Aberrant Methylation-Mediated Suppression of APAF1 in Myelodysplastic Syndrome.

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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.

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...

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...

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

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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.

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....

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

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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.

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

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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.

Myelodysplastic syndromes in Chernobyl clean-up workers.

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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.

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...

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....

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.

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.

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.

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

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

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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.

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

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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

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

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...

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.

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)

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

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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.

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

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.

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.

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

Directory of Open Access Journals (Sweden)

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.

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

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

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

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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.

Distinct neutrophil subpopulations phenotype by flow cytometry in myelodysplastic syndromes.

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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.

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.

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...

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

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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.

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

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

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.

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.

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.

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.

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.

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

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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

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.

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

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.

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...

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

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.

Síndromes mielodisplásicas: protocolo de exclusão Myelodysplastic syndrome: diagnostic protocol

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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

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

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...

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...

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...

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

[Marked hemosiderosis in myelodysplastic syndrome].

Science.gov (United States)

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.

BCOR and BCORL1 mutations in myelodysplastic syndromes and related disorders.

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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.

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

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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.

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

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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.

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...

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

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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.

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

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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.

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

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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

[Progress of cytogenetic detection in myelodysplastic syndromes].

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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.

The biology of myelodysplastic syndromes: unity despite heterogeneity

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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.

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

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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.

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

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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.

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

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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.

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

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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

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

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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.

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

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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

Managing myelodysplastic symptoms in elderly patients

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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

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

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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).

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

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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

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

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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.

Myelodysplastic syndromes and the role of iron overload.

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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.

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

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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.

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

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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.

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

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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,...

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

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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

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

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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.

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

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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.

Tumor suppressor microRNAs are downregulated in myelodysplastic syndrome with spliceosome mutations

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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....

657del5 mutation of the NBS1 gene in myelodysplastic syndrome

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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

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

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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.

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

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....

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

The Differencies in Adult and Pediatric Myelodysplastic Syndrome: A Review

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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.

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

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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...

The third International Congress on Myeloproliferative and Myelodysplastic Syndromes.

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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).

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

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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.

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.

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.

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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.

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

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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.

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

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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.

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

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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.

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

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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.

Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes

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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.

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)

MR imaging findings of the femoral marrow in myelodysplastic syndrome

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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).

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

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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.

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

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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.

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

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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.

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

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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.

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.)

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

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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.

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

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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

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

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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.

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

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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

[Constitutional mismatch repair deficiency syndrome].

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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.

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.

Fatores prognósticos nas síndromes mielodisplásicas Prognostic factors for myelodysplastic syndromes

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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.

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

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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

Asthma and risk of myelodysplastic syndromes

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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....

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

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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

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

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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.

Mechanisms of resistance to decitabine in the myelodysplastic syndrome.

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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.

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

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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.

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

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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

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

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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

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

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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.

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

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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.

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.

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.

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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.

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

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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.

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

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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.

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

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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

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

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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.

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

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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

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with radiation

NARCIS (Netherlands)

Radivoyevitch, T.; Sachs, R. K.; Gale, R. P.; Molenaar, R. J.; Brenner, D. J.; Hill, B. T.; Kalaycio, M. E.; Carraway, H. E.; Mukherjee, S.; Sekeres, M. A.; Maciejewski, J. P.

2016-01-01

Risks of acute myeloid leukemia (AML) and/or myelodysplastic syndromes (MDS) are known to increase after cancer treatments. Their rise-and-fall dynamics and their associations with radiation have, however, not been fully characterized. To improve risk definition we developed SEERaBomb R software for

[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.

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.).

Differential diagnosis of myelodysplastic syndrome and aplastic anemia using MRI

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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.

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

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.

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

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.

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.

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.

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.

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).

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.

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.

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.

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

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

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.

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

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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

Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

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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....

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

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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.

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

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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.

Suspected myelodysplastic/myeloproliferative neoplasm in a feline leukemia virus-negative cat.

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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.

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

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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.

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

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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

The second international congress on myeloproliferative and myelodysplastic syndromes.

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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

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

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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

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.

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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

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

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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

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

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

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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

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).

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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.

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

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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...

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

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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.

Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS

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Holm, Mette; Dybedahl, I; Holm, Mette

2014-01-01

This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks and a trans...... patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations....

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

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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.

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

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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.

Loss of RhoB expression enhances the myelodysplastic phenotype of mammalian diaphanous-related Formin mDia1 knockout mice.

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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.

Metabolic syndrome and cardiovascular risk

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Abdullah M Alshehri

2010-01-01

Full Text Available The constellation of dyslipidemia (hypertriglyceridemia and low levels of high-density lipoprotein cholesterol, elevated blood pressure, impaired glucose tolerance, and central obesity is now classified as metabolic syndrome, also called syndrome X. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria for use in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general, they include a combination of multiple and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics, commonly manifest a prothrombotic state as well as and a proinflammatory state. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB, increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C. The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of atherosclerotic cardiovascular disease (ASCVD risk factors, that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to the components of the syndrome present as well as the other, non-metabolic syndrome risk factors in a particular person.

Metabolic syndrome and cardiovascular risk

Directory of Open Access Journals (Sweden)

Abdullah M Alshehri

2010-11-01

Full Text Available The constellation of dyslipidemia (hypertriglyceridemia and low levels of high-density lipoprotein cholesterol, elevated blood pressure, impaired glucose tolerance, and central obesity is now classified as metabolic syndrome, also called syndrome X. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria for use in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general, they include a combination of multiple and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics, commonly manifest a prothrombotic state as well as and a proinflammatory state. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB, increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C. The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of atherosclerotic cardiovascular disease (ASCVD risk factors, that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to the components of the syndrome present as well as the other, non-metabolic syndrome risk factors in a particular person.

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.

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)

Donor Bone Marrow Transplant With or Without G-CSF in Treating Young Patients With Hematologic Cancer or Other Diseases

Science.gov (United States)

2017-03-29

Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Juvenile Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Childhood Acute Lymphoblastic Leukemia; Secondary Myelodysplastic Syndromes

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

Role of Hypomethylating Agents in the Treatment of Bone Marrow Failure

Science.gov (United States)

2016-10-01

of drugs ap- proved for the treatment of patients with higher-risk myelodysplastic syndromes (MDS). Azacitidine (AZA) was approved by the Food and...in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “ advertisement ” in accordance with 18 USC...decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT

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.

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)

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.

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

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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.

Metabolic Syndrome and Breast Cancer Risk.

Science.gov (United States)

Wani, Burhan; Aziz, Shiekh Aejaz; Ganaie, Mohammad Ashraf; Mir, Mohammad Hussain

2017-01-01

The study was meant to estimate the prevalence of metabolic syndrome in patients with breast cancer and to establish its role as an independent risk factor on occurrence of breast cancer. Fifty women aged between 40 and 80 years with breast cancer and fifty controls of similar age were assessed for metabolic syndrome prevalence and breast cancer risk factors, including age at menarche, reproductive status, live births, breastfeeding, and family history of breast cancer, age at diagnosis of breast cancer, body mass index, and metabolic syndrome parameters. Metabolic syndrome prevalence was found in 40.0% of breast cancer patients, and 18.0% of those in control group ( P = 0.02). An independent and positive association was seen between metabolic syndrome and breast cancer risk (odds ratio = 3.037; 95% confidence interval 1.214-7.597). Metabolic syndrome is more prevalent in breast cancer patients and is an independent risk factor for breast cancer.

Metabolic syndrome and cardiovascular risk among adults

Directory of Open Access Journals (Sweden)

Reem Hunain

2018-03-01

Full Text Available Background: Mortality and morbidity due cardiovascular diseases in India is on the rise. Metabolic Syndrome which is a collection of risk factors of metabolic origin, can greatly contribute to its rising burden. Aims & Objectives: The present study was conducted with the objective of estimating the prevalence of metabolic syndrome and 10-year cardiovascular risk among adults. Material & Methods: This hospital-based study included 260 adults aged 20-60 years. Metabolic Syndrome was defined using National Cholesterol Education Program –Adult Treatment Panel -3 criteria. The 10 year cardiovascular risk was estimated using Framingham risk scoring. Results: The overall prevalence of metabolic syndrome among the study participants was 38.8%. Age (41-60yrs, male gender and daily consumption of high salt items were positively associated with metabolic syndrome whereas consumption of occasional high sugar items showed an inverse association with metabolic syndrome. According to Framingham Risk Scoring, 14.3% of the participants belonged to intermediate/high risk category. Conclusion: With a high prevalence of metabolic syndrome and a considerable proportion of individuals with intermediate to high 10 yr CVD risk, there is a need to design strategies to prevent future cardiovascular events.

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

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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).

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

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.

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.

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.

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

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

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)

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.

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

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

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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.

Metabolic Syndrome Risk Profiles Among African American Adolescents

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Fitzpatrick, Stephanie L.; Lai, Betty S.; Brancati, Frederick L.; Golden, Sherita H.; Hill-Briggs, Felicia

2013-01-01

OBJECTIVE Although African American adolescents have the highest prevalence of obesity, they have the lowest prevalence of metabolic syndrome across all definitions used in previous research. To address this paradox, we sought to develop a model of the metabolic syndrome specific to African American adolescents. RESEARCH DESIGN AND METHODS Data from the National Health and Nutrition Examination Survey (2003–2010) of 822 nonpregnant, nondiabetic, African American adolescents (45% girls; aged 12 to 17 years) who underwent physical examinations and fasted at least 8 h were analyzed. We conducted a confirmatory factor analysis to model metabolic syndrome and then used latent profile analysis to identify metabolic syndrome risk groups among African American adolescents. We compared the risk groups on probability of prediabetes. RESULTS The best-fitting metabolic syndrome model consisted of waist circumference, fasting insulin, HDL, and systolic blood pressure. We identified three metabolic syndrome risk groups: low, moderate, and high risk (19% boys; 16% girls). Thirty-five percent of both boys and girls in the high-risk groups had prediabetes, a significantly higher prevalence compared with boys and girls in the low-risk groups. Among adolescents with BMI higher than the 85th percentile, 48 and 36% of boys and girls, respectively, were in the high-risk group. CONCLUSIONS Our findings provide a plausible model of the metabolic syndrome specific to African American adolescents. Based on this model, approximately 19 and 16% of African American boys and girls, respectively, are at high risk for having the metabolic syndrome. PMID:23093663

Metabolic syndrome and cardiometabolic risk in PCOS.

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Cussons, Andrea J; Stuckey, Bronwyn G A; Watts, Gerald F

2007-02-01

The cardiovascular risk associated with the polycystic ovary syndrome (PCOS) has recently attracted much interest. Women with PCOS are more likely to fulfill the diagnosis of the metabolic syndrome, a cluster of related cardiometabolic factors known to predict long-term risk of cardiovascular disease and type 2 diabetes. We review the literature pertaining to the link between the metabolic syndrome, cardiovascular disease, and PCOS. We focus on the influence of obesity and hyperandrogenemia, and on strategies for identifying cardiovascular risk in PCOS.

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

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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.

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.

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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

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....

Nuances of Morphology in Myelodysplastic Diseases in the Age of Molecular Diagnostics.

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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.

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

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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.

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

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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.

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

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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.

Constitutional trisomy 8 and Behçet syndrome.

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Becker, Kristin; Fitzgerald, Oliver; Green, Andrew J; Keogan, Mary; Newbury-Ecob, Ruth; Greenhalgh, Lynn; Withers, Stephen; Hollox, Edward J; Aldred, Patricia M R; Armour, John A L

2009-05-01

The characteristic clinical features of constitutional trisomy 8 include varying degrees of developmental delay, joint contractures and deep palmar and plantar creases. There is an established literature, which describes features of Behçet syndrome occurring in phenotypically normal individuals with myelodysplastic syndromes and trisomy 8 in their bone marrow. In this article, we describe four patients with constitutional trisomy 8, all with varying clinical phenotypes, who developed features of Behçet, in particular but not exclusively mucocutaneous ulceration. In addition, we examined gene copy numbers of the variable-number neutrophil defensin genes DEFA1A3 in one of the cases (case 1) and her parents, together with 14 cases of Behçet syndrome in comparison with 121 normal controls. The gene copy number was highest in case 1 (copy number 14) and was also increased in her parents (both copy number 9). However the mean copy number for DEFA1A3 among the 14 Behçet syndrome patients was actually lower (5.1) than among the controls (mean of 6.8 copies). Thus, we conclude that patients with constitutional trisomy 8 and those with trisomy 8 confined to the bone marrow are both at increased risk of developing features of Behçet syndrome. The mechanism may relate to increased chromosome 8 gene dosage with further analysis of candidate genes on chromosome 8 required.

Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

DEFF Research Database (Denmark)

Schmiegelow, Kjeld; Al-Modhwahi, Ibrahim; Andersen, Mette Klarskov

2009-01-01

Among 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16...... acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P...

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.

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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

Cardiovascular Risk Factors in the Antiphospholipid Syndrome

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Felipe Freire da Silva

2014-01-01

Full Text Available A major cause of morbidity and mortality in the context of the antiphospholipid syndrome (APS is the occurrence of thrombotic events. Besides the pathogenic roles of antiphospholipid antibodies (aPL, other risk factors and medical conditions, which are conditions for traditional risk of an individual without the APS, can coexist in this patient, raising their risk of developing thrombosis. Therefore, the clinical and laboratory investigation of comorbidities known to increase cardiovascular risk in patients with antiphospholipid antibody syndrome is crucial for the adoption of a more complete and effective treatment. Experimental models and clinical studies show evidence of association between APS and premature formation of atherosclerotic plaques. Atherosclerosis has major traditional risk factors: hypertension, diabetes mellitus, obesity, dyslipidemia, smoking, and sedentary lifestyle that may be implicated in vascular involvement in patients with APS. The influence of nontraditional risk factors as hyperhomocysteinemia, increased lipoprotein a, and anti-oxLDL in the development of thromboembolic events in APS patients has been studied in scientific literature. Metabolic syndrome with all its components also has been recently studied in antiphospholipid syndrome and is associated with arterial events.

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

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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

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.

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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

Psychosocial risk factors for the metabolic syndrome

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Pedersen, Jolene Masters; Lund, Rikke; Andersen, Ingelise

2016-01-01

Background/Objectives: Metabolic deregulations and development of metabolic syndrome may be an important pathway underlying the relationship between stress and cardiovascular disease. We aim to estimate the effect of a comprehensive range of psychosocial factors on the risk of developing metabolic.......11) to be risk factors for developing the metabolic syndrome in women, while vital exhaustion (OR 2.09, 95% CI 0.95 to 4.59) and intake of sleep medications (OR 2.54, 95% CI 0.92 to 5.96) may play a more important role in men. Conclusions: Experiencing major life events in work and adult life and....../or dysfunctional social networks is a risk factor for metabolic syndrome in women, and stress reactions such as vital exhaustion and intake of sleep medications may play a more important role in the development of metabolic syndrome men....

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

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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.

Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (I

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Chih-Ping Chen

2008-03-01

Full Text Available Fetuses with neural tube defects (NTDs maybe associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as acrocallosal syndrome, autosomal dominant brachydactyly-clinodactyly syndrome, Manouvrier syndrome, short rib-polydactyly syndrome, Disorganization (Ds-like human malformations, isolated hemihyper-plasia, X-linked NTDs, meroanencephaly, schisis association, diprosopus, fetal valproate syndrome, DiGeorge syndrome/velocardiofacial syndrome, Waardenburg syndrome, folic acid antagonists, diabetes mellitus, and obesity. NTDs associated with syndromes, disorders, and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.

Syndromes, disorders and maternal risk factors associated with neural tube defects (I).

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Chen, Chih-Ping

2008-03-01

Fetuses with neural tube defects (NTDs) may be associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as acrocallosal syndrome, autosomal dominant brachydactyly-clinodactyly syndrome, Manouvrier syndrome, short rib-polydactyly syndrome, Disorganization ( Ds )-like human malformations, isolated hemihyperplasia, X-linked NTDs, meroanencephaly, schisis association, diprosopus, fetal valproate syndrome, DiGeorge syndrome/velocardiofacial syndrome, Waardenburg syndrome, folic acid antagonists, diabetes mellitus, and obesity. NTDs associated with syndromes, disorders, and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.

Syndromes, Disorders and Maternal Risk Factors Associated With Neural Tube Defects (VII

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2008-09-01

Full Text Available Neural tube defects (NTDs may be associated with syndromes, disorders and maternal risk factors. This article provides a comprehensive review of the syndromes, disorders and maternal risk factors associated with NTDs, including DK phocomelia syndrome (von Voss-Cherstvoy syndrome, Siegel-Bartlet syndrome, fetal warfarin syndrome, craniotelencephalic dysplasia, Czeizel-Losonci syndrome, maternal cocaine abuse, Weissenbacher-Zweymüller syndrome, parietal foramina (cranium bifidum, Apert syndrome, craniomicromelic syndrome, XX-agonadism with multiple dysraphic lesions including omphalocele and NTDs, Fryns microphthalmia syndrome, Gershoni-Baruch syndrome, PHAVER syndrome, periconceptional vitamin B6 deficiency, and autosomal dominant Dandy-Walker malformation with occipital cephalocele. NTDs associated with these syndromes, disorders and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders and maternal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

The Metabolic Syndrome and Risk of Sudden Cardiac Death: The Atherosclerosis Risk in Communities Study.

Science.gov (United States)

Hess, Paul L; Al-Khalidi, Hussein R; Friedman, Daniel J; Mulder, Hillary; Kucharska-Newton, Anna; Rosamond, Wayne R; Lopes, Renato D; Gersh, Bernard J; Mark, Daniel B; Curtis, Lesley H; Post, Wendy S; Prineas, Ronald J; Sotoodehnia, Nona; Al-Khatib, Sana M

2017-08-23

Prior studies have demonstrated a link between the metabolic syndrome and increased risk of cardiovascular mortality. Whether the metabolic syndrome is associated with sudden cardiac death is uncertain. We characterized the relationship between sudden cardiac death and metabolic syndrome status among participants of the ARIC (Atherosclerosis Risk in Communities) Study (1987-2012) free of prevalent coronary heart disease or heart failure. Among 13 168 participants, 357 (2.7%) sudden cardiac deaths occurred during a median follow-up of 23.6 years. Participants with the metabolic syndrome (n=4444) had a higher cumulative incidence of sudden cardiac death than those without it (n=8724) (4.1% versus 2.3%, P metabolic syndrome, the metabolic syndrome was independently associated with sudden cardiac death (hazard ratio, 1.70, 95% confidence interval, 1.37-2.12, P metabolic syndrome criteria components. The risk of sudden cardiac death varied according to the number of metabolic syndrome components (hazard ratio 1.31 per additional component of the metabolic syndrome, 95% confidence interval, 1.19-1.44, P metabolic syndrome was associated with a significantly increased risk of sudden cardiac death irrespective of sex or race. The risk of sudden cardiac death was proportional to the number of metabolic syndrome components. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Cardiovascular risk in Turner syndrome.

Science.gov (United States)

Donato, Beatriz; Ferreira, Maria João

2018-06-01

Turner syndrome is a relatively common genetic disorder of female development, characterized by partial or complete absence of an X chromosome, with a variable clinical presentation. Congenital or acquired cardiovascular disease is highly prevalent and a major cause of early death in this syndrome. The most feared complication is aortic dissection, which can occur at a very young age and requires careful assessment of its risk factors. A systematic literature search identified sixty relevant publications. These were reviewed with regard to the increased risk of cardiovascular disease in women with Turner syndrome, especially in pregnancy. The most common congenital cardiovascular defects are presented and illustrated with appropriate iconography. The current recommendations regarding the screening and monitoring of cardiovascular disease in these patients are discussed. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Bullous Variant of Sweet’s Syndrome after Herpes Zoster Virus Infection

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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...

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

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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.

Myelodysplastic/ Myeloproliferative Neoplasms Treatment (PDQ®)—Health Professional Version

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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.

The metabolic syndrome: prevalence, CHD risk, and treatment.

Science.gov (United States)

Sarti, Cinzia; Gallagher, John

2006-01-01

An increased risk of coronary heart disease (CHD) morbidity and mortality is associated with the metabolic syndrome, a condition characterized by the concomitant presence of several abnormalities, including abdominal obesity, dyslipidemia, hypertension, insulin resistance (with or without glucose intolerance or diabetes), microalbuminuria, prothrombotic, and proinflammatory states. Estimates of the prevalence of the metabolic syndrome indicate that this condition is now common and likely to increase dramatically over the coming decades, in parallel with greater rates of obesity and Type 2 diabetes. Risk factors for the metabolic syndrome are already present in obese children and adolescents. Thus, identifying and treating all affected individuals promptly and optimally are critical to ensure that this potentially challenging healthcare burden is minimized. Here, we review the prevalence of the metabolic syndrome, dyslipidemias, and CHD risk. Although changes in lifestyle are fundamental to reducing many of the CHD risk factors associated with the metabolic syndrome, pharmacologic interventions also play an important role. Retrospective subanalyses of the effects of statins on coronary event rates and lipid levels in patients with the metabolic syndrome included in clinical trials indicate that these agents are beneficial in correcting the extensive lipid abnormalities that are frequently present in these individuals. However, the optimal management of metabolic syndrome dyslipidemia will depend on the outcomes of future prospective clinical trials. This review examines the underlying causes and prevalence of the metabolic syndrome and its impact on CHD morbidity and mortality and discusses the role of statins in optimizing its management.

Metabolic syndrome and the risk of adverse cardiovascular events after an acute coronary syndrome.

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Cavallari, Ilaria; Cannon, Christopher P; Braunwald, Eugene; Goodrich, Erica L; Im, KyungAh; Lukas, Mary Ann; O'Donoghue, Michelle L

2018-05-01

Background The incremental prognostic value of assessing the metabolic syndrome has been disputed. Little is known regarding its prognostic value in patients after an acute coronary syndrome. Design and methods The presence of metabolic syndrome (2005 International Diabetes Federation) was assessed at baseline in SOLID-TIMI 52, a trial of patients within 30 days of acute coronary syndrome (median follow-up 2.5 years). The primary endpoint was major coronary events (coronary heart disease death, myocardial infarction or urgent coronary revascularization). Results At baseline, 61.6% ( n = 7537) of patients met the definition of metabolic syndrome, 34.7% (n = 4247) had diabetes and 29.3% had both ( n = 3584). The presence of metabolic syndrome was associated with increased risk of major coronary events (adjusted hazard ratio (adjHR) 1.29, p metabolic syndrome was numerically but not significantly associated with the risk of major coronary events (adjHR 1.13, p = 0.06). Conversely, diabetes was a strong independent predictor of major coronary events in the absence of metabolic syndrome (adjHR 1.57, p metabolic syndrome identified patients at highest risk of adverse outcomes but the incremental value of metabolic syndrome was not significant relative to diabetes alone (adjHR 1.07, p = 0.54). Conclusions After acute coronary syndrome, diabetes is a strong and independent predictor of adverse outcomes. Assessment of the metabolic syndrome provides only marginal incremental value once the presence or absence of diabetes is established.

Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (II

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2008-03-01

Full Text Available Fetuses with neural tube defects (NTDs maybe associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as Currarino syndrome, sacral defect with anterior meningocele, Jarcho-Levin syndrome (spondylo-costal dysostosis, lateral meningocele syndrome, neurofibromatosis type I, Marfan syndrome, and hyperthermia. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.

Validation of cytogenetic risk groups according to International Prognostic Scoring Systems by peripheral blood CD34+FISH: results from a German diagnostic study in comparison with an international control group

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Braulke, Friederike; Platzbecker, Uwe; Müller-Thomas, Catharina; Götze, Katharina; Germing, Ulrich; Brümmendorf, Tim H.; Nolte, Florian; Hofmann, Wolf-Karsten; Giagounidis, Aristoteles A. N.; Lübbert, Michael; Greenberg, Peter L.; Bennett, John M.; Solé, Francesc; Mallo, Mar; Slovak, Marilyn L.; Ohyashiki, Kazuma; Le Beau, Michelle M.; Tüchler, Heinz; Pfeilstöcker, Michael; Nösslinger, Thomas; Hildebrandt, Barbara; Shirneshan, Katayoon; Aul, Carlo; Stauder, Reinhard; Sperr, Wolfgang R.; Valent, Peter; Fonatsch, Christa; Trümper, Lorenz; Haase, Detlef; Schanz, Julie

2015-01-01

International Prognostic Scoring Systems are used to determine the individual risk profile of myelodysplastic syndrome patients. For the assessment of International Prognostic Scoring Systems, an adequate chromosome banding analysis of the bone marrow is essential. Cytogenetic information is not available for a substantial number of patients (5%–20%) with dry marrow or an insufficient number of metaphase cells. For these patients, a valid risk classification is impossible. In the study presented here, the International Prognostic Scoring Systems were validated based on fluorescence in situ hybridization analyses using extended probe panels applied to cluster of differentiation 34 positive (CD34+) peripheral blood cells of 328 MDS patients of our prospective multicenter German diagnostic study and compared to chromosome banding results of 2902 previously published patients with myelodysplastic syndromes. For cytogenetic risk classification by fluorescence in situ hybridization analyses of CD34+ peripheral blood cells, the groups differed significantly for overall and leukemia-free survival by uni- and multivariate analyses without discrepancies between treated and untreated patients. Including cytogenetic data of fluorescence in situ hybridization analyses of peripheral CD34+ blood cells (instead of bone marrow banding analysis) into the complete International Prognostic Scoring System assessment, the prognostic risk groups separated significantly for overall and leukemia-free survival. Our data show that a reliable stratification to the risk groups of the International Prognostic Scoring Systems is possible from peripheral blood in patients with missing chromosome banding analysis by using a comprehensive probe panel (clinicaltrials.gov identifier:01355913). PMID:25344522

Validation of cytogenetic risk groups according to International Prognostic Scoring Systems by peripheral blood CD34+FISH: results from a German diagnostic study in comparison with an international control group.

