WorldWideScience

Sample records for high risk myelodysplastic

  1. 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

    PURPOSE: Promoter hypermethylation of, for example, tumor-suppressor genes, is considered to be an important step in cancerogenesis and a negative risk factor for survival in patients with myelodysplastic syndromes (MDS); however, its role for response to therapy has not been determined. This study...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Background Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ...... hybridization for del(5q31). DESIGN AND METHODS: Twenty-eight patients at diagnosis or with relapsed disease and not eligible for standard therapy (16 with acute myeloid leukemia, 12 with intermediate-risk 2 or high-risk myelodysplastic syndrome) were enrolled in this prospective phase II multicenter trial...

  3. Bone marrow dendritic cells are reduced in patients with high-risk myelodysplastic syndromes.

    Science.gov (United States)

    Saft, Leonie; Björklund, Elisabet; Berg, Elisabeth; Hellström-Lindberg, Eva; Porwit, Anna

    2013-03-01

    Dendritic cells (DC) are antigen-presenting cells that play a pivotal role in coordinating functions of the immune system. Previous studies suggest that bone marrow (BM) failure in myelodysplastic syndromes (MDS) may be in part immune-mediated, and that the high propensity for relapse may reflect decreased immune surveillance. This study aimed to assess the frequency of DC in BM samples from well-annotated untreated MDS patients by using 4-colour flow cytometry. DC levels were markedly reduced in all subtypes of MDS. The clinical impact of this finding on therapy response and relapse after, e.g. allogeneic stem cell transplantation warrants further investigation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. ID4 methylation predicts high risk of leukemic transformation in patients with myelodysplastic syndrome.

    Science.gov (United States)

    Wang, Hong; Wang, Xiao-Qin; Xu, Xiao-Ping; Lin, Guo-Wei

    2010-05-01

    Epigenetic gene silencing due to promoter methylation is observed in human cancers like acute myeloid leukemia (AML). Little is known about aberrant methylation in myelodysplastic syndrome (MDS), a heterogeneous clonal stem cell disorder with a approximately 30% risk of transformation into secondary AML. Recent evidence demonstrated that ID4, a negative regulator of transcription, may act as a tumor-suppressor gene. To clarify the role of ID4 in MDS, we employed methylation-specific PCR (MSP) to examine the methylation status of ID4 in 144 adult de novo MDS patients. We found that ID4 methylation was present in 35.4% (n=51) of these MDS patients and methylaiton was correlated significantly with World Health Organization (WHO) subtypes and International Prognostic Scoring System (IPSS) risk groups. Patients with advanced stages of WHO subtypes (45.8% vs. 21.3%, P=0.002) and higher risk IPSS subgroups (45.7% vs. 26.0%, P=0.014) exhibited a significantly higher frequency of ID4 methylation. The median survival of patients with ID4 methylation was shorter than patients without ID4 methylation (12.2 months vs. 26.9 months, P=0.005). Multivariate analysis indicated that ID4 methylation status was the independent factor that impacted leukemia-free survival (LFS). Disease in patients with ID4 methylation progressed more rapidly than those without ID4 methylation (P=0.047, HR=2.11). Our results suggest that ID4 may be a therapeutic target in MDS. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction...

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

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    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....

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

    Science.gov (United States)

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

    2017-12-01

    Karyotype according to the revised IPSS is a strong independent prognostic factor for overall survival (OS) in myelodysplastic syndromes (MDS), however established in untreated patients. The prognostic impact of cytogenetics and cytogenetic response (CyR) in MDS patients receiving azacitidine (AZA) remains uncertain. We examined the prognostic value of baseline cytogenetics and CyR for overall response rate (ORR) and OS in 702 AZA-treated higher risk MDS and low blast count acute myeloid leukemia (AML), including 493 (70%) with abnormal karyotype. None of the cytogenetic abnormalities had significant impact on ORR (43.9%) or complete response (15.35%), except 3q abnormalities and complex karyotypes, which were associated with a lower ORR. OS differed significantly across all R-IPSS cytogenetic subgroups (pimpact 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.

  8. 7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

    Science.gov (United States)

    2013-09-27

    Accelerated Phase Chronic Myelogenous 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; Myelodysplastic/Myeloproliferative Neoplasms; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  9. Identification and validation of the dopamine agonist bromocriptine as a novel therapy for high-risk myelodysplastic syndromes and secondary acute myeloid leukemia.

    Science.gov (United States)

    Liberante, Fabio Giuseppe; Pouryahya, Tara; McMullin, Mary-Frances; Zhang, Shu-Dong; Mills, Kenneth Ian

    2016-02-09

    Myelodysplastic syndromes (MDS) represent a broad spectrum of diseases characterized by their clinical manifestation as one or more cytopenias, or a reduction in circulating blood cells. MDS is predominantly a disease of the elderly, with a median age in the UK of around 75. Approximately one third of MDS patients will develop secondary acute myeloid leukemia (sAML) that has a very poor prognosis. Unfortunately, most standard cytotoxic agents are often too toxic for older patients. This means there is a pressing unmet need for novel therapies that have fewer side effects to assist this vulnerable group. This challenge was tackled using bioinformatic analysis of available transcriptomic data to establish a gene-based signature of the development and progression of MDS. This signature was then used to identify novel therapeutic compounds via statistically-significant connectivity mapping. This approach suggested re-purposing an existing and widely-prescribed drug, bromocriptine as a novel potential therapy in these disease settings. This drug has shown selectivity for leukemic cells as well as synergy with current therapies.

  10. There’s Risk, and Then There’s RISK: The Latest Clinical Prognostic Risk Stratification Models in Myelodysplastic Syndromes

    OpenAIRE

    Zeidan, Amer M.; Komrokji, Rami S.

    2013-01-01

    Myelodysplastic syndromes (MDS) include a diverse group of clonal hematopoietic disorders characterized by progressive cytopenias and propensity for leukemic progression. The biologic heterogeneity that underlies MDS translates clinically in wide variations of clinical outcomes. Several prognostic schemes were developed to predict the natural course of MDS, counsel patients, and allow evidence-based, risk-adaptive implementation of therapeutic strategies. The prognostic schemes divide patient...

  11. High response rate and improved exercise capacity and quality of life with a new regimen of darbepoetin alfa with or without filgrastim in lower-risk myelodysplastic syndromes: a phase II study by the GFM.

    Science.gov (United States)

    Kelaidi, C; Beyne-Rauzy, O; Braun, T; Sapena, R; Cougoul, P; Adès, L; Pillard, F; Lamberto, C; Lambert, C; Charniot, J C; Guerci, A; Choufi, B; Stamatoullas, A; Slama, B; De Renzis, B; Ame, S; Damaj, G; Boyer, F; Chaury, M P; Legros, L; Cheze, S; Testu, A; Gyan, E; Béné, M C; Rose, C; Dreyfus, F; Fenaux, P

    2013-05-01

    Darbepoetin (DAR), with or without granulocyte colony-stimulating factor (G-CSF), has proved effective in treating anemia in patients with lower-risk myelodysplastic syndrome (MDS), but its effects on quality of life (QoL) and exercise functioning are less well established. In this phase II study (no. NCT00443339), lower-risk MDS patients with anemia and endogenous erythropoietin (EPO) level <500 IU/L received DAR 500 μg once every 2 weeks for 12 weeks, with G-CSF added at week 12 in non-responders. Physical performance was assessed with the 6-min walking test and, for fit patients, maximal oxygen consumption (VO2max). QoL was evaluated using SF-36 and FACT-An tests. In 99 patients, erythroid response rate according to IWG 2006 criteria was 48 and 56 % at 12 and 24 weeks, respectively. Addition of G-CSF rescued 22 % of non-responders. In 48 % of the responders, interval between darbepoetin injections could be increased for maintenance treatment. Serum EPO level was the only independent predictive factor of response at 12 weeks, and its most discriminant cutoff value was 100 IU/L. QoL and VO2max showed improvement over time in responders, compared with non-responders. With a median follow-up of 52 months, median response duration was not reached, and 3-year cumulative incidence of acute myeloid leukemia and overall survival (OS) was 14.5 and 70 %, respectively. Baseline transfusion dependence, International Prognostic Score System (IPSS), and Revised IPSS accurately predicted OS from treatment onset. Tolerance of darbepoetin was good. In conclusion, this regimen of darbepoetin every 2 weeks yielded high response rates and prolonged response duration. Objective improvement in exercise testing and in patient-reported QoL confirms the clinical relevance of anemia correction with erythropoiesis-stimulating agents.

  12. Myelodysplastic syndromes: 2011 update on diagnosis, risk-stratification, and management.

    Science.gov (United States)

    Garcia-Manero, Guillermo

    2011-06-01

    The myelodysplastic (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older male and in individuals with prior exposure to cytotoxic therapy. Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry, or molecular genetics is complementary but not diagnostic. RISK-STRATIFICATION: Prognosis of patients with MDS can be calculated using a number of scoring systems. In general, all these scoring systems include analysis of peripheral cytopenias, percentage of blasts in the bone marrow, and cytogenetic characteristics. The most commonly used system is the International Prognostic Scoring System. This score divides patients into a lower risk subset (low and intermediate-1) and a higher risk subset (int-2 and high). Other more modern systems have been developed that allow more precise risk calculation. Therapy is selected based on risk, transfusion needs, percent of bone marrow blasts and more recently cytogenetic profile. Goals of therapy are different in lower risk patients than in higher risk. In lower risk, the goal is to decrease transfusion needs and transformation to higher risk disease or AML. In higher risk, the goal is to prolong survival. Current available therapies include growth factor support, lenalidomide, hypomethylating agents, intensive chemotherapy, and allogeneic stem cell transplantation. The use of lenalidomide has significant clinical activity in patients with lower risk disease, anemia, and a chromosome 5 alteration. 5-azacitidine and decitabine have activity in higher risk MDS. 5-azacitidine has been shown to improve survival in higher risk MDS. Additional supportive care measures may include the use of prophylactic antibiotics and iron chelation

  13. Myelodysplastic/ Myeloproliferative Neoplasms Treatment

    Science.gov (United States)

    ... Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Myelodysplastic/ ...

  14. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group

    NARCIS (Netherlands)

    Lubbert, M.; Suciu, S.; Baila, L.; Ruter, B.H.; Platzbecker, U.; Giagounidis, A.; Selleslag, D.; Labar, B.; Germing, U.; Salih, H.R.; Beeldens, F.; Muus, P.; Pfluger, K.H.; Coens, C.; Hagemeijer, A.; Eckart Schaefer, H.; Ganser, A.; Aul, C.; Witte, T.J.M. de; Wijermans, P.W.

    2011-01-01

    PURPOSE: To compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy. PATIENTS AND METHODS: Two-hundred thirty-three patients (median age, 70 years; range, 60 to 90 years)

  15. Awareness of acute myeloid leukaemia risk induced by diagnosis of a myelodysplastic syndrome.

    Science.gov (United States)

    Ousseine, Youssoufa M; Butow, Phyllis N; Julian-Reynier, Claire; Dring, Rebecca; Festy, Patrick; Fenaux, Pierre; Vey, Norbert; Mancini, Julien

    2016-07-01

    Myelodysplastic syndromes (MDS) can evolve to acute myeloid leukaemia (AML) in approximately 30% of cases. Knowing their AML risk is important for patients because it might impact adherence to care and psychological health. The aim of this study was to evaluate the awareness of AML risk among MDS patients and to study the factors associated with this awareness. A self-administered questionnaire was mailed to all members of French and Australian patients' national MDS associations. Data of 301 patients were analysed. Patients were satisfied with the information they had received, but 33.2% did not know that they had an increased risk of developing AML. Younger age, higher-risk MDS treatment, preferences for health-related information and satisfaction with information provided about treatment were the factors independently associated with awareness of AML risk. Compared to unaware patients, patients knowing their risk were more likely to participate in a hypothetical clinical trial (83.0% vs 72.4%, p=0.043). More efforts are needed to provide more systematic information about AML risk to patients wishing to know it. More research is needed to study if increasing awareness can lead to more active engagement of MDS patients in their care and can increase the rate of clinical trial participation. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  16. Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome.

    Science.gov (United States)

    Deschler, Barbara; Ihorst, Gabriele; Platzbecker, Uwe; Germing, Ulrich; März, Eva; de Figuerido, Marcelo; Fritzsche, Kurt; Haas, Peter; Salih, Helmut R; Giagounidis, Aristoteles; Selleslag, Dominik; Labar, Boris; de Witte, Theo; Wijermans, Pierre; Lübbert, Michael

    2013-02-01

    Myelodysplastic syndromes and acute myeloid leukemia exemplify the complexity of treatment allocation in older patients as options range from best supportive care, non-intensive treatment (e.g. hypomethylating agents) to intensive chemotherapy/hematopoietic cell transplantation. Novel metrics for non-disease variables are urgently needed to help define the best treatment for each older patient. We investigated the feasibility and prognostic value of geriatric/quality of life assessments aside from established disease-specific variables in 195 patients aged 60 years or over with myelodysplastic syndromes/acute myeloid leukemia. These patients were grouped according to treatment intensity and assessed. Assessment consisted of eight instruments evaluating activities of daily living, depression, mental functioning, mobility, comorbidities, Karnofsky Index and quality of life. Patients with a median age of 71 years (range 60-87 years) with myelodysplastic syndromes (n=63) or acute myeloid leukemia (n=132) were treated either with best supportive care (n=47), hypomethylating agents (n=73) or intensive chemotherapy/hematopoietic cell transplantation (n=75). After selection of variables, pathological activities of daily living and quality of life/fatigue remained highly predictive for overall survival in the entire patient group beyond disease-related risk factors adverse cytogenetics and blast count of 20% or over. In 107 patients treated non-intensively activities of daily living of less than 100 (hazard ratio, HR 2.94), Karnofsky Index below 80 (HR 2.34) and quality of life/'fatigue' of 50 or over (HR 1.77) were significant prognosticators. Summation of adverse features revealed a high risk of death (HR 9.36). In-depth evaluation of older patients prior to individual treatment allocation is feasible and provides additional information to standard assessment. Patients aged 60 years or over with newly diagnosed myelodysplastic syndromes/acute myeloid leukemia and

  17. Improved risk stratification by the integration of the revised international prognostic scoring system with the myelodysplastic syndromes comorbidity index.

    Science.gov (United States)

    van Spronsen, M F; Ossenkoppele, G J; Holman, R; van de Loosdrecht, A A

    2014-12-01

    Myelodysplastic syndromes (MDS) comprise bone marrow failure diseases with a diverse clinical outcome. For improved risk stratification, the International Prognostic Scoring System (IPSS) has recently been revised (IPSS-R). This single-centre study aimed to validate the IPSS-R and to evaluate prior prognostic scoring systems for MDS. We retrospectively analysed 363 patients diagnosed with MDS according to the FAB criteria between 2000 and 2012. The IPSS, MD Anderson Risk Model Score (MDAS), World Health Organisation (WHO)-classification based Prognostic Scoring System (WPSS), refined WPSS (WPSS-R), IPSS-R and MDS-Comorbidity Index (MDS-CI) were applied to 222 patients considered with primary MDS following the WHO criteria and their prognostic power was investigated. According to the IPSS-R, 18 (8%), 81 (37%), 50 (23%), 43 (19%) and 30 (13%) patients were classified as very low, low, intermediate, high and very high risk with, respectively, a median overall survival of 96 (95% Confidence interval (CI) not reached), 49 (95% CI 34-64), 22 (95% CI 0-49), 19 (95% CI 11-27) and 10 (95% CI 6-13) months (pMDS-CI refined the risk stratification of MDS patients stratified according to the IPSS-R. In conclusion, accounting for the disease status by means of the IPSS-R and comorbidity through the MDS-CI considerably improves the prognostic assessment in MDS patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression.

    Science.gov (United States)

    Jädersten, Martin; Saft, Leonie; Smith, Alexander; Kulasekararaj, Austin; Pomplun, Sabine; Göhring, Gudrun; Hedlund, Anette; Hast, Robert; Schlegelberger, Brigitte; Porwit, Anna; Hellström-Lindberg, Eva; Mufti, Ghulam J

    2011-05-20

    To determine the frequency of TP53 mutations and the level of p53 protein expression by immunohistochemistry (IHC) in low-risk myelodysplastic syndromes (MDS) with del(5q) and to assess their impact on disease progression. Pre- and postprogression bone marrow (BM) samples from 55 consecutive patients with International Prognostic Scoring System low risk (n = 32) or intermediate-1 risk (n = 23) were studied by next-generation sequencing of TP53. IHC for p53 was performed on 148 sequential BM samples. TP53 mutations with a median clone size of 11% (range, 1% to 54%) were detected in 10 patients (18%) already at an early phase of the disease. Mutations were equally common in low-risk and intermediate-1-risk patients and were associated with evolution to acute myeloid leukemia (5 of 10 v 7 of 45; P = .045). Nine of 10 patients carrying mutations showed more than 2% BM progenitors with strong p53 staining. The probability of a complete cytogenetic response to lenalidomide was lower in mutated patients (0 of 7 v 12 of 24; P = .024). By using sensitive deep-sequencing technology, we demonstrated that TP53 mutated populations may occur at an early disease stage in almost a fifth of low-risk MDS patients with del(5q). Importantly, mutations were present years before disease progression and were associated with an increased risk of leukemic evolution. TP53 mutations could not be predicted by common clinical features but were associated with p53 overexpression. Our findings indicate a previously unrecognized heterogeneity of the disease which may significantly affect clinical decision making.

  19. Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

    Science.gov (United States)

    ... Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Myelodysplastic/ ...

  20. Myelodysplastic syndromes: 2015 Update on diagnosis, risk-stratification and management.

    Science.gov (United States)

    Garcia-Manero, Guillermo

    2015-09-01

    The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy. Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry, or molecular genetics is complementary but not diagnostic. Risk-stratification: Prognosis of patients with MDS can be calculated using a number of scoring systems. In general, all these scoring systems include analysis of peripheral cytopenias, percentage of blasts in the bone marrow, and cytogenetic characteristics. The most commonly used system still is probably the International Prognostic Scoring System (IPSS). IPSS is being replaced by the new revised score IPSS-R. Therapy is selected based on risk, transfusion needs, percent of bone marrow blasts, and more recently cytogenetic and mutational profiles. Goals of therapy are different in lower risk patients than in higher risk. In lower risk, the goal is to decrease transfusion needs and transformation to higher risk disease or AML, as well as to improve survival. In higher risk, the goal is to prolong survival. Current available therapies include growth factor support, lenalidomide, hypomethylating agents, intensive chemotherapy, and allogeneic stem cell transplantation. The use of lenalidomide has significant clinical activity in patients with lower risk disease, anemia, and a chromosome 5 alteration. 5-Azacitidine and decitabine have activity in higher risk MDS. 5-Azacitidine has been shown to improve survival in higher risk MDS. A number of new molecular lesions have been described in MDS that may serve as new therapeutic targets or aid in the selection of currently available agents. Additional

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

    Science.gov (United States)

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

    2017-11-08

    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

  2. Comparison of risk stratification tools in predicting outcomes of patients with higher-risk myelodysplastic syndromes treated with azanucleosides.

    Science.gov (United States)

    Zeidan, A M; Sekeres, M A; Garcia-Manero, G; Steensma, D P; Zell, K; Barnard, J; Ali, N A; Zimmerman, C; Roboz, G; DeZern, A; Nazha, A; Jabbour, E; Kantarjian, H; Gore, S D; Maciejewski, J P; List, A; Komrokji, R

    2016-03-01

    Established prognostic tools in patients with myelodysplastic syndromes (MDS) were largely derived from untreated patient cohorts. Although azanucleosides are standard therapies for higher-risk (HR)-MDS, the relative prognostic performance of existing prognostic tools among patients with HR-MDS receiving azanucleoside therapy is unknown. In the MDS Clinical Research Consortium database, we compared the prognostic utility of the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), MD Anderson Prognostic Scoring System (MDAPSS), World Health Organization-based Prognostic Scoring System (WPSS) and the French Prognostic Scoring System (FPSS) among 632 patients who presented with HR-MDS and were treated with azanucleosides as the first-line therapy. Median follow-up from diagnosis was 15.7 months. No prognostic tool predicted the probability of achieving an objective response. Nonetheless, all five tools were associated with overall survival (OS, P=0.025 for the IPSS, P=0.011 for WPSS and Pfront transplantation or experimental approaches.

  3. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study

    Science.gov (United States)

    Fenaux, Pierre; Mufti, Ghulam J; Hellstrom-Lindberg, Eva; Santini, Valeria; Finelli, Carlo; Giagounidis, Aristoteles; Schoch, Robert; Gattermann, Norbert; Sanz, Guillermo; List, Alan; Gore, Steven D; Seymour, John F; Bennett, John M; Byrd, John; Backstrom, Jay; Zimmerman, Linda; McKenzie, David; Beach, C L; Silverman, Lewis R

    2014-01-01

    Summary Background Drug treatments for patients with high-risk myelodysplastic syndromes provide no survival advantage. In this trial, we aimed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens. Methods In a phase III, international, multicentre, controlled, parallel-group, open-label trial, patients with higher-risk myelodysplastic syndromes were randomly assigned one-to-one to receive azacitidine (75 mg/m² per day for 7 days every 28 days) or conventional care (best supportive care, low-dose cytarabine, or intensive chemotherapy as selected by investigators before randomisation). Patients were stratified by French–American–British and international prognostic scoring system classifications; randomisation was done with a block size of four. The primary endpoint was overall survival. Efficacy analyses were by intention to treat for all patients assigned to receive treatment. This study is registered with ClinicalTrials.gov, number NCT00071799. Findings Between Feb 13, 2004, and Aug 7, 2006, 358 patients were randomly assigned to receive azacitidine (n=179) or conventional care regimens (n=179). Four patients in the azacitidine and 14 in the conventional care groups received no study drugs but were included in the intention-to-treat efficacy analysis. After a median follow-up of 21·1 months (IQR 15·1–26·9), median overall survival was 24·5 months (9·9–not reached) for the azacitidine group versus 15·0 months (5·6–24·1) for the conventional care group (hazard ratio 0·58; 95% CI 0·43–0·77; stratified log-rank p=0·0001). At last follow-up, 82 patients in the azacitidine group had died compared with 113 in the conventional care group. At 2 years, on the basis of Kaplan-Meier estimates, 50·8% (95% CI 42·1–58·8) of patients in the azacitidine group were alive compared with 26·2% (18·7–34·3) in the conventional care group (p<0·0001). Peripheral cytopenias were the most

  4. A randomized phase II trial of azacitidine +/− epoetin-β in lower-risk myelodysplastic syndromes resistant to erythropoietic stimulating agents

    Science.gov (United States)

    Thépot, Sylvain; Ben Abdelali, Raouf; Chevret, Sylvie; Renneville, Aline; Beyne-Rauzy, Odile; Prébet, Thomas; Park, Sophie; Stamatoullas, Aspasia; Guerci-Bresler, Agnes; Cheze, Stéphane; Tertian, Gérard; Choufi, Bachra; Legros, Laurence; Bastié, Jean Noel; Delaunay, Jacques; Chaury, Marie Pierre; Sanhes, Laurence; Wattel, Eric; Dreyfus, Francois; Vey, Norbert; Chermat, Fatiha; Preudhomme, Claude; Fenaux, Pierre; Gardin, Claude

    2016-01-01

    The efficacy of azacitidine in patients with anemia and with lower-risk myelodysplastic syndromes, if relapsing after or resistant to erythropoietic stimulating agents, and the benefit of combining these agents to azacitidine in this setting are not well known. We prospectively compared the outcomes of patients, all of them having the characteristics of this subset of lower-risk myelodysplastic syndrome, if randomly treated with azacitidine alone or azacitidine combined with epoetin-β. High-resolution cytogenetics and gene mutation analysis were performed at entry. The primary study endpoint was the achievement of red blood cell transfusion independence after six cycles. Ninety-eight patients were randomised (49 in each arm). Median age was 72 years. In an intention to treat analysis, transfusion independence was obtained after 6 cycles in 16.3% versus 14.3% of patients in the azacitidine and azacitidine plus epoetin-β arms, respectively (P=1.00). Overall erythroid response rate (minor and major responses according to IWG 2000 criteria) was 34.7% vs. 24.5% in the azacitidine and azacitidine plus epoetin-β arms, respectively (P=0.38). Mutations of the SF3B1 gene were the only ones associated with a significant erythroid response, 29/59 (49%) versus 6/27 (22%) in SF3B1 mutated and unmutated patients, respectively, P=0.02. Detection of at least one “epigenetic mutation” and of an abnormal single nucleotide polymorphism array profile were the only factors associated with significantly poorer overall survival by multivariate analysis. The transfusion independence rate observed with azacitidine in this lower-risk population, but resistant to erythropoietic stimulating agents, was lower than expected, with no observed benefit of added epoetin, (clinicaltrials.gov identifier: 01015352). PMID:27229713

  5. Treatment Options for Myelodysplastic/Myeloproliferative Neoplasms

    Science.gov (United States)

    ... Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Myelodysplastic/ ...

  6. General Information about Myelodysplastic/Myeloproliferative Neoplasms

    Science.gov (United States)

    ... Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Myelodysplastic/ ...

  7. Treatment Option Overview (Myelodysplastic/Myeloproliferative Neoplasms)

    Science.gov (United States)

    ... Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Myelodysplastic/ ...

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

    Science.gov (United States)

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

    2016-10-01

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

  9. Multicenter comparison of CD34+ myeloid cell count by flow cytometry in low-risk myelodysplastic syndrome. Is it feasible?

    Science.gov (United States)

    Font, Patricia; Subirá, Dolores; Matarraz, Sergio; Benavente, Celina; Cedena, María Teresa; Morado, Marta; Pérez Corral, Ana; Bellón, José María; Díez-Martín, José Luis

    2017-06-15

    Accuracy of bone marrow (BM) blast count in low-risk myelodysplastic syndromes (MDS) still remains a challenge though it is essential for prognosis. We investigated whether the enumeration of CD34+ myeloid cells by flow cytometry immunophenotyping (FCI) could be used as a consistent parameter for clinical MDS studies. Six clinical centers entered the study and information on their FCI protocols was recorded. Sixty-seven flow cytometry listmodes from BM samples of patients with low-risk MDS with debris/aggregates. The frequency of discordant results increased with the accumulation of pitfalls (none, 16%; 1 pitfall, 40%; 2 pitfalls, 83%; P = 0.006). Finally, the use of a common gating strategy for analysis increased the percentage of files with "very good" agreement to 100%. Prevention of specific technical pitfalls is mandatory to reach a good reproducibility of CD34+ cell count among centers. These recommendations set the basis for laboratory standardization and enable the use of CD34+ cell enumeration as additional information in low-risk MDS patients. © 2017 International Clinical Cytometry Society. © 2017 International Clinical Cytometry Society.

  10. Smoking and alcohol and subsequent risk of myelodysplastic syndromes in Japan: the Japan Public Health Centre-based Prospective Study.

    Science.gov (United States)

    Ugai, Tomotaka; Matsuo, Keitaro; Sawada, Norie; Iwasaki, Motoki; Yamaji, Taiki; Shimazu, Taichi; Sasazuki, Shizuka; Inoue, Manami; Kanda, Yoshinobu; Tsugane, Shoichiro

    2017-09-01

    Smoking and alcohol are important modifiable risk factors for human cancers. However, few epidemiological studies have investigated their association with the risk of myelodysplastic syndromes (MDS). Here, we investigated the association of smoking and alcohol consumption and the risk of MDS in a large-scale population-based cohort study in Japan. We included 95 510 Japanese subjects (45 451 men and 50 059 women; age 40-69 years at baseline) and identified 70 MDS cases (50 men and 20 women) during 18·3 years of follow-up. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated using a Cox regression model adjusted for potential confounders. Smoking was marginally associated with an increased risk of MDS among men, with a HR for current smokers relative to never smokers of 2·11 (95% CI: 0·91-4·89). In contrast, alcohol consumption was associated with a dose-dependent decrease in the risk of MDS among men (nondrinkers: reference, occasional drinkers: HR = 0·48, 0·16-1·41; 0-299 g/week: HR = 0·37, 0·19-0·73; ≥300 g/week: HR = 0·49, 0·22-1·08, P for trend = 0·010). This study showed that alcohol has a significant protective effect on the risk of MDS. In addition, this study might indicate that smoking increases the risk of MDS among Japanese population, as it does in Western populations. © 2017 John Wiley & Sons Ltd.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Alexandra Søgaard Helbo

    2015-10-01

    Full Text Available 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 and silencing of the non-coding RNA VTRNA2-1 are correlated with poor outcomes in acute myeloid leukemia patients. In this study, we find that VTRNA1-2 and VTRNA1-3, both located on chromosome 5q, can be regulated and silenced by promoter DNA methylation, and that the hypomethylating agent 5-aza-2-deoxycytidine 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.

  13. Numerical chromosomal changes and risk of development of myelodysplastic syndrome--acute myeloid leukemia in patients with Fanconi anemia.

    Science.gov (United States)

    Mehta, Parinda A; Harris, Richard E; Davies, Stella M; Kim, Mi-Ok; Mueller, Robin; Lampkin, Beatrice; Mo, Jun; Myers, Kasiani; Smolarek, Teresa A

    2010-12-01

    Fanconi Anemia (FA) is an inherited bone marrow failure syndrome characterized by congenital abnormalities, progressive marrow failure and predisposition to myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and solid tumors. The most common acquired chromosomal aberrations in FA patients are trisomy of 1q and monosomy of chromosome 7; the latter is known to be associated with poor prognosis. A few reports also suggest that gains of 3q are associated with progression to MDS-AML and overall poor prognosis. It is not uncommon for patients with Fanconi anemia to have easily detectable (oligoclonal) chromosomal alterations in their still normal (nonmalignant) marrow, which makes it even more challenging to determine the import of such alterations. We conducted a retrospective longitudinal analysis of fluorescent in situ hybridization (FISH) analysis for gains in 1q and 3q and for monosomy 7 and 7q deletions on 212 bone marrow samples from 77 children with FA treated at our institution between 1987 and 2007. Given the baseline increased chromosomal instability and defective DNA repair in patients with FA, which leads to unbalanced chromosomal aberrations such as deletions, insertions, and translocations, for the purpose of this analysis an abnormal clone was defined as ≥10% abnormal cells. Chromosome 3 and 7 aberrations were associated with increased risk of developing MDS-AML (P = 0.019 and P < 0.001 respectively), although the significance of chromosome 3 aberrations disappeared when different observation times were accounted for. Gain of 1q alone did not predict development of MDS-AML. In conclusion, children with FA should be followed closely with FISH analyses, because some of the clonal chromosomal abnormalities may be early indicators of progression toward MDS-AML and thus also of the need for hematopoietic stem cell transplantation. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Value of infliximab (Remicade®) in patients with low-risk myelodysplastic syndrome: final results of a randomized phase II trial (EORTC trial 06023) of the EORTC Leukemia Group.

    Science.gov (United States)

    Baron, Frédéric; Suciu, Stefan; Amadori, Sergio; Muus, Petra; Zwierzina, Heinz; Denzlinger, Claudio; Delforge, Michel; Thyss, Antoine; Selleslag, Dominik; Indrak, Karel; Ossenkoppele, Gert; de Witte, Theo

    2012-04-01

    Tumor-necrosis factor alpha activity has been correlated to ineffective erythropoiesis in lower risk myelodysplastic syndromes. Infliximab (Remicade(®)) is an anti-tumor necrosis factor alpha chimeric antibody that is used in the treatment of patients with rheumatoid arthritis or Crohn's disease. Forty-six patients with myelodysplastic syndromes and a relatively low risk of developing acute leukemia were included in a randomized phase II study assessing the therapeutic activity of two dosages of infliximab administration (3 mg/kg vs. 5 mg/kg). The primary end point was the response rate. Responses were observed in 3 of 22 patients (13.1%) randomized to the 3 mg/kg arm, versus 0 of 21 patients randomized in the 5 mg/kg arm. According to the statistical design of the current study, neither of the two infliximab dose schedules tested showed sufficient activity as a single agent in this cohort of unselected patients with early myelodysplastic syndrome.

  15. Incidence of the myelodysplastic syndromes using a novel claims-based algorithm: high number of uncaptured cases by cancer registries.

    Science.gov (United States)

    Cogle, Christopher R; Craig, Benjamin M; Rollison, Dana E; List, Alan F

    2011-06-30

    The myelodysplastic syndromes (MDSs) are hematologically diverse hematopoietic stem cell malignancies primarily affecting older individuals. The incidence of MDS in the United States is estimated at 3.3 per 100 000; however, evidence suggests underreporting of MDS to centralized cancer registries. Contrary to clinical recommendations, registry guidelines from 2001-2010 required the capture of only one malignancy in the myeloid lineage and did not require blood count (BC) or bone marrow (BM) biopsy for MDS confirmation. To address these potential limitations, we constructed 4 claims-based algorithms to assess MDS incidence, applied the algorithms to the 2000-2008 Surveillance Epidemiology and End Results (SEER)-Medicare database, and assessed algorithm validity using SEER-registered MDS cases. Each algorithm required one or more MDS claims and accounted for recommended diagnostic services during the year before the first claim: 1+, 2+, 2 + BC, and 2 + BCBM (ordered by sensitivity). Each had moderate sensitivities (78.05%-92.90%) and high specificities (98.49%-99.84%), with the 2 + BCBM algorithm demonstrating the highest specificity. Based on the 2 + BCBM algorithm, the annual incidence of MDS is 75 per 100 000 persons 65 years or older-much higher than the 20 per 100 000 reported by SEER using the same sample.

  16. Value of infliximab (Remicade(R)) in patients with low-risk myelodysplastic syndrome: final results of a randomized phase II trial (EORTC trial 06023) of the EORTC Leukemia Group.

    NARCIS (Netherlands)

    Baron, F.; Suciu, S.; Amadori, S.; Muus, P.; Zwierzina, H.; Denzlinger, C.; Delforge, M.; Thyss, A.; Selleslag, D.; Indrak, K.; Ossenkoppele, G.; Witte, T.J. de

    2012-01-01

    Tumor-necrosis factor alpha activity has been correlated to ineffective erythropoiesis in lower risk myelodysplastic syndromes. Infliximab (Remicade((R))) is an anti-tumor necrosis factor alpha chimeric antibody that is used in the treatment of patients with rheumatoid arthritis or Crohn's disease.

  17. Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS)

    OpenAIRE

    Mailankody, Sham; Pfeiffer, Ruth M.; Kristinsson, Sigurdur Y.; Korde, Neha; Bjorkholm, Magnus; Goldin, Lynn R.; Turesson, Ingemar; Landgren, Ola

    2011-01-01

    Using population-based data from Sweden, we identified all multiple myeloma (MM) patients (n = 8740) and 5652 monoclonal gammopathy of undetermined significance (MGUS) patients diagnosed between 1986 and 2005. We calculated standardized incidence rates (SIRs) for all subsequent hematologic and nonhematologic malignancies for MM patients diagnosed before/after 1995 (introduction of high-dose melphalan/autologous stem cell transplantation [HDM-ASCT]) and 2000 (introduction of immunomodulatory d...

  18. Immune Mechanisms in Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

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

    2016-01-01

    Myelodysplastic syndrome (MDS) is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive sequencing efforts have revealed a range of mutations characteristic, but not specific, of MDS. Epidemiologically, autoimmune......-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...

  19. MYELODYSPLASTIC/MYELOPROLIFERATIVE DISEASES

    OpenAIRE

    I. N. Subortseva; A. I. Melikyan

    2016-01-01

    Chronic myeloid malignancies that have characteristics of both the myelodysplastic and myeloproliferative disorders allocated to myelodysplastic/myeloproliferative diseases (MDS/MPD) group in 2008 World Health Organization classification. This group includes chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical chronic myeloid leukemia, refractory anemia with ringed sideroblasts and thrombocytosis (RARS-T) and unclassified MDS/MPD. Except RARS-T diseases in this group ha...

  20. MYELODYSPLASTIC/MYELOPROLIFERATIVE DISEASES

    Directory of Open Access Journals (Sweden)

    I. N. Subortseva

    2016-01-01

    Full Text Available Chronic myeloid malignancies that have characteristics of both the myelodysplastic and myeloproliferative disorders allocated to myelodysplastic/myeloproliferative diseases (MDS/MPD group in 2008 World Health Organization classification. This group includes chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical chronic myeloid leukemia, refractory anemia with ringed sideroblasts and thrombocytosis (RARS-T and unclassified MDS/MPD. Except RARS-T diseases in this group have similar molecular characteristics and clinical manifestations, which require the study of biology, specific molecular markers, morphological features and a clearer definition of nosology. This review provides information on international guidelines for the diagnosis and treatment of MDS/MPD.

  1. Acquisition of cytogenetic abnormalities in patients with IPSS defined lower-risk myelodysplastic syndrome is associated with poor prognosis and transformation to acute myelogenous leukemia.

    Science.gov (United States)

    Jabbour, Elias; Takahashi, Koichi; Wang, Xuemei; Cornelison, A Megan; Abruzzo, Lynne; Kadia, Tapan; Borthakur, Gautam; Estrov, Zeev; O'Brien, Susan; Mallo, Mar; Wierda, William; Pierce, Sherry; Wei, Yue; Sole, Francisco; Chen, Rui; Kantarjian, Hagop; Garcia-Manero, Guillermo

    2013-10-01

    We hypothesized that the dynamic acquisition of cytogenetic abnormalities (ACA) during the follow up of myelodysplastic syndromes (MDS) could be associated with poor prognosis. We conducted a retrospective analysis of 365 patients with IPSS low or intermediate-1 risk MDS who had at least two consecutive cytogenetic analyses during the follow up. Acquisition of cytogenetic abnormalities was detected in 107 patients (29%). The most frequent alteration involved chromosome 7 in 21% of ACA cases. Median transformation-free and overall survival for patients with and without ACA were 13 vs. 52 months (P = 0.01) and 17 vs. 62 months (P = 0.01), respectively. By fitting ACA as a time-dependent covariate, multivariate Cox regression analysis showed that patients with ACA had increased risk of transformation (HR = 1.40; P = 0.03) or death (HR = 1.45; P = 0.02). Notably, female patients with therapy-related MDS (t-MDS) had an increased risk of developing ACA (OR = 5.26; P < 0.0001), although subgroup analysis showed that prognostic impact of ACA was not evident in t-MDS. In conclusion, ACA occurs in close to one third of patients with IPSS defined lower risk MDS, more common among patients with t-MDS, but has a significant prognostic impact on de novo MDS. Copyright © 2013 Wiley Periodicals, Inc.

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

    OpenAIRE

    Dinara, ZHARLYGANOVA; Hironori, HARADA; Yuka, HARADA; Sergey, SHINKAREV; Zhaxybay, ZHUMADILOV; Aigul, ZHUNUSOVA; Naylya J., TCHAIZHUNUSOVA; Kazbek N., APSALIKOV; Vadim, KEMAIKIN; Kassym, ZHUMADILOV; Noriyuki, KAWANO; Akiro, KIMURA; Masaharu, HOSHI; State Research Center Institute of Biophysics, Federal Medical Biological Agency; Semipalatinsk State Medical Academy

    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...

  3. Thalidomide in Treating Patients With Myelodysplastic Syndrome

    Science.gov (United States)

    2013-01-23

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

  4. Immune Mechanisms in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Andreas Glenthøj

    2016-06-01

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

  5. [Myelodysplastic syndrome classification].

    Science.gov (United States)

    Ghariani, Ines; Braham, Najia; Hassine, Mohsen; Kortas, Mondher

    2013-01-01

    Myelodysplastic syndromes (MDS) are myeloid disorders with various clinical and biological presentations. The French-American-British (FAB-1982) classification included five categories basing on morphology and bone marrow blast count. Three criteria are taken into account: 1) the percentage of blasts in peripheral blood and bone marrow, 2) the percentage of ringed sideroblasts, and 3) the number of monocytes in peripheral blood. The World Health Organization classification (WHO 2001, 2008) modifies the FAB system by also taking cytogenetic characteristics and molecular biology into consideration. The last classification (WHO-2008) takes into account: 1) the number of peripheral cytopenia, 2) the percentage of blasts in peripheral blood and bone marrow, 3) the percentage of ringed sideroblasts, 4) the possible presence of Auer Rods, and 5) the detection of a cytogenetic abnormality (the isolated 5q deletion). The following subgroups are defined: refractory cytopenia with unilineage dysplasia, refractory anemia with ringed sideroblasts, refractory cytopenia with multilineage dysplasia, refractory anemia with excess blasts, myelodysplastic syndrome unclassifiable and myelodysplastic syndrome with isolated del(5q).

  6. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1–risk myelodysplastic syndrome and thrombocytopenia

    Science.gov (United States)

    Giagounidis, Aristoteles; Mufti, Ghulam J; Fenaux, Pierre; Sekeres, Mikkael A; Szer, Jeffrey; Platzbecker, Uwe; Kuendgen, Andrea; Gaidano, Gianluca; Wiktor-Jedrzejczak, Wieslaw; Hu, Kuolung; Woodard, Paul; Yang, Allen S; Kantarjian, Hagop M

    2014-01-01

    BACKGROUND Thrombocytopenia in patients with myelodysplastic syndrome (MDS) is associated with shortened survival and an increased risk of evolution to acute myeloid leukemia (AML). In this study, the authors evaluated the efficacy of romiplostim in patients who had thrombocytopenia with low-risk/intermediate-1–risk MDS. METHODS Patients who had thrombocytopenia with low-risk/intermediate-1–risk MDS (N = 250) were randomized 2:1 to receive romiplostim or placebo weekly for 58 weeks. RESULTS The primary endpoint— the number of clinically significant bleeding events (CSBEs) per patient—had a hazard ratio for romiplostim:placebo of 0.83 (95% confidence interval, 0.66-1.05; P = .13). CSBEs were reduced significantly in the romiplostim group for patients who had baseline platelet counts ≥20 × 109/L (P < .0001). For patients who had baseline platelet counts <20 × 109/L, there was no difference in the number of CSBEs, but the platelet transfusion rates were higher in the placebo group (P < .0001), which may have affected the overall CSBE results in this group with severe thrombocytopenia. The incidence of bleeding events was reduced significantly in the romiplostim group (relative risk, 0.92), as were protocol-defined platelet transfusions (relative risk, 0.77). Platelet response rates according to 2006 International Working Group criteria were higher for the group that received romiplostim (odds ratio, 15.6). On the basis of interim data, an independent data monitoring committee advised halting study drug because of concerns regarding excess blasts and AML rates with romiplostim (interim hazard ratio, 2.51). At 58 weeks, the AML rates were 6% in the romiplostim group and 4.9% in the placebo group (hazard ratio, 1.20; 95% confidence interval, 0.38-3.84), and the overall survival rates were similar. CONCLUSIONS Romiplostim treatment in patients with low-risk/intermediate-1–risk MDS increased platelet counts and decreased the number of

  7. Relapsed and secondary disease drive the risk profile for invasive aspergillosis prior to stem cell transplantation in patients with acute myeloid leukemia or myelodysplastic syndrome.

    Science.gov (United States)

    van de Peppel, Robert J; Dekkers, Olaf M; von dem Borne, Peter A; de Boer, Mark G J

    2014-10-01

    Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) are at risk for invasive aspergillosis (IA) even prior to the introduction of stem cell transplantation (SCT). In times of increasing triazole resistance and changing use of antifungal prophylaxis, insight into the risk factors for IA is needed to improve strategies for preventing IA in this population. Consecutive patients who received remission-induction therapy for AML or MDS at the Leiden Academic Medical Centre were included. Instead of standard antifungal prophylaxis, an assertive protocol for diagnosis of suspected fungal infection was in place. IA was classified according to the revised European Organization for Research and Treatment of Cancer criteria. Potential predisposing characteristics for IA were compared by uni- and multivariate analyses. In 45 (25%) of 184 included episodes (167 patients), IA was diagnosed prior to SCT. A multivariate Cox regression model demonstrated that relapsed AML (hazard ratio [HR] 2.4; 95% confidence interval [CI], 1.1-5.1; P = 0.02), secondary AML (HR, 5.2; 95% CI, 2.3-11.8; P < 0.001), and prolonged duration of neutropenia (HR, 2.2; 95% CI, 1.2-4.0; P = 0.01) were independently associated with IA. Use of granulocyte-colony-stimulating factor showed a trend toward a protective effect (HR, 0.37; 95% CI, 0.1-31.0; P = 0.06). Relapsed AML, secondary AML, and duration of neutropenia were independent factors for determining the risk for development of IA prior to SCT. The results provide further guidance for antifungal stewardship programs when integrating individual patient tailored decision making in antifungal prophylaxis strategies. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. [Myelodysplastic syndrome--classification, prognosis and therapy].

    Science.gov (United States)

    Cermák, J; Michalová, K; Vítek, A

    2002-09-22

    The impact of classification, prognostic factors and treatment on survival and rate of leukemic transformation was analysed in 197 patients with primary myelodysplastic syndrome (MDS) treated in the Institute of Hematology and Blood Transfusion in the years 1980-2000. The patients were classified according to the FAB criteria and divided into risk groups according to the International Prognostic Scoring System (IPSS). A separate evaluation of 34 patients who underwent stem cell transplantation and of 163 of those not transplanted was performed. Median survival of not transplanted patients with RAEB (10.0 months) and RAEB-T (12.0 months) was significantly shorter than survival of RA (62.4 months) and RARS (48.1 months, P MDS when compared with supportive care. On the contrary, median survival of transplanted patients with RAEB and RAEB-T was 38.4 months in comparison to 11.5 months in those not transplanted (P MDS. Stem cell transplantation had a significant beneficial effect on survival of patients with RAEB or RAEB-T as well as of patients included in intermediate II. or high risk subgroups. The impact of stem cell transplantation on survival of patients with RA or with low or intermediate I. risk was not significant. Therefore, further criteria should be taken in account for indication of stem cell transplantation in these subgroups of patients.

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

    Science.gov (United States)

    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.

  10. Defining incidence, risk factors, and impact on survival of central line-associated blood stream infections following hematopoietic cell transplantation in acute myeloid leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Lukenbill, Joshua; Rybicki, Lisa; Sekeres, Mikkael A; Zaman, Muhammad Omer; Copelan, Alexander; Haddad, Housam; Fraser, Thomas; DiGiorgio, Megan J; Hanna, Rabi; Duong, Hien; Hill, Brian; Kalaycio, Matt; Sobecks, Ronald; Bolwell, Brian; Copelan, Edward

    2013-05-01

    Central line-associated blood stream infections (CLABSI) commonly complicate the care of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic stem cell transplantation (HCT). We developed a modified CLABSI (MCLABSI) definition that attempts to exclude pathogens usually acquired because of disruption of mucosal barriers during the vulnerable neutropenic period following HCT that are generally included under the original definition (OCLABSI). We conducted a retrospective study of all AML and MDS patients undergoing HCT between August 2009 and December 2011 at the Cleveland Clinic (N = 73), identifying both OCLABSI and MCLABSI incidence. The median age at transplantation was 52 years (range, 16 to 70); 34 had a high (≥3) HCT comorbidity index (HCT-CI); 34 received bone marrow (BM), 24 received peripheral stem cells (PSC), and 15 received umbilical cord blood cells (UCB). Among these 73 patients, 23 (31.5%) developed OCLABSI, of whom 16 (69.6%) died, and 8 (11%) developed MCLABSI, of whom 7 (87.5%) died. OCLABSI was diagnosed a median of 9 days from HCT: 5 days (range, 2 to 12) for UCB and 78 days (range, 7 to 211) for BM/PSC (P CBC (P definition to replace the OCLABSI definition, given its greater precision for identifying preventable infection in HCT patients. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  11. Myelodysplastic syndromes: therapeutic problems and decisions (review

    Directory of Open Access Journals (Sweden)

    S. V. Semochkin

    2012-01-01

    Full Text Available Myelodysplastic syndromes (MDS are a group of heterogeneous clonal disorders of myeloid hematopoietic stem cells characterized by an ineffective hematopoiesis associated with cytopenias, morphologic dysplasia and a progression to acute myeloid leukemia. The only potentially curative MDS treatment is hematopoietic stem cell transplantation, which is usually not even discussed because most patients with advanced age at diagnosis. Currently only three drugs are approved by US Food and Drug Administration (FDA and European Medicines Agency for therapy of MDS. For low and intermediate-1 risk MDS del(5q the novel immunomodulatory drug lenalidomide is asserted, and for intermediate-2 and high risk the two hypomethylating agents (azacitidine, decitabine are approved. The results of completed clinical trials demonstrating the efficacy and safety of these agents are presented. The new data indicating that the successful future of MDS treatment rests in the combination of multiple treatments modalities to achieve improved clinical outcomes are discussed in this review.

  12. [Myelodysplastic syndromes: pathophysiology, clinical and biological features].

    Science.gov (United States)

    Becha, Mohamed; Braham Jmili, Néjia

    2015-01-01

    Myelodysplastic syndromes (MDS) are hemopathies very common in geriatric practice. They are characterized by qualitative morphological abnormalities of one or more myeloid lineages responsible for an ineffective hematopoiesis, and therefore cytopenias of central origin contrasting with a usually rich bone marrow wealth. The MDS are asymptomatic in half of the cases and their discovery is a result of systematic blood analysis or tests to explore another disease. The evolution is marked by worsening cytopenias, and the risk of acute myeloid leukemia transformation with poor prognosis because frequently chemoresistant. The diagnosis of MDS is pronounced after a clinico-biological confrontation to discuss the differential diagnosis taking into account all clinical and cytological data, results of conventional cytogenetics and evolution after vitamin therapy. Knowledge more depth on MDS refine MDS classification criteria by developing successive classifications (FAB 1982, WHO 2001 and 2008) which aim the identification of MDS groups with clinical, biological and common prognostic. The treatment of MDS is essentially symptomatic. The development of new targeted therapeutic strategies enables high hopes in a context where treatment options are a difficult choice, because the advanced age of most patients. Finally, detailed knowledge of risk factors and prognostic scores are very useful to make the best treatment decisions.

  13. 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; 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

  14. Therapy-related myelodysplastic syndrome.

    Science.gov (United States)

    Candelaria, Myrna; Dueñas-Gonzalez, Alfonso

    2015-05-01

    Myelodysplastic syndrome (MDS) is a heterogeneous clonal disorder characterized by deregulation of apoptosis, dysplastic features in hematopoietic precursors, peripheral blood cytopenias and an increased risk for transformation to acute leukemia. Roughly 20% of MDS are therapy related (t-MDS), and this is considered an independent adverse prognostic factor. This review based on a comprehensive literature search provides an overview on the main features of t-MDS, including its epidemiology, risk factors, molecular pathogenesis, prognostic classifications and therapy. Increasing evidence points out that the most important event in t-MDS is genetic alterations in hematopoietic stem precursor cells, however, ineffective hematopoiesis may also result from abnormalities in the bone marrow microenvironment. Thus, novel views onto the processes of t-MDS are needed such as the osteohematology concept. On the other hand, the number of people living with and beyond cancer is increasing worldwide; thus, most emphasis should be placed on preventing secondary malignancies such as t-MDS. From this review, it becomes clear that we are in urgent need not only to deepen our understanding of the leukemogenesis mechanisms induced by exposure to chemotherapy and radiation but also to translate this knowledge into clinical strategies aimed at risk reduction.

  15. Clonal evolution in myelodysplastic syndromes

    NARCIS (Netherlands)

    da Silva-Coelho, Pedro; Kroeze, Leonie I.; Yoshida, Kenichi; Koorenhof-Scheele, Theresia N.; Knops, Ruth; van de Locht, Louis T.; de Graaf, Aniek O.; Massop, Marion; Sandmann, Sarah; Dugas, Martin; Stevens-Kroef, Marian J.; Cermak, Jaroslav; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; de Witte, Theo; Blijlevens, Nicole M. A.; Muus, Petra; Huls, Gerwin; van der Reijden, Bert A.; Ogawa, Seishi; Jansen, Joop H.

    2017-01-01

    Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide

  16. 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.

    Science.gov (United States)

    Blommestein, Hedwig M; Armstrong, Nigel; Ryder, Steve; Deshpande, Sohan; Worthy, Gill; Noake, Caro; Riemsma, Rob; Kleijnen, Jos; Severens, Johan L; Al, Maiwenn J

    2016-01-01

    The 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 abnormality, as part of the Institute's single technology appraisal (STA) process. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company's submission, the ERG review, and the NICE's subsequent decisions. The ERG reviewed the evidence for clinical and cost effectiveness of the technology, as submitted by the manufacturer to the NICE. The ERG searched for relevant additional evidence and validated the manufacturer's decision analytic model to examine the robustness of the cost-effectiveness results. Clinical effectiveness was obtained from a three-arm, European, randomized, phase III trial among red blood cell (RBC) transfusion-dependent patients with low-/intermediate-1-risk del5q31 MDS. The primary endpoint was RBC independence for ≥26 weeks, and was reached by a higher proportion of patients in the lenalidomide 10 and 5 mg groups compared with placebo (56.1 and 42.6 vs 5.9 %, respectively; both p OS). The de novo model of the manufacturer included a Markov state-transition cost-utility model implemented in Microsoft Excel. The base-case incremental cost-effectiveness ratio (ICER) of the manufacturer was £56,965. The ERG assessment indicated that the modeling structure represented the course of the disease; however, a few errors were identified and some of the input parameters were challenged. In response to the appraisal documentation, the company revised the economic model, which increased the ICER to £68,125 per quality-adjusted life-year. The NICE Appraisal Committee (AC) did not recommend lenalidomide as a cost-effective treatment. Subsequently, the

  17. Hereditary Predispositions to Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Sarah A. Bannon

    2016-05-01

    Full Text Available Myelodysplastic syndromes (MDS are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA, dyskeratosis congenita (DC, Diamond–Blackfan anemia (DBA, and Shwachman–Diamond syndrome (SBS, hallmarked by clinically-recognizable phenotypes (e.g., radial ray anomalies in FA and significantly increased risks for MDS and/or acute myeloid leukemia (AML in the setting of bone marrow failure. However, additional families with multiple cases of MDS or AML have long been reported in the medical literature with little known regarding potential hereditary etiologies. Over the last decade, genomic investigation of such families has revealed multiple genes conferring inherited risks for MDS and/or AML as the primary malignancy, including RUNX1, ANKRD26, DDX41, ETV6, GATA2, and SRP72. As these syndromes are increasingly appreciated in even apparently de novo presentations of MDS, it is important for hematologists/oncologists to become familiar with these newly-described syndromes. Herein, we provide a review of familial MDS syndromes and practical aspects of management in patients with predisposition syndromes.

  18. GSTT1 and GSTM1 polymorphisms and myelodysplastic syndrome risk: a systematic review and meta-analysis.

    Science.gov (United States)

    Dahabreh, Issa J; Giannouli, Stavroula; Gota, Vaia; Voulgarelis, Michael

    2010-04-01

    Glutathione-S-transferace polymorphisms may make hematopoietic lineage cells susceptible to genotoxicity following exposure to heavy metals or benzene. We conducted a systematic review and meta-analysis to define the effect of GSTM1 and GSTT1 null polymorphisms on MDS risk. We searched the PubMed and SCOPUS databases to identify peer-reviewed published case-control studies investigating the association between GSTT1 and/or GSTM1 null genotypes and development of MDS. Between-study heterogeneity was assessed using Cochran's Q statistic and the I(2) statistic. Odds ratios from individual studies were pooled using fixed and random effects models. Thirteen studies were considered eligible for the GSTT1 meta-analysis (1471 cases, 1907 controls) and 10 were considered eligible for the GSTM1 meta-analysis (1161 cases, 1668 controls). For the GSTT1 polymorphism, there was moderate between study heterogeneity (p(Q) = 0.01; I(2) = 52.3%) and the null genotype was significantly associated with increased risk of MDS development, random effects OR = 1.43 (95% CI, 1.09-1.89); p = 0.01. For the GSTM1 polymorphisms there was moderate between-study heterogeneity (p = 0.07; I(2) = 43.1%) and the random effects OR = 1.02 (95% CI, 0.82-1.28) was non-significant (p = 0.85). The GSTT1 null genotype is a significant risk factor for MDS development. Gene-environment interactions need to be further explored.

  19. Standardization of flow cytometry in myelodysplastic syndromes: report from the first European LeukemiaNet working conference on flow cytometry in myelodysplastic syndromes

    Science.gov (United States)

    van de Loosdrecht, Arjan A.; Alhan, Canan; Béné, Marie Christine; Della Porta, Matteo G.; Dräger, Angelika M.; Feuillard, Jean; Font, Patricia; Germing, Ulrich; Haase, Detlef; Homburg, Christa H.; Ireland, Robin; Jansen, Joop H.; Kern, Wolfgang; Malcovati, Luca; te Marvelde, Jeroen G.; Mufti, Ghulam J.; Ogata, Kiyoyuki; Orfao, Alberto; Ossenkoppele, Gert J.; Porwit, Anna; Preijers, Frank W.; Richards, Stephen J.; Schuurhuis, Gerrit Jan; Subirá, Dolores; Valent, Peter; van der Velden, Vincent H.J.; Vyas, Paresh; Westra, August H.; de Witte, Theo M.; Wells, Denise A.; Loken, Michael R.; Westers, Theresia M.

    2009-01-01

    The myelodysplastic syndromes are a group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more cell lineages and increased risk of evolution to acute myeloid leukemia (AML). Recent advances in immunophenotyping of hematopoietic progenitor and maturing cells in dysplastic bone marrow point to a useful role for multiparameter flow cytometry (FCM) in the diagnosis and prognostication of myelodysplastic syndromes. In March 2008, representatives from 18 European institutes participated in a European LeukemiaNet (ELN) workshop held in Amsterdam as a first step towards standardization of FCM in myelodysplastic syndromes. Consensus was reached regarding standard methods for cell sampling, handling and processing. The group also defined minimal combinations of antibodies to analyze aberrant immunophenotypes and thus dysplasia. Examples are altered numbers of CD34+ precursors, aberrant expression of markers on myeloblasts, maturing myeloid cells, monocytes or erythroid precursors and the expression of lineage infidelity markers. When applied in practice, aberrant FCM patterns correlate well with morphology, the subclassification of myelodysplastic syndromes, and prognostic scoring systems. However, the group also concluded that despite strong evidence for an impact of FCM in myelodysplastic syndromes, further (prospective) validation of markers and immunophenotypic patterns are required against control patient groups as well as further standardization in multi-center studies. Standardization of FCM in myelodysplastic syndromes may thus contribute to improved diagnosis and prognostication of myelodysplastic syndromes in the future. PMID:19546437

  20. Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome

    NARCIS (Netherlands)

    Deschler, B.; Ihorst, G.; Platzbecker, U.; Germing, U.; Marz, E.; Figuerido, M. de; Fritzsche, K.; Haas, P. de; Salih, H.R.; Giagounidis, A.; Selleslag, D.; Labar, B.; Witte, T.J. de; Wijermans, P.; Lubbert, M.

    2013-01-01

    Myelodysplastic syndromes and acute myeloid leukemia exemplify the complexity of treatment allocation in older patients as options range from best supportive care, non-intensive treatment (e.g. hypomethylating agents) to intensive chemotherapy/hematopoietic cell transplantation. Novel metrics for

  1. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme

    NARCIS (Netherlands)

    van der Helm, Lieke H.; Alhan, Canan; Wijermans, Pierre W.; van Marwijk Kooy, Marinus; Schaafsma, Ron; Biemond, Bart J.; Beeker, Aart; Hoogendoorn, Mels; van Rees, Bastiaan P.; de Weerdt, Okke; Wegman, Jurgen; Libourel, Ward J.; Luykx-de Bakker, Sylvia A.; Minnema, Monique C.; Brouwer, Rolf E.; Croon-de Boer, Fransien; Eefting, Matthijs; Jie, Kon-Siong G.; van de Loosdrecht, Arjan A.; Koedam, Jan; Veeger, Nic J. G. M.; Vellenga, Edo; Huls, Gerwin

    2011-01-01

    The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors

  2. Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents.

    Science.gov (United States)

    Santini, Valeria; Almeida, Antonio; Giagounidis, Aristoteles; Gröpper, Stefanie; Jonasova, Anna; Vey, Norbert; Mufti, Ghulam J; Buckstein, Rena; Mittelman, Moshe; Platzbecker, Uwe; Shpilberg, Ofer; Ram, Ron; Del Cañizo, Consuelo; Gattermann, Norbert; Ozawa, Keiya; Risueño, Alberto; MacBeth, Kyle J; Zhong, Jianhua; Séguy, Francis; Hoenekopp, Albert; Beach, C L; Fenaux, Pierre

    2016-09-01

    This international phase III, randomized, placebo-controlled, double-blind study assessed the efficacy and safety of lenalidomide in RBC transfusion-dependent patients with International Prognostic Scoring System lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. In total, 239 patients were randomly assigned (2:1) to treatment with lenalidomide (n = 160) or placebo (n = 79) once per day (on 28-day cycles). The primary end point was the rate of RBC transfusion independence (TI) ≥ 8 weeks. Secondary end points were RBC-TI ≥ 24 weeks, duration of RBC-TI, erythroid response, health-related quality of life (HRQoL), and safety. RBC-TI ≥ 8 weeks was achieved in 26.9% and 2.5% of patients in the lenalidomide and placebo groups, respectively (P 500 mU/mL). At week 12, mean changes in HRQoL scores from baseline did not differ significantly between treatment groups, which suggests that lenalidomide did not adversely affect HRQoL. Achievement of RBC-TI ≥ 8 weeks was associated with significant improvements in HRQoL (P < .01). The most common treatment-emergent adverse events were neutropenia and thrombocytopenia. Lenalidomide yields sustained RBC-TI in 26.9% of RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. Response to lenalidomide was associated with improved HRQoL. Treatment-emergent adverse event data were consistent with the known safety profile of lenalidomide. © 2016 by American Society of Clinical Oncology.

  3. Autoimmune diseases and myelodysplastic syndromes.

    Science.gov (United States)

    Komrokji, Rami S; Kulasekararaj, Austin; Al Ali, Najla H; Kordasti, Shahram; Bart-Smith, Emily; Craig, Benjamin M; Padron, Eric; Zhang, Ling; Lancet, Jeffrey E; Pinilla-Ibarz, Javier; List, Alan F; Mufti, Ghulam J; Epling-Burnette, Pearlie K

    2016-05-01

    Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation. © 2016 Wiley Periodicals, Inc.

  4. Implementation of erythroid lineage analysis by flow cytometry in diagnostic models for myelodysplastic syndromes.

    Science.gov (United States)

    Cremers, Eline M P; Westers, Theresia M; Alhan, Canan; Cali, Claudia; Visser-Wisselaar, Heleen A; Chitu, Dana A; van der Velden, Vincent H J; Te Marvelde, Jeroen G; Klein, Saskia K; Muus, Petra; Vellenga, Edo; de Greef, Georgina E; Legdeur, Marie-Cecile C J C; Wijermans, Pierre W; Stevens-Kroef, Marian J P L; Silva-Coelho, Pedro da; Jansen, Joop H; Ossenkoppele, Gert J; van de Loosdrecht, Arjan A

    2017-02-01

    Flow cytometric analysis is a recommended tool in the diagnosis of myelodysplastic syndromes. Current flow cytometric approaches evaluate the (im)mature myelo-/monocytic lineage with a median sensitivity and specificity of ~71% and ~93%, respectively. We hypothesized that the addition of erythroid lineage analysis could increase the sensitivity of flow cytometry. Hereto, we validated the analysis of erythroid lineage parameters recommended by the International/European LeukemiaNet Working Group for Flow Cytometry in Myelodysplastic Syndromes, and incorporated this evaluation in currently applied flow cytometric models. One hundred and sixty-seven bone marrow aspirates were analyzed; 106 patients with myelodysplastic syndromes, and 61 cytopenic controls. There was a strong correlation between presence of erythroid aberrancies assessed by flow cytometry and the diagnosis of myelodysplastic syndromes when validating the previously described erythroid evaluation. Furthermore, addition of erythroid aberrancies to two different flow cytometric models led to an increased sensitivity in detecting myelodysplastic syndromes: from 74% to 86% for the addition to the diagnostic score designed by Ogata and colleagues, and from 69% to 80% for the addition to the integrated flow cytometric score for myelodysplastic syndromes, designed by our group. In both models the specificity was unaffected. The high sensitivity and specificity of flow cytometry in the detection of myelodysplastic syndromes illustrates the important value of flow cytometry in a standardized diagnostic approach. The trial is registered at www.trialregister.nl as NTR1825; EudraCT n.: 2008-002195-10. Copyright© Ferrata Storti Foundation.

  5. Managing myelodysplastic symptoms in elderly patients

    Directory of Open Access Journals (Sweden)

    R Ria

    2009-10-01

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

  6. Managing myelodysplastic syndromes in very old patients: a teaching case report

    Directory of Open Access Journals (Sweden)

    Niscola P

    2013-04-01

    Full Text Available Pasquale Niscola, Massimiliano Palombi, Malgorzata Monika Trawinska, Andrea Tendas, Marco Giovannini, Laura Scaramucci, Alessio Perrotti, Paolo de Fabritiis Hematology Unit, Sant'Eugenio Hospital, Rome, Italy Abstract: The introduction of hypomethylating agents in the treatment of myelodysplastic syndromes (MDS has significantly changed the clinical scenario of these diseases, which afflict predominantly older individuals. However, some concerns regarding the optimal application of these innovative and costly agents in the treatment of geriatric high-risk MDS remain. We report here the case of a nonagenarian treated with hypomethylating agents achieving a long-lasting clinical response and a significant improvement in her functional status. Our case confirmed that functional status and biological status, rather than the chronological age alone, can substantially guide the plan of an appropriate treatment strategy in high-risk MDS patients; moreover, the current case emphasizes the need for targeted studies in the field of geriatric MDS in order to formulate guidelines on the appropriate use of these costly agents, so that candidate patients can receive adequate treatment to preserve their quality of life and life expectancy, but at the same time avoiding unnecessary costs deriving from the use of high-cost drugs for those in whom a significant therapeutic result cannot be reasonably expected. Keywords: myelodysplastic syndromes, azacitidine, older patients

  7. Clonal evolution in myelodysplastic syndromes

    OpenAIRE

    da Silva-Coelho, Pedro; Kroeze, Leonie I.; Yoshida, Kenichi; Koorenhof-Scheele, Theresia N.; Knops, Ruth; van de Locht, Louis T.; de Graaf, Aniek O.; Massop, Marion; Sandmann, Sarah; Dugas, Martin; Stevens-Kroef, Marian J.; Cermak, Jaroslav; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko

    2017-01-01

    Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5?11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without...

