Science.gov

Sample records for adult aml patients

  1. Acute Myeloid Leukemia (AML) Treatment in Adults (Beyond the Basics)

    MedlinePlus

    ... and returned by IV infusion. Because the transplanted stem cells do not come from another person, there is no "graft versus ... leukemia (AML) (The Basics) Patient information: Leukemia in adults (The ... (bone marrow transplantation) (Beyond the Basics) Professional ...

  2. Age-dependent frequencies of NPM1 mutations and FLT3-ITD in patients with normal karyotype AML (NK-AML).

    PubMed

    Schneider, Friederike; Hoster, Eva; Schneider, Stephanie; Dufour, Annika; Benthaus, Tobias; Kakadia, Purvi M; Bohlander, Stefan K; Braess, Jan; Heinecke, Achim; Sauerland, Maria C; Berdel, Wolfgang E; Buechner, Thomas; Woermann, Bernhard J; Feuring-Buske, Michaela; Buske, Christian; Creutzig, Ursula; Thiede, Christian; Zwaan, Michel C; van den Heuvel-Eibrink, Marry M; Reinhardt, Dirk; Hiddemann, Wolfgang; Spiekermann, Karsten

    2012-01-01

    Prognosis of AML in elderly patients is poor due to adverse patient characteristics and comorbidities. In addition, disease-associated parameters reveal differences between older and younger patients with AML. Survival in normal karyotype AML (NK-AML) is influenced by different clinical and molecular markers. The aim of this work was to investigate the frequencies of molecular markers in patients with NK-AML with a focus on NPM1 mutations and FLT3-ITD in different age groups. In the present study, we analyzed the frequencies of mutations of NPM1 and FLT3-ITD in a cohort of 1,321 adult patients and 148 children with AML treated within the AMLCG99, the AML98, and AML04 trials and their distribution in different age groups. Additionally, the frequencies of mutations in CEBPA genes, FLT3-TKD, and MLL-PTD were analyzed in the cohort with NK-AML (n = 729). Our data show that the presence of mutations of NPM1 (from 60% to 40%) and FLT3-ITD (from 50% to 20%) significantly decreased with age in adult AML. Consequently, the proportion of NPM1-/FLT3-ITD- patients increased with age. The decreasing frequency of NPM1 mutations in elderly patients was paralleled by a reduced complete remission (CR) rate in the elderly of 55% compared to 80% in the younger patients. By contrast, the frequencies of other gene mutations, like FLT3-TKD and MLL-PTD, and mutations in CEBPA were not age-dependent. The decreasing frequency of the favorable NPM1 mutations with increasing age may partially explain the worse outcome in the elderly patients. Furthermore, the increasing amount of elderly patients without NPM1 mutations or FLT3-ITD suggests that other molecular and clinical risk factors may influence prognosis in this age group. PMID:21744003

  3. AML Guide: Information for Patients and Caregivers

    MedlinePlus

    ... Planning About AML Treatments Relapsed or Refractory AML Stem Cell Transplantation Acute Promyelocytic Leukemia (APL) Treatment Acute Monocytic ... are made in the marrow. They begin as stem cells. Stem cells become red cells, white cells and ...

  4. AML Guide: Information for Patients and Caregivers

    MedlinePlus

    ... an example. The AML Guide I page 27 Late effects are medical problems that do not show up until years after treatment ends. Heart disease is ... AML need to see the doctor for follow-up care. Children who are treated for AML may ... should talk with their doctors about any long-term or late effects that may be related to their treatment. ...

  5. Sex disparity in childhood and young adult acute myeloid leukemia (AML) survival: Evidence from US population data.

    PubMed

    Hossain, Md Jobayer; Xie, Li

    2015-12-01

    Sex variation has been persistently investigated in studies concerning acute myeloid leukemia (AML) survival outcomes but has not been fully explored among pediatric and young adult AML patients. We detected sex difference in the survival of AML patients diagnosed at ages 0-24 years and explored distinct effects of sex across subgroups of age at diagnosis, race-ethnicity and AML subtypes utilizing the United States Surveillance Epidemiology and End Results (SEER) population based dataset of 4865 patients diagnosed with AML between 1973 and 2012. Kaplan-Meier survival function, propensity scores and stratified Cox proportional hazards regression were used for data analyses. After controlling for other prognostic factors, females showed a significant survival advantage over their male counterparts, adjusted hazard ratio (aHR, 95% confidence interval (CI): 1.09, 1.00-1.18). Compared to females, male patients had substantially increased risk of mortality in the following subgroups of: ages 20-24 years at diagnosis (aHR1.30), Caucasian (1.14), acute promyelocytic leukemia (APL) (1.35), acute erythroid leukemia (AEL) (1.39), AML with inv(16)(p13.1q22) (2.57), AML with minimum differentiation (1.47); and had substantially decreased aHR in AML t(9;11)(p22;q23) (0.57) and AML with maturation (0.82). Overall, females demonstrated increased survival over males and this disparity was considerably large in patients ages 20-24 years at diagnosis, Caucasians, and in AML subtypes of AML inv(16), APL and AEL. In contrast, males with AML t(9;11)(p22;q23), AML with maturation and age at diagnosis of 10-14 years showed survival benefit. Further investigations are needed to detect the biological processes influencing the mechanisms of these interactions. PMID:26520618

  6. CNS Involvement in AML Patient Treated with 5-Azacytidine

    PubMed Central

    Vasilatou, Diamantina; Papageorgiou, Sotirios; Bazani, Efthymia; Prasouli, Athina; Economopoulou, Christina; Roumpakis, Christoforos; Karakitsos, Petros; Dimitriadis, George; Pappa, Vasiliki

    2014-01-01

    Central nervous system (CNS) involvement in acute myeloid leukemia (AML) is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status. PMID:25197583

  7. CNS Involvement in AML Patient Treated with 5-Azacytidine.

    PubMed

    Vasilatou, Diamantina; Papageorgiou, Sotirios; Bazani, Efthymia; Prasouli, Athina; Economopoulou, Christina; Roumpakis, Christoforos; Karakitsos, Petros; Dimitriadis, George; Pappa, Vasiliki

    2014-01-01

    Central nervous system (CNS) involvement in acute myeloid leukemia (AML) is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status. PMID:25197583

  8. Reduced-intensity conditioned allogeneic SCT in adults with AML.

    PubMed

    Reshef, R; Porter, D L

    2015-06-01

    AML is currently the most common indication for reduced-intensity conditioned (RIC) allo-SCT. Reduced-intensity regimens allow a potent GVL response to occur with minimized treatment-related toxicity in patients of older age or with comorbidities that preclude the use of myeloablative conditioning. Whether RIC SCT is appropriate for younger and more standard risk patients is not well defined and the field is changing rapidly; a prospective randomized trial of myeloablative vs RIC (BMT-CTN 0901) was recently closed when early results indicated better outcomes for myeloablative regimens. However, detailed results are not available, and all patients in that study were eligible for myeloablative conditioning. RIC transplants will likely remain the standard of care as many patients with AML are not eligible for myeloablative conditioning. Recent publication of mature results from retrospective and prospective cohorts provide contemporary efficacy and toxicity data for these attenuated regimens. In addition, recent studies explore the use of alternative donors, introduce regimens that attempt to reduce toxicity without reducing intensity, and identify predictive factors that pave the way to personalized approaches. These studies paint a picture of the future of RIC transplants. Here we review the current status of RIC allogeneic SCT in AML. PMID:25730186

  9. Lower frequency of NPM1 and FLT3-ITD mutations in a South African adult de novo AML cohort

    PubMed Central

    Marshall, R. C.; Tlagadi, A.; Bronze, M.; Kana, V.; Naidoo, S.; Wiggill, T. M.; Carmona, S. C.

    2014-01-01

    Introduction Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of haemopoietic progenitor cells diagnosed in individuals of any age, but with a median age of 67 years at presentation in adults. Assessment of the mutation status of Nucleophosmin protein-1 (NPM1) and FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) are essential for the diagnosis, prognosis and treatment of AML. Methods A total of 160 de novo AML cases, both cytogenetically normal and abnormal, were analyzed for the presence of NPM1 and FLT3-ITD mutations and the results assessed in conjunction with epidemiological, clinical and laboratory findings. Results NPM1 mutations were found in 7.5%, while FLT3-ITD was present in 12% of these cases. Both of these were lower than expected. The median age at diagnosis of AML was 41 years and for the FLT3-ITD only cases, median age was 33 years; these ages were younger than expected. Conclusion The lower reported frequencies and younger median age at diagnosis of AML and these specific mutations may be contributed to by a number of factors including; effects of race on age of presentation, inclusion of patients diagnosed with de novo AML only and a generally younger median age of the South African population. PMID:24666762

  10. Genomic, immunophenotypic, and NPM1/FLT3 mutational studies on 17 patients with normal karyotype acute myeloid leukemia (AML) followed by aberrant karyotype AML at relapse.

    PubMed

    Wang, Eunice S; Sait, Sheila N J; Gold, David; Mashtare, Terry; Starostik, Petr; Ford, Laurie Ann; Wetzler, Meir; Nowak, Norma J; Deeb, George

    2010-10-15

    Normal karyotype (NK) is the most common cytogenetic group in acute myeloid leukemia (AML) diagnosis; however, up to 50% of these patients at relapse will have aberrant karyotype (AK) AML. To determine the etiology of relapsed AK AML cells, we evaluated cytogenetic, immunophenotypic, and molecular results of 17 patients with diagnostic NK AML and relapsed AK AML at our institute. AK AML karyotype was diverse, involving no favorable and largely (8 of 17) complex cytogenetics. Despite clear cytogenetic differences, immunophenotype and NPM1/FLT3 gene mutation status did not change between presentation and relapse in 83% (10 of 12) and 94% (15 of 16) cases, respectively. High-resolution array-based comparative genomic hybridization (aCGH) performed via paired aCGH on NK AML and AK AML samples from the same patient confirmed cytogenetic aberrations only in the relapse sample. Analysis of 16 additional diagnostic NK AML samples revealed no evidence of submicroscopic aberrations undetected by conventional cytogenetics in any case. These results favor evolution of NK AML leukemia cells with acquisition of novel genetic changes as the most common etiology of AK AML relapse as opposed to secondary leukemogenesis. Additional studies are needed to confirm whether AK AML cells represent selection of rare preexisting clones below aCGH detection and to further characterize the molecular lesions found at time of AK AML relapse. PMID:20875872

  11. [Correlation of adult AML Npm1 mutations with prognosis and its relationship with gene mutation of FLT3 and CEBPA].

    PubMed

    Bao, Li-Yan; Wang, Ji-Shi

    2010-02-01

    This study was aimed to investigate the correlation of 12th exon mutations in the npm1 gene with prognosis of adult AML patients and to explore the relationship of 12th exon mutation with other gene mutations. The specimen of bone marrow and peripheral blood from AML patients, the informations of medical history, symptoms, related image examinations, blood routine examination, NAP, oxygen saturation level in artery blood and EPO level in serum were collected; the bcr/abl fusion gene was detected by routine examination of bone marrow + biopsy + chromosome mapping + FISH. The patients were typed according to WHO classification. The DNA in cells was extracted, the npm1 gene mutation was detected by allele specific PCR combined were the sequencing. The results indicated that the npm1 heterozygote gene mutation was found in 72 out of 150 AML patients with normal cytogenetics (48%, 72/150). 48% patients showed a frameshift mutation in the C-terminal region of the NPM1 protein. The AML patients with npm1 gene mutation had specific clinical, phenotypic and genetic characteristics. The statistical analysis demonstrated the relationship between npm1 and flt3 ITDs. The patients with npm1 mutation showed a better response to induction therapy, furthermore, the overall survival (OS) rate of patients without flt3 ITD mutation was enhanced. The multivariate analysis demonstrated that the npm1 gene mutation and cebpa mutation positively correlated to the OS rate, and the correlation of flt3 mutation to OS rate showed negative. It is concluded that npm1 mutation is a favorable independent prognostic factor for adult AML patients with normal cytogenetics under conditions without FIT3 gene mutation. PMID:20137111

  12. Repression of GSK3 restores NK cell cytotoxicity in AML patients

    PubMed Central

    Parameswaran, Reshmi; Ramakrishnan, Parameswaran; Moreton, Stephen A.; Xia, Zhiqiang; Hou, Yongchun; Lee, Dean A.; Gupta, Kalpana; deLima, Marcos; Beck, Rose C.; Wald, David N.

    2016-01-01

    Natural killer cells from acute myeloid leukaemia patients (AML-NK) show a dramatic impairment in cytotoxic activity. The exact reasons for this dysfunction are not fully understood. Here we show that the glycogen synthase kinase beta (GSK3β) expression is elevated in AML-NK cells. Interestingly, GSK3 overexpression in normal NK cells impairs their ability to kill AML cells, while genetic or pharmacological GSK3 inactivation enhances their cytotoxic activity. Mechanistic studies reveal that the increased cytotoxic activity correlates with an increase in AML-NK cell conjugates. GSK3 inhibition promotes the conjugate formation by upregulating LFA expression on NK cells and by inducing ICAM-1 expression on AML cells. The latter is mediated by increased NF-κB activation in response to TNF-α production by NK cells. Finally, GSK3-inhibited NK cells show significant efficacy in human AML mouse models. Overall, our work provides mechanistic insights into the AML-NK dysfunction and a potential NK cell therapy strategy. PMID:27040177

  13. Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials.

    PubMed

    Gibson, B E S; Wheatley, K; Hann, I M; Stevens, R F; Webb, D; Hills, R K; De Graaf, S S N; Harrison, C J

    2005-12-01

    Between 1988 and 2002, 758 children with acute myeloid leukaemia (AML) were treated on Medical Research Council (MRC) AML 10 and AML 12. MRC AML 10 tested the role of bone marrow transplantation following four blocks of intensive chemotherapy and found that while both allogeneic bone marrow transplant (allo-BMT) and autologous bone marrow transplant (A-BMT) significantly reduced the relapse risk (RR), this did not translate into a significant improvement in overall survival (OS). A risk group stratification based on cytogenetics and response to the first course of chemotherapy derived from MRC AML 10 was used to deliver risk-directed therapy in MRC AML 12. Allo-BMT was limited to standard and poor risk patients and A-BMT was not employed. Instead, the benefit of an additional block of treatment was tested by randomising children to receive either four or five blocks of treatment in total. While the results of MRC AML 12 remain immature, there appears to be no survival advantage for a fifth course of treatment. The 5 year OS, disease-free survival (DFS), event-free survival (EFS) and RR in MRC AML 12 are 66, 61, 56 and 35%, respectively; at present superior to MRC AML 10, which had a 5-year OS, DFS, EFS and RR of 58, 53, 49 and 42%, respectively. MRC AML trials employ a short course of triple intrathecal chemotherapy alone for CNS-directed treatment and CNS relapse is uncommon. Improvements in supportive care have contributed to improved outcomes and the number of deaths in remission fell between trials. Anthracycline-related cardiotoxicity remains a concern and the current MRC AML 15 trial tests the feasibility of reducing anthracycline dosage without compromising outcome by comparing standard MRC anthracycline-based consolidation with high-dose ara-C. MRC studies suggest that the role of allo-BMT is limited in 1st CR and that there may be a ceiling of benefit from current or conventional chemotherapy. PMID:16304572

  14. The relapse risk of AML patients undergoing autologous transplantation correlates with the stem cell mobilizing potential.

    PubMed

    von Grünigen, Isabelle; Raschle, Joëlle; Rüsges-Wolter, Ilka; Taleghani, Behrouz Mansouri; Mueller, Beatrice U; Pabst, Thomas

    2012-11-01

    Autologous stem cell transplantation (ASCT) is widely used to consolidate first remission in AML. We determined the significance of circulating CD34+ cells at the day of blood stem cell collection in 78 AML patients. Patients mobilizing more than 60,000 CD34+ cells/ml had shorter overall survival (OS; P=0.0274), shorter time to progression (TTP; P=0.0014), and a higher relapse rate (P=0.0177). High levels of CD34+ cells were an independent marker for shorter OS and TTP in a multivariate analysis. These data suggest that ASCT is associated with unfavorable outcome in AML patients with high levels of mobilized peripheral CD34+ cells. PMID:22727508

  15. HAG regimen improves survival in adult patients with hypocellular acute myeloid leukemia

    PubMed Central

    Wang, Libing; Gao, Lei; Lü, Shuqin; Xi, Hao; Qiu, Huiying; Chen, Li; Chen, Jie; Ni, Xiong; Xu, Xiaoqian; Zhang, Weiping; Yang, Jianmin; Wang, Jianmin; Song, Xianmin

    2016-01-01

    Background Hypocellular acute myeloid leukemia (Hypo-AML) is a rare disease entity. Studies investigating the biological characteristics of hypo-AML have been largely lacking. We examined the clinical and biological characteristics, as well as treatment outcomes of hypo-AML in our institutes over a seven years period. Design and Methods We retrospectively analyzed data on 631 adult AML patients diagnosed according to the French-American-British (FAB) classification and WHO classification of tumors of haematopoietic and lymphoid tissue, including 43 patients with hypo-AML. Biological variables, treatment outcomes and follow-up data on hypo-AML patients were analyzed. Results Out of 631 AML patients, 47 (7.4%) were diagnosed as hypo-AML, out of which 43 patients were evaluable. Compared with non-hypocellular AML, hypo-AML patients tended to be older (P = 0.05), more likely to present with leukocytopenia (P < 0.01) and anterior hematological diseases (P = 0.02). The overall complete remission (CR) rate, disease free survival (DFS), and overall survival (OS) in hypo-AML patients were comparable to those in non-hypo AML patients. Twenty-seven (62.8%) patients with hypocellular AML were treated with the standard regimen of anthracyclines and cytarabine (XA) (associated CR rate: 51.9%; median OS: 7 months; median DFS: 6.5 months). Sixteen (37.2%) patients were treated with a priming regimen containing homoharringtonine, cytarabine and G-CSF (HAG) (associated CR rate: 81.25%; median OS: 16 months; median DFS: 16 months). Conclusions The overall prognosis of hypo-AML was not inferior to that of non-hypo AML. HAG regimen might increase response rates and improve survival in hypo-AML patients. PMID:26497216

  16. MicroRNA–mRNA Pairs Associated with Outcome in AML: From In Vitro Cell-Based Studies to AML Patients

    PubMed Central

    Bhise, Neha S.; Chauhan, Lata; Shin, Miyoung; Cao, Xueyuan; Pounds, Stanley; Lamba, Vishal; Lamba, Jatinder K.

    2016-01-01

    Cytarabine is the primary chemotherapeutic agent used for treatment of acute myeloid leukemia (AML). Disease relapse after initial remission remains one of the most pressing therapeutic challenges in the treatment of AML. Relapsed disease is often resistant to cytarabine and subsequent salvage therapy is ineffective. Recent studies have shown that some microRNAs (miRNAs) are associated with prognosis, but have not yet explored the role of miRNAs in cellular response to cytarabine. We identified 20 miRNAs that associate with the in vitro cytarabine chemo-sensitivity or apoptotic response of eight AML cell lines. Out of the 20 miRNAs, data on 18 miRNAs was available in AML patients from The Cancer Genome Atlas database. Our stepwise-integrated analyses (step 1 – miRNA–target mRNA that were significantly correlated in AML patients; step 2 – mRNAs from step 1 with significant association with overall survival (OS)) identified 23 unique miRNA–mRNA pairs predictive of OS in AML patients. As expected HOX genes (HOXA9, HOXB7, and HOXA10) were identified to be regulated by miRs as well as predictive of worse OS. Additionally, miR107-Myb, miR-378-granzyme B involved in granzyme signaling and miR10a-MAP4K4 were identified to be predictive of outcome through integrated analysis. Although additional functional validations to establish clinical/pharmacologic importance of miRNA–mRNA pairs are needed, our results from RNA electrophoretic mobility shift assay confirmed binding of miR-10a, miR-378, and miR-107 with their target genes GALNT1, GZMB, and MYB, respectively. Integration of pathogenic and pharmacologically significant miRNAs and miRNA–mRNA relationships identified in our study opens up opportunities for development of targeted/miRNA-directed therapies. PMID:26858643

  17. Impact of obesity in favorable-risk AML patients receiving intensive chemotherapy.

    PubMed

    Tavitian, Suzanne; Denis, Amélia; Vergez, François; Berard, Emilie; Sarry, Audrey; Huynh, Anne; Delabesse, Eric; Luquet, Isabelle; Huguet, Françoise; Récher, Christian; Bertoli, Sarah

    2016-02-01

    We assessed the influence of obesity on the characteristics and prognosis of acute myeloid leukemia (AML). Indeed, safety of intensive chemotherapy and outcome of obese AML patients in a real-life setting are poorly described, and chemotherapy dosing remains challenging. We included 619 consecutive genetically-defined cases of AML treated with intensive chemotherapy between 2004 and 2012. In this cohort, 93 patients (15%) were classified in the obese category according to WHO classification; 59% of them received capped doses of chemotherapy because of a body surface area above 2 m(2) . Obese patients were older and presented more often with cardiovascular comorbidities. Although obese patients had more frequently de novo AML, main characteristics of AML including white blood cell count, karyotype and mutations were well-balanced between obese and non-obese patients. After induction chemotherapy, early death and complete remission rates were similar. Overall (OS), event-free (EFS) and disease-free (DFS) survival were not significantly different compared to non-obese patients. However, in the European LeukemiaNet (ELN) favorable subgroup, obese patients had lower median OS, EFS and DFS than non-obese patients (18.4, 16.8 and 17.2 vs. 43.6, 31.8 and 29.7 months, respectively) and obesity showed a significant impact on OS (OR 2.54; P = 0.02) in multivariate models. Although we did not find any significant impact of obesity on outcome in the whole series, this study suggests that special efforts for chemotherapy dose optimization are needed in the ELN favorable subgroup since dose capping may be deleterious. PMID:26509505

  18. Improved outcome of pediatric patients with acute megakaryoblastic leukemia in the AML-BFM 04 trial.

    PubMed

    Schweitzer, Jana; Zimmermann, Martin; Rasche, Mareike; von Neuhoff, Christine; Creutzig, Ursula; Dworzak, Michael; Reinhardt, Dirk; Klusmann, Jan-Henning

    2015-08-01

    Despite recent advances in the treatment of children with acute megakaryoblastic leukemia (AMKL) using intensified treatment protocols, clear prognostic indicators, and treatment recommendations for this acute myeloid leukemia (AML) subgroup are yet to be defined. Here, we report the outcome of 97 pediatric patients with de novo AMKL (excluding Down syndrome [DS]) enrolled in the prospective multicenter studies AML-BFM 98 and AML-BFM 04 (1998-2014). AMKL occurred in 7.4 % of pediatric AML cases, at younger age (median 1.44 years) and with lower white blood cell count (mean 16.5 × 10(9)/L) as compared to other AML subgroups. With 60 ± 5 %, children with AMKL had a lower 5-year overall survival (5-year OS; vs. 68 ± 1 %, P log rank = 0.038). Yet, we achieved an improved 5-year OS in AML-BFM 04 compared to AML-BFM 98 (70 ± 6 % vs. 45 ± 8 %, P log rank = 0.041). Allogeneic hematopoietic stem cell transplantation in first remission did not provide a significant survival benefit (5-year OS 70 ± 11 % vs. 63 ± 6 %; P Mantel-Byar = 0.85). Cytogenetic data were available for n = 78 patients. AMKL patients with gain of chromosome 21 had a superior 5-year OS (80 ± 9 %, P log rank = 0.034), whereas translocation t(1;22)(p13;q13) was associated with an inferior 5-year event-free survival (38 ± 17 %, P log rank = 0.04). However, multivariate analysis showed that treatment response (bone marrow morphology on day 15 and 28) was the only independent prognostic marker (RR = 4.39; 95 % CI, 1.97-9.78). Interestingly, GATA1-mutations were detected in six patients (11 %) without previously known trisomy 21. Thus, AMKL (excluding DS) remains an AML subgroup with inferior outcome. Nevertheless, with intensive therapy regimens, a steep increase in the survival rates was achieved. PMID:25913479

  19. Deletion of CBFB in a patient with acute myelomonocytic leukemia (AML M4Eo) and inversion 16.

    PubMed

    Egan, Nicole; O'Reilly, John; Chipper, Lucia; Higgins, Melinda; Herrmann, Richard; Cannell, Paul

    2004-10-01

    Acute myelomonocytic leukemia with bone marrow eosinophilia (AML M4Eo) is a subtype of AML with distinct morphological features. Inversion (16)(p13.1q22), t(16;16)(p13.1;q22), and del(16)(q22) are nonrandom abnormalities associated with AML M4Eo and a favorable prognosis, compared with the standard risk group for AML. Deletions of the proximal region of the MYH11 gene located at 16p13.1 have been detected in about 20% of patients with inv(16), with an undetermined effect on patient survival. We present the case of a patient with AML M4Eo and inversion 16 with a distal deletion of the CBFB gene at 16q22 detected with fluorescence in situ hybridization. To our knowledge, only one previous report of a similar deletion has appeared in the literature. PMID:15381374

  20. OBESITY DOES NOT PRECLUDE SAFE AND EFFECTIVE MYELOABLATIVE HEMATOPOIETIC CELL TRANSPLANTATION (HCT) FOR ACUTE MYELOID LEUKEMIA (AML) IN ADULTS

    PubMed Central

    Navarro, Willis H.; Agovi, Manza-A.; Logan, Brent R.; Ballen, Karen; Bolwell, Brian J.; Frangoul, Haydar; Gupta, Vikas; Hahn, Theresa; Ho, Vincent T.; Juckett, Mark; Lazarus, Hillard M.; Litzow, Mark R.; Liesveld, Jane L.; Moreb, Jan S.; Marks, David I.; McCarthy, Philip L.; Pasquini, Marcelo C.; Rizzo, J. Douglas

    2010-01-01

    The incidence of excessive adiposity is increasing worldwide and is associated with numerous adverse health outcomes. We compared outcomes by body mass index (BMI) for adult patients with acute myeloid leukemia (AML) who underwent autologous (auto, n=373), related donor (RD, n=2041), or unrelated donor (URD, n=1801) allogeneic myeloablative hematopoietic cell transplantation (HCT) using marrow or peripheral blood stem cells reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1995-2004. Four weight groups by BMI (kg/m2) were defined: underweight < 18; normal 18 – 25; overweight >25 – 30; and obese > 30. Multivariable analysis referenced to the normal weight group showed an increased risk of death for underweight patients in the RD group (RR, 1.92; 95% CI, 1.28-2.89; P = 0.002) but not in the URD group. There were no other differences in outcomes among the other weight groups within the other HCT groups. Overweight and obese patients enjoyed a modest decrease in relapse incidence, though this did not translate into a survival benefit. Small numbers of patients limit the ability to better characterize the adverse outcomes seen in the underweight RD but not the underweight URD allogeneic HCT patients. Obesity alone should not be considered a barrier to HCT. PMID:20412867

  1. Outpatient supportive therapy after induction to remission therapy in adult acute myelogenous leukaemia (AML) is feasible: a multicentre study.

    PubMed

    Ruiz-Argüelles, G J; Apreza-Molina, M G; Alemán-Hoey, D D; Gómez-Almaguer, D; Marín-López, A; Mercado-Díaz, L

    1995-01-01

    Twenty-four adult patients with AML were treated with standard "7 + 3" chemotherapy. After administering the myeloablative drugs in the hospital, patients were instructed to continue their supportive treatment on an outpatient basis; they received ciprofloxacin, cotrimoxasole and itraconazole vo until the absolute granulocyte count rose above 1 x 10(9)/l. Platelet concentrates were given every other day until the platelet count rose above 20 x 10(9)/l. Complete remission (CR) was obtained in 87%. Fever developed in 29% and 2 cases were complicated by indwelling-catheter-related Pseudomona aeruginosa septicaemia, 1 Entamoeba hystolytica enteritis and 1 Pneumocystis carinii pneumonia; these patients were hospitalized to treat these infections specifically. In no case was the infection fatal. The median disease free-survival (DFS) was 17 months, 12-month DFS was 66%, and 30-month DFS was 17%. Our calculations have shown that 1700 USD/patient were saved by avoiding prolonged hospitalization; this may provide not only economical, but also psychological advantages to patients. PMID:7859871

  2. Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation.