Science.gov (United States)

Braulke, Friederike; Platzbecker, Uwe; Müller-Thomas, Catharina; Götze, Katharina; Germing, Ulrich; Brümmendorf, Tim H; Nolte, Florian; Hofmann, Wolf-Karsten; Giagounidis, Aristoteles A N; Lübbert, Michael; Greenberg, Peter L; Bennett, John M; Solé, Francesc; Mallo, Mar; Slovak, Marilyn L; Ohyashiki, Kazuma; Le Beau, Michelle M; Tüchler, Heinz; Pfeilstöcker, Michael; Nösslinger, Thomas; Hildebrandt, Barbara; Shirneshan, Katayoon; Aul, Carlo; Stauder, Reinhard; Sperr, Wolfgang R; Valent, Peter; Fonatsch, Christa; Trümper, Lorenz; Haase, Detlef; Schanz, Julie

2015-02-01

International Prognostic Scoring Systems are used to determine the individual risk profile of myelodysplastic syndrome patients. For the assessment of International Prognostic Scoring Systems, an adequate chromosome banding analysis of the bone marrow is essential. Cytogenetic information is not available for a substantial number of patients (5%-20%) with dry marrow or an insufficient number of metaphase cells. For these patients, a valid risk classification is impossible. In the study presented here, the International Prognostic Scoring Systems were validated based on fluorescence in situ hybridization analyses using extended probe panels applied to cluster of differentiation 34 positive (CD34(+)) peripheral blood cells of 328 MDS patients of our prospective multicenter German diagnostic study and compared to chromosome banding results of 2902 previously published patients with myelodysplastic syndromes. For cytogenetic risk classification by fluorescence in situ hybridization analyses of CD34(+) peripheral blood cells, the groups differed significantly for overall and leukemia-free survival by uni- and multivariate analyses without discrepancies between treated and untreated patients. Including cytogenetic data of fluorescence in situ hybridization analyses of peripheral CD34(+) blood cells (instead of bone marrow banding analysis) into the complete International Prognostic Scoring System assessment, the prognostic risk groups separated significantly for overall and leukemia-free survival. Our data show that a reliable stratification to the risk groups of the International Prognostic Scoring Systems is possible from peripheral blood in patients with missing chromosome banding analysis by using a comprehensive probe panel (clinicaltrials.gov identifier:01355913). Copyright© Ferrata Storti Foundation.

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...

Risk of the Burn-Out Syndrome in Caring Professions

OpenAIRE

Stecivová Fořtová, Irena

2007-01-01

This study (Risk of the Burnout Syndrome in Caring Professions) deals with the risk of the development of the Burnout Syndrome in Caring Professions, possible prevention and therapy. In the theoretical part the dissertation describes the Burnout Syndrome and the circumstances which lead to its beginning and development. In the practical part the dissertation describes the research on the frequency of symptoms of the Burnout Syndrome (enclosed is the questionnaire of the research) and assumed ...

Risk Syndromes and Scales Determining Risk in Schizophrenia and Other Psychoses

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Soner Cakmak

2015-12-01

Full Text Available Schizophrenia is a chronic disorder leading to lifelong deterioration of social and vocational functioning. Prodromal period, designates the time interval starting with emerging nonspecific signs and deficits and extending up to presentation of distinct and ongoing schizophrenic symptoms, is observed in most of schizophrenia patients. In schizophrenia, poor premorbid adjustment leads to a worse prognosis and thus early detection and intervention is required in prodromal period. To this end, under the heading of risk factors for schizophrenia and psychosis, classification and scales to determine the risk are being utilized. Most frequently used scales are; Bonn Scale for the Assessment of Basic Symptoms (BSABS, Comprehensive Assessment of At-Risk Mental States (CAARMS, Structured Interview for Psychosis-Risk Syndromes (SIPS. Through the light of these latest developments, recent edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-5 added psychosis risk syndrome or attenuated psychosis syndrome to indicate risk of transition to psychosis. These approaches revealed that the risk of progression to psychosis was not reliably correlated with fulfilled criteria, but abscence of criteria credibly predicted the unlikelihood of psychosis emergence. Evidently, concomitant premorbid features and prodromal symptoms significantly increase the risk of progression to psychosis and schizophrenia in comparison to normal population. Nevertheless, specification and elaboration of risk criteria will enhance reliability of risk determination. [Archives Medical Review Journal 2015; 24(4.000: 494-508

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.

How does genetic risk information for Lynch syndrome translate to risk management behaviours?

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Steel, Emma; Robbins, Andrew; Jenkins, Mark; Flander, Louisa; Gaff, Clara; Keogh, Louise

2017-01-01

There is limited research on why some individuals who have undergone predictive genetic testing for Lynch syndrome do not adhere to screening recommendations. This study aimed to explore qualitatively how Lynch syndrome non-carriers and carriers translate genetic risk information and advice to decisions about risk managment behaviours in the Australian healthcare system. Participants of the Australasian Colorectal Cancer Family Registry who had undergone predictive genetic testing for Lynch syndrome were interviewed on their risk management behaviours. Transcripts were analysed thematically using a comparative coding analysis. Thirty-three people were interviewed. Of the non-carriers ( n  = 16), 2 reported having apparently unnecessary colonoscopies, and 6 were unsure about what population-based colorectal cancer screening entails. Of the carriers ( n  = 17), 2 reported they had not had regular colonoscopies, and spoke about their discomfort with the screening process and a lack of faith in the procedure's ability to reduce their risk of developing colorectal cancer. Of the female carriers ( n  = 9), 2 could not recall being informed about the associated risk of gynaecological cancers. Non-carriers and female carriers of Lynch syndrome could benefit from further clarity and advice about appropriate risk management options. For those carriers who did not adhere to colonoscopy screening, a lack of faith in both genetic test results and screening were evident. It is essential that consistent advice is offered to both carriers and non-carriers of Lynch syndrome.

Modeling Marrow Failure and MDS for Novel Therapeutics

Science.gov (United States)

2017-03-01

syndrome (MDS) and leukemia is also markedly elevated in patients with inherited marrow failure syndromes compared to age-matched controls. Prognosis of...Novel Therapeutics W81XWH-16-1-0054 1. Introduction Clonal evolution is a potentially life threatening long-term complication of inherited and...The risk of early progression to myelodysplastic syndrome (MDS) and leukemia is also markedly elevated in patients with inherited marrow failure

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.

Framingham risk score for estimation of 10-years of cardiovascular diseases risk in patients with metabolic syndrome.

Science.gov (United States)

Jahangiry, Leila; Farhangi, Mahdieh Abbasalizad; Rezaei, Fatemeh

2017-11-13

There are a few studies evaluating the predictive value of Framingham risk score (FRS) for cardiovascular disease (CVD) risk assessment in patients with metabolic syndrome in Iran. Because of the emerging high prevalence of CVD among Iranian population, it is important to predict its risk among populations with potential predictive tools. Therefore, the aim of the current study is to evaluate the FRS and its determinants in patients with metabolic syndrome. In the current cross-sectional study, 160 patients with metabolic syndrome diagnosed according to the National Cholesterol Education Adult Treatment Panel (ATP) III criteria were enrolled. The FRS was calculated using a computer program by a previously suggested algorithm. Totally, 77.5, 16.3, and 6.3% of patients with metabolic syndrome were at low, intermediate, and high risk of CVD according to FRS categorization. The highest prevalence of all of metabolic syndrome components were in low CVD risk according to the FRS grouping (P metabolic syndrome and different FRS categorization among patients with metabolic syndrome were identified. High SBP and FSG were associated with meaningfully increased risk of CVD compared with other parameters. The study is not a trial; the registration number is not applicable.

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

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

Predictors of Obstructive Sleep Apnea Risk among Blacks with Metabolic Syndrome.

Science.gov (United States)

Rogers, A; Ravenell, J; Donat, M; Sexias, A; Ogedegbe, C; McFarlane, S I; Jean-Louis, G

Identification of risk factors for obstructive sleep apnea (OSA) is important to enable comprehensive intervention to reduce OSA-related cardiovascular disease (CVD). The metabolic syndrome outcome study (MetSO) provides a unique opportunity to address these factors. This study investigated risk of OSA among blacks with metabolic syndrome. The present study utilized data from MetSO, an NIH-funded cohort study of blacks with metabolic syndrome. A total of 1,035 patients provided data for the analysis. These included sociodemographic factors, health risks, and medical history. Physician-diagnosed conditions were obtained using an electronic medical record system (Allscripts, Sunrise Enterprise). Patients were diagnosed with metabolic syndrome using criteria articulated in the joint interim statement for harmonizing the metabolic syndrome. Patients with a score ≥6 on the Apnea Risk Evaluation System (ARES) questionnaire were considered at risk for OSA. Obesity is defined by body mass index (BMI ≥ 30 kg/m 2 ). Of the 1,035 patients screened in the MetSO cohort, 48.9% were at high risk for OSA. Using multivariate-adjusted logistic regression analysis, we observed that obesity was the strongest predictor of OSA risk (OR=1.59, 95%CI=1.24-2.04, pmetabolic syndrome.

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.

Cardiovascular risk in women with polycystic ovary syndrome.

Science.gov (United States)

Cho, L W; Atkin, S L

2007-12-01

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that has received an immense amount of attention in the recent years due to the possible associated risk of cardiovascular disease. Women with PCOS demonstrate an adverse cardiovascular profile characteristic of the cardiometabolic syndrome and an established risk of progression to type 2 diabetes. Despite the presence of cardiovascular risk factors and increased surrogate markers of cardiovascular disease, it is unclear if they develop accelerated atherosclerosis. This article summarized the recent development and findings of cardiovascular risk in women with PCOS, and finally the therapeutic options will be discussed.

Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (III

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2008-06-01

Full Text Available Fetuses with neural tube defects (NTDs may be associated with syndromes, disorders, and maternal and fetal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal and fetal risk factors associated with NTDs, such as omphalocele, OEIS (omphalocele-exstrophy-imperforate anus-spinal defects complex, pentalogy of Cantrell, amniotic band sequence, limb-body wall complex, Meckel syndrome, Joubert syndrome, skeletal dysplasia, diabetic embryopathy, and single nucleotide polymorphisms in genes of glucose metabolism. NTDs associated with syndromes, disorders, and maternal and fetal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multi facto rial NTDs. Perinatal identification of NTDs should alert the clinician to the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling. [Taiwan J Obstet Cynecol 2008;47(2:131-140

Syndromes, Disorders and Maternal Risk Factors Associated With Neural Tube Defects (VI

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2008-09-01

Full Text Available Neural tube defects (NTDs may be associated with syndromes, disorders, and maternal and fetal risk factors. This article provides a comprehensive review of the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, including maternal fumonisin consumption, periconceptional zinc deficiency, parental occupational exposure and residential proximity to pesticides, lower socioeconomic status, fetal alcohol syndrome, mutations in the VANGL1 gene, human athymic Nude/SCID fetus, and single nucleotide polymorphism in the NOS3 gene. NTDs associated with these syndromes, disorders, and maternal and fetal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

Clinical outcome and risk stratification in Brugada syndrome

Directory of Open Access Journals (Sweden)

Tadashi Wada, MD

2013-04-01

Full Text Available Since the first report on Brugada syndrome, various risk markers for the prediction of ventricular fibrillation (VF in patients with Brugada syndrome have been reported. Multicenter trials reported spontaneous type 1 electrocardiogram (ECG and disease symptoms as prognostic predictors. VF induction by programmed electrical stimulation is still controversial, and most of the studies have failed to prove its significance for the prediction of spontaneous VF episodes. In Japan, although most multicenter studies have shown that patients with type 1 ECG were at high risk, it is difficult to determine the indication for implantation of an implantable cardioverter defibrillator only based on the ECG type. Recent studies have added new risk markers, such as inferolateral early repolarization, fragmented QRS, and shorter effective refractory periods of the ventricle, in addition to type 1 ECG and symptoms. Here, we review the clinical outcome and indices reported as reliable prognostic factors of Brugada syndrome with a focus on the clinical and ECG markers for risk stratification.

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...

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

Risk factors for metabolic syndrome after liver transplantation

DEFF Research Database (Denmark)

Thoefner, Line Buch; Rostved, Andreas Arendtsen; Pommergaard, Hans-Christian

2018-01-01

syndrome after liver transplantation. METHODS: The databases Medline and Scopus were searched for observational studies evaluating prevalence and risk factors for metabolic syndrome after liver transplantation. Meta-analyses were performed based on odds ratios (ORs) from multivariable analyses...

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

Cardiovascular Risk Stratification in Patients with Metabolic Syndrome Without Diabetes or Cardiovascular Disease: Usefulness of Metabolic Syndrome Severity Score.

Science.gov (United States)

Masson, Walter; Epstein, Teo; Huerín, Melina; Lobo, Lorenzo Martín; Molinero, Graciela; Angel, Adriana; Masson, Gerardo; Millán, Diana; De Francesca, Salvador; Vitagliano, Laura; Cafferata, Alberto; Losada, Pablo

2017-09-01

The estimated cardiovascular risk determined by the different risk scores, could be heterogeneous in patients with metabolic syndrome without diabetes or vascular disease. This risk stratification could be improved by detecting subclinical carotid atheromatosis. To estimate the cardiovascular risk measured by different scores in patients with metabolic syndrome and analyze its association with the presence of carotid plaque. Non-diabetic patients with metabolic syndrome (Adult Treatment Panel III definition) without cardiovascular disease were enrolled. The Framingham score, the Reynolds score, the new score proposed by the 2013 ACC/AHA Guidelines and the Metabolic Syndrome Severity Calculator were calculated. Prevalence of carotid plaque was determined by ultrasound examination. A Receiver Operating Characteristic analysis was performed. A total of 238 patients were enrolled. Most patients were stratified as "low risk" by Framingham score (64%) and Reynolds score (70.1%). Using the 2013 ACC/AHA score, 45.3% of the population had a risk ≥7.5%. A significant correlation was found between classic scores but the agreement (concordance) was moderate. The correlation between classical scores and the Metabolic Syndrome Severity Calculator was poor. Overall, the prevalence of carotid plaque was 28.2%. The continuous metabolic syndrome score used in our study showed a good predictive power to detect carotid plaque (area under the curve 0.752). In this population, the calculated cardiovascular risk was heterogenic. The prevalence of carotid plaque was high. The Metabolic Syndrome Severity Calculator showed a good predictive power to detect carotid plaque.

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

[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.

Unrelated cord blood transplantation in adults with myelodysplasia or secondary acute myeloblastic leukemia: a survey on behalf of Eurocord and CLWP of EBMT

NARCIS (Netherlands)

Robin, M.; Sanz, G.F.; Ionescu, I.; Rio, B.; Sirvent, A.; Renaud, M.; Carreras, E.; Milpied, N.; Mohty, M.; Beguin, Y.; Bordigoni, P.; Witte, T.J.M. de; Picardi, A.; Purtill, D.; Gluckman, E.; Kroger, N.; Rocha, V.

2011-01-01

The aim of our study was to evaluate, through the Eurocord and European Group for Blood and Marrow Transplantation (EBMT) registries, outcomes and risk factors for outcomes in adult patients who underwent single or double unrelated cord blood transplantation (UCBT) for myelodysplastic syndrome (MDS)

Quality of life, physical function and MRI T2* in elderly low-risk MDS patients treated to a haemoglobin level of ≥120 g/L with darbepoetin alfa ± filgrastim or erythrocyte transfusions

DEFF Research Database (Denmark)

Nilsson-Ehle, Herman; Birgegård, Gunnar; Samuelsson, Jan

2011-01-01

Anaemia in low-risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin ± granulocyte colony-stimulating factor (G-CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels...... has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of >120 g/L....

Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer

Science.gov (United States)

2017-09-20

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Nonmalignant Neoplasm

The risk of metabolic syndrome and nutrition

Directory of Open Access Journals (Sweden)

Aleksandr Konstantinovich Kuntsevich

2015-02-01

Full Text Available In the present literature review modern epidemiological studies the role of nutrition in the prevalence of the metabolic syndrome. Were analyzed mainly work on the association of certain types of dietary intake of the population to the risk of metabolic syndrome in several Western and Asian countries. The purpose of these studies was to determine deemed "good" type and the "bad" type of food, risk assessment and exchange of metabolic disorders to determine the optimal dietary recommendations.  Application of factor and cluster analysis allowed in a number of studies to identify groups of products associated with a decrease in the prevalence of metabolic syndrome and to estimate the odds ratios of metabolic syndrome when compared with the "bad" diet.  A number of papers were obtained confirm the effectiveness of the Mediterranean diet in the prevention of metabolic disorders. Commitment to the traditional Western diet is associated with deterioration in health, compared with the recommended "healthy" diet.  Data from epidemiological studies nutrition and metabolic disorders associated with a number of diseases, may be useful in determining how the recommendations on the best type of feeding the population, so to identify ways to further research.

Identification of de Novo Fanconi Anemia in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

Science.gov (United States)

2016-05-13

Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); 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 Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Fanconi Anemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Science.gov (United States)

2018-02-16

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

MECHANISMS OF CARDIOVASCULAR DISEASE RISKS IN WOMEN WITH POLYCYSTIC OVARY SYNDROME

OpenAIRE

Katica Bajuk Studen; Janez Preželj; Tomaž Kocjan; Marija Pfeifer

2009-01-01

Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. The main features of the syndrome are clinical and/or laboratory signs of hyperandrogenism and menstrual cycle irregularities, although several variants of the definition of the syndrome exist. Conclusions PCOS is clearly associated with increased prevalence of cardiovascular disease risk factors. However, long term risk of cardiovascular disease morbidity and mortality ...

Methemoglobinemia in Young Patients With Hematologic Cancer or Aplastic Anemia Treated With Dapsone

Science.gov (United States)

2017-04-13

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Methemoglobinemia; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Nonmalignant Neoplasm

A Web-Based Stem Cell Transplant Support System or Standard Care in Young Patients Undergoing Stem Cell Transplant and Their Families

Science.gov (United States)

2011-07-11

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Ovarian Cancer; Psychosocial Effects of Cancer and Its Treatment; Sarcoma

Non-Ablative Allo HSCT For Hematologic Malignancies or SAA

Science.gov (United States)

2011-12-07

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Precancerous/Nonmalignant Condition; Small Intestine Cancer

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.

Guidelineness of the parameters using integrated test in down syndrome risk prediction

International Nuclear Information System (INIS)

Lee, Jin Won; Go, Sung Jin; Kang, Se Sik; Kim, Chang Soo

2016-01-01

This study was an evaluation of the significance of each parameter through aimed at pregnant women subjected to screening test(integrated test) in predicting risk of Down syndrome. We retrospectively analysed the correlation of risk of Down's syndrome with Nuchal Translucency(NT) images measured by ultrasound, Pregnancy Associated Plasma Protein A(PAPP-A), alpha-fetoprotein(AFP), unconjugated estriol(uE3), human chorionic gonadotrophin(hCG) and Inhibin A by maternal serum. As a result, a significant correlation with NT, uE3, hCG, Inhibin A is revealed with Down's syndrome risk(P<.001). In ROC analysis, AUC of Inhibin A is analysed as the biggest predictor of Down's syndrome(0.859). And the criterion for cut-off was inhibin A 1.4 MoM(sensitivity 81.8%, specificity 75.9%). In conclusion, Inhibin A was the most useful in parameters to predict Down's syndrome in the integrated test. If we make up for the weakness based on the cut-off value of parameters they will be able to be used as an independent indicator in the risk of Down's syndrome screening

Presence of Donor-Derived DNA in Semen Samples From Cancer Survivors Who Underwent Donor Stem Cell Transplant

Science.gov (United States)

2014-12-08

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

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)

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.

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.

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

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

An audit to assess the consequences of the use of a pluripotential risk syndrome: the case to move on from "psychosis risk syndrome (PRS) ".

Science.gov (United States)

Agius, Mark; Zaman, Rashid; Hanafy, Dean

2013-09-01

An audit has been carried out of the patients who have been assessed using the CAARMS tool in order to assess patients who have been judged to have a prodromal psychotic syndrome. Instead of advocating PRS, Johannessen & McGorry (Johannessen 2010), have offered an alternative: a 'Pluripotent risk syndrome'. This less specific prodrome reflects the unpredictable nature of "Ultra-High Risk" states which have been shown to be more likely to develop into a non-psychotic mood disorder than schizophrenia (Hoon 2012). The corollary this is thus; could patients who exhibit significant depressive features (regardless of diagnosis) be initially identified as having a 'Pluripotent risk syndrome'? Ten adult patients (6 males & 4 females, aged 19-26 years old) with four broad psychiatric diagnoses (Depression, Schizoaffective disorder, Borderline personality disorder and psychotic illness) were chosen from an anonimised database of the patients and their symptomatology as assessed by CAARMS was retrospectively assessed to see if the presence of depressive symptoms supported the case for a "Pluripotent risk syndrome". Though patients diagnosed with depression frequently exhibited depressive symptoms, psychotic symptoms were also apparent, albeit in comparatively decreased severity. Patients diagnosed with schizoaffective disorder had depressive symptoms more frequently than psychotic symptoms, but these were comparatively less severe. Borderline personality disorder patients exhibited depressive symptoms more frequently than psychotic symptoms. Psychotic illnesses frequently had depressive symptoms, but more typically (and unsurprisingly) had comparatively more severe psychotic than depressive symptoms. Hence we propose that the concept of a "Pluripotent risk syndrome" is in our view born out.

Risk factors in neuroleptic malignant syndrome.

Science.gov (United States)

Gupta, Vinay; Magon, Rakesh; Mishra, B P; Sidhu, G B S; Mahajan, Ranjiv

2003-01-01

Neuroleptic malignant syndrome (NMS) is an uncommon but potentially serious idiosyncratic response to neuroleptic antipsychotics. It usually affects young males, but the risk has been seen to increase with certain factors including the administration practices of antipsychotic neuroleptics in these individuals. Even though no predictors for NMS are yet known, this article highlights the findings on certain risk factors as seen from a series of fifteen patients who developed NMS. Cautious use of neuroleptics in those at risk, early recognition and institution of immediate management is important.

Characterizing genetic syndromes involved in cancer and radiogenic cancer risk

International Nuclear Information System (INIS)

Unrau, P.; Doerffer, K.

1998-01-01

The COG project 2806A (1995), reviewed the On-line Mendelian Inheritance in Man (OMIM) database of genetic syndromes to identify those syndromes, genes, and DNA sequences implicated in some way in the cancer process, and especially in radiogenic cancer risk. The current report describes a recent update of the survey in light of two years of further progress in the Human Genome project, and is intended to supply a comprehensive list of those genetic syndromes, genes, DNA sequences and map locations that define genes likely to be involved in cancer risk. Of the 8203 syndromes in OMIM in 1997 June, 814 are associated, even if marginally, with cancer. Of the 814 syndromes so linked, 672 have been mapped to a chromosome, and 476 have been mapped to a chromosome and had a DNA sequence associated with their messenger RNA (or cDNA) sequences. In addition, 35 syndromes have sequences not associated with map locations, and the remaining 107 have neither been mapped nor sequenced. We supply the list of the various genetic syndromes sorted by chromosome location and by OMIM descriptor, together with all the associated but unmapped and unsequenced syndromes. (author)

Characterizing genetic syndromes involved in cancer and radiogenic cancer risk

Energy Technology Data Exchange (ETDEWEB)

Unrau, P; Doerffer, K

1998-01-01

The COG project 2806A (1995), reviewed the On-line Mendelian Inheritance in Man (OMIM) database of genetic syndromes to identify those syndromes, genes, and DNA sequences implicated in some way in the cancer process, and especially in radiogenic cancer risk. The current report describes a recent update of the survey in light of two years of further progress in the Human Genome project, and is intended to supply a comprehensive list of those genetic syndromes, genes, DNA sequences and map locations that define genes likely to be involved in cancer risk. Of the 8203 syndromes in OMIM in 1997 June, 814 are associated, even if marginally, with cancer. Of the 814 syndromes so linked, 672 have been mapped to a chromosome, and 476 have been mapped to a chromosome and had a DNA sequence associated with their messenger RNA (or cDNA) sequences. In addition, 35 syndromes have sequences not associated with map locations, and the remaining 107 have neither been mapped nor sequenced. We supply the list of the various genetic syndromes sorted by chromosome location and by OMIM descriptor, together with all the associated but unmapped and unsequenced syndromes. (author) 1 tab., 4 figs.

Colorectal Cancer Risk in Patients With Lynch Syndrome and Inflammatory Bowel Disease.