  8. Hereditary Predispositions to Myelodysplastic Syndrome

    OpenAIRE

    Sarah A. Bannon; Courtney D. DiNardo

    2016-01-01

    Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA), dysker...

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

    Science.gov (United States)

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

    2017-06-01

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

  10. Myelodysplastic syndrome: classification and prognostic systems

    Directory of Open Access Journals (Sweden)

    Rosangela Invernizzi

    2011-12-01

    Full Text Available Myelodysplastic syndromes (MDS are acquired clonal disorders of hematopoiesis, that are characterized most frequently by normocellular or hypercellular bone marrow specimens, and maturation that is morphologically and functionally dysplastic. MDS constitute a complex hematological problem: differences in disease presentation, progression and outcome have made it necessary to use classification systems to improve diagnosis, prognostication and treatment selection. On the basis of new scientific and clinical information, classification and prognostic systems have recently been updated and minimal diagnostic criteria forMDS have been proposed by expert panels. In addition, in the last few years our ability to define the prognosis of the individual patient with MDS has improved. In this paper World Health Organization (WHO classification refinements and recent prognostic scoring systems for the definition of individual risk are highlighted and current criteria are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies.

  11. [Detecting high risk pregnancy].

    Science.gov (United States)

    Doret, Muriel; Gaucherand, Pascal

    2009-12-20

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

  12. Alpha-2-HS-glycoprotein plasma level decrease correlates with age in patients with myelodysplastic syndromes.

    Science.gov (United States)

    Majek, Pavel; Pecankova, Klara; Cermak, Jaroslav; Gasova, Zdenka; Prochazka, Bohumir; Dyr, Jan E

    2017-12-06

    It has been indicated in plasma proteomic studies on different myelodysplastic syndrome (MDS) cohorts that alpha-2-HS-glycoprotein could be a promising MDS biomarker candidate. The goal of this work was to estimate alpha-2-HS-glycoprotein (AHSG) plasma levels and its biomarker value in the low- and high-risk subgroups of MDS patients. The level of AHSG was estimated for 115 plasma samples using ELISA. The AHSG plasma level was found to be decreased significantly (p= 2.59 × 10-7) in MDS patients (515 ± 58 μg/ml) when compared to healthy controls (579 ± 64 μg/ml). Pearson and Spearman correlation analyses showed that age is the principal factor affecting the AHSG plasma level, rather than risk/diagnosis in MDS. In this work we demonstrate that although the total plasma level of AHSG is decreased in myelodysplastic syndrome patients, in particular in advanced MDS, that decrease correlates more strongly with age than with diagnosis within our studied cohort. Thus, according to the AHSG data gathered so far, AHSG total plasma level does not seem to be a suitable MDS biomarker, but its particular proteoforms should be considered for the next steps in MDS research.

  13. Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes.

    Science.gov (United States)

    Della Porta, Matteo Giovanni; Malcovati, Luca; Boveri, Emanuela; Travaglino, Erica; Pietra, Daniela; Pascutto, Cristiana; Passamonti, Francesco; Invernizzi, Rosangela; Castello, Alessandro; Magrini, Umberto; Lazzarino, Mario; Cazzola, Mario

    2009-02-10

    We studied bone marrow (BM) histologic abnormalities in myelodysplastic syndromes (MDS) classified according to WHO criteria to determine their clinical correlates and prognostic value. Three hundred one consecutive patients were retrospectively evaluated for BM fibrosis and CD34 immunoreactivity. Marrow fibrosis was assessed following the European consensus guidelines. Moderate to severe BM fibrosis was detected in 17% of cases and was associated with multilineage dysplasia (P = .001), high transfusion requirement (P WHO categories with excess of blasts (P according to International Prognostic Scoring System and WHO classification-based Prognostic Scoring System categories, BM fibrosis involved a shift to a one-step more advanced risk group. BM fibrosis identifies a distinct subgroup of MDS with multilineage dysplasia, high transfusion requirement, and poor prognosis and represents an independent prognostic factor that may be useful in clinical decision making. Furthermore, the presence of CD34+ cell clusters is an independent risk factor for progression to acute leukemia.

  14. Outcomes in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with isolated deletion 5q treated with lenalidomide: a subset analysis from the MDS-004 study

    Science.gov (United States)

    Giagounidis, Aristoteles; Mufti, Ghulam J; Mittelman, Moshe; Sanz, Guillermo; Platzbecker, Uwe; Muus, Petra; Selleslag, Dominik; Beyne-Rauzy, Odile; te Boekhorst, Peter; del Cañizo, Consuelo; Guerci-Bresler, Agnès; Nilsson, Lars; Lübbert, Michael; Quesnel, Bruno; Ganser, Arnold; Bowen, David; Schlegelberger, Brigitte; Göhring, Gudrun; Fu, Tommy; Benettaib, Bouchra; Hellström-Lindberg, Eva; Fenaux, Pierre

    2014-01-01

    Objective A subset analysis of the randomised, phase 3, MDS-004 study to evaluate outcomes in patients with International Prognostic Scoring System (IPSS)-defined Low-/Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) with isolated del(5q). Methods Patients received lenalidomide 10 mg/d (days 1–21; n = 47) or 5 mg/d (days 1–28; n = 43) on 28-d cycles or placebo (n = 45). From the placebo and lenalidomide 5 mg groups, 84% and 58% of patients, respectively, crossed over to lenalidomide 5 or 10 mg at 16 wk, respectively. Results Rates of red blood cell-transfusion independence (RBC-TI) ≥182 d were higher in the lenalidomide 10 mg (57.4%; P < 0.0001) and 5 mg (37.2%; P = 0.0001) groups vs. placebo (2.2%). Cytogenetic response rates (major + minor responses) were 56.8% (P < 0.0001), 23.1% (P = 0.0299) and 0%, respectively. Two-year cumulative risk of acute myeloid leukaemia progression was 12.6%, 17.4% and 16.7% in the lenalidomide 10 mg, 5 mg, and placebo groups, respectively. In a 6-month landmark analysis, overall survival was longer in lenalidomide-treated patients with RBC-TI ≥182 d vs. non-responders (P = 0.0072). The most common grade 3–4 adverse event was myelosuppression. Conclusions These data support the clinical benefits and acceptable safety profile of lenalidomide in transfusion-dependent patients with IPSS-defined Low-/Int-1-risk MDS with isolated del(5q). PMID:24813620

  15. Azathioprine-associated myelodysplastic syndrome in two patients with ulcerative colitis.

    Science.gov (United States)

    Ahmad, Omer F; Keane, Margaret G; McCartney, Sara; Khwaja, Asim; Bloom, Stuart L

    2013-07-01

    Azathioprine is a commonly used immunosuppressive agent in post-transplantation regimens and autoimmune diseases. An increased risk of lymphoma with thiopurine therapy in patients with inflammatory bowel disease has been described previously; however, there are few reported cases of azathioprine therapy-related myelodysplastic syndrome and acute myeloid leukaemia. We report two patients with ulcerative colitis who subsequently developed azathioprine-related myelodysplastic syndrome. It is imperative that gastroenterologists remain vigilant for this rare complication as this subset of patients has a particularly poor prognosis. These cases are also important in considering the risk of open-ended thiopurine therapy.

  16. Managing myelodysplastic symptoms in elderly patients.

    Science.gov (United States)

    Ria, R; Moschetta, M; Reale, A; Mangialardi, G; Castrovilli, A; Vacca, A; Dammacco, F

    2009-01-01

    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 marrow function, including the diminished capacity of response to stressors such as infection or myelosuppressive treatments. Through the integration of geriatric and oncological strategies, a personalized approach toward this unique population may be applied. As

  17. A phase 2, randomized, double-blind, multicenter study comparing siltuximab plus best supportive care (BSC) with placebo plus BSC in anemic patients with International Prognostic Scoring System low- or intermediate-1-risk myelodysplastic syndrome.

    Science.gov (United States)

    Garcia-Manero, Guillermo; Gartenberg, Gary; Steensma, David P; Schipperus, Martin R; Breems, Dimitri A; de Paz, Raquel; Valcárcel, David; Kranenburg, Britte; Reddy, Manjula; Komrokji, Rami S

    2014-09-01

    Interleukin-6 (IL-6) may play an important role in the pathophysiology of anemia of inflammation associated with myelodysplastic syndrome (MDS). This double-blind, placebo-controlled, phase 2 study assessed the efficacy and safety of siltuximab, a chimeric anti-IL-6 monoclonal antibody, in patients with low- and intermediate-1-risk MDS who require transfusions for MDS anemia. Patients were randomized in a 2:1 ratio to siltuximab 15 mg kg(-1) every 4 weeks + best supportive care (BSC) or placebo + BSC for 12 weeks. The primary endpoint was reduction in red blood cell (RBC) transfusions to treat MDS anemia, defined as ≥50% relative decrease and ≥2-unit absolute decrease in RBC transfusions. Fifty and 26 patients were randomized to the siltuximab and placebo groups, respectively. The study did not meet its prespecified hypothesis, with six (12%) patients in the siltuximab group and one (3.8%) in the placebo group having reductions in RBC transfusions (P = 0.271). At the time of the planned futility analysis, the prespecified cutoff criteria were not met, and the study was terminated early due to lack of efficacy. No unexpected safety findings were observed. In conclusion, compared to placebo, treatment with siltuximab did not reduce RBC transfusions in transfusion-dependent patients with low- and intermediate-1-risk MDS. Future studies might explore siltuximab in patients with less iron overload and with elevated IL-6 levels and/or using higher doses for MDS. © 2014 Wiley Periodicals, Inc.

  18. Comparison of Myelodysplastic Syndrome Prognostic Scoring Systems

    Science.gov (United States)

    Bektaş, Özlen; Üner, Ayşegül; Eliaçık, Eylem; Uz, Burak; Işık, Ayşe; Etgül, Sezgin; Bozkurt, Süreyya; Haznedaroğlu, İbrahim Celalettin; Göker, Hakan; Sayınalp, Nilgün; Aksu, Salih; Demiroğlu, Haluk; Özcebe, Osman İlhami; Büyükaşık, Yahya

    2016-01-01

    Objective: Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease. Patients are at risk of developing cytopenias or progression to acute myeloid leukemia. Different classifications and prognostic scoring systems have been developed. The aim of this study was to compare the different prognostic scoring systems. Materials and Methods: One hundred and one patients who were diagnosed with primary MDS in 2003-2011 in a tertiary care university hospital’s hematology department were included in the study. Results: As the International Prognostic Scoring System (IPSS), World Health Organization Classification-Based Prognostic Scoring System (WPSS), MD Anderson Prognostic Scoring System (MPSS), and revised IPSS (IPSS-R) risk categories increased, leukemia-free survival and overall survival decreased (p<0.001). When the IPSS, WPSS, MPSS, and IPSS-R prognostic systems were compared by Cox regression analysis, the WPSS was the best in predicting leukemia-free survival (p<0.001), and the WPSS (p<0.001) and IPSS-R (p=0.037) were better in predicting overall survival. Conclusion: All 4 prognostic systems were successful in predicting overall survival and leukemia-free survival (p<0.001). The WPSS was found to be the best predictor for leukemia-free survival, while the WPSS and IPSS-R were found to be the best predictors for overall survival. PMID:26376664

  19. Comparison of Myelodysplastic Syndrome Prognostic Scoring Systems

    Directory of Open Access Journals (Sweden)

    Özlen Bektaş

    2016-05-01

    Full Text Available Objective: Myelodysplastic syndrome (MDS is a clonal hematopoietic stem cell disease. Patients are at risk of developing cytopenias or progression to acute myeloid leukemia. Different classifications and prognostic scoring systems have been developed. The aim of this study was to compare the different prognostic scoring systems. Materials and Methods: One hundred and one patients who were diagnosed with primary MDS in 2003-2011 in a tertiary care university hospital’s hematology department were included in the study. Results: As the International Prognostic Scoring System (IPSS, World Health Organization Classification-Based Prognostic Scoring System (WPSS, MD Anderson Prognostic Scoring System (MPSS, and revised IPSS (IPSS-R risk categories increased, leukemia-free survival and overall survival decreased (p<0.001. When the IPSS, WPSS, MPSS, and IPSS-R prognostic systems were compared by Cox regression analysis, the WPSS was the best in predicting leukemia-free survival (p<0.001, and the WPSS (p<0.001 and IPSS-R (p=0.037 were better in predicting overall survival. Conclusion: All 4 prognostic systems were successful in predicting overall survival and leukemia-free survival (p<0.001. The WPSS was found to be the best predictor for leukemia-free survival, while the WPSS and IPSS-R were found to be the best predictors for overall survival.

  20. Clonal evolution in myelodysplastic syndromes

    Science.gov (United States)

    da Silva-Coelho, Pedro; Kroeze, Leonie I.; Yoshida, Kenichi; Koorenhof-Scheele, Theresia N.; Knops, Ruth; van de Locht, Louis T.; de Graaf, Aniek O.; Massop, Marion; Sandmann, Sarah; Dugas, Martin; Stevens-Kroef, Marian J.; Cermak, Jaroslav; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; de Witte, Theo; Blijlevens, Nicole M. A.; Muus, Petra; Huls, Gerwin; van der Reijden, Bert A.; Ogawa, Seishi; Jansen, Joop H.

    2017-01-01

    Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5–11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment. The application of disease-modifying therapy may create an evolutionary bottleneck after which more complex MDS, but also unrelated clones of haematopoietic cells, may emerge. In addition, subclones that acquired an additional mutation associated with treatment resistance (TP53) or disease progression (NRAS, KRAS) may be detected months before clinical changes become apparent. Monitoring the genetic landscape during the disease may help to guide treatment decisions. PMID:28429724

  1. [High dynamic risk cystoceles].

    Science.gov (United States)

    Salinas Casado, Jesús; Méndez Rubio, Santiago; Virseda Chamorro, Miguel; Pelaquim, Humberto; Silmi Moyano, Angel

    2010-06-01

    To assess the bladder compliance in a series of cystoceles referred for urodynamic study. Retrospective study of a series of patients with cystocele undergoing medical history, videurodynamic study, pelvic MRI and lower urinary tract, urological ultrasound and cystoscopy. We Excluded cases with neurogenic dysfunction and urinary infection. The terminology followed the criteria of the ICS, if not specified otherwise. The series includes 3333 cases of cystocele 616 of which are grade III cystocele. There were 3 cases with low bladder compliance; this is 0.0009% of total (1:1000) and 0.5% of grade III cystocele (1:200) All cases of cystocele whith low compliance were associated with feeling of a bulk in the vagina and functional symptoms of lower urinary tract(LUTS). No urinary incontinence was related to cough. These patients also showed urodynamic alterations in the voiding phase, type hypo / acontractile detrusor and postvoid residual. The patients were subjected to various techniques of abdominal and transvaginal cystocele repair (with preventive anti-incontinence surgery), getting a vagina bulk disappearance, improvement of symptoms of lower urinary tract function, normalization of bladder compliance and detrusor contractility, with elimination of the postvoid residual. Although they are not frequent, high-risk cystoceles should be discarded in high-grade cystocele that apart from low bladder accommodation, have a hipo/acontractile detrusor and postvoid residual. Surgical correction of cystocele not only reduces the bulk and LUTS, but normalizes urodynamic alterations.

  2. Perceptions of high risk sports.

    Science.gov (United States)

    Pedersen, D M

    1997-10-01

    High risk sports were rated as to risk, appeal, and likelihood of participation by 282 men and 162 women. Ascending order of perceived risk was skiing, scuba diving, bungee jumping, rock climbing, motorcycle racing, hang gliding, cliff jumping, and skydiving. Profile analysis showed stated likelihood of participation to be directly related to appeal and inversely related to perceived risk.

  3. High-Risk Pregnancy

    Science.gov (United States)

    ... risk? » Related A-Z Topics Diabetes Pregnancy Loss Preeclampsia and Eclampsia NICHD News Spotlights Podcast: NICHD launches PregSource to learn more about pregnancy News Release: NIH Begins Large HIV Treatment Study in Pregnant Women Spotlight: Zika Research after ...

  4. [A comparable analysis of IPSS and IPSS-R for evaluating prognosis of myelodysplastic syndrome].

    Science.gov (United States)

    Lei, Ye; Xu, Xiaoqian; Yang, Jianmin; Zhang, Weiping; Song, Xianmin; Cheng, Hui; Gong, Shenglan; Wang, Jianmin

    2014-12-01

    To investigate the patients' characteristics and efficacy of prognosis evaluation by International Prognosis Scoring System (IPSS) and Revised International Prognosis Scoring System (IPSS-R) in patients with myelodysplastic syndrome (MDS). Prognostic value of IPSS and IPSS-R was evaluated on clinical data from 159 MDS patients, according to WHO classification. With a median age of 44 years (range:15-80 years), MDS patients had the frequency of 38.56% with abnormal karyotype, including the most common abnormality +8 (20/153, 12.6%). 34 of 142 patients transformed into leukemia. Age and the level of β2 micro-globulin were the prognostic factors by multivariate analysis and IPSS-R had a better prognostic significance. The differences in cumulative survival between IPSS subgroups were significant (P0.05). There were statistical differences for IPSS-R low risk group vs high or very high risk group, and intermediate risk group vs high or very high risk group (Pcompared with those in Europe and America. The proportion of higher risk (worse than good karyotype) in IPSS-R was higher than that in Europe and America. Age and the level of β2 micro-globulin were prognostic factors. Both IPSS and IPSS-R were applicable in Chinese MDS patients and the latter performed better. Applying IPSS-R to re-stratify IPSS subgroups helps evaluate prognosis more accurately and improve treatment outcomes.

  5. MYELODYSPLASTIC SYNDROMES AND IRON CHELATION THERAPY

    Directory of Open Access Journals (Sweden)

    Emanuele Angelucci

    2017-03-01

    Full Text Available Over recent decades we have been fortunate to witness the advent of new technologies and of an expanded knowledge and application of chelation therapies to the benefit of patients with iron overload. However, extrapolation of learnings from thalassemia to the myelodysplastic syndromes (MDS has resulted in a fragmented and uncoordinated clinical evidence base. We’re therefore forced to change our understanding of MDS, looking with other eyes to observational studies that inform us about the relationship between iron and tissue damage in these subjects. The available evidence suggests that iron accumulation is prognostically significant in MDS, but levels of accumulation historically associated with organ damage (based on data generated in the thalassemias are infrequent. Emerging experimental data have provided some insight into this paradox, as our understanding of iron-induced tissue damage has evolved from a process of progressive bulking of organs through high-volumes iron deposition, to one of ‘toxic’ damage inflicted through multiple cellular pathways. Damage from iron may therefore occur prior to reaching reference thresholds, and similarly, chelation may be of benefit before overt iron overload is seen. In this review, we revisit the science and clinical evidence for iron overload in MDS to better characterise the iron overload phenotype in these patients, which is distinct from the classical transfusional and non-transfusional iron overload syndrome. We hope this will provide a conceptual framework to better understand the complex associations between anemia, iron and clinical outcomes, to accelerate progress in this area.

  6. Uncoding the genetic heterogeneity of myelodysplastic syndrome.

    Science.gov (United States)

    Lindsley, R Coleman

    2017-12-08

    Myelodysplastic syndrome (MDS) is a clinically heterogeneous disease characterized by functional impairment of hematopoiesis and abnormal bone marrow morphology. The type and severity of hematopoietic dysfunction in MDS are highly variable, and the kinetics of disease progression are difficult to predict. Genomic studies have shown that MDS is typically driven by a multistep somatic genetic process affecting a core set of genes. By definition, recurrent MDS driver mutations all drive clonal dominance, although they can have stereotyped positions in the clonal hierarchy or patterns of comutation association and exclusivity. Furthermore, environmental context, such as exposures to cytotoxic chemotherapy or the presence of germ-line predisposition, can influence disease pathogenesis and clinical outcomes. This review will address how an enhanced understanding of MDS genetics may enable refinement of current diagnostic schema, improve understanding of the pathogenesis of therapy-related MDS, and identify germ-line predispositions to development of MDS that are more common than recognized by standard clinical evaluation. © 2016 by The American Society of Hematology. All rights reserved.

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

    Science.gov (United States)

    2010-08-05

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

  8. A randomized, double-blind, placebo-controlled phase 2 study evaluating the efficacy and safety of romiplostim treatment of patients with low or intermediate-1 risk myelodysplastic syndrome receiving lenalidomide

    Directory of Open Access Journals (Sweden)

    Wang Eunice S

    2012-11-01

    Full Text Available Abstract Background Lenalidomide treatment in myelodysplastic syndrome (MDS may lead to thrombocytopenia and dose reductions/delays. This study evaluated the safety and tolerability of the thrombopoietin mimetic romiplostim and its effects on the incidence of clinically significant thrombocytopenic events (CSTEs in lower risk MDS patients receiving lenalidomide. Methods Patients were assigned to weekly placebo (n = 12 or romiplostim 500 μg (n = 14 or 750 μg (n = 13 for four 28-day lenalidomide cycles. Results The treatment groups were generally similar with respect to baseline disease characteristics. Del(5q abnormalities were noted in 1 (8% patient in the placebo group, 3 (21% in the romiplostim 500 μg group, and two (15% in the 750 μg group. CSTEs were noted in 8 (67% patients in the placebo group, 4 (29% in the romiplostim 500 μg group, and 8 (62% in the romiplostim 750 μg group. Throughout the study, median platelet counts trended lower in placebo-treated than in romiplostim-treated patients. Thrombocytopenia-related adjustments in lenalidomide occurred in 6 (50% patients in the placebo group, 5 (36% in the romiplostim 500 μg group, and 2 (15% in the 750 μg group. Although the percentages of patients who received platelet transfusions were similar across treatment groups, there was a trend toward lower numbers of transfusions in both romiplostim groups during each treatment cycle. There were two serious treatment-related adverse events during the treatment period (cerebrovascular accident, placebo; worsening thrombocytopenia, romiplostim 500 μg. Two patients (romiplostim 500 and 750 μg, respectively had an increase in bone marrow blasts to >20% during treatment, but had no post-treatment biopsy to confirm or exclude the diagnosis of progression to AML. Conclusions These data suggest that romiplostim administered to MDS patients during lenalidomide treatment may decrease the frequency of dose

  9. [Cell clonality in myelodysplastic syndrome].

    Science.gov (United States)

    Krejcová, H; Neuwirtová, R; Cermák, J; Belicková, M; Brdicka, R

    2002-01-01

    Myelodysplastic syndromes (MDS) are classified as oncohematologic, clonal diseases. However, some MDS subtypes lack malignant clinical features. Literary data on the clonality of blood cells in MDS are controversial. Therefore we examined the clonality in the group of our own MDS patients. We were especially interested in the comparison of the clonality of myeloid and lymphoid cell line-ages. Using X-chromosome inactivation methods based on polymorphism in human androgen receptor gene (HUMARA), iduronate sulphatase gene (IDS) and protein p55 gene, we assessed the clonality of granulocytes, monocytes and T-lymphocytes of 49 female patients with MDS and 12 control women of various ages. Though the results were heterogeneous, certain trends were observed: most frequently monoclonality of monocytes was found (51%), granulocytes were monoclonal in 33% of cases, monoclonal T lymphocytes only in 8% of cases. There was no case with monoclonal T lymphocytes and simultaneously polyclonal myeloid cell fractions. Results differ in relation to the subtypes of MDS. Among controls we observed monoclonality of myeloid cells in one case of an old lady. WE CONCLUDE: The results confirm the presence of malignant clone of myeloid cells in MDS, which can be of variable size. The examination of the clonality in MDS can be significant for the therapy decision. Monoclonal myeloid cells are found least frequently in refractory anemia, most frequently in RAEB-T. Monoclonality of cells in sideroblastic anemia is interesting. The prevailing polyclonality of T lymphocytes in MDS can be explained by the presence of a long-lived cell population originating from the period before the development of MDS. The role of the polyclonal memory T cells in the antitumor immunity in MDS is discussed.

  10. 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...... (AML). The dysplastic cells harbor chromosomal breakage, point mutations and promoter hyper-methylation of tumor suppressor genes.For most patients, who are not eligible for bone marrow transplantation, hypomethylating agents, such as azacitidine (AZA), are currently the only treatment option......), which could lead to increased immune recognition of tumor cells and immune-mediated tumor cell killing. CTA’s are known to be immunogenic and are only expressed at immunoprivileged sites and on malignant cells, making them attractive as targets for therapeutic cancer vaccination....

  11. An analysis of the demographic profile, clinical manifestations, investigations and outcome of paediatric myelodysplastic syndrome: A single centre, cross-sectional study

    Directory of Open Access Journals (Sweden)

    Appaji Lingegowda

    2015-09-01

    Full Text Available Purpose: Pediatric myelodysplastic syndrome (MDS is a relatively rare entity, with distinct clinical features and more aggressive course than its adult counterpart. The aim of this study was to analyze the incidence of pediatric myelodysplastic syndrome at a tertiary cancer care center in southern India along with clinical manifestations, investigations and outcome.Methods: On retrospective analysis of 1094 cases of pediatric hematological malignancies over a five-year period from September 2009 to August 2014, a total of seven cases of pediatric myelodysplastic syndrome were identified. Presenting complaints, physical examination, investigations including haemogram, biochemistry, bone marrow examination and cytogenetics were reviewed. The diagnosis of MDS was made if there was dysplasia in at least 10% of cells in two or more cell lineages. All patients were risk stratified using the revised IPSS. Results: Out of 1094 cases of pediatric hematological malignancies presenting at our institute within the study period, there were only seven cases of pediatric MDS with an incidence of 0.65%. There were no genetic predispositions nor any cases of therapy related MDS. The most common presentation was with fever and all patients had significant splenomegaly. All patients had anemia (Median-6.2 gm / dL with elevated WBC counts (Median-30,900 / uL and thrombocytopenia (Median-50,000 / uL. The marrow cytogenetics was normal in five patients. Most patients fell into the high and very high-risk category of the revised IPSS, with only two patients of low risk. All seven patients were given only supportive care but one progressed to AML for which he was treated with remission induction. Only two patients were alive at the time of analysis and median survival was 9 months. Conclusion: Pediatric MDS is a rare disease with a short clinical history, aggressive course and generally poor outcomes as compared to the adult variant. A hematopoietic stem cell

  12. Role of TIRAP in Myelodysplastic Syndromes

    Science.gov (United States)

    2015-04-01

    TIRAP over-expression in MDS is not known. Our objective is to investigate the mechanism of TIRAP-induced hematological abnormalities in a mouse bone...myelodysplastic syndromes: involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype . Blood. 2006 Jul 1;108(1):337-45

  13. 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...

  14. Myelodysplastic syndromes: histopathology as prognostic factor

    Directory of Open Access Journals (Sweden)

    Romeo Maura

    2001-01-01

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

  15. Mutations of myelodysplastic syndromes (MDS): An update.

    Science.gov (United States)

    Ganguly, Bani Bandana; Kadam, N N

    2016-01-01

    The plethora of knowledge gained on myelodysplastic syndromes (MDS), a heterogeneous pre-malignant disorder of hematopoietic stem cells, through sequencing of several pathway genes has unveiled molecular pathogenesis and its progression to AML. Evolution of phenotypic classification and risk-stratification based on peripheral cytopenias and blast count has moved to five-tier risk-groups solely concerning chromosomal aberrations. Increased frequency of complex abnormalities, which is associated with genetic instability, defines the subgroup of worst prognosis in MDS. However, the independent effect of monosomal karyotype remains controversial. Recent discoveries on mutations in RNA-splicing machinery (SF3B1, SRSF2, ZRSR2, U2AF1, U2AF2); DNA methylation (TET2, DNMT3A, IDH1/2); chromatin modification (ASXL1, EZH2); transcription factor (TP53, RUNX1); signal transduction/kinases (FLT3, JAK2); RAS pathway (KRAS, NRAS, CBL, NF1, PTPN11); cohesin complex (STAG2, CTCF, SMC1A, RAD21); DNA repair (ATM, BRCC3, DLRE1C, FANCL); and other pathway genes have given insights into the independent effects and interaction of co-occurrence of mutations on disease-phenotype. RNA-splicing and DNA methylation mutations appeared to occur early and are reported as 'founder' mutations in over 50% MDS patients. TET2 mutation, through altered DNA methylation, has been found to have independent prognostic response to hypomethylating agents. Moreover, presence of DNMT3A, TET2 and ASXL1 mutations in normal elderly individuals forms the basis of understanding that accumulation of somatic mutations may not cause direct disease-development; however, cooperation with other mutations in the genes that are frequently mutated in myeloid and other hematopoietic cancers might result in clonal expansion through self-renewal and/or proliferation of hematopoietic stem cells. Identification of small molecules as inhibitors of epigenetic mutations has opened avenues for tailoring targeted drug development. The

  16. Red cell alloimmunization is associated with development of autoantibodies and increased red cell transfusion requirements in myelodysplastic syndrome.

    Science.gov (United States)

    Singhal, Deepak; Kutyna, Monika M; Chhetri, Rakchha; Wee, Li Yan A; Hague, Sophia; Nath, Lakshmi; Nath, Shriram V; Sinha, Romi; Wickham, Nicholas; Lewis, Ian D; Ross, David M; Bardy, Peter G; To, Luen Bik; Reynolds, John; Wood, Erica M; Roxby, David J; Hiwase, Devendra K

    2017-12-01

    Up to 90% of patients with a myelodysplastic syndrome require red blood cell transfusion; nevertheless, comprehensive data on red cell alloimmunization in such patients are limited. This study evaluates the incidence and clinical impact of red cell alloimmunization in a large cohort of patients with myelodysplastic syndrome registered in the statewide South Australian-MDS registry. The median age of the 817 patients studied was 73 years, and 66% were male. The cumulative incidence of alloimmunization was 11%. Disease-modifying therapy was associated with a lower risk of alloimmunization while alloimmunization was significantly higher in patients with a revised International Prognostic Scoring System classification of Very Low, Low or Intermediate risk compared to those with a High or Very High risk (P=0.03). Alloantibodies were most commonly directed against antigens in the Rh (54%) and Kell (24%) systems. Multiple alloantibodies were present in 49% of alloimmunized patients. Although 73% of alloimmunized patients developed alloantibodies during the period in which they received their first 20 red cell units, the total number of units transfused was significantly higher in alloimmunized patients than in non-alloimmunized patients (90±100 versus 30±52; Pred cell transfusion intensity increased significantly following alloimmunization (2.8±1.3 versus 4.1±2.0; Pred cell transfusion requirements following alloimmunization, most probably due to development of additional alloantibodies and autoantibodies, resulting in subclinical/clinical hemolysis. Strategies to mitigate alloimmunization risk are critical for optimizing red cell transfusion support. Copyright© 2017 Ferrata Storti Foundation.

  17. Genetic Testing in Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    Science.gov (United States)

    Nardi, Valentina; Hasserjian, Robert P

    2016-03-01

    Cytogenetic analysis of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is essential for disease diagnosis, classification, prognostic stratification, and treatment guidance. Molecular genetic analysis of CEBPA, NPM1, and FLT3 is already standard of care in patients with AML, and mutations in several additional genes are assuming increasing importance. Mutational analysis of certain genes, such as SF3B1, is also becoming an important tool to distinguish subsets of MDS that have different biologic behaviors. It is still uncertain how to optimally combine karyotype with mutation data in diagnosis and risk-stratification of AML and MDS, particularly in cases with multiple mutations and/or several mutationally distinct subclones. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Lenalidomide: a brief review of its therapeutic potential in myelodysplastic syndromes

    Science.gov (United States)

    Giagounidis, Aristoteles A N; Germing, Ulrich; Haase, Sabine; Aul, Carlo

    2007-01-01

    Lenalidomide is a novel thalidomide analogue with enhanced immunomodulatory and antiangiogenic action lacking most of the typical thalidomide-associated adverse events. In myelodysplastic syndromes (MDS), it has been used primarily in the IPSS low- and intermediate-1 risk setting. Several trials have demonstrated its potential to lead to both erythroid and cytogenetic responses in these disease groups. In a clinical trial of patients with a del(5q) chromosomal abnormality, lenalidomide treatment resulted in red blood cell (RBC) transfusion independence in 67% of patients. Moreover, 45% of patients achieved a complete cytogenetic remission, and 28% achieved a minor cytogenetic remission. This result was independent of karyotype complexity. Lenalidomide might also induce long-term remissions in del(5q) patients with an elevated medullary blast count. In non-del(5q) patients, 43% of patients with confirmed low- and intermediate-1 risk achieved transfusion independence or a reduction of at least 50% of pre-treatment RBC transfusion levels. Adverse events are common but manageable and include neutropenia and thrombocytopenia, pruritus, rash, diarrhea, and others. Lenalidomide will prove an essential part in the armamentarium of MDS therapeutics. Combination therapies with cytokines, demethylating agents, tyrosine kinase inhibitors, or chemotherapy are being investigated and may show additional benefit in both low- and high risk MDS. PMID:18472976

  19. Myelodysplastic syndromes: Contemporary review and how we treat.

    Science.gov (United States)

    Gangat, Naseema; Patnaik, Mrinal M; Tefferi, Ayalew

    2016-01-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders with an inherent tendency for leukemic transformation. Diagnosis is currently based on the presence of peripheral blood cytopenias, peripheral blood and bone marrow dysplasia/blasts, and clonal cytogenetic abnormalities. With the advent of next generation sequencing, recurrent somatic mutations in genes involved in epigenetic regulation (TET2, ASXL1, EZH2, DNMT3A, IDH1/2), RNA splicing (SF3B1, SRSF2, U2AF1, ZRSR2), DNA damage response (TP53), transcriptional regulation (RUNX1, BCOR, ETV6) and signal transduction (CBL, NRAS, JAK2) have been identified in MDS. Conventional prognostication is by the revised International prognostic scoring system (IPSS-R) with additional adverse prognosis conferred by presence of ASXL1, EZH2, or TP53 mutations. Currently Food and Drug administration (FDA)-approved drugs for the treatment of MDS are not curative and their effect on survival is limited; they include the hypomethylating agents (HMA) azacitidine and decitabine and lenalidomide for MDS with isolated del(5q). To date, allogeneic stem cell transplant (ASCT) remains the only treatment option for possible cure. Given the current lack of drugs with convincing evidence of favorable effect on survival, we consider ASCT as the treatment of choice for most patients with symptomatic disease, and especially for those with high-risk disease. For nontransplant candidates, participation in clinical trials is preferred over conventional therapy. There is not one right way of treatment for patients who are not candidates for either ASCT or clinical trials and palliative drugs of choice depend on the clinical problem, such as symptomatic anemia (ESAs, danazol, HMA), thrombocytopenia (HMA), or neutropenia (myeloid growth factors). Conversely, there is no controlled evidence to support the use of iron chelating agents in MDS. Going forward, we believe it is time to incorporate mutation information in

  20. Myelodysplastic syndromes in Chernobyl clean-up workers.

    Science.gov (United States)

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

    2015-10-01

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

  1. 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

    2014-01-01

    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...... revealing 3*B TPMT heterozygosity. The patient was treated according to the NOPHO-AML 2004 protocol. Two years after the treatment, the patient presented with neutropenia and thrombocytopenia. Bone marrow, including fluorescent in situ hybridization and retrospective aCGH analysis, verified therapy......-related myelodysplastic syndrome with ring chromosome 6. DISCUSSION: The clinical course of this patient raises the possibility that low-activity TPMT genotypes may influence 6TG toxicity in patients with AML and lead to an increased risk of developing secondary malignant neoplasms....

  2. Spectrum of complex chromosomal aberrations in a myelodysplastic syndrome and a brief review

    Directory of Open Access Journals (Sweden)

    Bani Bandana Ganguly

    2016-01-01

    Full Text Available Myelodysplastic syndrome (MDS is a heterogeneous premalignant condition characterized by cytopenia, ineffective hematopoiesis, dysplastic marrow, and risk of progression to acute myeloid leukemia. Cytogenetic abnormalities, including del(3q/5q/7q/11q/12p/20q, monosomy 5/7, trisomy 8/19, i(17q, and -Y, are the indicators of diagnosis and risk stratification. The present case with bicytopenia detected with highly complex chromosome rearrangements with variability in numerical and structural combinations. Chromosome analysis was carried out following unstimulated marrow culture and G-banding. In addition to known MDS-aberrations, der(9p, der(12 dic(12;?19, +15, −18, and ring and marker chromosomes were recorded having, at least, nine abnormal chromosomes/cell. To our knowledge, this is the first case with all MDS-aberrations in one single individual. The case has been discussed in relevance to current MDS research. In the present case, i(17q/-17, der(12p, del(5q26, del(7q36, and del(20q11 indicate possible alterations in TP53, ETV6, IDH2, EZH2, and SRSF2 genes, which are responsible for pathomechanism, genetic instability, clonal evolution, and advancement of disease condition.

  3. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet.

    Science.gov (United States)

    Malcovati, Luca; Hellström-Lindberg, Eva; Bowen, David; Adès, Lionel; Cermak, Jaroslav; Del Cañizo, Consuelo; Della Porta, Matteo G; Fenaux, Pierre; Gattermann, Norbert; Germing, Ulrich; Jansen, Joop H; Mittelman, Moshe; Mufti, Ghulam; Platzbecker, Uwe; Sanz, Guillermo F; Selleslag, Dominik; Skov-Holm, Mette; Stauder, Reinhard; Symeonidis, Argiris; van de Loosdrecht, Arjan A; de Witte, Theo; Cazzola, Mario

    2013-10-24

    Within the myelodysplastic syndrome (MDS) work package of the European LeukemiaNet, an Expert Panel was selected according to the framework elements of the National Institutes of Health Consensus Development Program. A systematic review of the literature was performed that included indexed original papers, indexed reviews and educational papers, and abstracts of conference proceedings. Guidelines were developed on the basis of a list of patient- and therapy-oriented questions, and recommendations were formulated and ranked according to the supporting level of evidence. MDSs should be classified according to the 2008 World Health Organization criteria. An accurate risk assessment requires the evaluation of not only disease-related factors but also of those related to extrahematologic comorbidity. The assessment of individual risk enables the identification of fit patients with a poor prognosis who are candidates for up-front intensive treatments, primarily allogeneic stem cell transplantation. A high proportion of MDS patients are not eligible for potentially curative treatment because of advanced age and/or clinically relevant comorbidities and poor performance status. In these patients, the therapeutic intervention is aimed at preventing cytopenia-related morbidity and preserving quality of life. A number of new agents are being developed for which the available evidence is not sufficient to recommend routine use. The inclusion of patients into prospective clinical trials is strongly recommended.

  4. Spectrum of complex chromosomal aberrations in a myelodysplastic syndrome and a brief review.

    Science.gov (United States)

    Ganguly, Bani Bandana; Dolai, Tuphan Kanti; De, Rajib; Kadam, Nitin N

    2016-01-01

    Myelodysplastic syndrome (MDS) is a heterogeneous premalignant condition characterized by cytopenia, ineffective hematopoiesis, dysplastic marrow, and risk of progression to acute myeloid leukemia. Cytogenetic abnormalities, including del(3q/5q/7q/11q/12p/20q), monosomy 5/7, trisomy 8/19, i(17q), and -Y, are the indicators of diagnosis and risk stratification. The present case with bicytopenia detected with highly complex chromosome rearrangements with variability in numerical and structural combinations. Chromosome analysis was carried out following unstimulated marrow culture and G-banding. In addition to known MDS-aberrations, der(9p), der(12) dic(12;?19), +15, -18, and ring and marker chromosomes were recorded having, at least, nine abnormal chromosomes/cell. To our knowledge, this is the first case with all MDS-aberrations in one single individual. The case has been discussed in relevance to current MDS research. In the present case, i(17q)/-17, der(12p), del(5q26), del(7q36), and del(20q11) indicate possible alterations in TP53, ETV6, IDH2, EZH2, and SRSF2 genes, which are responsible for pathomechanism, genetic instability, clonal evolution, and advancement of disease condition.

  5. [Polycythemia vera terminating in myelodysplastic syndrome].

    Science.gov (United States)

    Kimura, S; Uoshima, N; Tanaka, R; Kobayashi, Y; Ozawa, M; Maruo, N; Kondo, M; Abe, T; Yoshida, Y

    1990-01-01

    A 77-year-old male, who had been treated with carboquone and busulfan for polycythemia vera (PV), developed myelodysplastic syndrome (MDS) 8 years later. On admission the peripheral blood revealed pancytopenia, but blastoid cells were not noted. The bone marrow showed hypercellularity, and functional and morphological abnormalities in trilineages of hemocytes. Cytogenetic study showed complex abnormalities involving chromosomes 5 and 7. We diagnosed this case as secondary MDS to alkylating agents. He was treated with 1, 25 (OH)2 vitamin D3. However, it was not effective and the percentage of myeloblasts increased to 14.4%. In spite of supportive therapy, he died of sepsis due to urinary tract infection.

  6. RARE CYTOGENETIC ABNORMALITIES IN MYELODYSPLASTIC SYNDROMES

    OpenAIRE

    Julie Schanz; Friederike Braulke; Detlef Haase

    2015-01-01

    The karyotype represents one of the main cornerstones for the International Prognostic Scoring System (IPSS) and the revised IPSS-R (IPSS-R) that are most widely used for prognostication in patients with myelodysplastic syndromes (MDS). The most frequent cytogenetic abnormalities in MDS, i.e. del(5q), -7/del(7q), +8, complex karyotypes, or -Y have been extensively explored for their prognostic impact. The IPSS-R also considers some less frequent abnormalities such as del(11q), isochromosome 1...

  7. Design and rationale of the QUAZAR Lower-Risk MDS (AZA-MDS-003) trial: a randomized phase 3 study of CC-486 (oral azacitidine) plus best supportive care vs placebo plus best supportive care in patients with IPSS lower-risk myelodysplastic syndromes and poor prognosis due to red blood cell transfusion-dependent anemia and thrombocytopenia.

    Science.gov (United States)

    Garcia-Manero, Guillermo; Almeida, Antonio; Giagounidis, Aristoteles; Platzbecker, Uwe; Garcia, Regina; Voso, Maria Teresa; Larsen, Stephen R; Valcarcel, David; Silverman, Lewis R; Skikne, Barry; Santini, Valeria

    2016-01-01

    CC-486 is an oral formulation of the epigenetic modifier azacitidine. In an expanded phase 1 trial, CC-486 demonstrated clinical and biological activity in patients with International Prognostic Scoring System (IPSS) lower-risk (low- and intermediate-1-risk) myelodysplastic syndromes (MDS) with poor prognostic features including anemia and/or thrombocytopenia who may have required red blood cell or platelet transfusions. The overall response rate was 40 %, including hematologic improvement in 28 % of patients and RBC transfusion independence sustained for 56 days in 47 % of patients with baseline transfusion dependence. Based on the results of this study, the randomized, placebo-controlled phase 3 QUAZAR Lower-Risk MDS trial (AZA-MDS-003) was initiated. The design and rationale for this trial comparing CC-486 with placebo for the treatment of patients with IPSS lower-risk MDS with poor prognostic features are described. Patients must have IPSS lower-risk MDS with red blood cell (RBC) transfusion-dependent anemia and thrombocytopenia. Eligible patients are randomized 1:1 to receive 300 mg of CC-486 or placebo once daily for the first 21 days of 28-day treatment cycles. Disease status assessments occur at the end of cycle 6 and patients may continue to receive treatment unless there is evidence of progressive disease, lack of efficacy, or unacceptable toxicity. The primary endpoint is RBC transfusion independence for ≥ 84 days, assessed according to International Working Group 2006 criteria. Secondary endpoints include overall survival, hematologic response including platelet response and erythroid response, RBC transfusion independence for ≥ 56 days, duration of RBC transfusion independence, time to RBC transfusion independence, rate of acute myeloid leukemia (AML) progression, time to AML progression, clinically significant bleeding events, safety, health-related quality of life, and healthcare resource utilization. This study will provide data

  8. Leptin-deficient obesity prolongs survival in a murine model of myelodysplastic syndrome.

    Science.gov (United States)

    Kraakman, Michael J; Kammoun, Helene L; Dragoljevic, Dragana; Al-Sharea, Annas; Lee, Man K S; Flynn, Michelle C; Stolz, Christian J; Guirguis, Andrew A; Lancaster, Graeme I; Chin-Dusting, Jaye; Curtis, David J; Murphy, Andrew J

    2018-01-25

    Obesity enhances the risk of developing myelodysplastic syndromes. However, the effect of obesity on survival is unclear. Obese people present with monocytosis due to inflammatory signals emanating from obese adipose tissue. We hypothesized that obesity-induced myelopoiesis would promote the transition of myelodysplastic syndrome to acute myeloid leukemia and accelerate mortality in obesity. Obese Ob/Ob mice or their lean littermate controls received a bone marrow transplant from NUP98-HOXD13 transgenic mice, a model of myelodysplastic syndrome. The metabolic parameters of the mice were examined throughout the course of the study, as were blood leukocytes. Myeloid cells were analyzed in the bone, spleen, liver and adipose tissue by flow cytometry halfway through the disease progression and at the endpoint. Survival curves were also calculated. Contrary to our hypothesis, transplantation of NUP98-HOXD13 bone marrow into obese recipient mice significantly increased survival time compared with lean recipient controls. While monocyte skewing was exacerbated in obese mice receiving NUP98-HOXD13 bone marrow, transformation to acute myeloid leukemia was not enhanced. Increased survival of obese mice was associated with a preservation of fat mass as well as increased myeloid cell deposition within the adipose tissue and a concomitant reduction in detrimental myeloid cell accumulation within other organs. This study revealed that obesity increases survival in animals with myelodysplastic syndrome. This may be due to the greater fat mass of Ob/Ob mice, which acts as a sink for myeloid cells, preventing their accumulation in other key organs such as the liver. Copyright © 2018, Ferrata Storti Foundation.

  9. Impact of tobacco usage on disease outcome in myelodysplastic syndromes.

    Science.gov (United States)

    Mishra, Asmita; Rollison, Dana E; Brandon, Thomas H; Al Ali, Najla H; Corrales-Yepez, Maria; Padron, Eric; Epling-Burnette, Pearlie K; Lancet, Jeffrey E; List, Alan F; Komrokji, Rami S

    2015-07-01

    We hypothesized that tobacco usage is an independent prognostic factor in patients with myelodysplastic syndromes (MDS). To evaluate the impact of tobacco usage in this population, we identified patients diagnosed with MDS in our Center's MDS database and reviewed individual charts retrospectively. Of the 767 MDS patients identified, 743 patients (97%) had a known tobacco usage history. Given that the majority of tobacco users were smokers, we stratified patients as having never smoked (never-smoker group) versus current or former smokers (ever-smoker group). Greater than 60% of ever-smokers were risk stratified as having low or intermediate-1 (int-1) risk at diagnosis based on the International Prognostic Scoring System for MDS. In patients with lower-risk MDS, we found that ever-smokers had an increased proportion of poor-risk karyotypes (8.8%) compared with never-smokers (2.4%) (P=0.003). The adverse effect of smoking was greatest in the low-risk and int-1-risk groups, where median overall survival was 69 months (95% CI 42-96) in never-smokers versus 48 months (95% CI 41-55) in ever-smokers (P=0.006). The median overall survival for never-smokers, former smokers, and current smokers was 69 months (95% CI 42-96), 50 months (95% CI 43-57), and 38 months (95% CI 23-53), respectively, in patients risk stratified as lower-risk MDS (P=0.01). Our findings suggest that tobacco usage negatively impacts overall survival in patients with lower-risk MDS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Impact of the International Prognostic Scoring System cytogenetic risk groups on the outcome of patients with primary myelodysplastic syndromes undergoing allogeneic stem cell transplantation from human leukocyte antigen-identical siblings: a retrospective analysis of the European Society for Blood and Marrow Transplantation-Chronic Malignancies Working Party

    NARCIS (Netherlands)

    Onida, F.; Brand, R.; Biezen, A. van; Schaap, M.; Borne, P.A. von dem; Maertens, J.; Beelen, D.W.; Carreras, E.; Alessandrino, E.P.; Volin, L.; Kuball, J.H.; Figuera, A.; Sierra, J.; Finke, J.; Kroger, N.; Witte, T.J. de

    2014-01-01

    Acquired chromosomal abnormalities are important prognostic factors in patients with myelodysplastic syndromes treated with supportive care and with disease-modifying therapeutic interventions, including allogeneic hematopoietic stem cell transplantation. To assess the prognostic impact of

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

    Science.gov (United States)

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

    2009-03-01

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

  12. Future directions in myelodysplastic syndrome: newer agents and the role of combination approaches.

    Science.gov (United States)

    Gore, Steven D; Hermes-DeSantis, Evelyn R

    2008-10-01

    Myelodysplastic syndrome (MDS) is not a single disease, but a collection of hematopoietic disorders that require newer strategies. Currently, azacitidine, decitabine, and lenalidomide are approved by the US Food and Drug Administration for the treatment of MDS. A recent study demonstrated an improved overall survival (24.4 months vs 15 months) in high-risk MDS patients receiving azacitidine plus best supportive care vs conventional care which has resulted in an updated label for this product. Conventional care consisted of supportive care alone or either low-dose ara-C or standard chemotherapy plus best supportive care. While these data are encouraging, newer agents such as vorinostat, MGCD0103, MS-275, and tipifarnib are currently being studied as monotherapy or in combinations with approved treatments for MDS. The goal of combining pharmacotherapy, such as the combination of DNA methylation inhibitors and histone deacetylase inhibitors, in the management of MDS is to increase the response rates and decrease the toxicities associated with treatment. Clinical experience in the use of combination products has given practitioners the empirical knowledge necessary to better treat patients with MDS. Utilizing convergent or complementary molecular mechanisms with in vitro or in vivo evidence of synergy is a fresher and maybe a more efficacious approach to combination therapy.

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

    Science.gov (United States)

    Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are composed of three major myeloid disorders: chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and atypical chronic myeloid leukemia (aCML). Learn about the clinical features and treatment of these leukemias.

  14. 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

  15. Strategic Role of Nuclear Inositide Signalling in Myelodysplastic Syndromes Therapy.

    Science.gov (United States)

    Manzoli, Lucia; Mongiorgi, Sara; Clissa, Cristina; Finelli, Carlo; Billi, Anna Maria; Poli, Alessandro; Quaranta, Marilisa; Cocco, Lucio; Follo, Matilde Y

    2014-10-13

    Nuclear inositide signalling is implicated in normal and pathological cell proliferation and differentiation in several distinct models. Among the key molecules of nuclear inositide pathways, phosphoinositide-phospholipase (PI-PLC) C β1 is essential for regulating hematopoiesis, particularly along myeloid and erythroid lineage. Moreover, Akt activation is associated with protein synthesis, via mTOR pathway, and with erythroid induction, through PI-PLCγ1 activation. Myelodysplastic syndromes (MDS) are a series of heterogeneous diseases characterized by ineffective hemopoiesis, with a variable risk of evolution into acute myeloid leukemia (AML). Therapeutic approaches for MDS include demethylating agents, such as azacitidine, aiming at reducing cell proliferation, and erythropoietin, useful for sustaining a normal erythropoiesis. In the last few years, a role for nuclear inositide signalling as a therapeutic target in MDS has been disclosed, in that PI-PLCβ1 increase is associated with azacitidine responsiveness, even when this drug is used in combination with other agents, and Akt is specifically activated in MDS at higher risk of AML evolution. On the other hand, recent data demonstrated that inositide signalling can also be involved in erythroid therapy, given the inhibitory effect of erythropoietin on PI-PLCβ1 and the activation of Akt/PI-PLCγ1 pathway, following the administration of erythropoietin. Here, we review the strategic role of nuclear inositide signalling in MDS, in pathogenesis and therapy.

  16. Nuclear inositide signaling in myelodysplastic syndromes.

    Science.gov (United States)

    Follo, Matilde Y; Mongiorgi, Sara; Finelli, Carlo; Clissa, Cristina; Ramazzotti, Giulia; Fiume, Roberta; Faenza, Irene; Manzoli, Lucia; Martelli, Alberto M; Cocco, Lucio

    2010-04-15

    Myelodysplastic syndromes (MDS) are defined as clonal hematopoietic stem-cell disorders characterized by ineffective hematopoiesis in one or more of the lineages of the bone marrow. Although distinct morphologic subgroups exist, the natural history of MDS is progression to acute myeloid leukemia (AML). However, the molecular the mechanisms the underlying MDS evolution to AML are not completely understood. Inositides are key cellular second messengers with well-established roles in signal transduction pathways, and nuclear metabolism elicited by phosphoinositide-specific phospholipase C (PI-PLC) beta1 and Akt plays an important role in the control of the balance between cell cycle progression and apoptosis in both normal and pathologic conditions. Recent findings evidenced the role played by nuclear lipid signaling pathways, which could become promising therapeutic targets in MDS. This review will provide a concise and updated revision of the state of art on this topic.

  17. Validation of the revised International Prognostic Scoring System in patients with myelodysplastic syndrome in Japan: results from a prospective multicenter registry.

    Science.gov (United States)

    Kawabata, Hiroshi; Tohyama, Kaoru; Matsuda, Akira; Araseki, Kayano; Hata, Tomoko; Suzuki, Takahiro; Kayano, Hidekazu; Shimbo, Kei; Zaike, Yuji; Usuki, Kensuke; Chiba, Shigeru; Ishikawa, Takayuki; Arima, Nobuyoshi; Nogawa, Masaharu; Ohta, Akiko; Miyazaki, Yasushi; Mitani, Kinuko; Ozawa, Keiya; Arai, Shunya; Kurokawa, Mineo; Takaori-Kondo, Akifumi

    2017-05-11

    The Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes has been conducting prospective registration, central review, and follow-up study for patients with aplastic anemia and myelodysplastic syndrome (MDS) since 2006. Using this database, we retrospectively analyzed the prognosis of patients with MDS. As of May 2016, 351 cases were registered in this database, 186 of which were eligible for the present study. Kaplan-Meier analysis showed that overall survival (OS) curves of the five risk categories stipulated by the revised international prognostic scoring system (IPSS-R) were reasonably separated. 2-year OS rates for the very low-, low-, intermediate-, high-, and very high-risk categories were 95, 89, 79, 35, and 12%, respectively. In the same categories, incidence of leukemic transformation at 2 years was 0, 10, 8, 56, and 40%, respectively. Multivariate analysis revealed that male sex, low platelet counts, increased blast percentage (>2%), and high-risk karyotype abnormalities were independent risk factors for poor OS. Based on these data, we classified Japanese MDS patients who were classified as intermediate-risk in IPSS-R, into the lower risk MDS category, highlighting the need for careful assessment of treatments within low- and high-risk treatment protocols.

  18. Clinical and biological implications of driver mutations in myelodysplastic syndromes.

    Science.gov (United States)

    Papaemmanuil, Elli; Gerstung, Moritz; Malcovati, Luca; Tauro, Sudhir; Gundem, Gunes; Van Loo, Peter; Yoon, Chris J; Ellis, Peter; Wedge, David C; Pellagatti, Andrea; Shlien, Adam; Groves, Michael John; Forbes, Simon A; Raine, Keiran; Hinton, Jon; Mudie, Laura J; McLaren, Stuart; Hardy, Claire; Latimer, Calli; Della Porta, Matteo G; O'Meara, Sarah; Ambaglio, Ilaria; Galli, Anna; Butler, Adam P; Walldin, Gunilla; Teague, Jon W; Quek, Lynn; Sternberg, Alex; Gambacorti-Passerini, Carlo; Cross, Nicholas C P; Green, Anthony R; Boultwood, Jacqueline; Vyas, Paresh; Hellstrom-Lindberg, Eva; Bowen, David; Cazzola, Mario; Stratton, Michael R; Campbell, Peter J

    2013-11-21

    Myelodysplastic syndromes (MDS) are a heterogeneous group of chronic hematological malignancies characterized by dysplasia, ineffective hematopoiesis and a variable risk of progression to acute myeloid leukemia. Sequencing of MDS genomes has identified mutations in genes implicated in RNA splicing, DNA modification, chromatin regulation, and cell signaling. We sequenced 111 genes across 738 patients with MDS or closely related neoplasms (including chronic myelomonocytic leukemia and MDS-myeloproliferative neoplasms) to explore the role of acquired mutations in MDS biology and clinical phenotype. Seventy-eight percent of patients had 1 or more oncogenic mutations. We identify complex patterns of pairwise association between genes, indicative of epistatic interactions involving components of the spliceosome machinery and epigenetic modifiers. Coupled with inferences on subclonal mutations, these data suggest a hypothesis of genetic "predestination," in which early driver mutations, typically affecting genes involved in RNA splicing, dictate future trajectories of disease evolution with distinct clinical phenotypes. Driver mutations had equivalent prognostic significance, whether clonal or subclonal, and leukemia-free survival deteriorated steadily as numbers of driver mutations increased. Thus, analysis of oncogenic mutations in large, well-characterized cohorts of patients illustrates the interconnections between the cancer genome and disease biology, with considerable potential for clinical application.

  19. [Cytogenetics of myelodysplastic syndromes and its impact as prognostic factor].

    Science.gov (United States)

    Borjas-Gutiérrez, César; Domínguez-Cruz, Martín Daniel; González-García, Juan Ramón

    2017-01-01

    Myelodysplastic syndromes (MDS) are a group of disorders of the hematopoietic stem cell. They are characterized by cytopenia(s), dysplasia of one or more cell lines, ineffective hematopoiesis, and an increased risk for developing acute myelogenous leukemia. The classification of MDS has been complicated due to the great heterogeneity in clinical phenotype as well as in the morphological and cytogenetic characteristics. The prognostic value of cytogenetic abnormalities in MDS has been analyzed in multicenter studies. This approach raised the development of the revised International Prognostic Scoring System (IPSS-R), which analyzes five prognostic variables, among which the cytogenetic study stands out. According to the cytogenetic findings, a classification of MDS in five subgroups was developed. Knowledge of the cytogenetic abnormalities has led to the study of genes involved in various chromosomal rearrangements. Moreover, DNA sequencing has helped to identify mutations in approximately 50 genes related to signal transduction, DNA methylation, transcriptional regulation, and RNA splicing. Therefore, the cytogenetic study should be used to improve the classification and therapeutic management of MDS. This approach will be an essential tool for the development of targeted therapy protocols.

  20. [Recent advances of molecular mechanisms influencing prognosis of myelodysplastic syndrome - review].

    Science.gov (United States)

    Guo, Juan; Chang, Chun-Kang; Li, Xiao

    2012-08-01

    Myelodysplastic syndrome (MDS) is clonal disorder of hematopoiesis characterized by inefficient hematopoiesis, peripheral blood cytopenias, aberrant differentiation, and risk of progression to acute myeloid leukemia. Although specific karyotypic abnormalities have been found to link to MDS for decades, more recent findings have demonstrated the importance of mutations within individual genes. The recent molecular abnormalities found in MDS include following gene mutation such as TET2, TP53, RUNX1, ASXL1, IDH1/IDH2, EZH2 and RAS. In this review, the recent advances of prognostic molecular markers of MDS and their biological and clinical significance are summarized.

  1. Monosomal karyotype predicts poor survival after allogeneic stem cell transplantation in chromosome 7 abnormal myelodysplastic syndrome and secondary acute myeloid leukemia

    NARCIS (Netherlands)

    Gelder, M. van; Wreede, L.C. de; Schetelig, J.; Biezen, A. van; Volin, L.; Maertens, J.; Robin, M.; Petersen, E.; Witte, T.J.M. de; Kroger, N.

    2013-01-01

    Treatment algorithms for poor cytogenetic-risk myelodysplastic syndrome (MDS), defined by chromosome 7 abnormalities or complex karyotype (CK), include allogeneic stem cell transplantation (alloSCT). We studied outcome of alloSCT in chromosome 7 abnormal MDS patients as this data are scarce in

  2. Early Detection of High Risk Pregnancy

    OpenAIRE

    Kurniawan, Arif; Sistiarani, Colti; Hariyadi, Bambang

    2017-01-01

    There are 30.939 pregnant women in Banyumas, with 6.206 cases referred due to high-risk pregnancies. Petahunan village in Pekuncen has the the highest incidence of high-risk pregnancies compared with other villages. The purpose of this study is to describe the implementation of early detection of high-risk pregnancies in Petahunan village, Pekuncen. This study used qualitative research methods with case study approach. Research instruments used in-depth interviews and focus group disscussion ...

  3. [Socioeconomic factors in high risk pregnancy].

    Science.gov (United States)

    Armas Domínguez, J; Shor Pinsker, V; Mac Gregor, C; Karchmer, S

    1977-05-01

    The study of high risk during pregnancy was undertaken to show the most viable ways for solving those problems affecting maternal-fetal morbidity and mortality. The authors are hopeful that in the future, the 2 branches of medicine, perinatology and obstetrics, will no longer differentiate between high risk for mother and fetus or neonate but will direct attention to what is high risk for 1 society in particular. These professionals will undertake an interdisciplinary approach of the problem to benefit society. (author's)

  4. Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes.

    Science.gov (United States)

    Germing, Ulrich; Strupp, Corinna; Kuendgen, Andrea; Isa, Shadi; Knipp, Sabine; Hildebrandt, Barbara; Giagounidis, Aristoteles; Aul, Carlo; Gattermann, Norbert; Haas, Rainer

    2006-12-01

    The aim of this study was a prospective validation of the World Health Organization (WHO) proposals for the classification of myelodysplastic syndromes (MDS) with respect to their prognostic relevance. We classified 1095 patients with MDS diagnosed at our institution between November 1999 and December 2004 according to French-American-British (FAB) and WHO criteria by central morphologic review. The study was not population-based, but included all newly diagnosed patients from different regions in Germany. Patients were followed for survival and disease evolution to acute myeloid leukemia (AML) through December 31th, 2005. According to the WHO classification, there were 89 cases of refractory anemia (RA), 293 of refractory cytopenias with multilineage dysplasia (RCMD), 31 RA with ringed sideroblasts (RARS), 139 RCMD with ringed sideroblasts (RCMD-RS), 142 RA with excess blasts (RAEB) I and 149 RAEB II and 52 patients with 5q- syndrome. The median survival of patients with RA or RARS was not reached, the median survival of patients with RCMD was 31 months, that of patients with RCMD-RS was 28 months, that of 5q- patients was 40 months, of RAEB I 27 months and of RAEB II 12 months. The cumulative risk of AML evolution 2 years after diagnosis was 0% in RA and RARS, 8% in 5q-, 9% in RCMD, 12% in RCMD-RS, 13% in RAEB I and 40% in RAEB II. The number of high-risk karyotypes was lower in patients with RA/RARS than in those with RCMD/RCMD-RS and RAEB I/RAEB II. Karyotype findings were major prognostic variables. The WHO classification is feasible and provides valuable prognostic information, even in a short-term prospective study. Together with cytogenetic data and other prognostic parameters, the WHO classification is very useful for clinical decision making.

  5. Diagnostic and prognostic significance of cytogenetics in adult primary myelodysplastic syndromes.

    Science.gov (United States)

    Jotterand, M; Parlier, V

    1996-10-01

    Cytogenetic analysis has proven to be a mandatory part of the diagnosis of myelodysplastic syndromes (MDS) as well as a major indicator for predicting clinical course and outcome. This review concentrates on the cytogenetic classifications, the incidence and types of chromosome defects and the prognostic significance of the karyotype in adult primary MDS. Two cytogenetic classifications are currently used: one is based on the karyotype complexity (normal, single, double or complex defects), the other on clonal status (all metaphases normal, abnormal or admixture of normal and abnormal clones). Chromosome abnormalities are of both numerical and structural types. Aside from the 5q-syndrome, no specific clinico-cytogenetic entity has been reported. However, several distinct clinical and cellular features have been identified that correlate with the presence of specific chromosome defects such as inv(3)/t(3;3), +6, t(5;12), del(17p) and del(20q). The presence of complex defects is associated with reduced survival and a high risk of leukemic transformation. Among single defects, specific abnormalities may define distinct prognostic groups. Patients with del(5q) as a sole chromosome defect and a refractory anemia without excess of blasts have a favourable prognosis. For patients with trisomy 8 or monosomy 7 there may be distinct types of clinical evolution. Most patients with the 3q21q26 syndrome have a short survival. The presence of two chromosome defects may constitute an independent cytogenetic entity probably associated with relative poor prognosis. Karyotypic evolution generally represents a poor risk factor. The combination of cytogenetics with clinical and hematological features has proven to provide for a better prediction of patients' survival, leukemic transformation and response to treatment. Several scoring systems have been developed. They have to be improved by the study of new patients according to strict clinical and cytogenetic criteria and by the

  6. 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

  7. Rare cytogenetic abnormalities in myelodysplastic syndromes.

    Science.gov (United States)

    Bacher, Ulrike; Schanz, Julie; Braulke, Friederike; Haase, Detlef

    2015-01-01

    The karyotype represents one of the main cornerstones for the International Prognostic Scoring System (IPSS) and the revised IPSS-R (IPSS-R) that are most widely used for prognostication in patients with myelodysplastic syndromes (MDS). The most frequent cytogenetic abnormalities in MDS, i.e. del(5q), -7/del(7q), +8, complex karyotypes, or -Y have been extensively explored for their prognostic impact. The IPSS-R also considers some less frequent abnormalities such as del(11q), isochromosome 17, +19, or 3q abnormalities. However, more than 600 different cytogenetic categories had been identified in a previous MDS study. This review aims to focus interest on selected rare cytogenetic abnormalities in patients with MDS. Examples are numerical gains of the chromosomes 11 (indicating rapid progression), of chromosome 14 or 14q (prognostically intermediate to favorable), -X (in females, with an intermediate prognosis), or numerical abnormalities of chromosome 21. Structural abnormalities are also considered, e.g. del(13q) that is associated with bone marrow failure syndromes and favorable response to immunosuppressive therapy. These and other rare cytogenetic abnormalities should be integrated into existing prognostication systems such as the IPSS-R. However, due to the very low number of cases, this is clearly dependent on international collaboration. Hopefully, this article will help to inaugurate this process.