    PubMed

    Schmid, Christoph; Labopin, Myriam; Socié, Gerard; Daguindau, Etienne; Volin, Liisa; Huynh, Anne; Bourhis, Jean Henri; Milpied, Noel; Cornelissen, Jan; Chevallier, Patrice; Maertens, Johan; Jindra, Pavel; Blaise, Didier; Lenhoff, Stig; Ifrah, Norbert; Baron, Frédéric; Ciceri, Fabio; Gorin, Claude; Savani, Bipin; Giebel, Sebastian; Polge, Emmanuelle; Esteve, Jordi; Nagler, Arnon; Mohty, Mohamad

    2015-10-22

    To analyze the influence of distinct combinations of molecular aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for cytogenetically normal acute myeloid leukemia (CN-AML), a retrospective registry analysis was performed on 702 adults undergoing HSCT in first complete remission (CR). Patients were grouped according to presence or absence of NPM1 mutations (NPM1(mut)) and FLT3 internal tandem duplications (FLT3-ITD). Double-negative patients were evaluated for mutations of the CCAAT/enhancer binding protein α gene (CEBPα). The influence of genotypes on relapse, non-relapse mortality, leukemia-free survival (LFS) and overall survival (OS), and a prognostic classification combining NPM1/FLT3-ITD profile and classical risk factors were calculated. Two-year OS from HSCT was 81 ± 5% in NPM1(mut)/FLT3(wt), 75 ± 3% in NPM1(wt)/FLT3(wt), 66 ± 3% in NPM1(mut)/FLT3-ITD, and 54 ± 7% in NPM1(wt)/FLT3-ITD (P = .003). Analysis of CEBPα among patients with NPM1(wt)/FLT3(wt) revealed excellent results both in patients with CEBPα(mut) and with a triple negative genotype (2-year OS: 100%/77 ± 3%). In a Cox-model of predefined variables, age, FLT3-ITD and >1 course of chemotherapy to reach CR were risk factors associated with inferior outcome, regardless of NPM1 mutational status, variations of transplant protocols, or development of graft-versus-host disease. In a prognostic risk classification, 2-year OS/LFS rates were 88 ± 3%/79 ± 4% without any, 77 ± 2%/73 ± 3% with one, and 53 ± 4%/50 ± 4 with ≥2 risk factors (P = .003/.002). PMID:26351297

  3. Hyperferritinemia at diagnosis predicts relapse and overall survival in younger AML patients with intermediate-risk cytogenetics.

    PubMed

    Lebon, Delphine; Vergez, François; Bertoli, Sarah; Harrivel, Véronique; De Botton, Stéphane; Micol, Jean-Baptiste; Marolleau, Jean-Pierre; Récher, Christian

    2015-08-01

    The prognostic value of ferritin level at diagnosis in AML patients is unknown. We studied 162 younger AML patients with intermediate-risk cytogenetics who received intensive chemotherapy. The median ferritin level at diagnosis was 633 μg/L and 128 (79%) patients had a ferritin level above the upper normal limit. Hyperferritinemia was significantly associated with a higher cumulative incidence of relapse as well as poorer disease-free and overall survival. In multivariate analysis, hyperferritinemia remained an independent poor prognosis factor. The level of ferritin at diagnosis has a major impact on relapse suggesting a link between inflammation, oxidative stress and chemoresistance in AML. PMID:26002512

  4. Daunorubicin Versus Mitoxantrone Versus Idarubicin As Induction and Consolidation Chemotherapy for Adults With Acute Myeloid Leukemia: The EORTC and GIMEMA Groups Study AML-10

    PubMed Central

    Mandelli, Franco; Vignetti, Marco; Suciu, Stefan; Stasi, Roberto; Petti, Maria-Concetta; Meloni, Giovanna; Muus, Petra; Marmont, Filippo; Marie, Jean-Pierre; Labar, Boris; Thomas, Xavier; Di Raimondo, Francesco; Willemze, Roel; Liso, Vincenzo; Ferrara, Felicetto; Baila, Liliana; Fazi, Paola; Zittoun, Robert; Amadori, Sergio; de Witte, Theo

    2009-01-01

    Purpose To compare the antitumor efficacy of three different anthracyclines in combination with cytarabine and etoposide in adult patients with newly diagnosed acute myeloid leukemia (AML). Patients and Methods We randomly assigned 2,157 patients (age range, 15 to 60 years) to receive intensive induction-consolidation chemotherapy containing either daunorubicin, idarubicin, or mitoxantrone. After achieving complete remission (CR), patients were assigned to undergo either allogeneic or autologous stem-cell transplantation (SCT), depending on the availability of a sibling donor. Results The overall CR rate (69%) was similar in the three groups. Autologous SCT was performed in 37% of cases in the daunorubicin arm versus only 29% and 31% in mitoxantrone and idarubicin, respectively (P < .001). However, the disease-free survival (DFS) and survival from CR were significantly shorter in the daunorubicin arm: the 5-year DFS was 29% versus 37% and 37% in mitoxantrone and idarubicin, respectively. The proportion of patients who underwent allogeneic SCT (22%) was equivalent in the three treatment groups, and the outcome was similar as well: the 5-year overall survival rates were 34%, 34%, and 31%, respectively. Conclusion In adult patients with AML who do not receive an allogeneic SCT, the use of mitoxantrone or idarubicin instead of daunorubicin enhances the long-term efficacy of chemotherapy. PMID:19826132

  5. Telomerase reverse transcriptase (TERT) A1062T mutation as a prognostic factor in Egyptian patients with acute myeloid leukemia (AML).

    PubMed

    Aref, Salah; El-Ghonemy, Mohamed Sabry; Abouzeid, Tarek Elsayed; El-Sabbagh, Amr Mohamed; El-Baiomy, Mohamed Ali

    2014-09-01

    This study aimed to evaluate the incidence and clinical and prognostic impact of TERT A1062T mutation in AML patients treated at Mansoura Oncology Center. Screening for TERT A1062T mutation in exon 15 of the TERT gene was performed on diagnostic DNA samples from 153 AML patients and 197 healthy subjects as a control group by using sequence-specific primers. TERT A1062T mutation was detected in 18 cases out of 153 patients (11.8 %) and in one out of 197 control group subjects (0.51 %). The achievement of complete remission was significantly higher in AML group with wild type as compared to that in the mutant one (53.3 vs 16.7 %, respectively). In addition, the relapse rate was significantly higher in the mutant patients as compared to those with wild type (62.5 vs 28.2 %, respectively). The AML patients with TERT (A1062T) mutation had shorter overall survival than patients with wild type (P = 0.001). In a multivariable analysis, TERT (A1062T) mutational status is independently worse predictor factor (P = 0.007) when controlling for cytogenetic status (P = <0.001), performance status (P = <0.001) and bone marrow blast cells (P = 0.001). In conclusion, TERT A1062T mutation is an independent negative prognostic factor in AML patients. Therefore, molecular testing for TERT A1062T mutation in patients with AML is recommended in order to delineate their prognostic status. PMID:25108601

  6. Mutated Nucleophosmin-1 (NPM1) in patients with Acute Myeloid Leukemia (AML) in remission and relapse

    PubMed Central

    Jain, Preetesh; Kantarjian, Hagop; Patel, Keyur; Faderl, Stefan; Garcia-Manero, Guillermo; Benjamini, Ohad; Borthakur, Gautam; Pemmaraju, Naveen; Kadia, Tapan; Daver, Naval; Nazha, Aziz; Luthra, Raja; Pierce, Sherry; Cortes, Jorge; Ravandi, Farhad

    2014-01-01

    Patients with newly diagnosed AML (n=360) including 137 (38%) with normal karyotype (NK) were evaluated. Overall, 60 (16.6%) patients including 46 of the 137 (33.5%) NK patients had NPM1 mutation at baseline. Thirty nine patients (30 NK) had available NPM1 status at the time of CR and all (100%) were negative for mutated NPM1. Among the patients with mutated NPM1 at baseline, 10/39 overall (25%) and 7/30 NK (23%) patients relapsed. NPM1 status was available for 8 patients (6 with NK) at the time of relapse. Among them, 7/8 overall (87%) and 5/6 NK (83%) patients had mutated NPM1, while 1/8 overall (12%) and 1/6 NK (16%) patients remained NPM1 wild type. Among the 300 patients (including 91 with NK) with wild type NPM1 at diagnosis, none acquired a mutated NPM1 clone, either at CR or at relapse. We conclude that mutated NPM1 is a stable and reliable prognostic marker in AML and can be used to assess MRD. PMID:24004182

  7. Peripheral Blood WT1 Expression Predicts Relapse in AML Patients Undergoing Allogeneic Stem Cell Transplantation

    PubMed Central

    Malagola, Michele; Skert, Cristina; Ruggeri, Giuseppina; Ribolla, Rossella; Bernardi, Simona; Borlenghi, Erika; Pagani, Chiara; Rossi, Giuseppe; Caimi, Luigi; Russo, Domenico

    2014-01-01

    To evaluate if WT1 expression may predict relapse after allo-SCT, we analyzed WT1 levels on peripheral blood (PB) and bone marrow (BM) before and after allo-SCT in 24 AML patients with WT1 overexpression at diagnosis. Five copies of WT1/ABL × 104 from PB were identified as the threshold value that correlated with relapse after allo-SCT. The same correlation was not identified when WT1 expression was assessed from bone marrow (BM). Eight out of 11 (73%) patients with a pre-allo-SCT PB-WT1 ≥ 5 and 4/13 (31%) patients with a pre-allo-SCT PB-WT1 < 5 relapsed, respectively (P = 0.04). The incidence of relapse was higher in patients with PB-WT1 ≥ 5 measured after allo-SCT, at the 3rd (56% versus 38%; P = 0.43) and at the 6th month (71% versus 20%; P = 0.03). Patients with pretransplant PB-WT1 < 5 had significantly better 2-year OS and LFS than patients with a PB-WT1 ≥ 5 (81% versus 0% and 63% versus 20%) (P = 0.02). Our data suggest the usefulness of WT1 monitoring from PB to predict the relapse in allotransplanted AML patients and to modulate the intensity of conditioning and/or the posttransplant immunosuppression in an attempt to reduce the posttransplant relapse risk. PMID:25202702

  8. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction: results from the UK NCRI AML17 trial in 1206 patients

    PubMed Central

    Russell, Nigel H.; Hills, Robert K.; Kell, Jonathan; Cavenagh, Jamie; Kjeldsen, Lars; McMullin, Mary-Frances; Cahalin, Paul; Dennis, Mike; Friis, Lone; Thomas, Ian F.; Milligan, Don; Clark, Richard E.

    2015-01-01

    Modifying induction therapy in acute myeloid leukemia (AML) may improve the remission rate and reduce the risk of relapse, thereby improving survival. Escalation of the daunorubicin dose to 90 mg/m2 has shown benefit for some patient subgroups when compared with a dose of 45 mg/m2, and has been recommended as a standard of care. However, 60 mg/m2 is widely used and has never been directly compared with 90 mg/m2. As part of the UK National Cancer Research Institute (NCRI) AML17 trial, 1206 adults with untreated AML or high-risk myelodysplastic syndrome, mostly younger than 60 years of age, were randomized to a first-induction course of chemotherapy, which delivered either 90 mg/m2 or 60 mg/m2 on days 1, 3, and 5 combined with cytosine arabinoside. All patients then received a second course that included daunorubicin 50 mg/m2 on days 1, 3, and 5. There was no overall difference in complete remission rate (73% vs 75%; odds ratio, 1.07 [0.83-1.39]; P = .6) or in any recognized subgroup. The 60-day mortality was increased in the 90 mg/m2 arm (10% vs 5% (hazard ratio [HR] 1.98 [1.30-3.02]; P = .001), which resulted in no difference in overall 2-year survival (59% vs 60%; HR, 1.16 [0.95-1.43]; P = .15). In an exploratory subgroup analysis, there was no subgroup that showed significant benefit, although there was a significant interaction by FLT3 ITD mutation. This trial is registered at http://www.isrctn.com as #ISRCTN55675535. PMID:25833957

  9. Donor Haplotype B of NK KIR Receptor Reduces the Relapse Risk in HLA-Identical Sibling Hematopoietic Stem Cell Transplantation of AML Patients.

    PubMed

    Impola, Ulla; Turpeinen, Hannu; Alakulppi, Noora; Linjama, Tiina; Volin, Liisa; Niittyvuopio, Riitta; Partanen, Jukka; Koskela, Satu

    2014-01-01

    Successful allogeneic hematopoietic stem cell transplantation (HSCT) depends not only on good HLA match but also on T-cell mediated graft-versus-leukemia (GvL) effect. Natural killer (NK) cells are able to kill malignant cells by receiving activation signal from the killer-cell immunoglobulin-like receptors (KIR) recognizing HLA molecules on a cancer cell. It has been recently reported that the risk of relapse in allogeneic hematopoietic stem cell transplantation (HSCT) is reduced in acute myeloid leukemia (AML) patients whose donors have several activating KIR genes or KIR B-motifs in unrelated donor setting, obviously due to enhanced GvL effect by NK cells. We studied the effect on relapse rate of donor KIR haplotypes in the HLA-identical adult sibling HSCT, done in a single center, in Helsinki University Central Hospital, Helsinki, Finland. Altogether, 134 patients with 6 different diagnoses were identified. Their donors were KIR genotyped using the Luminex and the SSP techniques. The clinical endpoint, that is, occurrence of relapse, was compared with the presence or absence of single KIR genes. Also, time from transplantation to relapse was analyzed. The patients with AML whose donors have KIR2DL2 or KIR2DS2 had statistically significantly longer relapse-free survival (P = 0.015). Our data support previous reports that donors with KIR B-haplotype defining genes have a lower occurrence of relapse in HSCT of AML patients. Determination of donor KIR haplotypes could be a useful addition for a risk assessment of HSCT especially in AML patients. PMID:25202311

  10. Donor Haplotype B of NK KIR Receptor Reduces the Relapse Risk in HLA-Identical Sibling Hematopoietic Stem Cell Transplantation of AML Patients

    PubMed Central

    Impola, Ulla; Turpeinen, Hannu; Alakulppi, Noora; Linjama, Tiina; Volin, Liisa; Niittyvuopio, Riitta; Partanen, Jukka; Koskela, Satu

    2014-01-01

    Successful allogeneic hematopoietic stem cell transplantation (HSCT) depends not only on good HLA match but also on T-cell mediated graft-versus-leukemia (GvL) effect. Natural killer (NK) cells are able to kill malignant cells by receiving activation signal from the killer-cell immunoglobulin-like receptors (KIR) recognizing HLA molecules on a cancer cell. It has been recently reported that the risk of relapse in allogeneic hematopoietic stem cell transplantation (HSCT) is reduced in acute myeloid leukemia (AML) patients whose donors have several activating KIR genes or KIR B-motifs in unrelated donor setting, obviously due to enhanced GvL effect by NK cells. We studied the effect on relapse rate of donor KIR haplotypes in the HLA-identical adult sibling HSCT, done in a single center, in Helsinki University Central Hospital, Helsinki, Finland. Altogether, 134 patients with 6 different diagnoses were identified. Their donors were KIR genotyped using the Luminex and the SSP techniques. The clinical endpoint, that is, occurrence of relapse, was compared with the presence or absence of single KIR genes. Also, time from transplantation to relapse was analyzed. The patients with AML whose donors have KIR2DL2 or KIR2DS2 had statistically significantly longer relapse-free survival (P = 0.015). Our data support previous reports that donors with KIR B-haplotype defining genes have a lower occurrence of relapse in HSCT of AML patients. Determination of donor KIR haplotypes could be a useful addition for a risk assessment of HSCT especially in AML patients. PMID:25202311

  11. Pediatric donor cell leukemia after allogeneic hematopoietic stem cell transplantation in AML patient from related donor.

    PubMed

    Bobadilla-Morales, Lucina; Pimentel-Gutiérrez, Helia J; Gallegos-Castorena, Sergio; Paniagua-Padilla, Jenny A; Ortega-de-la-Torre, Citlalli; Sánchez-Zubieta, Fernando; Silva-Cruz, Rocio; Corona-Rivera, Jorge R; Zepeda-Moreno, Abraham; González-Ramella, Oscar; Corona-Rivera, Alfredo

    2015-01-01

    Here we present a male patient with acute myeloid leukemia (AML) initially diagnosed as M5 and with karyotype 46,XY. After induction therapy, he underwent a HLA-matched allogeneic hematopoietic stem cell transplantation, and six years later he relapsed as AML M1 with an abnormal karyotype //47,XX,+10[2]/47,XX,+11[3]/48,XX,+10,+11[2]/46,XX[13]. Based on this, we tested the possibility of donor cell origin by FISH and molecular STR analysis. We found no evidence of Y chromosome presence by FISH and STR analysis consistent with the success of the allogeneic hematopoietic stem cell transplantation from the female donor. FISH studies confirmed trisomies and no evidence of MLL translocation either p53 or ATM deletion. Additionally 28 fusion common leukemia transcripts were evaluated by multiplex reverse transcriptase-polymerase chain reaction assay and were not rearranged. STR analysis showed a complete donor chimerism. Thus, donor cell leukemia (DCL) was concluded, being essential the use of cytological and molecular approaches. Pediatric DCL is uncommon, our patient seems to be the sixth case and additionally it presented a late donor cell leukemia appearance. Different extrinsic and intrinsic mechanisms have been considered to explain this uncommon finding as well as the implications to the patient. PMID:25674158

  12. DNMT3A R882 Mutations Predict a Poor Prognosis in AML: A Meta-Analysis From 4474 Patients.

    PubMed

    Yuan, Xiao-Qing; Peng, Li; Zeng, Wen-Jing; Jiang, Bin-Yuan; Li, Guan-Cheng; Chen, Xiao-Ping

    2016-05-01

    DNA (cytosine-5)-methyltransferase 3 alpha (DNMT3A) mutations were widely believed to be independently associated with inferior prognosis in acute myeloid leukemia (AML) patients. As dominant missense alterations in DNMT3A mutations, R882 mutations cause the focal hypomethylation phenotype. However, there remains debate on the influence of R882 mutations on AML prognosis. Thus, this meta-analysis aimed at further illustrating the prognostic power of DNMT3A R882 mutations in AML patients.Eligible studies were identified from 5 databases containing PubMed, Embase, Web of Science, Clinical Trials, and the Cochrane Library (up to October 25, 2015). Effects (hazard ratios [HRs] with 95% confidence interval [CI]) of relapse-free survival (RFS) and overall survival (OS) were pooled to estimate the prognostic power of mutant DNMT3A R882 in overall patients and subgroups of AML patients.Eight competent studies with 4474 AML patients including 694 with DNMT3A R882 mutations were included. AML patients with DNMT3A R882 mutations showed significant shorter RFS (HR = 1.40, 95% CI = 1.24-1.59, P < 0.001) and OS (HR = 1.47, 95% CI = 1.17-1.86, P = 0.001) in the overall population. DNMT3A R882 mutations predicted worse RFS and OS among the subgroups of patients under age 60 (RFS: HR = 1.44, 95% CI = 1.25-1.66, P < 0.001; OS: HR = 1.48, 95% CI = 1.15-1.90, P = 0.002), over age 60 (RFS: HR = 2.03, 95% CI = 1.40-2.93, P < 0.001; OS: HR = 1.85, 95% CI = 1.36-2.53, P < 0.001), cytogenetically normal (CN)-AML (RFS: HR = 1.52, 95% CI = 1.26-1.83, P < 0.001; OS: HR = 1.67, 95% CI = 1.16-2.41, P = 0.006), and non-CN-AML (RFS: HR = 1.96, 95% CI = 1.20-3.21, P = 0.006; OS: HR = 2.51, 95% CI = 1.52-4.15, P = 0.0038).DNMT3A R882 mutations possessed significant unfavorable prognostic influence on RFS and OS in AML patients. PMID:27149454

  13. Sorafenib plus all-trans retinoic acid for AML patients with FLT3-ITD and NPM1 mutations.

    PubMed

    Guenounou, Sarah; Delabesse, Eric; Récher, Christian

    2014-12-01

    Knowledge of the molecular basis of acute myeloid leukaemia has increased considerably in the past few years, and therapies targeting specific molecular defects of this disease are intensively investigated. Patients with both NPM1 and FLT3-ITD mutations encompass 20% of cytogenetically normal AML. The multikinase and FLT3 inhibitor, sorafenib, has shown some efficacy in patients with relapsed FLT3-ITD(+) AML. In addition, it is suggested that all-trans retinoic acid (ATRA) used in combination with chemotherapy has shown to improve outcome of patients harbouring NPM1 mutations. We report here the clinical course of three patients with refractory or relapsed FLT3-ITD(+) /NPM1(+) AML who achieved significant response upon sorafenib and ATRA combination. PMID:24689895

  14. Survival of AML patients relapsing after allogeneic hematopoietic cell transplantation: a CIBMTR study

    PubMed Central

    Bejanyan, Nelli; Weisdorf, Daniel J.; Logan, Brent R.; Wang, Hai-Lin; Devine, Steven M.; de Lima, Marcos; Bunjes, Donald W.; Zhang, Mei-Jie

    2015-01-01

    Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (alloHCT) remains a major therapeutic challenge. We studied outcomes of 1788 AML patients relapsing after alloHCT (1990–2010) during first or second complete remission (CR) to identify factors associated with longer post-relapse survival. Median time of post HCT relapse was 7 months (mo; range, 1–177). At relapse, 1231 patients (69%) received intensive therapy, including chemotherapy (CT) alone (n=660), donor lymphocyte infusion (DLI)±CT (n=202; %), or 2nd alloHCT±CT ±DLI (n=369), with subsequent CR rates of 29%. Median follow-up after relapse was 39 mo (range, <1–193). Survival for all patients was 23% at 1 year post-relapse; however, 3-yr overall survival correlated with time from HCT to relapse (4% for relapse during 1–6 mo period, 12% during 6 mo-2 yr, 26% during 2–3 yr, and 38% for ≥3 yr). In multivariable analysis, lower mortality was significantly associated with longer time from alloHCT to relapse (RR 0.55 for 6 mo-2 yr, RR 0.39 for 2–3 yr, and RR 0.28 for ≥3 yr; p<0.0001) and a 1st HCT using reduced-intensity conditioning (RR=0.77; 95% CI 0.66–0.88, p=0.0002). In contrast, inferior survival was associated with age >40 yr (RR=1.42, 95% CI 1.24–1.64; p<0.0001), active GVHD at relapse (RR=1.25, 95% CI 1.13–1.39; p<0.0001), adverse cytogenetics (RR=1.37, 95% CI 1.09–1.71; p=0.0062), mismatched URD (RR=1.61, 95% CI 1.22–2.13; p=0.0008), and use of cord blood for 1st HCT (RR=1.23, 95% CI 1.06–1.42; p=0.0078). AML relapse after alloHCT predicted poor survival; however, patients who relapsed ≥6 mo after their initial alloHCT had better survival and may benefit from intensive therapy such as 2nd alloHCT±DLI. PMID:25460355

  15. Treosulfan, Fludarabine and 2 Gy Total Body Irradiation Followed by Allogeneic Hematopoietic Cell Transplantation in Patients with MDS and AML

    PubMed Central

    Gyurkocza, Boglarka; Gutman, Jonathan; Nemecek, Eneida R.; Bar, Merav; Milano, Filippo; Ramakrishnan, Aravind; Scott, Bart; Fang, Min; Wood, Brent; Pagel, John M.; Baumgart, Joachim; Delaney, Colleen; Maziarz, Richard T.; Sandmaier, Brenda M.; Estey, Elihu H.; Appelbaum, Frederick R.; Storer, Barry E.; Deeg, H. Joachim

    2014-01-01

    Allogeneic hematopoietic cell transplantation (HCT) offers curative therapy for many patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics. In this prospective phase II trial we assessed the efficacy and toxicity of treosulfan, fludarabine and 2 Gy total body irradiation (TBI) as conditioning for allogeneic HCT in patients with MDS or AML. Ninety-six patients with MDS (n=36; 15 RMCD; 10 RAEB-1; 10 RAEB-2; 1 CMML-1) or AML (n=60; 35 CR1; 18 CR2; 3 advanced CR; 4 refractory relapse) were enrolled; median age was 51 (range: 1–60) years. Twelve patients had undergone a prior HCT with high intensity conditioning. Patients received intravenous (IV) treosulfan, 14 g/m2/day on days −6 to −4, IV fludarabine, 30 mg/m2/day on days −6 to −2, and 2 Gy TBI on day 0, followed by infusion of hematopoietic cells from related (n=27) or unrelated (n=69) donors. Graft-vs.-host disease prophylaxis consisted of tacrolimus and methotrexate. With a median follow-up of 30 months, the 2-year overall survival (OS), relapse incidence and non-relapse mortality were 73%, 27% and 8%, respectively. The incidences of grades II–IV (III–IV) acute and chronic graft-versus-host disease were 59% (10%) and 47%, respectively. Two-year OS was not significantly different between MDS patients with poor risk and good/intermediate risk cytogenetics (69% and 85%, respectively), or between AML patients with unfavorable and favorable/intermediate risk cytogenetics (64% and 76%, respectively). In AML patients, minimal residual disease (MRD; n=10) at the time of HCT predicted higher relapse incidence (70% vs. 18%) and lower OS (41% vs. 79%) at 2 years, when compared to patients without MRD. In conclusion, treosulfan, fludarabine and low-dose TBI provided effective conditioning for allogeneic HCT in patients with MDS or AML, and resulted in low relapse incidence, regardless

  16. A new model to predict remission status in AML patients based on day 14 bone marrow biopsy.

    PubMed

    Norkin, Maxim; Chang, Myron; An, Qi; Leather, Helen; Katragadda, Lakshmikanth; Li, Ying; Moreb, Jan S; May, W Stratford; Brown, Randy A; Hsu, Jack W; Hiemenz, John W; Wingard, John R; Cogle, Christopher R

    2016-07-01

    Although bone marrow evaluation on day 14 after initiation of induction chemotherapy (D14 BM) is a widely accepted practice in patients with acute myeloid leukemia (AML), it has suboptimal predictive value for predicting complete remission. We retrospectively analyzed pretreatment characteristics and post-induction response in a cohort of AML patients to determine if adding clinical and laboratory characteristics can improve the predictive value of the D14 BM evaluation. Among 297 patients treated for AML at the single institution 183 patients (61%) had leukemia-positive D14 BM. Of those, 94 were given reinduction chemotherapy and 89 were not. Of the 89 patients who did not receive reinduction, 32 (36%) subsequently achieved complete remission (CR) or complete remission with incomplete count recovery (CRi), and 57 (64%) had persistent disease. Persistent disease after positive D14 BM was more likely associated with higher percentage of D14 myeloblasts, a history of relapsed disease before induction, and higher risk disease compared to patients who subsequently achieved CR. Age, diagnostic white blood cell count, and the D14 BM cellularity did not influence the subsequent likelihood of achieving remission in patients with a positive D14 BM. A new mathematical equation was created and resulted in a positive predictive value of 83%, negative predictive value 90% and accuracy 88% for correctly identifying remission status after positive D14 BM in AML. The accuracy of predicting response using these additional parameters was significantly higher than without (0.88 vs. 0.80, P=0.002). Our new model provides better accuracy for predicting the likelihood of achieving remission and if validated in future studies may be useful for managing AML patients. PMID:27132034

  17. NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS).

    PubMed

    Schneider, Friederike; Hoster, Eva; Unterhalt, Michael; Schneider, Stephanie; Dufour, Annika; Benthaus, Tobias; Mellert, Gudrun; Zellmeier, Evelin; Bohlander, Stefan K; Feuring-Buske, Michaela; Buske, Christian; Braess, Jan; Fritsch, Susanne; Heinecke, Achim; Sauerland, Maria C; Berdel, Wolfgang E; Buechner, Thomas; Woermann, Bernhard J; Hiddemann, Wolfgang; Spiekermann, Karsten

    2009-05-21

    Mutations in the NPM1 gene represent the most frequent genetic alterations in patients with acute myeloid leukemia (AML) and are associated with a favorable outcome. In 690 normal karyotype (NK) AML patients the complete remission rates (CRs) and the percentage of patients with adequate in vivo blast cell reduction 1 week after the end of the first induction cycle were significantly higher in NPM1(+) (75% and 80%, respectively) than in NPM1(-) (57% and 57%, respectively) patients, but were unaffected by the FLT3-ITD status. Multivariate analyses revealed the presence of a NPM1 mutation as an independent positive prognostic factor for the achievement of an adequate day-16 blast clearance and a CR. In conclusion, NPM1(+) blast cells show a high in vivo sensitivity toward induction chemotherapy irrespective of the FLT3-ITD mutation status. These findings provide insight into the pathophysiology and help to understand the favorable clinical outcome of patients with NPM1(+) AML. PMID:19279329

  18. Invasive fungal infections in AML/MDS patients treated with azacitidine: a risk worth considering antifungal prophylaxis?