Science.gov (United States)

Derikx, Lauranne A A P; Smits, Lisa J T; van Vliet, Shannon; Dekker, Evelien; Aalfs, Cora M; van Kouwen, Mariëtte C A; Nagengast, Fokko M; Nagtegaal, Iris D; Hoogerbrugge, Nicoline; Hoentjen, Frank

2017-03-01

Lynch syndrome and inflammatory bowel diseases (IBD) are associated with an increased risk of colorectal cancer (CRC). However, it is not clear whether the risk of CRC is even higher for patients with a combination of Lynch syndrome and IBD. We investigated the risk for CRC in this subgroup by establishing a Lynch syndrome cohort from the Radboud University Medical Center (Nijmegen, The Netherlands) and the Academic Medical Center (Amsterdam, The Netherlands). Patients with heterozygous germline mutations in MLH1, MSH2 (and EPCAM deletion-mediated MSH2 methylation), MSH6, or PMS2 who were tested and/or treated from 1998 through 2014 were included. Patients who developed IBD were identified by linkage of this cohort to the Dutch nationwide Pathology Registry (PALGA). Subsequently, we compared the risk of CRC between Lynch syndrome patients with IBD and without IBD. Of 1046 patients with Lynch syndrome, 15 developed IBD (1.4%). Patients with Lynch syndrome and IBD were significantly younger (median age, 38.0 y) than patients with Lynch syndrome without IBD (median age, 52.0 y; P = .001). Nevertheless, a similar proportion of patients in each group developed CRC: 4 of the 15 patients (26.7%) with Lynch syndrome and IBD compared with 311 of the 1031 patients (30.2%) with Lynch syndrome without IBD. Patients with Lynch syndrome and IBD developed CRC at a younger age (median age, 36.0 y) than patients with Lynch syndrome without IBD (median age, 46.0 y; P = .045). However, the cumulative incidence of CRC was similar between groups (P = .121). All patients with Lynch syndrome and IBD who developed CRC had ulcerative colitis, producing a higher cumulative incidence of CRC for this IBD subgroup (P Lynch syndrome and IBD develop CRC risk at a younger age than patients without IBD; patients with ulcerative colitis are at especially high risk. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

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.

Risks of Metabolic Syndrome in Students of the Faculty of Health Sciences

Directory of Open Access Journals (Sweden)

Ersin Öğüş

2013-09-01

Full Text Available Background: Metabolic syndrome is highly prevalent in the adult population worldwide. Education may play an important role in preventing metabolic syndrome in young adults, especially those who are attending university. Such adults are at a critical point in their lives and make their own lifestyle choices that can affect their future health. Aims: The aims of this study were to determine the metabolic syndrome risk levels of students from the Faculty of Health Sciences. Study Design: Survey design study. Methods: In a questionnaire developed by the researchers to collect data in accordance with the relevant literature, the scale of the risk of metabolic syndrome was assessed. A stepwise logistic regression analysis was performed to determine the risks. Results: Important risk factors for metabolic syndrome were found to be gender, weight gain, “stress eating” excessive amounts of food, sleeping for more than 8 hours a day, feeling tired after sleep, belonging to a divided family, and eating whilst working on the computer. Conclusion: The students from the Faculty of Health Sciences, particularly because they are trained in the health sector, are expected to have more information about the risk factors of metabolic syndrome, and take necessary precautions to prevent it.

Metabolic syndrome and risk factors for non-alcoholic fatty liver disease

Directory of Open Access Journals (Sweden)

Mônica Rodrigues de Araújo Souza

2012-03-01

Full Text Available CONTEXT: Non-alcoholic fatty liver disease (NAFLD, hepatic manifestation of metabolic syndrome, has been considered the most common liver disease nowadays, which is also the most frequent cause of elevated transaminases and cryptogenic cirrhosis. The greatest input of fatty acids into the liver and consequent increased beta-oxidation contribute to the formation of free radicals, release of inflammatory cytokines and varying degrees of hepatocytic aggression, whose histological expression may vary from steatosis (HS to non-alcoholic steatohepatitis (NASH. The differentiation of these forms is required by the potential risk of progression to cirrhosis and development of hepatocellular carcinoma. OBJECTIVE: To review the literature about the major risk factors for NAFLD in the context of metabolic syndrome, focusing on underlying mechanisms and prevention. METHOD: PubMed, MEDLINE and SciELO data basis analysis was performed to identify studies describing the link between risk factors for metabolic syndrome and NAFLD. A combination of descriptors was used, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolic syndrome and risk factors. At the end, 96 clinical and experimental studies, cohorts, meta-analysis and systematic reviews of great impact and scientific relevance to the topic, were selected. RESULTS: The final analysis of all these data, pointed out the central obesity, type 2 diabetes, dyslipidemia and hypertension as the best risk factors related to NAFLD. However, other factors were highlighted, such as gender differences, ethnicity, genetic factors and the role of innate immunity system. How these additional factors may be involved in the installation, progression and disease prognosis is discussed. CONCLUSION: Risk factors for NAFLD in the context of metabolic syndrome expands the prospects to 1 recognize patients with metabolic syndrome at high risk for NAFLD, 2 elucidate pathways common to other co-morbidities, 3

Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer

Science.gov (United States)

2017-11-27

Chronic Myeloproliferative Disorders; Diamond-blackfan Anemia; Fanconi Anemia; Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Comparison of metabolic syndrome with growing epidemic syndrome Z in terms of risk factors and gender differences.

Science.gov (United States)

Uyar, Meral; Davutoğlu, Vedat; Aydın, Neriman; Filiz, Ayten

2013-05-01

The aim of this study is to compare metabolic syndrome with syndrome Z growing epidemic in terms of risk factors, demographic variables, and gender differences in our large cohort at southeastern area in Turkey. Data of patients admitted to sleep clinic in University of Gaziantep from January 2006 to January 2011 were retrospectively evaluated. ATP III and JNC 7 were used for defining metabolic syndrome and hypertension. Data of 761 patients were evaluated. Hypertension, diabetes mellitus, coronary artery disease, pulmonary hypertension, and left ventricular hypertrophy were more common in patients with syndrome Z than in patients without metabolic syndrome. Age, waist/neck circumferences, BMI, triglyceride, glucose, and Epworth sleepiness scale score were detected higher, whereas the minimum oxygen saturation during sleep was lower in patients with syndrome Z. Metabolic syndrome was more common in sleep apneic subjects than in controls (58 versus 30 %). Female sleep apneics showed higher rate of metabolic syndrome than those of males (74 versus 52 %). Hypertension, diabetes mellitus, coronary artery disease, and left ventricular hypertrophy were detected higher in males with syndrome Z than in males without metabolic syndrome. Snoring and excessive daytime sleepiness were detected higher in females with syndrome Z than in females without metabolic syndrome. Systemic/pulmonary hypertension, diabetes mellitus, and left ventricular hypertrophy were more common in females with syndrome Z than in females without metabolic syndrome. Complaints of headache and systemic/pulmonary hypertension were more common among females than males with syndrome Z. Female syndrome Z patients had lower minimum oxygen saturation than male patients with syndrome Z. Metabolic syndrome in sleep apneic patients is more prevalent than in controls. All metabolic syndrome parameters were significantly different among obstructive sleep apneic patients with respect to gender with more severe

Colorectal Cancer Risk in Patients With Lynch Syndrome and Inflammatory Bowel Disease

NARCIS (Netherlands)

Derikx, L.A.A.P.; Smits, L.J.T.; Lent-van Vliet, S. van; Dekker, E.; Aalfs, C.M.; Kouwen, M.C.A. van; Nagengast, F.M.; Nagtegaal, I.D.; Hoogerbrugge, N.; Hoentjen, F.

2017-01-01

Lynch syndrome and inflammatory bowel diseases (IBD) are associated with an increased risk of colorectal cancer (CRC). However, it is not clear whether the risk of CRC is even higher for patients with a combination of Lynch syndrome and IBD. We investigated the risk for CRC in this subgroup by

The risk for type B aortic dissection in Marfan syndrome.

Science.gov (United States)

den Hartog, Alexander W; Franken, Romy; Zwinderman, Aeilko H; Timmermans, Janneke; Scholte, Arthur J; van den Berg, Maarten P; de Waard, Vivian; Pals, Gerard; Mulder, Barbara J M; Groenink, Maarten

2015-01-27

Aortic dissections involving the descending aorta are a major clinical problem in patients with Marfan syndrome. The purpose of this study was to identify clinical parameters associated with type B aortic dissection and to develop a risk model to predict type B aortic dissection in patients with Marfan syndrome. Patients with the diagnosis of Marfan syndrome and magnetic resonance imaging or computed tomographic imaging of the aorta were followed for a median of 6 years for the occurrence of type B dissection or the combined end point of type B aortic dissection, distal aortic surgery, and death. A model using various clinical parameters as well as genotyping was developed to predict the risk for type B dissection in patients with Marfan syndrome. Between 1998 and 2013, 54 type B aortic dissections occurred in 600 patients with Marfan syndrome (mean age 36 ± 14 years, 52% male). Independent variables associated with type B aortic dissection were prior prophylactic aortic surgery (hazard ratio: 2.1; 95% confidence interval: 1.2 to 3.8; p = 0.010) and a proximal descending aorta diameter ≥27 mm (hazard ratio: 2.2; 95% confidence interval: 1.1 to 4.3; p = 0.020). In the risk model, the 10-year occurrence of type B aortic dissection in low-, moderate-, and high-risk patients was 6%, 19%, and 34%, respectively. Angiotensin II receptor blocker therapy was associated with fewer type B aortic dissections (hazard ratio: 0.3; 95% confidence interval: 0.1 to 0.9; p = 0.030). Patients with Marfan syndrome with prior prophylactic aortic surgery are at substantial risk for type B aortic dissection, even when the descending aorta is only slightly dilated. Angiotensin II receptor blocker therapy may be protective in the prevention of type B aortic dissections. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Metabolic syndrome among urban Indian young adults: prevalence and associated risk factors.

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Manjunath, Dinaker; Uthappa, Chengapp Kechamada; Kattula, Sri Rama; Allam, Ramesh Reddy; Chava, Nalini; Oruganti, Ganesh

2014-09-01

We estimated the prevalence of metabolic syndrome among urban Indian young adults (18-25 years) as defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), Internation Diabetes Federation (IDF), and Indian consensus statement criteria. We included 473 urban young adults through simple random sampling methodology to estimate the prevalence and associated risk factors for metabolic syndrome. Prevalence of metabolic syndrome was estimated to be 3.6 [95% confidence interval (CI) 2.2-5.8], 6.6% (95% CI 4.6-9.1), and 8.7% (95% CI 6.4-11.6) using the NCEP ATP III, IDF, and Indian consensus statement criteria, respectively. Men had significantly higher waist circumference, systolic blood pressure, fasting blood glucose, and triglycerides, whereas mean concentrations of both high-density lipoprotein cholesterol (HDL-C) and total cholesterol were significantly higher among women. Low HDL-C (38.9%), high blood pressure (26%), and central obesity (16.1%) were the most common component risk factors. Although less than 4% of normal weight adults met the criteria for metabolic syndrome, rates increased in overweight individuals and reached a prevalence of 87% in the obese participants. In all, 61.3% of the total population had one or more risk factors for metabolic syndrome. The prevalence of metabolic syndrome is high among urban young adults in India, and it increased with increase in body mass index (BMI). Each component risk factor in isolated form-increased BMI, smoking, and history of hypertension--is an associated risk factor for metabolic syndrome. Although it is unclear whether metabolic syndrome screening in young Indians as a means to prevent adverse cardiovascular health outcomes is appropriate, healthy lifestyles should nevertheless be encouraged, and young adults should be considered as an important group for cardiovascular risk reduction programs.

Guidelineness of the parameters using integrated test in down syndrome risk prediction

Energy Technology Data Exchange (ETDEWEB)

Lee, Jin Won [Graduate School of Catholic University of Pusan, Busan (Korea, Republic of); Go, Sung Jin; Kang, Se Sik; Kim, Chang Soo [Dept. Radiological Science, College of Health Sciences, Catholic University of Pusan, Busan (Korea, Republic of)

2016-12-15

This study was an evaluation of the significance of each parameter through aimed at pregnant women subjected to screening test(integrated test) in predicting risk of Down syndrome. We retrospectively analysed the correlation of risk of Down's syndrome with Nuchal Translucency(NT) images measured by ultrasound, Pregnancy Associated Plasma Protein A(PAPP-A), alpha-fetoprotein(AFP), unconjugated estriol(uE3), human chorionic gonadotrophin(hCG) and Inhibin A by maternal serum. As a result, a significant correlation with NT, uE3, hCG, Inhibin A is revealed with Down's syndrome risk(P<.001). In ROC analysis, AUC of Inhibin A is analysed as the biggest predictor of Down's syndrome(0.859). And the criterion for cut-off was inhibin A 1.4 MoM(sensitivity 81.8%, specificity 75.9%). In conclusion, Inhibin A was the most useful in parameters to predict Down's syndrome in the integrated test. If we make up for the weakness based on the cut-off value of parameters they will be able to be used as an independent indicator in the risk of Down's syndrome screening.

Baclofen-Amitriptyline Hydrochloride-Ketamine Gel in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer

Science.gov (United States)

2017-07-25

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neurotoxicity; Pain; Unspecified Adult Solid Tumor, Protocol Specific

[Burnout syndrome: a "true" cardiovascular risk factor].

Science.gov (United States)

Cursoux, Pauline; Lehucher-Michel, Marie-Pascale; Marchetti, Hélène; Chaumet, Guillaume; Delliaux, Stéphane

2012-11-01

The burnout syndrome is characterized by emotional exhaustion, depersonalization and reduced personal accomplishment in individuals professionally involved with others. The burnout syndrome is poorly recognized, particularly in France, as a distinct nosology from adaptation troubles, stress, depression, or anxiety. Several tools quantifying burnout and emotional exhaustion exist, the most spread is the questionnaire called Maslach Burnout Inventory. The burnout syndrome alters cardiovascular function and its neuroregulation by autonomic nervous system and is associated with: increased sympathetic tone to heart and vessels after mental stress, lowered physiological post-stress vagal rebound to heart, and lowered arterial baroreflex sensitivity. Job strain as burnout syndrome seems to be a real independent cardiovascular risk factor. Oppositely, training to manage emotions could increase vagal tone to heart and should be cardio-protective. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

American Ginseng in Treating Patients With Fatigue Caused by Cancer

Science.gov (United States)

2016-12-19

Chronic Myeloproliferative Disorders; Fatigue; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

Are certain fractures at increased risk for compartment syndrome after civilian ballistic injury?

Science.gov (United States)

Meskey, Thomas; Hardcastle, John; O'Toole, Robert V

2011-11-01

Compartment syndrome after ballistic fracture is uncommon but potentially devastating. Few data are available to help guide clinicians regarding risk factors for developing compartment syndrome after ballistic fractures. Our primary hypothesis was that ballistic fractures of certain bones would be at higher risk for development of compartment syndrome. A retrospective review at a Level I trauma center from 2001 through 2007 yielded 650 patients with 938 fractures resulting from gunshots. We reviewed all operative notes, clinic notes, discharge summaries, and data from our prospective trauma database. Cases in which the attending orthopedic surgeon diagnosed compartment syndrome and performed fasciotomy were considered cases with compartment syndrome. We excluded all prophylactic fasciotomies. Univariate analyses were conducted to identify risk factors associated with development of compartment syndrome. Twenty-six (2.8%) of the 938 fractures were associated with compartment syndrome. Only fibular (11.6%) and tibial (11.4%) fractures had incidence significantly higher than baseline for all ballistic fractures (p Ballistic fractures of the fibula and tibia are at increased risk for development of compartment syndrome over other ballistic fractures. We recommend increased vigilance when treating these injuries, particularly if the fracture is in the proximal aspect of the bone or is associated with vascular injury.

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.

Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD

Science.gov (United States)

2017-10-25

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Biphenotypic Leukemia; Acute Leukemia of Ambiguous Lineage; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Blastic Plasmacytoid Dendritic Cell Neoplasm; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Lymphoblastic Lymphoma; Myelodysplastic Syndrome With Excess Blasts; Myelodysplastic Syndrome With Excess Blasts-1; Myelodysplastic Syndrome With Excess Blasts-2; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Acute Lymphoblastic Leukemia; Refractory Acute Myeloid Leukemia

[Refeeding syndrome : Pathophysiology, risk factors, prevention, and treatment].

Science.gov (United States)

Wirth, R; Diekmann, R; Janssen, G; Fleiter, O; Fricke, L; Kreilkamp, A; Modreker, M K; Marburger, C; Nels, S; Pourhassan, M; Schaefer, R; Willschrei, H-P; Volkert, D

2018-04-01

Refeeding syndrome is a life-threatening complication that may occur after initiation of nutritional therapy in malnourished patients, as well as after periods of fasting and hunger. Refeeding syndrome can be effectively prevented and treated if its risk factors and pathophysiology are known. The initial measurement of thiamine level and serum electrolytes, including phosphate and magnesium, their supplementation if necessary, and a slow increase in nutritional intake along with close monitoring of serum electrolytes play an important role. Since refeeding syndrome is not well known and the symptoms can be extremely heterogeneous, this complication is poorly recognized, especially against the background of severe disease and multimorbidity. This overview aims to summarize the current knowledge and increase awareness about refeeding syndrome.

3'-Deoxy-3'-[18F] Fluorothymidine PET Imaging in Patients With Cancer

Science.gov (United States)

2017-12-05

Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unspecified Adult Solid Tumor, Protocol Specific

A unique rodent model of cardiometabolic risk associated with the metabolic syndrome and polycystic ovary syndrome.

Science.gov (United States)

Shi, Danni; Dyck, Michael K; Uwiera, Richard R E; Russell, Jim C; Proctor, Spencer D; Vine, Donna F

2009-09-01

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-/anovulation, and polycystic ovarian morphology and is a complex endocrine disorder that also presents with features of the metabolic syndrome, including obesity, insulin resistance, and dyslipidemia. These latter symptoms form cardiometabolic risk factors predisposing individuals to the development of type 2 diabetes and cardiovascular disease (CVD). To date, animal models to study PCOS in the context of the metabolic syndrome and CVD risk have been lacking. The aim of this study was to investigate the JCR:LA-cp rodent as an animal model of PCOS associated with the metabolic syndrome. Metabolic indices were measured at 6 and 12 wk, and reproductive parameters including ovarian morphology and estrous cyclicity were assessed at 12 wk or adulthood. At 6 wk of age, the cp/cp genotype of the JCR:LA-cp strain developed visceral obesity, insulin resistance, and dyslipidemia (hypertriglyceridemia and hypercholesterolemia) compared with control animals. Serum testosterone concentrations were not significantly different between groups at 6 wk of age. However, at 12 wk, the cp/cp genotype had higher serum testosterone concentrations, compared with control animals, and presented with oligoovulation, a decreased number of corpora lutea, and an increased number of total follicles, in particular atretic and cystic follicles. The cardiometabolic risk factors in the cp/cp animals were exacerbated at 12 wk including obesity, insulin resistance, and dyslipidemia. The results of this study demonstrate that the JCR:LA-cp rodent may be a useful PCOS-like model to study early mechanisms involved in the etiology of cardiometabolic risk factors in the context of both PCOS and the metabolic syndrome.

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

In silico cardiac risk assessment in patients with long QT syndrome

DEFF Research Database (Denmark)

Hoefen, Ryan; Reumann, Matthias; Goldenberg, Ilan

2012-01-01

The study was designed to assess the ability of computer-simulated electrocardiography parameters to predict clinical outcomes and to risk-stratify patients with long QT syndrome type 1 (LQT1).......The study was designed to assess the ability of computer-simulated electrocardiography parameters to predict clinical outcomes and to risk-stratify patients with long QT syndrome type 1 (LQT1)....

Cytomorphology review of 100 newly diagnosed lower-risk MDS patients in the European LeukemiaNet MDS (EUMDS) registry reveals a high inter-observer concordance

NARCIS (Netherlands)

Swart, L. de; Smith, A.; MacKenzie, M.; Symeonidis, A.; Neukirchen, J.; Mikulenkova, D.; Vallespi, T.; Zini, G.; Paszkowska-Kowalewska, M.; Kruger, A.; Saft, L.; Fenaux, P.; Bowen, D.; Hellstrom-Lindberg, E.; Cermak, J.; Stauder, R.; Tatic, A.; Holm, M.S.; Malcovati, L.; Madry, K.; Droste, J.A.; Blijlevens, N.M.; Witte, T.J. de; Germing, U.

2017-01-01

The European LeukemiaNet MDS (EUMDS) registry is collecting data of myelodysplastic syndrome (MDS) patients belonging to the IPSS low or intermediate-1 category, newly diagnosed by local cytologists. The diagnosis of MDS can be challenging, and some data report inter-observer variability with regard

Imaging of cardiovascular risk in patients with Turner's syndrome

International Nuclear Information System (INIS)

Marin, A.; Weir-McCall, J.R.; Webb, D.J.; Beek, E.J.R. van; Mirsadraee, S.

2015-01-01

Turner's syndrome is a disorder defined by an absent or structurally abnormal second X chromosome and affects around 1 in 2000 newborn females. The standardised mortality ratio in Turner's syndrome is around three-times higher than in the general female population, mainly as a result of cardiovascular disorders. Most striking is the early age at which Turner's syndrome patients develop the life-threatening complications of cardiovascular disorders compared to the general population. The cardiovascular risk stratification in Turner's syndrome is challenging and imaging is not systematically used. The aim of this article is to review cardiovascular risks in this group of patients and discuss a systematic imaging approach for early identification of cardiovascular disorders in these patients

Aprepitant, Granisetron, & Dexamethasone in Preventing Nausea & Vomiting in Pts. Receiving Cyclophosphamide Before a Stem Cell Transplant

Science.gov (United States)

2016-02-12

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

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.

Metabolic syndrome and metabolic risk profile according to polycystic ovary syndrome phenotype.

Science.gov (United States)

Bil, Enes; Dilbaz, Berna; Cirik, Derya Akdag; Ozelci, Runa; Ozkaya, Enis; Dilbaz, Serdar

2016-07-01

It is unknown which phenotype of polycystic ovary syndrome (PCOS) has a greater metabolic risk and how to detect this risk. The aim of this study was therefore to compare the incidence of metabolic syndrome (MetS) and metabolic risk profile (MRP) for different phenotypes. A total of 100 consecutive newly diagnosed PCOS women in a tertiary referral hospital were recruited. Patients were classified into four phenotypes according to the Rotterdam criteria, on the presence of at least two of the three criteria hyperandrogenism (H), oligo/anovulation (O) and PCO appearance (P): phenotype A, H + O + P; phenotype B, H + O; phenotype C, H + P; phenotype D, O + P. Prevalence of MetS and MRP were compared among the four groups. Based on Natural Cholesterol Education Program Adult Treatment Panel III diagnostic criteria, MetS prevalence was higher in phenotypes A and B (29.6% and 34.5%) compared with the other phenotypes (10.0% and 8.3%; P 3.8 was significantly higher in androgenic PCOS phenotypes. After logistic regression analysis, visceral adiposity index (VAI) was the only independent predictor of MetS in PCOS (P = 0.002). VAI was also significantly higher in phenotype B, when compared with the others (P risk of MetS among the four phenotypes, and VAI may be a predictor of metabolic risk in PCOS women. © 2016 Japan Society of Obstetrics and Gynecology.

Risk of the Metabolic Syndrome in Sexual Minority Women: Results from the ESTHER Study.

Science.gov (United States)

Kinsky, Suzanne; Stall, Ron; Hawk, Mary; Markovic, Nina

2016-08-01

Compared to heterosexuals, sexual minority women (SMW) have higher rates of the metabolic syndrome risk factors (e.g., obesity, smoking, heavy drinking, and depression). Yet, no published research has examined whether SMW have higher rates of the metabolic syndrome. The aim of this study is to describe the prevalence of the metabolic syndrome and its individual factors in a sample of heterosexuals and SMW, and identify whether SMW are at greater risk of having the metabolic syndrome. Data are from the Epidemiologic STudy of HEalth Risk in Women (ESTHER), a cross-sectional convenience sample of 479 SMW and 400 heterosexual women from Pittsburgh, Pennsylvania. Participants provided self-report questionnaire data, clinical data, and blood work. Compared to heterosexuals, SMW had higher mean waist circumference, fasting glucose, and systolic and diastolic blood pressure. Nearly one-quarter (24.3%) of SMW had the metabolic syndrome compared to 15.6% of heterosexual women (p = 0.002). After controlling for demographic and risk factors, SMW had a 44% higher risk of having the metabolic syndrome than heterosexuals (p = 0.031). To our knowledge, this is the first study to identify this health disparity in SMW. Future studies should explore differential risk of mortality and metabolic health between SMW and heterosexuals.

Perceived risk of prenatal diagnostic procedure-related miscarriage and Down syndrome among pregnant women.