  8. RARE CYTOGENETIC ABNORMALITIES IN MYELODYSPLASTIC SYNDROMES

    Directory of Open Access Journals (Sweden)

    Julie Schanz

    2015-04-01

    Full Text Available The karyotype represents one of the main cornerstones for the International Prognostic Scoring System (IPSS and the revised IPSS-R (IPSS-R that are most widely used for prognostication in patients with myelodysplastic syndromes (MDS. The most frequent cytogenetic abnormalities in MDS, i.e. del(5q, -7/del(7q, +8, complex karyotypes, or –Y have been extensively explored for their prognostic impact. The IPSS-R considers also some less frequent abnormalities such as del(11q, isochromosome 17, +19, or 3q abnormalities. However, more than 600 different cytogenetic categories had been identified in a previous MDS study. This review aims to focus interest on selected rare cytogenetic abnormalities in patients with MDS. Examples are numerical gains of the chromosomes 11 (indicating rapid progression, of chromosome 14 or 14q (prognostically intermediate to favorable, -X (in females, with an intermediate prognosis, or numerical abnormalities of chromosome 21. Structural abnormalities are also considered, e.g. del(13q that is associated with bone marrow failure syndromes and favorable response to immunosuppressive therapy. These and other rare cytogenetic abnormalities should be integrated into existing prognostication systems such as the IPSS-R. However, due to the very low number of cases, this is clearly dependent on international collaboration. Hopefully, this article will help to inaugurate this process.

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

    Science.gov (United States)

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

    2011-12-01

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

  10. Low risk and high risk human papillomaviruses (HPVs) and cervical ...

    African Journals Online (AJOL)

    Low risk and high risk human papillomaviruses (HPVs) and cervical cancer in Zimbabwe: epidemiological evidence. M Chirara, G A Stanczuk, S A Tswana, L Nystrom, S Bergstrom, S R Moyo, M J Nzara. Abstract. No Abstract. Central African Journal of Medicine Vol. 47 (2) 2001: pp. 32-34.

  11. Impact of the degree of anemia on the outcome of patients with myelodysplastic syndrome and its integration into the WHO classification-based Prognostic Scoring System (WPSS).

    Science.gov (United States)

    Malcovati, Luca; Della Porta, Matteo G; Strupp, Corinna; Ambaglio, Ilaria; Kuendgen, Andrea; Nachtkamp, Kathrin; Travaglino, Erica; Invernizzi, Rosangela; Pascutto, Cristiana; Lazzarino, Mario; Germing, Ulrich; Cazzola, Mario

    2011-10-01

    Anemia is an established negative prognostic factor in myelodysplastic syndromes but the relationship between its degree and clinical outcome is poorly defined. We, therefore, studied the relationship between severity of anemia and outcome in myelodysplastic syndrome patients. We studied 840 consecutive patients diagnosed with myelodysplastic syndromes at the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, and 504 patients seen at the Heinrich-Heine-University Hospital, Düsseldorf, Germany. Hemoglobin levels were monitored longitudinally and analyzed by means of time-dependent Cox's proportional hazards regression models. Hemoglobin levels lower than 9 g/dL in males (HR 5.56, P=0.018) and 8 g/dL in females (HR=5.35, P=0.026) were independently related to reduced overall survival, higher risk of non-leukemic death and cardiac death (Panemia, defined as hemoglobin below these thresholds, was found to be as effective as transfusion-dependency in the prognostic assessment. After integrating this definition of severe anemia into the WHO classification-based Prognostic Scoring System, time-dependent regression and landmark analyses showed that the refined model was able to identify risk groups with different survivals at any time during follow up. Accounting for severity of anemia through the WHO classification-based Prognostic Scoring System provides an objective criterion for prognostic assessment and implementation of risk-adapted treatment strategies in myelodysplastic syndrome patients.

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

    Science.gov (United States)

    Braun, Thorsten; Fenaux, Pierre

    2013-12-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  14. The proliferation index of specific bone marrow cell compartments from myelodysplastic syndromes is associated with the diagnostic and patient outcome.

    Directory of Open Access Journals (Sweden)

    Sergio Matarraz

    Full Text Available Myelodysplastic syndromes (MDS are clonal stem cell disorders which frequently show a hypercellular dysplastic bone marrow (BM associated with inefficient hematopoiesis and peripheral cytopenias due to increased apoptosis and maturation blockades. Currently, little is known about the role of cell proliferation in compensating for the BM failure syndrome and in determining patient outcome. Here, we analyzed the proliferation index (PI of different compartments of BM hematopoietic cells in 106 MDS patients compared to both normal/reactive BM (n = 94 and acute myeloid leukemia (AML; n = 30 cases using multiparameter flow cytometry. Our results show abnormally increased overall BM proliferation profiles in MDS which significantly differ between early/low-risk and advanced/high-risk cases. Early/low-risk patients showed increased proliferation of non-lymphoid CD34(+ precursors, maturing neutrophils and nucleated red blood cells (NRBC, while the PI of these compartments of BM precursors progressively fell below normal values towards AML levels in advanced/high-risk MDS. Decreased proliferation of non-lymphoid CD34(+ and NRBC precursors was significantly associated with adverse disease features, shorter overall survival (OS and transformation to AML, both in the whole series and when low- and high-risk MDS patients were separately considered, the PI of NRBC emerging as the most powerful independent predictor for OS and progression to AML. In conclusion, assessment of the PI of NRBC, and potentially also of other compartments of BM precursors (e.g.: myeloid CD34(+ HPC, could significantly contribute to a better management of MDS.

  15. The high frequency of the U2AF1 S34Y mutation and its association with isolated trisomy 8 in myelodysplastic syndrome in Asians, but not in Caucasians.

    Science.gov (United States)

    Kim, Seon Young; Kim, Kwantae; Hwang, Byungjin; Im, Kyongok; Park, Si Nae; Kim, Jung-Ah; Hwang, Sang Mee; Bang, Duhee; Lee, Dong Soon

    2017-10-01

    Mutational profiles of 153 Korean myelodysplastic syndrome (MDS) patients were investigated. Sequencing of 87 genes presented similar mutational profiles in Korean MDS patients compared with previous reports. The most frequently mutated genes were ASXL1 (22.9%), U2AF1 (16.3%), TP53 (13.7%), RUNX1 (10.5%), TET2 (10.5%), DNMT3A (8.5%), and SRSF2 (8.5%). The U2AF1 mutation frequency was higher, with different frequencies in the mutated sites of U2AF1 (S34Y, 6/25; S34F, 11/25; and Q157P 8/25). The U2AF1 S34Y mutation was strongly associated with isolated trisomy 8 (5/6, 83%) and was characterized by a younger age of MDS onset (median, 39 years). The S34F mutation was associated with trisomy 8 (6/11, 55%) and del(20q) (3/11, 27%). Data from 10 literatures (total 3460 patients) of 229 U2AF1-mutated cases revealed a significant association between the S34Y and trisomy 8 in Asians (P=0.0001), but not in Caucasians (P=0.080). We infer that U2AF1 S34 mutations characterize a distinct subgroup of MDS: younger age of onset and differential associations with particular cytogenetic aberrations depending on specific mutations [S34Y to +8; S34F to +8 and del(20q)]. The impact and causal relationship between U2AF1 S34 and trisomy 8 need to be elucidated, which might contribute to design of tailored treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. The clinical, haematological and morphological profile of patients with myelodysplastic syndromes: a single institution experience from Turkey.

    Science.gov (United States)

    Demirkan, Fatih; Alacacioglu, Inci; Piskin, Ozden; Ozsan, Hayri G; Akinci, Baris; Ozcan, Ali M; Yavuzsen, Tugba; Yuksel, Erdinc; Undar, Bulent

    2007-07-01

    In a retrospective analysis of 113 patients with primary myelodysplastic syndromes (MDS) diagnosed according to French-American-British (FAB) classification, we evaluated the prognostic impact of FAB and World Health Organisation (WHO) classifications, International Prognostic Scoring System (IPSS), and other clinical and laboratory variables. The median age was 69. IPSS could be applied to 75 patients classified according to the FAB criteria and to 50 patients reclassified according to the WHO criteria. At a median follow-up of 24 months, 22 patients (19.5 %) transformed to acute myelogenous leukaemia (AML). Overall survival (OS) of patients differed significantly between the FAB and WHO subgroups (p WHO classification, significant differences were observed in both OS and leukaemia free survival (LFS) between patients with RA/RARS and refractory cytopenia with multi-lineage dysplasia/refractory cytopenia with multi-lineage dysplasia and ringed sideroblasts (RCMD/RS-RCMD) (p = 0.0001). High-risk according to IPSS score and blood transfusion need were significantly predictive for a shorter survival and higher risk of transformation. Hemoglobin WHO classification for prediction of prognosis in MDS.

  17. High risk of permafrost thaw

    Science.gov (United States)

    E.A.G. Schuur; B.W. Abbott; W.B. Bowden; V. Brovkin; P. Camill; J.P. Canadell; F.S. Chapin; T.R. Christensen; J.P. Chanton; P. Ciais; P.M. Crill; B.T. Crosby; C.I. Czimczik; G. Grosse; D.J. Hayes; G. Hugelius; J.D. Jastrow; T. Kleinen; C.D. Koven; G. Krinner; P. Kuhry; D.M. Lawrence; S.M. Natali; C.L. Ping; A. Rinke; W.J. Riley; V.E. Romanovsky; A.B.K. Sannel; C. Schadel; K. Schaefer; Z.M. Subin; C. Tarnocai; M. Turetsky; K. M. Walter-Anthony; C.J. Wilson; S.A. Zimov

    2011-01-01

    Arctic temperatures are rising fast, and permafrost is thawing. Carbon released into the atmosphere from permafrost soils will accelerate climate change, but the magnitude of this effect remains highly uncertain. Our collective estimate is that carbon will be released more quickly than models suggest, and at levels that are cause for serious concern. We calculate that...

  18. Molecular pathology of myelodysplastic syndromes: new developments and implications for diagnosis and treatment.

    Science.gov (United States)

    Zhang, Xiaohui; Lancet, Jeffrey E; Zhang, Ling

    2015-01-01

    The diagnosis of myelodysplastic syndromes (MDS) has been based on clinical presentations, laboratory and morphological findings, and molecular and cytogenetic profiles. With the advent of single nucleotide polymorphism (SNP) microarrays and high throughput sequencing technologies, a tremendous amount of progress has been made toward better understanding of MDS genetic and molecular changes. Recurring genetic abnormalities have been revealed in up to 80-90% of MDS patients. We herein review clinical and pathological basis of MDS, the most up-to-date advances in molecular diagnostics of MDS, including current understanding of cytogenetic and molecular markers of MDS, and their implications for MDS diagnosis and therapy selection.

  19. Improving antenatal risk assessment in women exposed to high risks.

    Science.gov (United States)

    Perry, Natasha; Newman, Louise K; Hunter, Mick; Dunlop, Adrian

    2015-01-01

    Antenatal substance use and related psychosocial risk factors are known to increase the likelihood of child protection involvement; less is known about the predictive nature of maternal reflective functioning (RF) in this population. This preliminary study assessed psychosocial and psychological risk factors for a group of substance dependent women exposed to high risks in pregnancy, and their impact on child protection involvement. Pregnant women on opiate substitution treatment (n = 11) and a comparison group (n = 15) were recruited during their third trimester to complete measures of RF (Pregnancy Interview), childhood trauma, mental health and psychosocial assessments. At postnatal follow-up, RF was reassessed (Parent Development Interview - Revised Short Version) and mother-infant dyads were videotaped to assess emotional availability (EA). Child protection services were contacted to determine if any concerns had been raised for infant safety. Significant between-group differences were observed for demographics, psychosocial factors, trauma and mental health symptoms. Unexpectedly, no significant differences were found for RF or EA between groups. Eight women in the 'exposed to high risks' group became involved with child protection services. Reflective functioning was not significantly associated with psychosocial risk factors, and therefore did not mediate the outcome of child protection involvement. Women 'exposed to high risks' were equally able to generate a model of their own and their infants' mental states and should not be seen within a deficit perspective. Further research is required to better understand the range of risk factors that predict child protection involvement in high risk groups. © The Author(s) 2013.

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

    Directory of Open Access Journals (Sweden)

    Vasekova P

    2016-08-01

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

  1. The high-risk plaque initiative

    DEFF Research Database (Denmark)

    Falk, Erling; Sillesen, Henrik; Muntendam, Pieter

    2011-01-01

    The High-Risk Plaque (HRP) Initiative is a research and development effort to advance the understanding, recognition, and management of asymptomatic individuals at risk for a near-term atherothrombotic event such as myocardial infarction or stroke. Clinical studies using the newest technologies...

  2. High risk of permafrost thaw

    Energy Technology Data Exchange (ETDEWEB)

    Schuur, E.A.G.; Abbott, B.; Koven, C.D,; Riley, W.J.; Subin, Z.M.; al, et

    2011-11-01

    In the Arctic, temperatures are rising fast, and permafrost is thawing. Carbon released to the atmosphere from permafrost soils could accelerate climate change, but the likely magnitude of this effect is still highly uncertain. A collective estimate made by a group of permafrost experts, including myself, is that carbon could be released more quickly than models currently suggest, and at levels that are cause for serious concern. While our models of carbon emission from permafrost thaw are lacking, experts intimately familiar with these landscapes and processes have accumulated knowledge about what they expect to happen, based on both quantitative data and qualitative understanding of these systems. We (the authors of this piece) attempted to quantify this expertise through a survey developed over several years, starting in 2009. Our survey asked experts what percentage of surface permafrost they thought was likely to thaw, how much carbon would be released, and how much of that would be methane, for three time periods and under four warming scenarios that are part of the new IPCC Fifth Assessment Report.

  3. High risk pregnancy monitored antenatally at home

    NARCIS (Netherlands)

    Monincx, W. M.; Zondervan, H. A.; Birnie, E.; Ris, M.; Bossuyt, P. M.

    1997-01-01

    OBJECTIVE: Is domiciliary antenatal fetal surveillance for selected high risk pregnancies, a feasible alternative for hospital admission? DESIGN: A randomized controlled trial conducted at the Academical Medical Centre, Amsterdam, The Netherlands. SUBJECTS: Between September 1992 and June 1994, 76

  4. Erythropoietin inhibits osteoblast function in myelodysplastic syndromes via the canonical Wnt pathway.

    Science.gov (United States)

    Balaian, Ekaterina; Wobus, Manja; Weidner, Heike; Baschant, Ulrike; Stiehler, Maik; Ehninger, Gerhard; Bornhäuser, Martin; Hofbauer, Lorenz C; Rauner, Martina; Platzbecker, Uwe

    2018-01-01

    The effects of erythropoietin on osteoblasts and bone formation are controversial. Since patients with myelodysplastic syndromes often display excessively high erythropoietin levels, we aimed to analyze the effect of erythropoietin on osteoblast function in myelodysplastic syndromes and define the role of Wnt signaling in this process. Expression of osteoblast-specific genes and subsequent osteoblast mineralization was increased in mesenchymal stromal cells from healthy young donors by in vitro erythropoietin treatment. However, erythropoietin failed to increase osteoblast mineralization in old healthy donors and in patients with myelodysplasia, whereas the basal differentiation potential of the latter was already significantly reduced compared to that of age-matched controls ( P <0.01). This was accompanied by a significantly reduced expression of genes of the canonical Wnt pathway. Treatment of these cells with erythropoietin further inhibited the canonical Wnt pathway. Exposure of murine cells (C2C12) to erythropoietin also produced a dose-dependent inhibition of TCF/LEF promoter activity (maximum at 500 IU/mL, -2.8-fold; P <0.01). The decreased differentiation capacity of erythropoietin-pretreated mesenchymal stromal cells from patients with myelodysplasia could be restored by activating the Wnt pathway using lithium chloride or parathyroid hormone. Its hematopoiesis-supporting capacity was reduced, while reactivation of the canonical Wnt pathway in mesenchymal stromal cells could reverse this effect. Thus, these data demonstrate that erythropoietin modulates components of the osteo-hematopoietic niche in a context-dependent manner being anabolic in young, but catabolic in mature bone cells. Targeting the Wnt pathway in patients with myelodysplastic syndromes may be an appealing strategy to promote the functional capacity of the osteo-hematopoietic niche. Copyright© 2018 Ferrata Storti Foundation.

  5. Azacitidine: a review of its use in the management of myelodysplastic syndromes/acute myeloid leukaemia.

    Science.gov (United States)

    Keating, Gillian M

    2012-05-28

    Azacitidine (Vidaza®) is a pyrimidine nucleoside analogue of cytidine. This article reviews the clinical efficacy and tolerability of azacitidine in the treatment of patients with myelodysplastic syndromes (MDS)/acute myeloid leukaemia (AML), as well as summarizing its pharmacological properties. The randomized, multicentre Cancer and Leukemia Group B 9221 trial compared the efficacy of subcutaneous azacitidine with that of supportive care alone in patients with MDS fulfilling French-American-British (FAB) classification criteria. The overall response rate, the complete response rate and the complete plus partial response rate were significantly higher in patients receiving azacitidine than in those receiving supportive care alone. The randomized, open-label, multicentre AZA-001 trial compared the efficacy of subcutaneous azacitidine with that of conventional care in adults with higher-risk (i.e. International Prognostic Scoring System intermediate-2-risk or high-risk classification) MDS/AML. Prior to randomization, investigators preselected patients to the conventional care strategy considered most appropriate (i.e. best supportive care, low-dose cytarabine or intensive chemotherapy). The median duration of overall survival was significantly prolonged by 9.4 months in patients with higher-risk MDS receiving azacitidine versus those receiving conventional care. The survival benefit seen with azacitidine versus conventional care was maintained across various patient subgroups (e.g. in patients aged ≥75 years, in those who did not achieve complete remission and in patients with WHO-defined AML). The efficacy of subcutaneous or intravenous azacitidine was also shown in a noncomparative trial in Japanese patients with MDS fulfilling FAB classification criteria, and registry programmes in various countries support the efficacy of azacitidine in patients with MDS. Azacitidine was generally well tolerated in patients with MDS, including in the elderly. Across trials

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-04-15

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

  7. A phase II open-label study of the intravenous administration of homoharringtonine in the treatment of myelodysplastic syndrome.

    Science.gov (United States)

    Daver, N; Vega-Ruiz, A; Kantarjian, H M; Estrov, Z; Ferrajoli, A; Kornblau, S; Verstovsek, S; Garcia-Manero, G; Cortes, J E

    2013-09-01

    Homoharringtonine is an alkaloid inhibitor of protein synthesis with activity in myeloid malignancies. We report a phase II pilot study of homoharringtonine in myelodysplastic syndrome (MDS). Induction consisted of homoharringtonine at 2.5 mg/m(2) via continuous infusion for 7 days. Maintenance was given every 4 weeks. Nine patients were enrolled: five with refractory anaemia with excess blasts, two with refractory anaemia with excess blasts in transformation, one each with refractory anaemia and chronic myelomonocytic leukaemia respectively. Median age was 70 years (55-84) and 6 (66%) were male. Per International Prognostic Scoring System (IPSS) two patients were intermediate-1, five intermediate-2 and two high-risk. Median chemotherapy courses were one (1-3). One patient (11%) responded with complete haematological and cytogenetic remission after one course. Eight patients did not respond (four had stable disease, two progressed to acute leukaemia and two died during induction - from aspergillus pneumonia and intracerebral haemorrhage respectively). Grade 3/4 myelosuppression seen in 56% (5/9). Serious non-haematological toxicities included one case of grade 4 left bundle branch heart block and one grade 3 nephrotoxicity. Median time between courses was 42 days (35-72 days). In conclusion homoharringtonine might have clinical activity in some patients with MDS. © 2013 John Wiley & Sons Ltd.

  8. [Cyclosporine A based therapy for myelodysplastic syndrome].

    Science.gov (United States)

    Li, Zhen-Ling; Gong, Ming; Xu, Shao-Hua; Huang, Fan-Zhou; Chen, Yan-Rong; Ma, Yi-Gai

    2005-10-01

    To determine the efficacy and tolerance to cyclosporine A (CsA) based therapy in patients with myelodysplastic syndrome (MDS), 16 patients with MDS consisting of 10 refractory anemia (RA) and 6 refractory anemia with accessory blasts less than 10% (RAEB-1) were analyzed. Five patients had hypocellular bone marrows and 11 patients had normocellular or hypercellular marrows. The dose of CsA was 2.5-5.5 mg/(kg.d) for 2 weeks to 2 years (mean 8 months). Two out of 16 patients were treated with CsA alone, 14 patients were treated with CsA, recombinant human erythropoietin, androgens, 1, 25 dihydroxy vitamin D(3) or two or three of them combination with CsA. Treatment responses were classified according to the International Working Group (IWG) criteria as complete remission (CR), partial remission (PR), hematological improvement (HI) and no response (NR). Patients who obtained CR, PR or HI were defined as responders. The results showed that HI was observed in 12 patients, PR in 2 patients and NR in 2 patients. Total response rate was 87.5%. Response rates shown in neutrophil lineage, platelet and erythroid lineage were 83.3%, 66.7% and 60%, respectively; their shortest time required to obtain some hematologic improvement after initiation of CsA therapy was 2 weeks, 1 month and 1 month, respectively. Of 13 patients being transfusion-dependent before treatment, 3 patients did not need transfusion any more and 5 showed the reduced transfusion requirements after CsA therapy. In 10 patients with RA, 9 responded to CsA. Of 6 patients with RAEB, 1 patient had no response and died of RAEB-t and 5 patients had transient responses. One of the latter transformed to CMML and two relapsed. The total response rate decreased to 50% in the patients with CsA therapy lasting more than 3 months at the end of following-up. The adverse effects included hirsutism, hyperplastic gingiva, reversible hepatic and renal dysfunction. In conclusion, the usefulness of CsA based therapy for MDS-RA and

  9. Management of high-risk pregnancy.

    Science.gov (United States)

    Coco, L; Giannone, T T; Zarbo, G

    2014-08-01

    Today, 88% of pregnancies has a physiological course during which just basic care, while in 12% of cases there is a high-risk pregnancy that requires additional assistance and specific. The approach that should be used is that of supervision in all pregnant women considering their potential to have a normal pregnancy until there is no clear evidence to the contrary. Pregnancy is considered at risk if there are medical conditions that may affect maternal or fetal health or life of the mother, fetus or both. Among the risk factors for pregnancy there is first the woman's age, in fact the increase in high-risk pregnancies in the last 20 years is attributable to the increase in the average age of women who face pregnancy. In addition, the diet is very important during pregnancy and diabetes or autoimmune diseases often lead to the failure of a pregnancy. Risk factors for pregnancy, also, are the complications that occur during its course as hypertension during pregnancy, and infectious diseases. Fears and anxieties typical of a high-risk pregnancy prevent the couple to live happily in the months of gestation. Effective communication, control and early detection are important tools that doctors must be able to ensure that women in order to plan the best treatment strategies and to minimize the risks of maternal and / or fetal.

  10. Corticosteroid-responsive nephrotic syndrome in children with myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Bogdanović Radovan

    2002-01-01

    Full Text Available Several reports have documented various forms of glomerular diseases in adults with myelodysplastic syndromes (MDS, but similar reports in children are lacking. We describe two children with MDS-associated with steroid-responsive nephrotic syndrome (NS. Patient 1, who had MDS with myelofibrosis, presented also hepatosplenomegaly, pancytopenia, chronic hepatitis, moderate proteinuria, hypocomplementemia and elevated ANA titer. During initial prednisone treatment proteinuria markedly diminished and partial but transient haematological improvement occurred. Relapse subsequently occurred that was manifested by overt NS and pancytopenia. High doses of prednisolone led to remission of the renal disease but haematological remission did not occur. Persisting pancytopenia and repeated infections terminated in sepsis, two years after the onset of MDS. Patient 2, who had refractory anemia with clonal monosomy 19, manifested bowel disease, hepatospleno- megaly, anaemia and non-organic specific autoantibodies. Prednisone led to both clinical and haematological remission. Haematologic disease relapsed 12 months later, when nephrotic-range proteinuria, haematuria and mild azotaemia were also found. Corticosteroid treatment led to long-lasting renal and haematologic remission, maintained by a small dosage of prednisone. In both patients renal biopsy findings were consistent with those seen in idiopathic NS. A Medline search disclosed 16 cases of glomerulopathy in the course of MDS in adult patients. Clinical features included NS, usually accompanied by renal insufficiency with either acute, chronic, or rapidly progressive glomerulonephritis. On biopsy, membranous nephropathy, crescentic or mesangial proliferative glomerulonephritis and AL amyloidosis, were found. We conclude: (1 that glomerular disease may be present and should be searched for in patients with MDS; (2 that MDS can be added to the list of rare conditions associated with corticosteroid

  11. Pleural effusions in patients with acute leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Faiz, Saadia A; Bashoura, Lara; Lei, Xiudong; Sampat, Keeran R; Brown, Tiffany C; Eapen, George A; Morice, Rodolfo C; Ferrajoli, Alessandra; Jimenez, Carlos A

    2013-02-01

    Pleural effusions are rarely observed in patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN). Therefore the underlying etiology of pleural effusions and the efficacy and safety of pleural procedures in this population has not been well studied. In a retrospective review of cases from 1997 to 2007, we identified 111 patients with acute leukemia or MDS/MPN who underwent pleural procedures. Clinical characteristics were reviewed, and survival outcomes were estimated by Kaplan-Meier methods. A total of 270 pleural procedures were performed in 111 patients (69 AML, 27 ALL, 15 MDS/MPN). The main indications for pleural procedures were possible infection (49%) and respiratory symptoms (48%), and concomitant clinical symptoms included fever (34%), dyspnea (74%), chest pain (24%) and cough (37%). Most patients had active disease (61%). The most frequent etiology of pleural effusions was infection (47%), followed by malignancy (36%). Severe thrombocytopenia (platelet count < 20 × 10(3)/µL) was present in 43% of the procedures, yet the procedural complication rate was only 1.9%. Multivariate analysis revealed that older age, AML, MDS/MPN and active disease status were associated with a shorter median overall survival. Infection and malignant involvement are the most common causes of pleural effusion in patients with acute leukemia or MDS. After optimizing platelet count and coagulopathy, thoracentesis may be performed safely and with high diagnostic yield in this population. Survival in these patients is determined by the response to treatment of the hematologic malignancy.

  12. Anemia as the Main Manifestation of Myelodysplastic Syndromes.

    Science.gov (United States)

    Santini, Valeria

    2015-10-01

    Myelodysplastic syndromes (MDS) are a constellation of different diseases sharing anemia in the great majority of cases, and this cytopenia defines these pathologies and their most dramatic clinical manifestations. Anemia in MDS is due to ineffective erythropoiesis, with a high degree of apoptosis of marrow erythroid progenitors. These progenitors show distinctive dysplastic features that consent diagnosis, and are recognizable and differentiated, although not easily, from other morphologic alterations present in other types of anemia. Reaching the diagnosis of MDS in a macrocytic anemia and alleviating the symptoms of anemia are therefore an essential objective of the treating physician. In this work, the signs and symptoms of anemia in MDS, as well as its peculiar pathophysiology, are discussed. Erythopoietic stimulating agents (ESAs) are providing the best treatment for anemic MDS patients, but their use is still not approved by health agencies. While still waiting for this waiver, their clinical use is widespread and their effectivness is well known, as well as the dismal prognosis of patients who do not respond to ESAs and require transfusions. MDS with del5q constitute a unique model of anemia whose complex pathophysiology has been clarified at least partially, defining its link to ribosomal alterations likewise what observed in hereditary anemias like Blackfan Diamond anemia. Lenalidomide is the agent that has shown striking and specific erythropoietic activity in del5q MDS, and the basis of this response is starting to be understood. Several new agents are under evaluation for ESA refractory/relapsed MDS patients, targeting different putative mechanisms of ineffective erythropoiesis, and are here reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Electroconvulsive therapy during high-risk pregnancy.

    Science.gov (United States)

    Walker, R; Swartz, C M

    1994-09-01

    Pregnancy increases the risk of injury associated with mental illness. The varieties of malnutrition, substance abuse, and aggression that may accompany mental illness can injure the unborn child in more severe ways than the patient herself. Dangers associated with illness-related behavior can outweight the risks of pharmacotherapy, but no psychotropic drug is approved for use during pregnancy. Failure to produce a prompt or lasting remission of psychiatric symptoms also is a significant possibility with medication. The morbidity from continued illness and the incompletely described adverse effects of psychotropic drugs increases the attractiveness of ECT for severely depressed pregnant patients, especially with associated high-risk conditions. This paper discusses physiologic changes occurring during pregnancy and ECT and reviews contemporary monitors of maternal and fetal well-being. Guidelines are suggested for ECT during regular and high-risk pregnancies. The authors conclude that using additional precautions with high-risk pregnant patients permits ECT to be given with relative safety; medical and obstetric risk factors need not prevent its use.

  14. Fever of unknown origin due to preleukemia/myelodysplastic syndrome: the diagnostic importance of monocytosis with elevated serum ferritin levels.

    Science.gov (United States)

    Cunha, Burke A; Hamid, Naveed; Krol, Vitaly; Eisenstein, Lawrence

    2006-01-01

    Fever of unknown origin (FUO) is a common clinical diagnostic dilemma. In the elderly, causes of FUO most commonly include malignancy or infection, and less commonly include collagen vascular diseases. Among the collagen vascular diseases causing FUO in the elderly, polymyalgia rheumatica/temporal arteritis, and adult Still's disease (adult juvenile rheumatoid arthritis) are difficult diagnoses to prove. Among the infectious causes of FUO in the elderly are subacute bacterial endocarditis, intra-abdominal abscesses, and extrapulmonary tuberculosis. In the elderly, neoplastic causes of FUO include lymphomas, hepatomas, renal cell carcinomas, and hepatic or central nervous system metastases. Acute leukemias, particularly during "blast" transformation, may present as acute fevers in the absence of infection, but are rare causes of FUO. Preleukemia/myelodysplastic syndromes are exceedingly rare causes of FUO. We present a case of an elderly man who presented with findings that initially suggested adult Still's disease. Prolonged and profound monocytosis provided the key clue to his subsequent diagnosis of preleukemia/myelodysplastic syndrome. In this patient, a positive Naprosyn test result also suggested a neoplastic cause for his FUO. After months of prolonged fevers, myelocytes/metamyelocytes were eventually demonstrated in his peripheral smear during hospital evaluation. These findings, in concert with the persistent monocytosis, highly elevated ferritin levels, polyclonal gammopathy on serum protein electrophoresis, and eventual presence of myelocytes/metamyelocytes on peripheral smear, prompted a bone marrow test that demonstrated blast cells confirming the diagnosis of preleukemia myelodysplastic syndrome as the cause of this patient's FUO.

  15. Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes.

    Science.gov (United States)

    Della Porta, M G; Travaglino, E; Boveri, E; Ponzoni, M; Malcovati, L; Papaemmanuil, E; Rigolin, G M; Pascutto, C; Croci, G; Gianelli, U; Milani, R; Ambaglio, I; Elena, C; Ubezio, M; Da Via', M C; Bono, E; Pietra, D; Quaglia, F; Bastia, R; Ferretti, V; Cuneo, A; Morra, E; Campbell, P J; Orazi, A; Invernizzi, R; Cazzola, M

    2015-01-01

    The World Health Organization classification of myelodysplastic syndromes (MDS) is based on morphological evaluation of marrow dysplasia. We performed a systematic review of cytological and histological data from 1150 patients with peripheral blood cytopenia. We analyzed the frequency and discriminant power of single morphological abnormalities. A score to define minimal morphological criteria associated to the presence of marrow dysplasia was developed. This score showed high sensitivity/specificity (>90%), acceptable reproducibility and was independently validated. The severity of granulocytic and megakaryocytic dysplasia significantly affected survival. A close association was found between ring sideroblasts and SF3B1 mutations, and between severe granulocytic dysplasia and mutation of ASXL1, RUNX1, TP53 and SRSF2 genes. In myeloid neoplasms with fibrosis, multilineage dysplasia, hypolobulated/multinucleated megakaryocytes and increased CD34+ progenitors in the absence of JAK2, MPL and CALR gene mutations were significantly associated with a myelodysplastic phenotype. In myeloid disorders with marrow hypoplasia, granulocytic and/or megakaryocytic dysplasia, increased CD34+ progenitors and chromosomal abnormalities are consistent with a diagnosis of MDS. The proposed morphological score may be useful to evaluate the presence of dysplasia in cases without a clearly objective myelodysplastic phenotype. The integration of cytological and histological parameters improves the identification of MDS cases among myeloid disorders with fibrosis and hypocellularity.

  16. High risk process control system assessment methodology

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Venetia [Pontificia Universidade Catolica do Rio de Janeiro (PUC-Rio), RJ (Brazil); Zamberlan, Maria Cristina [National Institute of Tehnology (INT), Rio de Janeiro, RJ (Brazil). Human Reliability and Ergonomics Research Group for the Oil, Gas and Energy Sector

    2009-07-01

    The evolution of ergonomics methodology has become necessary due to the dynamics imposed by the work environment, by the increase of the need of human cooperation and by the high interaction between various sections within a company. In the last 25 years, as of studies made in the high risk process control, we have developed a methodology to evaluate these situations that focus on the assessment of activities and human cooperation, the assessment of context, the assessment of the impact of work of other sectors in the final activity of the operator, as well as the modeling of existing risks. (author)

  17. NAD(PH: quinone oxidoreductase 1 deficiency conjoint with marginal vitamin C deficiency causes cigarette smoke induced myelodysplastic syndromes.

    Directory of Open Access Journals (Sweden)

    Archita Das

    Full Text Available BACKGROUND: The etiology of myelodysplastic syndromes (MDS is largely unknown. Exposure to cigarette smoke (CS is reported to be associated with MDS risk. There is inconsistent evidence that deficiency of NAD(PH-quinone: oxidoreductase 1 (NQO1 increases the risk of MDS. Earlier we had shown that CS induces toxicity only in marginal vitamin C-deficient guinea pigs but not in vitamin C-sufficient ones. We therefore considered that NQO1 deficiency along with marginal vitamin C deficiency might produce MDS in CS-exposed guinea pigs. METHODOLOGY AND PRINCIPAL FINDINGS: Here we show that CS exposure for 21 days produces MDS in guinea pigs having deficiency of NQO1 (fed 3 mg dicoumarol/day conjoint with marginal vitamin C deficiency (fed 0.5 mg vitamin C/day. As evidenced by morphology, histology and cytogenetics, MDS produced in the guinea pigs falls in the category of refractory cytopenia with unilineage dysplasia (RCUD: refractory anemia; refractory thrombocytopenia that is associated with ring sideroblasts, micromegakaryocytes, myeloid hyperplasia and aneuploidy. MDS is accompanied by increased CD34(+ cells and oxidative stress as shown by the formation of protein carbonyls and 8-oxodeoxyguanosine. Apoptosis precedes MDS but disappears later with marked decrease in the p53 protein. MDS produced in the guinea pigs are irreversible. MDS and all the aforesaid pathophysiological events do not occur in vitamin C-sufficient guinea pigs. However, after the onset of MDS vitamin C becomes ineffective. CONCLUSIONS AND SIGNIFICANCE: CS exposure causes MDS in guinea pigs having deficiency of NQO1 conjoint with marginal vitamin C deficiency. The syndromes are not produced in singular deficiency of NQO1 or marginal vitamin C deficiency. Our results suggest that human smokers having NQO1 deficiency combined with marginal vitamin C deficiency are likely to be at high risk for developing MDS and that intake of a moderately large dose of vitamin C would prevent MDS.

  18. Treatment of high-risk smoldering myeloma.

    Science.gov (United States)

    Korde, Neha

    2016-12-01

    Multiple myeloma (MM) is a hematologic malignancy of the plasma cell that causes symptoms of bone pain, renal failure, and anemia. It is usually preceded by a precursor disease state, such as smoldering multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS), and traditional dogma dictates that treatment should be initiated on frank MM symptom development. Emerging evidence suggests that a defined group of "high-risk SMM" may benefit from early treatment, before organ damage and symptoms actually occur. The following article frames the evidence for treatment of high-risk SMM by defining risk categories, reviewing existing therapeutic trial data, and exploring the long-term biologic implications of early treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Not all risks are equal: the risk taking inventory for high-risk sports.

    Science.gov (United States)

    Woodman, Tim; Barlow, Matt; Bandura, Comille; Hill, Miles; Kupciw, Dominika; Macgregor, Alexandra

    2013-10-01

    Although high-risk sport participants are typically considered a homogenous risk-taking population, attitudes to risk within the high-risk domain can vary considerably. As no validated measure allows researchers to assess risk taking within this domain, we validated the Risk Taking Inventory (RTI) for high-risk sport across four studies. The RTI comprises seven items across two factors: deliberate risk taking and precautionary behaviors. In Study 1 (n = 341), the inventory was refined and tested via a confirmatory factor analysis used in an exploratory fashion. The subsequent three studies confirmed the RTI's good model-data fit via three further separate confirmatory factor analyses. In Study 2 (n = 518) and in Study 3 (n = 290), concurrent validity was also confirmed via associations with other related traits (sensation seeking, behavioral activation, behavioral inhibition, impulsivity, self-esteem, extraversion, and conscientiousness). In Study 4 (n = 365), predictive validity was confirmed via associations with mean accidents and mean close calls in the high-risk domain. Finally, in Study 4, the self-report version of the inventory was significantly associated with an informant version of the inventory. The measure will allow researchers and practitioners to investigate risk taking as a variable that is conceptually distinct from participation in a high-risk sport.

  20. Myelodysplastic changes mimicking MDS following treatment for osteosarcoma

    DEFF Research Database (Denmark)

    Løhmann, Ditte

    Myelodysplastic changes mimicking MDS following treatment for osteosarcoma Ditte Juel Adolfsen Løhmann, Department of Pediatrics, Aarhus University Hospital, Skejby, Denmark Authors: Ditte Juel Adolfsen Løhmann and Henrik Hasle. Therapy-related myelodysplastic syndrome/acute myeloid leukaemia (t-MDS....../AML) is a feared long-term complication of paediatric cancer including osteosarcoma. Few develop t-MDS/AML, but it is not known how many have significant haematological changes after finishing treatment for osteosarcoma. In this study we reviewed biochemistry from a consecutive series of children for up to two...... MDS (refractory anaemia with excess blasts) with monosomy 7 was found and a hematopoietic stem cell transplant was performed. In the other case MDS without excess of blasts was found and a spontaneous normalization of the biochemistry occurred. In conclusion in our study most patients treated...

  1. Breast MRI in high risk patients

    NARCIS (Netherlands)

    A.I.M. Obdeijn (Inge-Marie)

    2015-01-01

    markdownabstractAbstract In this thesis we address various indications of breast MRI, with the emphasis on the value of MRI in screening of women with high genetic risk for breast cancer, and especially in BRCA1 mutation carriers. We showed that in the era of up-to-date MRI expertise and

  2. Trends in emerging and high risk activities

    Science.gov (United States)

    Robert C. White; Richard Schreyer; Kent Downing

    1980-01-01

    Newly emerging and high risk activities have increased markedly in the last generation, yet little is known about trends in participation. Factors such as technological innovation and creative experimentation with traditional activities appear to play a major role in the development of new activities. Christy's criteria for mass demand in recreation are used to...

  3. [Analysis on laboratory and clinical characteristics in 65 cases of myelodysplastic syndrome].

    Science.gov (United States)

    Chen, Bao-An; Gao, Chong; Ding, Jie; Ding, Jia-Hua; Sun, Yun-Yu; Zhao, Gang; Cheng, Jian; Wang, Jun; Bao, Wen; Song, Hui-Hui; Xia, Guo-Hua; Ma, Jin-Long; Wu, Lan-Lan

    2009-12-01

    The aim of this study was to gain more insight into the understanding of myelodysplastic syndrome in the clinical and laboratory features. The clinical data of 65 patients with MDS were reviewed and analysed. According to FAB criteria, 65 patients were classified as follows: 27 patients with RA, 1 patient with RAS, 33 patients with RAEB, 3 patients with RAEB-T, and 1 patient with CMML. The median age of them was 66 years old (range 19-89 years), and 6 patients had a history of toxic exposure (secondary MDS). The bone marrow smears, bone marrow biopsy and cytogenetic examinations were performed in this study. The results showed that dysplasia was found in 64 patients examined with bone marrow smears (98.5%), among them trilineage dysplasia in 21 patients (32.3%), bilineage dysplasia in 33 patients (50.8%), only erythroid dysplasia in 8 cases (12.3%) and 2 patients (3.1%) only with myeloid dysplasia. The bone marrow biopsy was performed in 38 patients, abnormal localization of immature precursor (ALIP) occurred in 6 cases. 29 patients had abnormal karyotypes, accounting for 59.2% of the 49 patients subjected cytogenetic examination. The abnormal chromosome was the major cytogenetic abnormality, which occurred more often in secondary MDS and the patients with RAEB or RAEB-T. Among the 49 patients who had received cytogenetic examination, 15 patients transformed into AML with the incidence of 30.61%, but only 3 out of 20 patients in the group of normal chromosome transformed into AML (15%), while 12 out of 29 patients in the group of abnormal karyotypes transformed into AML (41.4%). The median time of following up was 35 months (range 2 - 106 months). The median survival time was 26.8 months and 8 months in the patients with normal karyotype and chromosome aberrations respectively. In conclusion, the incidence of MDS in our country is younger than that in Western countries, the rate of abnormal chromosome in high risk MDS is higher than that in low risk MDS. Meanwhile

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

    Directory of Open Access Journals (Sweden)

    Myrna Candelaria-Hernández

    2017-06-01

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

  5. Increased expression of HERG K+ channels contributes to myelodysplastic syndrome progression and displays correlation with prognosis stratification.

    Science.gov (United States)

    Lu, Li; Du, Wen; Liu, Wei; Guo, Dongmei; He, Xiaoqi; Li, Huiyu

    2016-12-01

    Human ether-a-go-go-related gene (HERG) K+ channels are shown to be aberrantly expressed in a variety of cancer cells where they play roles in contributing to cancer progression. Myelodysplastic syndromes (MDS) are a group of clinical heterogeneous disorders characterized by bone marrow failure and dysplasia of blood cells. However, the involvement of HERG K+ channels in MDS development is poorly understood. The expression of HERG K+ channels in untreated MDS, acute myeloid leukemia (AML) patients and the control group was detected by flow cytometry. The roles of HERG K+ channels in regulation of SKM-1 cell proliferation, apoptosis, and cell cycle were determined by CCK-8 assay and flow cytometry, respectively. We found that expression of HERG K+ channels in MDS patients was significantly higher than controls and was lower than AML. Percentage of HERG K+ channels on CD34+CD38- cells gradually increased from controls to high-grade MDS subtypes. And HERG K+ channel levels showed an ascending tendency from low-risk to high-risk MDS group. In addition, the CCK-8 assay, apoptosis and cell cycle analysis were performed and showed that blockage of HERG K+ channels decreased the proliferation of MDS cells but rarely had effects on cell apoptosis and cell cycle distribution. Our study demonstrated that HERG K+ channels might be a potential tumor marker of MDS. These channels were likely to contribute to MDS progression and were helpful for predicting prognosis of MDS. Inhibition of HERG K+ channels might be a novel therapeutic measure for MDS.

  6. 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.

  7. [New advance of research on prognostic factors in myelodysplastic syndrome--review].

    Science.gov (United States)

    Wei, Jia; Chen, Yan

    2008-12-01

    Myelodysplastic syndrome (MDS) represents a heterogeneous group of myeloid malignancies characterized by abnormal differentiation and maturation of myeloid cells, bone marrow failure, and a genetic instability with enhanced risk to transform to acute myeloid leukemia. Many factors influence on the prognosis of MDS. The prognosis of MDS subtypes has been changing with the application of World Health Organization (WHO) classification and different new prognostic scoring system, the technology development of cytogenetics and flow cytometry, and the advent of new drugs. A series of recent literatures are summarized on different prognostic factors of MDS. In this review, the controversy in application of WHO classification, MDS prognosis in relation with prognostic scoring system, cytogenetics, immunophenotype and therapeutics were discussed.

  8. 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.

  9. High-risk neighborhoods and high-risk families: the human ecology of child maltreatment.

    Science.gov (United States)

    Garbarino, J; Sherman, D

    1980-03-01

    Based on multiple regression analysis to identify the socioeconomic, demographic, and attitudinal correlates of neighborhood differences in the rate of child abuse and neglect, a pair of neighborhoods matched for socioeconomic level was selected, one high risk, the other low risk. Interviews with expert informants ranging from elementary school principals to mailmen were used to develop neighborhood profiles. Samples of families were drawn from each neighborhood and interviews conducted to identify stresses and supports, with special emphasis on sources of help, social networks, evaluation of the neighborhood, and use of formal family support systems. The results lend support to the concept of neighborhood "risk." Families in the high-risk neighborhood, though socioeconomically similar to families in the low-risk neighborhood, report less positive evaluation of the neighborhood as a context for child and family development. Furthermore, they reveal a general pattern of "social impoverishment" in comparison with families in the low-risk neighborhood.

  10. 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.

  11. New treatment strategies in myelodysplastic syndromes and acute myeloid leukemia : Hypomethylating agents and proteasome inhibitors

    NARCIS (Netherlands)

    van der Helm, Lidia Henrieke

    2016-01-01

    New treatment strategies in leukemia and myelodysplastic syndromes Treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is challenging, especially in the large group of patients older than 60 years. In these patients, results of standard chemotherapy are often disappointing

  12. BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

    Science.gov (United States)

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; 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

  13. Genomic analysis of bone marrow failure and myelodysplastic syndromes reveals phenotypic and diagnostic complexity.

    Science.gov (United States)

    Zhang, Michael Y; Keel, Siobán B; Walsh, Tom; Lee, Ming K; Gulsuner, Suleyman; Watts, Amanda C; Pritchard, Colin C; Salipante, Stephen J; Jeng, Michael R; Hofmann, Inga; Williams, David A; Fleming, Mark D; Abkowitz, Janis L; King, Mary-Claire; Shimamura, Akiko

    2015-01-01

    Accurate and timely diagnosis of inherited bone marrow failure and inherited myelodysplastic syndromes is essential to guide clinical management. Distinguishing inherited from acquired bone marrow failure/myelodysplastic syndrome poses a significant clinical challenge. At present, diagnostic genetic testing for inherited bone marrow failure/myelodysplastic syndrome is performed gene-by-gene, guided by clinical and laboratory evaluation. We hypothesized that standard clinically-directed genetic testing misses patients with cryptic or atypical presentations of inherited bone marrow failure/myelodysplastic syndrome. In order to screen simultaneously for mutations of all classes in bone marrow failure/myelodysplastic syndrome genes, we developed and validated a panel of 85 genes for targeted capture and multiplexed massively parallel sequencing. In patients with clinical diagnoses of Fanconi anemia, genomic analysis resolved subtype assignment, including those of patients with inconclusive complementation test results. Eight out of 71 patients with idiopathic bone marrow failure or myelodysplastic syndrome were found to harbor damaging germline mutations in GATA2, RUNX1, DKC1, or LIG4. All 8 of these patients lacked classical clinical stigmata or laboratory findings of these syndromes and only 4 had a family history suggestive of inherited disease. These results reflect the extensive genetic heterogeneity and phenotypic complexity of bone marrow failure/myelodysplastic syndrome phenotypes. This study supports the integration of broad unbiased genetic screening into the diagnostic workup of children and young adults with bone marrow failure and myelodysplastic syndromes. Copyright© Ferrata Storti Foundation.

  14. Major Risk Factors for Heart Disease: High Blood Cholesterol

    Science.gov (United States)

    ... Major Risk Factors for Heart Disease High Blood Cholesterol High blood cholesterol is another major risk factor for heart disease ... can do something about. The higher your blood cholesterol level, the greater your risk for developing heart ...

  15. Analyzing transformation of myelodysplastic syndrome to secondary acute myeloid leukemia using a large patient database.

    Science.gov (United States)

    Shukron, Ofir; Vainstein, Vladimir; Kündgen, Andrea; Germing, Ulrich; Agur, Zvia

    2012-09-01

    One-third of patients with myelodysplastic syndrome (MDS) progress to secondary acute myeloid leukemia (sAML), with its concomitant poor prognosis. Recently, multiple mutations have been identified in association with MDS-to-sAMLtransition, but it is still unclear whether all these mutations are necessary for transformation. If multiple independent mutations are required for the transformation, sAML risk should increase with time from MDS diagnosis. In contrast, if a single critical biological event determines sAML transformation; its risk should be constant in time elapsing from MDS diagnosis. To elucidate this question, we studied a database of 1079 patients with MDS. We classified patients according to the International Prognostic Scoring System (IPSS), using either the French-American-British (FAB) or the World Health Organization (WHO) criteria, and statistically analyzed the resulting transformation risk curves of each group. The risk of transformation after MDS diagnosis remained constant in time within three out of four risk groups, and in all four risk groups, when patients were classified according to FAB or to the WHO-determined criteria, respectively. Further subdivision by blast percentage or cytogenetics had no influence on this result. Our analysis suggests that a single random biological event leads to transformation to sAML, thus calling for the exclusion of time since MDS diagnosis from the clinical decision-making process. Copyright © 2012 Wiley Periodicals, Inc.

  16. Cytogenetics and comorbidity predict outcomes in older myelodysplastic syndrome patients after allogeneic stem cell transplantation using reduced intensity conditioning.

    Science.gov (United States)

    Yucel, Orhan Kemal; Saliba, Rima M; Rondon, Gabriella; Ahmed, Sairah; Alousi, Amin; Bashir, Qaiser; Ciurea, Stefan O; Popat, Uday; Khouri, Isa; Marin, David; Rezvani, Katy; Kebriaei, Partow; Shpall, Elizabeth J; Champlin, Richard E; Oran, Betül

    2017-07-15

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment with a curative potential for myelodysplastic syndrome (MDS) patients. Allo-HSCT has substantial risks, particularly in the elderly, and its role for older MDS patients has yet to be defined. We analyzed 88 MDS patients aged ≥ 60 years with allo-HSCT after reduced intensity conditioning regimens over the last decade. The study cohort had high risk features; 47 of 88 (53.4%) patients were > 65 years of age, 24 (27%) patients had cytogenetic abnormalities consistent with monosomal karyotype (MKpos), 33 (38%) patients had histological subtype of RAEB-1 and RAEB-2 at diagnosis, and 45 (51%) patients had a hematopoietic cell transplantation-comorbidity index (HCT-CI) of ≥ 3. The 3-year incidence of progression, transplant-related mortality (TRM), and overall survival (OS) were 26% (95% confidence interval [CI], 18%-37%), 35% (95% CI, 26%-47%), and 41% (95% CI, 30%-52%), respectively. MKpos was the only prognostic factor that increased the risk of disease progression compared with good-risk cytogenetics (hazard ratio [HR] = 9.5, P = .003) as well as MKneg (HR = 3.3, P = .01). For TRM, HCT-CI ≥ 3, but not age >65 years, was associated with worse outcomes (HR = 3.1, P = .007). Cytogenetics and HCT-CI enabled us to identify prognostic groups for OS. MKpos patients had the worst 3-year OS (17%), whereas patients with good-risk cytogenetics and HCT-CI < 3 had the best OS (92%). Our results confirm that allo-HSCT can provide long-term survival in older MDS patients. Cytogenetics and HCT-CI identify prognostic risk groups and guide selection of older MDS patients who are candidates for allo-HSCT. Cancer 2017;123:2661-70. © 2017 American Cancer Society. © 2017 American Cancer Society.

  17. Defining high risk in endovascular aneurysm repair.

    Science.gov (United States)

    Mastracci, Tara M; Greenberg, Roy K; Hernandez, Adrian V; Morales, Catherine

    2010-05-01

    Long-term survival benefit contrasted with rupture risk should determine which patients are suitable for abdominal aortic aneurysm (AAA) intervention. Our aim was to develop a model capable of predicting long-term survival based on preoperative characteristics. A prospective cohort study using Cox regression modeling. We aimed to associate preoperative characteristics with long-term mortality, and create a predictive nomogram, which was then externally validated on an independent cohort (697 patients) who underwent endovascular abdominal aortic aneurysm (AAA) repair. We pooled the results of 412 patients undergoing endovascular repair of infrarenal and juxtarenal aneurysm who were high risk (average Glasgow aneurysm scores of 72.8 [SD 10.4]). Despite anatomic differences, there were no statistically significant differences in perioperative or long-term outcomes between infrarenal and juxtarenal aneurysms (log rank test, P = .5). Data from this group (64% infrarenal aneurysms and 36% juxtarenal aneurysms) were randomly and evenly split into a model development and test group. Independent predictors of mortality included in the model are age, aneurysm diameter, history of peripheral artery disease, chronic obstructive pulmonary disease (COPD), or congestive heart failure, requirement for supplemental home oxygen, and use of salicylates. Internal validation reveals good calibration and discriminative ability (c-statistic 0.68 [95% confidence interval 0.65-0.71]). External validation confirms good calibration. In the context of acceptable perioperative results, long-term mortality risk can be predicted in endovascular AAA repair and must be balanced against risk of rupture to determine which patients should be offered treatment. Copyright (c) 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  18. Myelodysplastic syndrome with trisomy 11 associated with polycythemia vera.

    Science.gov (United States)

    Ohyashiki, K; Nagasu, M; Hojo, H; Iwabuchi, A; Ohyashiki, J H; Toyama, K

    1989-06-01

    A 52-year-old male with myelodysplastic syndrome (MDS) who had a prior history of polycythemia vera is reported. Chromosome analysis revealed that the bone marrow and blood cells at the MDS phase contained trisomy of chromosome 11 as the sole cytogenetic change. Trisomy 11 is rarely found in hematologic neoplasia, and all of the reported cases with trisomy 11 were diagnosed as having nonlymphocytic neoplasia. In this report, a correlation between the chromosome change and leukemia/MDS developed in polycythemia vera is discussed.

  19. Marked thrombocytosis in a child with advanced myelodysplastic syndrome.

    Science.gov (United States)

    Claviez, Alexander; Ngoumou, Bona; Harder, Lana; Baumann, Irith; Niemeyer, Charlotte

    2004-04-01

    Myelodysplastic syndromes (MDS) are clonal disorders characterized by ineffective hematopoiesis with rare occurrence in childhood. Conversely to adult affected patients, refractory anemia with ringed sideroblasts and the 5q-syndrome, which are associated with thrombocytosis are virtually absent in the pediatric age group. We describe the case of an 1-year-old boy with advanced MDS, specifically refractory anemia with excess of blasts who presented with leukocytopenia and anemia but marked thrombocytosis at diagnosis. Thrombocytosis resolved without therapy. This case illustrates the relationship between MDS and myeloproliferative disorders.

  20. Highly Enhanced Risk Management Emergency Satellite

    DEFF Research Database (Denmark)

    Dalmeir, Michael; Gataullin, Yunir; Indrajit, Agung

    HERMES (Highly Enhanced Risk Management Emergency Satellite) is potential European satellite mission for global flood management, being implemented by Technical University Munich and European Space Agency. With its main instrument - a reliable and precise Synthetic Aperture Radar (SAR) antenna...... - and its orbit characteristics (covering the whole earth surface in 3 days, low altitude), HERMES will provide stand-alone-data for: flood disaster monitoring, flood forecasting and flood prevention. Data obtained by HERMES can be used for commercial soil type maps (e.g. for optimized land use). As only...... highly effective and orbit proven hardware is used, HERMES is designed to be reliable, precise and of low cost. The project can be extended for use on other space bodies (planets) for rapid observation of the planetary surface....

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

    Science.gov (United States)

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

    1985-06-01

    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. The myelodysplastic phase, with or without evolution to acute leukemia, is a highly lethal disease with a median survival comparable to that of the patients who present with

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

    Science.gov (United States)

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

    2016-08-19

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

  3. Use of azacitidine for myelodysplastic syndromes: controversial issues and practical recommendations.

    Science.gov (United States)

    Kim, Yoo-Jin; Jang, Jun Ho; Kwak, Jae-Yong; Lee, Je-Hwan; Kim, Hyeoung-Joon

    2013-06-01

    Azacitidine is recommended for patients with higher-risk myelodysplastic syndromes (MDS) who are not eligible for intensive therapy or for patients with lower-risk MDS who have thrombocytopenia or neutropenia or have anemia that is unresponsive to other therapies. However, standard treatment with azacitidine has not been optimized and many issues about the use of azacitidine remain unresolved. The use of azacitidine is expanding rapidly, but limited comparative clinical trial data are available to (i) define the optimal use of azacitidine in patients with higher-risk MDS or around the time of allogeneic hematopoietic stem cell transplantation, (ii) identify those patients with lower-risk MDS who may benefit from treatment, and (iii) guide physicians on alternative therapies after treatment failure. Increasing evidence suggests that the clinical features, prognostic factors, and cytogenetic profiles of patients with MDS in Asia differ significantly from those of patients in Western countries, so the aim of this review is to summarize the evidence and provide practical recommendations on the use of azacitidine in patients with MDS in the Republic of Korea. Evidence considered in this review is based on published clinical data and on the clinical experience of an expert panel from the acute myeloid leukemia/MDS Working Party of the Korean Society of Hematology.

  4. [Antiphospholipid antibodies in high-risk pregnancy].

    Science.gov (United States)

    Nestorowicz, B; Ostanek, L; Ronin-Walknowska, E; Fiedorowicz-Fabrycy, I; Skoczowska, M; Czajkowska, E; Fischer, K

    2000-06-01

    Recently the connection of antiphospholipid antibodies (aPLs) presence with pregnancy loss and complications in pregnancy has been observed APLs related obstetric complications include: miscarriages after 10 weeks, IUGR, intrauterine foetal death, preeclampsia and severe preeclampsia. Our objective was to determine the aPLs prevalence in patients with recurrent pregnancy loss and/or complicated pregnancy. We examined 154 pregnant women aged 19-42 (average of 29.1) with recurrent pregnancy loss, current pregnancy complicated by preeclampsia and severe preeclampsia and/or IUGR, thrombotic episodes, thrombocytopenia or autoimmune disease. In all the patients anticardiolipin antibodies (aCL) were determined at least twice using ELISA and their coagulation system was tested including lupus anticoagulant (LA) test. In justified cases immunological examinations detecting connective tissue systemic diseases were conducted. Increased aCL titre was detected in 54 (34.4%) women. Statistically significant risk of increased aCL titre was observed in patients with autoimmunological diseases (RR = 4.3). Increased, but Statistically insignificant, risk of high aCL titre was observed in patients with venous thrombosis (RR = 2.45) as well as in patients with thrombocytopenia (RR = 2.45). LA prevailed significantly more often in patients with venous thrombosis episodes (RR = 6.33) and with autoimmunological diseases (RR = 17.4). Preterm deliveries were significantly more frequent in pregnant women with increased aCL titre and/or LA. Moreover, in this group foetal death and preterm stillbirth more often occurred. The above mentioned risks increased when aCL and LA coexisted. No relation between increased aPLs and miscarriage frequency was observed. 1) Increased aPLs titre prevail in multiparas with bad obstetrical anamnesis and with pathological course in present pregnancy, 2) increased aPLs titre prevail in patients with autoimmunological diseases, 3) increased aPLs titre are

  5. Prenatal screening with evaluated high risk scores.

    Science.gov (United States)

    Papiernik, E; Grangé, G

    1999-01-01

    This paper reviews data that support the effectiveness of the French approach of using risk scoring for evaluating the risk of preterm delivery. This approach, which was developed in 1969 and spread to obstetricians and midwives throughout France in the early 1970s, includes systematic information about the recognition of uterine contractions, advice about reduction of physical exercise, and the prescription of work-leave for women with heavy or physically demanding work loads. The effectiveness of this prevention strategy is assessed using three different data sets: an evaluation of a preterm prevention program in the Alsace Region of France, five successive French national sample surveys which collected data on pregnant women, and a study of the effectiveness of a prevention program for twins in the district of Haut de Seine near Paris. The authors show that the rate of preterm birth in France declined substantially, but that the decline was concentrated among singleton spontaneous births. Since the 1970s induced preterm births have increased, and, interventions have not reduced the high rates of preterm birth among twins.

  6. High-risk obstetrics, medicolegal problems.

    Science.gov (United States)

    Herczeg, J

    1997-02-01

    The perinatal period is one of the most dangerous time of life. The responsibilities of the obstetricians are multifold. It is very difficult to draw a line between good and substandard care, therefore in perinatology and especially in high-risk obstetrical cases there are no absolute rules of management. The lay public is convinced through media channels, that modern reproductive research eliminated all the risks and hazards associated with childbirths, therefore only 100% healthy babies are accepted. Pregnancy is regarded as a 'success story' and if the baby is born with neurological defects (cerebral palsy) the parents and their advisors feel, that someone responsible for the defect should be found in the chain of management. This attitude starts a legal battle focusing on the events of labor and delivery. But in most cases it is very difficult to determine if a peripartal neonatal encephalopathy originated from the time period of labor and delivery, or started weeks earlier during pregnancy as an unnoticed event. Perinatal morbidity indicators are best based on neonatal clinical signs, which are predictive of later morbidity of the child. Neonatal seizures within 48 h of delivery of the baby could be a good index of later morbidity.

  7. Biclonal chromosomal aberrations in a child with myelodysplastic syndrome.

    Science.gov (United States)

    Jakab, Z; Balogh, E; Kiss, C; Pajor, L; Oláh, E

    1999-01-01

    Hematological malignancies and premalignant diseases are generally of monoclonal origin. The prognostic and therapeutic significance of finding two genetically independent clones remains to be determined. We followed a case of childhood myelodysplastic syndrome showing biclonal chromosomal abnormalities (+8, -7) by conventional cytogenetic examination and double target fluorescence in situ hybridization (FISH). A 7-year-old girl presented with Plaut-Vincent angina and leukopenia. The cytogenetic aberration of +8 was the first sign to suggest MDS. Serial bone marrow controls, prompted by a progressive clinical course detected myelodysplastic changes and a new clonal aberration (-7). The presence of -7 and +8 in two independent clones was verified by double-target FISH. While at diagnosis and during cytokine treatment more cells showed +8, after successful all-trans retinoic acid (ATRA) therapy, the clone with -7 predominated. Following allogeneic bone marrow transplantation the patient displayed donor-derived hematopoesis. Our data stress the significance of cytogenetic and FISH examinations in detecting specific genetic abnormalities and progressive clonal changes as an indicator and guideline for therapy. Different cell clones characterized by different genetic changes might be associated with different biologic features reflected in their response to treatment.

  8. Suicide risk assessment in high-risk adolescents.

    Science.gov (United States)

    Gray, Barbara P; Dihigo, Sharolyn K

    2015-09-13

    A significant number of adolescents experience depression and other mental health disorders that may put them at risk for suicide. Mental health assessment is an important component of primary healthcare. Depression and suicide risk screening can assist healthcare providers in preventing suicides.

  9. High body mass index and cancer risk

    DEFF Research Database (Denmark)

    Benn, Marianne; Tybjærg-Hansen, Anne; Smith, George Davey

    2016-01-01

    alleles was associated with a 3 % higher BMI (P cancer. In instrumental variable analysis for a 10 kg/m(2) higher genetically determined BMI the odds ratio for any non-skin cancer was 1.16 (0.64-2.09), with a corresponding observational estimate of 0.94 (0.88-1.01). Using......High body mass index (BMI) has been associated with increased risk of some cancer. Whether these reflect causal associations is unknown. We examined this issue. Using a Mendelian randomisation approach, we studied 108,812 individuals from the general population. During a median of 4.7 years...... of follow-up (range 0-37), 8002 developed non-skin cancer, 3347 non-melanoma skin cancer, 1396 lung cancer, 637 other smoking related cancers, 1203 colon cancer, 159 kidney cancer, 1402 breast cancer, 1062 prostate cancer, and 2804 other cancers. Participants were genotyped for five genetic variants...

  10. Safety culture in high-risk industries.

    Science.gov (United States)

    Martyka, Joanna; Lebecki, Kazimierz

    2014-01-01

    This paper addresses the question of whether adopting safety culture improves hazard prevention in enterprises characterized by high primary risk. To answer this question, sample underground coal mines were examined to investigate the basic elements of the safety culture of employees. This paper presents the results of a diagnosis of the basic elements of the safety culture of supervisors (midlevel managers) and blue-collar workers in 3 underground coal mines. The study used 2 techniques: a Likert-type scale and a questionnaire. The results indicate the need to introduce changes in the safety culture of underground coal mine employees. This study also presents the conditions for improvement. Special attention was paid to (a) the conditions for improving safety culture and (b) a programme for modifying risky behaviours.

  11. Prolonged administration of azacitidine with or without entinostat for myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes: results of the US Leukemia Intergroup trial E1905.