    PubMed

    Pomares, Helena; Arnan, Montserrat; Sánchez-Ortega, Isabel; Sureda, Anna; Duarte, Rafael F

    2016-08-01

    The aim of this study is to analyse the risk of invasive fungal infection (IFI) and the need for antifungal prophylaxis in patients with acute myeloid leukaemia and myelodysplastic syndromes (AML/MDS) treated with azacitidine. We retrospectively analysed the incidence of IFI according to EORTC-MSG criteria in 121 consecutive AML/MDS patients receiving 948 azacitidine courses (median 5, range 1-43) between June 2007 and June 2015. Four cases of IFI (two possible, one probable aspergillosis and one proven candidemia) occurred in this series. The incidence rate of proven/probable IFI was 0.21% per treatment cycle and 1.6% per patient treated for the whole series, and 0.73% per treatment cycle and 4.1% per patient treated in those with severe neutropenia. Two patients died from IFI, leading to an IFI-attributable mortality rate of 1.65% per patient and 0.21% per treatment cycle. The numbers needed to treat with prophylaxis to prevent one case of IFI are 238 azacitidine cycles or 30 patients throughout their whole treatment course, and 137 azacitidine cycles or 24 patients among those with severe neutropenia. AML/MDS patients treated with azacitidine, including those with severe prolonged neutropenia, have a very low risk of IFI which does not justify the use of antifungal prophylaxis. PMID:27027972

  19. Interactions and relevance of blast percentage and treatment strategy among younger and older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

    PubMed

    DiNardo, Courtney D; Garcia-Manero, Guillermo; Pierce, Sherry; Nazha, Aziz; Bueso-Ramos, Carlos; Jabbour, Elias; Ravandi, Farhad; Cortes, Jorge; Kantarjian, Hagop

    2016-02-01

    Acute myeloid leukemia (AML) is defined as ≥20% myeloblasts, representing a change from original guidelines where ≤30% blasts were considered as myelodysplastic syndromes (MDS), and 20-29% blasts classified as refractory anemia with excess blasts in transformation (RAEB-T). Whether the diagnostic bone marrow blast percentage has current value with regards to patient prognostication or identification of optimal treatment strategies is unclear. We retrospectively studied 1652 treatment-naïve adults with MDS or AML and ≥10% blasts from January 2000 to April 2014. Patients with 20-29% blasts were more similar to MDS patients in terms of advanced age, increased frequency of poor-risk cytogenetics, lower WBC count, and less frequent NPM1 and FLT3-ITD mutations. Median overall survival of MDS and RAEB-T were similar, 16.0 and 16.0 months, compared to 13.5 months for AML with ≥30% blasts (P = 0.045). Multivariate analysis showed inferior survival with increased age (HR 1.81 age 60-69, HR 2.68 age ≥70, P < 0.0005); poor-risk cytogenetics (HR 2.25, P < 0.0005); therapy-related disease (HR 1.44, P < 0.0005); and markers of proliferative disease including WBC ≥25 × 10(9) /L (HR 1.35, P = 0.0003), elevated LDH count (HR 1.24, P = 0.0015), and peripheral blasts (HR 1.25, P = 0.004). Among younger patients (≤60 years), intensive AML-type therapy resulted in similar outcomes regardless of blast percentage, suggesting this to be optimal therapy in this context. Among older patients (≥70 years), patients with 20-29% blasts had similar outcomes to patients with <20% blasts, and better than those with ≥30% blasts. In addition, among older patients, epigenetic therapy provided at least equivalent outcome to intensive chemotherapy. PMID:26799610

  20. FLT3 and NPM1 mutations in a cohort of AML patients and detection of a novel mutation in tyrosine kinase domain of FLT3 gene from Western India.

    PubMed

    Ghosh, Kanjaksha; Swaminathan, Suchitra; Madkaikar, Manisha; Gupta, Maya; Kerketta, Lily; Vundinti, Baburao

    2012-11-01

    Acute myeloid leukemia (AML) is an aggressive hematological disorder characterized by the loss of ability of the hematopoietic progenitor cells to differentiate and proliferate normally leading to an accumulation of immature myeloid cells in the bone marrow. Several novel molecular genetic aberrations in FLT3 and NPM1 have been shown to have a prognostic impact in AML, particularly in those having normal karyotype. Though there is substantial amount of data on these mutations from western literature, there is surprisingly little data from Indian subcontinent on the frequency of this mutation in AML patients from India. The present study screens a large cohort of non-acute promyelocytic leukemia (APL) AML patients (207 patients) for the presence of FLT3 and NPM1 mutations and further correlates with cytogenetics, immunophenotypic characteristics and with follow-up data wherever available. During the course of study, 56 APL patients were also studied. Briefly, both FLT3 (internal tandem duplication (ITD) in 19.4% and tyrosine kinase domain (TKD) in 9%) and NPM1 mutations were detected in 28.4% of the total non-APL AML patients screened showing distinct correlations with hematologic, immunophenotypic, cytogenetics characteristics and follow-up. With regards to adult APL patients, 22.2 and 32.6% of the patients showed FLT3 and NPM1 mutation, respectively. In the pediatrics age group (<15 years), 23 and 16% of patients with APL showed FLT3 and NPM1 mutation, respectively, while in non-APL patient is this age group, 23% of patients showed both FLT3 and NPM1 mutation. NPM1 mutation was distinctly uncommon in younger age group of patients. In contrast to report elsewhere, most of our FLT3 mutation was in exon 11 rather than in exon 12. FLT3 mutation due to ITD or TKD mutation was detected in 2:1 ratio in our patients and a new TKD mutation was also detected S840G in an M5 patient who did not go into remission and had a short survival of 3 months from diagnosis. Generally

  1. Case report of FLT3-ITD-positive AML patient 11 years after living donor liver transplantation.

    PubMed

    Taniai, N; Yoshida, H; Kawano, Y; Uchida, E

    2014-04-01

    With the increasing number of long-term survivors of living donor liver transplantation, the occurrence of secondary cancer is sometimes reported. Solid tumors such as lymphomas are mainly observed. However, only 8 cases of leukemia have been reported so far. For patients younger than 15 years old, leukemia developed in 4 within 3 years after the liver transplantation, whereas acute lymphoblastic leukemia developed in only 1 patient. This is the first case report of a patient in whom FLT3-ITD-positive acute myeloid leukemia (AML) developed more than 10 years after living donor liver transplantation for congenital biliary atresia. AML developed in a 14-year-old boy 11 years after living donor liver transplantation from his father. The patient received the transplant at the age of 3 years and was treated with tacrolimus and methylprednisolone for transplant rejection. Eleven years posttransplantation, he visited the hospital with general malaise and anemia. Blood tests revealed an elevated white blood cell count of 60,100/μL, and the patient was diagnosed with AML. Chromosome analysis revealed a t(6; 9) (p23 q34) translocation; moreover, genetic testing revealed a FLT3-ITD-positive mutation. We started treatment in accordance with the Tokyo Children's Cancer Study Group AML99 protocol. With chemotherapy treatment, the patient achieved complete remission. After chemotherapy, we performed stem cell transplantation from his father. Other patients were reported in relatively early stages after liver transplantation, but our case was more than 10 years posttransplantation. The association with the onset of congenital bile duct atresia and leukemia is still not clear, but we consider the possibility that long-term immunosuppressive drugs contribute to developing leukemia. PMID:24767404

  2. Patient Eye Examinations - Adults

    MedlinePlus

    ... Examinations, Adults Patient Eye Examinations, Children Refractive Errors Scientists in the Laboratory Visual Acuity Testing Patient Eye Examinations, Adults × Warning message Automatic fallback to the cURL connection method kicked in to handle the request. Result code ...

  3. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts.

    PubMed

    Dombret, Hervé; Seymour, John F; Butrym, Aleksandra; Wierzbowska, Agnieszka; Selleslag, Dominik; Jang, Jun Ho; Kumar, Rajat; Cavenagh, James; Schuh, Andre C; Candoni, Anna; Récher, Christian; Sandhu, Irwindeep; Bernal del Castillo, Teresa; Al-Ali, Haifa Kathrin; Martinelli, Giovanni; Falantes, Jose; Noppeney, Richard; Stone, Richard M; Minden, Mark D; McIntyre, Heidi; Songer, Steve; Lucy, Lela M; Beach, C L; Döhner, Hartmut

    2015-07-16

    This multicenter, randomized, open-label, phase 3 trial evaluated azacitidine efficacy and safety vs conventional care regimens (CCRs) in 488 patients age ≥65 years with newly diagnosed acute myeloid leukemia (AML) with >30% bone marrow blasts. Before randomization, a CCR (standard induction chemotherapy, low-dose ara-c, or supportive care only) was preselected for each patient. Patients then were assigned 1:1 to azacitidine (n = 241) or CCR (n = 247). Patients assigned to CCR received their preselected treatment. Median overall survival (OS) was increased with azacitidine vs CCR: 10.4 months (95% confidence interval [CI], 8.0-12.7 months) vs 6.5 months (95% CI, 5.0-8.6 months), respectively (hazard ratio [HR] was 0.85; 95% CI, 0.69-1.03; stratified log-rank P = .1009). One-year survival rates with azacitidine and CCR were 46.5% and 34.2%, respectively (difference, 12.3%; 95% CI, 3.5%-21.0%). A prespecified analysis censoring patients who received AML treatment after discontinuing study drug showed median OS with azacitidine vs CCR was 12.1 months (95% CI, 9.2-14.2 months) vs 6.9 months (95% CI, 5.1-9.6 months; HR, 0.76; 95% CI, 0.60-0.96; stratified log-rank P = .0190). Univariate analysis showed favorable trends for azacitidine compared with CCR across all subgroups defined by baseline demographic and disease features. Adverse events were consistent with the well-established safety profile of azacitidine. Azacitidine may be an important treatment option for this difficult-to-treat AML population. This trial was registered at www.clinicaltrials.gov as #NCT01074047. PMID:25987659

  4. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts

    PubMed Central

    Seymour, John F.; Butrym, Aleksandra; Wierzbowska, Agnieszka; Selleslag, Dominik; Jang, Jun Ho; Kumar, Rajat; Cavenagh, James; Schuh, Andre C.; Candoni, Anna; Récher, Christian; Sandhu, Irwindeep; Bernal del Castillo, Teresa; Al-Ali, Haifa Kathrin; Martinelli, Giovanni; Falantes, Jose; Noppeney, Richard; Stone, Richard M.; Minden, Mark D.; McIntyre, Heidi; Songer, Steve; Lucy, Lela M.; Beach, C. L.; Döhner, Hartmut

    2015-01-01

    This multicenter, randomized, open-label, phase 3 trial evaluated azacitidine efficacy and safety vs conventional care regimens (CCRs) in 488 patients age ≥65 years with newly diagnosed acute myeloid leukemia (AML) with >30% bone marrow blasts. Before randomization, a CCR (standard induction chemotherapy, low-dose ara-c, or supportive care only) was preselected for each patient. Patients then were assigned 1:1 to azacitidine (n = 241) or CCR (n = 247). Patients assigned to CCR received their preselected treatment. Median overall survival (OS) was increased with azacitidine vs CCR: 10.4 months (95% confidence interval [CI], 8.0-12.7 months) vs 6.5 months (95% CI, 5.0-8.6 months), respectively (hazard ratio [HR] was 0.85; 95% CI, 0.69-1.03; stratified log-rank P = .1009). One-year survival rates with azacitidine and CCR were 46.5% and 34.2%, respectively (difference, 12.3%; 95% CI, 3.5%-21.0%). A prespecified analysis censoring patients who received AML treatment after discontinuing study drug showed median OS with azacitidine vs CCR was 12.1 months (95% CI, 9.2-14.2 months) vs 6.9 months (95% CI, 5.1-9.6 months; HR, 0.76; 95% CI, 0.60-0.96; stratified log-rank P = .0190). Univariate analysis showed favorable trends for azacitidine compared with CCR across all subgroups defined by baseline demographic and disease features. Adverse events were consistent with the well-established safety profile of azacitidine. Azacitidine may be an important treatment option for this difficult-to-treat AML population. This trial was registered at www.clinicaltrials.gov as #NCT01074047. PMID:25987659

  5. Immune responses to WT1 in patients with AML or MDS after chemotherapy and allogeneic stem cell transplantation.

    PubMed

    Casalegno-Garduño, Rosaely; Schmitt, Anita; Spitschak, Alf; Greiner, Jochen; Wang, Lei; Hilgendorf, Inken; Hirt, Carsten; Ho, Anthony D; Freund, Mathias; Schmitt, Michael

    2016-04-01

    Wilms' tumor gene 1 (WT1) is overexpressed in leukemia and WT1-derived CD8(+) T-cell epitopes for immunotherapies targeting WT1 have been defined. Here, we analyzed expression of WT1 in 226 peripheral blood and bone marrow samples from patients with acute myeloid leukemia or myelodysplastic syndrome (AML/MDS) before and after allogeneic stem cell transplantation (SCT). Transcripts were assessed by quantitative polymerase chain reaction, and WT1-specific CD8+ cytotoxic T cells (CTL) were monitored by tetramer staining and enzyme-linked immunospot (ELISPOT) assays. Reduction of WT1 levels correlated with a longer survival (p < 0.01). Increment of WT1 transcripts eventually resulted in relapse and subsequent death of the patients. In patients with longer survival and continuous complete remission (cCR) after SCT, higher and enduring frequencies of WT1-specific CTL than in patients developing a relapse were detected. These cells were effector T cells secreting interferon gamma and granzyme B. In summary, WT1 is a suitable marker for the detection of minimal residual disease after SCT or chemotherapy. A rising WT1 signal correlated with a dismal prognosis of the patients. WT1-specific CD8(+) T cells might contribute to the maintenance of a cCR. Targeting WT-1 by peptide/protein vaccination as well as adoptive transfer of genetically modified T cells are future options in the individualized therapy for AML/MDS patients. PMID:26519872

  6. Azacitidine might be beneficial in a subgroup of older AML patients compared to intensive chemotherapy: a single centre retrospective study of 227 consecutive patients

    PubMed Central

    2013-01-01

    Background Treatment options in older acute myeloid leukaemia (AML) patients include intensive chemotherapy, best supportive care (BSC), and hypomethylating agents. Currently, limited data is available on hypomethylating agents in older AML patients in unselected patient populations. Methods To compare the effectiveness of azacitidine with conventional therapy, we collected data of 227 consecutive AML patients (≥60 years) who were treated with azacitidine (N = 26), intensive chemotherapy (N = 90), or BSC (N = 97). Results Azacitidine-treated patients were older and had more comorbidities, but lower white blood cell- and bone marrow blast counts compared with intensive chemotherapy patients. Complete or partial response was achieved in 42% of azacitidine-treated patients and in 73% of intensive chemotherapy patients (P = 0.005). However, the overall survival (OS) was similar (1-year-OS 57% versus 56%, P = 0.93; 2-year-OS 35% versus 35%, P = 0.92), and remained similar after correction for risk factors in a multivariate analysis. Patients treated with BSC had an inferior OS (1-year- and 2-year-OS 16% and 2%, P < 0.001). Compared to intensive chemotherapy, azacitidine-treated patients spent less days in the hospital (median in first three months 0.5 versus 56, P < 0.001), and needed less red blood cell and platelet transfusions (median per month 2.7 versus 7, P < 0.001 and 0.3 versus 5, P < 0.001) in the first three months. Conclusions Azacitidine treatment is associated with a comparable OS but higher tolerability in a subgroup of older AML patients compared with intensive chemotherapy. Patients receiving BSC had a poor prognosis. PMID:23587459

  7. Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia.

    PubMed

    Müller-Tidow, C; Tschanter, P; Röllig, C; Thiede, C; Koschmieder, A; Stelljes, M; Koschmieder, S; Dugas, M; Gerss, J; Butterfaß-Bahloul, T; Wagner, R; Eveslage, M; Thiem, U; Krause, S W; Kaiser, U; Kunzmann, V; Steffen, B; Noppeney, R; Herr, W; Baldus, C D; Schmitz, N; Götze, K; Reichle, A; Kaufmann, M; Neubauer, A; Schäfer-Eckart, K; Hänel, M; Peceny, R; Frickhofen, N; Kiehl, M; Giagounidis, A; Görner, M; Repp, R; Link, H; Kiani, A; Naumann, R; Brümmendorf, T H; Serve, H; Ehninger, G; Berdel, W E; Krug, U

    2016-03-01

    DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients. PMID:26522083

  8. Recovery of ovarian function and pregnancy in a patient with AML after myeloablative busulphan-based conditioning regimen.

    PubMed

    Balashov, Dmitry N; Papusha, Ludmila I; Nazarenko, Tatiana A; Trakhtman, Pavel E; Revishvili, Nino A; Maschan, Alexei A; Persiantseva, Marina I; Andriutsa, Anna V; Skorobogatova, Elena V; Skvortsova, Yulia V; Rumiantsev, Alexander G

    2011-05-01

    We report a rare case of ovarian function recovery and pregnancy after hormone-replacement therapy (HRT) in the acute myeloblastic leukemia (AML) patient in third complete remission received hematopoietic stem cell transplantation (HSCT) with busulphan-based conditioning regimen. Successful engraftment of the donor cells and full donor's chimerism was achieved without the signs of leukemia. One year after HSCT the patient received a course of HRT as a treatment of hypergonadotropic hypogonadism. After 12 months of HRT the recovery of ovarian function was confirmed. Eight years after the HSCT spontaneous pregnancy occurred; heartbeat of the fetus was registered on week 7. Three weeks later a nonsevere vaginal bleeding occurred and the ultrasound examination showed a nondeveloping pregnancy. Genetic examination of the abortion material showed a full triploid genotype (69 XXX). To our knowledge this is a first case of ovarian function restoration and spontaneous pregnancy in a AML patient after multiple courses of high-dose chemotherapy and busulphan-based myeloablative conditioning for HSCT. PMID:21423042

  9. Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-25

    Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults; AML (Adult) With 11q23 (MLL) Abnormalities; AML (Adult) With Del(5q); AML (Adult) With Inv(16)(p13;q22); AML (Adult) With t(16;16)(p13;q22); AML (Adult) With t(8;21)(q22;q22); Secondary AML (Adult); Untreated AML (Adult)

  10. A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS.

    PubMed

    Keilholz, Ulrich; Letsch, Anne; Busse, Antonia; Asemissen, Anne Marie; Bauer, Sandra; Blau, Igor Wolfgang; Hofmann, Wolf-Karsten; Uharek, Lutz; Thiel, Eckhard; Scheibenbogen, Carmen

    2009-06-25

    This study investigated the immunogenicity of Wilms tumor gene product 1 (WT1)-peptide vaccination in WT1-expressing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients without curative treatment option. Vaccination consisted of granulocyte-macrophage colony-stimulating factor subcutaneously days 1 to 4, and WT1.126-134 peptide and 1 mg keyhole limpet hemocyanin on day 3. The initial 9 patients received 4 vaccinations biweekly, then monthly, and the subsequent 10 patients received continual biweekly vaccination. Seventeen AML patients and 2 refractory anemia with excess blasts patients received a median of 11 vaccinations. Treatment was well tolerated. Objective responses in AML patients were 10 stable diseases (SDs) including 4 SDs with more than 50% blast reduction and 2 with hematologic improvement. An additional 4 patients had clinical benefit after initial progression, including 1 complete remission and 3 SDs. WT1 mRNA levels decreased at least 3-fold from baseline in 35% of patients. In 8 of 18 patients, WT1-tetramer(+) T cells increased in blood and in 8 of 17 patients in bone marrow, with a median frequency in bone marrow of 0.18% at baseline and 0.41% in week 18. This WT1 vaccination study provides immunologic, molecular, and preliminary evidence of potential clinical efficacy in AML patients, warranting further investigations. PMID:19389880

  11. Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML

    ClinicalTrials.gov

    2015-01-22

    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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  12. Increased C-kit intensity is a poor prognostic factor for progression-free and overall survival in patients with newly diagnosed AML.

    PubMed

    Advani, Anjali S; Rodriguez, Cristina; Jin, Tao; Jawde, Rony Abou; Saber, Wael; Baz, Rachid; Kalaycio, Matt; Sobecks, Ronald; Sekeres, Mikkael; Tripp, Barbara; Hsi, Eric

    2008-06-01

    C-kit, a tyrosine kinase receptor, is expressed on most myeloid blasts and is thought to be important in the pathogenesis of AML. Activation of the c-kit receptor leads to phosphorylation and activation of downstream signaling proteins, which are important for cell survival and proliferation. Here, we discuss the prognostic impact of c-kit intensity, measured using the mean fluorescent index (MFI) in patients with newly diagnosed AML. On multivariate analysis, c-kit MFI>20.3 correlated with a decreased progression-free survival and overall survival, independent of known prognostic factors (age, white blood count at diagnosis and cytogenetics). Whether inhibiting c-kit in patients with AML will alter prognosis is the basis of ongoing clinical trials. PMID:17928050

  13. Treatment Options for Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  14. Stages of Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  15. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  16. Role of autologous hematopoietic stem cell transplantation according to the NPM1/FLT3-ITD molecular status for cytogenetically normal AML patients: a GOELAMS study.

    PubMed

    Guièze, Romain; Cornillet-Lefebvre, Pascale; Lioure, Bruno; Blanchet, Odile; Pigneux, Arnaud; Recher, Christian; Bonmati, Caroline; Fegueux, Nathalie; Bulabois, Claude-Eric; Bouscary, Didier; Vey, Norbert; Delain, Martine; Turlure, Pascal; Himberlin, Chantal; Harousseau, Jean-Luc; Dreyfus, Francois; Béné, Marie C; Ifrah, Norbert; Chevallier, Patrice

    2012-12-01

    The choice of postremission therapy for acute myeloid leukemia (AML) patients is now based on the blasts' cytogenetic and molecular profile. However, the potential benefit of autologous hematopoietic stem cell transplantation (auto-HSCT) according to the NPM1/FLT3-ITD status has been poorly studied in AML patients with a normal karyotype (NK). Therefore, we evaluated the NPM1/FLT3-ITD molecular status in 135 NK-AML patients treated by allogeneic HSCT (allo-HSCT), auto-HSCT, or chemotherapy as consolidation therapy within the GOELAMS LAM-2001 trial. In univariate analyzes, 4-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher for NPM1+/FLT3-ITD- patients compared with patients presenting another molecular profile (61 vs. 43% and 72 vs. 48%, P = 0.02 and P = 0.01, respectively). In the NPM1+/FLT3-ITD- subgroup, there was no benefit for allo-HSCT or auto-HSCT vs. chemotherapy (4-year LFS: 71, 56, and 60%; 4-year OS: 73, 71, and 60%, respectively; P = NS). For patients with other NPM1/FLT3-ITD molecular profiles, allo-HSCT was found to be the best consolidation therapy, whereas auto-HSCT was associated with a better outcome when compared with chemotherapy (allo-HSCT-, auto-HSCT-, and chemotherapy-related 4-year LFS: 68, 44, and 36%, P = 0.004; 4-year OS: 68, 52, and 29%, respectively, P = 0.02). Our study indicates that allo-HSCT and auto-HSCT provide similar outcomes compared with chemotherapy as consolidation for NPM1+/FLT3-ITD- NK-AML patients. For NK-AML patients with an adverse molecular profile, auto-HSCT could represent an alternative therapeutic approach when no human leukocyte antigen-matched allogeneic donor is available. PMID:22911473

  17. Generation of a cord blood-derived Wilms Tumor 1 dendritic cell vaccine for AML patients treated with allogeneic cord blood transplantation

    PubMed Central

    de Haar, Colin; Plantinga, Maud; Blokland, Nina JG; van Til, Niek P; Flinsenberg, Thijs WH; Van Tendeloo, Viggo F; Smits, Evelien L; Boon, Louis; Spel, Lotte; Boes, Marianne; Boelens, Jaap Jan; Nierkens, Stefan

    2015-01-01

    The poor survival rates of refractory/relapsed acute myeloid leukemia (AML) patients after haematopoietic cell transplantation (HCT) requires the development of additional immune therapeutic strategies. As the elicitation of tumor-antigen specific cytotoxic T lymphocytes (CTLs) is associated with reduced relapses and enhanced survival, enhanced priming of these CTLs using an anti-AML vaccine may result in long-term immunity against AML. Cord blood (CB), as allogeneic HCT source, may provide a unique setting for such post-HCT vaccination, considering its enhanced graft-versus-leukemia (GvL) effects and population of highly responsive naïve T cells. It is our goal to develop a powerful and safe immune therapeutic strategy composed of CB-HCT followed by vaccination with CB CD34+-derived dendritic cells (DCs) presenting the oncoprotein Wilms Tumor-1 (WT1), which is expressed in AML-blasts in the majority of patients. Here, we describe the optimization of a clinically applicable DC culture protocol. This two-step protocol consisting of an expansion phase followed by the differentiation toward DCs, enables us to generate sufficient cord blood-derived DCs (CBDCs) in the clinical setting. At the end of the culture, the CBDCs exhibit a mature surface phenotype, are able to migrate, express tumor antigen (WT1) after electroporation with mRNA encoding the full-length WT1 protein, and stimulate WT1-specific T cells. PMID:26451309

  18. Protective effect of CMV reactivation on relapse after allogeneic hematopoietic cell transplantation in AML patients is influenced by their conditioning regimen

    PubMed Central

    Manjappa, Shivaprasad; Bhamidipati, Pavan Kumar; Stokerl-Goldstein, Keith E.; DiPersio, John F.; Uy, Geoffrey L.; Westervelt, Peter; Liu, Jingxia; Schroeder, Mark A.; Vij, Ravi; Abboud, Camille N.; Fehniger, Todd A; Cashen, Amanda F.; Pusic, Iskra; Jacoby, Meagan; Meera, Srinidhi J.; Romee, Rizwan

    2014-01-01

    Cytomegalovirus (CMV) reactivation after allogeneic hematopoietic cell transplant (allo-HCT) has been associated with reduced risk of relapse in patients with acute myeloid leukemia (AML). However the influence of the conditioning regimen on this protective effect of CMV reactivation after allo-HCT is relatively unexplored. To address this, we evaluated the risk of relapse in 264 AML patients who received T cell replete, 6/6 HLA matched sibling or 10/10 HLA matched unrelated donor transplantation at a single institution between 2006 and 2011. Out of these 264 patients, 206 received myeloablative (MA) and 58 received reduced intensity conditioning (RIC) regimens. CMV reactivation was observed in 88 patients with MA conditioning and 37 patients with RIC. At a median follow up of 299 days, CMV reactivation was associated with significantly lower risk of relapse in patients who received MA conditioning both in univariate (P= .01) and multivariate analyses (hazard ratio of 0.5246, P= .006), however CMV reactivation did not significantly affect the risk of relapse in our RIC cohort. These results confirm the protective effect of CMV reactivation on relapse in AML patients after allo-HCT reported by previous studies, however they suggest that this protective effect of CMV reactivation on relapse is influenced by the conditioning regimen used with the transplant. PMID:24120526

  19. Extended survival and reduced risk of AML progression in erythroid-responsive lenalidomide-treated patients with lower-risk del(5q) MDS

    PubMed Central

    List, A F; Bennett, J M; Sekeres, M A; Skikne, B; Fu, T; Shammo, J M; Nimer, S D; Knight, R D; Giagounidis, A

    2014-01-01

    Lenalidomide is the approved treatment for patients with red blood cell (RBC) transfusion-dependent lower-risk myelodysplastic syndromes (MDS) and chromosome 5q deletion (del(5q)). We report the long-term outcomes (median follow-up 3.2 years) in patients treated with lenalidomide in the MDS-003 trial. RBC transfusion independence (TI) ⩾8 weeks was achieved in 97 of 148 treated patients (65.5%), with a median response duration of 2.2 years. Partial or complete cytogenetic response was achieved by 63 of 88 evaluable patients (71.6%). Median overall survival (OS) was longer in patients achieving RBC-TI ⩾8 weeks (4.3 vs 2.0 years in non-responders; P<0.0001) or cytogenetic response (4.9 vs 3.1 years in non-responders; P=0.010). Time to acute myeloid leukemia (AML) progression was longer in patients achieving RBC-TI ⩾8 weeks or any cytogenetic response versus non-responders (P=0.001 and P=0.0002, respectively). In a landmark multivariate analysis, RBC-TI ⩾8 weeks was associated with prolonged OS (P<0.001) and a trend toward reduced relative risk of AML progression (P=0.080). Among these lower-risk MDS patients with del(5q), lenalidomide was associated with prolonged RBC-TI and cytogenetic responses, which were linked to improved OS and reduced risk of AML progression. PMID:24150217

  20. [Correlation of NPM1, FLT3-ITD mutations with leukocyte count and myeloblasts percentage in AML patients with normal karyotype].