Science.gov (United States)

Caughey, Aaron B; Washington, A Eugene; Kuppermann, Miriam

2008-03-01

The objective of the study was to identify correlates of perceived risk of carrying a Down syndrome-affected fetus or experiencing a procedure-related miscarriage among a diverse group of pregnant women. We conducted a cross-sectional survey of 1081 English-, Spanish-, or Chinese-speaking women receiving prenatal care in the San Francisco Bay area. Perceived risk of procedure-related miscarriage or carrying a Down syndrome-affected fetus was assessed using a linear rating scale from 0 (no risk) to 1 (high risk). Bivariate and multivariable analyses were used to explore associations between maternal characteristics including age, race/ethnicity, and socioeconomic status and perceived risks of carrying a Down syndrome-affected fetus or experiencing a procedure-related miscarriage. Women aged 35 years old or older had a higher perceived risk of Down syndrome than younger women (0.28 vs 0.22 on a scale from 0 to 1, P self-perceived health status (+0.08, P = .045). Latinas (+0.11, P = .008), women with an annual income less than $35,000 (+0.09, P = .003), and those who had difficulty conceiving (+0.09, P = .026) had higher perceived procedure-related miscarriage risk. Among women aged 35 years or older, perceived risk of carrying a Down syndrome-affected fetus was associated with the inclination to undergo prenatal diagnosis. Women's perceived risks of carrying a Down syndrome-affected fetus or having a procedure-related miscarriage are associated with numerous characteristics that have not been shown to be associated with the actual risks of these events. These perceived risks are associated with prenatal diagnostic test inclination. Understanding patients' risk perceptions and effectively communicating risk is critical to helping patients make informed decisions regarding use of invasive prenatal testing.

Opioid Titration Order Sheet or Standard Care in Treating Patients With Cancer Pain

Science.gov (United States)

2012-08-04

Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

Methadone, Morphine, or Oxycodone in Treating Pain in Patients With Cancer

Science.gov (United States)

2012-11-09

Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

Evaluating the Risk of Metabolic Syndrome Based on an Artificial Intelligence Model

Directory of Open Access Journals (Sweden)

Hui Chen

2014-01-01

Full Text Available Metabolic syndrome is worldwide public health problem and is a serious threat to people's health and lives. Understanding the relationship between metabolic syndrome and the physical symptoms is a difficult and challenging task, and few studies have been performed in this field. It is important to classify adults who are at high risk of metabolic syndrome without having to use a biochemical index and, likewise, it is important to develop technology that has a high economic rate of return to simplify the complexity of this detection. In this paper, an artificial intelligence model was developed to identify adults at risk of metabolic syndrome based on physical signs; this artificial intelligence model achieved more powerful capacity for classification compared to the PCLR (principal component logistic regression model. A case study was performed based on the physical signs data, without using a biochemical index, that was collected from the staff of Lanzhou Grid Company in Gansu province of China. The results show that the developed artificial intelligence model is an effective classification system for identifying individuals at high risk of metabolic syndrome.

Victims of Chinese famine in early life have increased risk of metabolic syndrome in adulthood.

Science.gov (United States)

Yu, Caizheng; Wang, Jing; Wang, Fei; Han, Xu; Hu, Hua; Yuan, Jing; Miao, Xiaoping; Yao, Ping; Wei, Sheng; Wang, Youjie; Liang, Yuan; Zhang, Xiaomin; Guo, Huan; Pan, An; Zheng, Dan; Tang, Yuhan; Yang, Handong; Wu, Tangchun; He, Meian

2018-02-05

To investigate the association of exposure to the Chinese famine during early life with metabolic syndrome risk in adults. There were 7,915 participants from Dongfeng-Tongji cohort were included in the present study. Participants were classified as non-exposed group, fetal exposed group, early childhood-, mid childhood-, and late childhood-exposed groups, respectively. Metabolic syndrome was defined according to International Diabetes Foundation criteria (2005). Logistic regression model was used to explore the association between famine exposure in early life and metabolic syndrome risk in adults. The metabolic syndrome prevalence in non-, fetal-, early childhood-, mid childhood-, and late childhood- exposed groups were 25.2%, 26.9%, 30.3%, 32.7%, and 32.7%, respectively. Compared with non-exposed group, participants exposed to famine in the fetal (0.96, 95% CI: 0.77-1.20), early childhood (1.24, 95% CI: 1.01-1.52), mid childhood (1.39, 95% CI: 1.13-1.72), and late childhood (1.33, 95% CI: 1.08-1.63) had higher metabolic syndrome prevalence risk in adults after adjustment for potential confounders (P for trend metabolic syndrome prevalence risk than non-exposed women (P for trend metabolic syndrome prevalence risk (P for interaction = 0.0001). Results in the present study indicated that exposure to famine in early life increases the risk of metabolic syndrome in adulthood, particularly in women. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Risk factors and prevalence of burnout syndrome in the nursing profession.

Science.gov (United States)

Cañadas-De la Fuente, Guillermo A; Vargas, Cristina; San Luis, Concepción; García, Inmaculada; Cañadas, Gustavo R; De la Fuente, Emilia I

2015-01-01

The burnout syndrome is beginning to be regarded as an occupational illness of high prevalence among nursing in Spain. Individuals suffering from the syndrome manifest important health problems. More information about prevalence and risk factors for burnout is needed to prevent the syndrome and to determine the most appropriate clinical interventions when the disorder appears. Burnout levels were evaluated in a group of nurses. The objectives of this study were to estimate the prevalence of burnout, to identify the variables related to burnout and to propose a risk profile for this syndrome among the nursing personnel. The study was carried out in public health centers in Andalusia (Spain). The sample consisted of 676 nursing professionals from public health centers. Dependent variables were the three Burnout dimensions: emotional exhaustion, depersonalization and personal accomplishment. Independent variables were socio-demographic, organizational, personality-related variables. The nurses manifested average to high burnout levels. There were statistically significant differences in burnout levels associated with the following variables: age, gender, marital status, having children, level of healthcare, type of work shift, healthcare service areas and conducting administrative tasks. Burnout was also associated with personality-related variables. The prevalence of burnout among nursing professionals is high. Gender, age, marital status, level of healthcare, work shift and healthcare service areas predicted at least one of the dimensions of the syndrome. Neuroticism, agreeability, extraversion and conscientiousness are personality traits that predict at least two of the dimensions of burnout syndrome in nurses. Therefore, personality factors should be considered in any theory of risk profiles for developing burnout syndrome in the nursing profession. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Metabolic Syndrome and Cardiovascular Risk Factors after Hematopoietic Cell Transplantation in Severe Mucopolysaccharidosis Type I (Hurler Syndrome).

Science.gov (United States)

Braunlin, Elizabeth; Steinberger, Julia; DeFor, Todd; Orchard, Paul; Kelly, Aaron S

2018-02-01

Hematopoietic cell transplantation is a life-saving procedure, but one associated with increasing long-term cardiovascular risk requiring frequent long-term follow-up. This therapy has significantly lengthened survival in mucopolysaccharidosis type IH (Hurler syndrome), a disease with known coronary artery involvement. Metabolic syndrome-a constellation of central obesity, high blood pressure, low high-density lipoprotein cholesterol, elevated triglycerides, and fasting blood glucose-is associated with increased cardiovascular risk, and occurs when any 3 or more of these 5 components is present within a single individual. The incidence of metabolic syndrome and its components is poorly defined after transplantation for Hurler syndrome. Chart review of all long-term survivors of hematopoietic cell transplantation for Hurler syndrome ≥9 years of age for factors comprising the metabolic syndrome: obesity, high blood pressure, low high-density lipoprotein cholesterol, elevated triglycerides, and fasting blood glucose. Sixty-three patients were evaluated, 20 of whom had components of the metabolic syndrome available for review. There was no significant difference in age at transplantation, sex, number of transplants, pretransplant radiation, or percent engraftment between those with and without these data. Median follow-up after transplantation for the 20 patients with data was 14.3 years. Only 1 (5%) patient of this group fulfilled the criteria for metabolic syndrome. Fifty-three percent of the patients had 1 or more components of metabolic syndrome: the most common was high blood pressure occurring in 40%. Metabolic syndrome is uncommon in this cohort of long-term survivors of hematopoietic cell transplantation for Hurler syndrome but almost half of the patients had 1 or more components of the syndrome, with high blood pressure being the most common. Further studies are needed to develop guidelines in this diagnosis as well as other nonmalignant diseases of children

Chronic periodontitis with multiple risk factor syndrome: a case report.

Science.gov (United States)

Shimoe, Masayuki; Yamamoto, Tadashi; Iwamoto, Yoshihiro; Shiomi, Nobuyuki; Maeda, Hiroshi; Nishimura, Fusanori; Takashiba, Shogo

2011-07-01

Multiple risk factor syndrome is a clustering of cardiovascular risk factors, such as diabetes, dyslipidemia, hypertension, and obesity associated epidemiologically with insulin resistance. This report describes the clinical course of a patient suffering from severe periodontitis with multiple risk factor syndrome, and discusses the association between periodontal infection and systemic health. The patient had a history of type 2 diabetes, dyslipidemia, and hypertension for over 10 years. At baseline, her hemoglobin A1 c was 8.1%. However, she had no diabetic complications except periodontitis. The IgG antibody titers against Porphyromonas gingivalis FDC 381 and SU63 were elevated above the mean of healthy subjects +2 standard deviations. Intensive periodontal treatment, including periodontal surgery, was performed to reduce periodontal infection and bacteremia. Her systemic and periodontal conditions were evaluated longitudinally for 10 years. Following periodontal treatment, antibody titers against Porphyromonas gingivalis and hemoglobin A1c values were significantly improved. The other clinical data and medication for her systemic condition also remained stable during supportive periodontal therapy. However, she developed myocardial infarction, and showed continuous deterioration of hemoglobin A1 c level and periodontitis. The long-term clustering of risk factors, such as diabetes, dyslipidemia, hypertension, and periodontitis, are associated with the development of myocardial infarction. Treatment of systemic conditions in combination with comprehensive periodontal treatment is important in management of patients with multiple risk factor syndrome.

Physical activity and the risk of colorectal cancer in Lynch syndrome.

Science.gov (United States)

Dashti, S Ghazaleh; Win, Aung Ko; Hardikar, Sheetal S; Glombicki, Stephen E; Mallenahalli, Sheila; Thirumurthi, Selvi; Peterson, Susan K; You, Y Nancy; Buchanan, Daniel D; Figueiredo, Jane C; Campbell, Peter T; Gallinger, Steven; Newcomb, Polly A; Potter, John D; Lindor, Noralane M; Le Marchand, Loic; Haile, Robert W; Hopper, John L; Jenkins, Mark A; Basen-Engquist, Karen M; Lynch, Patrick M; Pande, Mala

2018-06-14

Greater physical activity is associated with a decrease in risk of colorectal cancer for the general population; however, little is known about its relationship with colorectal cancer risk for people with Lynch syndrome, carriers of inherited pathogenic mutations in genes affecting DNA mismatch repair (MMR). We studied a cohort of 2,042 MMR gene mutations carriers (n=807, diagnosed with colorectal cancer), from the Colon Cancer Family Registry. Self-reported physical activity in three age-periods (20-29, 30-49, and ≥50 years) was summarized as average metabolic equivalent of task hours per week (MET-h/week) during the age-period of cancer diagnosis or censoring (near-term exposure), and across all age-periods preceding cancer diagnosis or censoring (long-term exposure). Weighted Cox regression was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for the association between physical activity and colorectal cancer risk. Near-term physical activity was associated with a small reduction in the risk of colorectal cancer (HR ≥35 vs. Lynch syndrome, however, further confirmation is warranted. The potential modifying effect of physical activity on colorectal cancer risk for people with Lynch syndrome could be useful for risk prediction and support counseling advice for lifestyle modification to reduce cancer risk. This article is protected by copyright. All rights reserved. © 2018 UICC.

Turner syndrome and meningioma: support for a possible increased risk of neoplasia in Turner syndrome.

Science.gov (United States)

Pier, Danielle B; Nunes, Fabio P; Plotkin, Scott R; Stemmer-Rachamimov, Anat O; Kim, James C; Shih, Helen A; Brastianos, Priscilla; Lin, Angela E

2014-01-01

Neoplasia is uncommon in Turner syndrome, although there is some evidence that brain tumors are more common in Turner syndrome patients than in the general population. We describe a woman with Turner syndrome (45,X) with a meningioma, in whom a second neoplasia, basal cell carcinomas of the scalp and nose, developed five years later in the absence of therapeutic radiation. Together with 7 cases of Turner syndrome with meningioma from a population-based survey in the United Kingdom, and 3 other isolated cases in the literature, we review this small number of patients for evidence of risk factors related to Turner syndrome, such as associated structural anomalies or prior treatment. We performed histological and fluorescent in situ hybridization (FISH) of 22q (NF2 locus) analyses of the meningeal tumor to search for possible molecular determinants. We are not able to prove causation between these two entities, but suggest that neoplasia may be a rare associated medical problem in Turner syndrome. Additional case reports and extension of population-based studies are needed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Azacitidine improves outcome in higher-risk MDS patients with chromosome 7 abnormalities: a retrospective comparison of GESMD and GFM registries.

Science.gov (United States)

Díez-Campelo, María; Lorenzo, Jose I; Itzykson, Raphael; Rojas, Silvia M; Berthon, Céline; Luño, Elisa; Beyne-Rauzy, Odile; Perez-Oteyza, Jaime; Vey, Norbert; Bargay, Joan; Park, Sophie; Cedena, Teresa; Bordessoule, Dominique; Muñoz, Juan A; Gyan, Emmanuel; Such, Esperanza; Visanica, Sorin; López-Cadenas, Félix; de Botton, Stéphane; Hernández-Rivas, Jesús M; Ame, Shanti; Stamatoullas, Aspasia; Delaunay, Jacques; Salanoubat, Celia; Isnard, Françoise; Guieze, Romain; Pérez Guallar, Joan; Badiella, Llorenc; Sanz, Guillermo; Cañizo, Consuelo; Fenaux, Pierre

2018-05-01

Treatment with azacitidine (AZA) has been suggested to be of benefit for higher-risk myelodysplastic syndrome (HR-MDS) patients with chromosome 7 abnormalities (Abn 7). This retrospective study of 235 HR-MDS patients with Abn 7 treated with AZA (n = 115) versus best supportive care (BSC; n = 120), assessed AZA treatment as a time-varying variable in multivariable analysis. A Cox Regression model with time-interaction terms of overall survival (OS) at different time points confirmed that, while chromosome 7 cytogenetic categories (complex karyotype [CK] versus non-CK) and International Prognostic Scoring System risk (high versus intermediate-2) retained poor prognosis over time, AZA treatment had a favourable impact on OS during the first 3 years of treatment compared to BSC (Hazard ratio [HR] 0·5 P MDS and cytogenetic abnormalities involving chromosome 7, especially for those with CK. © 2018 John Wiley & Sons Ltd.

Increased risk of epilepsy in children with Tourette syndrome: A population-based case-control study.

Science.gov (United States)

Wong, Lee Chin; Huang, Hui-Ling; Weng, Wen-Chin; Jong, Yuh-Jyh; Yin, Yun-Ju; Chen, Hong-An; Lee, Wang-Tso; Ho, Shinn-Ying

2016-01-01

The association between epilepsy and Tourette syndrome has rarely been investigated. In this retrospective cohort study, we analyzed a dataset of 1,000,000 randomly sampled individuals from the Taiwan National Health Insurance Research Database to determine the risk of epilepsy in children with Tourette syndrome. The study cohort consisted of 1062 patients with Tourette syndrome aged ≤ 18 years, and the control group consisted of three times the number of age- and sex-matched patients without Tourette syndrome, who were insurants, from the same database during the same period. The Tourette syndrome group had an 18.38-fold increased risk of epilepsy than the control group [hazard ratio=18.38, 95% confidence interval (CI)=8.26-40.92; PTourette syndrome group with comorbidities remained high (hazard ratio=16.27, 95% CI=6.26-18.46; PTourette syndrome is associated with a higher risk of epilepsy. A close follow-up of children with Tourette syndrome for the development of epilepsy is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Metabolic syndrome, C-reactive protein and cardiovascular risk in psoriasis patients: a cross-sectional study*

Science.gov (United States)

Paschoal, Renato Soriani; Silva, Daniela Antoniali; Cardili, Renata Nahas; Souza, Cacilda da Silva

2018-01-01

Background Psoriasis has been associated with co-morbidities and elevated cardiovascular risk. Objectives To analyze the relationships among metabolic syndrome, cardiovascular risk, C-reactive protein, gender, and Psoriasis severity. Methods In this cross-sectional study, plaque Psoriasis patients (n=90), distributed equally in gender, were analyzed according to: Psoriasis Area and Severity Index, cardiovascular risk determined by the Framingham risk score and global risk assessment, C-reactive protein and metabolic syndrome criteria (NCEPT-ATP III). Results Metabolic syndrome frequency was 43.3% overall, without significance between genders (P=0.14); but women had higher risk for obesity (OR 2.56, 95%CI 1.02-6.41; P=0.04) and systemic arterial hypertension (OR 3.29, 95%CI 1.39-7.81; P=0.006). The increase in the Psoriasis Area and Severity Index also increased the risk for metabolic syndrome (OR 1.060, 95%CI 1.006-1.117; P=0.03). Absolute 10-year cardiovascular risk was higher in males (P=0.002), but after global risk assessment, 51.1% patients, 52.2% women, were re-classified as high-intermediate cardiovascular risk; without significance between genders (P=0.83). C-reactive protein level was elevated nearly six-fold overall, higher in metabolic syndrome (P=0.05), systemic arterial hypertension (P=0.004), and high-intermediate 10-year cardiovascular risk patients (Preactive protein patients (t=1.98; P=0.05). Study limitations Restricted sample, hospital-based and representative of a single center and no specification of psoriatic arthritis. Conclusions Psoriasis, metabolic syndrome, systemic arterial hypertension and age share the increase in C-reactive protein, which could implicate in additional burden for increasing the cardiovascular risk and be an alert for effective interventions. PMID:29723366

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 ...

Is Pseudoexfoliation Syndrome a Risk Factor for Cerebro Vascular Disease?

Science.gov (United States)

Kan, Emrah; Yılmaz, Ahmet; Demirağ, Mehmet Derya; Çalık, Murat

2017-01-01

To determine the relationship between cerebro vascular disease and pseudoexfoliation syndrome. This cross-sectional case control study consisted of 50 patients with ischemic-type cerebro vascular disease and 50 control subjects. All subjects were investigated for diabetes mellitus and hypertension status and underwent a detailed ophthalmic examination. A diagnosis of pseudoexfoliation syndrome was made if characteristic greyish particulate matter was found on the anterior lens capsule after pupillary dilatation by slit-lamp examination. All subjects were compared in terms of pseudoexfoliation syndrome, diabetes mellitus, and hypertension. Pearson Chi Square and Student's t test were used for statistical analysis. Logistic regression analyses of the risk factors between groups were also made. The presence of pseudoexfoliation syndrome was significantly higher in patients with cerebro vascular disease when compared to the control subjects (p = 0.02). The frequency of diabetes mellitus was similar between the two groups. Arterial hypertension was significantly more frequent in the patient group when compared to the control subjects (p cerebro vascular disease. In the present study, we found that pseudoexfoliation syndrome frequency was found to be higher in patients with cerebro vascular disease than in control subjects. A slit-lamp examination of the eye could be an important marker that indicates the risk of cerebro vascular disease. We recommend an evaluation of all subjects with pseudoexfoliation syndrome for the presence of cerebro vascular disease. Longitudinal studies with larger populations are needed to confirm this relationship.

Aortic root pathology in Marfan syndrome increases the risk of migraine with aura

DEFF Research Database (Denmark)

Koppen, H; Vis, J C; Gooiker, D J

2012-01-01

To assess the lifetime prevalence of migraine in patients with Marfan syndrome (MFS) and to investigate a history of aortic root replacement (AR) as a possible risk factor.......To assess the lifetime prevalence of migraine in patients with Marfan syndrome (MFS) and to investigate a history of aortic root replacement (AR) as a possible risk factor....

Metabolic syndrome as a risk factor for neurological disorders.

Science.gov (United States)

Farooqui, Akhlaq A; Farooqui, Tahira; Panza, Francesco; Frisardi, Vincenza

2012-03-01

The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the hypothalamic 'bodyweight/appetite/satiety set point,' resulting in the initiation and development of metabolic syndrome. Metabolic syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer's disease. The molecular mechanism underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However, it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders such as stroke, Alzheimer's disease and depression. The purpose of this review is not only to describe the involvement of brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical changes in stroke, Alzheimer's disease and depression to a wider audience of neuroscientists with the hope that this discussion will initiate more studies on the relationship between metabolic syndrome and neurological disorders. © Springer Basel AG 2011

Fanconi Anemia — Case Report of Rare Aplastic Anemia at Child

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Deaconu Alina

2014-06-01

Full Text Available Introduction: Fanconi anemia is an autosomal recessive disease characterized by congenital abnormalities, defective haematopoiesis, and a high risk of developing acute myeloid leukaemia, myelodysplastic syndrome and cancers. FA was first described in 1927 by the Swiss pediatrician Guido Fanconi. The diagnosis is based on morphological abnormalities, hematologic abnormalities (pancytopenia, macrocytic anemia and progressive bone marrow failure and genetic tests (cariograma.

Association of Serum Adiponectin Levels with Metabolic Syndrome Risk Factors in Malay Adults

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Nur Firdaus Isa

2017-09-01

Full Text Available Introduction: This study aimed to investigate the relationship between serum adiponectin and metabolic syndrome in adults living in rural Malaysia. Methods: A total of 299 Malay adults (men=124; women = 175 with a mean age 48.8 (11.7 years were recruited. Measurements for waist circumference and blood pressure were taken before drawing an overnight fasting blood samples. Biochemical tests for triglycerides, HDL cholesterol, glucose and serum adiponectin concentration were measured. Results: Our results show that the adiponectin level in the subjects with metabolic syndrome was significantly lower than those without metabolic syndrome (p < 0.05. Among the metabolic syndrome risk factors, adiponectin level was significantly associated with hypertriglyceridemia and reduced HDL cholesterol (p < 0.001. Conclusion: The outcome from this study which highlights the association of hypoadiponectinemia with risk factors of metabolic syndrome in Malay adults, suggests that the reduced level of adiponectin may play a pivotal role in the development of metabolic syndrome in this ethnic group.

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.

Aspects of Cardiometabolic Risk in Women with Polycystic Ovary Syndrome.

Science.gov (United States)

Paterakis, Thomas S; Diamanti-Kandarakis, Evanthia

2014-12-01

Women with polycystic ovary syndrome (PCOS), the most common endocrine disorder among women of reproductive age, exhibit an adverse cardiovascular risk profile characteristic of the cardiometabolic syndrome. These women, compared with age- and body mass index-matched women without PCOS, appear to present a higher risk of insulin resistance, glucose intolerance, and dyslipidemia, and possibly a higher rate of type 2 diabetes mellitus and cardiovascular disease. However, despite the presence of cardiovascular risk factors and increased surrogate markers of cardiovascular disease, it is unclear whether they have accelerated atherosclerosis and greater mortality, the latter mainly because of a lack of endpoint studies. This article addresses, summarizes, and discusses salient data from the existing literature, including gaps and uncertainties, aspects, and mechanisms related to the spectrum of adverse cardiometabolic profile factors in women with PCOS.

Association of Sweet's Syndrome and Systemic Lupus Erythematosus

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J. L. Barton

2011-01-01

Full Text Available Sweet's syndrome is an acute febrile neutrophilic dermatosis which usually presents as an idiopathic disorder but can also be drug induced, associated with hematopoetic malignancies and myelodysplastic disorders, and more, infrequently, observed in autoimmune disorders. Sweet's syndrome has been reported in three cases of neonatal lupus, three cases of hydralazine-induced lupus in adults, and in nine pediatric and adult systemic lupus erythematosus (SLE patients. We describe three additional adult cases of Sweet's associated with SLE and provide a focused review on nondrug-induced, nonneonatal SLE and Sweet's. In two of three new cases, as in the majority of prior cases, the skin rash of Sweet's paralleled underlying SLE disease activity. The pathogenesis of Sweet's remains elusive, but evidence suggests that cytokine dysregulation may be central to the clinical and pathological changes in this condition, as well as in SLE. Further research is needed to define the exact relationship between the two conditions.

Risk of Gonadoblastoma Development in Patients with Turner Syndrome with Cryptic Y Chromosome Material.

Science.gov (United States)

Kwon, Ahreum; Hyun, Sei Eun; Jung, Mo Kyung; Chae, Hyun Wook; Lee, Woo Jung; Kim, Tae Hyuk; Kim, Duk Hee; Kim, Ho-Seong

2017-06-01

Current guidelines recommend that testing for Y chromosome material should be performed only in patients with Turner syndrome harboring a marker chromosome and exhibiting virilization in order to detect individuals who are at high risk of gonadoblastoma. However, cryptic Y chromosome material is suggested to be a risk factor for gonadoblastoma in patients with Turner syndrome. Here, we aimed to estimate the frequency of cryptic Y chromosome material in patients with Turner syndrome and determine whether Y chromosome material increased the risk for development of gonadoblastoma. A total of 124 patients who were diagnosed with Turner syndrome by conventional cytogenetic techniques underwent additional molecular analysis to detect cryptic Y chromosome material. In addition, patients with Turner syndrome harboring Y chromosome cell lines had their ovaries removed prophylactically. Finally, we assessed the occurrence of gonadoblastoma in patients with Turner syndrome. Molecular analysis demonstrated that 10 patients had Y chromosome material among 118 patients without overt Y chromosome (8.5%). Six patients with overt Y chromosome and four patients with cryptic Y chromosome material underwent oophorectomy. Histopathological analysis revealed that the occurrence of gonadoblastoma in the total group was 2.4%, and gonadoblastoma occurred in one of six patients with an overt Y chromosome (16.7%) and 2 of 10 patients with cryptic Y chromosome material (20.0%). The risk of developing gonadoblastoma in patients with cryptic Y chromosome material was similar to that in patients with overt Y chromosome. Therefore, molecular screening for Y chromosome material should be recommended for all patients with Turner syndrome to detect individuals at a high risk of gonadoblastoma and to facilitate proper management of the disease.

