants that segregated fully or to a large degree with the disease in the pedigrees. It is possible to find rare high risk variants for common complex diseases through a family-based approach. One study using a family approach and NGS to find rare variants in migraine has already been published but with strong limitations. More studies are under way.

  2. Combined anticoagulation and antiplatelet therapy for high-risk patients with atrial fibrillation: a systematic review.

    Science.gov (United States)

    Lane, D A; Raichand, S; Moore, D; Connock, M; Fry-Smith, A; Fitzmaurice, D A

    2013-07-01

    publications that reported reviews, which added no further data. There was variation in the population, types and doses of ACT and APT, definitions of outcomes, and length of follow-up between the studies. There was a paucity of directly randomised high-quality RCTs, whereas non-randomised comparisons were found to have significant confounding factors. No studies looked at the effect of ACT plus APT compared with ACT alone on vascular events in patients with AF following acute coronary syndrome (ACS) or percutaneous coronary intervention. In most studies, significant differences in event rates were not seen between the patients on combined therapy compared with those on ACT alone for outcomes such as stroke (including haemorrhagic and ischaemic strokes), rates of transient ischaemic attacks, composite end points of stroke and systemic embolism (SE), SE alone, acute myocardial infarction, mortality (vascular or all cause) or bleeding events. There was conflicting evidence regarding rates of major adverse events consisting of composite end points, although event rates were generally low. An attempt was made to identify all of the available evidence around the subject despite the dearth of directly randomised studies using a robust review methodology. There was a paucity of directly randomised evidence to undertake a meta-analysis for the merits of one technology over another. The selection criteria were kept necessarily broad with regard to the population, intervention and comparator in order to capture all relevant studies. This systematic review suggests that there is still insufficient evidence to advocate a clear benefit of the addition of APT to ACT compared with ACT alone in reducing the risk of vascular events in a population of patients at high risk of TEs resulting from AF. It is recommended that a definitive prospective RCT needs to be undertaken in a population at high risk of atherosclerotic coronary artery and other vascular events in addition to being at high risk

  3. Checking the predictive accuracy of basic symptoms against ultra high-risk criteria and testing of a multivariable prediction model: Evidence from a prospective three-year observational study of persons at clinical high-risk for psychosis.

    Science.gov (United States)

    Hengartner, M P; Heekeren, K; Dvorsky, D; Walitza, S; Rössler, W; Theodoridou, A

    2017-09-01

    The aim of this study was to critically examine the prognostic validity of various clinical high-risk (CHR) criteria alone and in combination with additional clinical characteristics. A total of 188 CHR positive persons from the region of Zurich, Switzerland (mean age 20.5 years; 60.2% male), meeting ultra high-risk (UHR) and/or basic symptoms (BS) criteria, were followed over three years. The test battery included the Structured Interview for Prodromal Syndromes (SIPS), verbal IQ and many other screening tools. Conversion to psychosis was defined according to ICD-10 criteria for schizophrenia (F20) or brief psychotic disorder (F23). Altogether n=24 persons developed manifest psychosis within three years and according to Kaplan-Meier survival analysis, the projected conversion rate was 17.5%. The predictive accuracy of UHR was statistically significant but poor (area under the curve [AUC]=0.65, Pthinking of binary at-risk criteria is necessary in order to improve the prognosis of psychotic disorders. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Limited numbers of apoptotic cells in fresh paraffin embedded bone marrow samples of patients with myelodysplastic syndrome

    NARCIS (Netherlands)

    Brada, SJL; van de Loosdrecht, AA; Koudstaal, J; de Wolf, JTM; Vellenga, E

    In myelodysplasia (MDS) the precise mechanism of ineffective erythropoiesis is not fully elucidated, but it is suggested that apoptosis may contribute to this process. We performed TdT-mediated dUTP-nick end labelling (TUNEL) staining of paraffin embedded bone marrow specimens to assess the amount

  5. New proposals of the WHO working group (2016) for the diagnosis of myelodysplastic syndromes (MDS): Characteristics of refined MDS types.

    Science.gov (United States)

    Strupp, Corinna; Nachtkamp, Kathrin; Hildebrandt, Barbara; Giagounidis, Aristoteles; Haas, Rainer; Gattermann, Norbert; Bennett, John M; Aul, Carlo; Germing, Ulrich

    2017-06-01

    Based on centrally diagnosed 3528 patients in the Düsseldorf registry, we validated the new proposals for the classification of the MDS by the WHO working group: 256 patients were diagnosed as MDSSLD (7,3%), 978 MDSMLD (27,7%), 227 MDS RS SLD (6,4%); 321 MDS RS MLD (9,1%), 159 MDS del(5q) (4,5%), 481 MDSEB 1 (13,6%), 620 MDSEB 2 (17,6%), and 148 MDS-U (4,2%). 352 patients (16,9% of the non blastic types) changed the category, mainly moving from RCMD to MDS RS MLD, RCUD and RCMD to MDS del(5q). Median survival times of the refined groups differed from more than 60 months in the MDSSLD (RS) groups, 37 months in the MDSMLD (RS) groups, 79 months of the MDS del(5q) group and 21 and 11 months in the MDSEB 1 and 2 groups, respectively. The difference between the groups with regard to the risk of AML evolution was also impressing. No major changes were made with regard to the MDS-U categories. In summary, the proposals of the WHO group for the classification of MDS are thoughtful, taking into account biologic parameters of the diseases, a more precise wording, to some extend pragmatic and feasible. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. The Role of mDia1 in the Aberrant Innate Immune Signaling in del(5q) Myelodysplastic Syndromes

    Science.gov (United States)

    2016-10-01

    inflammation and regulates myeloproliferation and oncogenic transformation ( Boldin et al., 2011). Our previous work reveals that mDia1, flanked by the two...RNA extraction and quantitative real time-PCR RNA isolation, complementary DNA synthesis and quantitative real time-PCR were performed as previously...compared to the DWT control mice (Keerthivasan et al., 2014; Boldin et al., 2011). In comparison, the DKO mice developed significant age-related anemia

  7. Beals Syndrome

    Science.gov (United States)

    ... the syndrome. How does Beals syndrome compare with Marfan syndrome? People with Beals syndrome have many of the ... bone) and aortic enlargement problems as people with Marfan syndrome, and treatments for these problems are the same. ...

  8. Toxoplasma gondii seropositivity and co-infection with TORCH pathogens in high-risk patients from Qatar.

    Science.gov (United States)

    Abu-Madi, Marawan A; Behnke, Jerzy M; Dabritz, Haydee A

    2010-04-01

    Testing of patients who are deemed to be at high risk for TORCH pathogens, e.g., pregnant women, their fetuses, neonates, and acquired immunodeficiency syndrome (AIDS) patients, is important so that specific treatment can be initiated. This study included 1,857 such patients between 2005 and 2008. Logistic regression was used to evaluate factors associated with Toxoplasma gondii seropositivity. Among 823 women of childbearing age, 35.1% and 5.2% tested positive for T. gondii IgG and IgM, respectively. Three infants nationality, positive cytomegalovirus (CMV) and herpes simplex virus (HSV)-1 serostatus, and negative rubella IgG results. The decreasing prevalence of IgM antibodies between 2005 and 2008 suggested that exposure to T. gondii from food or environmental sources declined over this period in Qatar. Population-based studies of newborns would be helpful to accurately estimate incidence of c