    PubMed

    Su, Long; Li, Wei; Cui, Jiu-Wei; Tan, Ye-Hui; Yang, Yan; Liu, Xiao-Liang; Yu, Ping; Hu, Rui-Ping; Wang, Li-Li; Gao, Su-Jun

    2013-06-01

    This study was aimed to investigate the correlation of NPM1 and FLT3-ITD mutations with leukocyte count in peripheral blood and bone marrow blasts in patients with acute myeloid leukemia (AML). Fifty-one acute myeloid leukemia patients with normal karyotype from January 2009 to December 2011 were enrolled in this study. The clinical data of 51 cases were analyzed retrospectively. Out of 52 cases 22 were male, and 29 were female. The median age was 47 years old (ranged from 14 to 83 years old). The de novo patients were examined by bone marrow cytomorphology and blood routine analysis. Polymerase chain reaction was used to analyze the NPM1 and FLT3-ITD mutations. The results showed that the patients with NPM1 mutations had higher leukocyte count compared with those without mutations (30.7×10(9)/L vs 8.6×10(9)/L, P = 0.002). FLT3-ITD mutation was related to higher leukocyte count (42.38×10(9)/L vs 11.45×10(9)/L without mutation, P = 0.033) and blasts (74.0% vs 60.25% without mutation, P = 0.036). The leukocyte count and percentage of bone marrow blasts were lowest in the patients with neither mutations, and gradually increasing in the NPM1(-) mutation, FLT3-ITD(-) mutation, and NPM1(+) mutation, FLT3-ITDI(+) mutation, and NPM1(+)/FLT3-ITD(+) mutation groups (P < 0.05). The patients tended to have NPM1 (P = 0.002) and FLT3-ITD (P = 0.033) mutations when their leukocyte counts were more than 12.55×10(9)/L and 37.85×10(9)/L, respectively. Those with bone marrow blast more than 72.25% showed higher rate of FLT3-ITD mutation (P = 0.008). Patients with NPM1 mutations had higher complete remission rate than those without NPM1 mutation (78.13% vs 40.0%, χ(2) = 4.651, P = 0.031) after remission induction therapy. It is concluded that both NPM1 and FLT3-ITD mutations are linked to higher leukocyte count and blast percentage, suggesting that both mutations may be associated with increased proliferation of leukemia cells, and may have a synergistic function in stimulating

  1. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial.

    PubMed

    Middeke, J M; Herbst, R; Parmentier, S; Bug, G; Hänel, M; Stuhler, G; Schäfer-Eckart, K; Rösler, W; Klein, S; Bethge, W; Bitz, U; Büttner, B; Knoth, H; Alakel, N; Schaich, M; Morgner, A; Kramer, M; Sockel, K; von Bonin, M; Stölzel, F; Platzbecker, U; Röllig, C; Thiede, C; Ehninger, G; Bornhäuser, M; Schetelig, J

    2016-02-01

    In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), long-term disease control can only be achieved by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the safety and efficacy of clofarabine-based salvage therapy. The study was designed as phase II, multicenter, intent-to-transplant (ITT) study. A total of 84 patients with r/r AML were enrolled. All patients received at least one cycle of CLARA (clofarabine 30 mg/m(2) and cytarabine 1 g/m(2), days 1-5). Chemo-responsive patients with a donor received HSCT in aplasia after first CLARA. Generally, HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine (4 × 30 mg/m(2)) and melphalan (140 mg/m(2)). The median patient age was 61 years (range 40-75). On day 15 after start of CLARA, 26% of patients were in a morphologically leukemia-free state and 79% exposed a reduction in bone marrow blasts. Overall, 67% of the patients received HSCT within the trial. The primary end point, defined as complete remission after HSCT, was achieved by 60% of the patients. According to the ITT, overall survival at 2 years was 43% (95% confidence interval (CI), 32-54%). The 2-year disease-free survival for transplanted patients was 52% (95% CI, 40-69%). Clofarabine-based salvage therapy combined with allogeneic HSCT in aplasia shows promising results in patients with r/r AML. PMID:26283567

  2. Revealing very small FLT3 ITD mutated clones by ultra-deep sequencing analysis has important clinical implications in AML patients

    PubMed Central

    Zuffa, Elisa; Franchini, Eugenia; Papayannidis, Cristina; Baldazzi, Carmen; Simonetti, Giorgia; Testoni, Nicoletta; Abbenante, Maria Chiara; Paolini, Stefania; Sartor, Chiara; Parisi, Sarah; Marconi, Giovanni; Cattina, Federica; Bochicchio, Maria Teresa; Venturi, Claudia; Ottaviani, Emanuela; Cavo, Michele; Martinelli, Giovanni

    2015-01-01

    FLT3 internal tandem duplication (ITD), one of the most frequent mutations in Acute Myeloid Leukemia (AML), is reported to be an unstable marker, as it can evolve from FLT3 ITD- to ITD+ during the disease course. A single-gene sensitive mutational screening approach may be helpful for better clarifying the exact timing of mutation occurrence, especially when FLT3 ITD appears to occur late, at disease progression. We developed an amplicon-based ultra-deep-sequencing (UDS) approach for FLT3 mutational screening. We exploited this highly sensitive technology for the retrospective screening of diagnosis, relapse and follow-up samples of 5 out of 256 cytogenetically normal (CN-) AML who were FLT3 wild-type at presentation, but tested ITD+ at relapse or disease progression. Our study revealed that all patients carried a small ITD+ clone at diagnosis, which was undetectable by routine analysis (0,2–2% abundance). The dynamics of ITD+ clones from diagnosis to disease progression, assessed by UDS, reflected clonal evolution under treatment pressure. UDS appears as a valuable tool for FLT3 mutational screening and for the assessment of minimal residual disease (MRD) during follow-up, by detecting small ITD+ clones that may survive chemotherapy, evolve over time and definitely worsen the prognosis of CN-AML patients. PMID:26384303

  3. Successful management of pulmonary hemorrhage and aspergillosis in a patient with acute myeloid leukemia (AML-M3).

    PubMed

    Gunbatar, Hulya; Demir, Cengiz; Kara, Erdal; Esen, Ramazan; Sertogullarindan, Bunyamin; Asker, Selvi

    2015-01-01

    A 35-year-old man presented with a one month history of gingival bleeding. He was diagnosed with Acute Myeloid Leukemia (AML-M3). During treatment he developed alveolar hemorrhage for which he was treated with a steroid. After the steroid treatment he developed a nodule, a cavitary lesion and atelectasia in the left lung. He was treated with voriconazole. After therapy with voriconazole his lesion significantly decreased. This case illustrates the efficacy and safety of antifungal therapy with voriconazole for aspergillosis complicated by AML. PMID:26744658

  4. Successful management of pulmonary hemorrhage and aspergillosis in a patient with acute myeloid leukemia (AML-M3)

    PubMed Central

    Gunbatar, Hulya; Demir, Cengiz; Kara, Erdal; Esen, Ramazan; Sertogullarindan, Bunyamin; Asker, Selvi

    2015-01-01

    A 35-year-old man presented with a one month history of gingival bleeding. He was diagnosed with Acute Myeloid Leukemia (AML-M3). During treatment he developed alveolar hemorrhage for which he was treated with a steroid. After the steroid treatment he developed a nodule, a cavitary lesion and atelectasia in the left lung. He was treated with voriconazole. After therapy with voriconazole his lesion significantly decreased. This case illustrates the efficacy and safety of antifungal therapy with voriconazole for aspergillosis complicated by AML. PMID:26744658

  5. Do AML patients with DNMT3A exon 23 mutations benefit from idarubicin as compared to daunorubicin? A single center experience

    PubMed Central

    Sarry, Jean-Emmanuel; Mansat-De Mas, Véronique; Dobbelstein, Sophie; Dastugue, Nicole; Strzelecki, Anne-Claire; Cavelier, Cindy; Creancier, Laurent; Pillon, Arnaud; Kruczynski, Anna; Demur, Cécile; Sarry, Audrey; Huguet, Françoise; Huynh, Anne

    2011-01-01

    Mutations in DNMT3A encoding DNA methyltransferase 3A were recently described in patients with acute myeloid leukemia. To assess their prognostic significance, we determined the mutational status of DNMT3A exon 23 in 288 patients with AML excluding acute promyelocytic leukemia, aged from 18 to 65 years and treated in Toulouse University Hospital. A mutation was detected in 39 patients (13.5%). All DNMT3A exon 23+ patients had intermediate-risk cytogenetics. Mutations significantly correlated with a higher WBC count (p<0.001), NPM1 (p<0.001) and FLT3-ITD mutations (p=0.027). DNMT3A mutations were conserved through xenotransplantation in immunodeficient mice. No difference in outcome between DNMT3A exon 23+ and DNMT3A exon 23- patients was found even if the results were stratified by NPM1 or FLT3-ITD status. However, DNMT3A exon 23+ patients had better median DFS (not reached vs 11.6 months, p=0.009) and OS (not reached vs 14.3 months, p=0.005) as compared to DNMT3A exon 23- patients when treated with idarubicin, whereas patients treated with daunorubicin had similar outcome regardless the DNMT3A status. This study shows that DNMT3A mutations have no impact on outcome but could be a predictive factor for response to idarubicin and thus, could have a direct influence in the way AML patients should be managed. PMID:22081665

  6. Idarubicin and cytarabine in combination with gemtuzumab ozogamicin (IAGO) for untreated patients with high-risk MDS or AML evolved from MDS: a phase II study from the EORTC and GIMEMA Leukemia Groups (protocol 06013).

    PubMed

    de Witte, Theo; Suciu, Stefan; Meert, Liv; Halkes, Constantijn; Selleslag, Dominik; Bron, Dominique; Amadori, Sergio; Willemze, Roel; Muus, Petra; Baron, Frédéric

    2015-12-01

    The primary objective of this trial was to assess the feasibility, toxicity profile, and antitumor activity of gemtuzumab ozogamicin (GO) combined with a chemotherapy remission-induction regimen in adults with untreated high-risk myelodysplastic syndrome (HR-MDS) or secondary acute myeloid leukemia (sAML). In this phase II trial, 30 patients with median age of 58 years received 1 day of GO as a 1-h infusion at the dose level of 5 mg/m(2) on day 7 of the remission-induction course further consisting of a continuous infusion of cytarabine 100 mg/m(2)/day for 10 days and idarubicin 12 mg/m(2)/day on days 1, 3, and 5. A consolidation course, consisting of intermediate-dose cytarabine (A) and idarubicin (I) followed by hematopoietic stem cell transplantation (HSCT) was planned for patients in complete remission (CR). The primary endpoints were response rate (CR/CRi) and severe toxicity rate. The secondary endpoint(s) were survival and progression-free survival (PFS) from start of treatment. Thirteen patients (43 %) achieved CR (eight patients) or CR with incomplete hematopoietic recovery (CRi) (five patients). In patients who achieved CR or CRi, the median time to recovery of neutrophils to 0.5 × 10(9)/l and of platelets to >50 × 10(9)/l was 29 and 30 days, respectively. Grade 3 to 4 severe toxicities occurred in nine patients. The most prominent was liver toxicity, as shown by elevated bilirubin levels in 16 patients and one case of nonfatal veno-occlusive disease (VOD). All 13 patients with CR/CRi received consolidation therapy, which was followed by allogeneic HSCT in five patients and autologous HSCT in three patients. According to the statistical design of the study, the idarubicin and cytarabine in combination with gemtuzumab ozogamicin (IAGO) regimen did not show sufficient activity to warrant further exploration of this regimen in adult patients with HR-MDS or sAML. PMID:26410352

  7. CD4(+)and CD8(+)T-cell reactions against leukemia-associated- or minor-histocompatibility-antigens in AML-patients after allogeneic SCT.

    PubMed

    Steger, Brigitte; Milosevic, Slavoljub; Doessinger, Georg; Reuther, Susanne; Liepert, Anja; Braeu, Marion; Schick, Julia; Vogt, Valentin; Schuster, Friedhelm; Kroell, Tanja; Busch, Dirk H; Borkhardt, Arndt; Kolb, Hans-Jochem; Tischer, Johanna; Buhmann, Raymund; Schmetzer, Helga

    2014-04-01

    T-cells play an important role in the remission-maintenance in AML-patients (pts) after SCT, however the role of LAA- (WT1, PR1, PRAME) or minor-histocompatibility (mHag, HA1) antigen-specific CD4(+) and CD8(+)T-cells is not defined. A LAA/HA1-peptide/protein stimulation, cloning and monitoring strategy for specific CD8(+)/CD4(+)T-cells in AML-pts after SCT is given. Our results show that (1) LAA-peptide-specific CD8+T-cells are detectable in every AML-pt after SCT. CD8(+)T-cells, recognizing two different antigens detectable in 5 of 7 cases correlate with long-lasting remissions. Clonal TCR-Vβ-restriction exemplarily proven by spectratyping in PRAME-specific CD8(+)T-cells; high PRAME-peptide-reactivity was CD4(+)-associated, as shown by IFN-γ-release. (2) Two types of antigen-presenting cells (APCs) were tested for presentation of LAA/HA1-proteins to CD4(+)T-cells: miniEBV-transduced lymphoblastoid cells (B-cell-source) and CD4-depleted MNC (source for B-cell/monocyte/DC). We provide a refined cloning-system for proliferating, CD40L(+)CD4(+)T-cells after LAA/HA1-stimulation. CD4(+)T-cells produced cytokines (GM-CSF, IFN-γ) upon exposure to LAA/HA1-stimulation until after at least 7 restimulations and demonstrated cytotoxic activity against naive blasts, but not fibroblasts. Antileukemic activity of unstimulated, stimulated or cloned CD4(+)T-cells correlated with defined T-cell-subtypes and the clinical course of the disease. In conclusion we provide immunological tools to enrich and monitor LAA/HA1-CD4(+)- and CD8(+)T-cells in AML-pts after SCT and generate data with relevant prognostic value. We were able to demonstrate the presence of LAA-peptide-specific CD8(+)T-cell clones in AML-pts after SCT. In addition, we were also able to enrich specific antileukemic reactive CD4(+)T-cells without GvH-reactivity upon repeated LAA/HA1-protein stimulation and limiting dilution cloning. PMID:24315637

  8. The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.

    PubMed

    Burnett, Alan K; Milligan, Donald; Goldstone, Anthony; Prentice, Archibald; McMullin, Mary-Frances; Dennis, Michael; Sellwood, Elizabeth; Pallis, Monica; Russell, Nigel; Hills, Robert K; Wheatley, Keith

    2009-05-01

    The acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress. PMID:19291085

  9. AML engraftment in the NOD/SCID assay reflects the outcome of AML: implications for our understanding of the heterogeneity of AML

    PubMed Central

    Pearce, Daniel J.; Taussig, David; Zibara, Kazem; Smith, Lan-Lan; Ridler, Christopher M.; Preudhomme, Claude; Young, Bryan D.; Rohatiner, Ama Z.; Lister, T. Andrew; Bonnet, Dominique

    2006-01-01

    The nonobese diabetic/severe combined immunodeficient (NOD/SCID) assay is the current model for assessment of human normal and leukemic stem cells. We explored why 51% of 59 acute myeloid leukemia (AML) patients were unable to initiate leukemia in NOD/SCID mice. Increasing the cell dose, using more permissive recipients, and alternative tissue sources did not cause AML engraftment in most previously nonengrafting AML samples. Homing of AML cells to the marrow was the same between engrafters and nonengrafters. FLT3 internal tandem duplication (ITD) and nucleophosmin mutations occurred at a similar frequency in engrafters and nonengrafters. The only variable that was related to engraftment ability was the karyotypically defined risk stratification of individual AML cases. Of interest, follow-up of younger patients with intermediate-risk AML revealed a significant difference in overall survival between NOD/SCID engrafting and nonengrafting AMLs. Hence, the ability of AML to engraft in the NOD/SCID assay seems to be an inherent property of AML cells, independent of homing, conditioning, or cell frequency/source, which is directly related to prognosis. Our results suggest an important difference between leukemic initiating cells between engrafting and nonengrafting AML cases that correlates with treatment response. PMID:16234360

  10. Effectivity of a strategy in elderly AML patients to reach allogeneic stem cell transplantation using intensive chemotherapy: Long-term survival is dependent on complete remission after first induction therapy.

    PubMed

    von dem Borne, P A; de Wreede, L C; Halkes, C J M; Marijt, W A F; Falkenburg, J H F; Veelken, H

    2016-07-01

    Intensive chemotherapy followed by allogeneic stem cell transplantation (alloSCT) can cure AML. Most studies on alloSCT in elderly AML report results of highly selected patient cohorts. Hardly any data exist on the effectiveness of prospective strategies intended to bring as many patients as possible to transplant. Between 2006 and 2011 we implemented a treatment algorithm for all newly diagnosed AML patients aged 61-75 years, consisting of intensive chemotherapy cycles to induce complete remission, followed by alloSCT. 44 of 60 (73%) newly diagnosed elderly AML patients started with chemotherapy. By meticulously following our algorithm in almost all patients, we could induce complete remission (CR) in 66% of patients starting with chemotherapy, and transplant 32% of these patients in continuous CR. Main reasons for failure were early relapse (16%), early death (14%), primary refractory disease (9%), and patient or physician decision to stop treatment (16%). Patients in continuous CR after first induction benefit most with 36% long-term survival. Patients not in CR after first induction benefit less; although additional chemotherapy induces CR in 45% of these patients, only 23% are transplanted and no long-term survival is observed, mainly due to relapse. Long-term survival in the group of 44 patients is 9% (median 4.5 years after alloSCT). Considering that 27% of patients do not start with chemotherapy and 64% of patients starting with chemotherapy do not reach alloSCT, the reasons for failure presented here should be used as a guide to develop new treatment algorithms to improve long-term survival in elderly AML patients. PMID:27123833

  11. [Radiation-induced and therapy-related AML/MDS].

    PubMed

    Inaba, Toshiya

    2009-10-01

    Radiation induced acute myeloid leukemia (AML) was recognized a century ago, soon after mankind found radiation. Atomic bomb survivors developed de novo AML with relatively short latency with very high frequency. By contrast, excess occurrence of myelodysplastic syndrome (MDS) as well as solid tumors was found decades late. This difference may be due to etiology that many de novo AML patients harbor chimeric leukemogenic genes caused by chromosomal translocations, while MDS patients rarely carry chimeras. In addition, epigenetic change would play important roles. Therapy related leukemia is mainly caused by topoisomerase II inhibitors that cause de novo AML with an 11q23 translocation or by alkyrating agents that induce MDS/AML with an AML1 point mutation and monosomy 7. PMID:19860183

  12. The applicability of the WHO classification in paediatric AML. A NOPHO-AML study.

    PubMed

    Sandahl, Julie D; Kjeldsen, Eigil; Abrahamsson, Jonas; Ha, Shau-Yin; Heldrup, Jesper; Jahnukainen, Kirsi; Jónsson, Ólafur G; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Forestier, Erik; Hasle, Henrik

    2015-06-01

    The World Health Organization (WHO) classification of myeloid leukaemia was revised in 2008. It incorporates newly recognized entities and emphasizes the pivotal role of cytogenetic abnormalities. The aim of this study was to evaluate the usability of the WHO classification when applied to a large population-based paediatric acute myeloid leukaemia (AML) cohort. We included children diagnosed with de novo AML, 0-18 years of age from the Nordic countries and Hong Kong from 1993 to 2012. Data were retrieved from the Nordic Society for Paediatric Haematology and Oncology AML database and patients classified according to the WHO 2008 classification. A successful karyotype was available in 97% of the cases. AML with recurrent genetic abnormalities were present in 262 (41%) and 94 (15%) were classified as AML with myelodysplasia-related changes (AML-MDS). WHO classifies patients with monosomy 7 and del(7q) into one group. We found that -7 (n = 14) had significantly poorer outcome than del(7q) (n = 11); 5-year event-free survival 26% vs. 67%, (P = 0·02), and 5-year overall survival 51% vs. 90%, (P = 0·04). The largest group was the highly heterogeneous AML not otherwise specified (NOS) (n = 280) (44%). In conclusion, the WHO classification allocated 15% to AML-MDS, 44% to NOS and grouped together entities with clearly different outcome, therefore limiting the applicability of the current WHO classification in children with AML. PMID:25819835

  13. Transcriptome Profiling of Pediatric Core Binding Factor AML

    PubMed Central

    Hsu, Chih-Hao; Nguyen, Cu; Yan, Chunhua; Ries, Rhonda E.; Chen, Qing-Rong; Hu, Ying; Ostronoff, Fabiana; Stirewalt, Derek L.; Komatsoulis, George; Levy, Shawn

    2015-01-01

    The t(8;21) and Inv(16) translocations disrupt the normal function of core binding factors alpha (CBFA) and beta (CBFB), respectively. These translocations represent two of the most common genomic abnormalities in acute myeloid leukemia (AML) patients, occurring in approximately 25% pediatric and 15% of adult with this malignancy. Both translocations are associated with favorable clinical outcomes after intensive chemotherapy, and given the perceived mechanistic similarities, patients with these translocations are frequently referred to as having CBF-AML. It remains uncertain as to whether, collectively, these translocations are mechanistically the same or impact different pathways in subtle ways that have both biological and clinical significance. Therefore, we used transcriptome sequencing (RNA-seq) to investigate the similarities and differences in genes and pathways between these subtypes of pediatric AMLs. Diagnostic RNA from patients with t(8;21) (N = 17), Inv(16) (N = 14), and normal karyotype (NK, N = 33) were subjected to RNA-seq. Analyses compared the transcriptomes across these three cytogenetic subtypes, using the NK cohort as the control. A total of 1291 genes in t(8;21) and 474 genes in Inv(16) were differentially expressed relative to the NK controls, with 198 genes differentially expressed in both subtypes. The majority of these genes (175/198; binomial test p-value < 10−30) are consistent in expression changes among the two subtypes suggesting the expression profiles are more similar between the CBF cohorts than in the NK cohort. Our analysis also revealed alternative splicing events (ASEs) differentially expressed across subtypes, with 337 t(8;21)-specific and 407 Inv(16)-specific ASEs detected, the majority of which were acetylated proteins (p = 1.5x10-51 and p = 1.8x10-54 for the two subsets). In addition to known fusions, we identified and verified 16 de novo fusions in 43 patients, including three fusions involving NUP98 in six patients

  14. Novel evidence that pituitary gonadotropins directly stimulate human leukemic cells-studies of myeloid cell lines and primary patient AML and CML cells

    PubMed Central

    Abdelbaset-Ismail, Ahmed; Borkowska, Sylwia; Janowska-Wieczorek, Anna; Tonn, Torsten; Rodriguez, Cesar; Moniuszko, Marcin; Bolkun, Lukasz; Koloczko, Janusz; Eljaszewicz, Andrzej; Ratajczak, Janina; Ratajczak, Mariusz Z.; Kucia, Magda

    2016-01-01

    We recently reported that normal hematopoietic stem cells express functional pituitary sex hormone (SexH) receptors. Here we report for the first time that pituitary-secreted gonadotrophins stimulate migration, adhesion, and proliferation of several human myeloid and lymphoid leukemia cell lines. Similar effects were observed after stimulation of human leukemic cell lines by gonadal SexHs. This effect seems to be direct, as the SexH receptors expressed by leukemic cells responded to stimulation by phosphorylation of MAPKp42/44 and AKTser473. Furthermore, in parallel studies we confirmed that human primary patient-derived AML and CML blasts also express several functional SexH receptors. These results shed more light on the potential role of SexHs in leukemogenesis and, in addition, provide further evidence suggesting a developmental link between hematopoiesis and the germline. PMID:26701888

  15. Novel evidence that pituitary gonadotropins directly stimulate human leukemic cells-studies of myeloid cell lines and primary patient AML and CML cells.

    PubMed

    Abdelbaset-Ismail, Ahmed; Borkowska, Sylwia; Janowska-Wieczorek, Anna; Tonn, Torsten; Rodriguez, Cesar; Moniuszko, Marcin; Bolkun, Lukasz; Koloczko, Janusz; Eljaszewicz, Andrzej; Ratajczak, Janina; Ratajczak, Mariusz Z; Kucia, Magda

    2016-01-19

    We recently reported that normal hematopoietic stem cells express functional pituitary sex hormone (SexH) receptors. Here we report for the first time that pituitary-secreted gonadotrophins stimulate migration, adhesion, and proliferation of several human myeloid and lymphoid leukemia cell lines. Similar effects were observed after stimulation of human leukemic cell lines by gonadal SexHs. This effect seems to be direct, as the SexH receptors expressed by leukemic cells responded to stimulation by phosphorylation of MAPKp42/44 and AKTser473. Furthermore, in parallel studies we confirmed that human primary patient-derived AML and CML blasts also express several functional SexH receptors. These results shed more light on the potential role of SexHs in leukemogenesis and, in addition, provide further evidence suggesting a developmental link between hematopoiesis and the germline. PMID:26701888

  16. Adult Acute Myeloid Leukemia Long-term Survivors

    PubMed Central

    Cheng, M. Jennifer; Hourigan, Christopher S.; Smith, Thomas J.

    2014-01-01

    The number of leukemia patients and survivors is growing. This review summarizes what is known regarding the health related quality of life (HRQOL) and medical complications associated with acute myeloid leukemia (AML) disease and treatment and highlights understudied aspects of adult AML survivorship care, and potential novel areas for intervention. PMID:25243197

  17. Hematogones: a sensitive prognostic factor for Chinese adult patients with acute myeloid leukemia

    PubMed Central

    Li, L.; Fu, R.; Zhang, T.; Xie, X.; Liu, J.; Tao, J.; Song, J.; Liu, H.; Zhang, W.; Lu, W.; Shao, Z.

    2016-01-01

    Background Hematogones (hgs) are normal B-lymphocyte precursors that increase in some hematologic diseases. Many studies indicate that hgs might be a favourable prognostic factor. We thus considered it important to determine whether hgs are also a prognostic factor for Chinese adult patients with acute myeloid leukemia (aml) and whether the hg-positive and hg-negative groups show any serologic or phenotypic differences. Methods Chinese adult aml patients (n = 177) who were all initially hg-negative underwent standard chemotherapy and were thereafter divided into hg-positive and hg-negative groups according to hg levels in bone marrow during their first remission. Results The follow-up study confirmed that survival duration (both leukemia-free and overall) was significantly greater in the hg-positive group than in the hg-negative group and was accompanied by a lower relapse rate. A retrospective study of patient characteristics at the time of first diagnosis revealed some differences between the hg-positive and the hg-negative groups, including elevations in white blood cells, lactate dehydrogenase, and β2-microglobulin in the hg-negative group. Retrospective phenotypic analysis revealed a significantly lower proportion of abnormal chromosome karyotype and CD34 expression in hg-positive patients. Finally, we evaluated whether additional intensive chemotherapy after standard chemotherapy could further increase hgs. Conclusions The present work verified the validity of hgs as a prognostic factor for Chinese adult patients with aml. Compared with hg-negative patients, hg-positive patients not only experienced longer survival and a lower relapse rate, but they also had some serologic and phenotypic characteristics that are all considered indicators of better outcome. Additional intensive chemotherapy could further increase the level of hgs, which might imply better clinical results. PMID:27122980

  18. Can a Female Donor for a Male Recipient Decrease Relapse Rate for Patients with AML Treated with Allogeneic Hematopoietic Stem Cell Transplantation?