    Science.gov (United States)

    Prebet, Thomas; Sun, Zhuoxin; Figueroa, Maria E; Ketterling, Rhett; Melnick, Ari; Greenberg, Peter L; Herman, James; Juckett, Mark; Smith, Mitchell R; Malick, Lisa; Paietta, Elisabeth; Czader, Magdalena; Litzow, Mark; Gabrilove, Janice; Erba, Harry P; Gore, Steven D; Tallman, Martin S

    2014-04-20

    Although azacitidine (AZA) improves survival in patients with high-risk myelodysplastic syndrome, the overall response remains approximately 50%. Entinostat is a histone deacetylase inhibitor that has been combined with AZA with significant clinical activity in a previous phase I dose finding study. Open label phase II randomized trial comparing AZA 50 mg/m(2)/d given for 10 days ± entinostat 4 mg/m(2)/d day 3 and day 10. All subtypes of myelodysplasia, chronic myelomonocytic leukemia, and acute myeloid leukemia with myelodysplasia-related changes were eligible for the study. The primary objective was the rate of hematologic normalization (HN; complete remission + partial remission + trilineage hematological improvement). One hundred forty-nine patients were analyzed, including 97 patients with myelodysplastic syndrome and 52 patients with acute myeloid leukemia. In the AZA group, 32% (95% CI, 22% to 44%) experienced HN and 27% (95% CI, 17% to 39%) in the AZA + entinostat group. Both arms exceeded the HN rate of historical control (Cancer and Leukemia Group B 9221 trial), but only the AZA group fulfilled the primary objective of the study. Rates of overall hematologic response were 46% and 44%, respectively. Median overall survivals were 18 months for the AZA group and 13 months for the AZA + entinostat group. The combination arm led to less demethylation compared with the monotherapy arm, suggesting pharmacodynamic antagonism. Addition of entinostat to AZA did not increase clinical response as defined by the protocol and was associated with pharmacodynamic antagonism. However, the prolonged administration of AZA by itself seems to increase HN rate compared with standard dosing and warrants additional investigation.

  12. Prescription of the High Risk Narcotics and Trading or Illicit Purchasing of High Risk Narcotics

    Directory of Open Access Journals (Sweden)

    Nicoleta-Elena Buzatu

    2012-05-01

    Full Text Available The present essay will analyze the offence of prescribing high risk narcotics and trading or illicit purchasing of high risk narcotics, as it was regulated - together with other offences - by Law no 143 of July 26, 2000 on preventing and fighting against the traffic and illicit consumption of narcotics. The same law defines the meaning of such a phrase “substances which are under national control” by mentioning the fact that they are the narcotics and their precursors listed in Annexes I-IV of the law. The analysis of the offence of prescribing the high risk narcotics and trading or illicit purchasing of high risk narcotics is following the already known structure mentioned in the doctrine and which consists of: object and subjects of the offence, its constituent content: the objective side with its material element, the immediate consequence and causality connections; the subjective side of the offence, as well as forms and modalities of these offences, and the applicable sanctions, of course.

  13. Outcomes for patients with chronic lymphocytic leukemia and acute leukemia or myelodysplastic syndrome.

    Science.gov (United States)

    Tambaro, F P; Garcia-Manero, G; O'Brien, S M; Faderl, S H; Ferrajoli, A; Burger, J A; Pierce, S; Wang, X; Do, K-A; Kantarjian, H M; Keating, M J; Wierda, W G

    2016-02-01

    Acute leukemia (AL) and myelodysplastic syndrome (MDS) are uncommon in chronic lymphocytic leukemia (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 analog combined with alkylating agent±CD20 monoclonal antibody. Twelve cases had no prior CLL treatment. Among 38 cases with AL, 33 had acute myelogenous leukemia (AML), 3 had acute lymphoid leukemia (ALL; 1 Philadelphia chromosome positive), 1 had biphenotypic and 1 had extramedullary (bladder) AML. Unfavorable AML karyotype was noted in 26, and intermediate risk in 7 patients. 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 International Prognostic Scoring System (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 very poor; AL/MDS occurred without prior CLL treatment. Effective therapies for these patients are desperately needed.

  14. Challenging Propofol Sedation in Gastrointestinal Endoscopy: High Risk Patients and High Risk Procedures

    Directory of Open Access Journals (Sweden)

    Eduardo Redondo-Cerezo

    2012-12-01

    Full Text Available Sedation is increasingly becoming a must for most endoscopic procedures. Non-anesthesiologist administration of propofol is the standard of practice in many European countries. Nevertheless, despite anesthesiology societies concerns about sedation guided by endoscopist, practitioners find some limits to propofol administration, related to high risk patients or high risk and complex procedures, which can be long lasting and technically challenging. The main patient related risk factors for sedation are elderly patients, obesity, ASA≥3 patients, individuals with craniofacial abnormalities or with pharyngolaringeal tumors, patients with an acute gastrointestinal bleeding, under pain medications, sedatives, antidepressants, or who consume significant amounts of alcohol or drugs. Procedure related risk factors have more to do with the duration and complexity of the procedure than with other factors, in which considering a general anesthesia allows the endoscopist to concentrate on a difficult task. Published papers addressing the most challenging sedation groups in endoscopy are exploring and even trespassing previously assumed frontiers, and new scenarios are opening to the endoscopist, increasing his/her autonomy, reducing costs and giving patients levels of comfort previously unknown. In this review we analyse each risk group determining the ones in which a sedation protocol could be widely applied, and other in which the published evidence does not guarantee a safe endoscopist guided propofol sedation.

  15. Modeling HIV Risk in Highly Vulnerable Youth

    Science.gov (United States)

    Huba, G. J.; Panter, A. T.; Melchior, Lisa A.; Trevithick, Lee; Woods, Elizabeth R.; Wright, Eric; Feudo, Rudy; Tierney, Steven; Schneir, Arlene; Tenner, Adam; Remafedi, Gary; Greenberg, Brian; Sturdevant, Marsha; Goodman, Elizabeth; Hodgins, Antigone; Wallace, Michael; Brady, Russell E.; Singer, Barney; Marconi, Katherine

    2003-01-01

    This article examines the structure of several HIV risk behaviors in an ethnically and geographically diverse sample of 8,251 clients from 10 innovative demonstration projects intended for adolescents living with, or at risk for, HIV. Exploratory and confirmatory factor analyses identified 2 risk factors for men (sexual intercourse with men and a…

  16. Modeling HIV risk in highly vulnerable youth

    NARCIS (Netherlands)

    Huba, GJ; Panter, AT; Melchior, LA; Trevithick, L; Woods, ER; Wright, E; Feudo, R; Tierney, S; Schneir, A; Tenner, A; Remafedi, G; Greenberg, B; Sturdevant, M; Goodman, E; Hodgins, A; Wallace, M; Brady, RE; Singer, B; Marconi, K

    2003-01-01

    This article examines the structure of several HIV risk behaviors in an ethnically and geographically diverse sample of 8,251 clients from 10 innovative demonstration projects intended for adolescents living with, or at risk for, HIV. Exploratory and confirmatory factor analyses identified 2 risk

  17. The Alder-Reilly anomaly in association with the myelodysplastic syndrome.

    Science.gov (United States)

    Ghandi, M K; Howard, M R; Hamilton, P J

    1996-03-01

    We describe the Alder-Reilly morphological abnormality in an elderly man with a myelodysplastic syndrome (MDS). The literature pertaining to abnormal neutrophil hypergranulation is reviewed and the possible role of myelodysplasia in its causation is discussed.

  18. Recent advances in the understanding of iron overload in sideroblastic myelodysplastic syndrome.

    NARCIS (Netherlands)

    Cuijpers, M.L.H.; Raymakers, R.A.P.; Mackenzie, M.W.; Witte, T.J.M. de; Swinkels, D.W.

    2010-01-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal haematopoietic stem cell malignancies. A subgroup, the so-called sideroblastic MDS, shows ring sideroblasts in the bone marrow aspirate that represent mitochondrial iron accumulation. Patients with sideroblastic MDS also develop

  19. Clinical management of gastrointestinal disturbances in patients with myelodysplastic syndromes receiving iron chelation treatment with deferasirox

    NARCIS (Netherlands)

    Nolte, F.; Angelucci, E.; Beris, P.; Macwhannell, A.; Selleslag, D.; Schumann, C.; Xicoy, B.; Almeida, A.; Guerci-Bresler, A.; Sliwa, T.; Muus, P.; Porter, J.; Hofmann, W.K.

    2011-01-01

    Myelodysplastic syndromes are characterized by ineffective hematopoiesis resulting in peripheral cytopenias. The majority of patients is dependent on regular transfusions of packed red blood cells leading to a secondary iron overload which might result in organ damage. Therefore, sufficient iron

  20. Prevalence and Risk Factors of High Risk Human Papillomavirus ...

    African Journals Online (AJOL)

    Cervical cancer is the most common female cancer in northern Nigeria, yet the pattern of infection with human papillomavirus, the principal aetiologic agent is unknown. This was a preliminary study conducted in two referral hospitals in order to establish base-line data on the prevalence and risk factors for the infection in ...

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

    Directory of Open Access Journals (Sweden)

    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.

  2. [Hematologic response predictor factors in adults with myelodysplastic syndromes (SMD) treated with cyclosporin A (CSA)].

    Science.gov (United States)

    Zamora-Pérez, Elia; López-Karpovitch, Xavier

    2015-01-01

    Myelodysplastic syndromes (MDS) are clonal diseases of hematopoietic cells. The International Prognostic Scoring System (IPSS) is the risk scale most employed in MDS. Cyclosporin A (CsA) has been used in the treatment of cytopenias in MDS. To evaluate hematologic response and identify response predictive factors in adults with MDS treated with CsA. Patients with MDS diagnosed according World Health Organization (WHO) classification were recruited from January 1997 to June 2012. All patients were classified with IPSS, IPSS revised (IPSS-R),WHO Prognostic Scoring System (WPSS), and WPSS revised (WPSS-R) risk scales. Cyclosporin A was administered orally at a dose of 5 mg/kg/day. Hematologic response was evaluated following the International Working Group for MDS (2006 version) criteria. Inclusion criteria were met by 32 patients. Median age was 56.5 years, with a median follow-up of 3.1 years. Hematologic response was 56.2% and erythrocyte independence transfusion was found in 42.9% of patients. Age,hemoglobin level, and WPSS at diagnosis were independent predictive factors for CsA response. Survival was longer in responder than in nonresponder CsA patients (p=0.06). Cyclosporin A induced hematologic response in >50% of patients with MDS aged <57 years, with Hb<8 g/dl and low WPSS at diagnosis.

  3. [Analysis of the karyotype abnormalities and its prognostic in 298 patients with myelodysplastic syndrome].

    Science.gov (United States)

    Yan, Xuefen; Wei, Juying; Wang, Jinghan; Ren, Yanling; Zhou, Xinping; Mei, Chen; Ye, Li; Xie, Lili; Hu, Chao; Jin, Jie; Tong, Hongyan

    2015-04-01

    To investigate the relationship between cytogenetic markers with World Health Organization (WHO) classification, disease progress and prognosis in cases with primary myelodysplastic syndromes (MDS). 298 patients with de novo MDS from the first affiliated hospital of medical school, Zhejiang University were enrolled in the retrospective analysis of WHO classification, karyotype, and prognosis. Follow-up study was also conducted. The WHO classifications at first diagnosis were as follows: refractory cytopenia with unilineage dysplasia (RCUD), 18 cases; refractory anemia with ring sideroblasts (RARS), 8 cases; refractory cytopenia with multiline dysplasia (RCMD), 104 cases; refractory anemia with excess blasts-1, 76 cases; refractory anemia with excess blasts-2, 85 cases; MDS unclassified (MDS-U), 5 cases involved; and single del (5q), 2 cases. 39.6% of MDS patients carried karyotypic abnormalities. Among them, the frequency of numerical abnormalities, structural abnormalities and the existence of composite abnormalities were 45, 31, and 42, respectively. The composite abnormalities were unbalanced translocations and complex chromosomal abnormalities. The incidence of both karyotypic abnormalities and complex chromosomal abnormalities in RAEB group was higher than that in non-RAEB group (Pkaryotypic abnormalities (Pkaryotypic abnormalities, had worse prognosis than those with normal chromosomes. Karyotype was identified with an independent risk factor in MDS patients. Therefore, the information on cytogenetic analysis was critical for diagnosis, prognosis and individual treatment. MDS patients presenting+8 chromosome, an intermediate risk factor, were associated with a poorer outcome compared to cases with normal chromosomes in RAEB group.

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

    Science.gov (United States)

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

    2013-10-31

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

  5. Myelodysplastic and myeloproliferative neoplasms: updates on the overlap syndromes.

    Science.gov (United States)

    Thota, Swapna; Gerds, Aaron T

    2018-04-01

    Myelodysplastic and myeloproliferative neoplasms (MDS/MPN) is a rare and distinct group of myeloid neoplasms with overlapping MDS and MPN features. Next generation sequencing studies have led to an improved understanding of MDS/MPN disease biology by identifying recurrent somatic mutations. Combining the molecular findings to patho-morphologic features has improved the precision of diagnosis and prognostic models in MDS/MPN. We discuss and highlight these updates in MDS/MPN nomenclature and diagnostic criteria per revised 2016 WHO classification of myeloid neoplasms in this article. There is an ongoing effort for data integration allowing for comprehensive genomic characterization, development of improved prognostic tools, and investigation for novel therapies using an international front specific for MDS/MPN. In this article, we discuss updates in prognostic models and current state of treatment for MDS/MPN.

  6. Primary myelodysplastic syndrome in Jordan: a single-centre experience.

    Science.gov (United States)

    Awidi, Abdalla; Magableh, Ahmad; Taimeh, Ziad; Ayyad, Hashim; Bsoul, Nazzal; Tarawneh, Musleh

    2009-01-01

    Study of the disease patterns and clinical evaluation of myelodysplastic syndrome (MDS). A retrospective analysis was carried out on 85 patients, with MDS who were followed up over a period of 23 years at Jordan University Hospital, Amman, Jordan. Cases were analyzed according to the French, American and British Classification. Of the 85 patients, 42 (49.4%) were females and 43 (50%) males; mean age was 59 +/- 19 years (range 18-88). Most subtypes found in patients were refractory anemia (RA) in 27 (31.8%) and RA with excess blasts (RAEB) in 28 (32.9%). Adverse prognostic indicators were RAEB subtype and requirement for blood transfusion. Our findings showed that MDSs appeared at a younger age and tended to be of the aggressive subtype. Chronic myelomonocytic leukemia subtype seemed to appear dominantly in men. Copyright 2009 S. Karger AG, Basel.

  7. Myelodysplastic Syndromes and Acute Myeloid Leukemia in the Elderly

    Science.gov (United States)

    Klepin, Heidi D.

    2015-01-01

    Synopsis Myelodysplastic syndromes and acute myeloid leukemia are hematologic diseases that frequently affect older adults. Treatment is challenging due the morbidity of the disease and toxicity of associated treatments with strategies ranging from best supportive care to hematopoietic stem cell transplantation. Management of older adults with MDS and AML needs to be individualized accounting for both the heterogeneity of disease biology and patient characteristics which can influence life expectancy and treatment tolerance. While treatment options continue to expand for older adults, clinical trials accounting for the heterogeneity of tumor biology and physiologic changes of aging are needed to define optimal standards of care. Incorporating outcomes addressing quality of life, symptoms, maintenance of independence, and health care utilization is necessary to inform patient-centered decision-making. This review highlights key evidence related to management of older adults with MDS and AML and highlights future directions for research. PMID:26614866

  8. [Case of sarcoidosis with myelodysplastic syndrome in an elderly woman].

    Science.gov (United States)

    Horie, Masafumi; Noguchi, Satoshi; Tanaka, Wakae; Yoshihara, Hisanao; Kawakami, Masaki; Suzuki, Masaru; Sakamoto, Yoshio; Oka, Teruaki

    2010-12-01

    An 85-year-old woman, who had been given a diagnosis of myelodysplastic syndrome with refractory anemia 2 years previously and required blood transfusion once a month, was admitted with complaints of fever, general fatigue, and dry cough. A chest X-ray film showed multiple small nodules in bilateral lung fields which were not observed 1 month previously. Although smear and culture tests for acid-fast bacilli in her bronchoalveolar lavage fluid, urine, and bone marrow aspiration fluid were all negative, miliary tuberculosis was strongly suspected. Antituberculosis drugs were administered, but neither her symptoms nor chest X-ray findings improved. Five months later, right oculomotor nerve palsy, followed by left abducens nerve paralysis occurred. Lumber puncture examination revealed lymphocytosis, and increased protein and ACE levels, suggesting neurosarcoidosis. A transbronchial lung biopsy specimen demonstrated non-caseating epithelioid granulomas. Oral administration of 30 mg/day prednisolone improved her symptoms as well as the chest X-ray findings.

  9. Spliceosome mutations in myelodysplastic syndromes and chronic myelomonocytic leukemia.

    Science.gov (United States)

    Chesnais, Virginie; Kosmider, Olivier; Damm, Frederik; Itzykson, Raphael; Bernard, Olivier A; Solary, Eric; Fontenay, Michaela

    2012-11-01

    The recently discovered spliceosome mutations represent a group of acquired genetic alterations that affect both myeloid and lymphoid malignancies. A substantial proportion of patients with myelodysplastic syndromes (MDS), chronic myelomonocytoic leukemia (CMML) or chronic lymphocytic leukemia (CLL) harbor such mutations, which are often missense in type. Genotype-phenotype correlations have been observed, including the clustering of ring sideroblasts with SF3B1 mutations in MDS. Spliceosome mutations might result in defective small nuclear ribonucleoprotein complexes assembly on the pre-mRNA, deregulated global and alternative mRNA splicing, nuclear-cytoplasm export, and unpliced mRNA degradation, and thus may alter the expression of multiple genes. In the current review, we discuss the potential role of these mutations in cell transformation and how they could impact the therapeutic approaches.

  10. The role of histone methyltransferase EZH2 in myelodysplastic syndromes.

    Science.gov (United States)

    Xu, Feng; Li, Xiao

    2012-04-01

    Previous epigenetics research in myelodysplastic syndromes (MDS) mainly focused on the DNA methylation of tumor suppressor genes. Recent studies reported that around 6% of MDS patients have several EZH2 mutations including missense, frameshift and truncated mutations. Histone methyltransferase EZH2 plays a critical role in epigenetic regulation as a bridge between histone methylation/deacetylation and DNA methylation. EZH2 is frequently overexpressed and considered to be an oncogene in cancers; nevertheless, EZH2 is considered as a candidate tumor suppressor gene in MDS due to EZH2 mutations associated with poor survival. Many questions still need further discussion. Moreover, 3-deazaneplanocin can reduce EZH2 levels and H3K27 trimethylation, and synergistic effects are seen in combination with DNA demethylation agents or histone deacetylation inhibitors. All of the above give us more chances to improve epigenetic therapy in MDS. Therefore, the molecular mechanisms of EZH2 in tumorigenesis and the role of EZH2 in MDS are studied.

  11. IMPORTANCE OF CLASSICAL MORPHOLOGY IN THE DIAGNOSIS OF MYELODYSPLASTIC SYNDROME

    Directory of Open Access Journals (Sweden)

    Rosangela Invernizzi

    2015-04-01

    Full Text Available Myelodysplastic syndromes (MDS are hematopoietic stem cell disorders characterized by dysplastic, ineffective, clonal and neoplastic hematopoiesis. MDS represent a complex hematological problem: differences in disease presentation, progression and outcome  have necessitated the use of classification systems to improve diagnosis, prognostication and treatment selection. However, since a single biological or genetic reliable diagnostic marker has not yet been discovered for MDS, quantitative and qualitative dysplastic morphological alterations of bone marrow precursors and of peripheral blood cells are still fundamental for diagnostic classification. In this paper World Health Organization (WHO classification refinements and current minimal diagnostic criteria proposed by expert panels are highlighted and related problematic issues are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies. Although in the future morphology should be supplemented with new molecular techniques, the morphological approach, at least for the moment, is still the cornerstone for the diagnosis and classification of these disorders.

  12. Communicating about risk: strategies for situations where public concern is high but the risk is low

    OpenAIRE

    Claire Hooker; Adam Capon; Julie Leask

    2017-01-01

    In this article, we summarise research that identifies best practice for communicating about hazards where the risk is low but public concern is high. We apply Peter Sandman’s ‘risk = hazard + outrage’ formulation to these risks, and review factors associated with the amplification of risk signals. We discuss the structures that determine the success of risk communication strategies, such as the capacity for early communication to ‘capture’ the dominant representation of risk issues, the impo...

  13. [Anesthesiological management of the high-risk surgical patient].

    Science.gov (United States)

    Bertoldi, G; Avalle, M

    1980-03-01

    Evaluation of the anaesthesiological risk in surgical patients is described and an account is given of results obtained with an association of ketamin and NLA II in 57 high-risk patients subjected to general surgical management.

  14. Advanced Risk Analysis for High-Performing Organizations

    National Research Council Canada - National Science Library

    Alberts, Christopher; Dorofee, Audrey

    2006-01-01

    ...) are not readily identified using traditional risk analysis techniques. High-performing organizations have the basic skills needed to identify and manage these new types of risk, but lack sufficient techniques...

  15. Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial

    Science.gov (United States)

    de Witte, Theo; Hagemeijer, Anne; Suciu, Stefan; Belhabri, Amin; Delforge, Michel; Kobbe, Guido; Selleslag, Dominik; Schouten, Harry C.; Ferrant, Augustin; Biersack, Harald; Amadori, Sergio; Muus, Petra; Jansen, Joop H.; Hellström-Lindberg, Eva; Kovacsovics, Tibor; Wijermans, Pierre; Ossenkoppele, Gert; Gratwohl, Alois; Marie, Jean-Pierre; Willemze, Roel

    2010-01-01

    Background Allogeneic stem cell transplantation is usually considered the only curative treatment option for patients with advanced or transformed myelodysplastic syndromes in complete remission, but post-remission chemotherapy and autologous stem cell transplantation are potential alternatives, especially in patients over 45 years old. Design and Methods We evaluated, after intensive anti-leukemic remission-induction chemotherapy, the impact of the availability of an HLA-identical sibling donor on an intention-to treat basis. Additionally, all patients without a sibling donor in complete remission after the first consolidation course were randomized to either autologous peripheral blood stem cell transplantation or a second consolidation course consisting of high-dose cytarabine. Results The 4-year survival of the 341 evaluable patients was 28%. After achieving complete remission, the 4-year survival rates of patients under 55 years old with or without a donor were 54% and 41%, respectively, with an adjusted hazard ratio of 0.81 (95% confidence interval [95% CI], 0.49–1.35) for survival and of 0.67 (95% CI, 0.42–1.06) for disease-free survival. In patients with intermediate/high risk cytogenetic abnormalities the hazard ratio in multivariate analysis was 0.58 (99% CI, 0.22–1.50) (P=0.14) for survival and 0.46 (99% CI, 0.22–1.50) for disease-free survival (P=0.03). In contrast, in patients with low risk cytogenetic characteristics the hazard ratio for survival was 1.17 (99% CI, 0.40–3.42) and that for disease-free survival was 1.02 (99% CI, 0.40–2.56). The 4-year survival of the 65 patients randomized to autologous peripheral blood stem cell transplantation or a second consolidation course of high-dose cytarabine was 37% and 27%, respectively. The hazard ratio in multivariate analysis was 1.22 (95% CI, 0.65–2.27) for survival and 1.02 (95% CI, 0.56–1.85) for disease-free survival. Conclusions Patients with a donor and candidates for allogeneic stem

  16. Systemic immunomodulatory strategies in high-risk corneal transplantation

    Directory of Open Access Journals (Sweden)

    Tulio B Abud

    2017-01-01

    Full Text Available The cornea is the most commonly transplanted tissue in the body. Although corneal grafts generally have high success rates, transplantation onto inflamed and vascularized host beds, or so-called high-risk corneal transplantation, has a high rate of graft rejection. The management of this high-risk corneal transplantation is challenging and involves numerous measures. One of the key measures to prevent graft rejection in these cases is the use of systemic immunosuppressive agents. In this article, we will review the systemic immunosuppressive agents most commonly used for high-risk corneal transplantation, which include corticosteroids, cysclosporine A, tacrolimus, mycophenolate mofetil, and rapamycin. Benefits, risks, and published data on the use of these medications for high-risk corneal transplantation will be detailed. We will also summarize novel immunoregulatory approaches that may be used to prevent graft rejection in high-risk corneal transplantation.

  17. Increase of IRF-1 gene expression and impairment of T regulatory cells suppression activity on patients with myelodysplastic syndrome: A longitudinal one-year study.

    Science.gov (United States)

    Perazzio, Aline S B; Oliveira, José Salvador R; Figueiredo, Vera L P; Chauffaille, Maria de Lourdes L F

    2017-04-01

    Studies have demonstrated that abnormalities in interferon regulatory factor-1 (IRF-1) expression might develop myelodysplastic syndromes (MDS). IRF-1 was described as modulator of T regulatory (Treg) cells by suppressing Foxp3 on mice. We aimed to determine the role of Treg and IRF-1 in MDS. Thirty-eight MDS patients fulfilling WHO criteria and classified according to risk scores were evaluated at time 0 (T0) and after 12 months (T12) for: Treg suppression activity in coculture with T effector (Teff) cells; IRF-1 and Foxp3 genetic expression by qRT-PCR; IL-2, -4, -6, -10, -17, TNFα and IFNγ production by Cytometric Bead Array. No differences in Foxp3 expression (T0=0.06±0.06 vs T12=0.06±0.12, p=0.5), Treg number (T0=5.62±2.84×10 5 vs T12=4.87±2.62×10 5 ; p=0.3) and Teff percentage (T0=16.8±9.56% vs T12=13.1±6.3%; p=0.06) were observed on T12. Low risk MDS patients showed a higher number of Treg (5.2±2.6×10 5 ) versus high risk group (2.6±1.2×10 5 , p=0.03). Treg suppression activity was impaired on T0 and T12.Cytokine production and IRF-1 expression were increased on T12. The correlation between IRF-1 and FoxP3 was negative (r 2 =0.317, p=0.045) on T0. These results suggest a hyper activity of the immune system, probably secondary to Treg suppression activity impairment. This state may induce the loss of tolerance culminating in the proliferation of MDS clones. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Prolonged Isotretinoin in Ultra High-Risk Neuroblastoma.

    Science.gov (United States)

    Cash, Thomas; Alazraki, Adina; Qayed, Muna; Katzenstein, Howard M

    2017-01-01

    Patients with high-risk neuroblastoma remain a therapeutic challenge with significant numbers of patients failing to respond sufficiently to initial therapy. These patients with poor response to induction are considered as ultra high-risk and are in need of novel treatment strategies. Isotretinoin is part of the standard of care treatment for patients with high-risk disease who undergo high-dose chemotherapy with autologous stem cell rescue although some have questioned the optimal administration schedule. Prolonged use of isotretinoin was well tolerated and may have contributed to long-term survival in a group of patients with ultra high-risk neuroblastoma.

  19. Heterogeneity of Psychosis Risk Within Individuals at Clinical High Risk: A Meta-analytical Stratification

    NARCIS (Netherlands)

    Fusar-Poli, Paolo; Cappucciati, Marco; Borgwardt, Stefan; Woods, Scott W.; Addington, Jean; Nelson, Barnaby; Nieman, Dorien H.; Stahl, Daniel R.; Rutigliano, Grazia; Riecher-Rössler, Anita; Simon, Andor E.; Mizuno, Masafumi; Lee, Tae Young; Kwon, Jun Soo; Lam, May M. L.; Perez, Jesus; Keri, Szabolcs; Amminger, Paul; Metzler, Sibylle; Kawohl, Wolfram; Rössler, Wulf; Lee, Jimmy; Labad, Javier; Ziermans, Tim; An, Suk Kyoon; Liu, Chen-Chung; Woodberry, Kristen A.; Braham, Amel; Corcoran, Cheryl; McGorry, Patrick; Yung, Alison R.; McGuire, Philip K.

    2016-01-01

    Individuals can be classified as being at clinical high risk (CHR) for psychosis if they meet at least one of the ultra-high-risk (UHR) inclusion criteria (brief limited intermittent psychotic symptoms [BLIPS] and/or attenuated psychotic symptoms [APS] and/or genetic risk and deterioration syndrome

  20. Incidence of Myelodysplastic Syndrome in UK Petroleum Distribution and Oil Refinery Workers, 1995–2011

    Directory of Open Access Journals (Sweden)

    Tom Sorahan

    2016-05-01

    Full Text Available The incidence of myelodysplastic syndrome (MDS experienced by cohorts of 16,467 petroleum distribution workers and 28,554 oil refinery workers has been investigated. Study subjects were all those male employees first employed at one of 476 UK petroleum distribution centres or eight UK oil refineries in the period 1946–1974; all subjects had a minimum of twelve months employment with some employment after 1st January, 1951. Observed numbers (Obs of MDS cases were compared with expectations based on national incidence rates for the period 1995–2011. The overall standardised registration ratio (SRR was 73 (Obs = 17 in petroleum distribution workers for the age-range 15–84 years, and 77 (Obs = 21 for the age-range 15–99 years. The overall SRR was 81 (Obs = 29 in oil refinery workers for the age-range 15–84 years, and 83 (Obs = 36 for the age-range 15–99 years. More detailed analyses were carried out in terms of year of registration, period from hire, decade of hire, and duration of employment. The overall SRR findings did not provide clear evidence for the presence of an occupational cancer hazard, and provide no support for the hypothesis that low-level benzene exposure has an important effect on the risks of MDS.

  1. Incidence of Myelodysplastic Syndrome in UK Petroleum Distribution and Oil Refinery Workers, 1995–2011

    Science.gov (United States)

    Sorahan, Tom; Mohammed, Nuredin

    2016-01-01

    The incidence of myelodysplastic syndrome (MDS) experienced by cohorts of 16,467 petroleum distribution workers and 28,554 oil refinery workers has been investigated. Study subjects were all those male employees first employed at one of 476 UK petroleum distribution centres or eight UK oil refineries in the period 1946–1974; all subjects had a minimum of twelve months employment with some employment after 1st January, 1951. Observed numbers (Obs) of MDS cases were compared with expectations based on national incidence rates for the period 1995–2011. The overall standardised registration ratio (SRR) was 73 (Obs = 17) in petroleum distribution workers for the age-range 15–84 years, and 77 (Obs = 21) for the age-range 15–99 years. The overall SRR was 81 (Obs = 29) in oil refinery workers for the age-range 15–84 years, and 83 (Obs = 36) for the age-range 15–99 years. More detailed analyses were carried out in terms of year of registration, period from hire, decade of hire, and duration of employment. The overall SRR findings did not provide clear evidence for the presence of an occupational cancer hazard, and provide no support for the hypothesis that low-level benzene exposure has an important effect on the risks of MDS. PMID:27164123

  2. Incidence of Myelodysplastic Syndrome in UK Petroleum Distribution and Oil Refinery Workers, 1995-2011.

    Science.gov (United States)

    Sorahan, Tom; Mohammed, Nuredin

    2016-05-06

    The incidence of myelodysplastic syndrome (MDS) experienced by cohorts of 16,467 petroleum distribution workers and 28,554 oil refinery workers has been investigated. Study subjects were all those male employees first employed at one of 476 UK petroleum distribution centres or eight UK oil refineries in the period 1946-1974; all subjects had a minimum of twelve months employment with some employment after 1st January, 1951. Observed numbers (Obs) of MDS cases were compared with expectations based on national incidence rates for the period 1995-2011. The overall standardised registration ratio (SRR) was 73 (Obs = 17) in petroleum distribution workers for the age-range 15-84 years, and 77 (Obs = 21) for the age-range 15-99 years. The overall SRR was 81 (Obs = 29) in oil refinery workers for the age-range 15-84 years, and 83 (Obs = 36) for the age-range 15-99 years. More detailed analyses were carried out in terms of year of registration, period from hire, decade of hire, and duration of employment. The overall SRR findings did not provide clear evidence for the presence of an occupational cancer hazard, and provide no support for the hypothesis that low-level benzene exposure has an important effect on the risks of MDS.

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

    Science.gov (United States)

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

    2017-09-26

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

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

    Science.gov (United States)

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

    2016-09-27

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

  5. SLC7A5 act as a potential leukemic transformation target gene in myelodysplastic syndrome

    Science.gov (United States)

    Ma, Yan; Song, Jing; Chen, Bobin; Xu, Xiaoping; Lin, Guowei

    2016-01-01

    Objective Myelodysplastic syndromes (MDS) are a heterogenous group of clonal hematopoietic stem cell disorders characterized by increased risk of leukemic transformation. This study identifies microRNAs(miRNA) and miRNA targets that might represent leukemic transformation markers for MDS. Methods Based on our previously established nested case-control study cohort of MDS patients, we chose paired patients to undergo Angilent 8 × 15K human miRNA microarrays. Target prediction analysis was administrated using targetscan 5.1 software. We further investigated the function of target gene in MDS cell line using siRNA method, including cell proliferation, cell apoptosis, cell cycle and electron microscope. Results Finally we screened a subset of 7 miRNAs to be significantly differentially expressed between the case (at the end of follow up with leukemic transformation) and control group (at the end of follow up without leukemic transformation). Target prediction analysis revealed SLC7A5 was the common target gene of these 7 miRNAs. Further study on the function of SLC7A5 gene in SKM-1 cell line showed that downregulation of SLC7A5 inhibited SKM-1 cells proliferation, increased apoptosis and caused cell cycle arrest in the G0/G1 stage. Conclusion Our data indicate that SLC7A5 gene may act as a potential leukemic transformation target gene in MDS. PMID:26657287

  6. Role of flow cytometry in diagnostics of myelodysplastic syndromes--beyond the WHO 2008 classification.

    Science.gov (United States)

    Porwit, Anna

    2011-11-01

    Multiparameter flow cytometry (FCM) is an excellent method to follow the expression patterns of differentiation antigens using monoclonal antibodies to surface and cytoplasmic proteins. Although several authors described various aberrant immunophenotypic features in the bone marrow of patients with myelodysplastic syndromes (MDS), the World Health Organization 2008 classification recommended that, only if 3 or more phenotypic abnormalities are found involving 1 or more of the myeloid lineages can the aberrant FCM findings be considered suggestive of MDS. In the absence of conclusive morphologic and/or cytogenetic features, FCM abnormalities alone were considered not sufficient to establish MDS diagnosis and further follow-up of the patients was recommended. Review of the literature gives accumulating evidence that FCM has become an important part of the integrated diagnostic work-up of patients with suspected MDS. Several studies have also reported FCM findings significant for prognosis and therapy choice in MDS patients. Technical progress in multicolor FCM and new analysis programs, together with ongoing efforts to standardize the methodology, will make it possible to apply FCM in individual risk assessment and choice of best therapy for MDS patients.

  7. Recent advances in the understanding of iron overload in sideroblastic myelodysplastic syndrome.

    Science.gov (United States)

    Cuijpers, Maria L H; Raymakers, Reinier A P; Mackenzie, Marius A; de Witte, Theo J M; Swinkels, Dorine W

    2010-05-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal haematopoietic stem cell malignancies. A subgroup, the so-called sideroblastic MDS, shows ring sideroblasts in the bone marrow aspirate that represent mitochondrial iron accumulation. Patients with sideroblastic MDS also develop systemic iron overload and generally have a low-risk MDS. Therefore it is important to understand the mechanisms responsible for iron accumulation and the associated toxicity in these patients. Recently, low levels of the iron-regulatory peptide hepcidin were found to contribute to body iron overload in beta-thalassaemia patients. A similar mechanism may account for systemic iron accumulation in sideroblastic MDS. Mitochondrial iron accumulation is observed in several subtypes of MDS, and predominantly in refractory anaemia with ring sideroblasts. The presence of ring sideroblasts is also the diagnostic hallmark in patients with inherited forms of sideroblastic anaemia. The ever-increasing insights into the affected pathways in inherited sideroblastic anaemia may lead to a better comprehension of the pathogenesis of mitochondrial iron accumulation in MDS patients. Overall, an improved understanding of the mechanisms responsible for iron overload in MDS will lead to novel treatment strategies to reduce both systemic and mitochondrial iron overload, resulting in less tissue damage and more effective erythropoiesis.

  8. Counselling and adverse event management for patients with myelodysplastic syndromes undergoing azacitidine therapy: a practice standard for Canadian nurses.

    Science.gov (United States)

    Murray, Cindy; Wereley, Annie; Nixon, Shannon; Hua-Yung, Carol; von Riedemann, Sarah; Kurtin, Sandra

    2012-01-01

    Azacitidine (5-azacytidine, VIDAZA) is a disease-modifying agent that improves survival, reduces transfusion dependence, and reduces progression to acute myeloid leukemia in patients with higher risk myelodysplastic syndromes. Azacitidine injection is associated with characteristic adverse events (AEs) that must be managed in order for patients to stay on therapy and achieve optimal therapeutic outcomes. These AEs include injection-site reactions, cytopenias, and gastrointestinal effects. Oncology nurses are uniquely positioned to provide patient support and counselling, thereby helping patients and their families set clear expectations for azacitidine therapy. This article presents a nursing standard designed to support Canadian oncology nurses in the key areas of counselling for patients initiating and continuing azacitidine, as well as nursing strategies for prevention and management of azacitidine-associated AEs. Many of the general principles discussed in this nursing standard can be applied broadly to many diseases and treatments.

  9. Evaluation of Risk Management Strategies for a Low-Cost, High-Risk Project

    Science.gov (United States)

    Shishko, Robert; Jorgensen, Edward J.

    1996-01-01

    This paper summarizes work in progress to define and implement a risk management process tailored to a low-cost, high-risk, NASA mission -the Microrover Flight Experiment (MFEX, commonly called the Mars microrover).

  10. Standardizing care for high-risk patients in spine surgery: the Northwestern high-risk spine protocol.

    Science.gov (United States)

    Halpin, Ryan J; Sugrue, Patrick A; Gould, Robert W; Kallas, Peter G; Schafer, Michael F; Ondra, Stephen L; Koski, Tyler R

    2010-12-01

    Review article of current literature on the preoperative evaluation and postoperative management of patients undergoing high-risk spine operations and a presentation of a multidisciplinary protocol for patients undergoing high-risk spine operation. To provide evidence-based outline of modifiable risk factors and give an example of a multidisciplinary protocol with the goal of improving outcomes. Protocol-based care has been shown to improve outcomes in many areas of medicine. A protocol to evaluate patients undergoing high-risk procedures may ultimately improve patient outcomes. The English language literature to date was reviewed on modifiable risk factors for spine surgery. A multidisciplinary team including hospitalists, critical care physicians, anesthesiologists, and spine surgeons from neurosurgery and orthopedics established an institutional protocol to provide comprehensive care in the pre-, peri-, and postoperative periods for patients undergoing high-risk spine operations. An example of a comprehensive pre-, peri-, and postoperative high-risk spine protocol is provided, with focus on the preoperative assessment of patients undergoing high-risk spine operations and modifiable risk factors. Standardizing preoperative risk assessment may lead to better outcomes after major spine operations. A high-risk spine protocol may help patients by having dedicated physicians in multiple specialties focusing on all aspects of a patients care in the pre-, intra-, and postoperative phases.

  11. High-Risk and Low-Risk Human Papillomavirus and the Absolute Risk of Cervical Intraepithelial Neoplasia or Cancer

    DEFF Research Database (Denmark)

    Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian

    2014-01-01

    OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test. METHODS: In this prospective cohort study, consecutive liquid-based cer......OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test. METHODS: In this prospective cohort study, consecutive liquid...

  12. Comparison of unrelated cord blood and peripheral blood stem cell transplantation in adults with myelodysplastic syndrome after reduced-intensity conditioning regimen: a collaborative study from Eurocord (Cord blood Committee of Cellular Therapy & Immunobiology Working Party of EBMT) and Chronic Malignancies Working Party

    NARCIS (Netherlands)

    Robin, M.; Ruggeri, A.; Labopin, M.; Niederwieser, D.; Tabrizi, R.; Sanz, G.; Bourhis, J.H.; Biezen, A. van; Koenecke, C.; Blaise, D.; Tischer, J.; Craddock, C.; Maillard, N.; Mohty, M.; Russel, N.; Schetelig, J.; Finke, J.; Gluckman, E.; Witte, T.J. de; Rocha, V.; Kroger, N.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment in patients with higher risk myelodysplastic syndrome (MDS), but the choice of the optimal alternative stem cell source is still a subject of debate in patients lacking an HLA-matched sibling donor. Here, we report on

  13. A pilot phase I dose finding safety study of the thrombopoietin-receptor agonist, eltrombopag, in patients with myelodysplastic syndrome treated with azacitidine.

    Science.gov (United States)

    Svensson, Tobias; Chowdhury, Onima; Garelius, Hege; Lorenz, Fryderyk; Saft, Leonie; Jacobsen, Sten-Eirik; Hellström-Lindberg, Eva; Cherif, Honar

    2014-11-01

    Thrombocytopenia is an independent adverse prognostic factor in patients with Myelodysplastic syndromes (MDS). Azacitidine, first-line treatment for the majority of patients with higher-risk MDS, is associated with aggravated thrombocytopenia during the first cycles. Eltrombopag is a novel thrombopoietin receptor agonist, which also has been shown to inhibit proliferation of leukaemia cell lines in vitro. This phase I clinical trial was designed to explore the safety and tolerability of combining eltrombopag with azacitidine in patients with MDS. In addition, we assessed the potential effects of eltrombopag on hematopoietic stem and progenitor cells (HSPCs) from included patients. Previously untreated patients with MDS eligible for treatment with azacitidine and with a platelet count <75 × 10(9) /L were included. Patients received eltrombopag in dose escalation cohorts during three cycles of azacitidine. Twelve patients, with a median age of 74 yr, were included. Severe adverse events included infectious complications, deep vein thrombosis and transient ischaemic attack. The maximal tolerated eltrombopag dose was 200 mg qd. Complete remission or bone marrow remission was achieved in 4 of 12 patients. Platelet counts improved or remained stable in 9 of 12 patients despite azacitidine treatment. No increase in blast count, disease progression, or bone marrow fibrosis related to study medication was reported. Eltrombopag did not induce cycling of HSPCs. The combination of eltrombopag with azacitidine in high-risk MDS patients is feasible and well tolerated. Improvements in platelet counts and the potential antileukaemic effect of eltrombopag should be explored in a randomised study. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. High Blood Pressure, Afib and Your Risk of Stroke

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More High Blood Pressure, AFib and Your Risk of Stroke Updated:Aug ... have a stroke for the first time have high blood pressure . And an irregular atrial heart rhythm — a condition ...

  15. Elite High Schools Breed Higher Risk of Addiction

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_166144.html Elite High Schools Breed Higher Risk of Addiction: Study ... from drug addiction, new research suggests. Teens at elite U.S. high schools seem to face a higher ...

  16. Sexual risk behaviours of high school female learners in Mbonge ...

    African Journals Online (AJOL)

    Introduction: since female learners in high schools in Cameroon fall within the age group hardest hit by HIV/AIDS, it is assumed that these learners might be exposed to sexual risk behaviours. However, little has been explored on the sexual risk behaviours of high school female learners in Cameroon. This study aimed at ...

  17. Alcohol consumption and high risk sexual behaviour among female ...

    African Journals Online (AJOL)

    Alcohol consumption has been associated with high risk sexual behaviour among key populations such as female sex workers. We explored the drivers of alcohol consumption and its relationship to high risk sexual behaviour. Participants were drawn from a cohort of 1 027 women selected from 'hot spots' in the suburbs of ...

  18. Correlation between high-risk pregnancy and developmental delay ...

    African Journals Online (AJOL)

    Background: The future development of children is considered more than ever now due to the advances in medical knowledge and thus the increase in survival rates of high-risk infants. This study investigated the correlation between high-risk pregnancy and developmental delay in children aged 4- 60 months. Methods: ...

  19. High Risk Behavior among Adolescent Mothers: The Problem in Context.

    Science.gov (United States)

    Kissman, Kris

    1998-01-01

    Discusses the particular consequences of high-risk behavior for adolescent women, including unintended pregnancies, sexually transmitted diseases, school dropout and poverty, developmental disabilities, and poor school performance. Considers the role of male partners in teenage women's high risk behavior. Describes prevention efforts such as…

  20. Elevated level of serum triglyceride among high risk stress bank ...

    African Journals Online (AJOL)

    The objective of this study was to estimate lipid profile among high risk stress bank employees' correlated with heart disorders in Riyadh, Saudi Arabia. A total of 129 patients with high risk stress employees were involved in this study, which were divided into 69 males and 60 females between the age of 25 to 55 years.

  1. Prevalence and risk factors of obesity and high blood pressure ...

    African Journals Online (AJOL)

    Risk factors for these diseases have been well studied in high income countries but less studied in developing countries. Objective: The study was to document the prevalence and risk factors of Obesity and high blood pressure among healthy adults in a military settlement in Ibagwa, Southern Nigeria. The study also sought ...

  2. Early Molecular Stratification of High-risk Primary Biliary Cholangitis.

    Science.gov (United States)

    Hardie, Claire; Green, Kile; Jopson, Laura; Millar, Ben; Innes, Barbara; Pagan, Sarah; Tiniakos, Dina; Dyson, Jessica; Haniffa, Muzlifah; Bigley, Venetia; Jones, David E; Brain, John; Walker, Lucy J

    2016-12-01

    High-risk primary biliary cholangitis (PBC), defined by inadequate response at one year to Ursodeoxycholic acid (UDCA), is associated with disease progression and liver transplantation. Stratifying high-risk patients early would facilitate improved approaches to care. Using long-term follow-up data to define risk at presentation, 6 high-risk PBC patients and 8 low-risk patients were identified from biopsy, transplant and biochemical archival records. Formalin-fixed paraffin-embedded (FFPE) liver biopsies taken at presentation were graded (Scheuer and Nakanuma scoring) and gene expression analysed using the NanoString® nCounter PanCancer Immunity 770-gene panel. Principle component analysis (PCA) demonstrated discrete gene expression clustering between controls and high- and low-risk PBC. High-risk PBC was characterised by up-regulation of genes linked to T-cell activation and apoptosis, INF-γ signalling and leukocyte migration and down-regulation of those linked to the complement pathway. CDKN1a, up-regulated in high-risk PBC, correlated with significantly increased expression of its gene product, the senescence marker p21 WAF1/Cip , by biliary epithelial cells. Our findings suggest high- and low-risk PBC are biologically different from disease outset and senescence an early feature in high-risk disease. Identification of a high-risk 'signal' early from standard FFPE tissue sections has clear clinical utility allowing for patient stratification and second-line therapeutic intervention. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  3. High Center Volume Does Not Mitigate Risk Associated with Using High Donor Risk Organs in Liver Transplantation.

    Science.gov (United States)

    Beal, Eliza W; Black, Sylvester M; Mumtaz, Khalid; Hayes, Don; El-Hinnawi, Ashraf; Washburn, Kenneth; Tumin, Dmitry

    2017-09-01

    High-risk donor allografts increase access to liver transplant, but potentially reduce patient and graft survival. It is unclear whether the risk associated with using marginal donor livers is mitigated by increasing center experience. The United Network for Organ Sharing registry was queried for adult first-time liver transplant recipients between 2/2002 and 12/2015. High donor risk was defined as donor risk index >1.9, and 1-year patient and graft survival were compared according to donor risk index in small and large centers. Multivariable Cox regression estimated the hazard ratio (HR) associated with using high-risk donor organs, according to a continuous measure of annual center volume. The analysis included 51,770 patients. In 67 small and 67 large centers, high donor risk index predicted increased mortality (p = 0.001). In multivariable analysis, high-donor risk index allografts predicted greater mortality hazard at centers performing 20 liver transplants per year (HR 1.35; 95% CI 1.22, 1.49; p transplant. Specific strategies to mitigate the risk of liver transplant involving high-risk donors are needed, in addition to accumulation of center expertise.

  4. Prognosis of Carotid Endarterectomy in High Risk Patients

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    MH Modaghegh

    2016-04-01

    Full Text Available Introduction: Carotid Endarterectomy (CE can be mentioned as a valuable theraputic method for primary and secondary prevention of stroke, provided it can be performed in vascular surgery centers with a low surgical risk. Thus, the present study aimed to assess prognosis of CE in high risk patients of an Iranian vascular surgery center. Methods: This prospective observational study consisted of 50 high risk CE patients during 2011-14 in Mashhad University of Medical Sciences. All the high risk CE were performed by a vascular surgeon and a surgical carotid shunt was placed in each CE. Neurologic evaluation was performed before CE and serial neurologic axamination was done after CE by a neurologist. Surgical complications including stroke, death and lower cranial nerve palsy were recorded for 30 days after operation. Results: The study results revealed that 80% of high risk CE patients had symptomatic carotid stenosis on the operation side and 80% had carotid stenosis contralateral to the operation side. Thirteen high risk CE were performed simultaneously with coronary artery by pass graft and 24 patients were demonstrated to have diabetes. Post surgical death and stroke in the high risk CE patients were reported 2% and 4%, respectively. Lower cranial nerve palsy appeared in 2% of patients. Conclusion: The 6% post operative stroke and death rate in the high risk CE patients are comparable to best vascular surgery centers in Europe and North America.

  5. Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells.

    Science.gov (United States)

    Pellagatti, A; Cazzola, M; Giagounidis, A; Perry, J; Malcovati, L; Della Porta, M G; Jädersten, M; Killick, S; Verma, A; Norbury, C J; Hellström-Lindberg, E; Wainscoat, J S; Boultwood, J

    2010-04-01

    To gain insight into the molecular pathogenesis of the myelodysplastic syndromes (MDS), we performed global gene expression profiling and pathway analysis on the hematopoietic stem cells (HSC) of 183 MDS patients as compared with the HSC of 17 healthy controls. The most significantly deregulated pathways in MDS include interferon signaling, thrombopoietin signaling and the Wnt pathways. Among the most significantly deregulated gene pathways in early MDS are immunodeficiency, apoptosis and chemokine signaling, whereas advanced MDS is characterized by deregulation of DNA damage response and checkpoint pathways. We have identified distinct gene expression profiles and deregulated gene pathways in patients with del(5q), trisomy 8 or -7/del(7q). Patients with trisomy 8 are characterized by deregulation of pathways involved in the immune response, patients with -7/del(7q) by pathways involved in cell survival, whereas patients with del(5q) show deregulation of integrin signaling and cell cycle regulation pathways. This is the first study to determine deregulated gene pathways and ontology groups in the HSC of a large group of MDS patients. The deregulated pathways identified are likely to be critical to the MDS HSC phenotype and give new insights into the molecular pathogenesis of this disorder, thereby providing new targets for therapeutic intervention.

  6. Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal cells

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    Aanei, Carmen Mariana, E-mail: caanei@yahoo.com [Laboratoire Hematologie, CHU de Saint-Etienne, 42055, Saint-Etienne (France); Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi (Romania); Eloae, Florin Zugun [Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi (Romania); Flandrin-Gresta, Pascale [Laboratoire Hematologie, CHU de Saint-Etienne, 42055, Saint-Etienne (France); CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne (France); Tavernier, Emmanuelle [Service Hematologie Clinique, Institut de Cancerologie de la Loire, 42270, Saint-Priest-en-Jarez (France); CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne (France); Carasevici, Eugen [Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi (Romania); Guyotat, Denis [Service Hematologie Clinique, Institut de Cancerologie de la Loire, 42270, Saint-Priest-en-Jarez (France); CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne (France); Campos, Lydia [Laboratoire Hematologie, CHU de Saint-Etienne, 42055, Saint-Etienne (France); CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne (France)

    2011-11-01

    Direct cell-cell contact between haematopoietic progenitor cells (HPCs) and their cellular microenvironment is essential to maintain 'stemness'. In cancer biology, focal adhesion (FA) proteins are involved in survival signal transduction in a wide variety of human tumours. To define the role of FA proteins in the haematopoietic microenvironment of myelodysplastic syndromes (MDS), CD73-positive mesenchymal stromal cells (MSCs) were immunostained for paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} and p130CAS, and analysed for reactivity, intensity and cellular localisation. Immunofluorescence microscopy allowed us to identify qualitative and quantitative differences, and subcellular localisation analysis revealed that in pathological MSCs, paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} formed nuclear molecular complexes. Increased expression of paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} and enhanced nuclear co-localisation of these proteins correlated with a consistent proliferative advantage in MSCs from patients with refractory anaemia with excess blasts (RAEB) and negatively impacted clonogenicity of HPCs. These results suggest that signalling via FA proteins could be implicated in HPC-MSC interactions. Further, because FAK is an HSP90{alpha}/{beta} client protein, these results suggest the utility of HSP90{alpha}/{beta} inhibition as a target for adjuvant therapy for myelodysplasia.

  7. 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.

  8. Standards and Impact of Hematopathology in Myelodysplastic Syndromes (MDS)

    Science.gov (United States)

    Valent, Peter; Orazi, Attilio; Büsche, Guntram; Schmitt-Gräff, Annette; George, Tracy I.; Sotlar, Karl; Streubel, Berthold; Beham-Schmid, Christine; Cerny-Reiterer, Sabine; Krieger, Otto; van de Loosdrecht, Arjan; Kern, Wolfgang; Ogata, Kiyoyuki; Wimazal, Friedrich; Csomor, Judit; Várkonyi, Judit; Sperr, Wolfgang R.; Werner, Martin; Kreipe, Hans; Hans-Peter, Horny

    2010-01-01

    The diagnosis, classification, and prognostication of patients with myelodysplastic syndromes (MDS) are usually based on clinical parameters, analysis of peripheral blood and bone marrow smears, and cytogenetic determinants. However, a thorough histologic and immunohistochemical examination of the bone marrow is often required for a final diagnosis and exact classification in these patients. Notably, histology and immunohistology may reveal dysplasia in megakaryocytes or other bone marrow lineages and/or the presence of clusters of CD34-positive precursor cells. In other cases, histology may reveal an unrelated or co-existing hematopoietic neoplasm, or may support the conclusion the patient is suffering from acute myeloid leukemia rather than MDS. Moreover, histologic investigations and immunohistology may reveal an increase in tryptase-positive cells, a coexisting systemic mastocytosis, or bone marrow fibrosis, which is of prognostic significance. To discuss diagnostic algorithms, terminologies, parameters, and specific issues in the hematopathologic evaluation of MDS, a Working Conference involving a consortium of US and EU experts, was organized in June 2010. The outcomes of the conference and resulting recommendations provided by the faculty, are reported in this article. These guidelines should assist in the diagnosis, classification, and prognostication in MDS in daily practice as well as in clinical trials. PMID:21317447

  9. DIAGNOSTIC UTILITY OF FLOW CYTOMETRY IN MYELODYSPLASTIC SYNDROMES.

    Directory of Open Access Journals (Sweden)

    Matteo Della Porta

    2017-02-01

    Full Text Available The pathological hallmark of myelodysplastic syndromes (MDS is marrow dysplasia, which representsthe basis of the WHO classification of these disorders. This classification provides clinicians with a useful tool for defining the different subtypes of MDS and individual prognosis. The WHO proposal has raised some concern regarding minimal diagnostic criteria particularly in patients with normal karyotype without robust morphological markers of dysplasia (such as ring sideroblasts or excess of blasts. Therefore, there is clearly a need to refine the accuracy to detect marrow dysplasia. Flow cytometry (FCM immunophenotyping has been proposed as a tool to improve the evaluation of marrow dysplasia. Rationale for the application of FCM in the diagnostic work up of MDS is that immunophenotyping is an accurate method for quantitative and qualitative evaluation of hematopoietic cells and that MDS have been found to have abnormal expression of several cellular antigens. To become clinically applicable, FCM analysis should be based on parameters with sufficient specificity and sensitivity, data should be reproducible between different operators and the results should be easily understood by clinicians. In this review, we discuss the most relevant progresses in detection of marrow dysplasia by FCM in MDS

  10. Pleural effusions in acute and chronic leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Faiz, Saadia A; Sahay, Sandeep; Jimenez, Carlos A

    2014-07-01

    Pulmonary manifestations have been well described in leukemia, but pleural disease is less common. This review highlights pleural effusions in acute and chronic leukemia and myelodysplastic syndrome (MDS) based on the evidence to date. Diagnostic workup and recommendations for the management of these effusions are also outlined. Pleural effusions in patients with leukemia are most often due to infection and to a lesser extent leukemic infiltration of the pleura. The prognostic implications of these effusions are unclear, but survival is most likely determined by the underlying malignancy and its response to treatment. New therapies have changed survival in these patients, and some of these treatments, such as tyrosine kinase inhibitors, have emerged as important causes for these effusions. Pleural interventions may be accomplished with few complications. Pleural effusions may occur with acute and chronic leukemia and MDS. Infection remains the most common cause. Malignant pleural effusions tend to occur in advanced disease in chronic leukemia, but they can be seen at any time with acute leukemia and MDS. With standard precautions, pleural procedures may be performed safely in this population. In cases of unclear cause, pleural and bone marrow biopsy should be considered.

  11. Classification of childhood aplastic anemia and myelodysplastic syndrome.

    Science.gov (United States)

    Niemeyer, Charlotte M; Baumann, Irith

    2011-01-01

    Hypoplastic BM disorders in children and adolescents comprise a broad spectrum of disorders. Acquired severe aplastic anemia (SAA), refractory cytopenia of childhood (RCC), a subtype of myelodysplastic syndrome (MDS), and inherited BM failure (IBMF) disorders are the main and most difficult hematological differential diagnoses. Whereas IBMF disorders can often be diagnosed by their clinical features and/or underlying genetic aberrations, the morphological distinction between SAA and hypocellular RCC has been controversial. The histopathological pattern of RCC consists of islands of immature erythroid precursors accompanied by sparsely distributed granulocytic cells. Megakaryocytes are significantly decreased or absent and, rarely, micromegakaryocytes are detected on immunohistochemistry. Because fatty tissue between areas of hematopoiesis can mimic SAA, 2 biopsies are recommended to facilitate the detection of representative BM spaces. Recent data indicate that the response to immunosuppressive therapy is inferior in RCC compared with SAA. Furthermore, approaches to allogeneic hematopoietic transplantation differ. Controlled prospective clinical studies in patients with hypoplastic BM failure disorders will require comprehensive guidelines for diagnosing SAA, RCC, and the different IBMF disorders.

  12. Case Report: Myelodysplastic syndrome- associated myeloid sarcoma: an unusual clinical presentation of a rare disease.

    Science.gov (United States)

    Horvath, Emoke; Demian, Smaranda; Nagy, Elod

    2016-01-01

    Myeloid sarcoma results from the extramedullary homing and proliferation of immature myeloid precursors. We present the timeline, events and diagnostic pitfalls related to a 66 year-old male patient's case, admitted to the Hematology Clinic for pancytopenia, fever, weight loss and fatigue. The severe cytopenia and the few blasts observed in his blood smear indicated a bone marrow biopsy. The bone marrow showed hypercellularity and multilineage dysplasia with the presence of 15% myeloblasts. After the biopsy, he promptly developed paraplegia and nuclear magnetic resonance revealed an epidural tumour which was then resected.In the epidural tumour mass blast-like, round cells were observed with a complex immunophenotype, characterized by myeloperoxidase, CD117, CD15, CD99, leucocyte common antigen positivity and a high Ki-67 proliferation index. Considering the main differential diagnostic issues, the final diagnosis was stated as myelodysplastic syndrome-associated myeloid sarcoma. The prognosis was unfavourable, the bone marrow was quickly invaded by proliferating blast cells, and despite chemotherapy attempts, the patient died.

  13. High Framingham risk score decreases quality of life in adults

    Directory of Open Access Journals (Sweden)

    Christian Yosaputra

    2010-04-01

    Full Text Available Cardiovascular disease (CVD risk factors, such as diabetes, hypertension, hypercholesterolemia, smoking, and obesity tend to occur together in the general population. Increasing prevalence of multiple CVD risk factors has been related to increased risk of death from coronary heart disease and stroke. Studies have suggested that people with several risk factors of CVD may have impaired health-related quality of life. The objective of this study was to assess the association of CVD risk factors with quality of life (QOL among adults aged 40 to 65 years. A cross-sectional study was conducted involving 220 subjects 40 - 65 years of age at a health center. The CVD risk factors were assessed using the Framingham risk score that is the standard instrument for assessment of the risk of a first cardiac event. The risk factors assessed were age, smoking, blood pressure, total cholesterol and high density lipoprotein cholesterol concentrations. QOL was assessed by means of the WHOQOL-BREF instrument that had been prevalidated. The results of the study showed that 28.2% of subjects were smokers, 56.4% had stage 1 hypertension, 42.8% high total cholesterol and 13.6% low HDL cholesterol. The high risk group amounted to 45.5% and 42.3% constitued an intermediate risk group. High CVD risk scores were significantly associated with a low QOL for all domains (physical, psychological, social and environment (p=0.000. Preventing or reducing the multiple CVD risk factors to improve QOL is necessary among adults.

  14. Cost-effectiveness of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infections among high-risk neutropenic patients in Spain

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    Grau Santiago

    2012-04-01

    Full Text Available Abstract Background We evaluated the cost-effectiveness of posaconazole compared with standard azole therapy (SAT; fluconazole or itraconazole for the prevention of invasive fungal infections (IFI and the reduction of overall mortality in high-risk neutropenic patients with acute myelogenous leukaemia (AML or myelodysplastic syndromes (MDS. The perspective was that of the Spanish National Health Service (NHS. Methods A decision-analytic model, based on a randomised phase III trial, was used to predict IFI avoided, life-years saved (LYS, total costs, and incremental cost-effectiveness ratio (ICER; incremental cost per LYS over patients' lifetime horizon. Data for the analyses included life expectancy, procedures, and costs associated with IFI and the drugs (in euros at November 2009 values which were obtained from the published literature and opinions of an expert committee. A probabilistic sensitivity analysis (PAS was performed. Results Posaconazole was associated with fewer IFI (0.05 versus 0.11, increased LYS (2.52 versus 2.43, and significantly lower costs excluding costs of the underlying condition (€6,121 versus €7,928 per patient relative to SAT. There is an 85% probability that posaconazole is a cost-saving strategy compared to SAT and a 97% probability that the ICER for posaconazole relative to SAT is below the cost per LYS threshold of €30,000 currently accepted in Spain. Conclusions Posaconazole is a cost-saving prophylactic strategy (lower costs and greater efficacy compared with fluconazole or itraconazole in high-risk neutropenic patients.

  15. 'High-risk' pregnancy after perinatal loss: understanding the label.

    Science.gov (United States)

    Simmons, Heather A; Goldberg, Lisa S

    2011-08-01

    to explore women's experience of living with a 'high-risk' pregnancy following a perinatal loss. a feminist phenomenological methodology provided the framework for the research study. the experience of 'high-risk' pregnancy following perinatal loss of seven women receiving care at a tertiary health centre in Atlantic Canada was explored by way of conversational interviews and reflective journaling. four themes emerged through thematic analysis and researcher interpretation: (1) understanding the meaning in the label of 'high-risk' pregnancy, (2) relational engagement with the unborn infant, (3) insight and acceptance of the influence of previous loss, and (4) essentiality of information. Taken together, these four themes represent the storied text embedded in the research study. The focus of attention in this article is based solely on the first theme, understanding the meaning in the label of 'high-risk' pregnancy, in so far as this fosters an ability to attend to the interpretive text in the methodological manner appropriate to phenomenological inquiry. although previous research indicates that the label of 'high-risk' in pregnancy is often associated with increased anxiety and fear, findings from this study suggest that a 'high-risk' pregnancy following perinatal loss results in women embracing the 'high-risk' label. By recognising the possibility that women experiencing 'high-risk' pregnancy following perinatal loss may perceive the label of 'high-risk' pregnancy in a positive way, nurses, midwives and other health-care providers may begin to alter their practices when caring for these women in current health-care environments. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Autoimmune Hepatitis and Seronegative Hepatitis Associated With Myelodysplastic Syndrome in Children.

    Science.gov (United States)

    Rasmussen, Line K; Stenbøg, Elisabeth V; Kerndrup, Gitte B; Hasle, Henrik

    2016-11-01

    An association between hepatitis and aplastic anemia (AA) is known as hepatitis-associated AA, and is characterized by an acute attack of hepatitis followed by the development of AA. We report 2 clinical cases of acute seronegative hepatitis in which pancytopenia with mild dysplasia developed after 3 months; however, neither of our cases fulfilled the histological criteria of AA, but rather myelodysplastic syndrome. This novel association bears considerable resemblance to hepatitis-associated AA, and raises the question of whether hepatitis-associated dysmyelopoiesis should be included in the spectrum of hypocellular myelodysplastic syndrome.

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

    Directory of Open Access Journals (Sweden)

    José Vassallo

    2009-08-01

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

  18. Radical prostatectomy in clinically localized high-risk prostate cancer

    DEFF Research Database (Denmark)

    Røder, Martin Andreas; Berg, Kasper Drimer; Christensen, Ib Jarle

    2013-01-01

    Abstract Objective. The optimal therapeutic strategy for high-risk localized prostate cancer (PCa) is controversial. Supported by randomized trials, the combination of external beam radiation therapy (EBRT) and endocrine therapy (ET) is advocated by many, while radical prostatectomy (RP......) is regarded as primary therapy by others. This study examined the outcome for high-risk localized PCa patients treated with RP. Material and methods. Of 1300 patients who underwent RP, 231 were identified as high-risk. Patients were followed for biochemical recurrence (BCR) (defined as prostate...

  19. A prognostic model of therapy-related myelodysplastic syndrome for predicting survival and transformation to acute myeloid leukemia.