What is the risk of developing pigmentary glaucoma from pigment dispersion syndrome?

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Siddiqui, Yasmin; Ten Hulzen, Richard D; Cameron, J Douglas; Hodge, David O; Johnson, Douglas H

2003-06-01

To determine the probability of converting from pigment dispersion syndrome to pigmentary glaucoma. Retrospective community-based study of all newly diagnosed cases of pigment dispersion syndrome or pigmentary glaucoma. Subjects were patients newly diagnosed with pigment dispersion syndrome or pigmentary glaucoma from 1976 to 1999 in Olmsted County, Minnesota. Criteria for pigment dispersion syndrome were two of three signs: midperipheral, radial iris transillumination defects; Krukenberg spindle; heavy trabecular meshwork pigmentation. Criteria for pigmentary glaucoma were pigment dispersion syndrome and two of three findings: intraocular pressure (IOP) greater than 21 mm, optic nerve damage, or visual field loss. Kaplan-Meier survival curves were used to determine the probability of conversion to pigmentary glaucoma. A total of 113 patients were newly diagnosed with pigment dispersion syndrome over the 24-year period. Of these, 9 persons developed pigmentary glaucoma or elevated IOP requiring therapy. The probability of converting to pigmentary glaucoma was 10% at 5 years and 15% at 15 years. An additional 23 patients were found to have pigmentary glaucoma at their initial examination. The mean age at diagnosis of pigmentary glaucoma was 42 +/- 12 years; 78% of patients were male, whereas 58% of patients with pigmentary dispersion syndrome glaucoma were male. The most significant risk factor for conversion to pigmentary glaucoma was an IOP greater than 21 mm Hg at initial examination, whereas age, refractive error, and family history of glaucoma were not correlated with conversion. The risk of developing pigmentary glaucoma from pigment dispersion syndrome was 10% at 5 years and 15% at 15 years. Young, myopic men were most likely to have pigmentary glaucoma. An IOP greater than 21 mm Hg at initial examination was associated with an increased risk of conversion.

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

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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

Association between television viewing and the risk of metabolic syndrome in a community-based population

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Liu Chiu-Shong

2008-06-01

Full Text Available Abstract Background As a result of metabolic syndrome becoming an important issue during recent decades, many studies have explored the risk factors contributing to its development. However, less attention has been paid to the risk associated with sedentary behavior, especially television viewing. This study examined the association between television viewing time and the risk of having metabolic syndrome in a population of Taiwanese subjects. Methods This community-based cross-sectional study included 2,353 subjects (1,144 men and 1,209 women aged 40 and over from October, 2004 to September, 2005. Information about the time spent watching TV was obtained using a self-administered questionnaire. The definition of metabolic syndrome was according to the Third Report of the National Cholesterol Education Program's Adult Treatment Panel modified for Asians. Results Compared to subjects who viewed TV 20 hr/week had a 1.50-fold (95% confidence intervals (CI: 1.10, 2.03 risk for men and a 1.93-fold (95% CI: 1.37, 2.71 risk for women of having metabolic syndrome, after adjusting for physical activity and other covariates. Stratifying by the three categories of total activity levels, TV viewing time > 20 hr/week was found to still hold a significant risk for having metabolic syndrome in the lowest of the three categories of total activity level for men and in all three categories of total activity level for women. Conclusion The findings suggest that TV viewing is an independent risk factor associated with metabolic syndrome in Taiwanese people.

Total-Body Irradiation and Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

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2017-12-11

Adult Acute Myeloid Leukemia in Remission; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndrome; Childhood Renal Cell Carcinoma; Chronic Myelomonocytic Leukemia; Clear Cell Renal Cell Carcinoma; de Novo Myelodysplastic Syndrome; Metastatic Renal Cell Cancer; Previously Treated Myelodysplastic Syndrome; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Renal Medullary Carcinoma; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

[Prevalence of metabolic syndrome and cardiovascular risk in an urban area of Murcia].

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Fernández-Ruiz, Virginia E; Paniagua-Urbano, José A; Solé-Agustí, María; Ruiz-Sánchez, Alfonso; Gómez-Marín, José

2014-11-01

It is extensive scientific literature that has defined the metabolic syndrome as a precursor of cardiovascular disease. To estimate the prevalence of metabolic syndrome and cardiovascular risk in the population of a basic health area of Murcia. Cross sectional study population of the district health "The Esparragal" random sample of the population between 18 and 86 years living in the area. Personal history were collected and held a relevant clinical, anthropometric data and analytics for the estimation of Metabolic Syndrome and Cardiovascular Risk following criteria dictated by the current literature, adjusted for sex and age. The mean age of the study population was 59.34 ± 14.79 years, with 52.5% males. The overall prevalence of metabolic syndrome criteria World Health Organization is presented 36.8%, a figure increased under International Diabetes Ferderation recommendations to 58.2% and according to National Cholesterol Education Program, an estimated 53.5%. The presentation of this syndrome is slightly higher in men (54.1 versus 52.8 %), and in parallel with increasing age (p < 0.001). The prevalence of people at high risk of cardiovascular disease is 32.1 % (95 % CI 29.4 to 34.8), with 45.2 % (95% CI 41.2 to 49.2) in men and 17.6% (95% CI 14.4 to 20.8) in women. The prevalence of metabolic syndrome and cardiovascular risk in the study population is the highest found in Spain in population studies, indicating an invaluable population on which preventive measures. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Identification and Characterization of Prodromal Risk Syndromes in Young Adolescents in the Community: A Population-Based Clinical Interview Study.

LENUS (Irish Health Repository)

2012-02-01

While a great deal of research has been conducted on prodromal risk syndromes in relation to help-seeking individuals who present to the clinic, there is a lack of research on prodromal risk syndromes in the general population. The current study aimed first to establish whether prodromal risk syndromes could be detected in non-help-seeking community-based adolescents and secondly to characterize this group in terms of Axis-1 psychopathology and general functioning. We conducted in-depth clinical interviews with a population sample of 212 school-going adolescents in order to assess for prodromal risk syndromes, Axis-1 psychopathology, and global (social\\/occupational) functioning. Between 0.9% and 8% of the community sample met criteria for a risk syndrome, depending on varying disability criteria. The risk syndrome group had a higher prevalence of co-occurring nonpsychotic Axis-1 psychiatric disorders (OR = 4.77, 95% CI = 1.81-12.52; P < .01) and poorer global functioning (F = 24.5, df = 1, P < .0001) compared with controls. Individuals in the community who fulfill criteria for prodromal risk syndromes demonstrate strong similarities with clinically presenting risk syndrome patients not just in terms of psychotic symptom criteria but also in terms of co-occurring psychopathology and global functioning.

OBESITY AND METABOLIC SYNDROME IN CHILDREN AND YOUTH: A HEALTH RISK WE CANNOT AFFORD

OpenAIRE

Serge P. von Duvillard

2012-01-01

Ample observational and empirical evidence has been provided that indicates that childhood metabolic syndrome risk factors inevitably lead to significantly more profound health risk factors of developing potent adulthood metabolic syndrome. Much of these data has been provided from medical, nutritional, health, pediatric, physical education and associated communities. Perhaps the most visible and observable health risk factor among children (here referred to as youth) is the childhood obesit...

Risk of cardiovascular events in people prescribed glucocorticoids with iatrogenic Cushing's syndrome: cohort study.

Science.gov (United States)

Fardet, Laurence; Petersen, Irene; Nazareth, Irwin

2012-07-30

To investigate whether there is an increased risk of cardiovascular events in people who exhibit iatrogenic Cushing's syndrome during treatment with glucocorticoids. Cohort study. 424 UK general practices contributing to The Health Improvement Network database. People prescribed systemic glucocorticoids and with a diagnosis of iatrogenic Cushing's syndrome (n = 547) and two comparison groups: those prescribed glucocorticoids and with no diagnosis of iatrogenic Cushing's syndrome (n = 3231) and those not prescribed systemic glucocorticoids (n = 3282). Incidence of cardiovascular events within a year after diagnosis of iatrogenic Cushing's syndrome or after a randomly selected date, and association between iatrogenic Cushing's syndrome and risk of cardiovascular events. 417 cardiovascular events occurred in 341 patients. Taking into account only the first event by patient (coronary heart disease n = 177, heart failure n = 101, ischaemic stroke n = 63), the incidence rates of cardiovascular events per 100 person years at risk were 15.1 (95% confidence interval 11.8 to 18.4) in those prescribed glucocorticoids and with a diagnosis of iatrogenic Cushing's syndrome, 6.4 (5.5 to 7.3) in those prescribed glucocorticoids without a diagnosis of iatrogenic Cushing's syndrome, and 4.1 (3.4 to 4.8) in those not prescribed glucocorticoids. In multivariate analyses adjusted for sex, age, intensity of glucocorticoid use, underlying disease, smoking status, and use of aspirin, diabetes drugs, antihypertensive drugs, lipid lowering drugs, or oral anticoagulant drugs, the relation between iatrogenic Cushing's syndrome and cardiovascular events was strong (adjusted hazard ratios 2.27 (95% confidence interval 1.48 to 3.47) for coronary heart disease, 3.77 (2.41 to 5.90) for heart failure, and 2.23 (0.96 to 5.17) for ischaemic cerebrovascular events). The adjusted hazard ratio for any cardiovascular event was 4.16 (2.98 to 5.82) when the group prescribed glucocorticoids and with

Sweetened beverage consumption and increased risk of metabolic syndrome in Mexican adults.

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Denova-Gutiérrez, Edgar; Talavera, Juan O; Huitrón-Bravo, Gerardo; Méndez-Hernández, Pablo; Salmerón, Jorge

2010-06-01

To examine the relationship between sweetened beverage consumption and components of the metabolic syndrome in a Mexican population. We performed a cross-sectional analysis of data from selected adults participating in the baseline assessment of the Health Workers Cohort Study. Information on participants' sociodemographic characteristics, dietary patterns and physical activity were collected via self-administered questionnaires. Sweetened beverage consumption was evaluated through a validated semi-quantitative FFQ. Anthropometric and clinical measures were assessed with standardized procedures. The definition of metabolic syndrome was determined using criteria from the National Cholesterol Education Program Adult Treatment Panel III. The associations of interest were evaluated by means of linear and logistic regression models. The Mexican states of Morelos and Mexico. A total of 5240 individuals aged 20 to 70 years (mean 39.4 (sd 11.5) years) were evaluated. Overweight/obesity prevalence was 56.6 %. The prevalence of metabolic syndrome in this sample was 26.6 %. We found that for each additional daily sweetened beverage serving consumed, participants experienced an average increase of 0.49 mmol/l in TAG and a decrease in HDL cholesterol of 0.31 mmol/l. Subjects consuming more than two servings of sweetened beverages daily were at 2.0 times greater risk of metabolic syndrome than those who did not consume sweetened beverages. We also observed that higher sweetened beverage consumption increased the risk of all components of the metabolic syndrome. Our data support the hypothesis that sweetened beverage consumption increases the risk of metabolic syndrome in Mexican adults, possibly by providing excess energy and large amounts of rapidly absorbable sugars.

Risk Factors for the Development of Postembolization Syndrome after Transarterial Chemoembolization for Hepatocellular Carcinoma Treatment

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Mariana Lima

2018-01-01

Full Text Available Introduction: Hepatic transarterial chemoembolization is a widely used technique for the treatment of hepatocellular carcinoma. The most common complication of this procedure is postembolization syndrome. The main objective of this study was to assess risk factors for the development of postembolization syndrome. Material and Methods: Single-centre retrospective analysis of 563 hepatic transarterial chemoembolization procedures from January 1st, 2014 – December 31st, 2015. Hepatic transarterial chemoembolization was performed with ½ - 2 vials of 100 - 300 μm microspheres loaded with doxorubicin. Patients who experienced postembolization syndrome were identified based on prolongation of hospitalization due to pain, fever, nausea and/or vomiting. A control group with the patients who did not have postembolization syndrome was randomly created (three controls for one case. Descriptive analysis and multivariate logistic regression were performed. Results: The overall prevalence of postembolization syndrome was 6.2%. Hepatic transarterial chemoembolization with doxorubicin dosage above 75 mg (more than one vial, the size of the largest nodule and female gender had statistically significant relation with development of postembolization syndrome (p = 0.030, p = 0.046 and p = 0.037, respectively. Discussion: Doxorrubicin dosage above 75 mg is associated with a higher risk of postembolization syndrome. This result can be helpful for decision-making in clinical practice, whenever it is possible to avoid a higher dose without compromising the efficacy of the treatment. The size of the largest nodule and female gender also constitute risk factors for postembolization syndrome. The other variables studied were not related to the development of postembolization syndrome. Conclusion: The dose of doxorrubicin, the size of the largest nodule treated and female gender are potential risk factors for the development of postembolization syndrome after hepatic

Coronary artery disease risk in young women with polycystic ovary syndrome.

Science.gov (United States)

Ding, Dah-Ching; Tsai, I-Ju; Wang, Jen-Hung; Lin, Shinn-Zong; Sung, Fung-Chang

2018-02-02

Women with polycystic ovary syndrome are characterized by obesity, menstruation irregularity, hirsutism and infertility, and prevalent with cardiometabolic comorbidities, but population-based studies on the risk of developing coronary artery disease are limited. From claims data of the Taiwan National Health Insurance, we identified 8048 women with polycystic ovary syndrome aged 15-49 years newly diagnosed in 1998-2013, and 32192 women without the syndrome and CAD as controls, frequency matched by age and diagnosis date. By the end of 2013, after a mean follow-up period of 5.9 years, the overall incidence of coronary artery disease was 63% higher in women with polycystic ovary syndrome than in controls (2.25 vs. 1.38 per 1000 person-years). The adjusted hazard ratio [aHR] of coronary artery disease was 1.44 (95% confidence interval (CI) = 1.14-1.81) for women with polycystic ovary syndrome, compared with controls. Hazards of coronary artery disease were significant during follow-up periods of 3-4 years (aHR = 1.52, 95% CI = 1.00-2.30) and of 5-9 years (aHR = 1.58, 95% CI = 1.07-2.32). The incidence of coronary artery disease increased further in those with cardiometabolic comorbidities. Among women with polycystic ovary syndrome, those with comorbid diabetes had an incidence of 35.2 per 1000 person-years, 20-fold greater than those without cardiometabolic comorbidities. In conclusion, women with polycystic ovary syndrome are at an elevated risk of coronary artery disease. Preventive interventions should be provided to them, particularly for those with the comorbidity of metabolism symptom.

A two fold risk of metabolic syndrome in a sample of patients with schizophrenia: do consanguinity and family history increase risk?

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Bener, Abdulbari; Al-Hamaq, Abdulla O A A; Dafeeah, Elnour E

2014-01-01

Patients with schizophrenia are at greater risk for metabolic syndrome (MetS) and other cardiovascular risk factors. The objective of the study was to examine the prevalence of metabolic syndrome (MetS) and its criteria among patients with schizophrenia (Sz) according to the revised criteria of NCEP ATP III and assess which component contributed to the increased risk of the MetS in schizophrenia patients. This was a matched case-control study. Outpatient clinics of the Psychiatry department and Primary Health Care (PHC) Centers of the Supreme Council of Health, State of Qatar. The study was carried out among patients with schizophrenia (SZ) and healthy subjects above 20 years old. The study based on matched by age and gender of 233 cases and 466 controls. The survey was conducted from June 2010 to May 2011. Face to face interviews were conducted using a structured questionnaire followed by laboratory tests. Metabolic syndrome was defined using the National Cholesterol Education Program - Third Adult Treatment Panel (ATP III). The prevalence of metabolic syndrome among schizophrenic patients (36.5%) were significantly higher than healthy subjects (18.7%) (pmetabolic abnormalities compared to men. The study indicated that metabolic syndrome was highly prevalent in patients with schizophrenia. The female gender was significantly associated with a higher prevalence of metabolic syndrome. The identification and clinical management of this high risk group is of great importance. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Cardiometabolic risk in patients with polycystic ovary syndrome.

Science.gov (United States)

Ozegowska, Katarzyna; Pawelczyk, Leszek

2015-11-01

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in premenopausal women, associated with risk of metabolic syndrome and cardiovascular disease (CVD). CVD risk evaluation is recommended for PCOS patients. This study aimed to evaluate the risk of CVD in PCOS patients and to identify the best predictors for metabolic and cardiovascular disturbances. The study included 169 PCOS patients and 110 healthy women in reproductive age. We estimated cardiovascular risk according to American Heart Association and Androgen Excess-PCOS Society criteria that classified patients as metabolically unhealthy (MU) or metabolically healthy (MH). The PCOS group had significantly higher body mass index (BMI), waist circumference, and waist-to-hip ratio (P PCOS patients (8.9%). No obesity was observed in the control group. Waist circumference ≥ 80 cm was presented in 44% of PCOS patients in comparison to 14.5% of control participants (P PCOS population (P PCOS-MH group had the highest high-density lipoprotein (HDL) levels. ROC curves were used to indicate parameters diagnosing metabolically unhealthy women and revealed that WC, BMI and HC seem to be the strongest predictors of metabolic disturbances in PCOS but in the healthy population in reproductive age biochemical findings such as low HDL or increased fasting glycemia presented stronger predictive value than patients' anthropometric features. Physicians need to remember to adopt different diagnostic approach while seeking metabolic complications in these different groups of women.

Mechanisms, Risk Factors, and Management of Acquired Long QT Syndrome: A Comprehensive Review

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Eleftherios M. Kallergis

2012-01-01

Full Text Available Long QT syndrome is characterized by prolongation of the corrected QT (QTc interval on the surface electrocardiogram and is associated with precipitation of torsade de pointes (TdP, a polymorphic ventricular tachycardia that may cause sudden death. Acquired long QT syndrome describes pathologic excessive prolongation of the QT interval, upon exposure to an environmental stressor, with reversion back to normal following removal of the stressor. The most common environmental stressor in acquired long QT syndrome is drug therapy. Acquired long QT syndrome is an important issue for clinicians and a significant public health problem concerning the large number of drugs with this adverse effect with a potentially fatal outcome, the large number of patients exposed to these drugs, and our inability to predict the risk for a given individual. In this paper, we focus on mechanisms underlying QT prolongation, risk factors for torsades de pointes and describe the short- and long-term treatment of acquired long QT syndrome.

Cardiovascular risks and metabolic syndrome in Hong Kong Chinese women with polycystic ovary syndrome.

Science.gov (United States)

Cheung, L P; Ma, R C W; Lam, P M; Lok, I H; Haines, C J; So, W Y; Tong, P C Y; Cockram, C S; Chow, C C; Goggins, W B

2008-06-01

Women with polycystic ovary syndrome (PCOS) frequently exhibit central obesity, glucose intolerance, atherogenic dyslipidaemia and hypertension which are characteristic features of the metabolic syndrome (MetS). A total of 295 premenopausal Chinese women with PCOS diagnosed by the Rotterdam criteria (mean age: 30.2 +/- 6.4 years) and 98 control subjects without PCOS were evaluated for prevalence of MetS and cardiovascular risk factors, including dyslipidaemia and dysglycaemia. Using the 2005 modified Adult Treatment Panel III criteria, MetS (presence of three or more risk factors) was found in 24.9% of PCOS women compared to 3.1% of controls. The prevalence of MetS in PCOS women increased from 16.7% at under 30 years of age to 53.3% at over 40 years. MetS was also more prevalent in overweight and obese (41.3%) than normal-weight PCOS women (0.9%). However, multivariate regression analysis showed that women with PCOS had a 5-fold increase in risk of MetS (odds ratio 4.90; 95% confidence interval: 1.35-17.84) compared with women without PCOS even after controlling for age and BMI, suggesting PCOS alone is an independent risk factor for MetS. There is high prevalence of MetS in Hong Kong Chinese women with PCOS despite their relatively young age. Recognition of these cardiometabolic risk factors requires a high level of awareness in conjunction with early and regular screening.

Risk of Guillain-Barré syndrome after seasonal influenza vaccination and influenza health-care encounters: a self-controlled study.

Science.gov (United States)

Kwong, Jeffrey C; Vasa, Priya P; Campitelli, Michael A; Hawken, Steven; Wilson, Kumanan; Rosella, Laura C; Stukel, Therese A; Crowcroft, Natasha S; McGeer, Allison J; Zinman, Lorne; Deeks, Shelley L

2013-09-01

The possible risk of Guillain-Barré syndrome from influenza vaccines remains a potential obstacle to achieving high vaccination coverage. However, influenza infection might also be associated with Guillain-Barré syndrome. We aimed to assess the risk of Guillain-Barré syndrome after seasonal influenza vaccination and after influenza-coded health-care encounters. We used the self-controlled risk interval design and linked universal health-care system databases from Ontario, Canada, with data obtained between 1993 and 2011. We used physician billing claims for influenza vaccination and influenza-coded health-care encounters to ascertain exposures. Using fixed-effects conditional Poisson regression, we estimated the relative incidence of hospitalisation for primary-coded Guillain-Barré syndrome during the risk interval compared with the control interval. We identified 2831 incident admissions for Guillain-Barré syndrome; 330 received an influenza vaccine and 109 had an influenza-coded health-care encounter within 42 weeks before hospitalisation. The risk of Guillain-Barré syndrome within 6 weeks of vaccination was 52% higher than in the control interval of 9-42 weeks (relative incidence 1·52; 95% CI 1·17-1·99), with the greatest risk during weeks 2-4 after vaccination. The risk of Guillain-Barré syndrome within 6 weeks of an influenza-coded health-care encounter was greater than for vaccination (15·81; 10·28-24·32). The attributable risks were 1·03 Guillain-Barré syndrome admissions per million vaccinations, compared with 17·2 Guillain-Barré syndrome admissions per million influenza-coded health-care encounters. The relative and attributable risks of Guillain-Barré syndrome after seasonal influenza vaccination are lower than those after influenza illness. Patients considering immunisation should be fully informed of the risks of Guillain-Barré syndrome from both influenza vaccines and influenza illness. Canadian Institutes of Health Research

Elevation of isoprostanes in polycystic ovary syndrome and its relationship with cardiovascular risk factors.

Science.gov (United States)

Calzada, M; López, N; Noguera, J A; Mendiola, J; Torres, A M

2018-04-23

To evaluate the plasma level of 8-isoprostanes in women with polycystic ovary syndrome. To also investigate whether there is a relationship between 8-isoprostanes and several cardiovascular risk factors. A total of 125 women with polycystic ovary syndrome and 169 healthy women were enrolled in this case-control study. 8-Isoprostanes and different parameters were measured in all subjects. Patients were evaluated for the presence of polycystic ovary syndrome according to the Rotterdam Consensus Conference criteria. 8-Isoprostanes levels were significantly higher in patients with polycystic ovary syndrome (138.4 ± 104.1 pg/mL) compared with control group (68.6 ± 34.3 pg/mL) (p polycystic ovary syndrome patients with high 8-isoprostanes than those with normal 8-isoprostanes (p polycystic ovary syndrome group had a positive correlation with waist circumference, triglycerides, low-density lipoprotein cholesterol, apolipoprotein B, homocysteine, insulin, homeostatic model assessment for insulin resistance. Patients with polycystic ovary syndrome have higher 8-isoprostanes levels and it is associated with several cardiovascular risk factors.