    PubMed Central

    Kongtim, Piyanuch; Di Stasi, Antonio; Rondon, Gabriela; Chen, Julianne; Adekola, Kehinde; Popat, Uday; Oran, Betul; Kebriaei, Partow; Andersson, Borje S.; Champlin, Richard E.; Ciurea, Stefan O.

    2015-01-01

    The mismatched minor histocompatibility antigens present on Y chromosome (H-Y) in male recipients receiving stem cells from female donors may contribute to graft-versus-leukemia effect (GVL) and results in reduce relapse rate especially in patients with high-risk disease. We retrospectively compared the outcomes of male AML patients who received an allogeneic hematopoietic stem cell transplant (HSCT) from female donors (F-M) (174 patients) versus other gender combinations (667 patients). Median age was 50 years (range 18–74 years). For the whole group, the one-year cumulative incidence of relapse was significantly lower in F-M group (34.1% versus 41.3%, p=0.044) while non-relapse mortality (NRM) was higher (23.2% versus 15.7%, p=0.004). For patients younger than 50 years beyond first complete remission, the F-M group was associated with lower relapse rate (42.5% versus 55.2%, p=0.045) whereas NRM was not significantly different (35.8% versus 25.5%, p=0.141). Although survival was not significantly improved, transplantation from a female donor for male recipient was associated with a lower relapse rate. When relapse is most common concern for treatment failure, especially for younger patients, a female donor for a male recipient might be beneficial to decrease relapse rate post-transplant. Future studies are needed to explore how H-Y mismatch may improve survival post-transplant. PMID:25540936

  19. Rational Combinations of Targeted Agents in AML

    PubMed Central

    Bose, Prithviraj; Grant, Steven

    2015-01-01

    Despite modest improvements in survival over the last several decades, the treatment of AML continues to present a formidable challenge. Most patients are elderly, and these individuals, as well as those with secondary, therapy-related, or relapsed/refractory AML, are particularly difficult to treat, owing to both aggressive disease biology and the high toxicity of current chemotherapeutic regimens. It has become increasingly apparent in recent years that coordinated interruption of cooperative survival signaling pathways in malignant cells is necessary for optimal therapeutic results. The modest efficacy of monotherapy with both cytotoxic and targeted agents in AML testifies to this. As the complex biology of AML continues to be elucidated, many “synthetic lethal” strategies involving rational combinations of targeted agents have been developed. Unfortunately, relatively few of these have been tested clinically, although there is growing interest in this area. In this article, the preclinical and, where available, clinical data on some of the most promising rational combinations of targeted agents in AML are summarized. While new molecules should continue to be combined with conventional genotoxic drugs of proven efficacy, there is perhaps a need to rethink traditional philosophies of clinical trial development and regulatory approval with a focus on mechanism-based, synergistic strategies. PMID:26113989

  20. Acute myeloid leukemia in the older adults.

    PubMed

    Almeida, Antonio M; Ramos, Fernando

    2016-01-01

    AML is an aggressive hematological malignancy with highest incidence in the older adults. The adverse features of AML in the elderly, and the frailties and comorbidities frequently present in them, make their management a particularly difficult therapeutic challenge. In this context, it is important to assess carefully patient- as well as disease-associated prognostic features with validated tools. The fittest patients should be considered for curative therapy, such as bone marrow transplantation, whereas low intensity options may be more appropriate for frail patients. Here we review how to assess patients with elderly AML and the treatments options available for them. PMID:27408788

  1. Immunohistochemistry and molecular analyses in myeloid sarcoma of the breast in a patient with relapse of NPM1-mutated and FLT3-mutated AML after allogeneic stem cell transplantation.

    PubMed

    Choschzick, Matthias; Bacher, Ulrike; Ayuk, Francis; Lebeau, Annette

    2010-06-01

    Myeloid sarcoma of the breast is a rare manifestation of acute myeloid leukaemia (AML). This report describes a patient who was diagnosed with AML FAB M2. Molecular analysis showed evidence of an NPM1 mutation (subtype A) and internal tandem duplications of the FLT3 gene (FLT3-ITD). Eight months after allogeneic stem cell transplantation, the patient developed a palpable mass in the left breast initially suspected as breast carcinoma. Core needle biopsy of the lesion resulted in diagnosis of myeloid sarcoma. Molecular analysis of formalin-fixed specimens of the breast tumour confirmed the known FLT3 and NPM1 gene mutations. Immunohistochemically, an aberrant cytoplasmic staining pattern for NPM1 and overexpression of FLT3 were demonstrated. The myeloid sarcoma showed complete transient resolution following treatment with the kinase inhibitor sorafenib. However, the patient developed bone marrow relapse and died in fatal cerebral haemorrhage 1 year after initial diagnosis of AML. In summary, combined molecular and immunohistochemical examination of NPM1 and FLT3 is helpful in the diagnosis of extramedullary manifestations of AML in core needle biopsies. PMID:20360144

  2. Mutation or loss of Wilms' tumor gene 1 (WT1) are not major reasons for immune escape in patients with AML receiving WT1 peptide vaccination

    PubMed Central

    2010-01-01

    Background Efficacy of cancer vaccines may be limited due to immune escape mechanisms like loss or mutation of target antigens. Here, we analyzed 10 HLA-A2 positive patients with acute myeloid leukemia (AML) for loss or mutations of the WT1 epitope or epitope flanking sequences that may abolish proper T cell recognition or epitope presentation. Methods All patients had been enrolled in a WT1 peptide phase II vaccination trial (NCT00153582) and ultimately progressed despite induction of a WT1 specific T cell response. Blood and bone marrow samples prior to vaccination and during progression were analyzed for mRNA expression level of WT1. Base exchanges within the epitope sequence or flanking regions (10 amino acids N- and C-terminal of the epitope) were assessed with melting point analysis and sequencing. HLA class I expression and WT1 protein expression was analyzed by flow cytometry. Results Only in one patient, downregulation of WT1 mRNA by 1 log and loss of WT1 detection on protein level at time of disease progression was observed. No mutation leading to a base exchange within the epitope sequence or epitope flanking sequences could be detected in any patient. Further, no loss of HLA class I expression on leukemic blasts was observed. Conclusion Defects in antigen presentation caused by loss or mutation of WT1 or downregulation of HLA molecules are not the major basis for escape from the immune response induced by WT1 peptide vaccination. PMID:20092642

  3. [Prognostic significance of cytogenetic changes in patients with acute myeloid leukemia (AML). (Analysis of results in 105 patients treated at the Hemato-oncology Clinic of the University Hospital in Olomouc from 1997 to 2000].

    PubMed

    Jarosová, M; Indrák, K; Holzerová, M; Hubácek, J; Faber, E; Papajík, T; Raida, L; Szotkowski, T; Knotková, R; Hlusí, T; Jedlicková, K; Pikalová, Z; Sulovská, I

    2001-09-01

    Chromosomal aberrations are one of the most important prognostic factors in patients with acute myeloid leukemia (AML). This work present analysis of conventional cytogenetic results completed by fluorescence in situ hybridization (FISH) obtained from 105 patients in the time of diagnosis of AML. The median age of patients was 51 years (range 19-79 years), with slight predominance of women (female to male ratio 1.2:1). The evaluated group involved all patients with AML diagnosis, treated by intensive induction chemotherapy in the Department of Hematology-oncology, University Hospital, Olomouc during last 4 years with assessable cytogenetic results. Chromosomal changes were found in 63 (60%) patients. The most often affected chromosomes in succession of frequency were 8, 17, 7, 5, 11, 15, 16 a 21. Based on found specific and frequent chromosomal changes the patients were divided into 3 prognostic subgroups and the significance of chromosomal aberrations was evaluated. The subgroup of 17 patients with good prognosis consisted of a patients with acute promyelocytic leukemia with translocation t(15;17), 4 patients with t(8;21) and 4 patients with inv(16). 14 patients of 17 live in complete remission, median of overall survival (OS) is 63 weeks. The subgroup of intermediate prognosis was formed by 60 patients, 42 had normal karyotype and 18 patients had other chromosomal abnormalities. Median OS of this group was 35 weeks. The third subgroup with poor prognosis consisted of 28 patients with changes of chromosomes 3, 5, 7, 11 and complex karyotype. 64.3% of patients received complete remission and median OS was 35 weeks. Statistical evaluation of OS showed significant difference (p = 0.002) in subgroup with good prognosis versus subgroup with poor prognosis and in subgroup with good prognosis versus subgroup with intermediate prognosis (p = 0.014). Statistical significance of OS in subgroup with intermediate prognosis versus subgroup with poor prognosis was not proved (p

  4. Toll-like receptor 9, NOD2 and IL23R gene polymorphisms influenced outcome in AML patients transplanted from HLA-identical sibling donors.

    PubMed

    Elmaagacli, A H; Steckel, N; Ditschkowski, M; Hegerfeldt, Y; Ottinger, H; Trenschel, R; Koldehoff, M; Beelen, D W

    2011-05-01

    We evaluated the influence of gene polymorphisms of TLR9 (T1237C; T1486C), IL23R (A1142G), and NOD2 SNP8 (R702W), SNP12 (G908R) and SNP13 (1007fs) on outcome of hematopoietic SCT in a homogenous group of 142 AML patients after non-T-cell-depleted myeloablative transplantation from HLA-identical sibling donors. In our retrospective study, we found that TLR9 gene variant at 1486 influenced transplant outcome. Estimated 5-year OS in patients with the CC gene variant of TLR9 was 70.2% compared with 44.8% (P<0.027) in patients with TC/TT of TLR9 gene. No significant influences on 5-year OS were found for gene polymorphisms of NOD2 or IL23R (A1142G) in this study group. The 5-year treatment-related mortality was lowest in patients with CC gene variant of TLR9 (7.8 vs 23.1%; NS). Acute GVHD grade III-IV was higher in patients with NOD2 gene variants (28 vs 12.8%; P=0.065). In contrast, patients transplanted from donors with the gene variant of IL23R had no occurrence of severe acute GVHD grade III-IV (0 vs 18.4%; P<0.048). However, multivariate analysis confirmed the influence of NOD2 gene variants on the occurrence of acute GVHD grade II-IV after transplant. These results suggest that the gene variants of TLR9, NOD2 and Il23R had influence on the outcome of transplant. PMID:20622911

  5. Acute myelogenous leukemia (AML) - children

    MedlinePlus

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  6. IS THE AMPLIFICATION OF c-MYC, MLL AND RUNX1 GENES IN AML AND MDS PATIENTS WITH TRISOMY 8, 11 AND 21 A FACTOR FOR A CLONAL EVOLUTION IN THEIR KARYOTYPE?

    PubMed

    Angelova, S; Spassov, B; Nikolova, V; Christov, I; Tzvetkov, N; Simeonova, M

    2015-01-01

    The aim of our study was 1) to define if the amplification of c-MYC, MLL and RUNX1 genes is related to the progressive changes of the karyotype in patients with AML and MDS with trisomy 8, 11 and 21 (+8, +11 and +21) in bone marrow and 2) can that amplification be accepted as part of the clonal evolution (CE). Karyotype analysis was performed in 179 patients with AML or MDS with the different chromosomal aberrations (CA) aged 16-81. The findings were distributed as follow: initiating balanced CA (n = 60), aneuploidia (n = 55), unbalanced CA (n = 64). Amplification of c-MYC, MLL and RUNX1 genes by means of fluorescence in situ hybridization (FISH) was found in 35% (7 out of 20) of AML and MDS patients with +8, +11 u +21 as single CA in their karyotype; in 63.6% of pts (7 out of 11)--with additional numerical or structural CA and in 75% (9 out of 12)--with complex karyotype. We assume that the amplification of the respective chromosomal regions in patients with +8, +11 and +21 is related to CE. Considering the amplification as a factor of CE, we established 3 patterns of karyotype development depending on the type of the initiating CA in it. Significant statistical differences were found between the three patterns regarding the karyotype distribution in the different stages of progression (p < 0.001). PMID:26214902

  7. High titer autoantibodies to GM-CSF in patients with AML, CML and MDS are associated with active disease

    PubMed Central

    Sergeeva, A; Ono, Y; Rios, R; Molldrem, JJ

    2012-01-01

    Antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) can be induced when GM-CSF is used as an adjuvant to solid tumor vaccination. Neutralizing anti-GM-CSF IgG has been associated with pulmonary alveolar proteinosis (PAP), and secondary PAP has been linked to myeloid leukemia. We studied 69 patients with acute myeloid leukemia, chronic myeloid leukemia and myelodysplastic syndrome, including 19 patients who received GM-CSF with peptide antigen and incomplete Freund's adjuvant in a vaccine trial for the presence or induction of anti-GM-CSF antibodies. Anti-GM-CSF IgG were present in 36 (52%) patients with myeloid leukemia compared to only 1 of 33 (3%) healthy subjects (P=0.008) and in none of 6 patients with lymphoid leukemia (P=0.0001). Antibody titers were unaffected by vaccination. Anti-GM-CSF IgA and IgM were found in 33 and 20% of patients, respectively; IgA from two patients neutralized GM-CSF. Strikingly, while anti-GM-CSF IgG titers were higher in patients with active disease (n=52) versus those in complete remission (n=14, P=0.0009), GM-CSF expression was not increased in either group. These data are first to show that anti-GM-CSF antibodies of multiple isotypes are present in patients with active myeloid leukemia without PAP and may be useful markers of disease activity. PMID:18216869

  8. The identification of a novel TP53 cancer susceptibility mutation through whole genome sequencing of a patient with therapy-related AML

    PubMed Central

    Link, Daniel C.; Schuettpelz, Laura G.; Shen, Dong; Wang, Jinling; Walter, Matthew J.; Kulkarni, Shashikant; Payton, Jacqueline E.; Ivanovich, Jennifer; Goodfellow, Paul J.; Le Beau, Michelle; Koboldt, Daniel C.; Dooling, David J.; Fulton, Robert S.; Bender, R. Hugh F.; Fulton, Lucinda L.; Delehaunty, Kimberly D.; Fronick, Catrina C.; Appelbaum, Elizabeth L.; Schmidt, Heather; Abbott, Rachel; O'Laughlin, Michelle; Chen, Ken; McLellan, Michael D.; Varghese, Nobish; Nagarajan, Rakesh; Heath, Sharon; Graubert, Timothy A.; Ding, Li; Ley, Timothy J.; Zambetti, Gerard P.; Wilson, Richard K.; Mardis, Elaine R.

    2011-01-01

    Context The identification of patients with inherited cancer susceptibility syndromes facilitates early diagnosis, prevention, and treatment. However, in many cases of suspected cancer susceptibility, the family history is unclear and genetic testing of common cancer susceptibility genes is unrevealing. Objective To apply whole-genome sequencing to a patient with suspected cancer susceptibility (and lacking a clear family history of cancer and no BRCA1 and BRCA2 mutations) to identify rare or novel germline variants in cancer susceptibility genes. Design, Setting, and Participant Skin (normal) and bone marrow (leukemia) DNA were obtained from a patient with early-onset breast and ovarian cancer and therapy-related acute myeloid leukemia (t-AML), and analyzed with: 1) whole genome sequencing using paired end reads; 2) SNP genotyping; 3) RNA expression profiling; and 4) spectral karyotyping. Main Outcome Measures Structural variants, copy number alterations, single nucleotide variants and small insertions and deletions (indels) were detected and validated using the above platforms. Results Whole genome sequencing revealed a novel, heterozygous 3 Kb deletion removing exons 7-9 of TP53 in the patient’s normal skin DNA, which was homozygous in the leukemia DNA as a result of uniparental disomy. In addition, a total of 28 validated somatic single nucleotide variations or indels in coding genes, 8 somatic structural variants, and 12 somatic copy number alterations were detected in the patient’s leukemia genome. Conclusions Whole genome sequencing can identify novel, cryptic variants in cancer susceptibility genes in addition to providing unbiased information on the spectrum of mutations in a cancer genome. PMID:21505135

  9. Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy.

    PubMed

    Bruedigam, Claudia; Bagger, Frederik O; Heidel, Florian H; Paine Kuhn, Catherine; Guignes, Solene; Song, Axia; Austin, Rebecca; Vu, Therese; Lee, Erwin; Riyat, Sarbjit; Moore, Andrew S; Lock, Richard B; Bullinger, Lars; Hill, Geoffrey R; Armstrong, Scott A; Williams, David A; Lane, Steven W

    2014-12-01

    Acute myeloid leukemia (AML) is an aggressive and lethal blood cancer maintained by rare populations of leukemia stem cells (LSCs). Selective targeting of LSCs is a promising approach for treating AML and preventing relapse following chemotherapy, and developing such therapeutic modalities is a key priority. Here, we show that targeting telomerase activity eradicates AML LSCs. Genetic deletion of the telomerase subunit Terc in a retroviral mouse AML model induces cell-cycle arrest and apoptosis of LSCs, and depletion of telomerase-deficient LSCs is partially rescued by p53 knockdown. Murine Terc(-/-) LSCs express a specific gene expression signature that can be identified in human AML patient cohorts and is positively correlated with patient survival following chemotherapy. In xenografts of primary human AML, genetic or pharmacological inhibition of telomerase targets LSCs, impairs leukemia progression, and delays relapse following chemotherapy. Altogether, these results establish telomerase inhibition as an effective strategy for eliminating AML LSCs. PMID:25479751

  10. Telomerase Inhibition Effectively Targets Mouse and Human AML Stem Cells and Delays Relapse Following Chemotherapy

    PubMed Central

    Bruedigam, Claudia; Bagger, Frederik O.; Heidel, Florian H.; Kuhn, Catherine Paine; Guignes, Solene; Song, Axia; Austin, Rebecca; Vu, Therese; Lee, Erwin; Riyat, Sarbjit; Moore, Andrew S.; Lock, Richard B.; Bullinger, Lars; Hill, Geoffrey R.; Armstrong, Scott A.; Williams, David A.; Lane, Steven W.

    2014-01-01

    SUMMARY Acute myeloid leukemia (AML) is an aggressive and lethal blood cancer maintained by rare populations of leukemia stem cells (LSCs). Selective targeting of LSCs is a promising approach for treating AML and preventing relapse following chemotherapy, and developing such therapeutic modalities is a key priority. Here, we show that targeting telomerase activity eradicates AML LSCs. Genetic deletion of the telomerase subunit Terc in a retroviral mouse AML model induces cell cycle arrest and apoptosis of LSCs, and depletion of telomerase-deficient LSCs is partially rescued by p53 knockdown. Murine Terc−/− LSCs express a specific gene expression signature that can be identified in human AML patient cohorts and is positively correlated with patient survival following chemotherapy. In xenografts of primary human AML, genetic or pharmacological inhibition of telomerase targets LSCs, impairs leukemia progression, and delays relapse following chemotherapy. Together, these results establish telomerase inhibition as an effective strategy for eliminating AML LSCs. PMID:25479751

  11. Are immunoconjugates approaching "standard of care" in AML?

    PubMed

    Estey, Elihu

    2013-09-01

    It seems clear that immunoconjugates, the combinations of antibodies with toxins, will play a role in therapy of acute myeloid leukemia (AML). It is also clear that sole emphasis on an average trial result is misplaced in AML, as the example of gentuzumab ozogamicin illustrates. Gemtuzumab added to chemotherapy can improve survival in many patients with newly diagnosed disease. The future of immunoconjugates, however, may rest on further defining the relation between CD33 and the AML stem cell and its importance in therapy. Three immunoconjugates with the cell surface antigens CD33, CD45, and CD30 will be reviewed here. PMID:24309528

  12. Update on rational targeted therapy in AML.

    PubMed

    Shafer, Danielle; Grant, Steven

    2016-07-01

    Acute myeloid leukemia (AML) remains a challenge to both patients and clinicians. Despite improvements in our understanding of the disease, treatment has changed minimally and outcomes remain poor for the majority of patients. Within the last decade, there have been an increasing number of potential targets and pathways identified for development in AML. The classes of agents described in this review include but are not limited to epigenetic modifiers such as IDH inhibitors, BET inhibitors, and HDAC inhibitors as well as cell cycle and signaling inhibitors such as Aurora kinase inhibitors and CDK inhibitors. While the developments are encouraging, it is unlikely that targeting a single pathway will result in long-term disease control. Accordingly, we will also highlight potential rational partners for the novel agents described herein. PMID:26972558

  13. Update on rational targeted therapy in AML

    PubMed Central

    Shafer, Danielle; Grant, Steven

    2016-01-01

    Acute myeloid leukemia (AML) remains a challenge to both patients and clinicians. Despite improvements in our understanding of the disease, treatment has changed minimally and outcomes remain poor for the majority of patients. Within the last decade, there have been an increasing number of potential targets and pathways identified for development in AML. The classes of agents described in this review include but are not limited to epigenetic modifiers such as IDH inhibitors, BET inhibitors, and HDAC inhibitors as well as cell cycle and signaling inhibitors such as Aurora kinase inhibitors and CDK inhibitors. While the developments are encouraging, it is unlikely that targeting a single pathway will result in long-term disease control. Accordingly, we will also highlight potential rational partners for the novel agents described herein. PMID:26972558

  14. Valproic acid triggers differentiation and apoptosis in AML1/ETO-positive leukemic cells specifically.

    PubMed

    Zapotocky, Michal; Mejstrikova, Ester; Smetana, Karel; Stary, Jan; Trka, Jan; Starkova, Julia

    2012-06-28

    Valproic acid (VPA) has extensive effects on leukemic blasts through its inhibition of histone deacetylases. The main goal of this study was to identify the subgroup of patients who may benefit most from VPA treatment. We examined the significance of t(8;21) chromosomal aberration for VPA treatment response among acute myeloid leukemia (AML) patients by direct comparison of AML1/ETO-negative vs. positive leukemic cell-lines as well as bone marrow blasts from AML patients. In t(8;21) AML, leukemogenesis is supposed to be induced via aberrant recruitment of histone deacetylases. AML cell lines of different genotypes (Kasumi-1, Kasumi-6, MV4;11, K562) and diagnostic bone marrow samples from patients were treated with VPA. VPA induced apoptosis in AML1/ETO-positive and MLL-AF4-positive cells in a dose-dependent manner. Differentiation, as indicated by changes in immunophenotype, was observed only in AML1/ETO-positive cells. VPA increased the expression of AML1 target genes - PU.1, C/EBPa, BPI and IGFBP7 only in AML1/ETO-positive cells. This AML1/ETO-specific effect was confirmed also using patient blasts isolated at the time of diagnosis. AML1/ETO-positive leukemia shows specific mechanism of VPA residing from differentiation followed by apoptosis that is accompanied by an increase in the expression of repressed AML1 target genes. Our data suggest that AML1/ETO-positive patients might derive the greatest benefit from VPA treatment. PMID:22261333

  15. Mouse models of human AML accurately predict chemotherapy response

    PubMed Central

    Zuber, Johannes; Radtke, Ina; Pardee, Timothy S.; Zhao, Zhen; Rappaport, Amy R.; Luo, Weijun; McCurrach, Mila E.; Yang, Miao-Miao; Dolan, M. Eileen; Kogan, Scott C.; Downing, James R.; Lowe, Scott W.

    2009-01-01

    The genetic heterogeneity of cancer influences the trajectory of tumor progression and may underlie clinical variation in therapy response. To model such heterogeneity, we produced genetically and pathologically accurate mouse models of common forms of human acute myeloid leukemia (AML) and developed methods to mimic standard induction chemotherapy and efficiently monitor therapy response. We see that murine AMLs harboring two common human AML genotypes show remarkably diverse responses to conventional therapy that mirror clinical experience. Specifically, murine leukemias expressing the AML1/ETO fusion oncoprotein, associated with a favorable prognosis in patients, show a dramatic response to induction chemotherapy owing to robust activation of the p53 tumor suppressor network. Conversely, murine leukemias expressing MLL fusion proteins, associated with a dismal prognosis in patients, are drug-resistant due to an attenuated p53 response. Our studies highlight the importance of genetic information in guiding the treatment of human AML, functionally establish the p53 network as a central determinant of chemotherapy response in AML, and demonstrate that genetically engineered mouse models of human cancer can accurately predict therapy response in patients. PMID:19339691

  16. Mouse models of human AML accurately predict chemotherapy response.

    PubMed

    Zuber, Johannes; Radtke, Ina; Pardee, Timothy S; Zhao, Zhen; Rappaport, Amy R; Luo, Weijun; McCurrach, Mila E; Yang, Miao-Miao; Dolan, M Eileen; Kogan, Scott C; Downing, James R; Lowe, Scott W

    2009-04-01

    The genetic heterogeneity of cancer influences the trajectory of tumor progression and may underlie clinical variation in therapy response. To model such heterogeneity, we produced genetically and pathologically accurate mouse models of common forms of human acute myeloid leukemia (AML) and developed methods to mimic standard induction chemotherapy and efficiently monitor therapy response. We see that murine AMLs harboring two common human AML genotypes show remarkably diverse responses to conventional therapy that mirror clinical experience. Specifically, murine leukemias expressing the AML1/ETO fusion oncoprotein, associated with a favorable prognosis in patients, show a dramatic response to induction chemotherapy owing to robust activation of the p53 tumor suppressor network. Conversely, murine leukemias expressing MLL fusion proteins, associated with a dismal prognosis in patients, are drug-resistant due to an attenuated p53 response. Our studies highlight the importance of genetic information in guiding the treatment of human AML, functionally establish the p53 network as a central determinant of chemotherapy response in AML, and demonstrate that genetically engineered mouse models of human cancer can accurately predict therapy response in patients. PMID:19339691

  17. The leukemogenic t(8;21) fusion protein AML1-ETO controls ribosomal RNA genes and associates with nucleolar organizing regions at mitotic chromosomes

    PubMed Central

    Bakshi, Rachit; Zaidi, Sayyed K.; Pande, Sandhya; Hassan, Mohammad Q.; Young, Daniel W.; Lian, Jane B.; van Wijnen, Andre J.; Stein, Janet L.; Stein, Gary S.