    Science.gov (United States)

    Quintás-Cardama, Alfonso; Daver, Naval; Kim, Hawk; Dinardo, Courtney; Jabbour, Elias; Kadia, Tapan; Borthakur, Gautam; Pierce, Sherry; Shan, Jianqin; Cardenas-Turanzas, Marylou; Cortes, Jorge; Ravandi, Farhad; Wierda, William; Estrov, Zeev; Faderl, Stefan; Wei, Yue; Kantarjian, Hagop; Garcia-Manero, Guillermo

    2014-10-01

    We evaluated the characteristics of a cohort of patients with myelodysplastic syndrome (MDS) related to therapy (t-MDS) to create a prognostic model. We identified 281 patients with MDS who had received previous chemotherapy and/or radiotherapy for previous malignancy. Potential prognostic factors were determined using univariate and multivariate analyses. Multivariate Cox regression analysis identified 7 factors that independently predicted short survival in t-MDS: age ≥ 65 years (hazard ratio [HR], 1.63), Eastern Cooperative Oncology Group performance status 2-4 (HR, 1.86), poor cytogenetics (-7 and/or complex; HR, 2.47), World Health Organization MDS subtype (RARs or RAEB-1/2; HR, 1.92), hemoglobin (HR, 2.24), platelets (HR, 2.01), and transfusion dependency (HR, 1.59). These risk factors were used to create a prognostic model that segregated patients into 3 groups with distinct median overall survival: good (0-2 risk factors; 34 months), intermediate (3-4 risk factors; 12 months), and poor (5-7 risk factors; 5 months) (P < .001) and 1-year leukemia-free survival (96%, 84%, and 72%, respectively, P = .003). This model also identified distinct survival groups according to t-MDS therapy. In summary, we devised a prognostic model specifically for patients with t-MDS that predicted overall survival and leukemia-free survival. This model might facilitate the development of risk-adapted therapeutic strategies. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. A social work study high-risk behavior among teenagers

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Iravani

    2012-01-01

    Full Text Available Teenagers are believed the people who are supposed to build the world's future. High-risk behaviors such as addiction to drugs, smoking cigarettes, sex, etc. could significantly hurts teenagers and there must be some supporting programs to reduce these issues as much as possible. This paper performs an empirical investigation to study the different factors influencing high- risk behavior among teenagers who live in a city of Esfahan, Iran. The proposed study designs a questionnaire and distribute between two groups of female and male teenagers. The results indicate that while there is a meaningful relationship between high-risk behaviors and average high school marks among male students there is no meaningful relationship between high-risk behaviors and high school grades among female students. The results also indicate that there is a meaningful difference between gender and high-risk behavior. The season of birth for female and male students is another important factor for having high-risk behaviors. While the order of birth plays an important role among male students, the order of birth is not an important factor among female teenagers. Finally, the results indicate that teenagers' parental financial affordability plays a vital role on both female and male teenagers.

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

    African Journals Online (AJOL)

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

  2. Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Vinayak Muralidhar

    2016-02-01

    Full Text Available Purpose : Recent retrospective data suggest that brachytherapy (BT boost may confer a cancer-specific survival benefit in radiation-managed high-risk prostate cancer. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4 + 4 = 8, PSA 20 ng/ml. Material and methods: We identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aN0M0 intermediate- to high-risk prostate cancer diagnosed 2004-2011 treated with external beam radiation therapy (EBRT only or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM after EBRT + BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors. Results : EBRT + BT was not associated with an improvement in 5-year PCSM compared to EBRT alone among patients with favorable high-risk disease (1.6% vs. 1.8%; adjusted hazard ratio [AHR]: 0.56; 95% confidence interval [CI]: 0.21-1.52, p = 0.258, and intermediate-risk disease (0.8% vs. 1.0%, AHR: 0.83, 95% CI: 0.59-1.16, p = 0.270. Others with high-risk disease had significantly lower 5-year PCSM when treated with EBRT + BT compared with EBRT alone (3.9% vs. 5.3%; AHR: 0.73; 95% CI: 0.55-0.95; p = 0.022. Conclusions : Brachytherapy boost is associated with a decreased rate of PCSM in some men with high-risk prostate cancer but not among patients with favorable high-risk disease. Our results suggest that the recently-defined “favorable high-risk” category may be used to personalize therapy for men with high-risk disease.

  3. Multiplex ligation-dependent probe amplification assay identifies additional copy number changes compared with R-band karyotype and provide more accuracy prognostic information in myelodysplastic syndromes.

    Science.gov (United States)

    Wang, Jingya; Ai, Xiaofei; Qin, Tiejun; Xu, Zefeng; Zhang, Yue; Liu, Jinqin; Li, Bing; Fang, Liwei; Zhang, Hongli; Pan, Lijuan; Hu, Naibo; Qu, Shiqiang; Cai, Wenyu; Ru, Kun; Jia, Yujiao; Huang, Gang; Xiao, Zhijian

    2017-01-03

    Cytogenetic analysis provides important diagnostic and prognostic information for patients with Myelodysplastic syndromes (MDS) and plays an essential role in the International Prognostic Scoring System (IPSS) and the revised International Prognostic Scoring System (IPSS-R). Multiplex ligation-dependent probe amplification (MLPA) assay is a recently developed technique to identify targeted cytogenetic aberrations in MDS patients. In the present study, we evaluated the results obtained using an MLPA assay in 437 patients with MDS to determine the efficacy of MLPA analysis. Using R-banding karyotyping, 45% (197/437) of MDS patients had chromosomal abnormalities, whereas MLPA analysis detected that 35% (153/437) of MDS cases contained at least one copy-number variations (CNVs) .2/5 individuals (40%) with R-band karyotype failures had trisomy 8 detected using only MLPA. Clonal cytogenetic abnormalities were detected in 20/235 (8.5%) MDS patients with a normal R-band karyotype, and 12/20 (60%) of those patients were reclassified into a higher-risk IPSS-R prognostic category. When sequencing and cytogenetics were combined, the fraction of patients with MDS-related oncogenic lesions increased to 87.3% (233/267 cases). MLPA analysis determined that the median OS of patients with a normal karyotype (n=218) was 65 months compared with 27 months in cases with an aberrant karyotype (P=0.002) in 240 patients with normal or failed karyotypes by R-banding karyotyping. The high-resolution MPLA assay is an efficient and reliable method that can be used in conjunction with R-band karyotyping to detect chromosomal abnormalities in patients with suspected MDS. MLPA may also provide more accurate prognostic information.

  4. Multiplex ligation-dependent probe amplification assay identifies additional copy number changes compared with R-band karyotype and provide more accuracy prognostic information in myelodysplastic syndromes

    Science.gov (United States)

    Xu, Zefeng; Zhang, Yue; Liu, Jinqin; Li, Bing; Fang, Liwei; Zhang, Hongli; Pan, Lijuan; Hu, Naibo; Qu, Shiqiang; Cai, Wenyu; Ru, Kun; Jia, Yujiao; Huang, Gang; Xiao, Zhijian

    2017-01-01

    Cytogenetic analysis provides important diagnostic and prognostic information for patients with Myelodysplastic syndromes (MDS) and plays an essential role in the International Prognostic Scoring System (IPSS) and the revised International Prognostic Scoring System (IPSS-R). Multiplex ligation-dependent probe amplification (MLPA) assay is a recently developed technique to identify targeted cytogenetic aberrations in MDS patients. In the present study, we evaluated the results obtained using an MLPA assay in 437 patients with MDS to determine the efficacy of MLPA analysis. Using R-banding karyotyping, 45% (197/437) of MDS patients had chromosomal abnormalities, whereas MLPA analysis detected that 35% (153/437) of MDS cases contained at least one copy-number variations (CNVs) .2/5 individuals (40%) with R-band karyotype failures had trisomy 8 detected using only MLPA. Clonal cytogenetic abnormalities were detected in 20/235 (8.5%) MDS patients with a normal R-band karyotype, and 12/20 (60%) of those patients were reclassified into a higher-risk IPSS-R prognostic category. When sequencing and cytogenetics were combined, the fraction of patients with MDS-related oncogenic lesions increased to 87.3% (233/267 cases). MLPA analysis determined that the median OS of patients with a normal karyotype (n=218) was 65 months compared with 27 months in cases with an aberrant karyotype (P=0.002) in 240 patients with normal or failed karyotypes by R-banding karyotyping. The high-resolution MPLA assay is an efficient and reliable method that can be used in conjunction with R-band karyotyping to detect chromosomal abnormalities in patients with suspected MDS. MLPA may also provide more accurate prognostic information. PMID:27906673

  5. Physical activity barriers and motivators among high-risk employees.

    Science.gov (United States)

    Paguntalan, John C; Gregoski, Mathew

    2016-11-22

    Worksite wellness programs offer an ideal setting to target high-risk sedentary workers to improve health status. Lack of physical activity is associated with increased risk for coronary heart disease and mortality. Despite the risks, the number of sedentary workers is increasing. This study examined the perceived barriers and motivators for physical activity among employees at high-risk for coronary heart disease. A purposive sample of 24 high-risk workers participating in a wellness program in rural South Carolina were enrolled in the study. Qualitative data was obtained through semi-structured face-to-face interviews. Grounded theory was used to analyze qualitative data, and identify overarching themes. Physical limitations due to pain and weakness, lack of motivation, and lack of time emerged as the main barriers to physical activity. Family relationships were reported as the strongest motivator along with social support and potential health benefits. Findings highlight the unique experience of high-risk workers with physical activity. The findingsunderscore the need to design and implement effective interventions specifically designed to meet the needs of high-risk employees.

  6. DASH - Youth Risk Behavior Surveillance System (YRBSS): High School

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1991-2015. High School Dataset. The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health behaviors among youth and young...

  7. Suicide Risk Especially High for U.S. Farmers

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_166800.html Suicide Risk Especially High for U.S. Farmers Other occupations ... Two decades after the U.S. farm crisis, the suicide rate among American farmers remains much higher than ...

  8. Sensation seeking in males involved in recreational high risk sports

    National Research Council Canada - National Science Library

    Guszkowska, M; Bołdak, A

    2010-01-01

    ...) of Zuckerman was applied.Results show, that high risk sports males are featured by stronger need of sensations in comparison to control group and this concerned all but one aspect of sensation seeking variable...

  9. High prevalence of cardiovascular risk factors in Durban South ...

    African Journals Online (AJOL)

    High prevalence of cardiovascular risk factors in Durban South African Indians: The Phoenix Lifestyle Project. ... All participants had demographic, anthropometric and biochemical measurements using the modified World Health Organization (WHO) STEPwise survey methods. Hypertension, obesity, lipid abnormalities and ...

  10. Psychological characteristics in high-risk MSM in China

    National Research Council Canada - National Science Library

    Chen, Guanzhi; Li, Yang; Zhang, Beichuan; Yu, Zengzhao; Li, Xiufang; Wang, Lixin; Yu, Ziming

    2012-01-01

    .... To date, little is known regarding the behavioral, social and psychological characteristics in Chinese MSM, which makes the implementation of preventive and therapeutic strategies for this high-risk...

  11. Treating Patients with High-Risk Smoldering Myeloma

    Science.gov (United States)

    In this phase III clinical trial, patients with smoldering myeloma classified as high risk for progression will be randomly assigned to undergo standard observation or six 4-week courses of treatment with the drug lenalidomide.

  12. High alcohol consumption causes high IgE levels but not high risk of allergic disease

    DEFF Research Database (Denmark)

    Lomholt, Frederikke K; Nielsen, Sune F; Nordestgaard, Børge G

    2016-01-01

    .2-2.5) for 1 allergic disease, 3.9 (95% CI, 3.5-4.4) for 2 allergic diseases, and 7.5 (95% CI, 6.2-9.0) for 3 allergic diseases. High alcohol consumption was associated with high IgE levels but not with high risk of allergic disease. The odds ratio for high versus low IgE levels per 1 alcoholic drink per week......BACKGROUND: High alcohol consumption is associated with high IgE levels in observational studies; however, whether high alcohol consumption leads to high IgE levels and allergic disease is unclear. OBJECTIVE: We tested the hypothesis that high alcohol consumption is associated with high IgE levels...... for the alcohol-metabolizing enzymes alcohol dehydrogenase 1B (ADH-1B; rs1229984) and alcohol dehydrogenase 1c (ADH-1C; rs698). Observationally, we investigated associations between IgE levels and allergic disease (allergic asthma, rhinitis, and eczema) and between alcohol consumption and IgE levels and allergic...

  13. The biology of myelodysplastic syndromes: unity despite heterogeneity

    Directory of Open Access Journals (Sweden)

    Azra Raza

    2010-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Taichun Qin

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

  15. Down-regulation of EZH2 expression in myelodysplastic syndromes.

    Science.gov (United States)

    Cabrero, Monica; Wei, Yue; Yang, Hui; Ganan-Gomez, Irene; Bohannan, Zach; Colla, Simona; Marchesini, Matteo; Bravo, Guillermo Montalban; Takahashi, Koichi; Bueso-Ramos, Carlos; Garcia-Manero, Guillermo

    2016-05-01

    EZH2 genetic mutations are common in myelodysplastic syndrome (MDS), which implies that this gene has a pathophysiological role in the disease. To further characterize molecular alterations of EZH2, and their potential prognostic impact in MDS, we assessed EZH2 RNA expression in primary bone marrow CD34+ cells from 78 patients. We found that 47% of patients have reduced EZH2 expression compared to normal controls. Further analyses revealed that EZH2 is significantly underexpressed in patients bearing chromosome 7 or 7q deletions (7-alt) when compared to controls, diploid patients, and patients with other cytogenetic alterations (pEZH2 underexpression (median OS 55 vs. 36 months; p=0.71). Importantly, this trend became significant when the analysis was restricted to the subset of cases without alterations in chromosome 7 (62 vs. 36 months; p=0.033). Furthermore, our previous work has identified a spectrum of innate immune genes in MDS CD34+ cells that are deregulated via abnormal promoter histone methylation. Because EZH2 is a key regulator of histone methylation, we assessed the relationship between deregulation of these genes and EZH2 underexpression. We observed that the mRNA levels of 11 immune genes were higher in the EZH2 underexpression group and that immune gene expression was significantly higher in patients with concomitant EZH2 underexpression and KDM6B (also known as JMJD3, an H3K27 demethylase) overexpression. Taken together, these data indicate that EZH2 underexpression may have unique impact on the molecular pathogenesis and prognosis in MDS and be an important marker for patients without chromosome 7 alteration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Increasing incidence of myelodysplastic syndromes: real or fictitious?

    Science.gov (United States)

    Aul, C; Germing, U; Gattermann, N; Minning, H

    1998-01-01

    Over the past 10-20 years, there has been a growing interest in the myelodysplastic syndromes (MDS). Due to difficulties of diagnosis, classification and case recording, the epidemiological features of MDS are still poorly defined. Recently, a number of cancer registries have published data on the regional occurrence of MDS, suggesting that MDS are much more common than previously thought. The crude incidence of MDS in these studies was 3.5-12.6 per 100,000 population per year. In people over the age of 70 years, incidence rates varied between 15 and 50 per 100,000 per year. Contrary to the assumption of most hematologists, cancer surveys usually failed to demonstrate a rising incidence of MDS. In those studies showing a significant increase in MDS, the rising number of cases was probably due to increased physician awareness and extended use of invasive diagnostic procedures in elderly people. Differences in incidence figures between regional studies may be attributed to several causes, including regional variations in disease incidence, small and ill-defined reference populations, bias due to patient referral patterns, varying intensity of diagnostic procedures and different observation periods. Because of the paucity of clinical symptoms and insignificance of morphological bone marrow changes particularly in early stage MDS, the currently available incidence figures are likely to underestimate the true incidence of MDS. Large-scale epidemiological studies are required for obtaining truly representative statistics on the incidence and prevalence of the MDS. In industrialized countries, a dramatic increase in these disorders can be expected over the next few decades due to the 'greying' of the population.

  17. Altered neutrophil maturation patterns that limit identification of myelodysplastic syndromes.

    Science.gov (United States)

    Monaghan, Sara A; Surti, Urvashi; Doty, Ketah; Craig, Fiona E

    2012-07-01

    Altered neutrophil maturation patterns have been reported useful for identification of myelodysplastic syndromes (MDS). Neutrophil maturation patterns based on CD11b, CD13, and CD16 were visually and numerically evaluated in 19 control, 23 MDS, 37 nondiagnostic for MDS (NDM) specimens, and 19 also processed 1 and 2 days subsequently. In contrast to maturation patterns illustrated previously by others as "normal," 84% of controls displayed diminished acquisition of CD16, imparting a contracted appearance. Such divergence from published "normal" patterns was usually mild-moderate, considered nonspecific, and associated with delayed processing: longer intervals between collection and processing (median 20.5 vs. 5.2 h), and following 1 and 2 days delay. Findings restricted to nonspecific contraction were found in 56% MDS and 78% NDM specimens. Evaluation for aberrant patterns was still performed with mild-moderate contraction present, but concern for over interpretation led to use of an equivocal-aberrant category. Nine cases had aberrant or equivocal-aberrant patterns (seven MDS, two NDM) with distinct visual alterations that differed from nonspecific contraction and had numerical evidence for a left shift: myeloblasts increased (67%) and least mature neutrophils (CD11b-/low, CD16-/low) increased (78%). Although evidence for a left shift was associated with MDS, it was also seen in NDM specimens with a synchronous left shift. Neutrophil maturation patterns that diverge from previously illustrated "normal" patterns, not specific for MDS, may be common in some settings. Laboratories seeking to implement FC evaluation for MDS must determine which findings have sufficient specificity for MDS within their own practice and patient population. Copyright © 2012 International Clinical Cytometry Society.

  18. Vaginal micronized progesterone and risk of preterm delivery in high-risk twin pregnancies

    DEFF Research Database (Denmark)

    Klein, K; Rode, L; Nicolaides, K H

    2011-01-01

    OBJECTIVES: Progesterone treatment reduces the risk of preterm delivery in high-risk singleton pregnancies. Our aim was to evaluate the preventive effect of vaginal progesterone in high-risk twins. METHODS: This was a subanalysis of a Danish-Austrian, double-blind, placebo-controlled, randomized...... trial (PREDICT study), in which women with twin pregnancies were randomized to daily treatment with progesterone or placebo pessaries from 20-24 weeks until 34 weeks' gestation. This subpopulation consisted of high-risk pregnancies, defined by the finding of cervical length ≤ 10th centile at 20-24 weeks...... (10.6%) of the 677 women participating in the PREDICT study, the pregnancy was considered to be high-risk, including 47 with cervical length ≤ 10th centile, 28 with a history of preterm delivery or late miscarriage and three fulfilling both criteria. Baseline characteristics for progesterone...

  19. High-Risk Human Papillomavirus Targets Crossroads in Immune Signaling

    OpenAIRE

    Bart Tummers; van der Burg, Sjoerd H

    2015-01-01

    Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellu...

  20. Outcomes of parental investment in high-risk children.

    Science.gov (United States)

    Bugental, Daphne Blunt; Corpuz, Randy; Samec, Rachel

    2013-09-01

    This study assesses the combined effects of children's early medical risk (e.g., preterm status) and parental investment levels (time spent in provision of care to target children as opposed to other family members) on children's response to novel, potentially distressing stimuli. While engaged in play activities, children were exposed to stimuli that were either neutral (a speaker on television with a calm voice) or threatening (a speaker with an angry voice). A significant interaction between children's risk status and parental investment was found only for threatening stimuli. High-risk children with high-investing parents showed high visual engagement with potentially threatening responses, whereas high-risk children with low-investing parents were more likely to show visual avoidance. No comparable effects were found for low-risk children. Findings were interpreted as showing that high-risk children with a history of high parental investment are more likely to attend to potentially threatening events, an adaptive response in the presence of reliable support. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. High-risk smoldering myeloma: Perspective on watchful monitoring.

    Science.gov (United States)

    Leng, Siyang; Lentzsch, Suzanne

    2016-12-01

    In a 2008 paper, Dispenzieri and colleagues at the Mayo Clinic proposed a risk stratification system for patients with smoldering multiple myeloma (SMM) based on the presence of three risk factors: serum M-protein ≥3 g/dL, bone marrow plasma cell percentage ≥10%, and a free light chain (FLC) ratio (κ to λ) of either ≤0.125 or ≥8. The patient in this vignette has all three risk factors, classifying him as high-risk, with an associated median time to progression (TTP) of 1.9 years. This is significantly worse than a patient with intermediate-risk (median TTP 5.1 years) or low-risk (10 years) disease. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-06-01

    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.

  3. Molecular Testing in Myelodysplastic Syndromes for the Practicing Oncologist: Will the Progress Fulfill the Promise?

    Science.gov (United States)

    Nazha, Aziz; Sekeres, Mikkael A; Gore, Steven D; Zeidan, Amer M

    2015-09-01

    Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic neoplasms that are driven by somatically acquired genetic mutations and epigenetic alterations. Accurate risk stratification is essential for delivery of risk-adaptive therapeutic interventions. The current prognostic tools sum the impact of clinical, pathologic, and laboratory parameters. Newer technologies with next-generation targeted deep sequencing and whole-genome and -exome sequencing have identified several recurrent mutations that play a vital role in the pathophysiology of MDS and the impact of these genetic changes on disease phenotype. Equally important, well-annotated databases of MDS patients with paired clinicopathologic and genetic data have enabled better understanding of the independent prognostic impact of several molecular mutations on important clinical endpoints such as overall survival and probability of leukemic progression. Cumulative evidence suggests that genomic data can also be used clinically to aid with the diagnosis, prognosis, prediction of response to specific therapies, and the development of novel and rationally targeted therapies. However, the optimal use of this mutational profiling remains a work in progress and currently there is no standard set of genes or techniques that are recommended for routine use in the clinic. In this review, we discuss the genomic revolution and its impact on our understanding of MDS biology and risk stratification. We also discuss the current role and the challenges of the application of genetic mutational data into daily clinical practice and how future research could help improve the prognostication precision and specific therapy selection for patients with MDS. Heterogeneity in clinical outcomes of MDS is partly related to interpatient variability of recurrent somatic mutations that drive disease phenotype and progression. Although clinical risk stratification tools have functioned well in prognostication for patients with MDS

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

    Directory of Open Access Journals (Sweden)

    Kathy L McGraw

    Full Text Available 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.

  5. Predicting reattendance at a high-risk breast cancer clinic.

    Science.gov (United States)

    Ormseth, Sarah R; Wellisch, David K; Aréchiga, Adam E; Draper, Taylor L

    2015-10-01

    The research about follow-up patterns of women attending high-risk breast-cancer clinics is sparse. This study sought to profile daughters of breast-cancer patients who are likely to return versus those unlikely to return for follow-up care in a high-risk clinic. Our investigation included 131 patients attending the UCLA Revlon Breast Center High Risk Clinic. Predictor variables included age, computed breast-cancer risk, participants' perceived personal risk, clinically significant depressive symptomatology (CES-D score ≥ 16), current level of anxiety (State-Trait Anxiety Inventory), and survival status of participants' mothers (survived or passed away from breast cancer). A greater likelihood of reattendance was associated with older age (adjusted odds ratio [AOR] = 1.07, p = 0.004), computed breast-cancer risk (AOR = 1.10, p = 0.017), absence of depressive symptomatology (AOR = 0.25, p = 0.009), past psychiatric diagnosis (AOR = 3.14, p = 0.029), and maternal loss to breast cancer (AOR = 2.59, p = 0.034). Also, an interaction was found between mother's survival and perceived risk (p = 0.019), such that reattendance was associated with higher perceived risk among participants whose mothers survived (AOR = 1.04, p = 0.002), but not those whose mothers died (AOR = 0.99, p = 0.685). Furthermore, a nonlinear inverted "U" relationship was observed between state anxiety and reattendance (p = 0.037); participants with moderate anxiety were more likely to reattend than those with low or high anxiety levels. Demographic, medical, and psychosocial factors were found to be independently associated with reattendance to a high-risk breast-cancer clinic. Explication of the profiles of women who may or may not reattend may serve to inform the development and implementation of interventions to increase the likelihood of follow-up care.

  6. Communicating about risk: strategies for situations where public concern is high but the risk is low.

    Science.gov (United States)

    Hooker, Claire; Capon, Adam; Leask, Julie

    2017-01-15

    In this article, we summarise research that identifies best practice for communicating about hazards where the risk is low but public concern is high. We apply Peter Sandman's 'risk = hazard + outrage' formulation to these risks, and review factors associated with the amplification of risk signals. We discuss the structures that determine the success of risk communication strategies, such as the capacity for early communication to 'capture' the dominant representation of risk issues, the importance of communicating uncertainty, and the usefulness of engaging with communities. We argue that, when facing trade-offs in probable outcomes from communication, it is always best to choose strategies that maintain or build trust, even at the cost of initial overreactions. We discuss these features of successful risk communication in relation to a range of specific examples, particularly opposition to community water fluoridation, Ebola, and routine childhood immunisation.

  7. Communicating about risk: strategies for situations where public concern is high but the risk is low

    Directory of Open Access Journals (Sweden)

    Claire Hooker

    2017-02-01

    Full Text Available In this article, we summarise research that identifies best practice for communicating about hazards where the risk is low but public concern is high. We apply Peter Sandman’s ‘risk = hazard + outrage’ formulation to these risks, and review factors associated with the amplification of risk signals. We discuss the structures that determine the success of risk communication strategies, such as the capacity for early communication to ‘capture’ the dominant representation of risk issues, the importance of communicating uncertainty, and the usefulness of engaging with communities. We argue that, when facing trade-offs in probable outcomes from communication, it is always best to choose strategies that maintain or build trust, even at the cost of initial overreactions. We discuss these features of successful risk communication in relation to a range of specific examples, particularly opposition to community water fluoridation, Ebola, and routine childhood immunisation.

  8. Genomic analysis of high-risk smoldering multiple myeloma.

    Science.gov (United States)

    López-Corral, Lucía; Mateos, María Victoria; Corchete, Luis A; Sarasquete, María Eugenia; de la Rubia, Javier; de Arriba, Felipe; Lahuerta, Juan-José; García-Sanz, Ramón; San Miguel, Jesús F; Gutiérrez, Norma C

    2012-09-01

    Smoldering myeloma is an asymptomatic plasma cell dyscrasia with a heterogeneous propensity to progress to active myeloma. In order to investigate the biology of smoldering myeloma patients with high risk of progression, we analyzed the genomic characteristics by FISH, SNP-arrays and gene expression profile of a group of patients with high-risk smoldering myeloma included in a multicenter randomized trial. Chromosomal abnormalities detected by FISH and SNP-arrays at diagnosis were not associated to risk of progression to symptomatic myeloma. However, the overexpression of four SNORD genes (SNORD25, SNORD27, SNORD30 and SNORD31) was correlated with shorter time to progression (Psmoldering patients who progressed to symptomatic myeloma were sequentially analyzed, newly acquired lesions together with an increase in the proportion of plasma cells carrying a given abnormality were observed. These findings suggest that gene expression profiling is a valuable technique to identify smoldering myeloma patients with high risk of progression. (Clinical Trials NCT00443235).

  9. Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

    Science.gov (United States)

    2013-01-15

    Childhood Acute Erythroleukemia (M6); 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 Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; 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

  10. High alcohol consumption causes high IgE levels but not high risk of allergic disease.

    Science.gov (United States)

    Lomholt, Frederikke K; Nielsen, Sune F; Nordestgaard, Børge G

    2016-11-01

    High alcohol consumption is associated with high IgE levels in observational studies; however, whether high alcohol consumption leads to high IgE levels and allergic disease is unclear. We tested the hypothesis that high alcohol consumption is associated with high IgE levels and allergic disease both observationally and genetically using a Mendelian randomization design free of reverse causation and largely free of confounding. Among 111,408 subjects aged 20 to 100 years from the general population, 50,019 had plasma IgE measurements, and 102,270 were genotyped for the alcohol-metabolizing enzymes alcohol dehydrogenase 1B (ADH-1B; rs1229984) and alcohol dehydrogenase 1c (ADH-1C; rs698). Observationally, we investigated associations between IgE levels and allergic disease (allergic asthma, rhinitis, and eczema) and between alcohol consumption and IgE levels and allergic disease. Genetically, we explored potential causal relationships between alcohol consumption and IgE levels and allergic disease. The multivariable adjusted odds ratio for IgE levels greater than versus less than 150 kU/L and compared with subjects without allergic disease was 2.3 (95% CI, 2.2-2.5) for 1 allergic disease, 3.9 (95% CI, 3.5-4.4) for 2 allergic diseases, and 7.5 (95% CI, 6.2-9.0) for 3 allergic diseases. High alcohol consumption was associated with high IgE levels but not with high risk of allergic disease. The odds ratio for high versus low IgE levels per 1 alcoholic drink per week higher consumption was 1.12 (95% CI, 1.02-1.23) genetically and 1.01 (95% CI, 1.01-1.02) observationally; for allergic disease, the corresponding odds ratios were 0.96 (95% CI, 0.92-1.00) genetically and 1.00 (95% CI, 1.00-1.00) observationally. High alcohol consumption is associated observationally and genetically with high IgE levels but not with high risk of allergic disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. Concurrent loss of Ezh2 and Tet2 cooperates in the pathogenesis of myelodysplastic disorders.

    Science.gov (United States)

    Muto, Tomoya; Sashida, Goro; Oshima, Motohiko; Wendt, George R; Mochizuki-Kashio, Makiko; Nagata, Yasunobu; Sanada, Masashi; Miyagi, Satoru; Saraya, Atsunori; Kamio, Asuka; Nagae, Genta; Nakaseko, Chiaki; Yokote, Koutaro; Shimoda, Kazuya; Koseki, Haruhiko; Suzuki, Yutaka; Sugano, Sumio; Aburatani, Hiroyuki; Ogawa, Seishi; Iwama, Atsushi

    2013-11-18

    Polycomb group (PcG) proteins are essential regulators of hematopoietic stem cells. Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN). In our patient cohort, EZH2 mutations were also found and often coincided with tet methylcytosine dioxygenase 2 (TET2) mutations. Consistent with these findings, deletion of Ezh2 alone was enough to induce MDS/MPN-like diseases in mice. Furthermore, concurrent depletion of Ezh2 and Tet2 established more advanced myelodysplasia and markedly accelerated the development of myelodysplastic disorders including both MDS and MDS/MPN. Comprehensive genome-wide analyses in hematopoietic progenitor cells revealed that upon deletion of Ezh2, key developmental regulator genes were kept transcriptionally repressed, suggesting compensation by Ezh1, whereas a cohort of oncogenic direct and indirect polycomb targets became derepressed. Our findings provide the first evidence of the tumor suppressor function of EZH2 in myeloid malignancies and highlight the cooperative effect of concurrent gene mutations in the pathogenesis of myelodysplastic disorders.

  12. Quality of life measurement in patients with transfusion-dependent myelodysplastic syndromes

    NARCIS (Netherlands)

    Jansen, A. J. G.; Essink-Bot, M.-L.; Beckers, E. A. M.; Hop, W. C. J.; Schipperus, M. R.; van Rhenen, D. J.

    2003-01-01

    The myelodysplastic syndromes (MDS) are clonal disorders characterized by dysplasia in at least two myeloid cell lines. Fatigue is one of the most significant symptoms. MDS patients are treated with blood transfusions to improve their health-related quality of life (HRQoL). A cross-sectional pilot

  13. Stem cell transplantation for leukemias following myelodysplastic syndromes or secondary to cytotoxic therapy.

    NARCIS (Netherlands)

    Witte, T.J.M. de; Oosterveld, M.; Span, L.F.R.; Muus, P.; Schattenberg, A.V.M.B.

    2002-01-01

    Two main forms of therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) have been recognized. The most frequent type, occurring after treatment with alkylating agents, is characterized by abnormalities of chromosomes 5 and/or 7 and t-MDS/AML following treatment with

  14. Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes.

    NARCIS (Netherlands)

    Nikoloski, G.; Langemeijer, S.M.C.; Kuiper, R.P.; Knops, R.; Massop, M.; Tonnissen, E.R.; Heijden, A. van der; Scheele, T.N.; Berghe, P. van den; Witte, T.J.M. de; Reijden, B.A. van der; Jansen, J.H.

    2010-01-01

    In myelodysplastic syndromes (MDS), deletions of chromosome 7 or 7q are common and correlate with a poor prognosis. The relevant genes on chromosome 7 are unknown. We report here that EZH2, located at 7q36.1, is frequently targeted in MDS. Analysis of EZH2 deletions, missense and frameshift

  15. A quantitative evaluation of erythropoiesis in myelodysplastic syndromes using multiparameter flow cytometry

    DEFF Research Database (Denmark)

    Jensen, I M; Hokland, M; Hokland, P

    1993-01-01

    By staining human bone marrow cells with a monoclonal antibody reacting with erythroid precursor cells (AS-E1) and propidium iodide, we have evaluated the proliferative capacity of erythropoiesis in patients with myelodysplastic syndromes (MDS) using flow cytometry. Comparing 36 patients (13 RA...

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

    DEFF Research Database (Denmark)

    Pastor, Victor B; Sahoo, Sushree; Boklan, Jessica

    2017-01-01

    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 7 patients from 4 unrelated pedigrees presenting with myelodisplastic syndrome and loss of chromosome ...

  17. The risk ogf high-risk jobs : psychological health consequences in forensic physicians and ambulance workers

    NARCIS (Netherlands)

    Ploeg, E. van der

    2003-01-01

    The risk of high-risk jobs: Psychological health consequences in forensic doctors and ambulance workers This thesis has shown that forensic physicians and ambulance personnel frequently suffer from psychological complaints as a result of dramatic events and sources of chronic work stress. A

  18. Risk factors for congenital anomalies in high risk pregnant women: A ...

    African Journals Online (AJOL)

    Tella Sunitha

    2016-05-14

    May 14, 2016 ... Abstract Background: High Risk Pregnancy (HRP) is a condition where mother or developing fetus or both are at increased risk of complications during or after pregnancy and birth. There are no studies so far which have characterized congenital anomalies (CAs) in HRP women with dif- ferent previous ...

  19. Risk factors for congenital anomalies in high risk pregnant women: A ...

    African Journals Online (AJOL)

    Tella Sunitha

    2016-05-14

    May 14, 2016 ... Rubella;. CMV and HSV. Abstract Background: High Risk Pregnancy (HRP) is a condition where mother or developing fetus or both are at increased risk of complications during or after pregnancy and birth. There are no studies so far which have characterized congenital anomalies (CAs) in HRP women ...

  20. On risk, leverage and banks: do highly leveraged banks take on excessive risk?

    NARCIS (Netherlands)

    Koudstaal, M.; van Wijnbergen, S.

    2012-01-01

    This paper deals with the relation between excessive risk taking and capital structure in banks. Examining a quarterly dataset of U.S. banks between 1993 and 2010, we find that equity is valued higher when more risky portfolios are chosen when leverage is high, and that more risk taking has a

  1. Clinical risk factors for gestational hypertensive disorders in pregnant women at high risk for developing preeclampsia

    NARCIS (Netherlands)

    Wong, Tsz Y.; Groen, Henk; Faas, Marijke M.; van Pampus, Maria G.

    2013-01-01

    Objectives: To evaluate clinical risk factors for the development of gestational hypertensive disorders in a group of pregnant women at high risk for developing preeclampsia. Secondly we evaluated the incidence and recurrence rate of preeclampsia and pregnancy-induced hypertension. Study design: A

  2. Who Takes Risks in High-Risk Sports? A Typological Personality Approach

    Science.gov (United States)

    Castanier, Carole; Le Scanff, Christine; Woodman, Tim

    2010-01-01

    We investigated the risk-taking behaviors of 302 men involved in high-risk sports (downhill skiing, mountaineering, rock climbing, paragliding, or skydiving). The sportsmen were classified using a typological approach to personality based on eight personality types, which were constructed from combinations of neuroticism, extraversion, and…

  3. Risk behaviors for the health of adolescents from High School

    Directory of Open Access Journals (Sweden)

    José Henrique Ramos

    2009-09-01

    Full Text Available Objective: To investigate the risk behaviors (smoking addiction, alcoholism, drug use and sexual risk behavior of adolescents from High School. Methods: It was an analytical and cross-sectional study. The sample consisted of 720 scholars (252 boys and 468 girls from the age group of 16 to 17 years-old, from three public schools in Florianopolis/SC. The data was collected through two types of self administrated questionnaires; one for the parents and another one for the students, from March to December, 2005. The studied variables were legal and illegal drug use and sexual risk behavior. The descriptive statistics and the chi- squared test were used to carry out the data analysis Results: The beginning of risk behaviors occurred between 14 and 15 years old, for both genders. It was observed that 26 (3.6% scholars drank alcohol regularly; 38 (5.3% smoked daily; 66 (9.2 % were drug users or had used drugs several times and 14 (2% were drug dependents. Concerning to sexual risk behavior, 318 (44.5% scholars had sexual risk behavior and from those, 97 (13.6% did not always use condom. From the studied sample, 545 (76.5% scholars did not present any risk behavior. Among risk behaviors, sexual risk prevailed (42.5%. Conclusion: The number of adolescents with risk behavior was not high. Nevertheless, there is a small proportion of adolescents that smoke, drink and do drugs and have sexual risk behavior. This points out to the need of a bigger supervision and guidance for these students.

  4. Early Parental Adaptation, Prenatal Distress, and High-Risk Pregnancy.

    Science.gov (United States)

    Dollberg, Daphna G; Rozenfeld, Tamir; Kupfermincz, Michael

    2016-09-01

    To examine the examined the effects of high risk pregnancy and prenatal distress on parental postnatal adaptation. A sample of 111 expecting parents, consisting of 32 high risk pregnancy (HRP) mothers and 21 spouses and 36 matched low risk pregnancy (LRP) mothers and 22 spouses completed reports of depression symptoms (BDI) and pregnancy related concerns prenatally. At three months postpartum, parent-infant direct observations and reports of parenting alliance (PAI), stress (PSI-SF), satisfaction and efficacy (PSOC) were gathered. Data was analyzed with GLM multivariate analyses and the actor-partner interdependence model. Parents' prenatal BDI predicted postnatal parental stress. BDI and concerns predicted postnatal satisfaction, but only for mothers. Mother's concerns predicted low maternal and high paternal parenting alliance. Partner effect was found so that high concerns predicted high reports of parenting alliance by spouse. Mean-group differences were found between HRP and LRP during parent-infant observations, so that HRP parents displayed lower sensitivity and reciprocity. Prenatal distress, and to some degree high risk pregnancy, are risk factors that may interfere with the early formation of parent-infant relationship. Clinical implications of these findings are presented. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. The risk of hydrogen explosion in a submarine p. IV The implementation of high risk projects

    Directory of Open Access Journals (Sweden)

    Kłos Ryszard

    2017-06-01

    Full Text Available This series of articles on high risk projects looks at the example of the modernisation of hydrogen incinerators on a submarine. The article describes problems connected with the management of such a project.

  6. Cumulative Experiences of Violence among High-Risk Urban Youth

    Science.gov (United States)

    Taylor, Catherine A.; Boris, Neil W.; Heller, Sherryl Scott; Clum, Gretchen A.; Rice, Janet C.; Zeanah, Charles H.

    2008-01-01

    This study examines type-specific and cumulative experiences of violence among a vulnerable population of youth. Sixty high-risk, shelter-dwelling, urban youth were interviewed regarding their history of childhood maltreatment, exposure to community violence (ECV), and experience with intimate partner violence (IPV). Results show a high prevalence…

  7. An assessment of high risk sexual behaviour and HIV transmission ...

    African Journals Online (AJOL)

    Method: A total of 300 randomly selected migrant oil workers were assessed using structured questionnaires to evaluate key highrisk sexual behavioral parameters such as multiplicity of sexual partners, bisexuality (closet homosexuality), high grade sexual behaviour and lesbianism. Sampling period was two months with ...

  8. High risk drinking and college students' self-perceptions.

    Science.gov (United States)

    Araujo, Gabriel C; Wong, Eugene H

    2005-12-01

    The present study examined the relationship between high risk drinking and college students' self-perceptions. High risk drinking was defined as the consumption of four or more drinks in a row for women and five or more drinks in a row for men during a single sitting (within the last year). Historical trends regarding college-age drinking indicate that 44% of college students fit the criteria for high risk drinking at least once over the past year. A survey was administered to 210 college students (52 men and 158 women) between 18 and 22 years of age (M = 20.9, SD = 1.3) to assess their use of alcohol and their self-perceptions. Students' self-perceptions were measured with four subscales from the Neemann-Harter Self-perception Profile for College Students. Students either volunteered to participate in this study outside of class or were solicited during class. It was predicted that students' self-perceptions would differ significantly depending upon their alcohol consumption, i.e., 17.1% were Abstainers, 25.2% were Nonproblem Drinkers, and 57.6% were High Risk Drinkers. Analysis gave significant difference on Global Self-worth between students who abstained and those who were High Risk Drinkers. However, students' perceptions of Scholastic Competence, Intellectual Ability, and Social Acceptance did not differ significantly for the alcohol consumption groups. In addition to high risk drinking, a number of other variables were associated with self-perceptions, such as high school alcohol use, low high school GPA, and students' reported academic involvement. These relations are discussed.

  9. Psychological characteristics in high-risk MSM in China.

    Science.gov (United States)

    Chen, Guanzhi; Li, Yang; Zhang, Beichuan; Yu, Zengzhao; Li, Xiufang; Wang, Lixin; Yu, Ziming

    2012-01-20

    Men who have sex with men (MSM) have become a high-risk group of HIV infection in China. To date, little is known regarding the behavioral, social and psychological characteristics in Chinese MSM, which makes the implementation of preventive and therapeutic strategies for this high-risk subpopulation of people extremely difficult. A total of 714 questionnaires were retrieved from the database of a Chinese government-sponsored National Key Research Project titled "Risk Analysis and Strategic Prevention of HIV Transmission from MSM to the General Population in China". The respondents were categorized into a high-risk group and a control group. Their behavioral, social and psychological characteristics were comparatively analyzed. Of the 714 MSM analyzed, 59 (8.26%) had high-risk homosexual behaviors. This sub-group of MSM had a higher in-marriage rate, a higher monthly income, heavier alcohol consumption and more serious problems with sexual abuse in childhood, intentional suicide attempts and mistaken assumption on condom's role in protecting HIV infection, as compared with the control group (P discrimination (P > 0.05). A vast majority of the individuals in both behavior categories expressed support of legally protected gay clubs as well as gay marriage legislation in China. There was a strong correlation between high-risk behaviors and sexual abuse in childhood, alcohol drinking, income level and a mistaken belief in perfect HIV protection through the use of condoms. MSM with and without high-risk homosexual behaviors have different social and psychological characteristics, which should be taken into account when implementing behavioral and therapeutic interventions aimed at preventing HIV/AIDS transmission among MSM as well as from MSM to the general population in China.

  10. Telomerase activation by genomic rearrangements in high-risk neuroblastoma.

    Science.gov (United States)

    Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L; Sand, Frederik; Heuckmann, Johannes M; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Gloeckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R; Savelyeva, Larissa; Watkins, Simon C; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H; Herrmann, Carl; O'Sullivan, Roderick J; Westermann, Frank; Thomas, Roman K; Fischer, Matthias

    2015-10-29

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours.

  11. Psychological characteristics in high-risk MSM in China

    Directory of Open Access Journals (Sweden)

    Chen Guanzhi

    2012-01-01

    Full Text Available Abstract Background Men who have sex with men (MSM have become a high-risk group of HIV infection in China. To date, little is known regarding the behavioral, social and psychological characteristics in Chinese MSM, which makes the implementation of preventive and therapeutic strategies for this high-risk subpopulation of people extremely difficult. Methods A total of 714 questionnaires were retrieved from the database of a Chinese government-sponsored National Key Research Project titled "Risk Analysis and Strategic Prevention of HIV Transmission from MSM to the General Population in China". The respondents were categorized into a high-risk group and a control group. Their behavioral, social and psychological characteristics were comparatively analyzed. Results Of the 714 MSM analyzed, 59 (8.26% had high-risk homosexual behaviors. This sub-group of MSM had a higher in-marriage rate, a higher monthly income, heavier alcohol consumption and more serious problems with sexual abuse in childhood, intentional suicide attempts and mistaken assumption on condom's role in protecting HIV infection, as compared with the control group (P P > 0.05. A vast majority of the individuals in both behavior categories expressed support of legally protected gay clubs as well as gay marriage legislation in China. There was a strong correlation between high-risk behaviors and sexual abuse in childhood, alcohol drinking, income level and a mistaken belief in perfect HIV protection through the use of condoms. Conclusions MSM with and without high-risk homosexual behaviors have different social and psychological characteristics, which should be taken into account when implementing behavioral and therapeutic interventions aimed at preventing HIV/AIDS transmission among MSM as well as from MSM to the general population in China.

  12. Factors Influencing Cancer Risk Perception in High Risk Populations: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Tilburt Jon C

    2011-05-01

    Full Text Available Abstract Background Patients at higher than average risk of heritable cancer may process risk information differently than the general population. However, little is known about clinical, demographic, or psychosocial predictors that may impact risk perception in these groups. The objective of this study was to characterize factors associated with perceived risk of developing cancer in groups at high risk for cancer based on genetics or family history. Methods We searched Ovid MEDLINE, Ovid Embase, Ovid PsycInfo, and Scopus from inception through April 2009 for English-language, original investigations in humans using core concepts of "risk" and "cancer." We abstracted key information and then further restricted articles dealing with perceived risk of developing cancer due to inherited risk. Results Of 1028 titles identified, 53 articles met our criteria. Most (92% used an observational design and focused on women (70% with a family history of or contemplating genetic testing for breast cancer. Of the 53 studies, 36 focused on patients who had not had genetic testing for cancer risk, 17 included studies of patients who had undergone genetic testing for cancer risk. Family history of cancer, previous prophylactic tests and treatments, and younger age were associated with cancer risk perception. In addition, beliefs about the preventability and severity of cancer, personality factors such as "monitoring" personality, the ability to process numerical information, as well as distress/worry also were associated with cancer risk perception. Few studies addressed non-breast cancer or risk perception in specific demographic groups (e.g. elderly or minority groups and few employed theory-driven analytic strategies to decipher interrelationships of factors. Conclusions Several factors influence cancer risk perception in patients at elevated risk for cancer. The science of characterizing and improving risk perception in cancer for high risk groups, although

  13. HIFU therapy for patients with high risk prostate cancer

    Science.gov (United States)

    Solovov, V. A.; Vozdvizhenskiy, M. O.; Matysh, Y. S.

    2017-03-01

    Objectives. Patients with high-risk prostate cancer undergoing radical prostatectomy, external beam radiation therapy (EBRT) combined with androgen deprivation therapy (ADT) or ADT alone. The widely accepted definition of high-risk prostate was first proposed by D'Amico based on a pretreatment Gleason score of ≥8, clinical stage T3, PSA level ≥20 ng/mL. There is no trial that compares traditional methods of treatment of such patients with HIFU therapy. Here we explored the effectiveness of the HIFU in multimodal treatment for patients with high risk prostate cancer. Materials & Methods. 701 patients with high risk prostate cancer were treated in our center between September 2007 and December 2013. Gleason score were 8-10, stage T3N0M0, age 69 (58-86) years, mean PSA before treatment 43.3 (22.1-92.9) ng/ml, mean prostate volume - 59.3 (38-123) cc. 248 patients were treated by HIFU. We compare this group of patients with patients who undertook EBRT: number 196, and ADT: number 257. Mean follow-up time 58 months (6-72). Results. The 5-year overall survival rates in patients after HIFU were 73.8 %, after EBRT - 63.0 % and after ADT - 18.1%. Conclusions. Our experience showed that HIFU therapy in combined treatment were successful for high risk prostate cancer.

  14. Detection of high risk campylobacteriosis clusters at three geographic levels

    Directory of Open Access Journals (Sweden)

    Jennifer Weisent

    2011-11-01

    Full Text Available Campylobacteriosis is a leading cause of bacterial gastroenteritis in the United States and many other developed countries. Understanding the spatial distribution of this disease and identifying high-risk areas is vital to focus resources for prevention and control measures. In addition, determining the appropriate scale for geographical analysis of surveillance data is an area of concern to epidemiologists and public health officials. The purpose of this study was to (i compare standardized risk estimates for campylobacteriosis in Tennessee over three distinct geographical scales (census tract, zip code and county subdivision, and (ii identify and investigate high-risk spatial clustering of campylobacteriosis at the three geographical scales to determine if clustering is scale dependent. Significant high risk clusters (P <0.05 were detected at all three spatial scales. There were overlaps in regions of high-risk and clusters at all three geographic levels. At the census tract level, spatial analysis identified smaller clusters of finer resolution and detected more clusters than the other two levels. However, data aggregation at zip code or county subdivision yielded similar findings. The importance of this line of research is to create a framework whereby economically efficient disease control strategies become more attainable through improved geographical precision and risk detection. Accurate identification of disease clusters for campylobacteriosis can enable public health personnel to focus scarce resources towards prevention and control programmes on the most at-risk populations. Consistent results at multiple spatial levels highlight the robustness of the geospatial techniques utilized in this study. Furthermore, analyses at the zip code and county subdivision levels can be useful when address level information (finer resolution data are not available. These procedures may also be used to help identify regionally specific risk factors for

  15. Personality and sensation seeking in high-risk sports

    OpenAIRE

    Polona Klinar; Stojan Burnik; Tanja Kajtna

    2017-01-01

    Background: Personality represents a relatively consistent and unique sum of psychological, cognitive and physical characteristics of an individual. Sensation seeking is defined as an action, characterized by the search for different, new, complex and intensive emotions and experiences and preparedness to take physical, social, legal and financial risks in order to achieve these experiences.Objective: We were looking for differences in personality and sensation seeking between high-risk sport...

  16. Correlates of hopelessness in the high suicide risk police occupation

    OpenAIRE

    Violanti, John M.; Andrew, Michael E.; Mnatsakanova, Anna; Hartley, Tara A.; Fekedulegn, Desta; Burchfiel, Cecil M.

    2015-01-01

    Police officers are chronically exposed to work stress. We examined specific stressors that may be associated with hopelessness, a possible risk factor for suicide in this high suicide risk population. The study included 378 officers (276 men and 102 women) with complete data. Analysis of variance was used to estimate mean levels of hopelessness scores as associated with stress, adjusted for age, gender, and race/ ethnicity. Posttraumatic symptoms were tested as a modifier of the association ...

  17. A novel risk classification paradigm for patients with impaired glucose tolerance and high cardiovascular risk.

    Science.gov (United States)

    Bethel, M Angelyn; Chacra, Antonio R; Deedwania, Prakash; Fulcher, Gregory R; Holman, Rury R; Jenssen, Trond; Kahn, Steven E; Levitt, Naomi S; McMurray, John J V; Califf, Robert M; Raptis, Sotirios A; Thomas, Laine; Sun, Jie-Lena; Haffner, Steven M

    2013-07-15

    We used baseline data from the NAVIGATOR trial to (1) identify risk factors for diabetes progression in those with impaired glucose tolerance and high cardiovascular risk, (2) create models predicting 5-year incident diabetes, and (3) provide risk classification tools to guide clinical interventions. Multivariate Cox proportional hazards models estimated 5-year incident diabetes risk and simplified models examined the relative importance of measures of glycemia in assessing diabetes risk. The C-statistic was used to compare models; reclassification analyses compare the models' ability to identify risk groups defined by potential therapies (routine or intensive lifestyle advice or pharmacologic therapy). Diabetes developed in 3,254 (35%) participants over 5 years median follow-up. The full prediction model included fasting and 2-hour glucose and hemoglobin A1c (HbA1c) values but demonstrated only moderate discrimination for diabetes (C = 0.70). Simplified models with only fasting glucose (C = 0.67) or oral glucose tolerance test values (C = 0.68) had higher C statistics than models with HbA1c alone (C = 0.63). The models were unlikely to inappropriately reclassify participants to risk groups that might receive pharmacologic therapy. Our results confirm that in a population with dysglycemia and high cardiovascular risk, traditional risk factors are appropriate predictors and glucose values are better predictors than HbA1c, but discrimination is moderate at best, illustrating the challenges of predicting diabetes in a high-risk population. In conclusion, our novel risk classification paradigm based on potential treatment could be used to guide clinical practice based on cost and availability of screening tests. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Epigenetic landscape of the TERT promoter: a potential biomarker for high risk AML/MDS.

    Science.gov (United States)

    Zhao, Xin; Tian, Xin; Kajigaya, Sachiko; Cantilena, Caroline R; Strickland, Stephen; Savani, Bipin N; Mohan, Sanjay; Feng, Xingmin; Keyvanfar, Keyvan; Dunavin, Neil; Townsley, Danielle M; Dumitriu, Bogdan; Battiwalla, Minoo; Rezvani, Katayoun; Young, Neal S; Barrett, A John; Ito, Sawa

    2016-11-01

    Although recent observations implicate the importance of telomerase activity in acute myeloid leukaemia (AML), the roles of epigenetic regulations of the TERT gene in leukaemogenesis, drug resistance and clinical prognosis in AML are not fully understood. We developed a quantitative pyrosequencing-based methylation assay covering the TERT proximal promoter and a partial exon 1 (TERTpro/Ex1) region and tested both cell lines and primary leukaemia cells derived from AML and AML with preceding myelodysplastic syndrome (AML/MDS) patients (n = 43). Prognostic impact of methylation status of the upstream TERT promoter region was assessed by the Kaplan-Meier method. The activity of the telomerase inhibitor, imetelstat, was measured using leukaemia cell lines. The TERTpro/Ex1 region was highly methylated in all cell lines and primary leukaemia cells showed diverse methylation profiles. Most cases showed hypermethylated regions at the upstream TERTpro/Ex1 region, which were associated with inferior patient survival. TERTpro/Ex1 methylation status was correlated with the cytotoxicity to imetelstat and its combination with hypomethylating agent enhanced the cytotoxicity of imetelstat. AML cell lines and primary blasts harbour distinct TERTpro/Ex1 methylation profiles that could serve as a prognostic biomarker of AML. However, validation in a large cohort of patients is necessary to confirm our findings. © 2016 John Wiley & Sons Ltd.

  19. Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

    Science.gov (United States)

    2016-12-08

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  20. Allogeneic Hematopoietic Stem Cell Transplantation Is Underutilized in Older Patients with Myelodysplastic Syndromes.

    Science.gov (United States)

    Getta, Bartlomiej M; Kishtagari, Ashwin; Hilden, Patrick; Tallman, Martin S; Maloy, Molly; Gonzales, Patrick; Castro-Malaspina, Hugo; Perales, Miguel-Angel; Giralt, Sergio; Tamari, Roni; Klimek, Virginia

    2017-07-01

    Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative treatment for myelodysplastic syndrome (MDS). The proportion of MDS patients referred for transplantation evaluation, those undergoing transplantation, and the reasons for not undergoing transplantation are unknown. In this retrospective analysis, predefined HCT eligibility and indications criteria were applied to 362 unselected patients with newly diagnosed MDS seen by leukemia faculty between 2008 and 2015 at Memorial Sloan Kettering Cancer Center. Two hundred ninety-four patients (81%) were deemed eligible for transplantation and among these, transplantation was considered indicated in 244 (83%). Of these, 158 of 244 (65%) were referred for transplantation evaluation at a median of 3.9 months from diagnosis. Overall 120 of 362 (33%) underwent transplantation at a median of 7.7 months from diagnosis. Metastatic solid-organ malignancy was the major reason for transplantation ineligibility (54%), and death due to MDS, which occurred in 41% of candidates who did not undergo transplantation, was the major reason for not undergoing transplantation. Factors associated with a lower likelihood of referral for transplantation evaluation included age ≥65 (P < .001), ≥2 comorbidities (P = .008), intermediate-1/low risk MDS (P < .001), <5% blasts at diagnosis (overall P < .001), having Medicare/Medicaid health insurance (P < .001), not being married (P = .017), and diagnosis between 2008 and 2011 (P = .035). On multivariate analysis adjusting for all of the previous factors, diagnosis between 2008 and 2011 (P < .001), age ≥65 (P = .001), and <5% blasts at diagnosis (overall P = .031) were associated with a lower likelihood of referral for transplantation evaluation. Factors associated with a lower likelihood of undergoing transplantation included age ≥65 (P < .001), ≥2 comorbidities (P = .003), intermediate-1/low risk MDS (P < .001), <5% blasts (overall P

  1. High-Risk Stress Fractures: Diagnosis and Management.

    Science.gov (United States)

    McInnis, Kelly C; Ramey, Lindsay N

    2016-03-01

    Stress fractures are common overuse injuries in athletes. They occur during periods of increased training without adequate rest, disrupting normal bone reparative mechanisms. There are a host of intrinsic and extrinsic factors, including biochemical and biomechanical, that put athletes at risk. In most stress fractures, the diagnosis is primarily clinical, with imaging indicated at times, and management focused on symptom-free relative rest with advancement of activity as tolerated. Overall, stress fractures in athletes have an excellent prognosis for return to sport, with little risk of complication. There is a subset of injuries that have a greater risk of fracture progression, delayed healing, and nonunion and are generally more challenging to treat with nonoperative care. Specific locations of high-risk stress fracture include the femoral neck (tension side), patella, anterior tibia, medial malleolus, talus, tarsal navicular, proximal fifth metatarsal, and great toe sesamoids. These sites share a characteristic region of high tensile load and low blood flow. High-risk stress fractures require a more aggressive approach to evaluation, with imaging often necessary, to confirm early and accurate diagnosis and initiate immediate treatment. Treatment consists of nonweight-bearing immobilization, often with a prolonged period away from sport, and a more methodic and careful reintroduction to athletic activity. These stress fractures may require surgical intervention. A high index of suspicion is essential to avoid delayed diagnosis and optimize outcomes in this subset of stress fractures. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  2. Assessment of Primitive Reflexes in High-risk Newborns.

    Science.gov (United States)

    Sohn, Min; Ahn, Youngmee; Lee, Sangmi

    2011-12-01

    Assessment of primitive reflexes is one of the earliest, simplest, and most frequently used assessment tools among health care providers for newborns and young infants. However, very few data exist for high-risk infants in this topic. Among the various primitive reflexes, this study was undertaken particularly to describe the sucking, Babinski and Moro reflexes in high-risk newborns and to explore their relationships with clinical variables. This study is a cross-sectional descriptive study. Sixty seven high-risk newborns including full-term infants required intensive care as well as premature infants were recruited in a neonatal intensive care unit using convenient sampling method. The sucking, Babinski and Moro reflexes were assessed and classified by normal, abnormal and absence. To explore their relationships with clinical variables, birth-related variables, brain sonogram results, and behavioral state (the Anderson Behavioral State Scale, ABSS) and mental status (the Infant Coma Scale, ICS) were assessed. The sucking reflex presented a normal response most frequently (63.5%), followed by Babinski reflex (58.7%) and Moro reflex (42.9%). Newborns who presented normal sucking and Babinski reflex responses were more likely to have older gestational age, heavier birth and current weight, higher Apgar scores, shorter length of hospitalization, better respiratory conditions, and better mental status assessed by ICS, but not with Moro reflex. High risk newborns presented more frequent abnormal and absence responses of primitive reflex and the proportions of the responses varied by reflex. Further researches are necessary in exploring diverse aspects of primitive reflexes and revealing their clinical implication in the high-risk newborns that are unique and different to normal healthy newborns. Primitive reflex; High risk infants; Korean; Moro reflex; Sucking reflex; Babinski reflex; The Anderson Behavioral State Scale; Infant Coma Scale.

  3. Feedback signals in myelodysplastic syndromes: increased self-renewal of the malignant clone suppresses normal hematopoiesis.

    Science.gov (United States)

    Walenda, Thomas; Stiehl, Thomas; Braun, Hanna; Fröbel, Julia; Ho, Anthony D; Schroeder, Thomas; Goecke, Tamme W; Rath, Björn; Germing, Ulrich; Marciniak-Czochra, Anna; Wagner, Wolfgang

    2014-04-01

    Myelodysplastic syndromes (MDS) are triggered by an aberrant hematopoietic stem cell (HSC). It is, however, unclear how this clone interferes with physiologic blood formation. In this study, we followed the hypothesis that the MDS clone impinges on feedback signals for self-renewal and differentiation and thereby suppresses normal hematopoiesis. Based on the theory that the MDS clone affects feedback signals for self-renewal and differentiation and hence suppresses normal hematopoiesis, we have developed a mathematical model to simulate different modifications in MDS-initiating cells and systemic feedback signals during disease development. These simulations revealed that the disease initiating cells must have higher self-renewal rates than normal HSCs to outcompete normal hematopoiesis. We assumed that self-renewal is the default pathway of stem and progenitor cells which is down-regulated by an increasing number of primitive cells in the bone marrow niche--including the premature MDS cells. Furthermore, the proliferative signal is up-regulated by cytopenia. Overall, our model is compatible with clinically observed MDS development, even though a single mutation scenario is unlikely for real disease progression which is usually associated with complex clonal hierarchy. For experimental validation of systemic feedback signals, we analyzed the impact of MDS patient derived serum on hematopoietic progenitor cells in vitro: in fact, MDS serum slightly increased proliferation, whereas maintenance of primitive phenotype was reduced. However, MDS serum did not significantly affect colony forming unit (CFU) frequencies indicating that regulation of self-renewal may involve local signals from the niche. Taken together, we suggest that initial mutations in MDS particularly favor aberrant high self-renewal rates. Accumulation of primitive MDS cells in the bone marrow then interferes with feedback signals for normal hematopoiesis--which then results in cytopenia.

  4. An erythroid differentiation signature predicts response to lenalidomide in myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Benjamin L Ebert

    2008-02-01

    Full Text Available Lenalidomide is an effective new agent for the treatment of patients with myelodysplastic syndrome (MDS, an acquired hematopoietic disorder characterized by ineffective blood cell production and a predisposition to the development of leukemia. Patients with an interstitial deletion of Chromosome 5q have a high rate of response to lenalidomide, but most MDS patients lack this deletion. Approximately 25% of patients without 5q deletions also benefit from lenalidomide therapy, but response in these patients cannot be predicted by any currently available diagnostic assays. The aim of this study was to develop a method to predict lenalidomide response in order to avoid unnecessary toxicity in patients unlikely to benefit from treatment.Using gene expression profiling, we identified a molecular signature that predicts lenalidomide response. The signature was defined in a set of 16 pretreatment bone marrow aspirates from MDS patients without 5q deletions, and validated in an independent set of 26 samples. The response signature consisted of a cohesive set of erythroid-specific genes with decreased expression in responders, suggesting that a defect in erythroid differentiation underlies lenalidomide response. Consistent with this observation, treatment with lenalidomide promoted erythroid differentiation of primary hematopoietic progenitor cells grown in vitro.These studies indicate that lenalidomide-responsive patients have a defect in erythroid differentiation, and suggest a strategy for a clinical test to predict patients most likely to respond to the drug. The experiments further suggest that the efficacy of lenalidomide, whose mechanism of action in MDS is unknown, may be due to its ability to induce erythroid differentiation.

  5. A calcium- and calpain-dependent pathway determines the response to lenalidomide in myelodysplastic syndromes

    Science.gov (United States)

    Fang, Jing; Liu, Xiaona; Bolanos, Lyndsey; Barker, Brenden; Rigolino, Carmela; Cortelezzi, Agostino; Oliva, Esther N; Cuzzola, Maria; Grimes, H Leighton; Fontanillo, Celia; Komurov, Kakajan; MacBeth, Kyle; Starczynowski, Daniel T

    2017-01-01

    Despite the high response rates of individuals with myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)) to treatment with lenalidomide (LEN) and the recent identification of cereblon (CRBN) as the molecular target of LEN, the cellular mechanism by which LEN eliminates MDS clones remains elusive. Here we performed an RNA interference screen to delineate gene regulatory networks that mediate LEN responsiveness in an MDS cell line, MDSL. We identified GPR68, which encodes a G-protein-coupled receptor that has been implicated in calcium metabolism, as the top candidate gene for modulating sensitivity to LEN. LEN induced GPR68 expression via IKAROS family zinc finger 1 (IKZF1), resulting in increased cytosolic calcium levels and activation of a calcium-dependent calpain, CAPN1, which were requisite steps for induction of apoptosis in MDS cells and in acute myeloid leukemia (AML) cells. In contrast, deletion of GPR68 or inhibition of calcium and calpain activation suppressed LEN-induced cytotoxicity. Moreover, expression of calpastatin (CAST), an endogenous CAPN1 inhibitor that is encoded by a gene (CAST) deleted in del(5q) MDS, correlated with LEN responsiveness in patients with del(5q) MDS. Depletion of CAST restored responsiveness of LEN-resistant non-del(5q) MDS cells and AML cells, providing an explanation for the superior responses of patients with del(5q) MDS to LEN treatment. Our study describes a cellular mechanism by which LEN, acting through CRBN and IKZF1, has cytotoxic effects in MDS and AML that depend on a calcium- and calpain-dependent pathway. PMID:27294874

  6. Assessing karyotype precision by microarray-based comparative genomic hybridization in the myelodysplastic/myeloproliferative syndromes

    Science.gov (United States)

    2010-01-01

    Background Recent genome-wide microarray-based research investigations have revealed a high frequency of submicroscopic copy number alterations (CNAs) in the myelodysplastic syndromes (MDS), suggesting microarray-based comparative genomic hybridization (aCGH) has the potential to detect new clinically relevant genomic markers in a diagnostic laboratory. Results We performed an exploratory study on 30 cases of MDS, myeloproliferative neoplasia (MPN) or evolving acute myeloid leukemia (AML) (% bone marrow blasts ≤ 30%, range 0-30%, median, 8%) by aCGH, using a genome-wide bacterial artificial chromosome (BAC) microarray. The sample data were compared to corresponding cytogenetics, fluorescence in situ hybridization (FISH), and clinical-pathological findings. Previously unidentified imbalances, in particular those considered submicroscopic aberrations (deletions were found in three patients at time of AML transformation. Other hidden CNAs involved 3q26.2/EVI1, 5q22/APC, 5q32/TCERG1,12p13.1/EMP1, 12q21.3/KITLG, and 17q11.2/NF1. Gains of CCND2/12p13.32 were detected in two patients. aCGH failed to detect a balanced translocation (n = 1) and low-level clonality (n = 4) in five karyotypically aberrant samples, revealing clinically important assay limitations. Conclusions The detection of previously known and unknown genomic alterations suggests that aCGH has considerable promise for identification of both recurring microscopic and submicroscopic genomic imbalances that contribute to myeloid disease pathogenesis and progression. These findings suggest that development of higher-resolution microarray platforms could improve karyotyping in clinical practice. PMID:21078186

  7. Quantifying the risk of respiratory infection in healthcare workers performing high-risk procedures.

    Science.gov (United States)

    Macintyre, C R; Seale, H; Yang, P; Zhang, Y; Shi, W; Almatroudi, A; Moa, A; Wang, X; Li, X; Pang, X; Wang, Q

    2014-09-01

    This study determined the risk of respiratory infection associated with high-risk procedures (HRPs) performed by healthcare workers (HCWs) in high-risk settings. We prospectively studied 481 hospital HCWs in China, documented risk factors for infection, including performing HRPs, measured new infections, and analysed whether HRPs predicted infection. Infection outcomes were clinical respiratory infection (CRI), laboratory-confirmed viral or bacterial infection, and an influenza infection. About 12% (56/481) of the study participants performed at least one HRP, the most common being airway suctioning (7·7%, 37/481). HCWs who performed a HRP were at significantly higher risk of developing CRI and laboratory-confirmed infection [adjusted relative risk 2·9, 95% confidence interval (CI) 1·42-5·87 and 2·9, 95% CI 1·37-6·22, respectively]. Performing a HRP resulted in a threefold increase in the risk of respiratory infections. This is the first time the risk has been prospectively quantified in HCWs, providing data to inform occupational health and safety policies.