Managing the risk of cancer in Cowden syndrome: a case report

Directory of Open Access Journals (Sweden)

Hammami Sonia

2012-07-01

Full Text Available Abstract Introduction Cowden syndrome is a rare cancer predisposition syndrome inherited in an autosomal-dominant fashion. The syndrome is characterized by hamartomatous polyps that affect multiple organs: skin, mucous membranes, thyroid, breast, gastrointestinal tract, endometrium and brain. It is also associated with an increased risk of developing malignancy in many tissues but especially breast, thyroid and endometrium. Case presentation We present the case of a 30-year-old Tunisian woman with mental retardation who presented to our facility with rectal hamartomatous polyps. Her medical history included fibrocystic disease of the breast over the last three years. A physical examination revealed macrocephaly, hyperkeratotic papules on the mid-facial skin, palmoplantar keratosis and oral mucosal papillomatosis. A breast examination revealed nodular breast tissue bilaterally and a diffuse thyroid goiter. Our patient was clinically euthyroid. A total thyroidectomy was performed. A histopathologic examination revealed thyroid papillary carcinoma. A gastrointestinal evaluation revealed esophageal and gastric polyps. Biopsies showed hyperplastic and adenomatous lesions associated with Helicobacter pylori. A final diagnosis of Cowden syndrome was made according to the syndrome testing criteria adapted by the US National Comprehensive Cancer Network. A prophylactic bilateral mastectomy was proposed but refused by our patient. Our patient was kept under surveillance for breast and colorectal malignancies. Conclusions Early and accurate diagnosis of Cowden syndrome is essential because it is a cancer predisposition syndrome that carries an increased risk for developing malignancy in many tissues, especially breast and thyroid. For this reason, education regarding the signs and symptoms of cancer is important. All patients must be screened for malignancies and options for prophylactic mastectomy should be discussed. Guidelines for cancer screening

DIETARY RISK FACTORS OF METABOLIC SYNDROME IN DIBRUGARH DISTRICT OF ASSAM

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Tulika Goswami Mahanta

2017-07-01

Full Text Available BACKGROUND As India is considered as the diabetic capital of the world, a huge burden of undiagnosed Metabolic Syndrome (MetS is a possibility. Early intervention can be planned if MetS can be detected early along with risk factor assessment to avert cardiovascular morbidities. The aim of this study was to assess the dietary risk factor of metabolic syndrome. MATERIALS AND METHODS Community based cross-sectional study was conducted in Dibrugarh District of Assam with multistep sampling. Study area, i.e. four rural sub-centres and two urban electoral blocks were selected randomly. From the list of population of selected area, the consenting eligible were included. Sample size was 1700 population with MetS. Socio-demographic information, World Health Organisation’s STEPS questionnaire for behavioural risk factors along with dietary history, anthropometric assessment and laboratory investigations were conducted in three stages. Food frequency questionnaire was used for dietary assessment. Statistical analysis was done using rates, ratio, proportion, univariate and multivariate analysis. RESULTS MetS was 47.6% (1606 of 3372 screened. Mean age of study population was 47.1 ± 10.9 years. Behavioural risk factors like tobacco, alcohol consumption was high and significantly associated with metabolic syndrome (p= 0.000. Similarly financial stress, feeling stressed in last one year (p=0.034, lower physical activity level were also significantly associated with metS (p=0.000. Consumption of meat (p=0.000, egg (p=0.000, fast food (p=0.000, pickled vegetable (p=0.000 and sweet snacks (p=0.000 was found significantly higher amongst those with metabolic syndrome. Significant association was also seen with number of meals served per day and metS (p=0.000. CONCLUSION Dietary risk factors of cardiovascular diseases were rampant amongst persons with MetS. Dietary risk factor survey and counselling on healthy diet can be implemented in these population to give

Radiation effects on cancer risks in the life span study cohort

International Nuclear Information System (INIS)

Kodama, K.; Ozasa, K.; Katayama, H.; Shore, R. E.; Okubo, T.

2012-01-01

To determine late health effects of radiation in atomic bomb survivors, the Radiation Effects Research Foundation has been conducting studies on the Life Span Study (LSS) population, which consists of 93 000 atomic bomb survivors and 27.000 controls. A recent report on the incidence of solid cancers estimates that at the age of 70 y, after exposure at the age of 30 y, solid-cancer rates increase by about 35 % per Gy for men and 58 % per Gy for women. The age-at-exposure is an important risk modifier. Furthermore, it seems that radiation-associated increases in cancer rates persist throughout life. In addition, radiation has similar effects upon first-primary and second-primary cancer risks. A recent report on leukemia mortality suggested that the effect of radiation on leukemia mortality persisted for more than five decades. In addition, a significant dose-response for myelodysplastic syndrome is found in Nagasaki LSS members 40-60 y after radiation exposure. In view of the nature of the continuing increase in solid cancers, the LSS should continue to provide important new information on cancer risks, as most survivors still alive today were exposed to the atomic bomb radiation under the age of 20 y and are now entering their cancer-prone years. (authors)

Cancer risks and immunohistochemical profiles linked to the Danish MLH1 Lynch syndrome founder mutation

DEFF Research Database (Denmark)

Therkildsen, Christina; Isinger-Ekstrand, Anna; Ladelund, Steen

2012-01-01

Founder mutations with a large impact in distinct populations have been described in Lynch syndrome. In Denmark, the MLH1 c.1667+2_1667_+8TAAATCAdelinsATTT mutation accounts for 25 % of the MLH1 mutant families. We used the national Danish hereditary nonpolyposis colorectal cancer register...... to estimate the cumulative lifetime risks for Lynch syndrome-associated cancer in 16 founder mutation families with comparison to 47 other MLH1 mutant families. The founder mutation conferred comparable risks for colorectal cancer (relative risks, RR, of 0.99 for males and 0.79 for females) and lower risks...... in 68 % with extensive inter-tumor variability despite the same underlying germline mutation. In conclusion, the Danish MLH1 founder mutation that accounts for a significant proportion of Lynch syndrome and is associated with a lower risk for extracolonic cancers....

NPAS2 and PER2 are linked to risk factors of the metabolic syndrome

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Aromaa Arpo

2009-05-01

Full Text Available Abstract Background Mammalian circadian clocks control multiple physiological events. The principal circadian clock generates seasonal variations in behavior as well. Seasonality elevates the risk for metabolic syndrome, and evidence suggests that disruption of the clockwork can lead to alterations in metabolism. Our aim was to analyze whether circadian clock polymorphisms contribute to seasonal variations in behavior and to the metabolic syndrome. Methods We genotyped 39 single-nucleotide polymorphisms (SNP from 19 genes which were either canonical circadian clock genes or genes related to the circadian clockwork from 517 individuals drawn from a nationwide population-based sample. Associations between these SNPs and seasonality, metabolic syndrome and its risk factors were analyzed using regression analysis. The p-values were corrected for multiple testing. Results Our findings link circadian gene variants to the risk factors of the metabolic syndrome, since Npas2 was associated with hypertension (P-value corrected for multiple testing = 0.0024 and Per2 was associated with high fasting blood glucose (P-value corrected for multiple testing = 0.049. Conclusion Our findings support the view that relevant relationships between circadian clocks and the metabolic syndrome in humans exist.

Is Apolipoprotein E4 an Important Risk Factor for Dementia in Persons with Down Syndrome?

Science.gov (United States)

Rohn, Troy T; McCarty, Katie L; Love, Julia E; Head, Elizabeth

2014-12-08

Down syndrome is one of the most common genetic causes of intellectual disability and is characterized by a number of behavioral as well as cognitive symptoms. Triplication of all or part of human chromosome 21 has been considered as the main cause of Down syndrome. Due to the location of the amyloid precursor protein on chromosome 21, many of the neuropathological features of early-onset Alzheimer's disease including senile plaques and neurofibrillary tangles are also present in Down syndrome patients who are either demented or nondemented. Significant advances in medical treatment have increased longevity in people with Down syndrome resulting in an increased population that may be subjected to many of the same risk factors as those with Alzheimer's disease. It is well established that harboring one or both apolipoprotein E4 alleles greatly increases the risk for Alzheimer's disease. However, whether apolipoprotein E4 contributes to an earlier onset of dementia or increased mortality in Down syndrome patients is still a matter of debate. The purpose of this mini review is to provide an updated assessment on apolipoprotein E4 status and risk potential of developing dementia and mortality associated with Down syndrome.

Radiotherapy- and Chemotherapy-Induced Myelodysplasia Syndrome

Science.gov (United States)

Sun, Li-Min; Lin, Cheng-Li; Lin, Ming-Chia; Liang, Ji-An; Kao, Chia-Hung

2015-01-01

Abstract This study explored which kinds of cancer are related to a higher incidence of subsequent myelodysplastic syndrome (MDS) after radiotherapy (RT) and chemotherapy (CT). We performed a nested case–control study by using data from the Taiwanese National Health Insurance (NHI) system. The case group included cancer patients who developed MDS. For the control group, 4 cancer patients without MDS were frequency-matched with each MDS case by age, sex, year of cancer diagnosis, and MDS index year. A multivariable logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Overall, cancer patients who received RT or CT exhibited secondary MDS more frequently than did those who did not (RT: OR = 1.53; 95% CI = 1.33–1.77; CT: OR = 1.51; 95% CI = 1.25–1.82). Analysis by cancer site showed that RT increased the risk of MDS for patients with stomach, colorectal, liver, breast, endometrial, prostate, and kidney cancers. By contrast, CT was more likely to increase the risk of MDS for patients with lung, endometrial, and cervical cancers. Further analysis revealed that RT and CT seemed to have a positive interaction. The major limitation of this study was the lack of certain essential data in the NHI Research Database, such as data regarding cancer stage and treatment dose details. This population-based nested case–control study determined that RT and CT predisposed patients in Taiwan to the development of MDS. This effect was more prominent when both modalities were used. PMID:25929909

Downregulation but lack of promoter hypermethylation or somatic mutations of the potential tumor suppressor CXXC5 in MDS and AML with deletion 5q

DEFF Research Database (Denmark)

Treppendahl, Marianne Bach; Möllgård, L; Hellström-Lindberg, E

2013-01-01

During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells, identify......During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells...

Time-dependent changes in mortality and transformation risk in MDS.

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Pfeilstöcker, Michael; Tuechler, Heinz; Sanz, Guillermo; Schanz, Julie; Garcia-Manero, Guillermo; Solé, Francesc; Bennett, John M; Bowen, David; Fenaux, Pierre; Dreyfus, Francois; Kantarjian, Hagop; Kuendgen, Andrea; Malcovati, Luca; Cazzola, Mario; Cermak, Jaroslav; Fonatsch, Christa; Le Beau, Michelle M; Slovak, Marilyn L; Levis, Alessandro; Luebbert, Michael; Maciejewski, Jaroslaw; Machherndl-Spandl, Sigrid; Magalhaes, Silvia M M; Miyazaki, Yasushi; Sekeres, Mikkael A; Sperr, Wolfgang R; Stauder, Reinhard; Tauro, Sudhir; Valent, Peter; Vallespi, Teresa; van de Loosdrecht, Arjan A; Germing, Ulrich; Haase, Detlef; Greenberg, Peter L

2016-08-18

In myelodysplastic syndromes (MDSs), the evolution of risk for disease progression or death has not been systematically investigated despite being crucial for correct interpretation of prognostic risk scores. In a multicenter retrospective study, we described changes in risk over time, the consequences for basal prognostic scores, and their potential clinical implications. Major MDS prognostic risk scoring systems and their constituent individual predictors were analyzed in 7212 primary untreated MDS patients from the International Working Group for Prognosis in MDS database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. Hazards regarding mortality and acute myeloid leukemia transformation diminished over time from diagnosis in higher-risk MDS patients, whereas they remained stable in lower-risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and were essentially equivalent after 5 years. This fact led to loss of prognostic power of different scoring systems considered, which was more pronounced for survival. Inclusion of age resulted in increased initial prognostic power for survival and less attenuation in hazards. If needed for practicability in clinical management, the differing development of risks suggested a reasonable division into lower- and higher-risk MDS based on the IPSS-R at a cutoff of 3.5 points. Our data regarding time-dependent performance of prognostic scores reflect the disparate change of risks in MDS subpopulations. Lower-risk patients at diagnosis remain lower risk whereas initially high-risk patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making. © 2016 by The American Society of Hematology.

Programmed Ventricular Stimulation for Risk Stratification in the Brugada Syndrome: A Pooled Analysis

NARCIS (Netherlands)

Sroubek, Jakub; Probst, Vincent; Mazzanti, Andrea; Delise, Pietro; Hevia, Jesus Castro; Ohkubo, Kimie; Zorzi, Alessandro; Champagne, Jean; Kostopoulou, Anna; Yin, Xiaoyan; Napolitano, Carlo; Milan, David J.; Wilde, Arthur; Sacher, Frederic; Borggrefe, Martin; Ellinor, Patrick T.; Theodorakis, George; Nault, Isabelle; Corrado, Domenico; Watanabe, Ichiro; Antzelevitch, Charles; Allocca, Giuseppe; Priori, Silvia G.; Lubitz, Steven A.

2016-01-01

The role of programmed ventricular stimulation in identifying patients with Brugada syndrome at the highest risk for sudden death is uncertain. We performed a systematic review and pooled analysis of prospective, observational studies of patients with Brugada syndrome without a history of sudden

Risks of bleeding and thrombosis in intensive care unit patients with haematological malignancies

DEFF Research Database (Denmark)

Russell, Lene; Holst, Lars Broksø; Kjeldsen, Lars

2017-01-01

products and risk factors for bleeding in an adult population of ICU patients with haematological malignancies. METHODS: We screened all patients with acute leukaemia and myelodysplastic syndrome admitted to a university hospital ICU during 2008-2012. Bleeding in ICU was scored according to the WHO grading...... lower and upper airways and upper GI tract. Thirty-nine (59%) of the 66 patients had severe or debilitating (WHO grade 3 or 4) bleeding. The median platelet count on the day of grade 3 or 4 bleeding was 23 × 109 per litre (IQR 13-39). Nine patients (8%) died in ICU following a bleeding episode; five...... was the cause of death in four patients. The median platelet count was 20 × 109 per litre (15-48) at the time of thrombosis. The patients received a median of 6 units of red blood cells, 1 unit of fresh frozen plasma and 8 units of platelet concentrates in ICU. CONCLUSIONS: Severe and debilitating bleeding...

Characterizing cardiovascular risk in women with polycystic ovary syndrome: more than the sum of its parts?

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Chang, Alice Y; Wild, Robert A

2009-07-01

Polycystic ovary syndrome (PCOS), a condition of irregular menses and androgen excess, is the most common endocrinopathy of young women. Insulin resistance is a well-established feature among many women with PCOS, even in the nonobese. Therefore, it is not surprising that PCOS is frequently associated with cardiovascular risk factors and the metabolic syndrome. However, it is not known whether PCOS is an independent risk factor for atherosclerosis and cardiovascular (CV) events or whether CV risk is attributable to associated risk factors. We review previous studies on CV risk and disease in women with PCOS, describing the pitfalls and challenges in ascribing CV risk to PCOS. Women with PCOS might be partly reassured that their relative risk approximates that of the metabolic syndrome (RR 1.5) and also strongly counseled at the individual level about the greatest potential threat to their CV health, the development of type 2 diabetes.

Increased risk of concurrent gastroesophageal reflux disease among patients with Sjögren's syndrome: A nationwide population-based study.

Science.gov (United States)

Chang, Chen-Shu; Liao, Chun-Hui; Muo, Chih-Hsin; Kao, Chia-Huang

2016-06-01

Little data is available on the risk of gastroesophageal reflux disease in patients diagnosed with Sjögren's syndrome. We identified 4650 Sjögren's syndrome patients between 2000 and 2011 from the National Health Insurance Research Database. Each Sjögren's syndrome patient was matched to 4 controls based on age, sex, and index year, and all subjects were followed up from the index date to December 31, 2011. Cox proportional hazards regression model was used to estimate the risk of gastroesophageal reflux disease. The risk of gastroesophageal reflux disease for Sjögren's syndrome patients was 2.41-fold greater than that for the comparison cohort after adjusting for age, sex, and comorbidities. In age stratified analyses, the youngest Sjögren's syndrome cohort (age: 20-44years old) had the highest risk (HR=3.02; 95% CI=2.48-3.69) and the lowest risk at age ≥65years (HR=1.95; 95% CI=1.61-2.36). Regardless of in subjects with and without comorbidity, Sjögren's syndrome patients had a higher risk than the controls. Sjögren's syndrome subjects with ischemic heart disease, hyperlipidemia and renal disease had the highest risk for gastroesophageal reflux disease compared with the comparison cohort without those diseases (HR=7.67; 95% CI=5.32-11.1). Patients with Sjögren's syndrome have a significantly greater risk of developing subsequent gastroesophageal reflux disease than the general population. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Cardiometabolic risk in polycystic ovary syndrome: a comparison of different approaches to defining the metabolic syndrome.

Science.gov (United States)

Cussons, Andrea J; Watts, Gerald F; Burke, Valerie; Shaw, Jonathan E; Zimmet, Paul Z; Stuckey, Bronwyn G A

2008-10-01

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and features in common with the metabolic syndrome (MetS)--factors shown to predict cardiovascular risk and type 2 diabetes. We investigated the prevalence and characteristics of the MetS in PCOS by three definitions-World Health Organization (WHO), National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP-III) and International Diabetes Federation (IDF)--and compared that with the background population. Cross-sectional study of 168 women with PCOS and 883 age-matched controls from the Australian Diabetes, Obesity and Lifestyle (AusDiab) study. Prevalence of the MetS in PCOS subjects was 33% by WHO, 37% by NCEP-ATP-III and 40% by IDF criteria, compared with 10% by NCEP-ATP-III and 13% by IDF in controls (P 30 kg/m(2)), and higher but not significantly so in overweight (BMI 25-30 kg/m(2)) women (P = 0.052). Dehydroepiandrosterone sulphate was associated with a lower risk of the MetS--Odds ratio 0.86 (95% confidence interval, 0.77-0.97, P = 0.011). An approximate 4-fold increase in the prevalence of the MetS in women with PCOS compared with the general population, consistent with the proposed major role of insulin and obesity in the syndrome, implies greater risk of cardiometabolic disease in women with PCOS. However, this estimate is likely to vary according to PCOS definition, ethnicity and different aetiological pathways to PCOS.

Evaluating the Risk of Metabolic Syndrome Based on an Artificial Intelligence Model

OpenAIRE

Chen, Hui; Xiong, Shenghua; Ren, Xuan

2014-01-01

Metabolic syndrome is worldwide public health problem and is a serious threat to people's health and lives. Understanding the relationship between metabolic syndrome and the physical symptoms is a difficult and challenging task, and few studies have been performed in this field. It is important to classify adults who are at high risk of metabolic syndrome without having to use a biochemical index and, likewise, it is important to develop technology that has a high economic rate of return to s...

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

Familial aggregation and linkage analysis with covariates for metabolic syndrome risk factors.

Science.gov (United States)

Naseri, Parisa; Khodakarim, Soheila; Guity, Kamran; Daneshpour, Maryam S

2018-06-15

Mechanisms of metabolic syndrome (MetS) causation are complex, genetic and environmental factors are important factors for the pathogenesis of MetS In this study, we aimed to evaluate familial and genetic influences on metabolic syndrome risk factor and also assess association between FTO (rs1558902 and rs7202116) and CETP(rs1864163) genes' single nucleotide polymorphisms (SNP) with low HDL_C in the Tehran Lipid and Glucose Study (TLGS). The design was a cross-sectional study of 1776 members of 227 randomly-ascertained families. Selected families contained at least one affected metabolic syndrome and at least two members of the family had suffered a loss of HDL_C according to ATP III criteria. In this study, after confirming the familial aggregation with intra-trait correlation coefficients (ICC) of Metabolic syndrome (MetS) and the quantitative lipid traits, the genetic linkage analysis of HDL_C was performed using conditional logistic method with adjusted sex and age. The results of the aggregation analysis revealed a higher correlation between siblings than between parent-offspring pairs representing the role of genetic factors in MetS. In addition, the conditional logistic model with covariates showed that the linkage results between HDL_C and three marker, rs1558902, rs7202116 and rs1864163 were significant. In summary, a high risk of MetS was found in siblings confirming the genetic influences of metabolic syndrome risk factor. Moreover, the power to detect linkage increases in the one parameter conditional logistic model regarding the use of age and sex as covariates. Copyright © 2018. Published by Elsevier B.V.

The metabolic syndrome: targeting dyslipidaemia to reduce coronary risk.

NARCIS (Netherlands)

Ginsberg, H.N.; Stalenhoef, A.F.H.

2003-01-01

The metabolic syndrome is a complex constellation of disorders, each one a significant risk factor for the development of cardiovascular disease (CVD). The increasing prevalence of this condition is a major concern for healthcare providers both in Europe and North America. The concern surrounding

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

Antipsychotic Medications and Risk of Acute Coronary Syndrome in Schizophrenia: A Nested Case-Control Study.

Directory of Open Access Journals (Sweden)

Hsing-Cheng Liu

Full Text Available This study assessed the risk of developing acute coronary syndrome requiring hospitalization in association with the use of certain antipsychotic medications in schizophrenia patients.A nationwide cohort of 31,177 inpatients with schizophrenia between the ages of 18 and 65 years whose records were enrolled in the National Health Insurance Research Database in Taiwan from 2000 to 2008 and were studied after encrypting the identifications. Cases (n = 147 were patients with subsequent acute coronary syndrome requiring hospitalization after their first psychiatric admission. Based on a nested case-control design, each case was matched with 20 controls for age, sex and the year of first psychiatric admission using risk-set sampling. The effects of antipsychotic agents on the development of acute coronary syndrome were assessed using multiple conditional logistic regression and sensitivity analyses to confirm any association.We found that current use of aripiprazole (adjusted risk ratio [RR] = 3.68, 95% CI: 1.27-10.64, p<0.05 and chlorpromazine (adjusted RR = 2.96, 95% CI: 1.40-6.24, p<0.001 were associated with a dose-dependent increase in the risk of developing acute coronary syndrome. Although haloperidol was associated with an increased risk (adjusted RR = 2.03, 95% CI: 1.20-3.44, p<0.01, there was no clear dose-dependent relationship. These three antipsychotic agents were also associated with an increased risk in the first 30 days of use, and the risk decreased as the duration of therapy increased. Sensitivity analyses using propensity score-adjusted modeling showed that the results were similar to those of multiple regression analysis.Patients with schizophrenia who received aripiprazole, chlorpromazine, or haloperidol could have a potentially elevated risk of developing acute coronary syndrome, particularly at the start of therapy.

Bone marrow morphology and disease progression in congenital thrombocytopenia: a detailed clinicopathologic and genetic study of eight cases.

Science.gov (United States)

Tsang, Hamilton C; Bussel, James B; Mathew, Susan; Liu, Yen-Chun; Imahiyerobo, Allison A; Orazi, Attilio; Geyer, Julia T

2017-04-01

Patients with congenital thrombocytopenia have an increased risk of developing myeloid neoplasms. In these cases, the morphologic distinction between disease at baseline and at progression is challenging. This report analyzes clinicopathologic features of congenital thrombocytopenia with long-term follow-up at one referral center. Records from the last 20 years were searched for cases of congenital thrombocytopenia with bone marrow biopsies and peripheral blood smears. The clinical, morphologic, immunophenotypic, and molecular features were analyzed. Six adult and two pediatric patients were identified (six male, two female). Age range at first biopsy was 1-47 (median, 31) years. Underlying diseases included thrombocytopenia-absent radius syndrome, congenital thrombocytopenia with radial-ulnar synostosis, MYH9-related disorder, shortened telomere syndrome, congenital thrombocytopenia with ANKRD26 mutation, and familial platelet disorder with predisposition to acute myeloid leukemia. Four patients had myelodysplastic/myeloproliferative neoplasm-like marrow changes such as hypercellularity, increased myeloid to erythroid ratio, numerous micromegakaryocytes (highlighted by CD42b), and marrow fibrosis. Two patients had marrow hypoplasia and two had unremarkable marrow morphology. Three patients-all in the myelodysplastic/myeloproliferative neoplasm-like group-developed disease progression characterized by erythroid and myeloid dysplasia, elevated bone marrow blasts, and new cytogenetic abnormalities. Unlike non-familial myeloid neoplasms, congenital thrombocytopenia patients in the myelodysplastic/myeloproliferative neoplasm-like group had a long and indolent clinical course (average age at disease progression, 47 years). In summary, three distinct morphologic types of congenital thrombocytopenia were identified: a hyperplastic myelodysplastic/myeloproliferative neoplasm-like group, a hypoplastic bone marrow failure-like group, and a group with relatively normal marrow

[Risk factors for metabolic syndrome in a case control study in Temuco, Chile].

Science.gov (United States)

Philco L, Patricia; Serón S, Pamela; Muñoz N, Sergio; Navia B, Pilar; Lanas Z, Fernando

2012-03-01

Metabolic syndrome is becoming an important public health problem in affluent societies. To identify factors associated to metabolic syndrome in a Southern Chilean city. Using a case control design, 200 participants, aged 35 to 70 years with at least three criteria for metabolic syndrome according to the National Cholesterol Education Program (NCEP_ATPIII) and 200 subjects with less than three criteria, were studied. Both groups were compared in terms of ethnic background, educational level, family history of diabetes and coronary artery disease, menopausal status, smoking, stress and depression, physical activity, changes in body mass index in the last five years and diet. Among subjects aged more than 54 years, among males and among overweight individuals, having a Mapuche origin was a risk factor with odds ratios (OR) of 7.2; 88 and 3.9 respectively. Among subjects aged more than 54 years, among women and among overweight individuals, a family history of diabetes was a risk factor with OR of 17.7; 3.2 and 3.9 respectively. Among subjects aged more than 54 years and among women a change in body mass index of more than three points was a risk factor with OR of 12.5 and 7.4, respectively. Depression also was a risk factor among subjects aged more than 54 years (OR 3.3). Regular consumption of wine was a protective factor among participants of more than 54 years, with an OR of 0.17. The risk factors for metabolic syndrome detected in this group of participants, were having a Mapuche origin, a family history of diabetes mellitus and depression. Wine consumption was associated with a lower risk.

Cardiometabolic Risk and Female Sexuality-Part I. Risk Factors and Potential Pathophysiological Underpinnings for Female Vasculogenic Sexual Dysfunction Syndromes.