    2010-01-01

    SUMMARY RUNX1/AML1 is required for definitive hematopoiesis and is frequently targeted by chromosomal translocation in acute myeloid leukemias (AML). The t(8;21) related AML1-ETO fusion protein blocks differentiation of myeloid progenitors. Here, we show by immunofluorescence microscopy that during interphase, endogenous AML1-ETO localizes to nuclear microenvironments distinct from those containing native RUNX1/AML1 protein. At mitosis, we clearly detect binding of AML1-ETO to nucleolar organizing regions (NORs) in AML derived Kasumi-1 cells and binding of RUNX1/AML1 to NORs in Jurkat cells. Both RUNX1/AML1 and AML1-ETO occupy ribosomal DNA repeats during interphase, as well as interact with the endogenous RNA Pol I transcription factor UBF-1. Promoter cytosine methylation analysis indicates that RUNX1/AML1 binds to rDNA repeats that are more highly CpG methylated than those bound by AML1-ETO. Down-regulation by RNA interference reveals that RUNX1/AML1 negatively regulates rDNA transcription, while AML1-ETO is a positive regulator in Kasumi-1 cells. Taken together, our findings identify a novel role for the leukemia-related AML1-ETO protein in epigenetic control of cell growth through upregulation of RNA Pol I-mediated ribosomal gene transcription, consistent with the hyper-proliferative phenotype of myeloid cells in AML patients. PMID:19001502

  18. Bone Marrow MicroRNA-335 Level Predicts the Chemotherapy Response and Prognosis of Adult Acute Myeloid Leukemia

    PubMed Central

    Yingchun, Li; Rong, Zhang; Kun, Yao; Ying, Yang; Zhuogang, Liu

    2015-01-01

    Abstract The aim of this study was to investigate the role of microRNA-335 (miR-335) in determining the treatment response and prognosis in adult acute myeloid leukemia (AML) patients receiving the cytarabine (Ara-C)-based chemotherapy. A total of 204 adult AML patients were collected. The miR-335 levels in serum and bone marrow samples from these patients were determined. All patients received Ara-C-based standard induction chemotherapy regimens. The treatment response to Ara-C-based chemotherapy was evaluated. All patients were followed for prognostic analyses. The levels of miR-335 in bone marrow and serum samples from adult AML patients achieving complete response were significantly higher than those without. The serum miR-335 level was not associated with the chemotherapy response and prognosis in these AML patients. In contrast, high bone marrow miR-335 level was significantly associated with a poor treatment response and also predicted a worse prognosis indicated by the relapse-free survival and overall survival periods in adult AML patients receiving Ara-C-based chemotherapy. Our finding suggests that bone marrow miR-335 level may be used as a marker to predict the chemotherapy response and prognosis in adult AML patients. PMID:26287405

  19. Design considerations for adult patient education.

    PubMed

    Walsh, P L

    1982-01-01

    A variety of factors require attention in the design of patient education programs for adults. Andragogy, the art and science of helping adults learn, describes certain conditions of learning that are more conducive to growth and development for adults and prescribes practices in the learning-teaching transaction to meet them. Stigma, a special discrepancy between virtual and actual social identity, reduces a patient's self-esteem and fosters a feeling of dependence on others for care. Anxiety related to diagnosis and illness creates a situation in which patients cannot productively learn. The stages in acceptance of diagnosis provide a roadmap for understanding a patient's feelings/psychological processes and insight into opportunities to intervene with patient education. The specific disease a patient has effects his ability to learn. Each of these factors is considered with implications described for designing and implementing patient education activities for adults. PMID:10258421

  20. Alkylator-Induced and Patient-Derived Xenograft Mouse Models of Therapy-Related Myeloid Neoplasms Model Clinical Disease and Suggest the Presence of Multiple Cell Subpopulations with Leukemia Stem Cell Activity

    PubMed Central

    Johnson, Carl; Gratzinger, Dita; Majeti, Ravindra

    2016-01-01

    Acute myeloid leukemia (AML) is a heterogeneous group of aggressive bone marrow cancers arising from transformed hematopoietic stem and progenitor cells (HSPC). Therapy-related AML and MDS (t-AML/MDS) comprise a subset of AML cases occurring after exposure to alkylating chemotherapy and/or radiation and are associated with a very poor prognosis. Less is known about the pathogenesis and disease-initiating/leukemia stem cell (LSC) subpopulations of t-AML/MDS compared to their de novo counterparts. Here, we report the development of mouse models of t-AML/MDS. First, we modeled alkylator-induced t-AML/MDS by exposing wild type adult mice to N-ethyl-N-nitrosurea (ENU), resulting in several models of AML and MDS that have clinical and pathologic characteristics consistent with human t-AML/MDS including cytopenia, myelodysplasia, and shortened overall survival. These models were limited by their inability to transplant clinically aggressive disease. Second, we established three patient-derived xenograft models of human t-AML. These models led to rapidly fatal disease in recipient immunodeficient xenografted mice. LSC activity was identified in multiple HSPC subpopulations suggesting there is no canonical LSC immunophenotype in human t-AML. Overall, we report several new t-AML/MDS mouse models that could potentially be used to further define disease pathogenesis and test novel therapeutics. PMID:27428079

  1. Alkylator-Induced and Patient-Derived Xenograft Mouse Models of Therapy-Related Myeloid Neoplasms Model Clinical Disease and Suggest the Presence of Multiple Cell Subpopulations with Leukemia Stem Cell Activity.

    PubMed

    Jonas, Brian A; Johnson, Carl; Gratzinger, Dita; Majeti, Ravindra

    2016-01-01

    Acute myeloid leukemia (AML) is a heterogeneous group of aggressive bone marrow cancers arising from transformed hematopoietic stem and progenitor cells (HSPC). Therapy-related AML and MDS (t-AML/MDS) comprise a subset of AML cases occurring after exposure to alkylating chemotherapy and/or radiation and are associated with a very poor prognosis. Less is known about the pathogenesis and disease-initiating/leukemia stem cell (LSC) subpopulations of t-AML/MDS compared to their de novo counterparts. Here, we report the development of mouse models of t-AML/MDS. First, we modeled alkylator-induced t-AML/MDS by exposing wild type adult mice to N-ethyl-N-nitrosurea (ENU), resulting in several models of AML and MDS that have clinical and pathologic characteristics consistent with human t-AML/MDS including cytopenia, myelodysplasia, and shortened overall survival. These models were limited by their inability to transplant clinically aggressive disease. Second, we established three patient-derived xenograft models of human t-AML. These models led to rapidly fatal disease in recipient immunodeficient xenografted mice. LSC activity was identified in multiple HSPC subpopulations suggesting there is no canonical LSC immunophenotype in human t-AML. Overall, we report several new t-AML/MDS mouse models that could potentially be used to further define disease pathogenesis and test novel therapeutics. PMID:27428079

  2. The molecular signature of AML mesenchymal stromal cells reveals candidate genes related to the leukemogenic process.

    PubMed

    Binato, Renata; de Almeida Oliveira, Nathalia Correa; Du Rocher, Barbara; Abdelhay, Eliana

    2015-12-01

    Acute myeloid leukemia (AML) is a heterogeneous disease characterized by myeloid precursor proliferation in the bone marrow, apoptosis reduction and differentiation arrest. Although there are several studies in this field, events related to disease initiation and progression remain unknown. The malignant transformation of hematopoietic stem cells (HSC) is thought to generate leukemic stem cells, and this transformation could be related to changes in mesenchymal stromal cell (hMSC) signaling. Thus, the aim of this work was to analyze the gene expression profile of hMSC from AML patients (hMSC-AML) compared to healthy donors hMSCs (hMSC-HD). The results showed a common molecular signature for all hMSC-AML. Other assays were performed with a large number of patients and the results confirmed a molecular signature that is capable of distinguishing hMSC-AML from hMSC-HD. Moreover, CCL2 and BMP4 genes encode secreted proteins that could affect HSCs. To verify whether these proteins are differentially expressed in AML patients, ELISA was performed with plasma samples. CCL2 and BMP4 proteins are differentially expressed in AML patients, indicating changes in hMSC-AML signaling. Altogether, hMSCs-AML signaling alterations could be an important factor in the leukemic transformation process. PMID:26279521

  3. Spontaneous remission in three cases of AML M5 with NPM1 mutation

    PubMed Central

    Camus, Vincent; Etancelin, Pascaline; Jardin, Fabrice; Lenain, Pascal; Contentin, Nathalie; Daliphard, Sylvie; Buchonnet, Gérard; Lemasle, Emilie; Lanic, Hélène; Leprêtre, Stéphane; Penther, Dominique; Dubois, Sydney; Tilly, Hervé; Bastard, Christian; Stamatoullas, Aspasia

    2015-01-01

    Key Clinical Message Patients with NPM1-mutated AML M5 who develop spontaneous remission (SR) after antibiotic therapy at diagnosis seem to form a favorable prognosis and chemo sensitive subtype. We report three cases of AML M5 patients with the same genotype that experienced transient SR and are now leukemia free after standard treatment. PMID:26576281

  4. Synergistic effect of sorafenib and cGvHD in patients with high-risk FLT3-ITD+AML allows long-term disease control after allogeneic transplantation.

    PubMed

    Tschan-Plessl, A; Halter, J P; Heim, D; Medinger, M; Passweg, J R; Gerull, S

    2015-11-01

    The multikinase inhibitor sorafenib has shown a strong anti-leukemic effect in FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML); however, remission is often transient. To better understand the role of sorafenib, we performed a retrospective analysis of all patients who received sorafenib in combination with allogeneic hematopoietic stem cell transplantation (HSCT) at our center. Seventeen patients with FLT3-ITD positive AML were treated with sorafenib in combination with allogeneic HSCT. Seven patients received sorafenib therapy pre- and posttransplant, and 10 patients were given sorafenib only posttransplant. Median duration of sorafenib treatment was 13 months (range 1-42); median dose was 600 mg (range 100-1200). Fourteen patients (82 %) achieved a complete remission (CR), while 5 patients (29 %) eventually developed progressive disease. Developing chronic graft-versus-host disease (GvHD) had a strong protective influence on the risk of sorafenib resistance (p = 0.028, HR 0.08, 95 % CI 0.01-0.76). In a total of 8 patients, sorafenib had to be stopped, paused or dose-reduced due to toxicity. In 5 patients with pronounced toxicity, we switched to an alternating dosing schedule with 1 month on/1 month off sorafenib. These patients subsequently remained in sustained complete molecular remission, with a median follow-up of 20 months. Our data indicate that sorafenib can achieve high rates of sustained remission in high-risk patients treated in combination with HSCT. PMID:26233683

  5. Hospital Patients Are Adult Learners.

    ERIC Educational Resources Information Center

    Caffarella, Rosemary S.

    Patient education is recognized by health care providers and patients themselves as an important component of adequate health care for hospital patients. Through this informational process, patients receive information about specific health problems, learn the necessary competencies to deal with them, and develop accepting attitudes toward the…

  6. High feasibility and antileukemic efficacy of fludarabine, cytarabine, and idarubicin (FLAI) induction followed by risk-oriented consolidation: A critical review of a 10-year, single-center experience in younger, non M3 AML patients.

    PubMed

    Guolo, Fabio; Minetto, Paola; Clavio, Marino; Miglino, Maurizio; Di Grazia, Carmen; Ballerini, Filippo; Pastori, Giordana; Guardo, Daniela; Colombo, Nicoletta; Kunkl, Annalisa; Fugazza, Giuseppina; Rebesco, Barbara; Sessarego, Mario; Lemoli, Roberto Massimo; Bacigalupo, Andrea; Gobbi, Marco

    2016-08-01

    About 105 consecutive acute myeloid leukemia (AML) patients treated with the same induction-consolidation program between 2004 and 2013 were retrospectively analyzed. Median age was 47 years. The first induction course included fludarabine (Flu) and high-dose cytarabine (Ara-C) plus idarubicin (Ida), with or without gemtuzumab-ozogamicin (GO) 3 mg/m(2) (FLAI-5). Patients achieving complete remission (CR) received a second course without fludarabine but with higher dose of idarubicin. Patients not achieving CR received an intensified second course. Patients not scheduled for early allogeneic bone marrow transplantation (HSCT) where planned to receive at least two courses of consolidation therapy with Ara-C. Our double induction strategy significantly differs from described fludarabine-containing regimens, as patients achieving CR receive a second course without fludarabine, to avoid excess toxicity, and Ara-C consolidation is administrated at the reduced cumulative dose of 8 g/m(2) per cycle. Toxicity is a major concern in fludarabine containing induction, including the recent Medical Research Council AML15 fludarabine, cytarabine, idaraubicin and G-CSF (FLAG-Ida) arm, and, despite higher anti-leukemic efficacy, only a minority of patients is able to complete the full planned program. In this article, we show that our therapeutic program is generally well tolerated, as most patients were able to receive subsequent therapy at full dose and in a timely manner, with a 30-day mortality of 4.8%. The omission of fludarabine in the second course did not reduce efficacy, as a CR rate of 83% was achieved and 3-year disease-free survival and overall survival (OS) were 49.6% and 50.9%, respectively. Our experience shows that FLAI-5/Ara-C + Ida double induction followed by risk-oriented consolidation therapy can result in good overall outcome with acceptable toxicity. Am. J. Hematol. 91:755-762, 2016. © 2016 Wiley Periodicals, Inc. PMID:27084986

  7. MicroRNAs Distinguish Cytogenetic Subgroups in Pediatric AML and Contribute to Complex Regulatory Networks in AML-Relevant Pathways

    PubMed Central

    Daschkey, Svenja; Röttgers, Silja; Giri, Anamika; Bradtke, Jutta; Teigler-Schlegel, Andrea; Meister, Gunter; Borkhardt, Arndt; Landgraf, Pablo

    2013-01-01

    Background The role of microRNAs (miRNAs), important post-transcriptional regulators, in the pathogenesis of acute myeloid leukemia (AML) is just emerging and has been mainly studied in adults. First studies in children investigate single selected miRNAs, however, a comprehensive overview of miRNA expression and function in children and young adults is missing so far. Methodology/Principal Findings We here globally identified differentially expressed miRNAs between AML subtypes in a survey of 102 children and adolescent. Pediatric samples with core-binding factor AML and promyelocytic leukemia could be distinguished from each other and from MLL-rearranged AML subtypes by differentially expressed miRNAs including miR-126, -146a, -181a/b, -100, and miR-125b. Subsequently, we established a newly devised immunoprecipitation assay followed by rapid microarray detection for the isolation of Argonaute proteins, the hallmark of miRNA targeting complexes, from cell line models resembling core-binding factor and promyelocytic leukemia. Applying this method, we were able to identify Ago-associated miRNAs and their targeted mRNAs. Conclusions/Significance miRNAs as well as their mRNA-targets showed binding preferences for the different Argonaute proteins in a cell context-dependent manner. Bioinformatically-derived pathway analysis suggested a concerted action of all four Argonaute complexes in the regulation of AML-relevant pathways. For the first time, to our knowledge, a complete AML data set resulting from carefully devised biochemical isolation experiments and analysis of Ago-associated miRNAs and their target-mRNAs is now available. PMID:23418555

  8. The addition of gemtuzumab ozogamicin to chemotherapy in adult patients with acute myeloid leukemia.

    PubMed

    Kell, Jonathan

    2016-04-01

    The treatment of acute myeloid leukaemia has remained largely unchanged for the last 30 years since the advent of combination chemotherapy with cytarabine arabinoside and daunorubicin with remission rates around 70% but with long term survival still only around 40% in young adults. Doses of chemotherapy have been pushed to the limit of toxicity. Gemtuzumab ozogamicin allows additional chemotherapy to be delivered to the leukaemic cells without significantly adding to toxicity since the active agent is coupled to a monoclonal anti-CD33 antibody. It was approved by the FDA in 2000 for the treatment of elderly patients with relapsed CD33 positive AML at a dose of 9mg/m(2) on two days two weeks apart. Almost at once, questions were raised about its safety, with a particular liver signal, and it was voluntarily withdrawn from practice in 2010. Many groups have been examining the role of gemtuzumab ozogamicin in combination with chemotherapy, usually at lower doses than originally recommended, with varying degrees of success and toxicity and gemtuzumab ozogamicin is now entering a period of rehabilitation. Currently it is only commercially available in Japan although it is currently also available in the UK Bloodwise AML18 study. PMID:26942450

  9. The influence of disease and comorbidity risk assessments on the survival of MDS and oligoblastic AML patients treated with 5-azacitidine: A retrospective analysis in ten centers of the "Rete Ematologica Lombarda".

    PubMed

    Molteni, Alfredo; Riva, Marta; Borin, Lorenza; Bernardi, Massimo; Pelizzari, Anna Maria; Freyrie, Alessandra; Porta, Matteo Della; Nichelatti, Michele; Ravano, Emanuele; Quaresmini, Giulia; Mariotti, Jacopo; Caramazza, Domenica; Ubezio, Marta; Guarco, Simona; Gigli, Federica; Greco, Rosa; Cairoli, Roberto; Morra, Enrica

    2016-03-01

    5-Azacytidine is an effective therapy in high risk MDS and oligoblastic AML. This "real life" analysis was made on 185 patients treated with 5-azacytidine in 10 centers afferent to REL ("Rete Ematologica Lombarda"), a network in Lombardia region. The aim was to assess the influence of disease and comorbidity risk assessments on the survival. The results confirm the utility of 5-azacitidine in prolonging OS regardless of advanced age and the presence of comorbidities. They also encourage an early treatment since patients with IPSS-R High risk MDS have better outcome with respect to Very High risk ones. According to the IPSS cytogenetic risk, there was no difference in the outcome between Intermediate and High risk patients. Nevertheless, a poorer cytogenetic risk, according to the IPSS-R cytogenetic stratification, negatively influenced the outcome. PMID:26852003

  10. Diagnosis of Adult Patients with Cystic Fibrosis.

    PubMed

    Nick, Jerry A; Nichols, David P

    2016-03-01

    The diagnosis of cystic fibrosis (CF) is being made with increasing frequency in adults. Patients with CF diagnosed in adulthood typically present with respiratory complaints, and often have recurrent or chronic airway infection. At the time of initial presentation individuals may appear to have clinical manifestation limited to a single organ, but with subclinical involvement of the respiratory tract. Adult-diagnosed patients have a good response to CF center care, and newly available cystic fibrosis transmembrane receptor-modulating therapies are promising for the treatment of residual function mutation, thus increasing the importance of the diagnosis in adults with unexplained bronchiectasis. PMID:26857767

  11. GFI1 as a novel prognostic and therapeutic factor for AML/MDS.

    PubMed

    Hönes, J M; Botezatu, L; Helness, A; Vadnais, C; Vassen, L; Robert, F; Hergenhan, S M; Thivakaran, A; Schütte, J; Al-Matary, Y S; Lams, R F; Fraszscak, J; Makishima, H; Radivoyevitch, T; Przychodzen, B; da Conceição Castro, S V; Görgens, A; Giebel, B; Klein-Hitpass, L; Lennartz, K; Heuser, M; Thiede, C; Ehninger, G; Dührsen, U; Maciejewski, J P; Möröy, T; Khandanpour, C

    2016-06-01

    Genetic and epigenetic aberrations contribute to the initiation and progression of acute myeloid leukemia (AML). GFI1, a zinc-finger transcriptional repressor, exerts its function by recruiting histone deacetylases to target genes. We present data that low expression of GFI1 is associated with an inferior prognosis of AML patients. To elucidate the mechanism behind this, we generated a humanized mouse strain with reduced GFI1 expression (GFI1-KD). Here we show that AML development induced by onco-fusion proteins such as MLL-AF9 or NUP98-HOXD13 is accelerated in mice with low human GFI1 expression. Leukemic cells from animals that express low levels of GFI1 show increased H3K9 acetylation compared to leukemic cells from mice with normal human GFI1 expression, resulting in the upregulation of genes involved in leukemogenesis. We investigated a new epigenetic therapy approach for this subgroup of AML patients. We could show that AML blasts from GFI1-KD mice and from AML patients with low GFI1 levels were more sensitive to treatment with histone acetyltransferase inhibitors than cells with normal GFI1 expression levels. We suggest therefore that GFI1 has a dose-dependent role in AML progression and development. GFI1 levels are involved in epigenetic regulation, which could open new therapeutic approaches for AML patients. PMID:26847026

  12. Sleep Disorders in Adult Sickle Cell Patients

    PubMed Central

    Sharma, Sunil; Efird, Jimmy T.; Knupp, Charles; Kadali, Renuka; Liles, Darla; Shiue, Kristin; Boettger, Peter; Quan, Stuart F.

    2015-01-01

    Study Objectives: While sleep apnea has been studied in children with sickle cell disease (SCD), little is known about sleep disorders in adult sickle cell patients. The objective of this study was to evaluate sleep disordered breathing and its polysomnographic characteristics in adult patients with sickle cell disease. Methods: The analysis cohort included 32 consecutive adult SCD patients who underwent a comprehensive sleep evaluation and overnight polysomnography in an accredited sleep center after reporting symptoms suggesting disordered sleep or an Epworth Sleepiness Scale score ≥ 10. Epworth score, sleep parameters, comorbid conditions, and narcotic use were reviewed and compared in patients with and without sleep disordered breathing. SCD complication rates in the two groups also were compared. Results: In adult SCD patients who underwent overnight polysomnography, we report a high prevalence (44%) of sleep disordered breathing. Disease severity was mild to moderate (mean apnea-hypopnea index = 17/h (95% CI: 10–24/h). Concomitant sleep disorders, including insomnia complaints (57%) and delayed sleep-phase syndrome (57%), also were common in this population. In this limited cohort, we did not find increased SCD complications associated with sleep disordered breathing in adult patients with sickle cell disease. Conclusions: A high burden of sleep disordered breathing and other sleep-related complaints were identified in the adult sickle cell population. Our results provide important information on this unique population. Citation: Sharma S, Efird JT, Knupp C, Kadali R, Liles D, Shiue K, Boettger P, Quan SF. Sleep disorders in adult sickle cell patients. J Clin Sleep Med 2015;11(3):219–223. PMID:25515282

  13. Significance of oncogenes and tumor suppressor genes in AML prognosis.

    PubMed

    Kavianpour, Maria; Ahmadzadeh, Ahmad; Shahrabi, Saeid; Saki, Najmaldin

    2016-08-01

    Acute myeloid leukemia (AML) is a heterogeneous disorder among hematologic malignancies. Several genetic alterations occur in this disease, which cause proliferative progression, reducing differentiation and apoptosis in leukemic cells as well as increasing their survival. In the genetic study of AML, genetic translocations, gene overexpression, and mutations effective upon biology and pathogenesis of this disease have been recognized. Proto-oncogenes and tumor suppressor genes, which are important in normal development of myeloid cells, are involved in the regulation of cell cycle and apoptosis, undergo mutation in this type of leukemia, and are effective in prognosis of AML subtypes. This review deals with these genes, the assessment of which can be important in the diagnosis and prognosis of patients as well as therapeutic outcome. PMID:27179964

  14. Preclinical efficacy of MEK inhibition in Nras-mutant AML

    PubMed Central

    Burgess, Michael R.; Hwang, Eugene; Firestone, Ari J.; Huang, Tannie; Xu, Jin; Zuber, Johannes; Bohin, Natacha; Wen, Tiffany; Kogan, Scott C.; Haigis, Kevin M.; Sampath, Deepak; Lowe, Scott; Shannon, Kevin

    2014-01-01

    Oncogenic NRAS mutations are highly prevalent in acute myeloid leukemia (AML). Genetic analysis supports the hypothesis that NRAS mutations cooperate with antecedent molecular lesions in leukemogenesis, but have limited independent prognostic significance. Using short hairpin RNA–mediated knockdown in human cell lines and primary mouse leukemias, we show that AML cells with NRAS/Nras mutations are dependent on continued oncogene expression in vitro and in vivo. Using the Mx1-Cre transgene to inactivate a conditional mutant Nras allele, we analyzed hematopoiesis and hematopoietic stem and progenitor cells (HSPCs) under normal and stressed conditions and found that HSPCs lacking Nras expression are functionally equivalent to normal HSPCs in the adult mouse. Treating recipient mice transplanted with primary NrasG12D AMLs with 2 potent allosteric mitogen-activated protein kinase kinase (MEK) inhibitors (PD0325901 or trametinib/GlaxoSmithKline 1120212) significantly prolonged survival and reduced proliferation but did not induce apoptosis, promote differentiation, or drive clonal evolution. The phosphatidylinositol 3-kinase inhibitor GDC-0941 was ineffective as a single agent and did not augment the activity of PD0325901. All mice ultimately succumbed to progressive leukemia. Together, these data validate oncogenic N-Ras signaling as a therapeutic target in AML and support testing combination regimens that include MEK inhibitors. PMID:25361812

  15. MYST2 acetyltransferase expression and Histone H4 Lysine acetylation are suppressed in AML.

    PubMed

    Sauer, Tim; Arteaga, Maria Francisca; Isken, Fabienne; Rohde, Christian; Hebestreit, Katja; Mikesch, Jan-Henrik; Stelljes, Matthias; Cui, Chunhong; Zhou, Fengbiao; Göllner, Stefanie; Bäumer, Nicole; Köhler, Gabriele; Krug, Utz; Thiede, Christian; Ehninger, Gerhard; Edemir, Bayram; Schlenke, Peter; Berdel, Wolfgang E; Dugas, Martin; Müller-Tidow, Carsten

    2015-09-01

    Chromatin-modifying enzymes are frequently altered in acute myeloid leukemia (AML). In the current study, we identified MYST2, a core histone acetyltransferase, to be suppressed in blast cells from AML patients compared with nonmalignant hematopoietic progenitor cells. Functionally, loss of MYST2 accelerated leukemic growth and colony formation, while forced expression of MYST2 induced H4K5 acetylation (H4K5Ac) and suppressed hematopoietic progenitor cell growth. Consistently, global H4K5Ac levels were frequently decreased in AML blasts. Low levels of H4K5Ac were most prominent in patients with complex karyotype AML and were associated with inferior overall survival in univariate but not multivariate analysis. ChIP-seq experiments in primary AML patients' blasts revealed widespread H4K5Ac deregulation, most prominent at gene promoters. Taken together, MYST2 is a repressed growth suppressor in AML mediating reduced acetylation of histone 4 at residue 5 and is associated with inferior AML patient survival. PMID:26072331

  16. Standard anatomical medullary locking (AML) versus tricalcium phosphate-coated AML femoral prostheses

    PubMed Central

    Johnston, D.W.C. (Bill); Davies, Donna M.; Beaupré, Lauren A.; Lavoie, Guy

    2001-01-01

    Objectives To compare the preliminary rate and amount of bony ingrowth and calcar resorption between patients receiving either a standard anatomical medullary locking (AML) or a tricalcium phosphate (TCP)-coated AML femoral prosthesis and to compare preliminary clinical results. Design A prospective, randomized, double-blind clinical trial. Setting An acute care tertiary institution. Patients Between January 1993 and March 1995, 92 patients underwent primary total hip arthroplasty (THA). They were randomized to 2 groups of 46 — a control group or a treatment group. Of the 46 subjects enrolled in each group, no significant differences were seen preoperatively with respect to age, sex, diagnosis, clinical and radiographic assessment. Seventy-one patients were followed up for 24 months. Interventions Insertion of either a standard AML femoral implant (control group) or a TCP-coated AML femoral implant (treatment group). Outcome measures The degree of hypertrophy, calcar atrophy and the number of spot welds on standard postoperative radiographs at 6, 12 and 24 months. Clinically, assessment according to the Société internationale de chirurgie orthopédique et de traumatologie (SICOT) scale and a 100-point visual analogue scale (VAS) for pain. Results There were no prosthetic stem revisions in either group at the 24-month follow-up. Radiographically, bony ingrowth was not significantly different in the TCP-coated stem, by χ2 analysis of the degree of hypertrophy and number of spot welds present. Also by χ2 analysis, the degree of calcar atrophy was not significantly different between groups. The mean VAS score for pain at 24 months was 12.5 for the control and 12.1 for the treatment group. No significant differences were seen in any of the clinical categories of the SICOT Scale over the 24-month interval. Conclusion The objective of TCP-coating — to increase the rate and amount of bony ingrowth while reducing the rate of calcar resorption in non-cemented THA

  17. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML.

    PubMed

    Wong, Terrence N; Miller, Christopher A; Klco, Jeffery M; Petti, Allegra; Demeter, Ryan; Helton, Nichole M; Li, Tiandao; Fulton, Robert S; Heath, Sharon E; Mardis, Elaine R; Westervelt, Peter; DiPersio, John F; Walter, Matthew J; Welch, John S; Graubert, Timothy A; Wilson, Richard K; Ley, Timothy J; Link, Daniel C

    2016-02-18

    There is interest in using leukemia-gene panels and next-generation sequencing to assess acute myelogenous leukemia (AML) response to induction chemotherapy. Studies have shown that patients with AML in morphologic remission may continue to have clonal hematopoiesis with populations closely related to the founding AML clone and that this confers an increased risk of relapse. However, it remains unknown how induction chemotherapy influences the clonal evolution of a patient's nonleukemic hematopoietic population. Here, we report that 5 of 15 patients with genetic clearance of their founding AML clone after induction chemotherapy had a concomitant expansion of a hematopoietic population unrelated to the initial AML. These populations frequently harbored somatic mutations in genes recurrently mutated in AML or myelodysplastic syndromes and were detectable at very low frequencies at the time of AML diagnosis. These results suggest that nonleukemic hematopoietic stem and progenitor cells, harboring specific aging-acquired mutations, may have a competitive fitness advantage after induction chemotherapy, expand, and persist long after the completion of chemotherapy. Although the clinical importance of these "rising" clones remains to be determined, it will be important to distinguish them from leukemia-related populations when assessing for molecular responses to induction chemotherapy. PMID:26631115

  18. Timothy Ley, M.D., Advocates for Personalized Medicine in AML - TCGA

    Cancer.gov

    Oncologist Dr. Timothy Ley talks about how repurposing of existing drugs based on better understanding of the genetic basis of acute myeloid leukemia (AML) can help patients receive personalized care.