  8. Humanized birth in high risk pregnancy: barriers and facilitating factors.

    Science.gov (United States)

    Behruzi, Roxana; Hatem, Marie; Goulet, Lise; Fraser, William; Leduc, Nicole; Misago, Chizuru

    2010-02-01

    The medical model of childbearing assumes that a pregnancy always has the potential to turn into a risky procedure. In order to advocate humanized birth in high risk pregnancy, an important step involves the enlightenment of the professional's preconceptions on humanized birth in such a situation. The goal of this paper is to identify the professionals' perception of the potential obstacles and facilitating factors for the implementation of humanized care in high risk pregnancies. Twenty-one midwives, obstetricians, and health administrator professionals from the clinical and academic fields were interviewed in nine different sites in Japan from June through August 2008. The interviews were audio taped, and transcribed with the participants' consent. Data was subsequently analyzed using content analysis qualitative methods. Professionals concurred with the concept that humanized birth is a changing and promising process, and can often bring normality to the midst of a high obstetric risk situation. No practice guidelines can be theoretically defined for humanized birth in a high risk pregnancy, as there is no conflict between humanized birth and medical intervention in such a situation. Barriers encountered in providing humanized birth in a high risk pregnancy include factors such as: the pressure of being responsible for the safety of the mother and the fetus, lack of the women's active involvement in the decision making process and the heavy burden of responsibility on the physician's shoulders, potential legal issues, and finally, the lack of midwifery authority in providing care at high risk pregnancy. The factors that facilitate humanized birth in a high risk include: the sharing of decision making and other various responsibilities between the physicians and the women; being caring; stress management, and the fact that the evolution of a better relationship and communication between the health professional and the patient will lead to a stress

  9. Personality and sensation seeking in high-risk sports

    Directory of Open Access Journals (Sweden)

    Polona Klinar

    2017-03-01

    Full Text Available Background: Personality represents a relatively consistent and unique sum of psychological, cognitive and physical characteristics of an individual. Sensation seeking is defined as an action, characterized by the search for different, new, complex and intensive emotions and experiences and preparedness to take physical, social, legal and financial risks in order to achieve these experiences.Objective: We were looking for differences in personality and sensation seeking between high-risk sports athletes and recreational athletes and the correlation between one's purpose to participate in high-risk sports and actual participation.Method: The data was acquired using three different questionnaires: Sensation Seeking Scale (forms SSS - V and SSS - VI and the Big Five Questionnaire. The sample consisted of 76 high-risk sports athletes and 51 recreational athletes. Data was analyzed using the SPSS statistical program.Results: The results were unexpected because we noticed differences between the two groups in which recreational athletes received higher results, especially in openness. Mostly results from such research show the converse - athletes of high-risk sports are more open. We did not find any difference between the two groups in sensation seeking. We found some correlations between personality traits and factors of Sensation Seeking Scale (SSS - V and SSS - VI. Openness and the Thrill and adventure seeking factor correlated in both versions of SSS.Conclusions: We conclude that high-risk sports athletes differ from recreational athletes, especially in openness. Also, we can confirm that both used versions of SSS are equally effective for analyzing sensation seeking.

  10. Multiple causes of high extinction risk in large mammal species.

    Science.gov (United States)

    Cardillo, Marcel; Mace, Georgina M; Jones, Kate E; Bielby, Jon; Bininda-Emonds, Olaf R P; Sechrest, Wes; Orme, C David L; Purvis, Andy

    2005-08-19

    Many large animal species have a high risk of extinction. This is usually thought to result simply from the way that species traits associated with vulnerability, such as low reproductive rates, scale with body size. In a broad-scale analysis of extinction risk in mammals, we find two additional patterns in the size selectivity of extinction risk. First, impacts of both intrinsic and environmental factors increase sharply above a threshold body mass around 3 kilograms. Second, whereas extinction risk in smaller species is driven by environmental factors, in larger species it is driven by a combination of environmental factors and intrinsic traits. Thus, the disadvantages of large size are greater than generally recognized, and future loss of large mammal biodiversity could be far more rapid than expected.

  11. Identification of high risk metropolitan intersection sites in Perth, Australia.

    Science.gov (United States)

    Hobday, Michelle; Chow, Kyle; Meuleners, Lynn; Argus, Fritha

    2017-09-01

    As convergence points for road users approaching from multiple directions, intersections have more opportunities for conflicts, thus higher crash risk than other parts of the road network. Given the limited resources available for road safety, it is important to identify high risk intersections so that they can be prioritised for infrastructure improvement. This study used a three-stage approach to identify intersections in Perth, Western Australia: using Road Trauma Risk Analysis, then Comparative Safety Performance Analysis and finally ranking the intersections by the KSI (Killed and Serious Injury) metric. These methodologies were developed by Main Roads Western Australia. Crash data from 2011 to 2015 were used in the analyses. The results identify the top high risk intersections for each intersection type (by speed environment and control type). Recommendations are made for extensions to this process to improve identification of high risk intersections, and the use of a taxonomy to identify candidate treatments. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  12. Granulocyte colony-stimulating factor inhibits spontaneous cytochrome c release and mitochondria-dependent apoptosis of myelodysplastic syndrome hematopoietic progenitors.

    Science.gov (United States)

    Tehranchi, Ramin; Fadeel, Bengt; Forsblom, Ann-Mari; Christensson, Birger; Samuelsson, Jan; Zhivotovsky, Boris; Hellstrom-Lindberg, Eva

    2003-02-01

    Low-risk myelodysplastic syndromes (MDS), including refractory anemia and sideroblastic anemia, are characterized by increased apoptotic death of erythroid progenitors. The signaling pathways that elicit this pathologic cell death in MDS have, however, remained unclear. Treatment with erythropoietin in combination with granulocyte colony-stimulating factor (G-CSF) may synergistically improve the anemia in patients with MDS, with a concomitant decrease in the number of apoptotic bone marrow precursors. Moreover, we have previously reported that G-CSF inhibits Fas-induced caspase activation in sideroblastic anemia (RARS). The present data demonstrate that almost 50% of erythroid progenitor cells derived from patients with MDS exhibit spontaneous release of cytochrome c from mitochondria with ensuing activation of caspase-9, whereas normal erythroid progenitors display neither of these features. G-CSF significantly inhibited cytochrome c release and suppressed apoptosis, most noticeably in cells from patients with sideroblastic anemia. Furthermore, inhibition of caspase-9 suppressed both spontaneous and Fas-mediated apoptosis of erythroid progenitors in all low-risk MDS cases studied. We propose that the increased sensitivity of MDS progenitor cells to death receptor stimulation is due to a constitutive activation of the mitochondrial axis of the apoptotic signaling pathway in these cells. These studies yield a mechanistic explanation for the beneficial clinical effects of growth factor administration in patients with MDS, and provide a model for the study of growth factor-mediated suppression of apoptosis in other bone marrow disorders.

  13. Recording of risk-factors and lifestyle counselling in patients at high risk for cardiovascular diseases in European primary care.

    NARCIS (Netherlands)

    Ludt, S.; Petek, D.; Laux, G.; Lieshout, J. van; Campbell, S.M.; Kunzi, B.; Glehr, M.; Wensing, M.J.

    2012-01-01

    BACKGROUND: Detection and registration of high risk for cardiovascular diseases (CVD) by assessing individual's absolute cardiovascular risk is recommended in clinical guidelines. Effective interventions to reduce cardiovascular risk are available, but not optimally implemented. The aim of this

  14. [Study on karyotypic abnormalities and its prognostic significance in Chinese patients with primary myelodysplastic syndromes].

    Science.gov (United States)

    Li, Lin; Liu, Xu-Ping; Nie, Ling; Yu, Ming-Hua; Zhang, Yue; Qin, Tie-Jun; Xiao, Zhi-Jian

    2009-04-01

    To investigate the features and prognostic significance of chromosomal karyotype in patients with primary myelodysplastic syndromes (MDS). Results of chromosomal karyotypes of 351 adult patients with primary MDS were retrospectively analyzed. Two hundred and thirty-seven cases (67.5%) had karyotypic abnormalities. Of them, 99 (41.7%) were numerical, 70 (29.5%) were structural, and 68 (28.8%) were complex abnormalities. In addition, among the 237 patients with chromosomal abnormalities, 130 (54.8%) showed single abnormality, 54 (22.8%) double abnormalities and 53 (22.4%) complex abnormalities (> or = 3 two independent aberrations). Four cases (1.7%) were multiploid. Aneuploidy or of chromosomal arm anomaly were detected all of the 46 chromosomes and the aberrations in frequent order were +8, -20/20q-, -7/7q-, -5/5q-, -18, -11/11q-/, +21, -Y, -21, -10, -16, -22, +9, del(12)(p12). The incidence of -5/5q- (5.1%) was lower in our series than in western countries (8.7% -23.4%) and 5q- syndrome was even less (0.3%). The incidences of +8 (19.1%) and -20/20q- (9.4%) were higher in our series than in western countries (1.2% -7.0%, 2.0% -3.5%, respectively). Chromosome translocations were detected in 31 cases (13.1%), including 12 novel translocations that have not been reported in MDS patients before. In addition, i(17)(q10) was detected in 9 cases (3.8%) of which 6 were simplex abnormality. Chromosomal duplication presented in 7 cases (3.0%) with 4 cases involved chromosome 1. According to IPSS chromosomal prognostic classification, the incidence of poor-risk karyotypes was increased in the advanced WHO subtypes (P chromosomal prognostic classification, the median OS of patients with good, intermediate and poor-risk cytogenetic subgroup were 51 (95% CI 25-77), 35 (95% CI 5-65) and 13 (95% CI 9-17) months, respectively (P = 0.004) and for NN-AN-AA karyotype classification, the median OS of NN, AN and AA were 51 (95% CI 24-78), 36 (95% CI 0.3-71) and 23 (95% CI 10-35) months

  15. High wall shear stress and high-risk plaque: an emerging concept.

    Science.gov (United States)

    Eshtehardi, Parham; Brown, Adam J; Bhargava, Ankit; Costopoulos, Charis; Hung, Olivia Y; Corban, Michel T; Hosseini, Hossein; Gogas, Bill D; Giddens, Don P; Samady, Habib

    2017-07-01

    In recent years, there has been a significant effort to identify high-risk plaques in vivo prior to acute events. While number of imaging modalities have been developed to identify morphologic characteristics of high-risk plaques, prospective natural-history observational studies suggest that vulnerability is not solely dependent on plaque morphology and likely involves additional contributing mechanisms. High wall shear stress (WSS) has recently been proposed as one possible causative factor, promoting the development of high-risk plaques. High WSS has been shown to induce specific changes in endothelial cell behavior, exacerbating inflammation and stimulating progression of the atherosclerotic lipid core. In line with experimental and autopsy studies, several human studies have shown associations between high WSS and known morphological features of high-risk plaques. However, despite increasing evidence, there is still no longitudinal data linking high WSS to clinical events. As the interplay between atherosclerotic plaque, artery, and WSS is highly dynamic, large natural history studies of atherosclerosis that include WSS measurements are now warranted. This review will summarize the available clinical evidence on high WSS as a possible etiological mechanism underlying high-risk plaque development.

  16. Characterization of patients at high risk of melanoma in Austria.

    Science.gov (United States)

    Müller, C; Wendt, J; Rauscher, S; Burgstaller-Muehlbacher, S; Sunder-Plassmann, R; Scheurecker, C; Richtig, E; Fae, I; Fischer, G; Pehamberger, H; Okamoto, I

    2016-06-01

    Risk of melanoma is determined by genetic and exogenous factors. Only a few studies have included both characteristics in a comprehensive multivariable analysis. To find determinants of patients at high risk of melanoma in Austria, including phenotype, genotype and lifestyle characteristics in comprehensive analyses. In total, 1668 patients with melanoma from the M3 case-control study were studied. Overall, 567 participants were sequenced for CDKN2A, 232 for CDK4, 123 for MITF encoding the variant E318K and 964 for MC1R. Patients with melanoma with a positive family history (n = 190, 11·6%), multiple primary melanomas (n = 261, 15·7%) and younger age (risk. All other patients with melanoma were defined as the reference group. We found significant differences between those two groups and between the high-risk subgroups (positive family history, multiple primary melanomas and younger age). Pigmentation phenotype was associated with the high-risk group in general (childhood freckling, odds ratio 1·46, P = 0·007; blond/reddish hair colour, odds ratio 1·43, P = 0·011). Patients with a positive family history and patients with early-onset disease were similar regarding both their phenotypic characteristics and external factors. Established high-risk mutations in CDKN2A were found in cases with a positive family history (n = 12) or multiple melanomas (n = 2). Moreover, we found three patients carrying the MITF p.E318K variant, two with a CDK4 variant and seven with nonsynonymous MC1R variants with undescribed biological significance, of which four were predicted as damaging. Austrian patients could represent a reservoir for novel genetic variants. Further investigation of populations in Central and Eastern Europe might reveal more novel and disease-relevant variants. © 2016 British Association of Dermatologists.

  17. Risk factors for the occurrence and spread of Highly Pathogenic ...

    African Journals Online (AJOL)

    Outbreaks of Highly Pathogenic Avian Influenza (HPAI) subtype H5N1 occurred previously for three consecutive years, 2006, 2007 and 2008 in Kano State, Nigeria, causing heavy economic losses to farmers and the government. It was against this background that risk factors for the occurrence and spread of HPAI H5N1 ...

  18. Health risk behaviours of high school learners and their perceptions ...

    African Journals Online (AJOL)

    Learners reported a high prevalence of health risk behaviours: 65% for alcohol use, 57% for sexual activity, 39% for tobacco use and 15% for drug use. 2. The predominant pattern of substance use ..... are predominantly from the lower and middle socio-economic groups. Learners generally do not know the family income.

  19. an assessment of high risk sexual behaviour and hiv transmission ...

    African Journals Online (AJOL)

    We did not also encounter any lesbian sexual orientation in this study. The distribution of. HRSB amongst the migrant oil wOrkers showed that the commonest variety was bisexuality (closet homosexuality) with 10(43.5%) followed by high-risk sexual behaviour 7(30.4%), while the least common was multiplicity of sexual ...

  20. High risk bladder cancer : current management and survival

    NARCIS (Netherlands)

    Leliveld-Kors, Anna; Bastiaannet, Esther; Doornweerd, Benjamin H J; Schaapveld, Michael; de Jong, Igle J

    2011-01-01

    Purpose: To evaluate the pattern of care in patients with high risk non muscle invasive bladder cancer (NMIBC) in the Comprehensive Cancer Center North-Netherlands (CCCN) and to assess factors associated with the choice of treatment, recurrence and progression free survival rates. Materials and

  1. Cyberbullying and Its Risk Factors among Chinese High School Students

    Science.gov (United States)

    Zhou, Zongkui; Tang, Hanying; Tian, Yuan; Wei, Hua; Zhang, Fengjuan; Morrison, Chelsey M.

    2013-01-01

    Cyberbullying has become a common occurrence among adolescents worldwide; however, it has yet to receive adequate scholarly attention in China, especially in the mainland. The present study investigated the epidemiological characteristics and risk factors of cyberbullying, utilizing a sample of 1,438 high school students from central China.…

  2. Sensation seeking in males involved in recreational high risk sports

    Directory of Open Access Journals (Sweden)

    M Guszkowska

    2010-09-01

    Full Text Available The study examined sensation seeking intensity level in males involved in recreational high risk sports and investigated whether its level depends on type of sport practised. Additionally, in case of parachutists, sport experience of study participants were scrutinised with regard to its possible impact on the level of sensation seeking.The research involved 217 males aged 17 to 45, practising recreational high risk sports, namely: parachuting (n=98; wakeboarding (n=30; snowboarding (n=30; scuba diving (n=22; alpinism (n=20; paragliding (n=17. The control group included 54 men not involved in sports. Polish version of Sensation Seeking Scale (SSS-IV of Zuckerman was applied.Results show, that high risk sports males are featured by stronger need of sensations in comparison to control group and this concerned all but one aspect of sensation seeking variable. The only exception was the need of intellectual stimulation. Except from the thrill and adventure seeking dimension, type of sport may also be an important determinant of sensation seeking. Men practising snowboard and wakeboard presented stronger need for sensations, especially in the dimension of experience seeking, disinhibition and boredom susceptibility. Sport experience (number of jumps in parachuting did not differentiate the level of sensation seeking among investigated parachutists. Population of sport high risk male takers was not homogeneous, and therefore in future research one should analyse specific sports (or events in a certain sport separately.

  3. Chorangioma of Placenta with High Risk Pregnancy: A Case Series

    African Journals Online (AJOL)

    Chorangioma of Placenta with High Risk Pregnancy: A Case Series. Uma S Andola, Shabnam Karangadan1, Sainath K Andola1, Rajashekhar Jewargikar1. Department of Obstetrics and Gynecology, 1Resident, Professor and Head of Department, Professor, Department of Pathology, Mahadevappa. Rampure Medical ...

  4. Monitoring paneer for Listeria monocytogenes - A high risk food ...

    African Journals Online (AJOL)

    A multiplex polymerase chain reaction (PCR) assay was developed and applied to spiked and natural paneer samples to detect Listeria monocytogenes, a high risk food pathogen. The sensitivity of the assay on L. monocytogenes spiked paneer samples was 104 cells prior to enrichment, was improved to 103 cells after 4 h ...

  5. anaesthetic challenges in a high risk parturient with myasthenia ...

    African Journals Online (AJOL)

    10 October 2013. ANAESTHETIC CHALLENGES IN A HIGH RISK PARTURIENT WITH MYASTHENIA GRAVIS UNDERGOING ... to highlight some of the challenges, the management and the lessons learnt during the management of this patient. .... be more appropriate if there is bulbar involvement, or severe respiratory ...

  6. High Risk Drinking among Non-Affiliated College Students

    Science.gov (United States)

    Smith, Margaret; Finneran, John; Droppa, Marj

    2014-01-01

    This study investigated the high risk drinking practices of unaffiliated college students who are not involved in formal athletics, fraternities, or sororities. Using a qualitative research design, the investigators interviewed students at a northeast public college in fall 2010 to learn about unaffiliated students' drinking experiences and their…

  7. Hypertensive patients and diabetes : A high-risk population

    NARCIS (Netherlands)

    Bilo, HJG; Gans, ROB

    1998-01-01

    Rising worldwide rates of diabetes mellitus heighten the need to maintain adequate metabolic control in diabetic patients and to control for other cardiovascular risk factors, such as lipid profile disturbances, high blood pressure, and smoking habits. This is especially the case in diabetic

  8. Risk management practices of high school principals regarding ...

    African Journals Online (AJOL)

    This study was undertaken to identify what the key safety concerns at schools in PE are, and to establish what the risk management practices implemented by principals at high schools in selected provinces are. This paper follows the approach that school principals are staff with the highest authority and legal liability for the ...

  9. Risk management practices of high school sport coaches and ...

    African Journals Online (AJOL)

    The purpose of this study was to identify the key safety dimensions of school sport, and to assess the risk management practices implemented by coaches and administrators at high schools. The aim was also to highlight the chief problems associated with safety in sport and to develop strategies to protect learners.

  10. Drug response prediction in high-risk multiple myeloma

    DEFF Research Database (Denmark)

    Vangsted, A J; Helm-Petersen, S; Cowland, J B

    2018-01-01

    A Drug Response Prediction (DRP) score was developed based on gene expression profiling (GEP) from cell lines and tumor samples. Twenty percent of high-risk patients by GEP70 treated in Total Therapy 2 and 3A have a progression-free survival (PFS) of more than 10years. We used available GEP data ...

  11. Detection of Patients at High Risk of Medication Errors

    DEFF Research Database (Denmark)

    Sædder, Eva Aggerholm; Lisby, Marianne; Nielsen, Lars Peter

    2016-01-01

    Medication errors (MEs) are preventable and can result in patient harm and increased expenses in the healthcare system in terms of hospitalization, prolonged hospitalizations and even death. We aimed to develop a screening tool to detect acutely admitted patients at low or high risk of MEs...

  12. Identifying patients at high risk for obstructive sleep apnoea ...

    African Journals Online (AJOL)

    Background: Obstructive sleep apnoea is associated with significant health consequences. A significant proportion of hospitalized patients at risk for obstructive sleep apnoea were never identified and referred for polysomnography for diagnosis. The objective of this study was to determine the factors associated with high ...

  13. The National Cross-Site Evaluation of High-Risk Youth Programs: Understanding Risk, Protection, and Substance Use among High-Risk Youth. Monograph Series.

    Science.gov (United States)

    Springer, J. Fred; Sambrano, Soledad; Sale, Elizabeth; Kasim, Rafa; Hermann, Jack

    This document summarizes findings from the Center for Substance Abuse Prevention's National Cross-Site Evaluation of High-Risk Youth Programs, which identified characteristics associated with strong substance abuse prevention outcomes in 48 prevention programs. Major findings include: as youth age, levels of risk and protection shift considerably,…

  14. Antiplatelet therapy in populations at high risk of atherothrombosis.

    Science.gov (United States)

    Faxon, David P; Nesto, Richard W

    2006-05-01

    Atherothrombosis is the most common cause of an acute ischemic event. Antiplatelet agents form the cornerstone of atherothrombosis prevention. The purpose of this article is to review the use of antiplatelet agents in patients that are at particularly high risk of atherothrombotic events. To undertake this review, we searched the literature to identify key studies on the use of antiplatelet agents in this group of patients. Antiplatelet agents, such as aspirin and clopidogrel, play a fundamental role in the treatment and management of secondary thrombotic events. The routine use of aspirin is recommended, as it has been shown to reduce the risk of thrombotic events by approximately 25%. Additional benefit has been demonstrated with clopidogrel, both as a monotherapy and in combination with aspirin. In the CAPRIE trial, 19,185 patients with atherosclerotic vascular disease were randomized to receive clopidogrel (75 mg/day) or aspirin (325 mg/day) for a mean duration of follow-up of 1.91 years. Clopidogrel provided an additional 8.7% relative risk reduction in the primary composite endpoint of ischemic stroke, myocardial infraction or vascular death compared with aspirin. In the CURE trial, the addition of clopidogrel to background aspirin was associated with a 20% relative risk reduction in a composite of death from cardiovascular causes, nonfatal myocardial infarction or stroke compared with aspirin alone. In patients undergoing PCI as part of the PCI-CURE substudy, clopidogrel was associated with a 30% relative reduction in the incidence of cardiovascular events in the first 30 days after intervention compared with aspirin. The benefits of antiplatelet therapy continue to be investigated. Whether dual antiplatelet therapy is superior to aspirin monotherapy for high-risk primary prevention is unknown. The ongoing CHARISMA trial aims to determine the relative efficacies of aspirin monotherapy and aspirin/clopidogrel combination therapy in a broad range of high-risk

  15. Systematic screening at diagnosis of -5/del(5)(q31), -7, or chromosome 8 aneuploidy by interphase fluorescence in situ hybridization in 110 acute myelocytic leukemia and high-risk myelodysplastic syndrome patients: concordances and discrepancies with conventional cytogenetics.

    NARCIS (Netherlands)

    Beyer, V.; Castagne, C.; Muhlematter, D.; Parlier, V.; Gmur, J.; Hess, U.; Kovacsovics, T.; Meyer-Monard, S.; Tichelli, A.; Tobler, A.; Jacky, E.; Schanz, U.; Bargetzi, M.; Hagemeijer, A.; Witte, T.J.M. de; Melle, G. van; Jotterand-Bellomo, M.

    2004-01-01

    To assess the contribution of interphase fluorescence in situ hybridization (I-FISH) toward the detection of recurring unbalanced chromosomal anomalies at diagnosis, a systematic screening of -5/del(5)(q31), -7, and chromosome 8 aneuploidy was performed on 110 patients with acute myelocytic leukemia

  16. Increased Cardiometabolic Risk and Worsening Hypoxemia at High Altitude.

    Science.gov (United States)

    Miele, Catherine H; Schwartz, Alan R; Gilman, Robert H; Pham, Luu; Wise, Robert A; Davila-Roman, Victor G; Jun, Jonathan C; Polotsky, Vsevolod Y; Miranda, J Jaime; Leon-Velarde, Fabiola; Checkley, William

    2016-06-01

    Miele, Catherine H., Alan R. Schwartz, Robert H. Gilman, Luu Pham, Robert A. Wise, Victor G. Davila-Roman, Jonathan C. Jun, Vsevolod Y. Polotsky, J. Jaime Miranda, Fabiola Leon-Velarde, and William Checkley. Increased cardiometabolic risk and worsening hypoxemia at high altitude. High Alt Med Biol. 17:93-100, 2016.-Metabolic syndrome, insulin resistance, diabetes, and dyslipidemia are associated with an increased risk of cardiovascular disease. While excessive erythrocytosis is associated with cardiovascular complications, it is unclear how worsening hypoxemia of any degree affects cardiometabolic risk factors in high-altitude populations. We studied the relationship between daytime resting oxyhemoglobin saturation and cardiometabolic risk factors in adult participants living in Puno, Peru (3825 m above sea level). We used multivariable logistic regression models to study the relationship between having a lower oxyhemoglobin saturation and markers of cardiometabolic risk. Nine hundred and fifty-four participants (mean age 55 years, 52% male) had information available on pulse oximetry and markers of cardiometabolic risk. Average oxyhemoglobin saturation was 90% (interquartile range 88%-92%) and 43 (4.5%) had excessive erythrocytosis. Older age, decreased height-adjusted lung function, and higher body mass index (BMI) were associated with having an oxyhemoglobin saturation ≤85%. When adjusting for age, sex, socioeconomic status, having excessive erythrocytosis, and site, we found that each 5% decrease in oxyhemoglobin saturation was associated with a higher adjusted odds of metabolic syndrome (OR = 1.35, 95% CI: 1.07-1.72, p 2 mass units (OR = 1.29, 95% CI: 1.00-1.67, p < 0.05), hemoglobin A1c ≥6.5% (OR = 1.66, 95% CI: 1.09-2.51, p < 0.04), and high sensitivity C-reactive protein (hs-CRP) ≥3 mg/L (OR = 1.46, 95% CI: 1.09-1.96, p < 0.01). In high-altitude populations in Puno, Peru, a higher BMI and lower pulmonary function were

  17. Beyond sensation seeking: affect regulation as a framework for predicting risk-taking behaviors in high-risk sport.

    Science.gov (United States)

    Castanier, Carole; Le Scanff, Christine; Woodman, Tim

    2010-10-01

    Sensation seeking has been widely studied when investigating individual differences in the propensity for taking risks. However, risk taking can serve many different goals beyond the simple management of physiological arousal. The present study is an investigation of affect self-regulation as a predictor of risk-taking behaviors in high-risk sport. Risk-taking behaviors, negative affectivity, escape self-awareness strategy, and sensation seeking data were obtained from 265 high-risk sportsmen. Moderated hierarchical regression analysis revealed significant main and interaction effects of negative affectivity and escape self-awareness strategy in predicting risk-taking behaviors: high-risk sportsmen's negative affectivity leads them to adopt risk-taking behaviors only if they also use escape self-awareness strategy. Furthermore, the affective model remained significant when controlling for sensation seeking. The present study contributes to an in-depth understanding of risk taking in high-risk sport.

  18. Organ-Sparing Marrow-Targeted Irradiation Before Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

    Science.gov (United States)

    2017-10-09

    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 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 Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  19. Wandering spleen: 'presentation in adolescent with high thrombotic risk'.

    Science.gov (United States)

    Tchidjou, Hyppolite K; Castelluzzo, Maria A; Messia, Virginia; Luciani, Matteo; Monti, Lidia; Grimaldi, Chiara; Bernardi, Stefania; D'Argenio, Patrizia

    2014-07-01

    The term 'wandering spleen' refers to an abnormal hypermobility of the spleen, which may be congenital or acquired. The absence or abnormal laxity of splenic ligaments combined with an abnormally long and mobile vascular pedicle predispose to complications such as torsion of the splenic pedicle, infarction and splenic vein thrombosis. The clinical presentation of such disease is highly variable. In this case, we describe an asymptomatic case of wandering spleen in high thrombotic risk patients with cavernoma of splenic vein and infarction of the spleen. Physical examination was normal except the enlarged and no tender consistency spleen palpable at left iliac fossa. Ultrasonography revealed enlarged spleniform mass below its normal position suggesting vascular impairment and subsequently has been confirmed by colour Doppler ultrasound and computed tomography. The family history was positive for ischemic thrombotic vascular diseases and the screening for thrombotic risk has revealed hyperhomocysteinemia, thrombophilic homozygous gene mutations for factor V (H1299R) and MTHFR (C677T). For high thrombotic risk, prophylaxis postsplenectomy was suggested according to the international recommendations with subcutaneous low molecular weight heparin, associated with a preventive treatment with acetyl salicylic acid and folic acid along with B-vitamin. This case report may be helpful for clinicians involved in the care of splenectomized patients, because it has shown the importance of an appropriate pre and postoperative antithrombotic management to reduce as soon as possible the risk of thrombotic events in such patients after splenectomy.

  20. Case Management Reduces Drinking During Pregnancy among High Risk Women.

    Science.gov (United States)

    May, Philip A; Marais, Anna-Susan; Gossage, J Phillip; Barnard, Ronel; Joubert, Belinda; Cloete, Marise; Hendricks, Natalie; Roux, Sumien; Blom, Annalien; Steenekamp, Jeanetta; Alexander, Theresa; Andreas, Romena; Human, Suzanne; Snell, Cudore; Seedat, Soraya; Parry, Charles C; Kalberg, Wendy O; Buckley, David; Blankenship, Jason

    2013-05-01

    Estimate the efficacy of Case Management (CM) for women at high risk for bearing a child with Fetal Alcohol Spectrum Disorders (FASD). Women were recruited from antenatal clinics and engaged in 18 months of CM. A South African community with a subculture of heavy, regular, weekend, recreational drinking and high documented rates of FASD. Forty-one women who were high risk for bearing a child with FASD. Statistical analysis of trends in drinking and other risk factors. At intake 87.8% were pregnant, most had previous alcohol-exposed pregnancies, most/all of their friends drink alcohol (67.5%), and 50.0% had stressful lives. CM was particularly valuable for pregnant women, as statistically significant reductions in alcohol risk were obtained for them in multiple variables: total drinks on weekends after six months of CM (p = .026) and estimated peak blood alcohol concentration (BAC) at six (p managers reduced maternal drinking at critical times, and therefore, alcohol exposure levels to the fetus.

  1. Youth risk behavior surveillance. National Alternative High School Youth Risk Behavior Survey, United States, 1998.

    Science.gov (United States)

    Grunbaum, J A; Kann, L; Kinchen, S A; Ross, J G; Gowda, V R; Collins, J L; Kolbe, L J

    2000-01-01

    Alternative high schools serve approximately 280,000 students nationwide who are at high risk for failing or dropping out of regular high school or who have been expelled from regular high school because of illegal activity or behavioral problems. Such settings provide important opportunities for delivering health promotion education and services to these youth and young adults. However, before this survey, the prevalence of health-risk behaviors among students attending alternative high schools nationwide was unknown. The Youth Risk Behavior Surveillance System (YRBSS) monitors the following six categories of priority health-risk behaviors among youth and young adults: behaviors that contribute to unintentional and intentional injuries; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs) (including human immunodeficiency virus [HIV] infection); unhealthy dietary behaviors; and physical inactivity. The national Alternative High School Youth Risk Behavior Survey (ALT-YRBS) is one component of the YRBSS; it was conducted in 1998 to measure priority health-risk behaviors among students at alternative high schools. The 1998 ALT-YRBS used a three-stage cluster sample design to produce a nationally representative sample of students in grades 9-12 in the United States who attend alternative high schools. The school response rate was 81.0%, and the student response rate was 81.9%, resulting in an overall response rate of 66.3%. This report summarizes results from the 1998 ALT-YRBS. The reporting period is February-May 1998. In the United States, 73.6% of all deaths among youth and young adults aged 10-24 years results from only four causes--motor vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1998 ALT-YRBS demonstrate that many students at alternative high schools engage in behaviors that increase their likelihood of death from these four causes

  2. Youth Risk Behavior Surveillance--National Alternative High School Youth Risk Behavior Survey, United States, 1998.

    Science.gov (United States)

    Grunbaum, J A; Kann, L; Kinchen, S A; Ross, J G; Gowda, V R; Collins, J L; Kolbe, L J

    1999-10-29

    Alternative high schools serve approximately 280,000 students nationwide who are at high risk for failing or dropping out of regular high school or who have been expelled from regular high school because of illegal activity or behavioral problems. Such settings provide important opportunities for delivering health promotion education and services to these youth and young adults. However, before this survey, the prevalence of health-risk behaviors among students attending alternative high schools nationwide was unknown. February-May 1998. The Youth Risk Behavior Surveillance System (YRBSS) monitors the following six categories of priority health-risk behaviors among youth and young adults: behaviors that contribute to unintentional and intentional injuries; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs) (including human immunodeficiency virus [HIV] infection); unhealthy dietary behaviors; and physical inactivity. The national Alternative High School Youth Risk Behavior Survey (ALT-YRBS) is one component of the YRBSS; it was conducted in 1998 to measure priority health-risk behaviors among students at alternative high schools. The 1998 ALT-YRBS used a three-stage cluster sample design to produce a nationally representative sample of students in grades 9-12 in the United States who attend alternative high schools. The school response rate was 81.0%, and the student response rate was 81.9%, resulting in an overall response rate of 66.3%. This report summarizes results from the 1998 ALT-YRBS. In the United States, 73.6% of all deaths among youth and young adults aged 10-24 years results from only four causes--motor vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1998 ALT-YRBS demonstrate that many students at alternative high schools engage in behaviors that increase their likelihood of death from these four causes. During the 30 days

  3. ASPHYXIA AND DEVELOPMENTAL OUTCOME IN HIGH RISK INFANTS

    Directory of Open Access Journals (Sweden)

    Valentina DUKOVSKA

    2010-04-01

    Full Text Available Asphyxia is a risk factor that is very often related to neuro-developmental issues in high risk infants and equally affects preterm and term infants, however its outcome on the developed brain differs from the outcome on the preterm brain.In preterm infants, asphyxia usually exerts a hemorrhagic or ischaemic event and periventricular leukomalacia.In term infants, asphyxia leads to cerebral edema and atrophy of the brain, which may later lead to hypoxic ischaemic encephalopathy (HIE.The number of term infants with HIE who have survived is lower than those of preterm infants, while the percentage of term infants with HIE who have neuro-developmental issues is higher. Preemies face more problems in their motor development as a result of the brain damage, while term infants suffer from encephalopathy and their cognitive abilities are more affected.We have conducted a study about the effects that asphyxia has on the developmental outcomes in high risk infants. In our study, we did a longitudinal developmental follow-up of 30 high risk infants and an evaluation of their developmental outcome using the Griffiths Mental Development Scales, from the 4th month of life until the end of the 36th month. First, we found that high risk infants had a much lower developmental outcome than the control group during the trial. Finally, we found that asphyxia makes a difference in the developmental outcome of preterm infants without asphyxia who have a very low birth weight, the preterm infants with asphyxia, and the term infants with HIE-II.

  4. Validation of the High-Risk Pregnancy Stress Scale in a sample of hospitalized Greek high-risk pregnant women.

    Science.gov (United States)

    Gourounti, Kleanthi; Karpathiotaki, Natassa; Karapanou, Vassiliki; Antzaklis, Panos; Daskalakis, Georgios

    2016-01-01

    The aim of the authors in this study was to determine the psychometric properties of the Greek adaptation of the High-Risk Pregnancy Stress Scale (HRPSS) in a sample of high-risk hospitalized pregnant women. The sample consisted of 133 high-risk pregnant women with gestational age from 9 to 37 weeks. Data were collected between February and June of 2014. HRPSS was "forward-backward" translated from English to Greek. Principal axis factoring with promax rotation was used to test the factor structure of the HRPSS. Measures of state anxiety (STAI) and depressive symptoms (EPDS) were used to assess the convergent validity of the HRPSS. Exploratory factor analysis suggested three factors: concerns of pregnancy, movement restriction, and isolation and restriction of external activities. Construct validity was confirmed by computing correlations between the HRPSS and constructions of anxiety and depressive symptoms. Internal consistency reliability was satisfactory (α = 0.813). The original factor structure of the HRPSS was only partly replicated. The results of the exploratory factor analysis suggested that a three-factor solution instead of a two-factor solution would be the most adequate. The HRPSS is an appropriate measure for assessing the levels of concerns regarding pregnancy outcome, movement restriction, isolation, and external activity restrictions in Greek high-risk pregnant women.

  5. The association of bladder myeloid sarcoma and unclassified myelodysplastic/myeloproliferative disease

    Directory of Open Access Journals (Sweden)

    Mehmet Sönmez

    2009-06-01

    Full Text Available Myeloid sarcoma of the urinary bladder is a rare disorder. We report a 71-year-old man with hematuria who had a diffuse myeloid sarcoma of the bladder. He was also under follow-up for unclassified myeloproliferative/myelodysplastic disorder, diagnosed two months before. Abdominal ultrasonography and computed tomography findings were normal. Diagnostic cystoscopy revealed patchy areas of mucosal swelling with hyperemia. Histopathological examination of biopsies demonstrated a neoplasm composed of blasts showing myeloperoxidase positivity by immunohistochemistry. To our knowledge, the current case is the first case of myeloid sarcoma in the urinary bladder without evidence of a mass lesion, with a concurrent diagnosis of unclassifiable myelodysplastic/myeloproliferative disease.

  6. Deferasirox-induced urticarial vasculitis in a patient with myelodysplastic syndrome.

    Science.gov (United States)

    Polat, Asude Kara; Belli, Asli Akin; Karakus, Volkan; Dere, Yelda

    2017-01-01

    Deferasirox is an iron chelator agent used in the treatment of diseases with iron overload, such as thalassemia and myelodysplastic syndrome. Although the majority of adverse reactions of deferasirox involve gastrointestinal symptoms and increase in serum creatinine and transaminases, skin rashes, such as maculopapular and urticarial eruptions, have also been reported. This study reports a case of myelodysplastic syndrome with urticarial vasculitis due to deferasirox therapy. Drug eruption was been confirmed by means of a challenge test, together with histopathological and clinical findings. To the best of our knowledge, we report the first case of deferasirox-induced urticarial vasculitis. Physicians should be aware of the possibility of urticarial vasculitis on deferasirox therapy and the fact that the discontinuation of the drug generally results in improvement.

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

    Science.gov (United States)

    Nazha, Aziz; Sekeres, Mikkael A

    2017-01-14

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

  8. Antenatal Care Utilisation and Content between Low-Risk and High-Risk Pregnant Women

    Science.gov (United States)

    Yeoh, Ping Ling; Hornetz, Klaus; Dahlui, Maznah

    2016-01-01

    Background The purpose of antenatal care is to monitor and improve the wellbeing of the mother and foetus. The World Health Organization recommends risk-oriented strategy that includes: (i) routine care to all women, (ii) additional care for women with moderately severe diseases and complications, (iii) specialised obstetrical and neonatal care for women with severe diseases and complications. Antenatal care is concerned with adequate care in order to be effective. Measurement for adequacy of antenatal care often applies indexes that assess initiation of care and number of visits. In addition, adequacy of care content should also be assessed. Results of studies in developed settings demonstrate that women without risk factors use antenatal services more frequently than recommended. Such over-utilisation is problematic for low-resourced settings. Moreover, studies show that a substantial proportion of high-risk women had utilisation or content of care below the recommended standard. Yet studies in developing countries have seldom included a comparison between low-risk and high-risk women. The purpose of the study was therefore to assess adequacy of care and pregnancy outcomes for the different risk groups. Methods A retrospective study using a multistage sampling technique, at public-funded primary health care clinics was conducted. Antenatal utilisation level was assessed using a modified Adequacy of Prenatal Care Utilisation index that measures the timing for initiation of care and observed-to-expected visits ratio. Adequacy of antenatal care content assessed compliance to routine care based on the local guidelines. Results Intensive or “adequate-plus” antenatal care utilisation as defined by the modified index was noted in over half of the low-risk women. On the other hand, there were 26% of the high-risk women without the expected intensive utilisation. Primary- or non-educated high-risk women were less likely to have a higher antenatal care utilisation

  9. Who takes risks in high-risk sport?: the role of alexithymia.

    Science.gov (United States)

    Barlow, Matthew; Woodman, Tim; Chapman, Caradog; Milton, Matthew; Stone, Daniel; Dodds, Tom; Allen, Ben

    2015-02-01

    People who have difficulty identifying and describing their emotions are more likely to seek out the experience of emotions in the high-risk domain. This is because the high-risk domain provides the experience of more easily identifiable emotions (e.g., fear). However, the continued search for intense emotion may lead such individuals to take further risks within this domain, which, in turn, would lead to a greater likelihood of experiencing accidents. Across three studies, we provide the first evidence in support of this view. In Study 1 (n = 762), alexithymia was associated with greater risk taking and a greater propensity to experience accidents and close calls. In Study 2 (n = 332) and Study 3 (n = 356), additional bootstrapped mediation models confirmed these relationships. The predictive role of alexithymia remained significant when controlling for sensation seeking (Study 1) and anhedonia (Study 2 and Study 3). We discuss the practical implications of the present model as they pertain to minimizing accidents and close calls in the high-risk domain.

  10. Aloimmunity against HLA class I antigens in patients with myelodysplastic syndrome and aplastic anemia

    OpenAIRE

    Daisy Maria Meireles Arruda

    2005-01-01

    Myelodysplastic syndrome (MDS) and aplastic anemia (AA) are two of the hematological disorders which present peripheral cytopenias, with extensive clinical manifestations that vary from slight anemia to severe pancytopenia; the latter requiring continuous transfusional reposition of red cell (RC) and platelet concentrates (PC), which can induce aloimunization in patients. Such patients can develop a post-transfusional refractory state, rendering further transfusions unviable. The objective of...

  11. An Analysis of microRNA Expression in the Myelodysplastic Syndromes Using Hematopoietic Stem Cells

    Science.gov (United States)

    2015-10-01

    disease  associated  cytogenetic  and  molecular   genetic ...the age-related predisposition for the development of MDS. 15. SUBJECT TERMS MicroRNAs, the myelodysplastic syndromes, hematopoietic stem cells...hematopoiesis   in   the   context   of   aging   and   its   likely   implication   in   the   age-­‐related   predisposition

  12. Etiological factors of myelo-dysplastic syndromes; Facteurs etiologiques des syndromes myelodysplasiques

    Energy Technology Data Exchange (ETDEWEB)

    Nisse, C. [Centre Hospitalier Universitaire, 59 - Lille (France)

    1997-09-01

    Specific epidemiologic data on myelo-dysplastic syndromes are rare. Analysis of data is in fact affected by problems of terminology and classification. The link between the exposure to ionizing radiation or alkylating agents and MDS is well established. Etiologic factors of acute leukemia, or new factors such as non ionizing radiation, solvent, ethylene oxide, glycol ethers, tobacco smoke, exhaust gases, agricultural work have been hypothesized but should be confirmed by other studies on MDS. (author)

  13. 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...SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT

  14. Chronic kidney disease and bleeding risk in patients at high cardiovascular risk: a cohort study.

    Science.gov (United States)

    Ocak, G; Rookmaaker, M B; Algra, A; de Borst, G J; Doevendans, P A; Kappelle, L J; Verhaar, M C; Visseren, F L

    2018-01-01

    Essentials The association between chronic kidney disease and bleeding is unknown. We followed 10 347 subjects at high cardiovascular risk for bleeding events. Chronic kidney disease was associated with a 1.5-fold increased bleeding risk. Especially albuminuria rather than decreased kidney function was associated with bleeding events. Background There are indications that patients with chronic kidney disease have an increased bleeding risk. Objectives To investigate the association between chronic kidney disease and bleeding in patients at high cardiovascular risk. Methods We included 10 347 subjects referred to the University Medical Center Utrecht (the Netherlands) from September 1996 to February 2015 for an outpatient visit with classic risk factors for arterial disease or with symptomatic arterial disease (Second Manifestation of Arterial disease [SMART] cohort). Patients were staged according to the KDIGO guidelines, on the basis of estimated glomerular filtration rate (eGFR) and albuminuria, and were followed for the occurrence of major hemorrhagic events until March 2015. Hazard ratios (HRs) with 95% confidence intervals (CIs) for bleeding were calculated with Cox proportional hazards analyses. Results The incidence rate for bleeding in subjects with chronic kidney disease was 8.0 per 1000 person-years and that for subjects without chronic kidney disease was 3.5 per 1000 person-years. Patients with chronic kidney disease (n = 2443) had a 1.5-fold (95% CI 1.2-1.9) increased risk of bleeding as compared with subjects without chronic kidney disease (n = 7904) after adjustment. Subjects with an eGFR of Chronic kidney disease is a risk factor for bleeding in patients with classic risk factors for arterial disease or with symptomatic arterial disease, especially in the presence of albuminuria. © 2017 University Medical Center Utrecht. Journal of Thrombosis and Haemostasis © 2017 International Society on Thrombosis and Haemostasis.

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

    DEFF Research Database (Denmark)

    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......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...... after Aza+Epo, giving a total response rate of 20%. Mutational screening revealed a high frequency of recurrent mutations. Although no single mutation predicted for response, SF3A1 (n=3) and DNMT3A (n=4) were only observed in non-responders. We conclude that Aza can induce TI in severely anemic MDS...... 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....

  16. Gang masculinity and high-risk sexual behaviours.

    Science.gov (United States)

    Dickson-Gomez, Julia; Quinn, Katherine; Broaddus, Michelle; Pacella, Maria

    2017-02-01

    High-risk sexual behaviours include practices such as relationship violence and substance use, which often cluster together among young people in high-risk settings. Youth gang members often show high rates of such behaviours, substance use and relationship violence. This paper draws on data from in-depth interviews with male and female gang members from six different gangs to explore the role of powerful socialising peer groups that set gender, sexual and relationship roles and expectations for their male and female members. High-risk sexual behaviours among gang members included sex with multiple partners and group sex. Gang norms included the belief that male members were sexually insatiable with multiple sexual partners and that female gang members should be sexually available to male members. Alcohol and drugs were seen to have a large influence on sexual desire and the inability to use condoms. Much sexual behaviour with gangs, such as group sex, was viewed with ambivalence and seen as somewhat coercive. Finally, gendered sexual expectations (boys as sexually insatiable and girls as sexually available) made forming long-term romantic relationships problematic for gang members. The influence of gang norms such as these must be addressed in future programmes and interventions with gang members.

  17. Environmental risk factors associated with bovine tuberculosis among cattle in high-risk areas.

    Science.gov (United States)

    Winkler, B; Mathews, F

    2015-11-01

    Our research shows that environmental features are important predictors of bovine tuberculosis (bTB) in British cattle herds in high-prevalence regions. Data from 503 case and 808 control farms included in the randomized badger culling trial (RBCT) were analysed. bTB risk increased in larger herds and on farms with greater areas of maize, deciduous woodland and marsh, whereas a higher percentage of boundaries composed of hedgerows decreased the risk. The model was tested on another case-control study outside RBCT areas, and here it had a much smaller predictive power. This suggests that different infection dynamics operate outside high-risk areas, although it is possible that unknown confounding factors may also have played a role. © 2015 The Author(s).

  18. Venous Thromboembolism Risk and Adequacy of Prophylaxis in High Risk Pregnancy in the Arabian Gulf.

    Science.gov (United States)

    Alsayegh, Faisal; Al-Jassar, Waleed; Wani, Salima; Tahlak, Muna; Albahar, Awatef; Al Kharusi, Lamya; Al-Tamimi, Halima; El-Taher, Faten; Mahmood, Naeema; Al-Zakwani, Ibrahim

    2016-01-01

    To estimate the prevalence of venous thromboembolism (VTE) risk factors in pregnancy and the proportion of pregnancies at risk of VTE that received the recommended prophylaxis according to the American College of Chest Physicians (ACCP) 2012 published guidelines in antenatal clinics in the Arabian Gulf. The evaluation of venous thromboembolism (EVE)-Risk project was a non-interventional, cross-sectional, multi-centre, multi-national study of all eligible pregnant women (≥17 years) screened during antenatal clinics from 7 centres in the Arabian Gulf countries (United Arab Emirates, Kuwait, Bahrain, Qatar and Oman). Pregnant women were recruited during a 3-month period between September and December 2012. Of 4,131 screened pregnant women, 32% (n=1,337) had ≥1 risk factors for VTE. Common VTE risk factors included obesity (76%), multiparity (33%), recurrent miscarriages (9.1%), varicose veins (6.9%), thrombophilia (2.6%), immobilization (2.0%), sickle cell disease (2.8%) and previous VTE (1.6%). Only 8.3% (n=111) of the high risk patients were on the recommended VTE prophylaxis. Enoxaparin was used in 80% (n=89) of the cases followed by tinzaparin (4%; n=4). Antiplatelet agents were prescribed in 11% (n=149) of pregnant women. Of those on anticoagulants (n=111), 59% (n=66) were also co-prescribed antiplatelet agents. Side effects (mainly local bruising at the injection site) were reported in 12% (n=13) of the cases. A large proportion of pregnant women in the Arabian Gulf countries have ≥1 VTE risk factor with even a smaller fraction on prophylaxis. VTE risk assessment must be adopted to identify those at risk who would need VTE prophylaxis.

  19. Reduced-Intensity Allogeneic Transplant for Acute Myeloid Leukemia and Myelodysplastic Syndrome Using Combined CD34-Selected Haploidentical Graft and a Single Umbilical Cord Unit Compared with Matched Unrelated Donor Stem Cells in Older Adults.

    Science.gov (United States)

    Tsai, Stephanie B; Rhodes, Joanna; Liu, Hongtao; Shore, Tsiporah; Bishop, Michael; Cushing, Melissa M; Gergis, Usama; Godley, Lucy; Kline, Justin; Larson, Richard A; Mayer, Sebastian; Odenike, Olatoyosi; Stock, Wendy; Wickrema, Amittha; van Besien, Koen; Artz, Andrew S

    2017-12-27

    Haplo/cord transplantation combines an umbilical cord blood (UCB) graft with CD34-selected haploidentical cells and results in rapid hematopoietic recovery followed by durable UCB engraftment. We compared outcomes of transplants in older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) who received either HLA-matched unrelated donor (MUD) cells or haplo/cord grafts. Between 2007 and 2013, 109 adults ages 50 and older underwent similar reduced-intensity conditioning with fludarabine and melphalan and antibody-mediated T cell depletion for AML (n = 83) or high-risk MDS (n = 26) followed by either a MUD (n = 68) or haplo/cord (n = 41) graft. Patient characteristics were similar for each graft source except for some patients receiving a haplo/cord transplant (P = .01). One half of the AML patients were not in remission. Two-year progression-free survival (PFS), overall survival (OS), and graft-versus-host disease-free relapse-free survival were 38%, 48%, and 32.1% for MUD and 33%, 48%, and 33.8% for haplo/cord transplants (P = .62 for PFS; P = .97 for OS; P= .84), respectively. Acute grades II to IV and chronic graft-versus-host-disease rates did not differ at 19.5% and 4.9% in haplo/cord compared with 25% and 7.4% after MUD (P = .53 and P = .62, respectively). Multivariate analysis confirmed no significant differences in transplant outcomes by donor type. Haplo/cord reduced-intensity transplantation achieves similar outcomes relative to MUD in older AML and MDS patients, making this a promising option for those without matched donors. Copyright © 2018. Published by Elsevier Inc.

  20. Clinical, hematological, and cytogenetic profile of adult myelodysplastic syndrome in a tertiary care center

    Directory of Open Access Journals (Sweden)

    Narayanan S

    2017-02-01

    Full Text Available Santhosh Narayanan Department of Medicine, Government Medical College, Kozhikode, Kerala, India Background: Myelodysplastic syndrome (MDS, a disorder of clonal hematopoiesis, is an important clinical entity, but most of the studies available are conducted among the Western population. Its etiological factors and clinicohematological profile in the Indian population are quite diverse. The information regarding its prognostic factors and cytogenetics is very scarce.Objectives: (1 To assess the clinicohematological profile, cytogenetics, prognostic factors, and outcome of MDS and (2 to study its progression to acute myeloid leukemia (AML in the selected patients over the study period.Methods: A prospective observational study was performed with patients from Department of Medicine and Hematology, Government Medical College, Kozhikode, who were diagnosed with MDS within the study period (from 1 January 2014 to 31 July 2015. Secondary causes of dysplasia were excluded. In possible cases, the international prognostic scoring system was followed. These patients were followed up for an additional 6 months to assess the progression of MDS to AML based on symptoms, signs, hemogram, or repeat peripheral smear/bone marrow studies.Results: Of the 60 patients, 73% were aged >60 years. Disease was common in males, with a male:female ratio of 7:3. Thirty-five percent of the patients were working in agricultural and allied fields and had pesticide exposure. Patients with prior radiation exposure had significant association with adverse outcome. Fatigue was the prominent symptom and was reported by 90% of the patients. Blasts were >5% in peripheral smear; bone marrow cytopenia and dysplasia at the time of diagnosis had significant association with risk of transforming to AML. Refractory anemia (RA, observed in 22 patients, was the most common type of MDS. Most of the patients with RA with excess blasts type-1 and RA with excess blasts type-2 transformed to AML

  1. Association of Therapy for Autoimmune Disease With Myelodysplastic Syndromes and Acute Myeloid Leukemia.

    Science.gov (United States)

    Ertz-Archambault, Natalie; Kosiorek, Heidi; Taylor, Gretchen E; Kelemen, Katalin; Dueck, Amylou; Castro, Janna; Marino, Robert; Gauthier, Susanne; Finn, Laura; Sproat, Lisa Z; Palmer, Jeanne; Mesa, Ruben A; Al-Kali, Aref; Foran, James; Tibes, Raoul

    2017-07-01

    Therapy-related myeloid neoplasms are a potentially life-threatening consequence of treatment for autoimmune disease (AID) and an emerging clinical phenomenon. To query the association of cytotoxic, anti-inflammatory, and immunomodulating agents to treat patients with AID with the risk for developing myeloid neoplasm. This retrospective case-control study and medical record review included 40 011 patients with an International Classification of Diseases, Ninth Revision, coded diagnosis of primary AID who were seen at 2 centers from January 1, 2004, to December 31, 2014; of these, 311 patients had a concomitant coded diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Eighty-six cases met strict inclusion criteria. A case-control match was performed at a 2:1 ratio. Odds ratio (OR) assessment for AID-directed therapies. Among the 86 patients who met inclusion criteria (49 men [57%]; 37 women [43%]; mean [SD] age, 72.3 [15.6] years), 55 (64.0%) had MDS, 21 (24.4%) had de novo AML, and 10 (11.6%) had AML and a history of MDS. Rheumatoid arthritis (23 [26.7%]), psoriasis (18 [20.9%]), and systemic lupus erythematosus (12 [14.0%]) were the most common autoimmune profiles. Median time from onset of AID to diagnosis of myeloid neoplasm was 8 (interquartile range, 4-15) years. A total of 57 of 86 cases (66.3%) received a cytotoxic or an immunomodulating agent. In the comparison group of 172 controls (98 men [57.0%]; 74 women [43.0%]; mean [SD] age, 72.7 [13.8] years), 105 (61.0%) received either agent (P = .50). Azathioprine sodium use was observed more frequently in cases (odds ratio [OR], 7.05; 95% CI, 2.35- 21.13; P myeloid neoplasm. The control and case cohorts had similar systemic exposures by agent category. No association was found for anti-tumor necrosis factor agents. Finally, no timeline was found for the association of drug exposure with the incidence in development of myeloid neoplasm.

  2. 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

  3. Alterações moleculares em síndrome mielodisplásica Molecular abnormalities in myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes L. F. Chauffaille

    2006-09-01

    hypothesis of tumor suppressor genes (TSG, but this theory does not explain the initial event that underlies growth advantage of hematopoietic progenitor cells, though, different mechanisms are involved such as oncogene activation, altered signaling components and transcription factors. Oncogene mutations, such as RAS, P53, PDGF, FLT3 and MLL, for instance, may contribute to the development of MDS. Tandem mutation of FLT3 is a genetic event that occurs late in the course of the disease and these patients tend to present unfavorable prognosis and imminent transformation into acute myeloid leukemia. Quantitative as well as qualitative abnormalities of transcription factors are detected in MDS and induce the unbalance or block in the differentiation of hematopoietic cells, that results in ineffective hematopoiesis. Epigenentic alterations are characterized by DNA methylation that exerts a role in controlling genic expression. Hypermethylation and inactivation of regulating genes act in the development of the disease. There is a high risk of MDS when p15INK4B is inactivated due to hypermethylation of its promoter. Telomere shortening correlates with complex karyotypes indicating genomic instability and poor prognosis.

  4. Multislice computed tomography in an asymptomatic high-risk population.

    Science.gov (United States)

    Romeo, Francesco; Leo, Roberto; Clementi, Fabrizio; Razzini, Cinzia; Borzi, Mauro; Martuscelli, Eugenio; Pizzuto, Francesco; Chiricolo, Gaetano; Mehta, Jawahar L

    2007-02-01

    Approximately 50% of all acute coronary syndromes occur in previously asymptomatic patients. This study evaluated the value of multislice computed tomography for early detection of significant coronary artery disease (CAD) in high-risk asymptomatic subjects. One hundred sixty-eight asymptomatic subjects with >or=1 major risk factor (hypertension, diabetes, hypercholesterolemia, family history, or smoking) and an inconclusive or unfeasible noninvasive stress test result (stress electrocardiography, echocardiography, or nuclear scintigraphy) were evaluated in an outpatient setting. After clinical examination and laboratory risk analysis, all patients underwent multislice computed tomographic (MSCT) coronary angiography within 1 week. In all subjects, conventional coronary angiography was also carried out. Multislice computed tomography displayed single-vessel CAD in 16% of patients, 2-vessel CAD in 7%, and 3-vessel CAD in 4%. Selective coronary angiography confirmed the results of multislice computed tomography in 99% of all patients. Sensitivity and specificity of MSCT coronary angiography were 100% and 98%, respectively, with a positive predictive value of 95% and a negative predictive value of 100%. In conclusion, MSCT coronary angiography is an excellent noninvasive technique for early identification of significant CAD in high-risk asymptomatic patients with inconclusive or unfeasible noninvasive stress test results.

  5. Atopic dermatitis in a high-risk cohort: natural history, associated allergic outcomes, and risk factors.

    Science.gov (United States)

    Carlsten, Chris; Dimich-Ward, Helen; Ferguson, Alexander; Watson, Wade; Rousseau, Roxanne; Dybuncio, Anne; Becker, Allan; Chan-Yeung, Moira

    2013-01-01

    Atopic dermatitis (AD) is commonly associated with asthma and other atopic disorders in childhood. To evaluate the natural history of AD and its association with other allergic outcomes in a high-risk cohort through the age of 7 years. A total of 373 high-risk infants, who had undergone a randomized controlled trial with intervention measures for primary prevention of asthma applied during the first year of life, were assessed for asthma, AD, and allergic sensitization at 1, 2, and 7 years. The multifaceted intervention program did not reduce AD despite reducing the prevalence of asthma significantly. Sixty-two children (16.6%) had AD during the first 2 years (early-onset AD); of these, 26 continue to have AD at the age of 7 years (persistent), whereas 36 no longer had the disease (nonpersistent) at the age of 7 years. Twenty-three children (6.2%) developed AD only after the age of 2 years (late-onset AD). Early-onset AD, persistent or nonpersistent, was associated with increased risk of allergic sensitization to food allergens within the first 2 years of life and asthma diagnosis at year 7. However, only persistent AD was associated with an increased risk of other atopic diseases and allergic sensitization to food and aeroallergens at year 7. Late-onset AD was not associated with atopic diseases or allergic sensitization at year 7 with the exception of Alternaria alternans. In this cohort of infants at high risk of asthma, early-onset persistent AD, which was highly associated with atopic sensitization, increased the risk of atopic diseases in later childhood and thus appears to be part of the atopic march. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Plaque At RISK (PARISK): prospective multicenter study to improve diagnosis of high-risk carotid plaques

    NARCIS (Netherlands)

    Truijman, M.T.; Kooi, M.E.; Dijk, A.; de Rotte, A.A.J.; van der Kolk, A.G.; Liem, M.; Schreuder, F.H.; Boersma, M.; Mess, W.H.; van Oostenbrugge, R.J.; Koudstaal, P.J.; Kappelle, L.J.; Nederkoorn, P.J.; Nederveen, A.J.; Hendrikse, J.; van der Steen, A.F.; Daemen, M.J.; van der Lugt, A.

    2014-01-01

    BACKGROUND: Patients with symptomatic carotid artery stenosis are at high risk for recurrent stroke. To date, the decision to perform carotid endarterectomy in patients with a recent cerebrovascular event is mainly based on degree of stenosis of the ipsilateral carotid artery. However, additional

  7. Risk factors for congenital anomalies in high risk pregnant women: A large study from South India

    Directory of Open Access Journals (Sweden)

    Tella Sunitha

    2017-01-01

    Conclusion: High prevalence of CAs was found in HRP women compared to general population. Low parental age contributed toward CAs in primi gravida women while consanguinity was found to be a predisposing factor for CAs in HRP with previous BOH. Toxoplasmosis conferred risk for CAs in HRP women with previous normal pregnancies.

  8. The small population of PIG-A mutant cells in myelodysplastic syndromes do not arise from multipotent hematopoietic stem cells.

    Science.gov (United States)

    Pu, Jeffrey J; Hu, Rong; Mukhina, Galina L; Carraway, Hetty E; McDevitt, Michael A; Brodsky, Robert A

    2012-08-01

    Patients with paroxysmal nocturnal hemoglobinuria harbor clonal glycosylphosphatidylinositol-anchor deficient cells arising from a multipotent hematopoietic stem cell acquiring a PIG-A mutation. Many patients with aplastic anemia and myelodysplastic syndromes also harbor small populations of glycosylphosphatidylinositol-anchor deficient cells. Patients with aplastic anemia often evolve into paroxysmal nocturnal hemoglobinuria; however, myelodysplastic syndromes seldom evolve into paroxysmal nocturnal hemoglobinuria. Here, we investigate the origin and clonality of small glycosylphosphatidylinositol-anchor deficient cell populations in aplastic anemia and myelodysplastic syndromes. We used peripheral blood flow cytometry to identify glycosylphosphatidylinositol-anchor deficient blood cells, a proaerolysin-resistant colony forming cell assay to select glycosylphosphatidylinositol-anchor deficient progenitor cells, a novel T-lymphocyte enrichment culture assay with proaerolysin selection to expand glycosylphosphatidylinositol-anchor deficient T lymphocytes, and PIG-A gene sequencing assays to identify and analyze PIG-A mutations in patients with aplastic anemia and myelodysplastic syndromes. Twelve of 15 aplastic anemia patients were found to harbor a small population of glycosylphosphatidylinositol-anchor deficient granulocytes; 11 of them were found to harbor a small population of glycosylphosphatidylinositol-anchor deficient erythrocytes, 10 patients were detected to harbor glycosylphosphatidylinositol-anchor deficient T lymphocytes, and 3 of them were detected only after T-lymphocyte enrichment in proaerolysin selection. PIG-A mutation analyses on 3 patients showed that all of them harbored a matching PIG-A mutation between CFU-GM and enriched T lymphocytes. Two of 26 myelodysplastic syndromes were found to harbor small populations of glycosylphosphatidylinositol-anchor deficient granulocytes and erythrocytes transiently. Bone marrow derived CD34(+) cells from 4

  9. Complex, not monosomal, karyotype is the cytogenetic marker of poorest prognosis in patients with primary myelodysplastic syndrome.

    Science.gov (United States)

    Valcárcel, David; Ademà, Vera; Solé, Francesc; Ortega, Margarita; Nomdedeu, Benet; Sanz, Guillermo; Luño, Elisa; Cañizo, Consuelo; de la Serna, Javier; Ardanaz, Maite; Marco, Victor; Collado, Rosa; Grau, Javier; Montoro, Julia; Mallo, Mar; Vallespí, Teresa

    2013-03-01

    Complex karyotype (CK) is the poorest risk factor in patients with myelodysplastic syndrome (MDS). It has recently been reported that monosomal karyotype (MK) worsens the prognosis of patients with CK. PATIENTS AND METHODS; We analyzed 1,054 adult patients with MDS with an abnormal karyotype from the Spanish Registry of MDS. The aim of the study was to describe the incidence, characteristics, and prognosis of MK; the main end points were overall survival (OS) and leukemia-free survival. MK was identified in 172 patients (16%), most of whom (88%) presented with CK. Variables significantly associated with OS were age (hazard ratio [HR], 1.90; P karyotype complexity (CK [three abnormalities]: HR, 1.81; P = .003; very CK [> three abnormalities]: HR, 2; P abnormalities of chromosome 5 and/or 7 (HR, 1.89; P karyotype complexity (CK: HR, 2.53; P = .002; very CK: HR, 2.77; P karyotype complexity, MK was not associated with OS or evolution to AML. In conclusion, these results demonstrate that the prognostic value of MK in MDS is not independent and is mainly the result of its strong association with number of chromosomal abnormalities.