Science.gov (United States)

Maseroli, Elisa; Scavello, Irene; Vignozzi, Linda

2018-05-02

Erectile dysfunction is recognized as an opportunity for preventing cardiovascular (CV) events, and assessing the impairment of penile vascular flow by Doppler ultrasound is an important tool to ascertain CV risk. Conversely, the role of genital vascular impairment in the pathophysiology of female sexual dysfunction (FSD) remains contentious. To focus on the current scientific support for an association between CV risk factors and female sexual health in the 1st part of a 2-part review. A thorough literature search of peer-reviewed publications on the associations between CV risk factors and FSD and their underlying mechanisms was performed using the PubMed database. We present a summary of the evidence from clinical studies and discuss the possible mechanisms providing the pathophysiologic bases of vasculogenic FSD syndromes. The peripheral sexual response in women is a vascular-dependent event, and evidence suggests that cardiometabolic-related perturbations in endothelial function can determine vascular insufficiency in female genital tissues. Although epidemiologic and observational studies demonstrate that the prevalence of FSD is higher in women with diabetes mellitus, a cause-effect relation between these clinical conditions cannot be assumed. Evidence on the effect of obesity, metabolic syndrome, and polycystic ovary syndrome on sexual function in women is controversial. Data on the associations of dyslipidemia and hypertension with FSD are limited. Common cardiometabolic alterations could affect vascular function in the female genital tract. Based on limited data, there is an association between CV risk factors and female sexual health in women; however, this association appears milder than in men. Maseroli E, Scavello I, Vignozzi L. Cardiometabolic Risk and Female Sexuality-Part I. Risk Factors and Potential Pathophysiological Underpinnings for Female Vasculogenic Sexual Dysfunction Syndromes. Sex Med Rev 2018;X:XXX-XXX. Copyright © 2018 International

Hematological abnormalities in adult patients with Down's syndrome.

LENUS (Irish Health Repository)

McLean, S

2012-02-01

BACKGROUND: There is a paucity of data regarding hematological abnormalities in adults with Down\\'s syndrome (DS). AIMS: We aimed to characterize hematological abnormalities in adult patients with DS and determine their long-term significance. METHODS: We retrospectively studied a cohort of nine DS patients referred to the adult hematology service in our institution between May 2001 and April 2008. Data collected were: full blood count (FBC), comorbidities, investigations performed, duration of follow-up and outcome to most recent follow-up. RESULTS: Median follow-up was 26 months (9-71). Of the nine patients, two had myelodysplastic syndrome (MDS) at presentation. Of these, one progressed, with increasing marrow failure, and requiring support with transfusions and gCSF. The remaining eight patients, with a variety of hematological abnormalities including leukopenia, macrocytosis, and thrombocytopenia, had persistently abnormal FBCs. However there was no evidence of progression, and no patient has evolved to acute myeloid leukemia (AML). CONCLUSIONS: MDS is a complication of DS and may require supportive therapy. However, minor hematological abnormalities are common in adult DS patients, and may not signify underlying marrow disease.

Prevalence and risk factors of moderate to severe obstructive sleep apnea syndrome in insomnia sufferers: a study on 1311 subjects.

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Hein, Matthieu; Lanquart, Jean-Pol; Loas, Gwénolé; Hubain, Philippe; Linkowski, Paul

2017-07-06

Several studies have investigated the prevalence and risk factors of insomnia in subjects with obstructive sleep apnea syndrome. However, few studies have investigated the prevalence and risk factors for obstructive sleep apnea syndrome in insomnia sufferers. Thus, the aim of this study was to examine the prevalence and risk factors of moderate to severe obstructive sleep apnea syndrome in a large sample of insomnia sufferers. Data from 1311 insomnia sufferers who were recruited from the research database of the sleep laboratory of the Erasme Hospital were analysed. An apnea-hypopnea index of ≥15 events per hour was used as the cut-off score for moderate to severe obstructive sleep apnea syndrome. Logistic regression analyses were conducted to examine clinical and demographic risk factors of moderate to severe obstructive sleep apnea syndrome in insomnia sufferers. The prevalence of moderate to severe obstructive sleep apnea syndrome in our sample of insomnia sufferers was 13.88%. Multivariate logistic regression analysis revealed that male gender, snoring, excessive daytime sleepiness, lower maintenance insomnia complaint, presence of metabolic syndrome, age ≥ 50 & 30 kg/m 2 , and CRP >7 mg/L were significant risk factors of moderate to severe obstructive sleep apnea syndrome in insomnia sufferers. Moderate to severe obstructive sleep apnea syndrome is a common pathology in insomnia sufferers. The identification of these different risk factors advances a new perspective for more effective screening of moderate to severe obstructive sleep apnea syndrome in insomnia sufferers.

[Occupational risk factors for radial tunnel syndrome in factory workers].

Science.gov (United States)

Roquelaure, Y; Raimbeau, G; Saint-Cast, Y; Martin, Y H; Pelier-Cady, M C

2003-12-01

The purpose of the study was to evaluate the professional and extraprofessional risk factors for radial tunnel syndrome (RTS) in employees of three large companies. Twenty-one cases of RTS were compared to 21 controls, matched for age, sex, and activity. In nine cases, RTS was associated with carpal tunnel syndrome. The analysis considered medical history, extraprofessional activity, and the ergonomic and organisational aspects of work. The study demonstrated three risk factors of RTS related to work conditions. The regular use of a force of at least 1 kg (OR = 9.1 (1.4-56.9)) more than 10 times per hour is the main biomechanical risk factor. Static work (OR = 5.9 (1.2-29.9)) as well as work with the elbow constantly extended 0 degree to 45 degrees, is strongly associated with an increased risk of RTS (OR = 4.9 (1.0-25.0)). Complete extension of the elbow associated with pronation and supination of the forearm may cause trauma to the radial nerve in the radial tunnel. On the other hand, we found no personal factors and no extraprofessional activities which were associated with an increased risk of RTS. This study shows that motions of the forearm requiring intense effort and performed with the elbow in extension and the forearm in pronation and supination increase the risk of RTS.

Increased Risk of Metabolic Syndrome in Patients with Vitiligo.

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Ataş, Hatice; Gönül, Müzeyyen

2017-05-05

Inflammatory and immune processes can be triggered in vitiligo due to a decreased number of melanocytes and their anti-inflammatory effects. Because of the systemic nature of vitiligo, metabolic abnormalities such as insulin resistance and lipid profile disturbances as well as skin involvement may be observed in vitiligo. To investigate the association between metabolic syndrome and vitiligo. Case-control study. The demographic, clinical and laboratory features in the subjects were compared according to presence of vitiligo and metabolic syndrome [patients (n=63) vs. gender-age matched controls (n=65) and metabolic syndrome positive (n=38) vs. negative (n=90)]. A logistic regression analysis was also used. We identified metabolic syndrome in 24 (38.1%) subjects with vitiligo and 14 (21.5%) subjects without vitiligo (p=0.04). Active vitiligo, segmental vitiligo, an increased duration of vitiligo and an increased percentage in the affected body surface area were determined to be independent predictors of metabolic syndrome [activity of vitiligo: p=0.012, OR (95% CI)=64.4 (2.5-1672); type of vitiligo: p=0.007, OR (95% CI)=215.1 (4.3-10725.8); duration of vitiligo: p=0.03, OR (95% CI)=1.4 (1.1-2.0); percentage of affected body surface area: p=0.07, OR (95% CI)=1.2 (0.98-1.5)]. The risk of developing metabolic syndrome is increased in patients with vitiligo. The poor clinical features of vitiligo, such as active, extended and segmental vitiligo with an increased duration of time, are independent predictors for developing metabolic syndrome.

Risk of metabolic syndrome in adolescents with polycystic ovarian syndrome: A systematic review and meta-analysis.

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Fazleen, Nur Ezza; Whittaker, Maxine; Mamun, Abdullah

2018-03-16

Polycystic ovarian syndrome (PCOS) is the commonest reproductive disorder in women and is closely associated with the development of metabolic syndrome (MetS). The objective of this systematic review and meta-analysis was to describe the risk of MetS in adolescent with PCOS to help diagnosing and preventing of morbidity and mortality later in life. Pubmed, Medline, EMBASE, CINAHL and other sources were searched for metabolic syndrome in adolescents with polycystic ovarian syndrome using PRISMA guidelines (Moher et al., 2009). All type of study design of women aged 10-20 reported association of PCOS with metabolic syndrome was included in this study. Meta-analysis was conducted for MetS and its individual component using bias adjusted quality effect model and we compare the results from quality effects with random effects and IVhet model. Data were presented as prevalence, odds ratio (95% confidence interval and mean difference (95% confidence interval). This systematic review included 9 studies while the meta-analysis included 7 studies. Meta-analysis showed that the odds of being experiencing MetS in PCOS groups was 2.69 (1.29, 5.60) times than girls without PCOS. The mean difference between girls with PCOS and without PCOS for systolic blood pressure was 5.00 (1.28, 8.72), diastolic blood pressure was 3.50 (0.48, 6.56), triglycerides level was 4.20 (-3.99, 12.45), glucose level was 1.30 (-0.46, 3.05), HDL level was -1.40 (-4.85, 2.00). This systematic review and meta-analysis support the hypothesis that the risk of MetS is much greater in adolescents with PCOS compared to the normal population. It is important to screen PCOS in early age to prevent MetS and its complications which lead to morbidity and mortality later in life. Copyright © 2018. Published by Elsevier Ltd.

Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed by Unrelated Donor Stem Cell Transplant in Treating Patients With Fanconi Anemia

Science.gov (United States)

2017-02-16

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); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; Fanconi Anemia; Previously Treated Myelodysplastic Syndromes

The Risk of Metabolic Syndrome among Institutionalized Adults with Intellectual Disabilities

Science.gov (United States)

Hsu, Shang-Wei; Yen, Chia-Feng; Hung, Wen-Jui; Lin, Lam-Ping; Wu, Chia-Ling; Lin, Jin-Ding

2012-01-01

People with metabolic syndrome (MS) are at increased risk of coronary heart disease and other health problems, such as diabetes and stroke. However, there is little previous information on the prevalence and determinants of MS among people with intellectual disabilities (IDs). The present study aimed to examine the prevalence of MS risk factors…

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

Snus use during the life-course and risk of the metabolic syndrome and its components.

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Byhamre, Marja Lisa; Gustafsson, Per E; Jansson, Jan-Håkan; Wennberg, Maria; Hammarström, Anne; Wennberg, Patrik

2017-12-01

We aimed to investigate the association between life-course exposure to snus and prevalence of the metabolic syndrome and its components in adulthood. Tobacco habits at baseline (age 16) and three follow-ups (ages 21, 30 and 43) were assessed among 880 participants in a population-based cohort in Northern Sweden. Presence of the metabolic syndrome at age 43 was ascertained using the International Diabetes Federation criteria. Odds ratios and CIs for risk of the metabolic syndrome and its components by snus use at 16, 21, 30 and 43 years were calculated using logistic regression. Cumulative snus use was defined as number of life periods (1-4) with current snus use. At age 43, 164 participants (18.6%) were current snus users. We found no association between exclusive snus use at the ages of 16, 21, 30 and 43 years and the metabolic syndrome at age 43 years. Snus use (among non-smokers) was associated with raised triglycerides and high blood pressure in crude analysis, but not in multivariable models. There was no association between cumulative snus use and risk of the metabolic syndrome. Cumulative snus use was associated with central obesity, raised triglycerides and impaired fasting glucose/diabetes mellitus type 2 in crude analyses, but not after adjustments. The health consequences of snus exposure from adolescence to mid-adulthood do not seem to include increased risk of the metabolic syndrome or its components. The cardio-metabolic risk of dual exposure to snus and cigarettes may warrant further attention.

Risk of cardiovascular events in people prescribed glucocorticoids with iatrogenic Cushing’s syndrome: cohort study

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Petersen, Irene; Nazareth, Irwin

2012-01-01

Objective To investigate whether there is an increased risk of cardiovascular events in people who exhibit iatrogenic Cushing’s syndrome during treatment with glucocorticoids. Design Cohort study. Setting 424 UK general practices contributing to The Health Improvement Network database. Participants People prescribed systemic glucocorticoids and with a diagnosis of iatrogenic Cushing’s syndrome (n=547) and two comparison groups: those prescribed glucocorticoids and with no diagnosis of iatrogenic Cushing’s syndrome (n=3231) and those not prescribed systemic glucocorticoids (n=3282). Main outcome measures Incidence of cardiovascular events within a year after diagnosis of iatrogenic Cushing’s syndrome or after a randomly selected date, and association between iatrogenic Cushing’s syndrome and risk of cardiovascular events. Results 417 cardiovascular events occurred in 341 patients. Taking into account only the first event by patient (coronary heart disease n=177, heart failure n=101, ischaemic stroke n=63), the incidence rates of cardiovascular events per 100 person years at risk were 15.1 (95% confidence interval 11.8 to 18.4) in those prescribed glucocorticoids and with a diagnosis of iatrogenic Cushing’s syndrome, 6.4 (5.5 to 7.3) in those prescribed glucocorticoids without a diagnosis of iatrogenic Cushing’s syndrome, and 4.1 (3.4 to 4.8) in those not prescribed glucocorticoids. In multivariate analyses adjusted for sex, age, intensity of glucocorticoid use, underlying disease, smoking status, and use of aspirin, diabetes drugs, antihypertensive drugs, lipid lowering drugs, or oral anticoagulant drugs, the relation between iatrogenic Cushing’s syndrome and cardiovascular events was strong (adjusted hazard ratios 2.27 (95% confidence interval 1.48 to 3.47) for coronary heart disease, 3.77 (2.41 to 5.90) for heart failure, and 2.23 (0.96 to 5.17) for ischaemic cerebrovascular events). The adjusted hazard ratio for any cardiovascular event was 4

Cardiometabolic Risks in Polycystic Ovary Syndrome: Non-Traditional Risk Factors and the Impact of Obesity.

Science.gov (United States)

Chiu, Wei-Ling; Boyle, Jacqueline; Vincent, Amanda; Teede, Helena; Moran, Lisa J

2017-01-01

Polycystic ovary syndrome (PCOS) is a common and complex endocrinopathy with reproductive, metabolic, and psychological features and significantly increased cardiometabolic risks. PCOS is underpinned by inherent insulin resistance and hyperandrogenism. Obesity, more common in PCOS, plays an important role in the pathophysiology, exacerbating hyperinsulinaemia and hyperandrogenism, leading to recommended first-line lifestyle intervention. Significant traditional and non-traditional risk factors are implicated in PCOS in addition to obesity-exacerbated cardiometabolic risks and are explored in this review to promote the understanding of this common metabolic and reproductive condition. © 2016 S. Karger AG, Basel.

Risk of Nephrotic Syndrome following Enteroviral Infection in Children: A Nationwide Retrospective Cohort Study.

Science.gov (United States)

Lin, Jiun-Nong; Lin, Cheng-Li; Yang, Chi-Hui; Lin, Ming-Chia; Lai, Chung-Hsu; Lin, Hsi-Hsun; Kao, Chia-Hung

2016-01-01

Nephrotic syndrome is a common chronic illness encountered during childhood. Infections have been identified as a cause of nephrotic syndrome. The aim of this study was to evaluate the association between enteroviral infection and nephrotic syndrome. A nationwide retrospective cohort study was conducted by analyzing data from the National Health Insurance Research Database in Taiwan. Children aged children were randomly selected as the comparison cohort. The primary endpoint was the occurrence of nephrotic syndrome. This study included 280,087 enterovirus-infected children and 280,085 non-enterovirus-infected children. The mean age of the enterovirus-infected children was 2.38 years, and 53.7% of these children were boys. The overall incidence densities of nephrotic syndrome for enterovirus- and non-enterovirus-infected children were 2.65 and 2.21 per 10,000 person-years, respectively. The enterovirus-infected cohort had a higher cumulative incidence of nephrotic syndrome than did the non-enterovirus-infected cohort (log-rank test, p = 0.01). Multivariable analyses revealed that children with enteroviral infection were significantly associated with an increased risk of nephrotic syndrome compared with those without enteroviral infection (adjusted hazard ratio, 1.20; 95% confidence interval, 1.04-1.39; p = 0.01), particularly in children infected with coxsackievirus. Subgroup analyses revealed that enterovirus-infected girls, children of blue-collar workers, and children without allergies had a higher risk of nephrotic syndrome than did children in the non-enterovirus-infected cohort. This study revealed a significant association between enteroviral infection and nephrotic syndrome. Additional studies elucidating the role and pathogenesis of enterovirus in nephrotic syndrome are warranted.

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.

Does the Risk of Metabolic Syndrome Increase in Thyroid Cancer Survivors?

Science.gov (United States)

Kim, Min-Hee; Huh, Jin-Young; Lim, Dong-Jun; Kang, Moo-Il

2017-07-01

The steep rise in thyroid cancer observed in recent decades has caused an increase in the population of long-term thyroid cancer survivors. Other than recurrences of cancer, the long-term health consequences of surviving thyroid cancer, particularly metabolic syndrome, have not yet been determined. The aim of this study was to estimate the risk of metabolic syndrome in thyroid cancer survivors. Population-based data from the Korean National Health and Nutrition Examination Survey (KNHANES) were used for the analysis. The data of KNHANES IV-VI from 2007-2014 were obtained. After excluding subjects who were under 19 years old, whose fasting interval was less than 8 hours, and whose data for predefined variables including metabolic syndrome components were incomplete, 34,347 subjects were analyzed. The incidence of metabolic syndrome and its components were evaluated in three groups: subjects with no history of thyroid cancer, subjects diagnosed with thyroid cancer within 3 years of the survey date, and subjects diagnosed more than 3 years before the survey date. Thyroid cancer diagnoses were made within 3 years of the survey date for 95 subjects (group 1, short-term survivors) and more than 3 years earlier than the survey date for 60 subjects (group 2, long-term survivors). Metabolic syndrome was frequently observed with clinical significance (odds ratio [OR] 1.986 [95% confidence interval [CI] 1.0-3.70], p = 0.030) in short-term survivors compared with subjects with no thyroid cancer history. Risks for having high blood pressure and high fasting glucose were estimated to be higher in the short-term survivor group (OR 2.115 [CI 1.23-3.64], p = 0.006 and OR 1.792 [CI 1.03-3.11], p = 0.038, respectively). No significant associations were noticed in the long-term survivor group when compared with the group with no thyroid cancer history. Risks for metabolic syndrome, especially high blood pressure and high fasting glucose, were increased in short

An Integrated Soft Computing Approach to Hughes Syndrome Risk Assessment.

Science.gov (United States)

Vilhena, João; Rosário Martins, M; Vicente, Henrique; Grañeda, José M; Caldeira, Filomena; Gusmão, Rodrigo; Neves, João; Neves, José

2017-03-01

The AntiPhospholipid Syndrome (APS) is an acquired autoimmune disorder induced by high levels of antiphospholipid antibodies that cause arterial and veins thrombosis, as well as pregnancy-related complications and morbidity, as clinical manifestations. This autoimmune hypercoagulable state, usually known as Hughes syndrome, has severe consequences for the patients, being one of the main causes of thrombotic disorders and death. Therefore, it is required to be preventive; being aware of how probable is to have that kind of syndrome. Despite the updated of antiphospholipid syndrome classification, the diagnosis remains difficult to establish. Additional research on clinically relevant antibodies and standardization of their quantification are required in order to improve the antiphospholipid syndrome risk assessment. Thus, this work will focus on the development of a diagnosis decision support system in terms of a formal agenda built on a Logic Programming approach to knowledge representation and reasoning, complemented with a computational framework based on Artificial Neural Networks. The proposed model allows for improving the diagnosis, classifying properly the patients that really presented this pathology (sensitivity higher than 85%), as well as classifying the absence of APS (specificity close to 95%).

Associations between Yogurt Consumption and Weight Gain and Risk of Obesity and Metabolic Syndrome: A Systematic Review.

Science.gov (United States)

Sayon-Orea, Carmen; Martínez-González, Miguel A; Ruiz-Canela, Miguel; Bes-Rastrollo, Maira

2017-01-01

The role of yogurt consumption in the risk of developing overweight, obesity, or metabolic syndrome has been the subject of epidemiologic studies over the last 10 y. A comprehensive literature search on MEDLINE and ISI Web of Knowledge from 1966 through June 2016 was conducted to examine the relation between yogurt consumption and weight gain, as well as the risk of overweight, obesity, or metabolic syndrome, in prospective cohort studies. Ten articles met all the inclusion criteria and were included in our systematic review. Of the 10 cohort studies, 3 analyzed the relation between yogurt consumption and the risk of overweight or obesity, 8 analyzed changes in waist circumference or weight changes, 3 studied the association with the risk of developing metabolic syndrome, and 1 studied the probability of abdominal obesity reversion. Although an inverse association between yogurt consumption and the risk of developing overweight or obesity was not fully consistent or always statistically significant, all studies but one showed in their point estimates inverse associations between yogurt consumption and changes in waist circumference, changes in weight, risk of overweight or obesity, and risk of metabolic syndrome during follow-up, although not all estimates were statistically significant (2 studies). Prospective cohort studies consistently suggested that yogurt consumption may contribute to a reduction in adiposity indexes and the risk of metabolic syndrome. Therefore, there is a need for more prospective studies and high-quality randomized clinical trials to confirm this apparent inverse association. © 2017 American Society for Nutrition.

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

T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts

Science.gov (United States)

2017-08-29

Acute Lymphoblastic Leukemia; Non Hodgkins Lymphoma; Myelodysplastic Syndrome; Acute Myeloid Leukemia; Chronic Myelogenous Leukemia; Hemophagocytic Lymphohistiocytosis (HLH); Familial Hemophagocytic Lymphohistiocytosis (FLH); Viral-associated Hemophagocytic Syndrome (VAHS); X-linked Lymphoproliferative Disease (XLP)

Acquired hemoglobin H disease in a patient with aplastic anemia evolving into acute myeloid leukemia

Directory of Open Access Journals (Sweden)

Maria Stella Figueiredo

Full Text Available CONTEXT: The prognosis of severe aplastic anemia has improved since the introduction of bone marrow transplantation and treatment with antithymocyte globulin. In contrast to the success of these protocols, studies with long term follow-up have shown the occurrence of clonal diseases such as paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome and acute leukemia in aplastic anemia. CASE REPORT: We report the first case of a Brazilian patient with aplastic anemia who developed myelodysplastic syndrome and acute myeloid leukemia showing acquired hemoglobin H and increased fetal hemoglobin.

Alimentary habits, physical activity, and Framingham global risk score in metabolic syndrome.

Science.gov (United States)

Soares, Thays Soliman; Piovesan, Carla Haas; Gustavo, Andréia da Silva; Macagnan, Fabrício Edler; Bodanese, Luiz Carlos; Feoli, Ana Maria Pandolfo

2014-04-01

Metabolic syndrome is a complex disorder represented by a set of cardiovascular risk factors. A healthy lifestyle is strongly related to improve Quality of Life and interfere positively in the control of risk factors presented in this condition. To evaluate the effect of a program of lifestyle modification on the Framingham General Cardiovascular Risk Profile in subjects diagnosed with metabolic syndrome. A sub-analysis study of a randomized clinical trial controlled blind that lasted three months. Participants were randomized into four groups: dietary intervention + placebo (DIP), dietary intervention + supplementation of omega 3 (fish oil 3 g/day) (DIS3), dietary intervention + placebo + physical activity (DIPE) and dietary intervention + physical activity + supplementation of omega 3 (DIS3PE). The general cardiovascular risk profile of each individual was calculated before and after the intervention. The study included 70 subjects. Evaluating the score between the pre and post intervention yielded a significant value (p study emphasizes the importance of lifestyle modification in the prevention and treatment of cardiovascular diseases.

Self-Management Training for Chinese Obese Children at Risk for Metabolic Syndrome: Effectiveness and Implications for School Health

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Ling, Jiying; Anderson, Laura M.; Ji, Hong

2015-01-01

This article reviews the results of a school-based self-management intervention for Chinese obese children at risk for metabolic syndrome. Twenty-eight Chinese obese children (M age?=?10 years) and their parents participated in the study. Metabolic syndrome risk factors were measured pre- and post-intervention. The risk factors included Body Mass…

Bloom syndrome in sibs: first reports of hepatocellular carcinoma and Wilms tumor with documented anaplasia and nephrogenic rests.

Science.gov (United States)

Jain, D; Hui, P; McNamara, J; Schwartz, D; German, J; Reyes-Múgica, M

2001-01-01

The triad of small body size, immunodeficiency, and sun-sensitive facial erythema characterizes the phenotype Bloom syndrome (BS), a rare autosomal recessive disorder with a striking predisposition to multiple types of cancers that arise earlier than expected in the general population. Here we report two sibs with BS. The older, a 15-year-old-girl, developed a hepatocellular carcinoma, a neoplasm not yet reported in association with BS. Her younger brother developed an anaplastic Wilms tumor (WT) associated with nephrogenic rests at the age of 31/2 years, and this was followed by a myelodysplastic syndrome. Complex cytogenetic abnormalities were identified in all three neoplasms. These examples expand the spectrum of malignancies occurring in BS to include liver cell neoplasms, and confirm the association of nephrogenic rests with WT, even in the setting of BS.