  19. [Difficult situations in radiotherapy: agitated adult patients].

    PubMed

    Noël, S; Noël, G

    2013-10-01

    The causes of agitation in adult patients are numerous. Agitation may cause difficulty or impossibility to initiate the radiotherapy technique but also can lead to accidents harmful to patients. However, the decision to not irradiate agitated patients may lead to a loss of curability chance or chance to palliate symptoms. Before taking such a decision, thinking about the possibilities available to calm the patient should be undertaken with the patient and the referring practitioners to attempt to make this therapy if it is considered major in the management of cancer. In all cases, current adaptations of radiotherapy should be used to deliver an effective radiation of a suitable time and safely. It is notable that the medical literature is extremely rare on this subject. PMID:23932645

  20. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups.

    PubMed

    Luskin, Marlise R; Lee, Ju-Whei; Fernandez, Hugo F; Abdel-Wahab, Omar; Bennett, John M; Ketterling, Rhett P; Lazarus, Hillard M; Levine, Ross L; Litzow, Mark R; Paietta, Elisabeth M; Patel, Jay P; Racevskis, Janis; Rowe, Jacob M; Tallman, Martin S; Sun, Zhuoxin; Luger, Selina M

    2016-03-24

    The initial report of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group trial E1900 (#NCT00049517) showed that induction therapy with high-dose (HD) daunorubicin (90 mg/m(2)) improved overall survival in adults <60 years old with acute myeloid leukemia (AML); however, at initial analysis, the benefit was restricted to younger patients (<50 years) and patients without unfavorable cytogenetics or aFLT3-ITD mutation. Here, we update the results of E1900 after longer follow-up (median, 80.1 months among survivors), focusing on the benefit of HD daunorubicin on common genetic subgroups. Compared with standard-dose daunorubicin (45 mg/m(2)), HD daunorubicin is associated with a hazard ratio (HR) for death of 0.74 (P= .001). Younger patients (<50 years) benefited from HD daunorubicin (HR, 0.66;P= .002), as did patients with favorable and intermediate cytogenetics (HR, 0.51;P= .03 and HR, 0.68;P= .01, respectively). Patients with unfavorable cytogenetics were shown to benefit from HD daunorubicin on multivariable analysis (adjusted HR, 0.66;P= .04). Patients withFLT3-ITD (24%),DNMT3A(24%), andNPM1(26%) mutant AML all benefited from HD daunorubicin (HR, 0.61,P= .009; HR, 0.62,P= .02; and HR, 0.50,P= .002; respectively). HD benefit was seen in the subgroup of older patients (50-60 years) with theFLT3-ITD orNPM1mutation. Additionally, the presence of anNPM1mutation confers a favorable prognosis only for patients receiving anthracycline dose intensification during induction. PMID:26755712

  1. How I treat MDS and AML in Fanconi anemia.

    PubMed

    Peffault de Latour, Régis; Soulier, Jean

    2016-06-16

    Fanconi anemia (FA) is the most frequent inherited cause of bone marrow failure (BMF). Most FA patients experience hematopoietic stem cell attrition and cytopenia during childhood, which along with intrinsic chromosomal instability, favor clonal evolution and the frequent emergence in their teens or young adulthood of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). To early identify and further predict bone marrow (BM) clonal progression and enable timely treatment, the follow-up of FA patients includes regular BM morphological and cytogenetic examinations. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment of FA patients with MDS or AML. Although questions remain concerning HSCT itself (including the need for pretransplant chemotherapy, the best conditioning regimen, and the optimal long-term follow-up of such patients especially regarding secondary malignancies), clonal evolution in the absence of significant BM dysplasia and blast cells can be difficult to address in FA patients, for whom the concept of preemptive HSCT is discussed. Illustrated by 3 representative clinical vignettes showing specific features of MDS and AML in FA patients, this paper summarizes our practical approach from diagnosis through treatment in this particular situation. PMID:27020090

  2. Activity of 8F4, a T-cell receptor-like anti-PR1/HLA-A2 antibody, against primary human AML in vivo.

    PubMed

    Sergeeva, A; He, H; Ruisaard, K; St John, L; Alatrash, G; Clise-Dwyer, K; Li, D; Patenia, R; Hong, R; Sukhumalchandra, P; You, M J; Gagea, M; Ma, Q; Molldrem, J J

    2016-07-01

    The PR1 peptide, derived from the leukemia-associated antigens proteinase 3 and neutrophil elastase, is overexpressed on HLA-A2 in acute myeloid leukemia (AML). We developed a high-affinity T-cell receptor-like murine monoclonal antibody, 8F4, that binds to the PR1/HLA-A2 complex, mediates lysis of AML and inhibits leukemia colony formation. Here, we explored whether 8F4 was active in vivo against chemotherapy-resistant AML, including secondary AML. In a screening model, coincubation of AML with 8F4 ex vivo prevented engraftment of all tested AML subtypes in immunodeficient NSG (NOD scid IL-2 receptor γ-chain knockout) mice. In a treatment model of established human AML, administration of 8F4 significantly reduced or eliminated AML xenografts and extended survival compared with isotype antibody-treated mice. Moreover, in secondary transfer experiments, mice inoculated with bone marrow from 8F4-treated mice showed no evidence of AML engraftment, supporting the possible activity of 8F4 against the subset of AML with self-renewing potential. Our data provide evidence that 8F4 antibody is highly active in AML, including chemotherapy-resistant disease, supporting its potential use as a therapeutic agent in patients with AML. PMID:27055866

  3. Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation in Intermediate-Risk Acute Myeloid Leukemia Adult Patients in First Complete Remission: A Meta-Analysis of Prospective Studies

    PubMed Central

    Zhu, Honghu; Dou, Liping; Liu, Daihong; Fu, Lin; Ma, Cong; Ma, Xuebin; Yao, Yushi; Zhou, Lei; Wang, Qian; Wang, Lijun; Zhao, Yu; Jing, Yu; Wang, Lili; Li, Yonghui; Yu, Li

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) and consolidation chemotherapy have been used to treat intermediate-risk acute myeloid leukemia (AML) patients in first complete remission (CR1). However, it is still unclear which treatments are most effective for these patients. The aim of our study was to analyze the relapse-free survival (RFS) and overall survival (OS) benefit of allogeneic HSCT (alloHSCT) for intermediate-risk AML patients in CR1. A meta-analysis of prospective trials comparing alloHSCT to non-alloHSCT (autologous HSCT [autoHSCT] and/or chemotherapy) was undertaken. We systematically searched PubMed, Embase, and the Cochrane Library though October 2014, using keywords and relative MeSH or Emtree terms, ‘allogeneic’; ‘acut*’ and ‘leukem*/aml/leukaem*/leucem*/leucaem*’; and ‘nonlympho*’ or ‘myelo*’. A total of 7053 articles were accessed. The primary outcomes were RFS and OS, while the secondary outcomes were treatment-related mortality (TRM) and relapse rate (RR). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for each outcome. The primary outcomes were RFS and OS, while the secondary outcomes were TRM and RR. We included 9 prospective controlled studies including 1950 adult patients. Patients with intermediate-risk AML in CR1 who received either alloHSCT or non-alloHSCT were considered eligible. AlloHSCT was found to be associated with significantly better RFS, OS, and RR than non-alloHSCT (HR, 0.684 [95% CI: 0.48, 0.95]; HR, 0.76 [95% CI: 0.61, 0.95]; and HR, 0.58 [95% CI: 0.45, 0.75], respectively). TRM was significantly higher following alloHSCT than non-alloHSCT (HR, 3.09 [95% CI: 1.38, 6.92]). However, subgroup analysis showed no OS benefit for alloHSCT over autoHSCT (HR, 0.99 [95% CI: 0.70, 1.39]). In conclusion, alloHSCT is associated with more favorable RFS, OS, and RR benefits (but not TRM outcomes) than non-alloHSCT generally, but does not have an OS advantage over autoHSCT specifically, in

  4. [Molecular target drugs for AML--current state and prospects for the future].

    PubMed

    Kohgo, Yutaka; Inamura, Junki; Shindo, Motohiro

    2014-06-01

    Acute myeloblastic leukemia (AML) is a disease which may be completely cured by intensive chemotherapy or stem cell transplantation. However, the prognoses are poor in elderly, refractory or recurrence cases. Molecular targeted drugs have been expected to improve the prognoses of patients with various cancers, but there are few kinds of molecular target drugs for AML. On the other hand, excellent drug exists such as tretinoin for acute promyelocytic leukemia. Molecular mechanisms have been elucidated in AML cells, and the molecules which can be the good target of the treatment have been identified. Novel molecular target drugs are also expected. PMID:25016805

  5. Hierarchy in gene expression is predictive of risk, progression, and outcome in adult acute myeloid leukemia

    NASA Astrophysics Data System (ADS)

    Tripathi, Shubham; Deem, Michael W.

    2015-02-01

    Cancer progresses with a change in the structure of the gene network in normal cells. We define a measure of organizational hierarchy in gene networks of affected cells in adult acute myeloid leukemia (AML) patients. With a retrospective cohort analysis based on the gene expression profiles of 116 AML patients, we find that the likelihood of future cancer relapse and the level of clinical risk are directly correlated with the level of organization in the cancer related gene network. We also explore the variation of the level of organization in the gene network with cancer progression. We find that this variation is non-monotonic, which implies the fitness landscape in the evolution of AML cancer cells is non-trivial. We further find that the hierarchy in gene expression at the time of diagnosis may be a useful biomarker in AML prognosis.

  6. Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia.

    PubMed

    Roboz, Gail J; Montesinos, Pau; Selleslag, Dominik; Wei, Andrew; Jang, Jun-Ho; Falantes, Jose; Voso, Maria T; Sayar, Hamid; Porkka, Kimmo; Marlton, Paula; Almeida, Antonio; Mohan, Sanjay; Ravandi, Farhad; Garcia-Manero, Guillermo; Skikne, Barry; Kantarjian, Hagop

    2016-02-01

    Older patients with acute myeloid leukemia (AML) have worse rates of complete remission and shorter overall survival than younger patients. The epigenetic modifier CC-486 is an oral formulation of azacitidine with promising clinical activity in patients with AML in Phase I studies. The Phase III, randomized, double-blind, placebo-controlled QUAZAR AML Maintenance trial (CC-486-AML-001) examines CC-486 maintenance therapy (300 mg/day for 14 days of 28-day treatment cycles) for patients aged ≥55 years with AML in first complete remission. The primary end point is overall survival. Secondary end points include relapse-free survival, safety, health-related quality of life and healthcare resource utilization. This trial will investigate whether CC-486 maintenance can prolong remission and improve survival for older patients with AML. PMID:26785287

  7. Prognostic factors of childhood and adolescent acute myeloid leukemia (AML) survival: evidence from four decades of US population data.

    PubMed

    Hossain, Md Jobayer; Xie, Li; Caywood, Emi H

    2015-10-01

    Growing insight into prognosis of pediatric acute myeloid leukemia (AML) survival has led to improved outcome over time and could be further enhanced through investigation using a large number of patients. To characterize the extent of the association of pediatric AML survival with its identified prognostic factors, we analyzed the United States population-based Surveillance Epidemiology and End Results (SEER) large dataset of 3442 pediatric AML patients diagnosed and followed between 1973 and 2011 using a Cox proportional hazards model stratified by year of diagnosis. Patients diagnosed between 10 and 19 years of age were at a higher risk of death compared to those diagnosed before age 10 (adjusted hazard ratio (aHR): 1.30, 95% confidence interval (CI): 1.17-1.44). African Americans (1.27, 1.09-1.48) and Hispanics (1.15, 1.00-1.32) had an elevated risk of mortality than Caucasians. Compared to the subtype acute promyelocytic leukemia, AML with minimal differentiation (2.44, 1.78-3.35); acute erythroid leukemia (2.34, 1.60-3.40); AML without maturation (1.87, 1.35-2.59); and most other AML subtypes had a higher risk of mortality, whereas AML with inv(16) had a substantially lower risk. Age at diagnosis, race-ethnicity, AML subtype, county level poverty and geographic region appeared as significant prognostic factors of pediatric AML survival in the US. Contrary to previous findings, the subtypes of AML with t(9;11)(p22;q23)MLLT3-MLL, AML without maturation and acute myelomonocytic leukemia emerged to be indicative of poor outcome. PMID:26159683

  8. Trisomy 8 in pediatric acute myeloid leukemia: A NOPHO-AML study.

    PubMed

    Laursen, Anne Cathrine Lund; Sandahl, Julie Damgaard; Kjeldsen, Eigil; Abrahamsson, Jonas; Asdahl, Peter; Ha, Shau-Yin; Heldrup, Jesper; Jahnukainen, Kirsi; Jónsson, Ólafur G; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Forestier, Erik; Hasle, Henrik

    2016-09-01

    Trisomy 8 (+8) is a common cytogenetic aberration in acute myeloid leukemia (AML); however, the impact of +8 in pediatric AML is largely unknown. We retrospectively investigated 609 patients from the NOPHO-AML database to determine the clinical and cytogenetic characteristics of +8 in pediatric AML and to investigate its prognostic impact. Complete cytogenetic data were available in 596 patients (98%) aged 0-18 years, diagnosed from 1993 to 2012, and treated according to the NOPHO-AML 1993 and 2004 protocols in the Nordic countries and Hong Kong. We identified 86 patients (14%) with +8. Trisomy 8 was combined with other cytogenetic aberrations in 68 patients (11%) (+8 other) and in 18 patients (3%), it was the sole abnormality (+8 alone). Trisomy 8 was associated with FAB M5 (36%) but otherwise clinically comparable with non-trisomy 8 patients. Trisomy 8 was favorable in patients of young age and with t(9;11). Trisomy 8 alone was associated with older age (median age 10.1 years), FAB M2 (33%), and FLT3-ITD mutations (58%). The 5-year event-free survival for patients with +8 alone was 50% and 5-year overall survival was 75%. In conclusion, +8 is one of the most common cytogenetic aberrations in pediatric AML. Trisomy 8 positive AML is a heterogeneous group and the majority of cases have additional cytogenetic aberrations. Patients with +8 alone differed from patients with +8 other and were associated with older age, FAB M2, and FLT3-ITD aberrations. There were no differences in survival despite the more frequent occurrence of FLT3-ITD in +8 alone. © 2016 Wiley Periodicals, Inc. PMID:27153159

  9. Single-agent GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-matched BMT for AML, ALL, and MDS

    PubMed Central

    Kanakry, Christopher G.; Tsai, Hua-Ling; Bolaños-Meade, Javier; Smith, B. Douglas; Gojo, Ivana; Kanakry, Jennifer A.; Kasamon, Yvette L.; Gladstone, Douglas E.; Matsui, William; Borrello, Ivan; Huff, Carol Ann; Swinnen, Lode J.; Powell, Jonathan D.; Pratz, Keith W.; DeZern, Amy E.; Showel, Margaret M.; McDevitt, Michael A.; Brodsky, Robert A.; Levis, Mark J.; Ambinder, Richard F.; Fuchs, Ephraim J.; Rosner, Gary L.; Jones, Richard J.

    2014-01-01

    High-dose, posttransplantation cyclophosphamide (PTCy) reduces severe graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT), but the impact of PTCy on long-term, disease-specific outcomes is unclear. We conducted a retrospective study of 209 consecutive adult patients transplanted for acute myeloid leukemia (AML, n = 138), myelodysplastic syndrome (n = 28), or acute lymphoblastic leukemia (ALL, n = 43) using PTCy as sole GVHD prophylaxis after myeloablative conditioning and HLA-matched–related or –unrelated T-cell–replete allografting. At alloBMT, 30% of patients were not in morphologic complete remission. The cumulative incidences of grades II to IV and III to IV acute GVHD at 100 days and chronic GVHD at 2 years were 45%, 11%, and 13%, respectively. Forty-three percent of patients did not require immunosuppression for any reason beyond PTCy. At 3 years, relapse cumulative incidence was 36%, disease-free survival was 46%, survival free of disease and chronic GVHD was 39%, and overall survival was 58%. Lack of remission at alloBMT, adverse cytogenetics, and low allograft nucleated cell dose were associated with inferior survival for AML patients. Minimal residual disease but not t(9;22) was associated with inferior outcomes for ALL patients. The ability to limit posttransplantation immunosuppression makes PTCy a promising transplantation platform for the integration of postgrafting strategies to prevent relapse. PMID:25316679

  10. The AML1-ETO fusion gene and the FLT3 length mutation collaborate in inducing acute leukemia in mice

    PubMed Central

    Schessl, Christina; Rawat, Vijay P.S.; Cusan, Monica; Deshpande, Aniruddha; Kohl, Tobias M.; Rosten, Patricia M.; Spiekermann, Karsten; Humphries, R. Keith; Schnittger, Susanne; Kern, Wolfgang; Hiddemann, Wolfgang; Quintanilla-Martinez, Leticia; Bohlander, Stefan K.; Feuring-Buske, Michaela; Buske, Christian

    2005-01-01

    The molecular characterization of leukemia has demonstrated that genetic alterations in the leukemic clone frequently fall into 2 classes, those affecting transcription factors (e.g., AML1-ETO) and mutations affecting genes involved in signal transduction (e.g., activating mutations of FLT3 and KIT). This finding has favored a model of leukemogenesis in which the collaboration of these 2 classes of genetic alterations is necessary for the malignant transformation of hematopoietic progenitor cells. The model is supported by experimental data indicating that AML1-ETO and FLT3 length mutation (FLT3-LM), 2 of the most frequent genetic alterations in AML, are both insufficient on their own to cause leukemia in animal models. Here we report that AML1-ETO collaborates with FLT3-LM in inducing acute leukemia in a murine BM transplantation model. Moreover, in a series of 135 patients with AML1-ETO–positive AML, the most frequently identified class of additional mutations affected genes involved in signal transduction pathways including FLT3-LM or mutations of KIT and NRAS. These data support the concept of oncogenic cooperation between AML1-ETO and a class of activating mutations, recurrently found in patients with t(8;21), and provide a rationale for therapies targeting signal transduction pathways in AML1-ETO–positive leukemias. PMID:16025155

  11. AML1/ETO oncoprotein is directed to AML1 binding regions and co-localizes with AML1 and HEB on its targets.

    PubMed

    Gardini, Alessandro; Cesaroni, Matteo; Luzi, Lucilla; Okumura, Akiko J; Biggs, Joseph R; Minardi, Simone P; Venturini, Elisa; Zhang, Dong-Er; Pelicci, Pier Giuseppe; Alcalay, Myriam

    2008-11-01

    A reciprocal translocation involving chromosomes 8 and 21 generates the AML1/ETO oncogenic transcription factor that initiates acute myeloid leukemia by recruiting co-repressor complexes to DNA. AML1/ETO interferes with the function of its wild-type counterpart, AML1, by directly targeting AML1 binding sites. However, transcriptional regulation determined by AML1/ETO probably relies on a more complex network, since the fusion protein has been shown to interact with a number of other transcription factors, in particular E-proteins, and may therefore target other sites on DNA. Genome-wide chromatin immunoprecipitation and expression profiling were exploited to identify AML1/ETO-dependent transcriptional regulation. AML1/ETO was found to co-localize with AML1, demonstrating that the fusion protein follows the binding pattern of the wild-type protein but does not function primarily by displacing it. The DNA binding profile of the E-protein HEB was grossly rearranged upon expression of AML1/ETO, and the fusion protein was found to co-localize with both AML1 and HEB on many of its regulated targets. Furthermore, the level of HEB protein was increased in both primary cells and cell lines expressing AML1/ETO. Our results suggest a major role for the functional interaction of AML1/ETO with AML1 and HEB in transcriptional regulation determined by the fusion protein. PMID:19043539

  12. Assisting sexually abused adults. Practical guide to interviewing patients.

    PubMed Central

    Leach, M. M.; Bethune, C.

    1996-01-01

    Millions of adults have been sexually abused. Patients often confide in their family physicians concerning their abuse. Physicians must understand their own issues surrounding sexual abuse and its sequelae before they attempt to treat sexually abused patients. The PLISSIT model offers a practical guide for assisting abused adult patients. PMID:8924817

  13. Decitabine enhances anti-CD33 monoclonal antibody BI 836858-mediated natural killer ADCC against AML blasts.

    PubMed

    Vasu, Sumithira; He, Shun; Cheney, Carolyn; Gopalakrishnan, Bhavani; Mani, Rajeswaran; Lozanski, Gerard; Mo, Xiaokui; Groh, Veronica; Whitman, Susan P; Konopitzky, Renate; Kössl, Christian; Bucci, Donna; Lucas, David M; Yu, Jianhua; Caligiuri, Michael A; Blum, William; Adam, Paul J; Borges, Eric; Rueter, Bjoern; Heider, Karl-Heinz; Marcucci, Guido; Muthusamy, Natarajan

    2016-06-01

    Acute myeloid leukemia (AML) is the most common type of acute leukemia, affecting older individuals at a median age of 67 years. Resistance to intensive induction chemotherapy is the major cause of death in elderly AML; hence, novel treatment strategies are warranted. CD33-directed antibody-drug conjugates (gemtuzumab ozogamicin) have been shown to improve overall survival, validating CD33 as a target for antibody-based therapy of AML. Here, we report the in vitro efficacy of BI 836858, a fully human, Fc-engineered, anti-CD33 antibody using AML cell lines and primary AML blasts as targets. BI 836858-opsonized AML cells significantly induced both autologous and allogeneic natural killer (NK)-cell degranulation and NK-cell-mediated antibody-dependent cellular cytotoxicity (ADCC). In vitro treatment of AML blasts with decitabine (DAC) or 5-azacytidine, 2 hypomethylating agents that show efficacy in older patients, did not compromise BI 836858-induced NK-cell-mediated ADCC. Evaluation of BI 836858-mediated ADCC in serial marrow AML aspirates in patients who received a 10-day course of DAC (pre-DAC, days 4, 11, and 28 post-DAC) revealed significantly higher ADCC in samples at day 28 post-DAC when compared with pre-DAC treatment. Analysis of ligands to activating receptors (NKG2D) showed significantly increased NKG2D ligand [NKG2DL] expression in day 28 post-DAC samples compared with pre-DAC samples; when NKG2DL receptor was blocked using antibodies, BI 836858-mediated ADCC was significantly decreased, suggesting that DAC enhances AML blast susceptibility to BI 836858 by upregulating NKG2DL. These data provide a rationale for combination therapy of Fc-engineered antibodies such as BI 836858 with azanucleosides in elderly patients with AML. PMID:27013443

  14. Sequencing the AML Genome, Transcriptome, and Epigenome

    PubMed Central

    Mardis, Elaine R.

    2014-01-01

    Leukemia is a disease that develops as a result of changes in the genomes of hematopoietic cells, a fact first appreciated by microscopic examination of the bone marrow cell chromosomes of affected patients. These studies revealed that specific subtypes of leukemia diagnosis correlated with specific chromosomal abnormalities, such as the t(15;17) of acute promyelocytic leukemia1 and the t(9;22) of chronic myeloid leukemia2. Over time, our genomic characterization of hematologic malignancies has moved beyond the resolution of the microscope to that of individual nucleotides in the analysis of whole genome sequencing data using state-of-the-art massively parallel sequencing (MPS) instruments and algorithmic analyses of the resulting data. In addition to studying the genomic sequence alterations that occur in patient’s genomes, these same instruments can decode the methylation landscape of the leukemia genome and the resulting RNA expression landscape of the leukemia transcriptome. Broad correlative analyses can then integrate these three data types to better inform researchers and clinicians about the biology of individual acute myeloid leukemia (AML) cases, facilitating improvements in care and prognosis. PMID:25311738

  15. miR-9 is a tumor suppressor in pediatric AML with t(8;21).

    PubMed

    Emmrich, S; Katsman-Kuipers, J E; Henke, K; Khatib, M E; Jammal, R; Engeland, F; Dasci, F; Zwaan, C M; den Boer, M L; Verboon, L; Stary, J; Baruchel, A; de Haas, V; Danen-van Oorschot, A A; Fornerod, M; Pieters, R; Reinhardt, D; Klusmann, J H; van den Heuvel-Eibrink, M M

    2014-05-01

    MicroRNAs (miRNAs) play a pivotal role in the regulation of hematopoiesis and development of leukemia. Great interest emerged in modulating miRNA expression for therapeutic purposes. In order to identify miRNAs, which specifically suppress leukemic growth of acute myeloid leukemia (AML) with t(8;21), inv(16) or mixed lineage leukemia (MLL) rearrangement by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases. Four miRNAs, specifically downregulated in MLL-rearranged, t(8;21) or inv(16) AMLs, were characterized by their tumor-suppressive properties in cell lines representing those respective cytogenetic groups. Among those, forced expression of miR-9 reduced leukemic growth and induced monocytic differentiation of t(8;21) AML cell lines in vitro and in vivo. The tumor-suppressive functions of miR-9 were specifically restricted to AML cell lines and primary leukemic blasts with t(8;21). On the other hand, these functions were not evident in AML blasts from patients with MLL rearrangements. We showed that miR-9 exerts its effects through the cooperation with let-7 to repress the oncogenic LIN28B/HMGA2 axis. Thus, miR-9 is a tumor suppressor-miR which acts in a stringent cell context-dependent manner. PMID:24270738

  16. Inversion and deletion of 16q22 defined by array CGH, FISH, and RT-PCR in a patient with AML.

    PubMed

    Dawson, Angelika J; Bal, Shibani; McTavish, Barry; Tomiuk, Michelle; Schroedter, Ingo; Ahsanuddin, Arshad N; Seftel, Matthew D; Vallente, Rhea; Mai, Sabine; Cotter, Philip D; Hovanes, Karine; Gorre, Mercedes; Gunn, Shelly R

    2011-06-01

    Acute myelomonocytic leukemia with eosinophilia is commonly associated with pericentric inversions of chromosome 16, involving the core binding factor beta gene (CBFB) on 16q22 and the myosin heavy chain gene (MYH11) on 16p13. The inv(16)(p13q22) results in a fusion gene comprising the 5'CBFB gene and the 3'MYH11 gene on the short arm of chromosome 16. The fusion gene interferes with the normal transcription of the CBFA/CBFB heterodimer and disrupts myeloid differentiation. The inv(16) is associated with a good prognosis. The inv(16) with deletion of the 3'CBFB region of the gene is a very rare occurrence. Although the number of cases is small, inv(16) with a deleted 3'CBFB seems to be associated with a poorer prognosis than that generally associated with inv(16). Our patient was a 30-year-old man with newly diagnosed acute myeloid leukemia who was found to have a CBFB-MYH11 fusion by reverse transcriptase-polymerase chain reaction. The high blast count and lack of differentiation were not typical for this entity and suggested clonal progression. The initial karyotype by conventional cytogenetic analysis, in all metaphases examined, was 46,XY,del(7)(q32),del(16)(q22). Fluorescence in situ hybridization analysis with a dual-color, break-apart probe corresponding to the CBFB gene locus (Abbott, Des Plaines, IL) showed a derivative chromosome 16 resulting from an inversion of the CBFB gene with a deletion of the 3'CBFB probe region. Oligonucleotide array comparative genetic hybridization analysis was performed on this patient's diagnostic bone marrow DNA referenced to a normal male control DNA by using the DNAarray Heme Profile (CombiMatrix Diagnostics, Irvine, CA) microarray. This analysis showed a 1.2 Mb loss of 16q22.1, which did not include loss of the 3'CBFB gene locus, but rather sequences distal to this locus. The DNAarray Heme Profile results illustrate the importance of microarray in the correct identification of abnormalities that will affect prognosis. PMID

  17. PD-1hiTIM-3+ T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation

    PubMed Central

    Kong, Y; Zhang, J; Claxton, D F; Ehmann, W C; Rybka, W B; Zhu, L; Zeng, H; Schell, T D; Zheng, H