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

    Science.gov (United States)

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

    2010-04-23

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

  11. Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes.

    Science.gov (United States)

    Damm, Frederik; Kosmider, Olivier; Gelsi-Boyer, Véronique; Renneville, Aline; Carbuccia, Nadine; Hidalgo-Curtis, Claire; Della Valle, Véronique; Couronné, Lucile; Scourzic, Laurianne; Chesnais, Virginie; Guerci-Bresler, Agnes; Slama, Bohrane; Beyne-Rauzy, Odile; Schmidt-Tanguy, Aline; Stamatoullas-Bastard, Aspasia; Dreyfus, François; Prébet, Thomas; de Botton, Stéphane; Vey, Norbert; Morgan, Michael A; Cross, Nicholas C P; Preudhomme, Claude; Birnbaum, Daniel; Bernard, Olivier A; Fontenay, Michaela

    2012-04-05

    A cohort of MDS patients was examined for mutations affecting 4 splice genes (SF3B1, SRSF2, ZRSR2, and U2AF35) and evaluated in the context of clinical and molecular markers. Splice gene mutations were detected in 95 of 221 patients. These mutations were mutually exclusive and less likely to occur in patients with complex cytogenetics or TP53 mutations. SF3B1(mut) patients presented with lower hemoglobin levels, increased WBC and platelet counts, and were more likely to have DNMT3A mutations. SRSF2(mut) patients clustered in RAEB-1 and RAEB-2 subtypes and exhibited pronounced thrombocytopenias. ZRSR2(mut) patients clustered in International Prognostic Scoring System intermediate-1 and intermediate-2 risk groups, had higher percentages of bone marrow blasts, and more often displayed isolated neutropenias. SRSF2 and ZRSR2 mutations were more common in TET2(mut) patients. U2AF35(mut) patients had an increased prevalence of chromosome 20 deletions and ASXL1 mutations. Multivariate analysis revealed an inferior overall survival and a higher AML transformation rate for the genotype ZRSR2(mut)/TET2(wt) (overall survival: hazard ratio = 3.3; 95% CI, 1.4-7.7; P = .006; AML transformation: hazard ratio = 3.6; 95% CI, 2-4.2; P = .026). Our results demonstrate that splice gene mutations are among the most frequent molecular aberrations in myelodysplastic syndrome, define distinct clinical phenotypes, and show preferential associations with mutations targeting transcriptional regulation.

  12. DNMT3A R882 mutations in patients with cytogenetically normal acute myeloid leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    El Ghannam, Doaa; Taalab, Mona M; Ghazy, Hayam F; Eneen, Asmaa F

    2014-01-01

    Several molecular markers have been described that help to classify patients with acute myeloid leukemia (AML), a heterogeneous hematopoietic tissue neoplasm, into risk groups. We determined the frequency of DNMT3A mutations, their associations with clinical and molecular characteristics and outcome, in primary, cytogenetically-normal AML (CN-AML) and CN-myelodysplastic syndrome (MDS). A total of 63 CN-AML and 16 CN-MDS patients were analyzed for mutations in DNMT3A, codon R822 by direct sequencing and mutation of NPM1 and FLT3/ITD. DNMT3A mutations were found in 17/63 (27%) of CN-AML and in 1/16 (6.3%) of CN-MDS patients. Patients with DNMT3A mutations were older (p=0.047), had higher white blood cell (WBC) counts (p=0.046), more often belonged to FAB groups M4 and M5 (p=0.017), and were more associated with NPM1 mutations (p=0.017), than those with wild-type DNMT3A. DNMT3A-mutated patients had shorter overall disease survival (pclassification of CN-AML. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  13. CD34/QBEND10 immunostaining in bone marrow biopsies: an additional parameter for the diagnosis and classification of myelodysplastic syndromes.

    Science.gov (United States)

    Baur, A S; Meugé-Moraw, C; Schmidt, P M; Parlier, V; Jotterand, M; Delacrétaz, F

    2000-02-01

    CD34/QBEND10 immunostaining has been assessed in 150 bone marrow biopsies (BMB) including 91 myelodysplastic syndromes (MDS), 16 MDS-related AML, 25 reactive BMB, and 18 cases where RA could neither be established nor ruled out. All cases were reviewed and classified according to the clinical and morphological FAB criteria. The percentage of CD34-positive (CD34 +) hematopoietic cells and the number of clusters of CD34+ cells in 10 HPF were determined. In most cases the CD34+ cell count was similar to the blast percentage determined morphologically. In RA, however, not only typical blasts but also less immature hemopoietic cells lying morphologically between blasts and promyelocytes were stained with CD34. The CD34+ cell count and cluster values were significantly higher in RA than in BMB with reactive changes (p<0.0001 for both), in RAEB than in RA (p=0.0006 and p=0.0189, respectively), in RAEBt than in RAEB (p=0.0001 and p=0.0038), and in MDS-AML than in RAEBt (p<0.0001 and p=0.0007). Presence of CD34+ cell clusters in RA correlated with increased risk of progression of the disease. We conclude that CD34 immunostaining in BMB is a useful tool for distinguishing RA from other anemias, assessing blast percentage in MDS cases, classifying them according to FAB, and following their evolution.

  14. Immunophenotype of myeloid granulocytes: a pilot study for distinguishing myelodysplastic syndrome and aplastic anemia by flow cytometry.

    Science.gov (United States)

    Huang, M; Li, J; Zhao, G; Sui, X; Zhao, X; Xu, H

    2010-06-01

    It is often difficult to distinguish myelodysplastic syndrome (MDS) from aplastic anemia (AA) because of the considerable clinical, cytologic histologic similarities between these two disorders; however, distinguishing between AA and MDS is of great importance because there is a higher risk of progression to acute leukemia in patients with MDS compared with AA. Up to now, CD34(+) cells in MDS and AA patients have been studied extensively; however, little information is available on myeloid granulocytes. The aim of this study was to determine whether immunophenotype of myeloid granulocytes in AA patients was different from that of MDS. Flow cytometry was used to assess the immunophenotype of myeloid granulocytes in 22 patients with MDS, 12 with AA, and 10 normal subjects. Our data showed that the percentages of CD13(+) granulocytes, CD33(+) granulocytes, CD34(+) granulocytes, and HLA-DR(+) granulocytes were significantly higher in patients with MDS than in AA patients and normal subjects (P granulocytes and CD10(+) granulocytes were significantly lower in patients with MDS than in AA patients and normal subjects (P 0.05). As refractory anemia progressing to refractory anemia with excess blasts, the percentages of CD13(+) granulocytes, CD33(+) granulocytes, CD34(+) granulocytes and HLA-DR(+) granulocytes were significantly increased, whereas, the percentage of CD15(+) granulocytes was significantly decreased (P granulocytes may be a useful parameter for the differential diagnosis of MDS and AA.

  15. Papillary thyroid microcarcinoma: the significance of high risk features.

    Science.gov (United States)

    Bradley, Nori L; Wiseman, Sam M

    2017-02-16

    Papillary carcinomas that measure 1.0cm or less are diagnosed as papillary thyroid microcarcinomas (PTMs). The clinical significance and recommendations for management of these PTMs is still evolving. The objective of the study was to compare the characteristics of small (PTM. We performed a retrospective analysis of these cases using Fisher's Exact Test. The statistical significance was set at p PTM and high risk features was observed only for extra-thyroidal cancer extension (ETE). Six of 57 large PTM (11%) but none of the 75 small PTM had ETE (p PTM (5/9 cases) and large PTM (4/9 cases). A distant metastases was diagnosed in association with a small PTM. For PTM, neither small cancer size, nor the absence of high-risk features, excluded the possibility of synchronous lymph node metastases.

  16. The Violence Risk Scale: Predictive Validity and Linking Changes in Risk with Violent Recidivism in a Sample of High-Risk Offenders with Psychopathic Traits

    Science.gov (United States)

    Lewis, Kathy; Olver, Mark E.; Wong, Stephen C. P.

    2013-01-01

    The Violence Risk Scale (VRS) uses ratings of static and dynamic risk predictors to assess violence risk, identify targets for treatment, and assess changes in risk following treatment. The VRS was rated pre- and posttreatment on a sample of 150 males, mostly high-risk violent offenders many with psychopathic personality traits. These individuals…

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

    Directory of Open Access Journals (Sweden)

    Alexandre G. Apa

    2006-09-01

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

  18. High risk bladder cancer: current management and survival

    Directory of Open Access Journals (Sweden)

    Anna M. Leliveld

    2011-04-01

    Full Text Available PURPOSE: To evaluate the pattern of care in patients with high risk non muscle invasive bladder cancer (NMIBC in the Comprehensive Cancer Center North-Netherlands (CCCN and to assess factors associated with the choice of treatment, recurrence and progression free survival rates. MATERIALS AND METHODS: Retrospective analysis of 412 patients with newly diagnosed high risk NMIBC. Clinical, demographic and follow-up data were obtained from the CCCN Cancer Registry and a detailed medical record review. Uni and multivariate analysis was performed to identify factors related to choice of treatment and 5 year recurrence and progression free survival. RESULTS: 74/412 (18% patients with high risk NMIBC underwent a transurethral resection (TUR as single treatment. Adjuvant treatment after TUR was performed in 90.7% of the patients treated in teaching hospitals versus 71.8 % in non-teaching hospitals (p 80 years OR 0.1 p = 0.001 and treatment in non-teaching hospitals (OR 0.25; p < 0.001 were associated with less adjuvant treatment after TUR. Tumor recurrence occurred in 191/392 (49% and progression in 84 /392 (21.4% patients. The mean 5-years progression free survival was 71.6% (95% CI 65.5-76.8. CONCLUSION: In this pattern of care study in high risk NMIBC, 18% of the patients were treated with TUR as single treatment. Age and treatment in non-teaching hospitals were associated with less adjuvant treatment after TUR. None of the variables sex, age, comorbidity, hospital type, stage and year of treatment was associated with 5 year recurrence or progression rates.

  19. Cryosurgical ablation of the prostate: high risk patient outcomes.

    Science.gov (United States)

    Prepelica, Kristofer L; Okeke, Zephaniah; Murphy, Alana; Katz, Aaron E

    2005-04-15

    The authors report their experience with cryosurgical ablation of the prostate in men with high-risk features for prostate carcinoma who were unwilling to undergo radical surgery or radiation therapy. Between January 1998 and April 2002, 65 men underwent primary cryosurgery for prostate carcinoma with high-risk features. All patients had biopsy-proven prostate carcinoma without evidence for metastatic disease on magnetic resonance images, computed tomography scans, or radionuclide images of bones. High-risk parameters were defined as either a prostate-specific antigen (PSA) level >/= 10 ng/mL, or a Gleason sum score >/= 8, or both. Patients who had undergone prior surgery, radiation therapy, or cryoablation for prostate carcinoma were excluded from the study. Patients were monitored with physical examination and PSA screening every 3 months and with radiologic imaging when indicated. The median patient age was 72 years (range, 41-86 years), and t he median follow-up was 35 months (range, 4-77 months). There were 2 patients (3.1%) with rectal pain and incontinence. Durable PSA biochemical disease-free survival was noted in 83.3% of patients according to the American Society for Therapeutic Radiology and Oncology (ASTRO) criteria. A 6-year Kaplan-Meier analysis revealed an 81.7% ASTRO survival probability as well as PSA nadir < 4.0 ng/mL and PSA nadir < 1.0 ng/mL projections of 50% and 35%, respectively. One of 8 postcryosurgery biopsies (12.5%) were positive. No patient had progressed at last follow-up, and the overall survival rate was 100%. Cryoablation was a feasible treatment option in patients with organ-confined prostate carcinoma who had high-risk features. Longer follow-up will be necessary to determine the effectiveness of this approach. (c) 2005 American Cancer Society.

  20. Comprehensive brain MRI segmentation in high risk preterm newborns.

    OpenAIRE

    Xintian Yu; Yanjie Zhang; Robert E Lasky; Sushmita Datta; Nehal A Parikh; Ponnada A Narayana

    2010-01-01

    Most extremely preterm newborns exhibit cerebral atrophy/growth disturbances and white matter signal abnormalities on MRI at term-equivalent age. MRI brain volumes could serve as biomarkers for evaluating the effects of neonatal intensive care and predicting neurodevelopmental outcomes. This requires detailed, accurate, and reliable brain MRI segmentation methods. We describe our efforts to develop such methods in high risk newborns using a combination of manual and automated segmentation too...

  1. Rosuvastatin: Role in Cardiovascular High-risk Patient

    Directory of Open Access Journals (Sweden)

    John E Feliciano-Alfonso

    2013-01-01

    Full Text Available Statins are the lipid-lowering drug family of first choice in situations of hypercholesterolemia or mixed dyslipidemia with predominant increase in cholesterol. The evidence shows conclusively that each one of the commercially available statins have proven benefits on outcomes of cardiovascular morbidity and mortality. However, rosuvastatin has certain pharmacokinetic efficacy and cost-effectiveness characteristics that make it an attractive molecule to be the statin of choice in patients at high cardiovascular risk.

  2. Impact of the revised International Prognostic Scoring System, cytogenetics and monosomal karyotype on outcome after allogeneic stem cell transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia evolving from myelodysplastic syndromes: a retrospective multicenter study of the European Society of Blood and Marrow Transplantation.

    Science.gov (United States)

    Koenecke, Christian; Göhring, Gudrun; de Wreede, Liesbeth C; van Biezen, Anja; Scheid, Christof; Volin, Liisa; Maertens, Johan; Finke, Jürgen; Schaap, Nicolaas; Robin, Marie; Passweg, Jakob; Cornelissen, Jan; Beelen, Dietrich; Heuser, Michael; de Witte, Theo; Kröger, Nicolaus

    2015-03-01

    The aim of this study was to determine the impact of the revised 5-group International Prognostic Scoring System cytogenetic classification on outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndromes or secondary acute myeloid leukemia who were reported to the European Society for Blood and Marrow Transplantation database. A total of 903 patients had sufficient cytogenetic information available at stem cell transplantation to be classified according to the 5-group classification. Poor and very poor risk according to this classification was an independent predictor of shorter relapse-free survival (hazard ratio 1.40 and 2.14), overall survival (hazard ratio 1.38 and 2.14), and significantly higher cumulative incidence of relapse (hazard ratio 1.64 and 2.76), compared to patients with very good, good or intermediate risk. When comparing the predictive performance of a series of Cox models both for relapse-free survival and for overall survival, a model with simplified 5-group cytogenetics (merging very good, good and intermediate cytogenetics) performed best. Furthermore, monosomal karyotype is an additional negative predictor for outcome within patients of the poor, but not the very poor risk group of the 5-group classification. The revised International Prognostic Scoring System cytogenetic classification allows patients with myelodysplastic syndromes to be separated into three groups with clearly different outcomes after stem cell transplantation. Poor and very poor risk cytogenetics were strong predictors of poor patient outcome. The new cytogenetic classification added value to prediction of patient outcome compared to prediction models using only traditional risk factors or the 3-group International Prognostic Scoring System cytogenetic classification. Copyright© Ferrata Storti Foundation.

  3. Postoperative chemoradiotherapy in high risk locally advanced gastric cancer

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    Song, Sang Hyuk; Chie, Eui Kyu; Kim, Kyu Bo; Lee, Hyuk Joon; Yang, Han Kwang; Han, Sae Won; Oh, Do Youn; Im, Seok Ah; Bang, Yung Jue; Ha, Sung W. [Seoul National University College of Medicine, Seoul(Korea, Republic of)

    2012-12-15

    To evaluate treatment outcome of patients with high risk locally advanced gastric cancer after postoperative chemoradiotherapy. Between May 2003 and May 2012, thirteen patients who underwent postoperative chemoradiotherapy for gastric cancer with resection margin involvement or adjacent structure invasion were retrospectively analyzed. Concurrent chemotherapy was administered in 10 patients. Median dose of radiation was 50.4 Gy (range, 45 to 55.8 Gy). The median follow-up duration for surviving patients was 48 months (range, 5 to 108 months). The 5-year overall survival rate was 42% and the 5-year disease-free survival rate was 28%. Major pattern of failure was peritoneal seeding with 46%. Loco-regional recurrence was reported in only one patient. Grade 2 or higher gastrointestinal toxicity occurred in 54% of the patients. However, there was only one patient with higher than grade 3 toxicity. Despite reported suggested role of adjuvant radiotherapy with combination chemotherapy in gastric cancer, only very small portion of the patients underwent the treatment. Results from this study show that postoperative chemoradiotherapy provided excellent locoregional control with acceptable and manageable treatment related toxicity in patients with high risk locally advanced gastric cancer. Thus, postoperative chemoradiotherapy may improve treatment result in terms of locoregional control in these high risk patients. However, as these findings are based on small series, validation with larger cohort is suggested.

  4. TOB-G: Tobacco Cessation Guidelines for High risk Populations

    Directory of Open Access Journals (Sweden)

    Panagiotis Behrakis

    2016-03-01

    Full Text Available The TOB-G project is funded under the EU 3rd Health Programme which is the main instrument that the Commission uses to implement the EU Health Strategy. The project started in June 2014 and will be completed in September 2017. The project consortium consists of 5 partners from 4 European countries (Belgium, Greece, Ireland and Romania. The TOB-G project aims to develop and implement an innovative and cost effective approach to prevent chronic diseases related to tobacco dependence by focusing on creating specialized tobacco cessation guidelines for populations of high risk including adolescents, pregnant women, adults with COPD, Cardiovascular disease and diabetes. The specialized guidelines for high risks groups will be developed according to ENSP’s evidence based and good practices in tobacco cessation. The smoking cessation guidelines contain strategies and recommendations designed to assist clinicians/ doctors in delivering and supporting effective treatments for tobacco use and dependence and will also be available within the context of an e-learning platform for European clinicians. Overall, the TOB-G project will enhance the overall European capacity in the treatment of tobacco dependence, through offering smoking cessation tools, appropriately assessed and fitted to the specific needs of high risk groups.

  5. Development of Financial Support Program for High Risk Pregnant Women.

    Science.gov (United States)

    Jeong, Ihnsook; Kim, Jiyun; Im, Sook Bin

    2016-06-01

    The purpose of this study was to develop a financial support program for high-risk pregnant women based on opinions obtained using a questionnaire survey. The program development involved two steps: (1) developing a questionnaire through reviewing previous financial support programs for maternal care and then validating it via professional consultation; and (2) drafting a financial support program. Sixty professionals, 26 high-risk pregnant women, and 100 program implementers completed the questionnaire between August 2014 and October 2014. Based on the obtained professional consultation and survey investigation, the framework of the financial support program was constructed. The suggested recipients were mothers with early labor pains, mothers who have been hospitalized for > 3 weeks, and mothers who used uterine stimulant Pitocin during hospitalization. All hospitalization, medication, and examination costs needed to be supported considering the income level of the recipient. A basic policy for financially supporting high-risk pregnant women has been developed. The efficacy and feasibility of the policy needs to be carefully examined in future studies.

  6. Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

    Science.gov (United States)

    2017-10-24

    Acute Biphenotypic Leukemia; Acute Erythroid Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Blasts Under 10 Percent of Bone Marrow Nucleated Cells; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Pancytopenia; Refractory Anemia; Secondary Acute Myeloid Leukemia

  7. Learning rate and temperament in a high predation risk environment

    Science.gov (United States)

    DePasquale, C.; Wagner, Tyler; Archard, G.A.; Ferguson, B.; Braithwaite, V.A.

    2014-01-01

    Living in challenging environments can influence the behavior of animals in a number of ways. For instance, populations of prey fish that experience frequent, nonlethal interactions with predators have a high proportion of individuals that express greater reaction to risk and increased activity and exploration—collectively known as temperament traits. Temperament traits are often correlated, such that individuals that are risk-prone also tend to be active and explore more. Spatial learning, which requires the integration of many sensory cues, has also been shown to vary in fish exposed to different levels of predation threat. Fish from areas of low predation risk learn to solve spatial tasks faster than fish from high predation areas. However, it is not yet known whether simpler forms of learning, such as learning associations between two events, are similarly influenced. Simple forms of associative learning are likely to be affected by temperament because a willingness to approach and explore novel situations could provide animals with a learning advantage. However, it is possible that routine-forming and inflexible traits associated with risk-prone and increased exploratory behavior may act in the opposite way and make risk-prone individuals poorer at learning associations. To investigate this, we measured temperament in Panamanian bishop fish (Brachyrhaphis episcopi) sampled from a site known to contain many predators. The B. episcopi were then tested with an associative learning task. Within this population, fish that explored more were faster at learning a cue that predicted access to food, indicating a link between temperament and basic learning abilities.

  8. Learning rate and temperament in a high predation risk environment.

    Science.gov (United States)

    DePasquale, C; Wagner, T; Archard, G A; Ferguson, B; Braithwaite, V A

    2014-11-01

    Living in challenging environments can influence the behavior of animals in a number of ways. For instance, populations of prey fish that experience frequent, nonlethal interactions with predators have a high proportion of individuals that express greater reaction to risk and increased activity and exploration-collectively known as temperament traits. Temperament traits are often correlated, such that individuals that are risk-prone also tend to be active and explore more. Spatial learning, which requires the integration of many sensory cues, has also been shown to vary in fish exposed to different levels of predation threat. Fish from areas of low predation risk learn to solve spatial tasks faster than fish from high predation areas. However, it is not yet known whether simpler forms of learning, such as learning associations between two events, are similarly influenced. Simple forms of associative learning are likely to be affected by temperament because a willingness to approach and explore novel situations could provide animals with a learning advantage. However, it is possible that routine-forming and inflexible traits associated with risk-prone and increased exploratory behavior may act in the opposite way and make risk-prone individuals poorer at learning associations. To investigate this, we measured temperament in Panamanian bishop fish (Brachyrhaphis episcopi) sampled from a site known to contain many predators. The B. episcopi were then tested with an associative learning task. Within this population, fish that explored more were faster at learning a cue that predicted access to food, indicating a link between temperament and basic learning abilities.

  9. NY-ESO-1 Vaccination in Combination with Decitabine Induces Antigen-Specific T-lymphocyte Responses in Patients with Myelodysplastic Syndrome.

    Science.gov (United States)

    Griffiths, Elizabeth A; Srivastava, Pragya; Matsuzaki, Junko; Brumberger, Zachary; Wang, Eunice S; Kocent, Justin; Miller, Austin; Roloff, Gregory W; Wong, Hong Yuen; Paluch, Benjamin E; Lutgen-Dunckley, Linda G; Martens, Brandon L; Odunsi, Kunle; Karpf, Adam R; Hourigan, Christopher S; Nemeth, Michael J

    2017-09-25

    Purpose: Treatment options are limited for patients with high-risk myelodysplastic syndrome (MDS). The azanucleosides, azacitidine and decitabine, are first-line therapy for MDS that induce promoter demethylation and gene expression of the highly immunogenic tumor antigen NY-ESO-1. We demonstrated that patients with acute myeloid leukemia (AML) receiving decitabine exhibit induction of NY-ESO-1 expression in circulating blasts. We hypothesized that vaccinating against NY-ESO-1 in patients with MDS receiving decitabine would capitalize upon induced NY-ESO-1 expression in malignant myeloid cells to provoke an NY-ESO-1-specific MDS-directed cytotoxic T-cell immune response. Experimental Design: In a phase I study, 9 patients with MDS received an HLA-unrestricted NY-ESO-1 vaccine (CDX-1401 + poly-ICLC) in a nonoverlapping schedule every four weeks with standard-dose decitabine. Results: Analysis of samples serially obtained from the 7 patients who reached the end of the study demonstrated induction of NY-ESO-1 expression in 7 of 7 patients and NY-ESO-1-specific CD4 + and CD8 + T-lymphocyte responses in 6 of 7 and 4 of 7 of the vaccinated patients, respectively. Myeloid cells expressing NY-ESO-1, isolated from a patient at different time points during decitabine therapy, were capable of activating a cytotoxic response from autologous NY-ESO-1-specific T lymphocytes. Vaccine responses were associated with a detectable population of CD141 Hi conventional dendritic cells, which are critical for the uptake of NY-ESO-1 vaccine and have a recognized role in antitumor immune responses. Conclusions: These data indicate that vaccination against induced NY-ESO-1 expression can produce an antigen-specific immune response in a relatively nonimmunogenic myeloid cancer and highlight the potential for induced antigen-directed immunotherapy in a group of patients with limited options. Clin Cancer Res; 24(5); 1-11. ©2017 AACR. See related commentary by Fuchs, p. 991 . ©2017 American

  10. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer

    NARCIS (Netherlands)

    Rodenhuis, S; Bontenbal, M; Beex, LVAM; Wagstaff, J; Richel, DJ; Nooij, MA; Voest, EE; Hupperets, P; van Tinteren, H; Peterse, HL; TenVergert, EM; de Vries, EGE

    2003-01-01

    BACKGROUND: The use of high-dose adjuvant chemotherapy for high-risk primary breast cancer is controversial. We studied its efficacy in patients with 4 to 9 or 10 or more tumor-positive axillary lymph nodes. METHODS: Patients younger than 56 years of age who had undergone surgery for breast cancer

  11. Efficacy of smartphone applications in high-risk pigmented lesions.

    Science.gov (United States)

    Ngoo, Alexander; Finnane, Anna; McMeniman, Erin; Tan, Jean-Marie; Janda, Monika; Soyer, H Peter

    2017-02-27

    Melanoma apps are smartphone applications that assess risk of pigmented lesions using a smartphone camera and underlying algorithm. We aimed to assess the capability of melanoma smartphone applications (apps) in making clinical decisions about risk, compared with lesion assessment by specialist trained dermatologists. A prospective study of 3 melanoma apps was conducted between 2015 and 2016, recruiting 30 patients with 57 pigmented lesions. Risk categories assigned by the apps were compared with the clinical decisions of two consultant dermatologists classifying lesions as 'suspicious' or 'benign'. Of the 42 lesions deemed clinically suspicious to a dermatologist, from 9 to 26 were classified as suspicious by the apps; of the 15 clinically benign lesions 3 to 15 were correctly classified as benign by the apps. The apps' sensitivity and specificity ranged from 21 to 72% and 27 to 100.0%, respectively, when compared with the specialists' decisions. Two apps were unable to analyse 14 and 18% of lesions submitted, respectively. Interrater agreement between dermatologists and apps was poor (κ = -0.01 SE = 0.16; P = 0.97) to slight (κ = 0.16 SE = 0.09; P = 0.12). None of the melanoma apps tested had high enough agreement with the dermatologist's clinical opinion to be considered to provide additional benefit to patients in assessing their skin for high-risk pigmented lesions. The low sensitivity in detecting lesions that are suspicious to a trained specialist may mean false reassurance is being given to patients. Development of highly sensitive and specific melanoma apps remains a work in progress. © 2017 The Australasian College of Dermatologists.

  12. Preterm birth risk at high altitude in Peru.

    Science.gov (United States)

    Levine, Lisa D; Gonzales, Gustavo F; Tapia, Vilma L; Gasco, Manuel; Sammel, Mary D; Srinivas, Sindhu K; Ludmir, Jack

    2015-02-01

    High altitude has been implicated in a variety of adverse pregnancy outcomes including preeclampsia and stillbirth. Smaller studies show conflicting data on the association between high altitude and preterm birth (PTB). The objective of this study was to assess the association between altitude and PTB. A retrospective cohort study was performed using data from the Perinatal Information System, which includes deliveries from 43 hospitals in Peru from 2000 through 2010. Altitude was classified into the following categories: low (0-1999 m), moderate (2000-2900 m), and high (3000-4340 m). The primary outcome was PTB (delivery <37 weeks). Secondary outcomes were cesarean delivery and small for gestational age (SGA). Deliveries less than 23 weeks are not included in the database. χ(2) analyses were performed to compare categorical variables, and a logistic regression was used to calculate the odds ratios and control for confounders. Clustering by hospital was accounted for using generalized estimating equations. A total of 550,166 women were included (68% low, 15% moderate, 17% high altitude). The overall PTB rate was 5.9%, with no difference in the PTB rate among the 3 altitudes (5.6%, 6.2%, 6.8%, P = .13). There was a significant difference in cesarean rates (28.0%, 26.6%, 20.6%, P < .001) with a 34% decreased risk at high vs low altitude adjusted for confounders (adjusted odds ratio, 0.66; 95% confidence interval, 0.51-0.85). There was a difference in SGA (3.3%, 3.6%, 5.0%, P = .02) with a 51% increased risk at high vs low altitude adjusted for confounders (adjusted odds ratio, 1.49; 95% confidence interval, 1.14-1.93). High altitude is not associated with PTB. At high altitude, the cesarean rate was reduced and the SGA rate was increased. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. INSTRUMENTS OF HIGH RISK SEXUAL BEHAVIOR ASSESSMENT: A SYSTEMATIC REVIEW.

    Science.gov (United States)

    Mirzaei, Mojtaba; Ahmadi, Khodabakhsh; Saadat, Seyed-Hassan; Ramezani, Mohammad Arash

    2016-02-01

    Sexual behavior is a complex activity affecting all aspects of human's life. Risky sexual behaviors impose negative outcomes on family, relationships and health. Unsafe sex is the second most leading cause of disability adjusted life years worldwide. Valid and reliable tools for assessment of risky sexual behaviors are necessary for implementing preventive measures. we searched Medline and the Cochrane Library of Systematic Reviews, with the keywords of "risky sexual behavior assessment", "sexual risk assessment", "high risk sexual behavior", "sexual risk taking". By reviewing references of the articles, some complementary studies were added. Assessment can be performed by questionnaire or non-questionnaire instruments. Questionnaires vary depending on their target population, evaluation of risky sexual behavior as a whole or focusing on an associated risk factor. In order to avoid usual biases in self reports, objective biomarker assessment of unprotected sex are employed. These markers include prostate specific antigen, chromosome Y DNA and Seminogelin. Risky sexual behavior can be assessed by various subjective and objective methods. While self-reports are more feasible, objective methods offer a higher degree of reliability. Further studies for finding more feasible methods of using biomarkers are recommended.

  14. Psychosocial differences in high risk versus low risk acute low-back pain patients.

    Science.gov (United States)

    Pulliam, C B; Gatchel, R J; Gardea, M A

    2001-03-01

    The current study built upon previous research that predicted with 90.7% accuracy which patients presenting with acute low-back pain go on to develop chronic disability problems. Fifty-seven patients were classified as high risk (HR) or low risk (LR) according to a predictive algorithm, and were evaluated with a variety of psychosocial measures. Overall, HR patients had more Axis I pathology than LR patients, and used poorer coping styles. Logistic regression analyses identified variables that differentiated, with 80% accuracy, between the HR and LR patients. The results highlight the importance of identifying patients who are at risk for developing chronic pain following acute injury so that prophylactic intervention can be offered before chronic pain disability status becomes entrenched.

  15. Myelodysplastic syndrome patients present more severe respiratory muscle impairment and reduced forced vital capacity: Is disordered inflammatory signaling the culprit?

    Directory of Open Access Journals (Sweden)

    Bruno Memória Okubo

    Full Text Available The ageing process is associated with gradual decline in respiratory system performance. Anemia is highly prevalent among older adults and usually associated with adverse outcomes. Myelodysplastic syndromes (MDS are a heterogeneous group of hematologic malignancies with increasing incidence with age and characterized by anemia and other cytopenias. The main objectives of this study were to evaluate respiratory muscle strength and lung function in elderly patients with anemia, compare data between myelodysplastic syndromes and non-clonal anemias and evaluate the influence of serum IL-8 level and NF-kB activity on deteriorate pulmonary function in this specific population.Individuals aged 60 and older with anemia secondary to MDS, non-clonal anemia and healthy elderly individuals.Forced expiratory volume in 1 second (FEV1, forced vital capacity (FVC, and FEV1/ FVC ratio were measured by spirometry. Respiratory muscle strength was evaluated by maximal static respiratory pressures measurement. IL-8 analysis was performed by ELISA and activity of NF-kB by chemiluminescent assay.Mean Hb concentration was comparable between patients with anemia. Significant differences were detected between all patients with anemia and controls for maximum-effort inspiratory mouth pressure (PImax and also for maximum-effort expiratory mouth pressure (PEmax. The MDS group recorded a significantly lower PImax and PEmax percent predicted when compared to non-clonal anemia group. For FVC and FEV1, a significant difference was found in anemic patients, with even significantly lower values for FVC and FEV1 in MDS group. No significant differences were detected for PImax and PEmax and spirometry parameters when anemic patients were stratified according to the degree of anemia. A significant negative impact in FVC (% pred, PImax (% pred and PEmax (% pred was observed in patients with MDS and higher levels of IL-8 or increased activity of NF-kB.A negative impact of anemia

  16. [Home care for the high-risk newborn infant].

    Science.gov (United States)

    Puddu, M

    2010-06-01

    With increased survival of extremely low birth weigh (ELBW) and very ill infants, a lot of them are discharged with unresolved medical issues that complicate their subsequent care. Infants born preterm with low birth weight who require neonatal intensive care experience a much higher rate of hospital readmission and death during the first year after birth compared with healthy term infants. Despite initial hospital care which is one of the most expensive of all kind of hospitalization, home care services are sometimes still sparse though the high risk of this group for failure to thrive, respiratory problems, developmental delays, parenting problems. In addition, societal and economic forces have come to bear on the timing and process of discharge and home care. Moreover it takes time for the family of a high-risk infant to prepare to care for their infant in a home setting and to obtain the necessary support services and mobilize community resources. Careful preparation for discharge, good follow-up and medical home after discharge may reduce these risks.

  17. Genomic loss of EZH2 leads to epigenetic modifications and overexpression of the HOX gene clusters in myelodysplastic syndrome

    Science.gov (United States)

    Chang, Chun-Kang; He, Qi; Wu, Ling-Yun; Zhang, Zheng; Shi, Wen-Hui; Guo, Juan; Zhu, Yang; Zhao, You-Shan; Gu, Shu-Cheng; Fei, Cheng-Ming; Li, Xiao

    2016-01-01

    The role of EZH2 in cancer is complex and may vary depending on cancer type or stage. We examined the effect of altered EZH2 levels on H3K27 methylation, HOX gene expression, and malignant phenotype in myelodysplastic syndrome (MDS) cell lines and an in vivo xenograft model. We also studied links between EZH2 expression and prognosis in MDS patients. Patients with high-grade MDS exhibited lower levels of EZH2 expression than those with low-grade MDS. Low EZH2 expression was associated with high percentages of blasts, shorter survival, and increased transformation of MDS into acute myeloid leukemia (AML). MDS patients frequently had reductions in EZH2 copy number. EZH2 knockdown increased tumor growth capacity and reduced H3K27me3 levels in both MDS-derived leukemia cells and in a xenograft model. H3K27me3 levels were reduced and HOX gene cluster expression was increased in MDS patients. EZH2 knockdown also increased HOX gene cluster expression by reducing H3K27me3, and H3K27 demethylating agents increased HOX gene cluster expression in MDS-derived cell lines. These findings suggest genomic loss of EZH2 contributes to overexpression of the HOX gene clusters in MDS through epigenetic modifications. PMID:26812882

  18. Subsequent primary malignancies and acute myelogenous leukemia transformation among myelodysplastic syndrome patients treated with or without lenalidomide.

    Science.gov (United States)

    Rollison, Dana E; Shain, Kenneth H; Lee, Ji-Hyun; Hampras, Shalaka S; Fulp, William; Fisher, Kate; Al Ali, Najla H; Padron, Eric; Lancet, Jeffrey; Xu, Qiang; Olesnyckyj, Martha; Kenvin, Laurie; Knight, Robert; Dalton, William; List, Alan; Komrokji, Rami S

    2016-07-01

    The few studies that have examined rates of acute myeloid leukemia (AML) transformation in lenalidomide-treated myelodysplastic syndrome (MDS) patients have been limited to deletion 5q MDS. The association between lenalidomide and subsequent primary malignancies (SPMs) in MDS patients has not been evaluated previously. We conducted a retrospective cohort study to evaluate the risk of both SPM and AML in association with lenalidomide. A cohort of MDS patients (n = 1248) treated between 2004 and 2012 at Moffitt Cancer Center were identified, and incident cases of SPM and AML transformation were ascertained. Using a nested case-control design, MDS controls were 1:1 matched to SPM (n = 41) and AML (n = 150) cases, on age and date of MDS diagnosis, gender, follow-up time, IPSS, and del (5q). Associations between lenalidomide and (1) SPM incidence and (2) AML transformation were estimated with hazards ratios (HR) and 95% confidence intervals (CIs) in the cohort and odds ratios (OR) in the case-control analysis. SPM incidence did not differ significantly between cohort MDS patients treated with (0.7 per 100 person-years) or without lenalidomide (1.4 per 100 person-years) (HR = 1.04, 95% CI = 0.40-2.74), whereas a significantly reduced SPM risk was observed in the case-control sample (OR = 0.03, 95% CI = transformation in the cohort analysis (HR = 0.75, 95% CI = 0.44-1.27) or in the case-control analyses (OR = 1.16, 95% CI = 0.52-2.56), after adjustment for potential confounders. Lenalidomide was not associated with increased risk of SPM or AML transformation in a large cohort of MDS patients mostly including nondeletion 5q MDS. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  19. Correlates of hopelessness in the high suicide risk police occupation.

    Science.gov (United States)

    Violanti, John M; Andrew, Michael E; Mnatsakanova, Anna; Hartley, Tara A; Fekedulegn, Desta; Burchfiel, Cecil M

    Police officers are chronically exposed to work stress. We examined specific stressors that may be associated with hopelessness, a possible risk factor for suicide in this high suicide risk population. The study included 378 officers (276 men and 102 women) with complete data. Analysis of variance was used to estimate mean levels of hopelessness scores as associated with stress, adjusted for age, gender, and race/ ethnicity. Posttraumatic symptoms were tested as a modifier of the association between stress and hopelessness. Increasing stress of administrative practices and lack of support were significantly associated with increasing hopelessness among officers (p hopelessness range: 1.64-2.65; and p hopelessness range 1.60-2.80, respectively). Posttraumatic stress disorder (PTSD) symptoms significantly modified the association between lack of organizational support and hopelessness (p hopelessness is associated with specific stressors in police work, and this is modified by posttraumatic symptomatology.

  20. Risk Factors Associated with Incident Syphilis in a Cohort of High-Risk Men in Peru.

    Directory of Open Access Journals (Sweden)

    Hayoung Park

    Full Text Available Syphilis is concentrated among high-risk groups, but the epidemiology of syphilis reinfection is poorly understood. We characterized factors associated with syphilis incidence, including reinfection, in a high-risk cohort in Peru.Participants in the NIMH CPOL trial were assessed at baseline and 2 annual visits with HIV/STI testing and behavioral surveys. Participants diagnosed with syphilis also attended 4- and 9-month visits. All participants underwent syphilis testing with RPR screening and TPPA confirmation. Antibiotic treatment was provided according to CDC guidelines. Reinfection was defined as a 4-fold titer increase or recurrence of seroreactivity after successful treatment with subsequent negative RPR titers. The longitudinal analysis used a Possion generalized estimating equations model with backward selection of variables in the final model (criteria P <0.02.Of 2,709 participants, 191 (7.05% were RPR-reactive (median 1:8, range 1:1-1:1024 with TPPA confirmation. There were 119 total cases of incident syphilis, which included both reinfection and first-time incident cases. In the bivariate analysis, the oldest 2 quartiles of age (incidence ratio (IR 3.84; P <0.001 and IR 8.15; P <0.001 and being MSM/TW (IR 6.48; P <0.001 were associated with higher risk of incident syphilis infection. Of the sexual risk behaviors, older age of sexual debut (IR 12.53; P <0.001, not being in a stable partnership (IR 1.56, P = 0.035, higher number of sex partners (IR 3.01; P <0.001, unprotected sex in the past 3 months (IR 0.56; P = 0.003, HIV infection at baseline (IR 3.98; P <0.001 and incident HIV infection during the study period (IR 6.26; P = 0.003 were all associated with incident syphilis. In the multivariable analysis, older age group (adjusted incidence ratio (aIR 6.18; P <0.001, men reporting having sex with a man (aIR 4.63; P <0.001, and incident HIV infection (aIR 4.48; P = 0.008 were significantly associated.We report a high rate of syphilis

  1. Risk Factors Associated with Incident Syphilis in a Cohort of High-Risk Men in Peru

    Science.gov (United States)

    Konda, Kelika A.; Roberts, Chelsea P.; Maguiña, Jorge L.; Leon, Segundo R.; Clark, Jesse L.; Coates, Thomas J.; Caceres, Carlos F.; Klausner, Jeffrey D.

    2016-01-01

    Background Syphilis is concentrated among high-risk groups, but the epidemiology of syphilis reinfection is poorly understood. We characterized factors associated with syphilis incidence, including reinfection, in a high-risk cohort in Peru. Methods Participants in the NIMH CPOL trial were assessed at baseline and 2 annual visits with HIV/STI testing and behavioral surveys. Participants diagnosed with syphilis also attended 4- and 9-month visits. All participants underwent syphilis testing with RPR screening and TPPA confirmation. Antibiotic treatment was provided according to CDC guidelines. Reinfection was defined as a 4-fold titer increase or recurrence of seroreactivity after successful treatment with subsequent negative RPR titers. The longitudinal analysis used a Possion generalized estimating equations model with backward selection of variables in the final model (criteria P <0.02). Results Of 2,709 participants, 191 (7.05%) were RPR-reactive (median 1:8, range 1:1–1:1024) with TPPA confirmation. There were 119 total cases of incident syphilis, which included both reinfection and first-time incident cases. In the bivariate analysis, the oldest 2 quartiles of age (incidence ratio (IR) 3.84; P <0.001 and IR 8.15; P <0.001) and being MSM/TW (IR 6.48; P <0.001) were associated with higher risk of incident syphilis infection. Of the sexual risk behaviors, older age of sexual debut (IR 12.53; P <0.001), not being in a stable partnership (IR 1.56, P = 0.035), higher number of sex partners (IR 3.01; P <0.001), unprotected sex in the past 3 months (IR 0.56; P = 0.003), HIV infection at baseline (IR 3.98; P <0.001) and incident HIV infection during the study period (IR 6.26; P = 0.003) were all associated with incident syphilis. In the multivariable analysis, older age group (adjusted incidence ratio (aIR) 6.18; P <0.001), men reporting having sex with a man (aIR 4.63; P <0.001), and incident HIV infection (aIR 4.48; P = 0.008) were significantly associated

  2. Entropy measure of credit risk in highly correlated markets

    Science.gov (United States)

    Gottschalk, Sylvia

    2017-07-01

    We compare the single and multi-factor structural models of corporate default by calculating the Jeffreys-Kullback-Leibler divergence between their predicted default probabilities when asset correlations are either high or low. Single-factor structural models assume that the stochastic process driving the value of a firm is independent of that of other companies. A multi-factor structural model, on the contrary, is built on the assumption that a single firm's value follows a stochastic process correlated with that of other companies. Our main results show that the divergence between the two models increases in highly correlated, volatile, and large markets, but that it is closer to zero in small markets, when asset correlations are low and firms are highly leveraged. These findings suggest that during periods of financial instability, when asset volatility and correlations increase, one of the models misreports actual default risk.

  3. 2017 Taiwan lipid guidelines for high risk patients

    Directory of Open Access Journals (Sweden)

    Yi-Heng Li

    2017-04-01

    Full Text Available In Taiwan, the prevalence of hyperlipidemia increased due to lifestyle and dietary habit changes. Low density lipoprotein cholesterol (LDL-C and non-high density lipoprotein cholesterol (non-HDL-C are all significant predicting factors of coronary artery disease in Taiwan. We recognized that lipid control is especially important in patients with existed atherosclerotic cardiovascular diseases (ASCVD, including coronary artery disease (CAD, ischemic stroke and peripheral arterial disease (PAD. Because the risk of ASCVD is high in patients with diabetes mellitus (DM, chronic kidney disease (CKD and familial hypercholesterolemia (FH, lipid control is also necessary in these patients. Lifestyle modification is the first step to control lipid. Weight reduction, regular physical exercise and limitation of alcohol intake all reduce triglyceride (TG levels. Lipid-lowering drugs include HMG-CoA reductase inhibitors (statins, cholesterol absorption inhibitors (ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors, nicotinic acids (niacin, fibric acids derivatives (fibrates, and long-chain omega-3 fatty acids. Statin is usually the first line therapy. Combination therapy with statin and other lipid-lowering agents may be considered in some clinical settings. For patients with acute coronary syndrome (ACS and stable CAD, LDL-C 40 in men and >50 mg/dL in women in DM. LDL-C increased CV risk in patients with CKD. In adults with glomerular filtration rate (GFR < 60 mL/min/1.73m2 without chronic dialysis (CKD stage 3–5, statin therapy should be initiated if LDL-C ≥ 100 mg/dL. Ezetimibe can be added to statin to consolidate the CV protection in CKD patients. Mutations in LDL receptor, apolipoprotein B and PCSK9 genes are the common causes of FH. Diagnosis of FH usually depends on family history, clinical history of premature CAD, physical findings of xanthoma or corneal arcus and high levels of LDL-C. In addition to conventional lipid

  4. Operational Collision Risk Management - Evaluating and Mitigating High-Risk Conjunction Events

    Science.gov (United States)

    Duncan, M.; Wysack, J.

    2011-09-01

    Operational collision threat characterization is now an essential component of space mission operations. Most spacecraft operators have some semblance of a process to evaluate and mitigate high-risk conjunction events. As the size of the space object catalog increases, satellite operators will be faced with more conjunction events to evaluate. Thus more sophisticated collision threat characterization and collision avoidance strategies must be implemented. This paper presents an overview of SpaceNav’s Collision Risk Management software. The software suite enables mission stakeholders to qualify high interest conjunction events. The tools produce various figures and graphs, which aid in analyzing event data. Optimal avoidance maneuver solutions are generated for a user defined set of goals and constraints.

  5. Old age, high risk medication, polypharmacy: a trilogy of risks in older patients with atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Wang Y

    2016-06-01

    Full Text Available Background: The safety of pharmacotherapy in atrial fibrillation (AF is compounded by a trilogy of risks old age, high-risk medications (e.g., antithrombotics, antiarrhythmics, polypharmacy due to multiple patient comorbidities. However, to date, scarce study has investigated the use of polypharmacy (including potentially inappropriate medication (PIM in AF patients, and how this may contribute to their overall risk of medication misadventure. Objectives: To review the extent of polypharmacy and PIM use in older patients (65 years or older with AF. Methods: Information was extracted from a database characterising a cohort of older AF patients treated in general practice in New South Wales, Australia. Patient characteristics, number and types of drugs, the degree of PIM use were recorded. The predictors for the use of polypharmacy in older AF patients were identified. Results: Overall, 367 patients (mean age 77.8 years were reviewed, among which 94.8% used 5 medications or more and over half used 10 medications or more. Cardiovascular agents were most commonly used (98.9%, followed by antithrombotics (90.7%. Among agents deemed PIMs, digoxin (30.2% was the most frequently used, followed by benzodiazepines (19.6%, and sotalol (9.8%. AF patients using polypharmacy were more likely to have low bleeding risk (OR=10.97, representing those patients in whom high-risk antithrombotics are mostly indicated. Patients with major-polypharmacy (5-9 medications are more likely to have obstructive pulmonary diseases (OR=2.32, upper gastrointestinal diseases (OR=2.02 and poor physical function (OR=1.04, but less likely to have cognitive impairment (OR=0.27. Conclusion: Polypharmacy affects oldest AF patients, comprising medications that are indicated for AF, yet regarded as PIMs. Patients with lower risk of bleeding, obstructive pulmonary diseases, upper gastrointestinal diseases and poor physical function are also at higher risk of using higher number of

  6. Fetal and umbilical Doppler ultrasound in high-risk pregnancies.

    Science.gov (United States)

    Alfirevic, Zarko; Stampalija, Tamara; Dowswell, Therese

    2017-06-13

    Abnormal blood flow patterns in fetal circulation detected by Doppler ultrasound may indicate poor fetal prognosis. It is also possible that false positive Doppler ultrasound findings could lead to adverse outcomes from unnecessary interventions, including preterm delivery. The objective of this review was to assess the effects of Doppler ultrasound used to assess fetal well-being in high-risk pregnancies on obstetric care and fetal outcomes. We updated the search of Cochrane Pregnancy and Childbirth's Trials Register on 31 March 2017 and checked reference lists of retrieved studies. Randomised and quasi-randomised controlled trials of Doppler ultrasound for the investigation of umbilical and fetal vessels waveforms in high-risk pregnancies compared with no Doppler ultrasound. Cluster-randomised trials were eligible for inclusion but none were identified. Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked. We assessed the quality of evidence using the GRADE approach. Nineteen trials involving 10,667 women were included. Risk of bias in trials was difficult to assess accurately due to incomplete reporting. None of the evidence relating to our main outcomes was graded as high quality. The quality of evidence was downgraded due to missing information on trial methods, imprecision in risk estimates and heterogeneity. Eighteen of these studies compared the use of Doppler ultrasound of the umbilical artery of the unborn baby with no Doppler or with cardiotocography (CTG). One more recent trial compared Doppler examination of other fetal blood vessels (ductus venosus) with computerised CTG.The use of Doppler ultrasound of the umbilical artery in high-risk pregnancy was associated with fewer perinatal deaths (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.52 to 0.98, 16 studies, 10,225 babies, 1.2% versus 1.7 %, number needed to treat (NNT) = 203; 95% CI 103 to 4352

  7. [Residual risk: The roles of triglycerides and high density lipoproteins].

    Science.gov (United States)

    Grammer, Tanja; Kleber, Marcus; Silbernagel, Günther; Scharnagl, Hubert; März, Winfried

    2016-06-01

    In clinical trials, the reduction of LDL-cholesterol (LDL-C) with statins reduces the incidence rate of cardiovascular events by approximately one third. This means, that a sizeable "residual risk" remains. Besides high lipoprotein (a), disorders in the metabolism of triglyceride-rich lipoproteins and high density liproteins have been implicated as effectors of the residual risk. Both lipoprotein parameters correlate inversely with each other. Therefore, the etiological contributions of triglycerides and / or of HDL for developing cardiovascular disease can hardly be estimated from either observational studies or from intervention studies. The largely disappointing results of intervention studies with inhibitors of the cholesteryl ester transfer protein and in particular the available set of genetically-epidemiological studies suggest that in the last decade, the importance of HDL cholesterol has been overvalued, while the importance of triglycerides has been underestimated. High triglycerides not always atherogenic, but only if they are associated with the accumulation relatively cholesterol-enriched, incompletely catabolized remnants of chylomicrons and very low density lipoproteins (familial type III hyperlipidemia, metabolic syndrome, diabetes mellitus). The normalization of the concentration of triglycerides and remnants by inhibiting the expression of apolipoprotein C3 is hence a new, promising therapeutic target. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Quantitative breast MRI radiomics for cancer risk assessment and the monitoring of high-risk populations

    Science.gov (United States)

    Mendel, Kayla R.; Li, Hui; Giger, Maryellen L.

    2016-03-01

    Breast density is routinely assessed qualitatively in screening mammography. However, it is challenging to quantitatively determine a 3D density from a 2D image such as a mammogram. Furthermore, dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is used more frequently in the screening of high-risk populations. The purpose of our study is to segment parenchyma and to quantitatively determine volumetric breast density on pre-contrast axial DCE-MRI images (i.e., non-contrast) using a semi-automated quantitative approach. In this study, we retroactively examined 3D DCE-MRI images taken for breast cancer screening of a high-risk population. We analyzed 66 cases with ages between 28 and 76 (mean 48.8, standard deviation 10.8). DCE-MRIs were obtained on a Philips 3.0 T scanner. Our semi-automated DCE-MRI algorithm includes: (a) segmentation of breast tissue from non-breast tissue using fuzzy cmeans clustering (b) separation of dense and fatty tissues using Otsu's method, and (c) calculation of volumetric density as the ratio of dense voxels to total breast voxels. We examined the relationship between pre-contrast DCE-MRI density and clinical BI-RADS density obtained from radiology reports, and obtained a statistically significant correlation [Spearman ρ-value of 0.66 (p < 0.0001)]. Our method within precision medicine may be useful for monitoring high-risk populations.

  9. Teamwork in high-risk environments analogous to space

    Science.gov (United States)

    Kanki, Barbara G.

    1990-01-01

    Mountaineering expeditions combine a number of factors which make them potentially good analogs to the planetary exploration facet of long-duration space missions. A study of mountain climbing teams was conducted in order to evaluate the usefulness of the environment as a space analog and to specifically identify the factors and issues surrounding teamwork and 'successful' team performance in two mountaineering environments. This paper focuses on social/organizational factors, including team size and structure, leadership styles and authority structure which were found in the sample of 22 climb teams (122 individuals). The second major issue discussed is the construction of a valid performance measure in this high-risk environment.

  10. High-Risk Cardiac Disease in Pregnancy: Part I.

    Science.gov (United States)

    Elkayam, Uri; Goland, Sorel; Pieper, Petronella G; Silverside, Candice K

    2016-07-26

    The incidence of pregnancy in women with cardiovascular disease is rising, primarily due to the increased number of women with congenital heart disease reaching childbearing age and the changing demographics associated with advancing maternal age. Although most cardiac conditions are well tolerated during pregnancy and women can deliver safely with favorable outcomes, there are some cardiac conditions that have significant maternal and fetal morbidity and mortality. The purpose of this paper is to review the available published reports and provide recommendations on the management of women with high-risk cardiovascular conditions during pregnancy. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Against the tide: climate change and high-risk cities

    Energy Technology Data Exchange (ETDEWEB)

    Dodman, David

    2008-11-15

    In the world's poorest and most vulnerable nations, most cities and towns face a distinct dual pressure: rapidly growing population and high vulnerability to the impacts of climate change. Drought, storms, flooding and sea level rise are likely to hit hardest here. These in turn put water supplies, infrastructure, health and livelihoods at risk in the very cities already struggling to provide or safeguard such key needs. An effective response demands capable local and national government and support from strong international networks in building capacity to cope. Most of the Least Developed Countries lack both.

  12. Epidural Anesthesia in a Patient with High Cardiac Risk

    Directory of Open Access Journals (Sweden)

    Tuğba Doğu

    2014-03-01

    Full Text Available Cardiac morbidity is the most common cause postoperative of mortality furthermore anesthesia technics are associated with cardiac morbidity and mortality. A 48-year-old male, 90 kg, ASA physical status IV patient underwent femoropopliteal bypass under epidural anesthesia. Comorbidities included atrial fibrillation, dilated cardiomyopathy and 20%  left ventricular ejection fraction. Epidural anesthesia was established with bupivacaine and fentanyl at L3-L4 intervertebral space. Hemodynamic stability and pain relief were established during and after the surgery. We consider that epidural anesthesia is preferable as an alternative regarding the risks of spinal anesthesia and general anesthesia for high cardiac risky patients.

  13. Mechanical Circulatory Support for High-Risk Pulmonary Embolism.

    Science.gov (United States)

    Elder, Mahir; Blank, Nimrod; Shemesh, Adi; Pahuja, Mohit; Kaki, Amir; Mohamad, Tamam; Schreiber, Theodore; Giri, Jay

    2018-01-01

    Temporary mechanical circulatory support (MCS) devices have a role in treating high-risk patients with pulmonary embolism with cardiogenic shock. Mechanical circulatory device selection should be made based on center experience and device-specific features. All current devices are effective in decreasing right arterial pressure and providing circulatory support of 4 to 5 L/min. The pulmonary artery pulsatility index may prove to be an unreliable method to assess right ventricular function. Careful clinical evaluation on an individual patient basis should determine the need for MCS. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Recommendations of activity restriction in high-risk pregnancy scenarios

    DEFF Research Database (Denmark)

    Bendix, Jane; Hegaard, Hanne Kristine; Bergholt, Thomas

    2015-01-01

    and the Danish Association of Midwives were asked to complete a tested, structured questionnaire. Results: We sent 1815 invitations; the overall response rate was 54%. A majority of clinicians recommended some form of activity restriction in the nine scenarios. The midwives recommended strict or moderate...... obstetricians and midwives prescribe activity restriction in most high-risk pregnancies. The degree of activity restriction and the presumed effect vary between clinicians. This may reflect different attitudes and lack of guidelines based on clinical studies of a possible benefit of activity restriction....

  15. Vaginal micronized progesterone and risk of preterm delivery in high-risk twin pregnancies: secondary analysis of a placebo-controlled randomized trial and meta-analysis

    DEFF Research Database (Denmark)

    Klein, K; Rode, L; Nicolaides, K H

    2011-01-01

    Progesterone treatment reduces the risk of preterm delivery in high-risk singleton pregnancies. Our aim was to evaluate the preventive effect of vaginal progesterone in high-risk twins.......Progesterone treatment reduces the risk of preterm delivery in high-risk singleton pregnancies. Our aim was to evaluate the preventive effect of vaginal progesterone in high-risk twins....

  16. At-risk high school seniors: Science remediation for Georgia's High School Graduation Test

    Science.gov (United States)

    Carroll, Carolyn M.

    State departments of education have created a system of accountability for the academic achievement of students under the mandate of the No Child Left Behind Act of 2001. The Georgia Department of Education established the Georgia High School Graduation Test (GHSGT) as their method of evaluating the academic achievement of high school students. The GHSGT consist of five sections and students must pass all five sections before students they are eligible to receive a diploma. The purpose of the study was to examine the effects of teacher-lead and computer based remediation for a group of high school seniors who have been unsuccessful in passing the science portion of the GHSGT. The objectives of this study include (a) Identify the most effective method of remediation for at-risk students on the science section of the GHSGT, and (b) evaluate the methods of remediation for at-risk students on the science section of GHSGT available to high school students. The participants of this study were at-risk seniors enrolled in one high school during the 2007-2008 school year. The findings of this research study indicated that at-risk students who participated in both types of remediation, teacher-led and computer-based, scored significantly higher than the computer-based remediation group alone. There was no significant relationship between the test scores and the number of times the students were tested.

  17. High-risk behaviors in teenage male athletes.

    Science.gov (United States)

    Forman, E S; Dekker, A H; Javors, J R; Davison, D T

    1995-01-01

    This project studied high-risk activities in adolescent male athletes (ages 13-19) compared with a control group of adolescent male and female nonathletes. All athletes surveyed participated in one or more interscholastic sports. The prevalence of drug use by athletes compared to nonathletes was determined. Of the 19 drugs observed in this study, all were shown to have a lower prevalence of use among athletes in their senior year of high school, compared to the comparison group. Among the more commonly abused substances by the athlete population, beer, wine and whiskey, cigarettes, and marijuana were shown to have a lower use rate, by 25.5, 39.9, 57.5, and 57.7%, respectively. The prevalence of drug use by adolescent male athletes compared to adolescent nonathletes was also studied. Of the 19 individual drugs surveyed, all demonstrated a lower prevalence of use among athletes in their senior year of high school compared to the national data. The second high-risk activity measured was sexual activity. Of the athletes, 45.5% stated that they had never had sexual intercourse, compared to 50.0% of the nonathletes. Of the sexually active athletes, 81.9% had their first intercourse at between 13 and 15 years of age, whereas only 67.8% of the nonathlete control group had done so. This difference diminished significantly at age 16 and above. The results of this study suggest that participation in athletics by male athletes may lead to a significant decrease in drug and alcohol use and abuse but, also may increase early sexual contact. These trends were seen throughout all 4 years of high school in the athletes studied.

  18. Protecting military personnel from high risk dietary supplements.

    Science.gov (United States)

    Deuster, Patricia A; Lieberman, Harris R

    2016-01-01

    It is legal tomarketmost naturally occurring substances as dietary supplements in the USA without manufacturers demonstrating they are safe or effective, and an endless variety of ingredients, from esoteric botanicals to unapproved pharmaceuticals, can be found in dietary supplements. Use of certain supplements can pose a risk, but since a robust reporting systemdoes not exist in the USA it is difficult to know which are problematic and the number of adverse events (AE) resulting from their use. Certain populations, includingmilitary personnel, aremore likely to use dietary supplements than the general population. Approximately 70% of military personnel take dietary supplements while about 50% of civilians do. Service members prefer supplements purported to enhance physical performance such as supposedly natural stimulants, protein and amino acids, and combination products. Since some of thesemay be problematic, Servicemembers are probably at higher risk of injury than the general population. Ten percent of military populations appear to be taking potentially risky supplements, and the US Department of Defense (DoD) has taken variousmeasures to protect uniformed personnel including education, policy changes, and restricting sales. Actions taken include launching Operation Supplement Safety (OPSS), introducing a High Risk Supplement list, educating health care professionals on reporting AE thatmight be associated with dietary supplements, recommending policy for reporting AE, and developing an online AE reporting system. OPSS is a DoD-wide effort to educate service members, leaders, health care providers, military families, and retirees on how to safely select supplements

  19. Carotid stenosis: what is the high-risk population?

    Directory of Open Access Journals (Sweden)

    Jong Hun Park

    Full Text Available OBJECTIVE: Prevention is the best treatment for cerebrovascular disease, which is why early diagnosis and the immediate treatment of carotid stenosis contribute significantly to reducing the incidence of stroke. Given its silent nature, 80% of stroke cases occur in asymptomatic individuals, emphasizing the importance of screening individuals with carotid stenosis and identifying high-risk groups for the disease. The aim of this study was to determine the prevalence and the most frequent risk factors for carotid stenosis. METHODS: A transversal study was conducted in the form of a stroke prevention campaign held on three nonconsecutive Saturdays. During the sessions, carotid stenosis diagnostic procedures were performed for 500 individuals aged 60 years or older who had systemic arterial hypertension and/or diabetes mellitus and/or coronary heart disease and/or a family history of stroke. RESULTS: The prevalence of carotid stenosis in the population studied was 7.4%, and the most frequent risk factors identified were mean age of 70 years, carotid bruit, peripheral obstructive arterial disease, coronary insufficiency and smoking. Independent predictive factors of carotid stenosis include the presence of carotid bruit or peripheral obstructive heart disease and/or coronary insufficiency. CONCLUSIONS: The population with peripheral obstructive heart disease and carotid bruit should undergo routine screening for carotid stenosis.

  20. [Relevance of diabetes in high cardiovascular risk hypertensive patients].

    Science.gov (United States)

    Segura, Julián; de la Sierra, Alejandro; Fernández, Sandra; Ruilope, Luis M

    2013-10-05

    The aim of this cross-sectional study was to compare the prevalence of target organ damage (TOD) and established cardiovascular disease (CVD) in a cohort of nondiabetic hypertensive patients with 3 or more cardiovascular risk factors (CVRF) against a group of hypertensives with type 2 diabetes. We included 4,725 hypertensive patients, 62% male, mean age 64 (SD 12) years, with type 2 diabetes mellitus, independently of the number of associated CVRF (N=2,608), or non-diabetics, in which case we required the presence of 3 CVRF (N=2,117). The prevalence of established CVD (clinical interview) and TOD (left ventricular hypertrophy by electrocardiogram, microalbuminuria and estimated glomerular filtration rate) were estimated. Hypertensive patients with type 2 diabetes had an older age and more marked obesity. Furthermore, these patients showed a higher prevalence of micro- and macroalbuminuria, renal failure, left ventricular hypertrophy, atherosclerotic plaques in carotid arteries and CVD compared with nondiabetic hypertensive patients with 3 or more CVRF. Multivariate analysis showed that the risk of TOD or established CVD were associated independently with the presence of diabetes. Hypertensive patients with type 2 diabetes have a higher prevalence of LOD and CVD compared to nondiabetic hypertensive patients with 3 or more CVRF. Although both situations are included in the high cardiovascular risk stratum, it would be expected an increased incidence of cardiovascular complications in hypertensive diabetic patients. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  1. Pharmacological management of dyslipidemia in high and very high cardiovascular risk patients

    Directory of Open Access Journals (Sweden)

    V. Pascual Fuster

    Full Text Available Dyslipaemia is one of the main risk factors in the development of cardiovascular diseases. Currently, there are different alternatives available (amongst which statins occupy a pre-eminent place, to optimise the treatment of patients at high or very high cardiovascular risk. Despite this, the percentage of patients that achieve good lipid control is low. The causes of the mismatch with proposed objectives include lack of patient adherence and therapeutic inertia. This review uses available evidence and the latest clinical guides as a basis to assess the pharmacological treatment of dyslipaemia in patients with a background of arteriosclerotic vascular disease, diabetes, chronic kidney disease, cardiovascular risk at ≥5% calculated by SCORE and familial hypercholesterolaemia. The treatment of hypertriglyceridemia is also reviewed along with the special consideration that poly-pharmacy deserves in patients treated with statins, making mention of the treatment of dyslipaemia with HIV infection. The global assessment of cardiovascular risk is of high priority to adapt treatment to the specific objectives of the c-LDL for each risk category.

  2. Case Report: Myelodysplastic syndrome- associated myeloid sarcoma: an unusual clinical presentation of a rare disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Emoke Horvath

    2016-02-01

    Full Text Available Myeloid sarcoma results from the extramedullary homing and proliferation of immature myeloid precursors. We present the timeline, events and diagnostic pitfalls related to a 66 year-old male patient’s case, admitted to the Hematology Clinic for pancytopenia, fever, weight loss and fatigue. The severe cytopenia and the few blasts observed in his blood smear indicated a bone marrow biopsy. The bone marrow showed hypercellularity and multilineage dysplasia with the presence of 15% myeloblasts. After the biopsy, he promptly developed paraplegia and nuclear magnetic resonance revealed an epidural tumour which was then resected.In the epidural tumour mass blast-like, round cells were observed with a complex immunophenotype, characterized by myeloperoxidase, CD117, CD15, CD99, leucocyte common antigen positivity and a high Ki-67 proliferation index. Considering the main differential diagnostic issues, the final diagnosis was stated as myelodysplastic syndrome-associated myeloid sarcoma. The prognosis was unfavourable, the bone marrow was quickly invaded by proliferating blast cells, and despite chemotherapy attempts, the patient died.