Adolescent Metabolic Syndrome Risk Is Increased with Higher Infancy Weight Gain and Decreased with Longer Breast Feeding

Directory of Open Access Journals (Sweden)

Kim Khuc

2012-01-01

Full Text Available Background. Prevalence of the metabolic syndrome is increasing in pediatric age groups worldwide. Meeting the criteria for the metabolic syndrome puts children at risk for later cardiovascular and metabolic disease. Methods. Using linear regression, we examined the association between infant weight gain from birth to 3 months and risk for the metabolic syndrome among 16- to 17-year-old Chilean adolescents (n=357, accounting for the extent of breastfeeding in infancy and known covariates including gender, birth weight, and socioeconomic status. Results. Participants were approximately half male (51%, born at 40 weeks of gestation weighing 3.5 kg, and 48% were exclusively breastfed for ≥90 days. Factors independently associated with increased risk of metabolic syndrome in adolescence were faster weight gain in the first 3 months of life (B=0.16, P<0.05 and male gender (B=0.24, P<0.05. Breastfeeding as the sole source of milk for ≥90 days was associated with significantly decreased risk of metabolic syndrome (B=−0.16. Conclusion. This study adds to current knowledge about early infant growth and breastfeeding and their long-term health effects.

Sudden infant death syndrome, childhood thrombosis, and presence of genetic risk factors for thrombosis

DEFF Research Database (Denmark)

Larsen, TB; Nørgaard-Pedersen, B; Lundemose, JB

2000-01-01

in the child. This prompted us to investigate these genetic markers of thromboembolic disease in 121 cases of sudden infant death syndrome and in relevant controls, in the expectation of a more frequent occurrence of these markers if thrombosis is an etiological factor in sudden infant death syndrome...... or unknown risk factors for thrombosis as possible etiological factors for sudden infant death syndrome. It is likely that we must continuously employ the exclusion principle on possible etiological causes in genetic material from a large group of victims of sudden infant death syndrome if the phenomenon...

Early Onset Childhood Obesity and Risk of Metabolic Syndrome

Centers for Disease Control (CDC) Podcasts

This podcast features Lorena Pacheco, a doctoral student at the University of California San Diego and one of the winners of PCD's 2017 Student Research Paper Contest. Lorena answers questions about her winning research, which focuses on the relationship between early onset obesity as a risk factor for increased metabolic syndrome in Chilean children.

Associations between Yogurt Consumption and Weight Gain and Risk of Obesity and Metabolic Syndrome: A Systematic Review1234

Science.gov (United States)

Martínez-González, Miguel A; Bes-Rastrollo, Maira

2017-01-01

The role of yogurt consumption in the risk of developing overweight, obesity, or metabolic syndrome has been the subject of epidemiologic studies over the last 10 y. A comprehensive literature search on MEDLINE and ISI Web of Knowledge from 1966 through June 2016 was conducted to examine the relation between yogurt consumption and weight gain, as well as the risk of overweight, obesity, or metabolic syndrome, in prospective cohort studies. Ten articles met all the inclusion criteria and were included in our systematic review. Of the 10 cohort studies, 3 analyzed the relation between yogurt consumption and the risk of overweight or obesity, 8 analyzed changes in waist circumference or weight changes, 3 studied the association with the risk of developing metabolic syndrome, and 1 studied the probability of abdominal obesity reversion. Although an inverse association between yogurt consumption and the risk of developing overweight or obesity was not fully consistent or always statistically significant, all studies but one showed in their point estimates inverse associations between yogurt consumption and changes in waist circumference, changes in weight, risk of overweight or obesity, and risk of metabolic syndrome during follow-up, although not all estimates were statistically significant (2 studies). Prospective cohort studies consistently suggested that yogurt consumption may contribute to a reduction in adiposity indexes and the risk of metabolic syndrome. Therefore, there is a need for more prospective studies and high-quality randomized clinical trials to confirm this apparent inverse association. PMID:28096138

OBESITY AND METABOLIC SYNDROME IN CHILDREN AND YOUTH: A HEALTH RISK WE CANNOT AFFORD

Directory of Open Access Journals (Sweden)

Serge P. von Duvillard

2012-12-01

Full Text Available Ample observational and empirical evidence has been provided that indicates that childhood metabolic syndrome risk factors inevitably lead to significantly more profound health risk factors of developing potent adulthood metabolic syndrome. Much of these data has been provided from medical, nutritional, health, pediatric, physical education and associated communities. Perhaps the most visible and observable health risk factor among children (here referred to as youth is the childhood obesity. Childhood obesity has reached epidemic proportions in western industrialized countries and is also becoming significantly more prevalent in Slovenia. The youth inactivity is attributed directly to epidemic and perhaps exponential occurrence of obesity in pediatric and youth populations. The symptoms and signs of metabolic syndrome have previously been attributed mostly to the adult population; however, similar observations have been identified and observed in young and very young segment of population. The typical risk factors of metabolic syndrome in youth, in adolescents, and in adulthood have been commonly identified to be: stress, overweight and obesity, sedentary life cycle, aging, diabetes mellitus, coronary heart disease, lipodystrophy and several others. This presentation will review and address several well known risk factors of developing metabolic syndrome in young years that directly contributes to adult obesity and are exhibited in significantly higher rates of hypertension, dyslipidemias, and insulin resistance, which are all risk factors for coronary heart disease, the leading cause of death in North America and may also apply to Slovenia. Many of these risk factors are modifiable (nutrition, smoking, sedentary life style, vigorous physical activity, reduction in TV and computer game times, etc. with specific emphasis on very young, young, adolescents and profound consequences for adulthood. Several recommendations will be proposed that may

Metabolic Vascular Syndrome: New Insights into a Multidimensional Network of Risk Factors and Diseases.

Science.gov (United States)

Scholz, Gerhard H; Hanefeld, Markolf

2016-10-01

Since 1981, we have used the term metabolic syndrome to describe an association of a dysregulation in lipid metabolism (high triglycerides, low high-density lipoprotein cholesterol, disturbed glucose homeostasis (enhanced fasting and/or prandial glucose), gout, and hypertension), with android obesity being based on a common soil (overnutrition, reduced physical activity, sociocultural factors, and genetic predisposition). We hypothesized that main traits of the syndrome occur early and are tightly connected with hyperinsulinemia/insulin resistance, procoagulation, and cardiovascular diseases. To establish a close link between the traits of the metabolic vascular syndrome, we focused our literature search on recent original work and comprehensive reviews dealing with the topics metabolic syndrome, visceral obesity, fatty liver, fat tissue inflammation, insulin resistance, atherogenic dyslipidemia, arterial hypertension, and type 2 diabetes mellitus. Recent research supports the concept that the metabolic vascular syndrome is a multidimensional and interactive network of risk factors and diseases based on individual genetic susceptibility and epigenetic changes where metabolic dysregulation/metabolic inflexibility in different organs and vascular dysfunction are early interconnected. The metabolic vascular syndrome is not only a risk factor constellation but rather a life-long abnormality of a closely connected interactive cluster of developing diseases which escalate each other and should continuously attract the attention of every clinician.

Nutrigenetics, metabolic syndrome risk and personalized nutrition.

Science.gov (United States)

Perez-Martinez, Pablo; Phillips, Catherine M; Delgado-Lista, Javier; Garcia-Rios, Antonio; Lopez-Miranda, Jose; Perez-Jimenez, Francisco

2013-11-01

The metabolic syndrome (MetS) is a constellation of metabolic risk factors reflecting overnutrition and sedentary lifestyle and its increasing prevalence is reaching epidemic proportions. The importance of MetS lies in its close association with the risk of cardiometabolic disease. In this scenario, the principal goals of pharmacological therapy for these patients are to achieve and maintain an optimal cardiometabolic control, including lipids, blood glucose and blood pressure; in order to prevent and treat potential complications. Moreover nutrition has commonly been accepted as a cornerstone of treatment for MetS, with the expectation that an appropriate intake of energy and nutrients will improve its control. However the question arises as to whether dietary therapy may require a more personalised approach. In this regard improvements in genetic analysis have enhanced our understanding of the role of genetics in this dietrelated condition. In this review we will present recent data highlighting the importance of gene-nutrient interactions in the context of MetS risk.

Circulating Levels of Uric Acid and Risk for Metabolic Syndrome.

Science.gov (United States)

Rubio-Guerra, Alberto F; Morales-López, Herlinda; Garro-Almendaro, Ana K; Vargas-Ayala, German; Durán-Salgado, Montserrat B; Huerta-Ramírez, Saul; Lozano-Nuevo, Jose J

2017-01-01

Hyperuricemia leads to insulin resistance, whereas insulin resistance decreases renal excretion of uric acid, both mechanisms link elevated serum uric acid with metabolic syndrome. The aim of this study is to evaluate the probability for the development of metabolic syndrome in low-income young adults with hyperuricaemia. We evaluated 103 patients less than 40 years of age, from a low-income population, and without history of cardiovascular disease, in all of them the presence of metabolic syndrome was assessed in accordance with the International Diabetes Federation criteria. In all patients, fasting serum uric acid levels were measured; hyperuricaemia was defined as serum uric acid values 6.5 mg/dl in men and 5.1 mg/dl in women. Statistical analysis was performed with odds ratio. 83 of our patients (80.5%) suffered metabolic syndrome, the odds ratio for the presence of metabolic syndrome in patients with hyperuricaemia was 5.1 (p=0.002, I.C 1.8- 14.5). When patients were evaluated by gender a significantly association between hyperuricaemia and metabolic syndrome was found in women (odds ratio 3.6, p=0.048, C.I. 1.0-12.9), and men (odds ratio 10.2, p= 0.015, IC 1.5-13.2). When uric acid was correlated with the components of metabolic syndrome, we only found a positive correlation with waist circumference (r=0.483). Our results showed a significant association between hyperuricemia and metabolic syndrome in low-income young adults in Mexico. DR is associated with estimated risk of CVD in type 2 diabetic patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Normal obstetric ultrasound reduces the risk of down syndrome in fetuses of older mothers

International Nuclear Information System (INIS)

Anderson, N. G.; Luehr, B.; Ng, R.

2006-01-01

The objective of this study is to determine whether a normal fetal morphology ultrasound scan in women older than 35 years reduces the risk of aneuploidy. We reviewed the results of amniocentesis and second trimester sonogram in all women older than 35 years from 1991 to 1995. None had prior screening. We excluded fetuses with structural anomalies. We determined the sensitivity and specificity of minor markers in detecting Down syndrome and also determined the reduction in risk of a normal sonogram. Among the 2060 women older than 35 years giving birth during the study period, 16 (0.78%) delivered an infant with Down syndrome. Of the 16 fetuses, two had no prenatal testing or ultrasound, two had invasive testing but no second trimester sonogram, five had a normal sonogram and seven had one or more sonographic markers of Down syndrome. At least 17% of women older than 35 years did not participate in prenatal testing or ultrasound. Ultrasound detected Down syndrome with a sensitivity of 59% (95% confidence interval: 45-72%), a false-positive rate of 10.6% (9.4-11.8%) and a positive predictor value of 1 in 9. The likelihood of having normal karyotype if the sonogram was normal was 0.46 (0.31-0.61). In women older than 35 years, a normal second trimester sonogram reduces the risk of Down syndrome by more than 50%. At least 17% of women older than 35 years do not participate in prenatal testing or ultrasound

Risk factors for post-thrombotic syndrome in patients with a first deep venous thrombosis

NARCIS (Netherlands)

Tick, L. W.; Kramer, M. H. H.; Rosendaal, F. R.; Faber, W. R.; Doggen, C. J. M.

2008-01-01

BACKGROUND: Post-thrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT). OBJECTIVES: To determine the risk of PTS after DVT and to assess risk factors for PTS. METHODS: Patients were recruited from the Multiple Environmental and Genetic Assessment (MEGA) study of risk

Sasang constitutional types for the risk prediction of metabolic syndrome: a 14-year longitudinal prospective cohort study.

Science.gov (United States)

Lee, Sunghee; Lee, Seung Ku; Kim, Jong Yeol; Cho, Namhan; Shin, Chol

2017-09-02

To examine whether the use of Sasang constitutional (SC) types, such as Tae-yang (TY), Tae-eum (TE), So-yang (SY), and So-eum (SE) types, increases the accuracy of risk prediction for metabolic syndrome. From 2001 to 2014, 3529 individuals aged 40 to 69 years participated in a longitudinal prospective cohort. The Cox proportional hazard model was utilized to predict the risk of developing metabolic syndrome. During the 14 year follow-up, 1591 incident events of metabolic syndrome were observed. Individuals with TE type had higher body mass indexes and waist circumferences than individuals with SY and SE types. The risk of developing metabolic syndrome was the highest among individuals with the TE type, followed by the SY type and the SE type. When the prediction risk models for incident metabolic syndrome were compared, the area under the curve for the model using SC types was significantly increased to 0.8173. Significant predictors for incident metabolic syndrome were different according to the SC types. For individuals with the TE type, the significant predictors were age, sex, body mass index (BMI), education, smoking, drinking, fasting glucose level, high-density lipoprotein (HDL) cholesterol level, systolic and diastolic blood pressure, and triglyceride level. For Individuals with the SE type, the predictors were sex, smoking, fasting glucose, HDL cholesterol level, systolic and diastolic blood pressure, and triglyceride level, while the predictors in individuals with the SY type were age, sex, BMI, smoking, drinking, total cholesterol level, fasting glucose level, HDL cholesterol level, systolic and diastolic blood pressure, and triglyceride level. In this prospective cohort study among 3529 individuals, we observed that utilizing the SC types significantly increased the accuracy of the risk prediction for the development of metabolic syndrome.

Pregnancy and the risk of torsades de pointes in congenital long-QT syndrome

NARCIS (Netherlands)

Meregalli, P. G.; Westendorp, I. C. D.; Tan, H. L.; Elsman, P.; Kok, W. E. M.; Wilde, A. A. M.

2008-01-01

Patients with congenital long-QT syndrome (LQTS) are at increased risk of ventricular arrhythmias during stressful situations. Large-scale studies have pointed out that affected individuals are particularly at risk in the period following pregnancy (post-partum). This is recognised especially for

Leisure-time exercise, physical activity during work and commuting, and risk of metabolic syndrome.

Science.gov (United States)

Kuwahara, Keisuke; Honda, Toru; Nakagawa, Tohru; Yamamoto, Shuichiro; Akter, Shamima; Hayashi, Takeshi; Mizoue, Tetsuya

2016-09-01

Data are limited regarding effect of intensity of leisure-time physical activity on metabolic syndrome. Furthermore, no prospective data are available regarding effect of occupational and commuting physical activity on metabolic syndrome. We compared metabolic syndrome risk by intensity level of leisure-time exercise and by occupational and commuting physical activity in Japanese workers. We followed 22,383 participants, aged 30-64 years, without metabolic syndrome until 2014 March (maximum, 5 years of follow-up). Physical activity was self-reported. Metabolic syndrome was defined by the Joint Statement criteria. We used Cox regression models to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of metabolic syndrome. During a mean follow-up of 4.1 years, 5361 workers developed metabolic syndrome. After adjustment for covariates, compared with engaging in no exercise, the HRs (95 % CIs) for metabolic equivalent hours of exercise per week were 0.99 (0.90, 1.08), 0.99 (0.90, 1.10), and 0.95 (0.83, 1.08), respectively, among individuals engaging in moderate-intensity exercise alone; 0.93 (0.75, 1.14), 0.81 (0.64, 1.02), and 0.84 (0.66, 1.06), among individuals engaging in vigorous-intensity exercise alone; and 0.90 (0.70, 1.17), 0.74 (0.62, 0.89), and 0.81 (0.69, 0.96) among individuals engaging in the two intensities. Higher occupational physical activity was weakly but significantly associated with lower risk of metabolic syndrome. Walking to and from work was not associated with metabolic syndrome. Vigorous-intensity exercise alone or vigorous-intensity combined with moderate-intensity exercise and worksite intervention for physical activity may help prevent metabolic syndrome for Japanese workers.

Effects of smoking and aerobic exercise on male college students' metabolic syndrome risk factors.

Science.gov (United States)

Kim, Jee-Youn; Yang, Yuhao; Sim, Young-Je

2018-04-01

[Purpose] The aim was to investigate the effects of university students' smoking and aerobic exercise on metabolic syndrome risk factors. [Subjects and Methods] Twenty-three male students were randomly assigned to the following groups: exercise smoker (n=6), non-exercise smoker (n=6), exercise non-smoker (n=6), and non-exercise non-smoker (n=5). A basketball exercise program was conducted three times per week (70 minutes per session) for 8 weeks with exercise intensity set at 50-80% of heart rate reserve. After 8 weeks, the variables of risk factors for metabolic syndrome were obtained. [Results] Systolic blood pressure and diastolic blood pressure were significantly decreased in the exercise non-smoker group and significantly increased in the non-exercise smoker group. Waist circumference was significantly reduced in both exercise groups regardless of smoking and significantly increased in the non-exercise smoker group. Triglyceride, high-density lipoprotein-cholesterol, and fasting plasma glucose showed no differences between the groups. [Conclusion] Obesity and smoking management should be conducted together for students as well as for those with metabolic syndrome risk factors. It is recommended that more students participate in such programs, and exercise programs should be further developed and diversified to prevent metabolic syndrome and cardiovascular diseases.

Compartment syndrome, rhabdomyolysis and risk of acute renal failure as complications of the lithotomy position.

NARCIS (Netherlands)

Bocca, G.; Moorselaar, R.J.A. van; Feitz, W.F.J.; Staak, F.H.J.M. van der; Monnens, L.A.H.

2002-01-01

Compartment syndrome, rhabdomyolysis and the risk of acute renal failure are potential complications of the lithotomy position. A six-year-old girl is described who developed a compartment syndrome with rhabdomyolysis after prolonged surgery in the lithotomy position. This complication occurred

A study of new potential risk factors for Down syndrome in Upper Egypt

African Journals Online (AJOL)

The well-established risk factor, advanced maternal age, was not found in many of the Down syndrome cases in Egypt, while other possible risk factors have not been well studied yet. In view of this, we have conducted the present study to clarify that issue and throw some lights on other potential risk factors in Down ...

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.

Associations between depressive syndromes and HIV risk behaviors among San Francisco men who have sex with men.

Science.gov (United States)

Chen, Yea-Hung; Raymond, Henry Fisher

2017-12-01

HIV prevention plans for men who have sex with men (MSM) are often multifaceted. They involve reduction of sexual risk behaviors, such as condomless intercourse, but also often include pharmaceutical approaches, such as early treatment of HIV-infected individuals with antiretroviral therapy (ART). Effectiveness is possibly threatened by individual-level factors, such as depression. In this study of 322 San Francisco MSM (240 HIV-uninfected individuals and 82 HIV-infected individuals, according to self-report), we examine associations between depressive syndromes and HIV risk behaviors (sexual risk behaviors and ART non-adherence). Our study failed to find evidence that depressive syndromes lead to increases in ART non-adherence (risk difference, RD: 27.9; 95% confidence interval, CI: -3.5, 59.3). However, the study does suggest an association between depressive syndromes and concurrence of non-adherence and potentially HIV-discordant condomless receptive anal intercourse (RD: 36.0; 95% CI: 5.2, 66.8). Among HIV-uninfected MSM, our study suggests negative associations between depressive syndromes and sexual risk behaviors. We recommend screening and treatment of depression among HIV-infected MSM.

Androgenetic alopecia as an indicator of metabolic syndrome and cardiovascular risk.

Science.gov (United States)

Ertas, Ragip; Orscelik, Ozcan; Kartal, Demet; Dogan, Ali; Ertas, Sule Ketenci; Aydogdu, Ebru Guler; Ascioglu, Ozcan; Borlu, Murat

2016-06-01

Numerous studies have investigated a probable association between androgenetic alopecia (AGA) and cardiovascular disease (CVD) by researching limited and dispersed parameters. We aimed to evaluate both traditional and non-traditional cardiovascular risk factors in male patients with early-onset AGA. This case-control study included 68 participants: 51 male patients with early-onset AGA and 17 healthy male controls. Patients with AGA were classified into three groups according to the Hamilton-Norwood scale and the presence of vertex hair loss. Traditional and non-traditional cardiovascular risk factors were examined in all study subjects. Metabolic syndrome was diagnosed in 25 patients with AGA and in two control subjects (p baldness and controls (p < 0.05). The pulse-wave velocity values were also found to be significantly higher in patients (p < 0.001). A limitation of this study was the small study population. In conclusion, vertex pattern AGA appears to be a marker for early atherosclerosis. This finding supports the hypothesis that early-onset AGA alone could be an independent risk factor for CVD and metabolic syndrome.

Frequency of conventional risk factors in patients with acute coronary syndrome in males and females

International Nuclear Information System (INIS)

Butt, Z.; Shahbaz, U.; Hashmi, A.T.; Naseem, T.; Khan, M.M.; Bukhari, M.H.

2010-01-01

Background: The frequency of conventional risk factors for acute coronary syndrome differs in women compared to men, both in the general population and in patients with acute coronary syndrome. Objective: To find out the frequency of conventional risk factors in patients with acute coronary syndrome in males and females that exists in Pakistani patient population. Design: Cross-sectional survey. Material and Methods: A total of one hundred patients with acute coronary syndrome who presented in the Cardiology Department, Mayo Hospital Lahore were interviewed between May, 2008 and March 2009. Patients were enquired about the presence of hypertension and diabetes mellitus. Information was also obtained regarding smoking and history of ischemic heart disease in their first degree relatives. Lipid profile was recorded from the investigation chart of every patient. Results: 91% of subjects had at least one risk factor out of four conventional factors. When comparing men and women, more women were hypertensive and diabetic (p = 0.003 and 0.009 respectively). None of the females had ever smoked as compared to 34% of males (P = <0.001). Conclusion: Women with acute coronary syndrome, when compared to men, have more prevalence of diabetes and hyper-tension, and less prevalence of smoking. Further research is needed to better understand the gender differences in various aspects of ischemic heart disease that exist in our population. (author)

The metabolic syndrome: validity and utility of clinical definitions for cardiovascular disease and diabetes risk prediction.

Science.gov (United States)

Cameron, Adrian

2010-02-01

The purpose of clinical definitions of the metabolic syndrome is frequently misunderstood. While the metabolic syndrome as a physiological process describes a clustering of numerous age-related metabolic abnormalities that together increase the risk for cardiovascular disease and type 2 diabetes, clinical definitions include obesity which is thought to be a cause rather than a consequence of metabolic disturbance, and several elements that are routinely measured in clinical practice, including high blood pressure, high blood glucose and dyslipidaemia. Obesity is frequently a central player in the development of the metabolic syndrome and should be considered a key component of clinical definitions. Previous clinical definitions have differed in the priority given to obesity. Perhaps more importantly than its role in a clinical definition, however, is obesity in isolation before the hallmarks of metabolic dysfunction that typify the syndrome have developed. This should be treated seriously as an opportunity to prevent the consequences of the global diabetes epidemic now apparent. Clinical definitions were designed to identify a population at high lifetime CVD and type 2 diabetes risk, but in the absence of several major risk factors for each condition, are not optimal risk prediction devices for either. Despite this, the metabolic syndrome has several properties that make it a useful construct, in conjunction with short-term risk prediction algorithms and sound clinical judgement, for the identification of those at high lifetime risk of CVD and diabetes. A recently published consensus definition provides some much needed clarity about what a clinical definition entails. Even this, however, remains a work in progress until more evidence becomes available, particularly in the area of ethnicity-specific waist cut-points. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Association of lifestyle risk factors with metabolic syndrome components: A cross-sectional study in Eastern India

Directory of Open Access Journals (Sweden)

Pragya Verma

2018-01-01

Full Text Available Background: Approximately 20%–25% of the world adult population and nearly 30% of Indians have metabolic syndrome disorder. Our objective was designed to find out the association between important nutrients and potential lifestyle risk factors such as diet, physical inactivity, and smoking and alcohol consumption with the number of metabolic syndrome components. Methods: This was a cross-sectional study. A total of 205 patients of metabolic syndrome were enrolled for this study. Diagnosis of metabolic syndrome was done on the basis of National Cholesterol Education Program Adult Treatment Panel III criteria (NCEP ATP III 2004.Dietary data were collected with the validated food frequency questionnaire and 24 h dietary recall method, and the nutrient intake was calculated with the specially designed software. Results: Unhealthy dietary habits were seen more among the participants who had more than 3 risk factors. Results showed the odds of taking> 5 times junk foods was 3 times higher (odds ratio [OR]: 2.97; 95% confidence interval [CI]: 1.61–5.47, and sweet dishes was 2.3 times higher (OR: 2.33; 95% CI: 1.28–4.24 among the participants who had 4–5 risk factors. However, milk and dairy products > 4 servings/day (OR: 0.54; 95% CI: 0.175–1.67 and pulses and legumes more than 2 servings/day (OR: 0.57; 95% CI: 0.25–1.29 was protective against hypertension. Mean carbohydrate, saturated fat, and sodium intake was significantly higher in the participants who had 4–5 metabolic risk factors compared to 3 risk factors (P < 0.0001. Conclusions: It was concluded that low intake of fruits, vegetables, and higher intake of flesh food and inadequate physical activity significantly associated with the metabolic syndrome risk factors.

Validating diagnoses from hospital discharge registers change risk estimates for acute coronary syndrome

DEFF Research Database (Denmark)

Joensen, Albert Marni; Schmidt, E.B.; Dethlefsen, Claus

2007-01-01

of acute coronary syndrome (ACS) diagnoses identified in a hospital discharge register changed the relative risk estimates of well-established risk factors for ACS. Methods All first-time ACS diagnoses (n=1138) in the Danish National Patient Registry were identified among male participants in the Danish...

Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts in Preventing GVHD in Children

Science.gov (United States)