  3. Reducing sexual risk behavior among high-risk couples in Northern India.

    Science.gov (United States)

    Jones, Deborah; Bagga, Rashmi; Nehra, Ritu; Deepika; Sethi, Sunil; Walia, Kamini; Kumar, Mahendra; Villar-Loubet, Olga; Lopez, Maria; Weiss, Stephen M

    2013-09-01

    With a population of 1.1 billion, India is considered to be a country in which effective prevention interventions could contain the development of a human immunodeficiency virus (HIV) epidemic. Heterosexual transmission accounts for 85 % of the extant HIV infections. This study sought to assess the feasibility of conducting a group, culturally tailored behavioral intervention and its impact on sexual barrier use, self-efficacy, knowledge, conflict resolution, and coping among high-risk heterosexual couples in Northern India. This pilot study was conducted at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India from February 2008 to January 2009. Thirty sexually active high-risk couples were drawn from a convenience sample of PGIMER patients attending infectious disease and family planning clinics. Couples participated in 1 month of three weekly gender-concordant behavioral intervention groups and were individually administered assessments preintervention and post-intervention. The intervention was tailored to the Northern Indian context and addressed sexual barrier use, human immunodeficiency virus (HIV)/sexually transmitted infection transmission, and cognitive behavioral skill building focusing on sexual negotiation and communication. The participants had a mean age of 32 years (men) and 29 years (women), and the majority had at least 10 years of education. At baseline, the majority reported inconsistent condom use (coping tactics. The results highlight the potential to successfully utilize a group intervention to discuss sensitive issues such as sexual risk behavior among both men and women. Strategies to improve condom use and communication without increasing intimate partner violence in high-risk couples may be an important adjunct to preventing the development of a generalized epidemic in India.

  4. High dislocation cumulative risk in THA versus hemiarthroplasty for fractures.

    Science.gov (United States)

    Poignard, Alexandre; Bouhou, Mohamed; Pidet, Olivier; Flouzat-Lachaniette, Charles-Henri; Hernigou, Philippe

    2011-11-01

    Although not all elderly patients with femoral neck fractures are candidates for THA, active, mentally competent, independent patients achieve the most durable functional scores with THA compared with hemiarthroplasty. However, a relatively high frequency of early or late dislocation could reduce the potential benefits with THA. We asked whether the incidence of first-time, recurrent dislocation, and revision differed in patients with hip fractures having THA or hemiarthroplasty. We retrospectively reviewed 380 patients with hip fractures (380 hips) who underwent THAs between 1995 and 1999, and compared them with 412 patients with hip fractures (412 hips) who underwent hemiarthroplasties between 1990 and 1994. The mean followup was 8 years (range, 1-20 years). THA had a higher early risk of first-time dislocation and a higher late risk: 19 (4.5%) of the 412 hips treated with hemiarthroplasty had at least one dislocation whereas 30 (8.1%) of the 380 hips treated with THA had at least one dislocation. The cumulative number of dislocations at the most recent followup (first time and recurrent dislocations) was 58 (13%) for the 380 THAs and 22 (5%) for the 412 hemiarthroplasties. At the 10-year followup, eight THAs (2%) had revision (six recurrent dislocations, two loosenings), and 42 hemiarthroplasties (10%) had revision (40 acetabular protrusions, one recurrent dislocation). The risk of revision for recurrent dislocation increases with THA, but it remains lower than the risk of revision for wear of cartilage and acetabular protrusion in hemiarthroplasty. Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

  5. Risk factors associated with developmental abnormalities among high-risk children attended at a multidisciplinary clinic.

    Science.gov (United States)

    Resegue, Rosa; Puccini, Rosana Fiorini; Silva, Edina Mariko Koga da

    2008-01-02

    Knowledge of risk factors associated with child development disorders is essential for delivering high-quality childcare. The objective here was to evaluate the relationships between risk factors and occurrences of developmental abnormalities among children attended at a reference clinic for children at risk of developmental abnormalities. Retrospective study at a multidisciplinary reference center, Embu, São Paulo. All cases followed up for more than three months between 1995 and 2003 were reviewed. The risk factors assessed were low birth weight, gestational age, length of stay in neonatal ward, perinatal asphyxia, mothers age 5 days, prematurity and mothers age 18 years and older. Low birth weight, history of perinatal asphyxia and mothers age continued to be significant in multivariate analysis. Special attention must be paid to the development of low birth weight infants and/or infants with histories of neonatal complications. Low birth weight is easily assessed and should be considered to be an important marker when defining guidelines for following up child development.

  6. Risk factors associated with developmental abnormalities among high-risk children attended at a multidisciplinary clinic

    Directory of Open Access Journals (Sweden)

    Rosa Resegue

    Full Text Available CONTEXT AND OBJECTIVE: Knowledge of risk factors associated with child development disorders is essential for delivering high-quality childcare. The objective here was to evaluate the relationships between risk factors and occurrences of developmental abnormalities among children attended at a reference clinic for children at risk of developmental abnormalities. DESIGN AND SETTING: Retrospective study at a multidisciplinary reference center, Embu, São Paulo. METHODS: All cases followed up for more than three months between 1995 and 2003 were reviewed. The risk factors assessed were low birth weight, gestational age, length of stay in neonatal ward, perinatal asphyxia, mother’s age 5 days, prematurity and mother’s age 18 years and older. Low birth weight, history of perinatal asphyxia and mother’s age continued to be significant in multivariate analysis. CONCLUSIONS: Special attention must be paid to the development of low birth weight infants and/or infants with histories of neonatal complications. Low birth weight is easily assessed and should be considered to be an important marker when defining guidelines for following up child development.

  7. Characterizing and reaching high-risk drinkers using audience segmentation.

    Science.gov (United States)

    Moss, Howard B; Kirby, Susan D; Donodeo, Fred

    2009-08-01

    Market or audience segmentation is widely used in social marketing efforts to help planners identify segments of a population to target for tailored program interventions. Market-based segments are typically defined by behaviors, attitudes, knowledge, opinions, or lifestyles. They are more helpful to health communication and marketing planning than epidemiologically defined groups because market-based segments are similar in respect to how they behave or might react to marketing and communication efforts. However, market segmentation has rarely been used in alcohol research. As an illustration of its utility, we employed commercial data that describes the sociodemographic characteristics of high-risk drinkers as an audience segment, including where they tend to live, lifestyles, interests, consumer behaviors, alcohol consumption behaviors, other health-related behaviors, and cultural values. Such information can be extremely valuable in targeting and planning public health campaigns, targeted mailings, prevention interventions, and research efforts. We described the results of a segmentation analysis of those individuals who self-reported to consume 5 or more drinks per drinking episode at least twice in the last 30 days. The study used the proprietary PRIZM (Claritas, Inc., San Diego, CA) audience segmentation database merged with the Center for Disease Control and Prevention's (CDC) Behavioral Risk Factor Surveillance System (BRFSS) database. The top 10 of the 66 PRIZM audience segments for this risky drinking pattern are described. For five of these segments we provided additional in-depth details about consumer behavior and the estimates of the market areas where these risky drinkers resided. The top 10 audience segments (PRIZM clusters) most likely to engage in high-risk drinking are described. The cluster with the highest concentration of binge-drinking behavior is referred to as the "Cyber Millenials." This cluster is characterized as "the nation's tech

  8. Physical performance following acute high-risk abdominal surgery

    DEFF Research Database (Denmark)

    Jønsson, Line Rokkedal; Ingelsrud, Lina Holm; Tengberg, Line Toft

    2018-01-01

    BACKGROUND: Acute high-risk abdominal (AHA) surgery is associated with high mortality, multiple postoperative complications and prolonged hospital stay. Further development of strategies for enhanced recovery programs following AHA surgery is needed. The aim of this study was to describe physical...... with regards to physical performance, using the Cumulated Ambulation Score (CAS; 0-6 points) to assess basic mobility and the activePAL monitor to assess the 24-hour physical activity level. We recorded barriers to independent mobilization. RESULTS: Fifty patients undergoing AHA surgery (mean age 61.4 ± 17...... for a median of 23.4 hours daily during the first week after AHA surgery, and the main barriers to independent mobilization were fatigue and abdominal pain. CONCLUSION: Patients who receive AHA surgery have very limited physical performance in the first postoperative week. Barriers to independent mobilization...

  9. 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.

  10. Neurophysiology for Detection of High Risk for Psychosis

    Directory of Open Access Journals (Sweden)

    Lara N. Pantlin

    2016-01-01

    Full Text Available Schizophrenia is a complex and often disabling disorder that is characterized by a wide range of social, emotional, and cognitive deficits. Increasing research suggests that the greatest social and cognitive therapeutic impact comes from early identification. The present study applied a well-established neurophysiological paradigm in the schizophrenia literature, mismatch negativity (MMN, to college students identified as high risk (HR for psychosis to investigate MMN as a potential biomarker for the onset of psychosis. The hypothesis was that HR would exhibit attenuated MMN amplitudes compared to controls, as has been established in individuals with chronic schizophrenia. Participants (N=121 were separated into Group 1 (controls (n1=72 and Group 2 (HR (n2=49 based on the established cutoff score of the 16-item Prodromal Questionnaire. Participants then completed a time based MMN paradigm during which brain activity was recorded with EEG. For all electrode locations, controls demonstrated significantly more negative amplitudes than HR (Cz: F(1,119=8.09, p=.005; Fz: F(1,119=5.74, p=.018; Pz: F(1,119=5.88, p=.017. Results suggested that MMN may assist in identifying those who appear high-functioning but may be at risk for later development of psychosis or cognitive and psychological difficulties associated with psychosis.

  11. Uncertainty Instability Risk Analysis of High Concrete Arch Dam Abutments

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    Xin Cao

    2017-01-01

    Full Text Available The uncertainties associated with concrete arch dams rise with the increased height of dams. Given the uncertainties associated with influencing factors, the stability of high arch dam abutments as a fuzzy random event was studied. In addition, given the randomness and fuzziness of calculation parameters as well as the failure criterion, hazard point and hazard surface uncertainty instability risk ratio models were proposed for high arch dam abutments on the basis of credibility theory. The uncertainty instability failure criterion was derived through the analysis of the progressive instability failure process on the basis of Shannon’s entropy theory. The uncertainties associated with influencing factors were quantized by probability or possibility distribution assignments. Gaussian random theory was used to generate random realizations for influence factors with spatial variability. The uncertainty stability analysis method was proposed by combining the finite element analysis and the limit equilibrium method. The instability risk ratio was calculated using the Monte Carlo simulation method and fuzzy random postprocessing. Results corroborate that the modeling approach is sound and that the calculation method is feasible.

  12. High-Risk Human Papillomavirus Targets Crossroads in Immune Signaling

    Science.gov (United States)

    Tummers, Bart; Van Der Burg, Sjoerd H.

    2015-01-01

    Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review. PMID:26008697

  13. [High oncogenic risk human papillomavirus and urinary bladder cancer].

    Science.gov (United States)

    Loran, O B; Sinyakova, L A; Gundorova, L V; Kosov, V A; Kosova, I V; Pogodina, I E; Kolbasov, D N

    2017-07-01

    To determine the role of human papillomavirus (HPV) of high oncogenic risk in the development of urinary bladder cancer. 100 patients (72 men and 28 women) aged 38 to 90 years (mean age 65+/-10 years) diagnosed with bladder cancer were examined and underwent treatment. Clinical assessment was complemented by enzyme-linked immunosorbent assays for the presence of antiviral antibodies to herpes simplex virus (HSV) type 1 and type 2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), urethra scraping for detecting high oncogenic risk HPV. Tumor tissue was sampled for PCR virus detection. Semi-quantitative analysis was used to evaluate the components of lymphocyte-plasmocyte and leukocyte infiltrates and cytopathic changes in tumor tissue. There were positive correlations between cytopathic cell changes (koylocytosis and intranuclear inclusions, as manifestations of HPV) and the level of antiviral antibodies, the presence of viruses in the tumor, as well as with the components of the lymphoid-plasmocyte infiltrate. Negative correlations were found between the presence of papillomatosis and the above changes. Human papillomavirus is believed to be a trigger for the initiation of a tumor in young patients with a latent infection (CMV and EBV, HSV, HPV). Cytopathic changes (kylocytosis and intranuclear inclusions) were associated with the activity and morphological features of herpes-viral infections. Their degree varied depending on the stage of the process, but not on the anaplasia degree. Papillomatosis is associated with a more favorable course of the tumor process.

  14. High-Risk Human Papillomavirus Targets Crossroads in Immune Signaling

    Directory of Open Access Journals (Sweden)

    Bart Tummers

    2015-05-01

    Full Text Available Persistent infections with a high-risk type human papillomavirus (hrHPV can progress to cancer. High-risk HPVs infect keratinocytes (KCs and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review.

  15. High-risk human papillomavirus targets crossroads in immune signaling.

    Science.gov (United States)

    Tummers, Bart; Burg, Sjoerd H Van Der

    2015-05-21

    Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review.

  16. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma.

    Science.gov (United States)

    Mateos, María-Victoria; Hernández, Miguel-Teodoro; Giraldo, Pilar; de la Rubia, Javier; de Arriba, Felipe; López Corral, Lucía; Rosiñol, Laura; Paiva, Bruno; Palomera, Luis; Bargay, Joan; Oriol, Albert; Prosper, Felipe; López, Javier; Olavarría, Eduardo; Quintana, Nuria; García, José-Luis; Bladé, Joan; Lahuerta, Juan-José; San Miguel, Jesús-F

    2013-08-01

    For patients with smoldering multiple myeloma, the standard of care is observation until symptoms develop. However, this approach does not identify high-risk patients who may benefit from early intervention. In this randomized, open-label, phase 3 trial, we randomly assigned 119 patients with high-risk smoldering myeloma to treatment or observation. Patients in the treatment group received an induction regimen (lenalidomide at a dose of 25 mg per day on days 1 to 21, plus dexamethasone at a dose of 20 mg per day on days 1 to 4 and days 12 to 15, at 4-week intervals for nine cycles), followed by a maintenance regimen (lenalidomide at a dose of 10 mg per day on days 1 to 21 of each 28-day cycle for 2 years). The primary end point was time to progression to symptomatic disease. Secondary end points were response rate, overall survival, and safety. After a median follow-up of 40 months, the median time to progression was significantly longer in the treatment group than in the observation group (median not reached vs. 21 months; hazard ratio for progression, 0.18; 95% confidence interval [CI], 0.09 to 0.32; Psmoldering myeloma delays progression to active disease and increases overall survival. (Funded by Celgene; ClinicalTrials.gov number, NCT00480363.).

  17. Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study.

    Science.gov (United States)

    Rogers, Heesun J; Vardiman, James W; Anastasi, John; Raca, Gordana; Savage, Natasha M; Cherry, Athena M; Arber, Daniel; Moore, Erika; Morrissette, Jennifer J D; Bagg, Adam; Liu, Yen-Chun; Mathew, Susan; Orazi, Attilio; Lin, Pei; Wang, Sa A; Bueso-Ramos, Carlos E; Foucar, Kathryn; Hasserjian, Robert P; Tiu, Ramon V; Karafa, Matthew; Hsi, Eric D

    2014-05-01

    Acute myeloid leukemia and myelodysplastic syndrome with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) have a poor prognosis. Indeed, the inv(3)(q21q26.2)/t(3;3)(q21;q26.2) has been recognized as a poor risk karyotype in the revised International Prognostic Scoring System. However, inv(3)(q21q26.2)/t(3;3)(q21;q26.2) is not among the cytogenetic abnormalities pathognomonic for diagnosis of acute myeloid leukemia irrespective of blast percentage in the 2008 WHO classification. This multicenter study evaluated the clinico-pathological features of acute myeloid leukemia/myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and applied the revised International Prognostic Scoring System to myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2). A total of 103 inv(3)(q21q26.2)/t(3;3)(q21;q26.2) patients were reviewed and had a median bone marrow blast count of 4% in myelodysplastic syndrome (n=40) and 52% in acute myeloid leukemia (n=63) (Pmyeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) (12.9 vs. 7.9 months; P=0.16). Eighty-three percent of patients died (median follow up 7.9 months). Complex karyotype, monosomal karyotype and dysgranulopoiesis (but not blast percentage) were independent poor prognostic factors in the entire cohort on multivariable analysis. The revised International Prognostic Scoring System better reflected overall survival of inv(3)(q21q26.2)/t(3;3)(q21;q26.2) than the International Prognostic Scoring System but did not fully reflect the generally dismal prognosis. Our data support consideration of myelodysplastic syndrome with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) as an acute myeloid leukemia with recurrent genetic abnormalities, irrespective of blast percentage.

  18. Management of dyslipidemia in the high-risk patient.

    Science.gov (United States)

    Stein, Evan A

    2002-12-01

    Lipid-lowering agents have been shown to reduce morbidity and mortality associated with coronary heart disease (CHD), particularly in high-risk patients. The identification and treatment of these patients should therefore be a high priority for clinicians. Guidelines from medical organizations, such as the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) and the American Diabetes Association (ADA), suggest that patients with low-density lipoprotein cholesterol (LDL-C) levels > or =130 mg/dL, and perhaps even those with levels > or =100 mg/dL, should receive drug therapy. Optimal LDL-C levels have been set at European guidelines, respectively. However, a recent survey shows that only about 20% of high-risk patients currently meet these goals. In order to achieve therapeutic targets for LDL-C, the statins are the foundation of treatment, as they are the most effective and best-tolerated form of lipid-lowering therapy. Other therapeutic options include bile acid sequestrants, niacin, and plant stanols, although seldom as monotherapy. Combination therapy with a statin and one of these other lipid-lowering agents can be useful in patients who are unable to achieve target lipid levels through monotherapy. There remains, however, a need for additional agents. Some of the new options for reducing LDL-C levels that may be available in the near future include 2 new statins, pitavastatin and rosuvastatin. In patients with heterozygous familial hypercholesterolemia, rosuvastatin, which is currently under review by the Food and Drug Administration (FDA), has been shown to produce significantly greater reductions in LDL-C than atorvastatin over its full dose range. In comparative clinical trials, it has also enabled more patients with primary hypercholesterolemia to meet lipid goals than atorvastatin, simvastatin, and pravastatin. Inhibitors of bile acid transport or cholesterol absorption may also have therapeutic value. The first cholesterol absorption

  19. Distinct evolutionary mechanisms for genomic imbalances in high-risk and low-risk neuroblastomas

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    Øra Ingrid

    2007-01-01

    Full Text Available Abstract Background Neuroblastoma (NB is the most common extracranial solid tumour of childhood. Several genomic imbalances correlate to prognosis in NB, with structural rearrangements, including gene amplification, in a near-diploid setting typically signifying high-risk tumours and numerical changes in a near-triploid setting signifying low-risk tumours. Little is known about the temporal sequence in which these imbalances occur during the carcinogenic process. Methods We have reconstructed the appearance of cytogenetic imbalances in 270 NBs by first grouping tumours and imbalances through principal component analysis and then using the number of imbalances in each tumour as an indicator of evolutionary progression. Results Tumours clustered in four sub-groups, dominated respectively by (1 gene amplification in double minute chromosomes and few other aberrations, (2 gene amplification and loss of 1p sequences, (3 loss of 1p and other structural aberrations including gain of 17q, and (4 whole-chromosome gains and losses. Temporal analysis showed that the structural changes in groups 1–3 were acquired in a step-wise fashion, with loss of 1p sequences and the emergence of double minute chromosomes as the earliest cytogenetic events. In contrast, the gains and losses of whole chromosomes in group 4 occurred through multiple simultaneous events leading to a near-triploid chromosome number. Conclusion The finding of different temporal patterns for the acquisition of genomic imbalances in high-risk and low-risk NBs lends strong support to the hypothesis that these tumours are biologically diverse entities, evolving through distinct genetic mechanisms.

  20. A Highly Predictive Risk Model for Pacemaker Implantation After TAVR.

    Science.gov (United States)

    Maeno, Yoshio; Abramowitz, Yigal; Kawamori, Hiroyuki; Kazuno, Yoshio; Kubo, Shunsuke; Takahashi, Nobuyuki; Mangat, Geeteshwar; Okuyama, Kazuaki; Kashif, Mohammad; Chakravarty, Tarun; Nakamura, Mamoo; Cheng, Wen; Friedman, John; Berman, Daniel; Makkar, Raj R; Jilaihawi, Hasan

    2017-10-01

    This study sought to develop a robust and definitive risk model for new permanent pacemaker implantation (PPMI) after SAPIEN 3 (third generation balloon expandable valve) (Edwards Lifesciences, Irvine, California) transcatheter aortic valve replacement (third generation balloon expandable valve TAVR), including calcification in the aortic-valvular complex (AVC). The association between calcium in the AVC and need for PPMI is poorly delineated after third generation balloon expandable valve TAVR. At Cedars-Sinai Heart Institute in Los Angeles, California, a total of 240 patients with severe aortic stenosis underwent third generation balloon expandable valve TAVR and had contrast computed tomography. AVC was characterized precisely by leaflet sector and region. The total new PPMI rate was 14.6%. On multivariate analysis for predictors of PPMI, pre-procedure third generation balloon expandable valve TAVR, right bundle branch block (RBBB), shorter membranous septum (MS) length, and noncoronary cusp device-landing zone calcium volume (NCC-DLZ CA) were included. Predictive probabilities were generated using this logistic regression model. If 3 pre-procedural risk factors were present, the c-statistic of the model for PPMI was area under the curve of 0.88, sensitivity of 77.1%, and specificity of 87.1%; this risk model had high negative predictive value (95.7%). The addition of the procedural factor of device depth to the model, with the parameter of difference between implantation depth and MS length, combined with RBBB and NCC-DLZ CA increased the c-statistic to 0.92, sensitivity to 94.3%, specificity to 83.8%, and negative predictive value to 98.8% CONCLUSIONS: By using a precise characterization of distribution of calcification in the AVC in a single-center, retrospective study, NCC-DLZ CA was found to be an independent predictor of new PPMI post-third generation balloon expandable valve TAVR. The findings also reinforce the importance of short MS length, pre

  1. High risk of unprecedented UK rainfall in the current climate.

    Science.gov (United States)

    Thompson, Vikki; Dunstone, Nick J; Scaife, Adam A; Smith, Doug M; Slingo, Julia M; Brown, Simon; Belcher, Stephen E

    2017-07-24

    In winter 2013/14 a succession of storms hit the UK leading to record rainfall and flooding in many regions including south east England. In the Thames river valley there was widespread flooding, with clean-up costs of over £1 billion. There was no observational precedent for this level of rainfall. Here we present analysis of a large ensemble of high-resolution initialised climate simulations to show that this event could have been anticipated, and that in the current climate there remains a high chance of exceeding the observed record monthly rainfall totals in many regions of the UK. In south east England there is a 7% chance of exceeding the current rainfall record in at least one month in any given winter. Expanding our analysis to some other regions of England and Wales the risk increases to a 34% chance of breaking a regional record somewhere each winter.A succession of storms during the 2013-2014 winter led to record flooding in the UK. Here, the authors use high-resolution climate simulations to show that this event could have been anticipated and that there remains a high chance of exceeding observed record monthly rainfall totals in many parts of the UK.

  2. HPV vaccine acceptability in high-risk Greek men.

    Science.gov (United States)

    Hoefer, Lea; Tsikis, Savas; Bethimoutis, George; Nicolaidou, Electra; Paparizos, Vassilios; Antoniou, Christina; Kanelleas, Antonios; Chardalias, Leonidas; Stavropoulos, Georgios-Emmanouil; Schneider, John; Charnot-Katsikas, Angella

    2017-09-22

    HPV is associated with malignancy in men, yet there is a lack of data on HPV knowledge, vaccine acceptability, and factors affecting vaccine acceptability in Greek men. This study aims to identify determinants of knowledge and willingness to vaccinate against HPV among high-risk Greek men. Men (n = 298) between the ages of 18 and 55 were enrolled from the STI and HIV clinics at "Andreas Syggros" Hospital in Athens, Greece from July-October 2015. Participants completed a survey on demographics, economic factors, sexual history, HPV knowledge, and vaccine acceptability. The majority of participants were younger than 40 (76.6%) and unmarried (84.6%). Our sample was 31.2% MSM (men who have sex with men), and 20.1% were HIV-positive. Most participants (>90%) were aware that HPV is highly prevalent in both men and women; however, fewer identified that HPV causes cancers in both sexes (68%) and that vaccination protects men and women (67%). Amongst participants, 76.7% were willing to vaccinate themselves against HPV, 71.4% an adolescent son, and 69.3% an adolescent daughter. HIV-positive men were more likely to be willing to vaccinate themselves (OR 2.83, p = .015), a son (OR 3.3, p = .015) or a daughter (3.01, p = .020). Higher income levels were associated with increased willingness to vaccinate oneself (OR 1.32, p = .027), a son (1.33, p = .032) or daughter (1.34, p = .027). Although there is a HPV knowledge gap, HPV vaccine acceptability is high despite lack of vaccine promotion to Greek men. Future studies should include lower-risk men to adequately inform public health efforts.

  3. Jacobsen distal 11q deletion syndrome with a myelodysplastic change of hemopoietic cells.

    Science.gov (United States)

    Lin, J H; Hou, J W; Teng, R J; Tien, H F; Lin, K H

    1998-02-03

    We describe a male infant with unusual facial appearance, relative pancytopenia, bilateral simian creases, and an accessory nipple. Cytogenetic analysis showed deletion of the long arm of chromosome 11 [46,XY,del(11)(pter-->q23.2:)]. Bone-marrow study showed a myelodysplastic change of hemopoietic cells compatible with peripheral blood findings. Pachygyria of the temporal and frontal lobes was demonstrated by magnetic resonance image (MRI) of the brain. We present our findings in order to contribute to the information on 11q23 deletion.

  4. An Analysis of MicroRNA Expression in the Myelodysplastic Syndromes Using Hematopoietic Stem Cells

    Science.gov (United States)

    2015-10-01

    predisposition for the development of MDS. 15. SUBJECT TERMS MicroRNAs, the myelodysplastic syndromes, hematopoietic stem cells...hematopoietic  stem  cells  (HSCs),  demonstrating   the  presence  of  disease  associated  cytogenetic  and  molecular   genetic ...hematopoiesis   in   the   context   of   aging   and   its   likely   implication   in   the   age-­‐related   predisposition

  5. YKL-40 in allogeneic hematopoietic cell transplantation after AML and myelodysplastic syndrome

    DEFF Research Database (Denmark)

    Kornblit, Brian; Wang, T; Lee, S J

    2016-01-01

    YKL-40, also called chitinase-3-like-1 protein, is an inflammatory biomarker that has been associated with disease severity in inflammatory and malignant diseases, including AML, multiple myeloma and lymphomas. The objective of the current study was to assess the prognostic value of pretransplant...... recipient and donor plasma YKL-40 concentrations in patients with AML (n=624) or myelodysplastic syndrome (n=157) treated with allogeneic hematopoietic cell transplantation (HCT). In recipients, the plasma YKL-40 concentrations were increased when the HCT-comorbidity index was ⩾5 (P=0.028). There were...

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

    Directory of Open Access Journals (Sweden)

    Jacob D. Kjelland

    2017-01-01

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

  7. Speech therapy procedures in high-risk newborns

    Directory of Open Access Journals (Sweden)

    Hipólito Virgílio Magalhães Júnior

    2010-06-01

    Full Text Available Objective: To investigate the speech therapy procedures performed in a neonatal ICU. Methods: A documental research based on registration records, comprised by a total of 34 newborns that required early stimulation by the speech therapy service in a neonatal ICU of a hospital with tertiary level of care. The study was held in the period between August, 2005 and January, 2006. From the sample, 14 children were female (41.2% and 20 were male (58.8%. The age of the newborns ranged from 3 to 57 life days. The studied variables included: risk conditions of the newborn, clinical assessment procedures, the intervention performed and the results obtained regarding weight. Results: The risk condition of preterm newborn (PTNB associated with respiratory distress syndrome (RDS was present in 25 (73.5% children. The initial weight of 15 (44.11% children ranged from 1170 to 1742 grams. The most widely discussed speech therapy procedures were the assessment of oral functions with identification of changes in sucking and swallowing in 25 (73.5% newborns and intervention by means of non-nutritive sucking in 18 (53% children. At the end of speech therapy, 19 (55.9% children weighed between 1742 to 2314 grams. Conclusions:The benefits of speech therapy performance were related to the identification of high-risk children who required intervention in oral functions and organization of the baby for feeding. It is assumed that the introduction of oral administration as quickly and safely as possible favored the improvement of the nutritional status of children and their clinical evolution

  8. Risk assessment of desert pollution on composite high voltage insulators.

    Science.gov (United States)

    El-Shahat, Mohammed; Anis, Hussein

    2014-09-01

    Transmission lines located in the desert are subjected to desert climate, one of whose features is sandstorms. With long accumulation of sand and with the advent of moisture from rain, ambient humidity and dew, a conductive layer forms and the subsequent leakage current may lead to surface discharge, which may shorten the insulator life or lead to flashover thus interrupting the power supply. Strategically erected power lines in the Egyptian Sinai desert are typically subject to such a risk, where sandstorms are known to be common especially in the spring. In view of the very high cost of insulator cleaning operation, composite (silicon rubber) insulators are nominated to replace ceramic insulators on transmission lines in Sinai. This paper examines the flow of leakage current on sand-polluted composite insulators, which in turn enables a risk assessment of insulator failure. The study uses realistic data compiled and reported in an earlier research project about Sinai, which primarily included grain sizes of polluting sand as well as their salinity content. The paper also uses as a case study an ABB-designed composite insulator. A three-dimensional finite element technique is used to simulate the insulator and seek the potential and electric field distribution as well as the resulting leakage current flow on its polluted surface. A novel method is used to derive the probabilistic features of the insulator's leakage current, which in turn enables a risk assessment of insulator failure. This study is expected to help in critically assessing - and thus justifying - the use of this type of insulators in Sinai and similar critical areas.

  9. Risk assessment of desert pollution on composite high voltage insulators

    Directory of Open Access Journals (Sweden)

    Mohammed El-Shahat

    2014-09-01

    Full Text Available Transmission lines located in the desert are subjected to desert climate, one of whose features is sandstorms. With long accumulation of sand and with the advent of moisture from rain, ambient humidity and dew, a conductive layer forms and the subsequent leakage current may lead to surface discharge, which may shorten the insulator life or lead to flashover thus interrupting the power supply. Strategically erected power lines in the Egyptian Sinai desert are typically subject to such a risk, where sandstorms are known to be common especially in the spring. In view of the very high cost of insulator cleaning operation, composite (silicon rubber insulators are nominated to replace ceramic insulators on transmission lines in Sinai. This paper examines the flow of leakage current on sand-polluted composite insulators, which in turn enables a risk assessment of insulator failure. The study uses realistic data compiled and reported in an earlier research project about Sinai, which primarily included grain sizes of polluting sand as well as their salinity content. The paper also uses as a case study an ABB-designed composite insulator. A three-dimensional finite element technique is used to simulate the insulator and seek the potential and electric field distribution as well as the resulting leakage current flow on its polluted surface. A novel method is used to derive the probabilistic features of the insulator’s leakage current, which in turn enables a risk assessment of insulator failure. This study is expected to help in critically assessing – and thus justifying – the use of this type of insulators in Sinai and similar critical areas.

  10. Contraception: Efficacy, Risks, Continuation Rates, and Use in High-Risk Women.

    Science.gov (United States)

    Batur, Pelin; Bowersox, Natalie; McNamara, Megan

    2016-08-01

    The clinical update serves as a brief review of recently published, high-impact, and potentially practice-changing journal articles summarized for our readers. Topics include menopause, sexual dysfunction, breast health, contraception, osteoporosis, and cardiovascular disease. In this clinical update, we selected recent publications relevant to the use of contraceptive methods. We highlight articles on continuation rates of long-acting reversible contraception versus nonlong-acting methods, updated risks of intrauterine devices, use of estrogen-containing contraceptives during anticoagulation for venous thromboembolic events, and the efficacy of oral and emergency contraception in women with elevated body mass index.

  11. High-risk biodegradable waste processing by alkaline hydrolysis.

    Science.gov (United States)

    Kalambura, Sanja; Voća, Neven; Krička, Tajana; Sindrak, Zoran; Spehar, Ana; Kalambura, Dejan

    2011-09-01

    Biodegradable waste is by definition degraded by other living organisms. Every day, meat industry produces large amounts of a specific type of biodegradable waste called slaughterhouse waste. Traditionally in Europe, this waste is recycled in rendering plants which produce meat and bone meal and fat. However, feeding animals with meat and bone meal has been banned since the outbreaks of bovine spongiform encephalopathy (BSE). In consequence, new slaughterhouse waste processing technologies have been developed, and animal wastes have now been used for energy production. Certain parts of this waste, such as brains and spinal cord, are deemed high-risk substances, because they may be infected with prions. Their treatment is therefore possible only in strictly controlled conditions. One of the methods which seems to bear acceptable health risk is alkaline hydrolysis. This paper presents the results of an alkaline hydrolysis efficiency study. It also proposes reuse of the obtained material as organic fertiliser, as is suggested by the analytical comparison between meat and bone meal and hydrolysate.

  12. High-risk bladder cancer: improving outcomes with perioperative chemotherapy

    Directory of Open Access Journals (Sweden)

    Daniel Y.C. Heng

    2011-12-01

    Full Text Available Despite treatment with radical cystectomy and pelvic lymph node dissection, muscle invasive bladder cancer has a relapse rate of 50%. Patients can develop regionally advanced or metastatic disease that ultimately leads to death. The addition of neoadjuvant or adjuvant chemotherapy to reduce the risk of relapse and death has been extensively studied over the past two decades. Two contemporary trials coupled with a recent meta-analysis evaluating neoadjuvant chemotherapy demonstrated a modest but real improvement in overall survival. This has made neoadjuvant chemotherapy a standard of care. Clinical trials evaluating adjuvant chemotherapy in patients with high-risk disease have been plagued with statistical flaws and have, therefore, been unable to define the survival impact of this approach. It is hoped that ongoing adjuvant trials that are powered to detect small but meaningful clinical differences will clarify the benefit of chemotherapy after cystectomy. Since there are theoretical advantages and disadvantages to each of these approaches, both are widely used in North America. The evidence behind each approach and potential future developments in this field will be described.

  13. High salivary estrogen and risk of developing pregnancy gingivitis.

    Science.gov (United States)

    Gürsoy, Mervi; Gürsoy, Ulvi Kahraman; Sorsa, Timo; Pajukanta, Riitta; Könönen, Eija

    2013-09-01

    Estrogen regulates the cellular functions of several tissues that may disturb the host response against bacteria. The present aim is to evaluate the contribution of estrogen to the severity of gingival inflammation during pregnancy. Salivary estrogen levels from 30 pregnant and 24 non-pregnant females were related to their periodontal health parameters, including visible plaque index (VPI) and bleeding on probing (BOP) from six sites per tooth. The pregnant group was examined three times during pregnancy and twice during postpartum, and the non-pregnant group was examined three times, once per subsequent month. Salivary estrogen levels increased significantly during the second (P high estrogen and high VPI levels had the highest frequency of pregnancy gingivitis. During the second and third trimesters, simultaneously enhanced estrogen levels and VPI scores brought an additional risk of developing gingivitis compared with a high VPI score alone. The present findings suggest that, during pregnancy, the estrogen level determines the magnitude of gingival inflammation developed against microbial plaque at the gingival margin.

  14. Chagas disease, a risk factor for high blood pressure.

    Science.gov (United States)

    Vicco, Miguel Hernán; Rodeles, Luz; Yódice, Agustina; Marcipar, Iván

    2014-12-01

    Chagas disease is a parasite infection caused by the protozoan Trypanosoma cruzi. Its most common complications is chronic Chagas heart disease but impairments of the systemic vasculature also has been observed. Although the different mechanisms that regulate blood pressure are disrupted, to our knowledge data on the association of hypertension and chronic Chagas disease are scarce. In this regard we evaluate whether Chagas disease constitutes a high blood pressure risk factor. We recruited 200 individuals, half of them with positive serology for T. cruzi. They were subjected to a complete clinical examination. The mean age of sampled individuals was 46.7 ± 12.3, and the mean of systolic and diastolic blood pressure were 124 ± 12 mmHg and 82 ± 10 mmHg, respectively. There were no between-group differences regarding age, sex distribution or body mass index. Chagas disease contributed significantly to high blood pressure (OR = 4, 95% CI 1.8323-7.0864, p = 0.0002). Our results reveal an important association between Chagas disease and high blood pressure, which should be contemplated by physicians in order to promote preventive cardiovascular actions in patients with Chagas disease.

  15. Characteristics of Violence among High Risk Adolescent Girls

    Science.gov (United States)

    Secor-Turner, Molly; Garwick, Ann; Sieving, Renee; Seppelt, Ann

    2013-01-01

    Introduction Recent evidence demonstrates increasing rates of violence involvement among adolescent girls. The objective of this study was to describe the types and sources of violence experienced within social contexts of adolescent girls at high risk for pregnancy. Method Qualitative data for this analysis are drawn from intervention summary reports of 116 girls participating in Prime Time, a youth development intervention for adolescent girls. Descriptive content analysis techniques were used to identify types and sources of violence experienced by girls within their daily contexts. Results Types of violence included physical fighting, witnessing violence, physical abuse, gang-related violence, verbal fighting, verbal abuse and sexual abuse. Sources of violence included family, peers and friends, romantic partners, community violence, and self-perpetrated. Many girls in this study experienced violence in multiple contexts. Discussion It is imperative that efforts to assess and prevent violence among adolescent girls pay attention to the social contexts in which these adolescents live. PMID:23623540

  16. Condom availability in high risk places and condom use

    DEFF Research Database (Denmark)

    Sandøy, Ingvild Fossgard; Blystad, Astrid; Shayo, Elizabeth H.

    2012-01-01

    and one in Zambia. The study was based on a triangulation of data collection methods in the three study districts: surveys in venues where people meet new sexual partners, population-based surveys and focus group discussions. The data was collected within an overall study on priority setting in health...... systems. Results At the time of the survey, condoms were observed in less than half of the high risk venues in two of the three districts and in 60% in the third district. Rural respondents in the population-based surveys perceived condoms to be less available and tended to be less likely to report condom......, its priority relative to other HIV/AIDS measures must be reassessed locally, nationally and regionally. In practical terms very clear supply chains of condoms to both formal and informal drinking places could make condom provision better and more reliable...

  17. College students' high-risk sexual behavior following alcohol consumption.

    Science.gov (United States)

    Anderson, P B; Mathieu, D A

    1996-01-01

    This study is a follow-up to a previous study assessing the relationship of alcohol consumption as a disinhibitor to high-risk sexual behavior. Results are based on survey data from 1,902 students attending 12 colleges. Sexual behaviors occurring after people had "let themselves drink more than normal in order to make it easier for them to have sex with someone" were assessed. At least once in the past year, 33.2% of the men and 17.4% of the women had met this criterion. In those instances, 76.3% of the men and 77.1% of the women initiated condom use for vaginal intercourse. Results are discussed in relation to partners' compliance following condom initiation and preventing the spread of HIV disease.

  18. Cyberbullying in those at Clinical High Risk for psychosis

    Science.gov (United States)

    Magaud, Emilie; Nyman, Karissa; Addington, Jean

    2012-01-01

    Aim Several studies suggest an association between experiences of childhood trauma including bullying and the development of psychotic symptoms. The use of communications technology has created a new media for bullying called ‘cyberbullying’. Research has demonstrated associations between traditional bullying and cyberbullying. Negative effects of cyberbullying appear similar in nature and severity to the reported effects of traditional bullying. Our aim was to examine the prevalence and correlates of cyberbullying in those at clinical high risk (CHR) for psychosis. Methods Fifty young people at CHR for psychosis were administered the Childhood Trauma Questionnaire with added questions about cyberbullying. Results Cyberbullying was reported in 38% of the sample. Those who experienced cyberbullying also reported experiencing previous trauma. Conclusion It is possible that cyberbullying may be a problem for those at CHR of psychosis and due to the vulnerable nature of these young people, may have longitudinal implications. PMID:23343259

  19. Cyberbullying in those at clinical high risk for psychosis.

    Science.gov (United States)

    Magaud, Emilie; Nyman, Karissa; Addington, Jean

    2013-11-01

    Several studies suggest an association between experiences of childhood trauma including bullying and the development of psychotic symptoms. The use of communications technology has created a new media for bullying called 'cyberbullying'. Research has demonstrated associations between traditional bullying and cyberbullying. Negative effects of cyberbullying appear similar in nature and severity to the reported effects of traditional bullying. Our aim was to examine the prevalence and correlates of cyberbullying in those at clinical high risk (CHR) for psychosis. Fifty young people at CHR for psychosis were administered the Childhood Trauma Questionnaire with added questions about cyberbullying. Cyberbullying was reported in 38% of the sample. Those who experienced cyberbullying also reported experiencing previous trauma. It is possible that cyberbullying may be a problem for those at CHR of psychosis, and due to the vulnerable nature of these young people may have longitudinal implications. © 2013 Wiley Publishing Asia Pty Ltd.

  20. Changeable naevi in people at high risk for melanoma.

    Science.gov (United States)

    Abbott, Nicola Cd; Pandeya, Nirmala; Ong, Natalie; McClenahan, Phil; Smithers, B Mark; Green, Adele; Soyer, H Peter

    2015-02-01

    Naevi may change in size, shape and colour due to multiple inherent and external factors. We observed naevi changing size in adults at high risk of melanoma, and assessed associations of change with demographic factors, skin type, sites of naevi and history of melanoma. In total, 29 participants with a personal or first-degree family history of melanoma or those deemed at high risk with multiple naevi of variable morphologies had all melanocytic naevi 0.5-1 cm imaged and their maximum diameter recorded. Maximum diameters from repeat imaging of naevi 12 months later were compared to baseline measurements. Newly appearing naevi ≥5 mm and naevi that grew or decreased in size by 20% or more were defined as changeable naevi. Associations between changeable naevi and participants' age, sex, skin type, body sites of naevi and personal and family history of melanoma were assessed. There was no difference in changeable naevus rates among sex, age or skin type. Among the body sites, the head and neck were most likely to have changeable naevi, and the upper limbs the least likely. A family history of melanoma almost tripled the likelihood of having changeable naevi compared with those without both personal and family melanoma history. Naevi can continue to change in size throughout adulthood, showing both increases and decreases in size as well as the appearance of new naevi. This has important clinical implications, in particular for sequential body imaging used for the detection of melanoma. © 2014 The Australasian College of Dermatologists.

  1. Smell identification in individuals at clinical high risk for schizophrenia.

    Science.gov (United States)

    Gill, Kelly Elizabeth; Evans, Elizabeth; Kayser, Jürgen; Ben-David, Shelly; Messinger, Julie; Bruder, Gerard; Malaspina, Dolores; Corcoran, Cheryl Mary

    2014-12-15

    Smell identification deficits exist in schizophrenia, and may be associated with its negative symptoms. Less is known about smell identification and its clinical correlates in individuals at clinical high risk (CHR) for schizophrenia and related psychotic disorders. We examined smell identification, symptoms and IQ in 71 clinical high-risk (CHR) subjects and 36 healthy controls. Smell identification was assessed using both the 40-item University of Pennsylvania Smell Identification Test (UPSIT; Doty, R.L., Shaman, P., Kimmelman, C.P., Dann, M.S., 1984. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. Laryngoscope 94, 176-178) and its extracted 12-item Brief Smell Identification Test (Goudsmit, N., Coleman, E., Seckinger, R.A., Wolitzky, R., Stanford, A.D., Corcoran, C., Goetz, R.R., Malaspina, D., 2003. A brief smell identification test discriminates between deficit and non-deficit schizophrenia. Psychiatry Research 120, 155-164). Smell identification did not significantly differ between CHR subjects and controls. Among CHR subjects, smell identification did not predict schizophrenia (N=19; 27%) within 2 years, nor was it associated with negative or positive symptoms. This is the third prospective cohort study to examine smell identification in CHR subjects, and overall, findings are inconclusive, similar to what is found for other disorders in adolescents, such as autism spectrum, attention deficit and anxiety disorders. Smell identification deficit may not have clear utility as a marker of emergent schizophrenia and related psychotic disorders. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. IDH mutations are closely associated with mutations of DNMT3A, ASXL1 and SRSF2 in patients with myelodysplastic syndromes and are stable during disease evolution.

    Science.gov (United States)

    Lin, Chien-Chin; Hou, Hsin-An; Chou, Wen-Chien; Kuo, Yuan-Yeh; Liu, Chieh-Yu; Chen, Chien-Yuan; Lai, Yan-Jun; Tseng, Mei-Hsuan; Huang, Chi-Fei; Chiang, Ying-Chieh; Lee, Fen-Yu; Liu, Ming-Chih; Liu, Chia-Wen; Tang, Jih-Luh; Yao, Ming; Huang, Shang-Yi; Ko, Bor-Sheng; Wu, Shang-Ju; Tsay, Woei; Chen, Yao-Chang; Tien, Hwei-Fang

    2014-02-01

    Current information about clinical significance of IDH mutations in myelodysplastic syndromes (MDS), their association with other genetic alterations and the stability during disease progression is limited. In this study, IDH mutations were identified in 4.6% of 477 patients with MDS based on the FAB classification and in 2.2 % of 368 patients based on the 2008 WHO classification. IDH mutations were closely associated with older age, higher platelet counts, and mutations of DNMT3A (36.4% vs. 8.7%, P IDH2 mutation was a poor prognostic factor for overall survival in patients with lower-risk MDS, based on international prognosis scoring system (IPSS), FAB classification, WHO classification, or revised IPSS (all P ≦ 0.001), but not in higher-risk groups. Sequential studies in 151 patients demonstrated that all IDH-mutated patients retained the same mutation during disease evolution while none of the IDH-wild patients acquired a novel mutation during follow-ups. In conclusion, IDH mutation is a useful biomarker for risk stratification of patients with lower-risk MDS. IDH mutations are stable during the clinical course. The mutation, in association with other genetic alterations, may play a role in the development, but not progression of MDS. Copyright © 2013 Wiley Periodicals, Inc.

  3. Family-related obesity risk factors and dietary behaviours in high-risk populations : associations with child weight development

    OpenAIRE

    Svensson, Viktoria

    2014-01-01

    Background Obesity rates in Swedish children are currently not increasing, however socioeconomic disparities are widening. Many children become obese as early as their preschool years. Hereditary and environmental family-related risk factors are the dominating determinants of child obesity, with parental obesity as the most important. Prevention is a high priority, and increased knowledge on risk factors specifically in high-risk populations is of vital importance for the development of e...

  4. Suicide Risk Is High for Psychiatric Patients Long After Discharge from Care

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_166107.html Suicide Risk Is High for Psychiatric Patients Long After ... that psychiatric patients are at high risk for suicide immediately after being discharged from a mental health ...

  5. Incarceration and high-risk sex partnerships among men in the United States

    National Research Council Canada - National Science Library

    Khan, Maria R; Doherty, Irene A; Schoenbach, Victor J; Taylor, Eboni M; Epperson, Matthew W; Adimora, Adaora A

    2009-01-01

    .... The associations between incarceration and high-risk sex partnerships may exist, in part, because incarceration disrupts stable sex partnerships, some of which are protective against high-risk sex partnerships...

  6. Model-based adaptive phase I trial design of post-transplant decitabine maintenance in myelodysplastic syndrome.

    Science.gov (United States)

    Han, Seunghoon; Kim, Yoo-Jin; Lee, Jongtae; Jeon, Sangil; Hong, Taegon; Park, Gab-Jin; Yoon, Jae-Ho; Yahng, Seung-Ah; Shin, Seung-Hwan; Lee, Sung-Eun; Eom, Ki-Seong; Kim, Hee-Je; Min, Chang-Ki; Lee, Seok; Yim, Dong-Seok

    2015-10-23

    This report focuses on the adaptive phase I trial design aimed to find the clinically applicable dose for decitabine maintenance treatment after allogeneic hematopoietic stem cell transplantation in patients with higher-risk myelodysplastic syndrome and secondary acute myeloid leukemia. The first cohort (three patients) was given the same initial daily dose of decitabine (5 mg/m(2)/day, five consecutive days with 4-week intervals). In all cohorts, the doses for Cycles 2 to 4 were individualized using pharmacokinetic-pharmacodynamic modeling and simulations. The goal of dose individualization was to determine the maximum dose for each patient at which the occurrence of grade 4 (CTC-AE) toxicities for both platelet and neutrophil counts could be avoided. The initial doses for the following cohorts were also estimated with the data from the previous cohorts in the same manner. In all but one patient (14 out of 15), neutrophil count was the dose-limiting factor throughout the cycles. In cycles where doses were individualized, the median neutrophil nadir observed was 1100/mm(3) (grade 2) and grade 4 toxicity occurred in 5.1 % of all cycles (while it occurred in 36.8 % where doses were not individualized). The initial doses estimated for cohorts 2 to 5 were 4, 5, 5.5, and 5 mg/m(2)/day, respectively. The median maintenance dose was 7 mg/m(2)/day. We determined the acceptable starting dose and individualized the maintenance dose for each patient, while minimizing the toxicity using the adaptive approach. Currently, 5 mg/m(2)/day is considered to be the most appropriate starting dose for the regimen studied. Clinicaltrials.gov NCT01277484.

  7. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making.

    Science.gov (United States)

    Malcovati, Luca; Porta, Matteo Giovanni Della; Pascutto, Cristiana; Invernizzi, Rosangela; Boni, Marina; Travaglino, Erica; Passamonti, Francesco; Arcaini, Luca; Maffioli, Margherita; Bernasconi, Paolo; Lazzarino, Mario; Cazzola, Mario

    2005-10-20

    The aim of this study was to evaluate the prognostic value of the WHO proposal, to assess the role of the main prognostic factors in myelodysplastic syndromes (MDSs) classified into WHO subgroups, and to estimate mortality (standardized mortality ratio [SMR]) and life expectancy in these groups as a basis for clinical decision making. Four hundred sixty-seven patients who were diagnosed as having de novo MDS at the Division of Hematology, University of Pavia (Pavia, Italy), between 1992 and 2002, were evaluated retrospectively for clinical and hematologic features at diagnosis, overall survival (OS), and progression to leukemia (leukemia-free survival). Significant differences in survival were noted between patients with refractory anemia (RA), refractory cytopenia with multilineage dysplasia, RA with excess blasts, type 1 (RAEB-1), and RAEB-2. The effect of demographic factors on OS was observed in MDS patients without excess blasts (age, P = .001; sex, P = .006), as in the general population. The mortality of RA patients 70 years or older did not differ significantly from that of the general population (SMR, 1.62; P = .06). Cytogenetics was the only International Prognostic Scoring System variable showing a prognostic value in MDS classified into WHO subgroups. Transfusion-dependent patients had a significantly shorter survival than patients who did not require transfusions (P WHO classification of MDSs has a relevant prognostic value. This classification, along with cytogenetics, might be useful in decisions regarding transplantation. MDS with isolated erythroid lineage dysplasia identifies a subset of truly low-risk patients, for whom a conservative approach is advisable.

  8. Identification of gene expression-based prognostic markers in the hematopoietic stem cells of patients with myelodysplastic syndromes.

    Science.gov (United States)

    Pellagatti, Andrea; Benner, Axel; Mills, Ken I; Cazzola, Mario; Giagounidis, Aristoteles; Perry, Janet; Malcovati, Luca; Della Porta, Matteo G; Jädersten, Martin; Verma, Amit; McDonald, Emma-Jane; Killick, Sally; Hellström-Lindberg, Eva; Bullinger, Lars; Wainscoat, James S; Boultwood, Jacqueline

    2013-10-01

    The diagnosis of patients with myelodysplastic syndromes (MDS) is largely dependent on morphologic examination of bone marrow aspirates. Several criteria that form the basis of the classifications and scoring systems most commonly used in clinical practice are affected by operator-dependent variation. To identify standardized molecular markers that would allow prediction of prognosis, we have used gene expression profiling (GEP) data on CD34+ cells from patients with MDS to determine the relationship between gene expression levels and prognosis. GEP data on CD34+ cells from 125 patients with MDS with a minimum 12-month follow-up since date of bone marrow sample collection were included in this study. Supervised principal components and lasso penalized Cox proportional hazards regression (Coxnet) were used for the analysis. We identified several genes, the expression of which was significantly associated with survival of patients with MDS, including LEF1, CDH1, WT1, and MN1. The Coxnet predictor, based on expression data on 20 genes, outperformed other predictors, including one that additionally used clinical information. Our Coxnet gene signature based on CD34+ cells significantly identified a separation of patients with good or bad prognosis in an independent GEP data set based on unsorted bone marrow mononuclear cells, demonstrating that our signature is robust and may be applicable to bone marrow cells without the need to isolate CD34+ cells. We present a new, valuable GEP-based signature for assessing prognosis in MDS. GEP-based signatures correlating with clinical outcome may significantly contribute to a refined risk classification of MDS.

  9. Diabetes Insipidus as an Initial Presentation of Myelodysplastic Syndrome: Diagnosis with Single-Nucleotide Polymorphism Array-Based Karyotyping.

    Science.gov (United States)

    Sun, Ruixue; Wang, Chun; Zhong, Xushu; Wu, Yu

    2016-04-01

    Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic diseases characterized by cytopenia, dysplasia and increased risk of development to acute myeloid leukemia (AML). Unfavorable cytogenetic changes such as complex karyotypes or chromosome 7 anomalies are predictive of the progression to AML and poor prognosis. Central diabetes insipidus (CDI) is the result of a deficiency of arginine vasopressin, and its major causes are idiopathic, primary or secondary tumors, neurosurgery and trauma. Importantly, CDI is a rare complication of MDS. To date, only 5 cases of MDS co-occurring with CDI have been reported; 3 of 5 had cytogenetic abnormalities uncovered by metaphase cytogenetics and 3 of 5 evolved to AML. Here, we describe a 74-year-old woman who presented with CDI as her initial symptom of MDS and eventually progressed to AML. The metaphase cytogenetics, combined with the single-nucleotide polymorphism array (SNP-A)-based karyotyping, with superiority in resolution and detecting copy number variation, revealed a complex karyotype that included monosomy of chromosome 7, deletion of 20q, and absence of heterogeneity (AOH) in more than one chromosome. To the best of our knowledge, this is the first case report of MDS co-occurring with CDI with numerous cytogenetic abnormalities revealed by the SNP-A-based karyotyping. Our case supports that the cytogenetic abnormalities may be associated with the clinical features and the prognosis of MDS co-occurring with CDI. The SNP-A-based karyotyping is helpful in revealing more subtle cytogenetic abnormalities and unveiling their roles in the pathogenesis of MDS.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Mother-Child Interactions in Depressed Children and Children at High Risk and Low Risk for Future Depression

    Science.gov (United States)

    Dietz, Laura J.; Birmaher, Boris; Williamson, Douglas E.; Silk, Jennifer S.; Dahl, Ronald E.; Axelson, David A.; Ehmann, Mary; Ryan, Neal D.

    2008-01-01

    A study to investigate the differences in mother and child interactions of depressed children and adolescents, nondepressed high-risk youths, and healthy controls was conducted. Results revealed increased family discord with depressed children whereas intermediate levels of control and disengagement were seen in families with high-risk children.

  12. Trends in sexual risk behaviors, by nonsexual risk behavior involvement, U.S. high school students, 1991-2007.

    Science.gov (United States)

    Santelli, John; Carter, Marion; Orr, Mark; Dittus, Patricia

    2009-04-01

    Adolescent health risk behaviors often occur together, suggesting that youth involvement with one risk behavior may inform understanding of other risk behaviors. We examined the association between involvement in nonsexual risk behaviors and trends among sexual behaviors. We analyzed 1991-2007 data (n = approximately 125,000) from the Youth Risk Behavior Survey, a nationally representative survey of high school students in the United States. We categorized students into groups based on lifetime (Lifetime Risk Scale) and recent involvement (Recent Risk Scale) in nonsexual risk behaviors, such as smoking and drug use. We examined each group's prevalence of and trends for four sexual behaviors: ever having had sexual intercourse, having four or more lifetime partners, current sexual activity, and use of contraception at last sex. Data were examined for linear and quadratic (U-shaped) change using logistic regression. Sexual behaviors varied considerably between youth engaged in no risk behaviors and those in the highest risk behavior groups: sevenfold for ever having had intercourse (13% vs. 87% in 2007) and threefold for four or more lifetime sexual partners (19% vs. 57%). Despite these differences, trends in sexual risk behaviors among youth engaged in multiple nonsexual risk behaviors and those engaged in few or no risk behaviors were remarkably similar. In contrast, sexual behaviors demonstrated a very different pattern of change from that found or nonsexual behaviors: sexual experience and having multiple sexual partners declined into the early 2000s and then increased, whereas nonsexual behaviors increased over time, peaked in the late 1990 s, and then declined. Youth who engaged in little risk taking and those who engaged in considerable risk taking showed similar trends over time. However, the pattern of changes in sexual and nonsexual risk behaviors were remarkably different, raising questions about the potential impact of interventions that would reduce

  13. Classifiying Accident Risks in High-rise Building Consruction

    OpenAIRE

    M. Asad, Abdurrahman

    2009-01-01

    Changes in the physical environment by doing various types of construction work at the same location creating a potential hazard with various levels of risk. Approaches to prevent accidents can only be carried out if risk assessment process has been finished. This process should provide a systematic and objective approach to assess hazards and risks posed which will provide an objective measurement for hazard identification. By applying Fine method as risk calculator on the information ob...

  14. Decontamination of High-risk Animal and Zoonotic Pathogens

    Science.gov (United States)

    Menrath, Andrea; Tomuzia, Katharina; Braeunig, Juliane; Appel, Bernd

    2013-01-01

    Preparedness for the decontamination of affected environments, premises, facilities, and products is one prerequisite for an immediate response to an animal disease outbreak. Various information sources provide recommendations on how to proceed in an outbreak situation to eliminate biological contaminants and to stop the spread of the disease. In order to facilitate the identification of the right decontamination strategy, we present an overview of relevant references for a collection of pathogenic agents. The choice of pathogens is based on a survey of lists containing highly pathogenic agents and/or biological agents considered to be potential vehicles for deliberate contamination of food, feed, or farm animals. European legislation and guidelines from national and international institutions were screened to find decontamination protocols for each of the agents. Identified recommendations were evaluated with regard to their area of application, which could be facilities and equipment, wastes, food, and other animal products. The requirements of a disinfectant for large-scale incidents were gathered, and important characteristics (eg, inactivating spectrum, temperature range, toxicity to environment) of the main recommended disinfectants were summarized to assist in the choice of a suitable and efficient approach in a crisis situation induced by a specific high-risk animal or zoonotic pathogen. The literature search revealed numerous relevant recommendations but also legal gaps for certain diseases, such as Q fever or brucellosis, and legal difficulties for the use of recommended disinfectants. A lack of information about effective disinfectants was identified for some agents. PMID:23971795

  15. Chances of Adverse Neonatal Outcome in High-Risk and Low-Risk Obstetrical Patients

    Directory of Open Access Journals (Sweden)

    Y. Krilova

    2008-01-01

    Full Text Available Objective To analyze and compare occurrence of adverse immediate neonatal outcomes in high and low-risk obstetrical population. Methods Retrospective cohort study of 2370 pregnant women. The odds of adverse outcomes (i.e. low Apgar score (1–4 points and intermediate Apgar score (5–8 points at 1 and 5 minutes of life, birth to a small-for-gestational-age neonate (below 90th percentile of birth weight, and requirement for advanced level II-III nursery care as well as odds of primary cesarean delivery–-were analyzed using logistic regression analysis. Results All of the studied outcomes were seen more often among the high-risk patients. When the outcomes were analyzed within a given group some interesting observations were made. The highest odds of abnormal Apgar scores (when compared to the low risk population were seen in patients with preeclampsia–-6.06 (95% CI 3.28; 11.22 and twin pregnancies–-odds ratio of 6.63 (95% CI 2.24; 19.67. Among Small-for-Gestational-Age newborns the most frequently identified maternal condition was preeclampsia (21.57%, out of all fetal conditions twin gestation (26.67% was number one identified scenario. The highest proportion of patients requiring advanced level nursery care (level II and III was observed in those with twin gestation, pregnancies complicated by hypertension with and without diabetes. The highest odds of having primary cesarean delivery in laboring patients (when compared to the low risk population were seen in the patients with IUGR fetus–-odds ratio of 26.78 [95% CI 7.65; 93.75], followed by macrosomia–-odds ratio 5.74 [95% CI 2.14; 15.41], preeclampsia–-odds ratio 5.52 [95% CI 3.14; 9.69]. For additional findings and more information on select conditions, please, refer to the full-text article. Conclusion The studied outcomes are useful markers of fetal/neonatal status and can be used to compare perinatal outcomes between different medical conditions, different locales and to

  16. To kill a kangaroo: understanding the decision to pursue high-risk/high-gain resources.

    Science.gov (United States)

    Jones, James Holland; Bird, Rebecca Bliege; Bird, Douglas W

    2013-09-22

    In this paper, we attempt to understand hunter-gatherer foraging decisions about prey that vary in both the mean and variance of energy return using an expected utility framework. We show that for skewed distributions of energetic returns, the standard linear variance discounting (LVD) model for risk-sensitive foraging can produce quite misleading results. In addition to creating difficulties for the LVD model, the skewed distributions characteristic of hunting returns create challenges for estimating probability distribution functions required for expected utility. We present a solution using a two-component finite mixture model for foraging returns. We then use detailed foraging returns data based on focal follows of individual hunters in Western Australia hunting for high-risk/high-gain (hill kangaroo) and relatively low-risk/low-gain (sand monitor) prey. Using probability densities for the two resources estimated from the mixture models, combined with theoretically sensible utility curves characterized by diminishing marginal utility for the highest returns, we find that the expected utility of the sand monitors greatly exceeds that of kangaroos despite the fact that the mean energy return for kangaroos is nearly twice as large as that for sand monitors. We conclude that the decision to hunt hill kangaroos does not arise simply as part of an energetic utility-maximization strategy and that additional social, political or symbolic benefits must accrue to hunters of this highly variable prey.

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

    Science.gov (United States)

    2017-10-08

    OW) a. Primary/Corresponding Author Haeusler. Kelly A 0-3/Capt 959th CSPS b. Krauland, Kevin J 0-4/ Maj 959th CSPS c. Hall, Jordan M 0-5/L TC C...Concurrent Myelodysplastic Syndrome with t(1 ;3) on Bone Marrow Examination • Authors: Capt Kelly A. Haeusler, MD, Maj Kevin J. Krauland, MD, LTC

  18. Empowering High-Risk Clients to Attain a Better Quality of Life: A Career Resiliency Framework

    Science.gov (United States)

    Rickwood, Rory R.; Roberts, Jillian; Batten, Suzanne; Marshall, Anne; Massie, Kendra

    2004-01-01

    Career counselors frequently encounter clients who are at high risk for career and life development difficulties. Research suggests there is a connection between resiliency and successful career development in high-risk clients. Many high-risk individuals have poor decision-making skills and lack motivation to succeed in life and career…

  19. Increased risk of eczema but reduced risk of early wheezy disorder from exclusive breast-feeding in high-risk infants

    DEFF Research Database (Denmark)

    Giwercman, Charlotte; Halkjaer, Liselotte B; Jensen, Signe Marie

    2010-01-01

    Breast-feeding is recommended for the prevention of eczema, asthma, and allergy, particularly in high-risk families, but recent studies have raised concern that this may not protect children and may even increase the risk. However, disease risk, disease manifestation, lifestyle, and the choice...... to breast-feed are interrelated, and therefore, analyzing true causal effects presents a number of methodologic challenges....

  20. A high dietary glycemic index increases total mortality in a Mediterranean population at high cardiovascular risk.

    Directory of Open Access Journals (Sweden)

    Itandehui Castro-Quezada

    Full Text Available OBJECTIVE: Different types of carbohydrates have diverse glycemic response, thus glycemic index (GI and glycemic load (GL are used to assess this variation. The impact of dietary GI and GL in all-cause mortality is unknown. The objective of this study was to estimate the association between dietary GI and GL and risk of all-cause mortality in the PREDIMED study. MATERIAL AND METHODS: The PREDIMED study is a randomized nutritional intervention trial for primary cardiovascular prevention based on community-dwelling men and women at high risk of cardiovascular disease. Dietary information was collected at baseline and yearly using a validated 137-item food frequency questionnaire (FFQ. We assigned GI values of each item by a 5-step methodology, using the International Tables of GI and GL Values. Deaths were ascertained through contact with families and general practitioners, review of medical records and consultation of the National Death Index. Cox regression models were used to estimate multivariable-adjusted hazard ratios (HR and their 95% CI for mortality, according to quartiles of energy-adjusted dietary GI/GL. To assess repeated measures of exposure, we updated GI and GL intakes from the yearly FFQs and used Cox models with time-dependent exposures. RESULTS: We followed 3,583 non-diabetic subjects (4.7 years of follow-up, 123 deaths. As compared to participants in the lowest quartile of baseline dietary GI, those in the highest quartile showed an increased risk of all-cause mortality [HR = 2.15 (95% CI: 1.15-4.04; P for trend  = 0.012]. In the repeated-measures analyses using as exposure the yearly updated information on GI, we observed a similar association. Dietary GL was associated with all-cause mortality only when subjects were younger than 75 years. CONCLUSIONS: High dietary GI was positively associated with all-cause mortality in elderly population at high cardiovascular risk.