    2015-01-01

    Prognosis of leukemia relapse post allogeneic stem cell transplantation (alloSCT) is poor and effective new treatments are urgently needed. T cells are pivotal in eradicating leukemia through a graft versus leukemia (GVL) effect and leukemia relapse is considered a failure of GVL. T-cell exhaustion is a state of T-cell dysfunction mediated by inhibitory molecules including programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3). To evaluate whether T-cell exhaustion and inhibitory pathways are involved in leukemia relapse post alloSCT, we performed phenotypic and functional studies on T cells from peripheral blood of acute myeloid leukemia patients receiving alloSCT. Here we report that PD-1hiTIM-3+ cells are strongly associated with leukemia relapse post transplantation. Consistent with exhaustion, PD-1hiTIM-3+ T cells are functionally deficient manifested by reduced production of interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In addition, these cells demonstrate a phenotype consistent with exhausted antigen-experienced T cells by losing TN and TEMRA subsets. Importantly, increase of PD-1hiTIM-3+ cells occurs before clinical diagnosis of leukemia relapse, suggesting their predictive value. Results of our study provide an early diagnostic approach and a therapeutic target for leukemia relapse post transplantation. PMID:26230954

  18. PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation.

    PubMed

    Kong, Y; Zhang, J; Claxton, D F; Ehmann, W C; Rybka, W B; Zhu, L; Zeng, H; Schell, T D; Zheng, H

    2015-01-01

    Prognosis of leukemia relapse post allogeneic stem cell transplantation (alloSCT) is poor and effective new treatments are urgently needed. T cells are pivotal in eradicating leukemia through a graft versus leukemia (GVL) effect and leukemia relapse is considered a failure of GVL. T-cell exhaustion is a state of T-cell dysfunction mediated by inhibitory molecules including programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3). To evaluate whether T-cell exhaustion and inhibitory pathways are involved in leukemia relapse post alloSCT, we performed phenotypic and functional studies on T cells from peripheral blood of acute myeloid leukemia patients receiving alloSCT. Here we report that PD-1(hi)TIM-3(+) cells are strongly associated with leukemia relapse post transplantation. Consistent with exhaustion, PD-1(hi)TIM-3(+) T cells are functionally deficient manifested by reduced production of interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In addition, these cells demonstrate a phenotype consistent with exhausted antigen-experienced T cells by losing TN and TEMRA subsets. Importantly, increase of PD-1(hi)TIM-3(+) cells occurs before clinical diagnosis of leukemia relapse, suggesting their predictive value. Results of our study provide an early diagnostic approach and a therapeutic target for leukemia relapse post transplantation. PMID:26230954

  19. CHK1 as a therapeutic target to bypass chemoresistance in AML.

    PubMed

    David, Laure; Fernandez-Vidal, Anne; Bertoli, Sarah; Grgurevic, Srdana; Lepage, Benoît; Deshaies, Dominique; Prade, Naïs; Cartel, Maëlle; Larrue, Clément; Sarry, Jean-Emmanuel; Delabesse, Eric; Cazaux, Christophe; Didier, Christine; Récher, Christian; Manenti, Stéphane; Hoffmann, Jean-Sébastien

    2016-01-01

    The nucleoside analog cytarabine, an inhibitor of DNA replication fork progression that results in DNA damage, is currently used in the treatment of acute myeloid leukemia (AML). We explored the prognostic value of the expression of 72 genes involved in various aspects of DNA replication in a set of 198 AML patients treated by cytarabine-based chemotherapy. We unveiled that high expression of the DNA replication checkpoint gene CHEK1 is a prognostic marker associated with shorter overall, event-free, and relapse-free survivals and determined that the expression of CHEK1 can predict more frequent and earlier postremission relapse. CHEK1 encodes checkpoint kinase 1 (CHK1), which is activated by the kinase ATR when DNA replication is impaired by DNA damage. High abundance of CHK1 in AML patient cells correlated with higher clonogenic ability and more efficient DNA replication fork progression upon cytarabine treatment. Exposing the patient cells with the high abundance of CHK1 to SCH900776, an inhibitor of the kinase activity of CHK1, reduced clonogenic ability and progression of DNA replication in the presence of cytarabine. These results indicated that some AML cells rely on an efficient CHK1-mediated replication stress response for viability and that therapeutic strategies that inhibit CHK1 could extend current cytarabine-based treatments and overcome drug resistance. Furthermore, monitoring CHEK1 expression could be used both as a predictor of outcome and as a marker to select AML patients for CHK1 inhibitor treatments. PMID:27625304

  20. Allogeneic hematopoietic cell transplant for AML: no impact of pre-transplant extramedullary disease on outcome.

    PubMed

    Goyal, S D; Zhang, M-J; Wang, H-L; Akpek, G; Copelan, E A; Freytes, C; Gale, R P; Hamadani, M; Inamoto, Y; Kamble, R T; Lazarus, H M; Marks, D I; Nishihori, T; Olsson, R F; Reshef, R; Ritchie, D S; Saber, W; Savani, B N; Seber, A; Shea, T C; Tallman, M S; Wirk, B; Bunjes, D W; Devine, S M; de Lima, M; Weisdorf, D J; Uy, G L

    2015-08-01

    The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature. PMID:25915806

  1. Clofarabine in combination with a standard remission induction regimen (cytosine arabinoside and idarubicin) in patients with previously untreated intermediate and bad-risk acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): phase I results of an ongoing phase I/II study of the leukemia groups of EORTC and GIMEMA (EORTC GIMEMA 06061/AML-14A trial).

    PubMed

    Willemze, R; Suciu, S; Muus, P; Halkes, C J M; Meloni, G; Meert, L; Karrasch, M; Rapion, J; Vignetti, M; Amadori, S; de Witte, T; Marie, J P

    2014-06-01

    This study aims to determine the maximum tolerated dose (MTD) of clofarabine combined with the EORTC-GIMEMA 3 + 10 induction regimen (idarubicin + cytosine arabinoside) in adults with untreated acute myelogenous leukemia or high-risk myelodysplastic syndrome. In this phase I trial, 25 patients (median age 56 years) received 5 days of clofarabine as 1-h infusion (arm A) or push injection (arm B) at the dose level of 5 × 10 or 5 × 15 mg/m(2)/day in an algorithmic dose escalation 3 + 3 design. A consolidation course (intermediate dose cytosine arabinoside, idarubicin) was planned for patients in complete remission (CR). Primary endpoint was safety and tolerance as measured by dose limiting toxicity (DLT); secondary endpoints were response rate, other grade III/IV toxicities, and hematological recovery after induction and consolidation. Five DLTs were observed (in arm A: one DLT at 10 mg/m(2)/day, three at 15 mg/m(2)/day; in arm B: one DLT at 15 mg/m(2)/day). Three patients receiving 15 mg/m(2)/day were withdrawn due to adverse events not classified as DLT. Prolonged hypoplasia was observed in five patients. CR + complete remission with incomplete recovery were achieved in 21 patients (11/12 (92 %) receiving clofarabine 10 mg/m(2)/day; 10/13 (77 %) receiving clofarabine 15 mg/m(2)/day). Clofarabine, 5 × 10 mg/m(2)/day, resulted in one DLT and no early treatment withdrawals. MTD of clofarabine combined with cytosine arabinoside and idarubicin is 5 × 10 mg/m(2)/day. PMID:24682421

  2. Prognostic Factors in Childhood Leukemia (ALL or AML)

    MedlinePlus

    ... for childhood leukemias Prognostic factors in childhood leukemia (ALL or AML) Certain factors that can affect a ... myelogenous leukemia (AML). Prognostic factors for children with ALL Children with ALL are often divided into risk ...

  3. The chimeric genes AML1/DS1 and AML1/EAP inhibit AML1B activation at the CSF1R promoter, but only AML1/MDS1 has tumor-promoter properties

    SciTech Connect

    Zent, C.S.; Matheiu, C.; Rowley, J.D.

    1996-02-06

    The (3;21)(q26;q22) translocation associated with treatment-related myelodysplastic syndrome, treatment-related acute myeloid leukemia, and blast crisis of chronic myeloid leukemia results in the expression of the chimeric genes AML1/EAP, AML1MDS1, and AML1/EVI1. AML1 (CBFA2), which codes for the {alpha} subunit of the heterodimeric transcription factor CBF, is also involved in the t(8;21), and the gene coding for the {beta} subunit (CBFB) is involved in the inv(16). These are two of the most common recurring chromosomal rearrangements in acute myeloid leukemia. CBF corresponds to the murine Pebp2 factor, and CBF binding sites are found in a number of eukaryotic and viral enhancers and promoters. We studied the effects of AML1/EAP and AML1/MDS1 at the AML1 binding site of the CSF1R (macrophage-colony-stimulating factor receptor gene) promoter by using reporter gene assays, and we analyzed the consequences of the expression of both chimeric proteins in an embryonic rat fibroblast cell line (Rat1A) in culture and after injection into athymic nude mice. Unlike AML1, which is an activator of the CSF1R promoter, the chimeric proteins did not transactivate the CSF1R promoter site but acted as inhibitors of AMLI (CBFA2). AML1/EAP and AML1/MDS1 expressed in adherent Rat1A cells decreased contact inhibition of growth, and expression of AML1/MDS1 was associated with acquisition of the ability to grow in suspension culture. Expression of AML1/MDS1 increased the tumorigenicity of Rat1A cells injected into athymic nude mice, whereas AML1/EAP expression provented tumor growth. These results suggest that expression of AML1/MDS1 can interfere with normal AML1 function, and that AML1/MDS1 has tumor-promoting properties in an embryonic rat fibroblast cell line. 26 refs., 5 figs.

  4. Small-molecule inhibition of BRD4 as a new potent approach to eliminate leukemic stem- and progenitor cells in acute myeloid leukemia (AML)

    PubMed Central

    Herrmann, Harald; Blatt, Katharina; Shi, Junwei; Gleixner, Karoline V.; Cerny-Reiterer, Sabine; Müllauer, Leonhard; Vakoc, Christopher R.; Sperr, Wolfgang R.; Horny, Hans-Peter; Bradner, James E.; Zuber, Johannes; Valent, Peter

    2012-01-01

    Acute myeloid leukemia (AML) is a life-threatening stem cell disease characterized by uncontrolled proliferation and accumulation of myeloblasts. Using an advanced RNAi screen-approach in an AML mouse model we have recently identified the epigenetic ‘reader’ BRD4 as a promising target in AML. In the current study, we asked whether inhibition of BRD4 by a small-molecule inhibitor, JQ1, leads to growth-inhibition and apoptosis in primary human AML stem- and progenitor cells. Primary cell samples were obtained from 37 patients with freshly diagnosed AML (n=23) or refractory AML (n=14). BRD4 was found to be expressed at the mRNA and protein level in unfractionated AML cells as well as in highly enriched CD34+/CD38− and CD34+/CD38+ stem- and progenitor cells in all patients examined. In unfractionated leukemic cells, submicromolar concentrations of JQ1 induced major growth-inhibitory effects (IC50 0.05-0.5 μM) in most samples, including cells derived from relapsed or refractory patients. In addition, JQ1 was found to induce apoptosis in CD34+/CD38− and CD34+/CD38+ stem- and progenitor cells in all donors examined as evidenced by combined surface/Annexin-V staining. Moreover, we were able to show that JQ1 synergizes with ARA-C in inducing growth inhibition in AML cells. Together, the BRD4-targeting drug JQ1 exerts major anti-leukemic effects in a broad range of human AML subtypes, including relapsed and refractory patients and all relevant stem- and progenitor cell compartments, including CD34+/CD38− and CD34+/CD38+ AML cells. These results characterize BRD4-inhibition as a promising new therapeutic approach in AML which should be further investigated in clinical trials. PMID:23249862

  5. A Crowdsourcing Approach to Developing and Assessing Prediction Algorithms for AML Prognosis.

    PubMed

    Noren, David P; Long, Byron L; Norel, Raquel; Rrhissorrakrai, Kahn; Hess, Kenneth; Hu, Chenyue Wendy; Bisberg, Alex J; Schultz, Andre; Engquist, Erik; Liu, Li; Lin, Xihui; Chen, Gregory M; Xie, Honglei; Hunter, Geoffrey A M; Boutros, Paul C; Stepanov, Oleg; Norman, Thea; Friend, Stephen H; Stolovitzky, Gustavo; Kornblau, Steven; Qutub, Amina A

    2016-06-01

    Acute Myeloid Leukemia (AML) is a fatal hematological cancer. The genetic abnormalities underlying AML are extremely heterogeneous among patients, making prognosis and treatment selection very difficult. While clinical proteomics data has the potential to improve prognosis accuracy, thus far, the quantitative means to do so have yet to be developed. Here we report the results and insights gained from the DREAM 9 Acute Myeloid Prediction Outcome Prediction Challenge (AML-OPC), a crowdsourcing effort designed to promote the development of quantitative methods for AML prognosis prediction. We identify the most accurate and robust models in predicting patient response to therapy, remission duration, and overall survival. We further investigate patient response to therapy, a clinically actionable prediction, and find that patients that are classified as resistant to therapy are harder to predict than responsive patients across the 31 models submitted to the challenge. The top two performing models, which held a high sensitivity to these patients, substantially utilized the proteomics data to make predictions. Using these models, we also identify which signaling proteins were useful in predicting patient therapeutic response. PMID:27351836

  6. A Crowdsourcing Approach to Developing and Assessing Prediction Algorithms for AML Prognosis

    PubMed Central

    Noren, David P.; Long, Byron L.; Norel, Raquel; Rrhissorrakrai, Kahn; Hess, Kenneth; Hu, Chenyue Wendy; Bisberg, Alex J.; Schultz, Andre; Engquist, Erik; Liu, Li; Lin, Xihui; Chen, Gregory M.; Xie, Honglei; Hunter, Geoffrey A. M.; Norman, Thea; Friend, Stephen H.; Stolovitzky, Gustavo; Kornblau, Steven; Qutub, Amina A.

    2016-01-01

    Acute Myeloid Leukemia (AML) is a fatal hematological cancer. The genetic abnormalities underlying AML are extremely heterogeneous among patients, making prognosis and treatment selection very difficult. While clinical proteomics data has the potential to improve prognosis accuracy, thus far, the quantitative means to do so have yet to be developed. Here we report the results and insights gained from the DREAM 9 Acute Myeloid Prediction Outcome Prediction Challenge (AML-OPC), a crowdsourcing effort designed to promote the development of quantitative methods for AML prognosis prediction. We identify the most accurate and robust models in predicting patient response to therapy, remission duration, and overall survival. We further investigate patient response to therapy, a clinically actionable prediction, and find that patients that are classified as resistant to therapy are harder to predict than responsive patients across the 31 models submitted to the challenge. The top two performing models, which held a high sensitivity to these patients, substantially utilized the proteomics data to make predictions. Using these models, we also identify which signaling proteins were useful in predicting patient therapeutic response. PMID:27351836

  7. The role of Clofarabine in the treatment of adults with acute myeloid leukemia.

    PubMed

    Fozza, Claudio

    2015-03-01

    The therapeutic scenario available for adult patients with acute myeloid leukemia (AML) has shown only partial progresses over the last few years. This is especially true for refractory and relapsed AML whose outcome is still extremely disappointing. In this context Clofarabine has offered new promising perspectives within first and second line protocols. This review will firstly describe the initial development in monotherapy, considering then the different potential combination strategies which include both polichemotherapeutic regimens and less conventional approaches with new generation drugs. The potential use of Clofarabine as induction treatment for patients candidate to stem cell transplantation and within conditioning regimens will be finally evaluated. PMID:25457773

  8. Mutant WT1 is associated with DNA hypermethylation of PRC2 targets in AML and responds to EZH2 inhibition.

    PubMed

    Sinha, Subarna; Thomas, Daniel; Yu, Linda; Gentles, Andrew J; Jung, Namyoung; Corces-Zimmerman, M Ryan; Chan, Steven M; Reinisch, Andreas; Feinberg, Andrew P; Dill, David L; Majeti, Ravindra

    2015-01-01

    Acute myeloid leukemia (AML) is associated with deregulation of DNA methylation; however, many cases do not bear mutations in known regulators of cytosine guanine dinucleotide (CpG) methylation. We found that mutations in WT1, IDH2, and CEBPA were strongly linked to DNA hypermethylation in AML using a novel integrative analysis of The Cancer Genome Atlas data based on Boolean implications, if-then rules that identify all individual CpG sites that are hypermethylated in the presence of a mutation. Introduction of mutant WT1 (WT1mut) into wild-type AML cells induced DNA hypermethylation, confirming mutant WT1 to be causally associated with DNA hypermethylation. Methylated genes in WT1mut primary patient samples were highly enriched for polycomb repressor complex 2 (PRC2) targets, implicating PRC2 dysregulation in WT1mut leukemogenesis. We found that PRC2 target genes were aberrantly repressed in WT1mut AML, and that expression of mutant WT1 in CD34(+) cord blood cells induced myeloid differentiation block. Treatment of WT1mut AML cells with short hairpin RNA or pharmacologic PRC2/enhancer of zeste homolog 2 (EZH2) inhibitors promoted myeloid differentiation, suggesting EZH2 inhibitors may be active in this AML subtype. Our results highlight a strong association between mutant WT1 and DNA hypermethylation in AML and demonstrate that Boolean implications can be used to decipher mutation-specific methylation patterns that may lead to therapeutic insights. PMID:25398938

  9. Physical and psychosocial challenges in adult hemophilia patients with inhibitors

    PubMed Central

    duTreil, Sue

    2014-01-01

    Numerous challenges confront adult hemophilia patients with inhibitors, including difficulty in controlling bleeding episodes, deterioration of joints, arthritic pain, physical disability, emotional turmoil, and social issues. High-intensity treatment regimens often used in the treatment of patients with inhibitors also impose significant scheduling, economic, and emotional demands on patients and their families or primary caregivers. A comprehensive multidisciplinary assessment of the physical, emotional, and social status of adult hemophilia patients with inhibitors is essential for the development of treatment strategies that can be individualized to address the complex needs of these patients. PMID:25093002

  10. Esculetin Downregulates the Expression of AML1-ETO and C-Kit in Kasumi-1 Cell Line by Decreasing Half-Life of mRNA

    PubMed Central

    Sawney, Sharad; Arora, Rashi; Aggarwal, Kamal K.; Saluja, Daman

    2015-01-01

    One of the most frequent genetic aberrations in acute myeloid leukemia (AML) is chromosomal translocation between AML1/RUNX1 on chromosome 21 and ETO gene on chromosome 8 resulting in the expression of chimeric oncogene AML1-ETO. Although patients with t(8;21) translocation have good prognosis, 5-year survival is observed only in 50% of the cases. AML1-ETO translocation is usually accompanied by overexpression of mutant C-Kit, a tyrosine kinase, which contributes to uncontrolled proliferation of premature blood cells leading to relapse and poor prognosis. We illustrate the potential use of esculetin on leukemic cell line, Kasumi-1, bearing t(8;21) translocation and mutated C-Kit gene. Esculetin decreases the expression of AML1-ETO at both protein and transcript level within 24 hours of treatment. Half-life of AML1-ETO mRNA was reduced from 7 hours to 1.5 hours. Similarly half-life of C-Kit mRNA was reduced to 2 hours from 5 hours in esculetin treated cells. Esculetin also perturbed the expression of ectopically expressed AML1-ETO in U937 cells. The decreased expression of AML1-ETO chimeric gene was associated with increased expression of LAT1 and RUNX3 genes, targets of AML1. We envisage that discovery of a drug candidate which could target both these mutated genes would be a considerable breakthrough for future application. PMID:25861270

  11. Approximate Quantification in Young, Healthy Older Adults', and Alzheimer Patients

    ERIC Educational Resources Information Center

    Gandini, Delphine; Lemaire, Patrick; Michel, Bernard Francois

    2009-01-01

    Forty young adults, 40 healthy older adults, and 39 probable AD patients were asked to estimate small (e.g., 25) and large (e.g., 60) collections of dots in a choice condition and in two no-choice conditions. Participants could choose between benchmark and anchoring strategies on each collection of dots in the choice condition and were required to…

  12. Initiation of MLL-rearranged AML is dependent on C/EBPα

    PubMed Central

    Ohlsson, Ewa; Hasemann, Marie Sigurd; Willer, Anton; Lauridsen, Felicia Kathrine Bratt; Rapin, Nicolas; Jendholm, Johan

    2014-01-01

    MLL-fusion proteins are potent inducers of oncogenic transformation, and their expression is considered to be the main oncogenic driving force in ∼10% of human acute myeloid leukemia (AML) patients. These oncogenic fusion proteins are responsible for the initiation of a downstream transcriptional program leading to the expression of factors such as MEIS1 and HOXA9, which in turn can replace MLL-fusion proteins in overexpression experiments. To what extent MLL fusion proteins act on their own during tumor initiation, or if they collaborate with other transcriptional regulators, is unclear. Here, we have compared gene expression profiles from human MLL-rearranged AML to normal progenitors and identified the myeloid tumor suppressor C/EBPα as a putative collaborator in MLL-rearranged AML. Interestingly, we find that deletion of Cebpa rendered murine hematopoietic progenitors completely resistant to MLL-ENL–induced leukemic transformation, whereas C/EBPα was dispensable in already established AMLs. Furthermore, we show that Cebpa-deficient granulocytic-monocytic progenitors were equally resistant to transformation and that C/EBPα collaborates with MLL-ENL in the induction of a transcriptional program, which is also apparent in human AML. Thus, our studies demonstrate a key role of C/EBPα in MLL fusion–driven transformation and find that it sharply demarcates tumor initiation and maintenance. PMID:24367003

  13. Coordinate regulation of residual bone marrow function by paracrine trafficking of AML exosomes.

    PubMed

    Huan, J; Hornick, N I; Goloviznina, N A; Kamimae-Lanning, A N; David, L L; Wilmarth, P A; Mori, T; Chevillet, J R; Narla, A; Roberts, C T; Loriaux, M M; Chang, B H; Kurre, P

    2015-12-01

    We recently demonstrated that acute myeloid leukemia (AML) cell lines and patient-derived blasts release exosomes that carry RNA and protein; following an in vitro transfer, AML exosomes produce proangiogenic changes in bystander cells. We reasoned that paracrine exosome trafficking may have a broader role in shaping the leukemic niche. In a series of in vitro studies and murine xenografts, we demonstrate that AML exosomes downregulate critical retention factors (Scf, Cxcl12) in stromal cells, leading to hematopoietic stem and progenitor cell (HSPC) mobilization from the bone marrow. Exosome trafficking also regulates HSPC directly, and we demonstrate declining clonogenicity, loss of CXCR4 and c-Kit expression, and the consistent repression of several hematopoietic transcription factors, including c-Myb, Cebp-β and Hoxa-9. Additional experiments using a model of extramedullary AML or direct intrafemoral injection of purified exosomes reveal that the erosion of HSPC function can occur independent of direct cell-cell contact with leukemia cells. Finally, using a novel multiplex proteomics technique, we identified candidate pathways involved in the direct exosome-mediated modulation of HSPC function. In aggregate, this work suggests that AML exosomes participate in the suppression of residual hematopoietic function that precedes widespread leukemic invasion of the bone marrow directly and indirectly via stromal components. PMID:26108689

  14. Oncogene- and drug resistance-associated alternative exon usage in acute myeloid leukemia (AML).

    PubMed

    Mohamed, Aminetou Mint; Balsat, Marie; Thenoz, Morgan; Koering, Catherine; Payen-Gay, Lea; Cheok, Meyling; Mortada, Hussein; Auboeuf, Didier; Pinatel, Christiane; El-Hamri, Mohamed; Dumontet, Charles; Cros, Emeline; Flandrin-Gresta, Pascale; Nibourel, Olivier; Preudhomme, Claude; Michallet, Mauricette; Thomas, Xavier; Nicolini, Franck; Solly, Françoise; Guyotat, Denis; Campos, Lydia; Wattel, Eric; Mortreux, Franck

    2016-01-19

    In addition to spliceosome gene mutations, oncogene expression and drug resistance in AML might influence exon expression. We performed exon-array analysis and exon-specific PCR (ESPCR) to identify specific landscapes of exon expression that are associated with DEK and WT1 oncogene expression and the resistance of AML cells to AraC, doxorubicin or azacitidine. Data were obtained for these five conditions through exon-array analysis of 17 cell lines and 24 patient samples and were extended through qESPCR of samples from 152 additional AML cases. More than 70% of AEUs identified by exon-array were technically validated through ESPCR. In vitro, 1,130 to 5,868 exon events distinguished the 5 conditions from their respective controls while in vivo 6,560 and 9,378 events distinguished chemosensitive and chemoresistant AML, respectively, from normal bone marrow. Whatever the cause of this effect, 30 to 80% of mis-spliced mRNAs involved genes unmodified at the whole transcriptional level. These AEUs unmasked new functional pathways that are distinct from those generated by transcriptional deregulation. These results also identified new putative pathways that could help increase the understanding of the effects mediated by DEK or WT1, which may allow the targeting of these pathways to prevent resistance of AML cells to chemotherapeutic agents. PMID:26284582

  15. Survival in patients with acute myeloblastic leukemia in Germany and the United States: Major differences in survival in young adults.

    PubMed

    Pulte, Dianne; Jansen, Lina; Castro, Felipe A; Krilaviciute, Agne; Katalinic, Alexander; Barnes, Benjamin; Ressing, Meike; Holleczek, Bernd; Luttmann, Sabine; Brenner, Hermann

    2016-09-15

    Previous epidemiologic studies on AML have been limited by the rarity of the disease. Here, we present population level data on survival of patients with AML in Germany and the United States (US). Data were extracted from 11 population-based cancer registries in Germany and the Surveillance, Epidemiology, and End Results (SEER13) database in the US. Patients diagnosed with AML in 1997-2011 were included. Period analysis was used to estimate 5-year relative survival (RS) and trends in survival in the early 21st century. Overall 5-year age-adjusted RS for patients with AML in 2007-2011 was greater in Germany than in the US at 22.8% and 18.8%, respectively. Five-year RS was higher in Germany than in the US at all ages, with particularly large differences at ages 15-24 for whom 5-year RS was 64.3% in Germany and 55.0% in the US and 35-44, with 5-year RS estimates of 61.8% in Germany and 46.6% in the US. Most of the difference in 5-year RS was due to higher 1-year RS, with overall 1-year RS estimates of 47.0% in Germany and 38.5% in the US. A small increase in RS was observed between 2003-2005 and 2009-2011 in both countries, but no increase in survival was observed in either country for ages 75+. To our knowledge, this is the first detailed description of AML survival in Germany. Comparison to the US suggests that further analysis into risk factors for poor outcomes in AML in the US may be useful in improving survival. PMID:27176899

  16. Molecular cytogenetic findings in a three-way novel variant of t(1;8;21)(p35;q22;q22): a unique relocation of the AML1/ETO fusion gene 1p35 in AML-M2.

    PubMed

    Ahmad, Firoz; Kokate, Prajakta; Chheda, Pratiksha; Dalvi, Rupa; Das, Bibhu Ranjan; Mandava, Swarna

    2008-01-15

    Acute myeloid leukemia (AML) is a malignant neoplasm of hematopoietic stem cells characterized by an abnormal proliferation of myeloid precursors, a reduced rate of apoptosis, and an arrest in cellular differentiation. The present report deals with the results of hematologic, immunophenotypic, cytogenetic, fluorescence in situ hybridization (FISH), and molecular analyses of a 53-year-old female patient diagnosed with AML-M2. Cytogenetic and FISH analysis revealed a complex translocation involving three chromosomes showing t(1;8;21)(p35;q22;q22). The observation of breakpoints at 8q22 and 21q22 suggests a rearrangement of the ETO and AML1 genes, respectively. Using a dual-color FISH test with ETO and AML1 probes, an AML1/ETO fusion signal on the derivative 1p35 instead of der(8) was demonstrated. To the best of our knowledge, this is the first report about the relocation of the AML1/ETO fusion gene to the 1p35 rather than der(8), suggesting the presence of a novel variant of t(8;21)(q22;q22) in the observed patient. PMID:18206543

  17. Infectious complications in children with acute myeloid leukemia: decreased mortality in multicenter trial AML-BFM 2004

    PubMed Central

    Bochennek, K; Hassler, A; Perner, C; Gilfert, J; Schöning, S; Klingebiel, T; Reinhardt, D; Creutzig, U; Lehrnbecher, T

    2016-01-01

    Infections are an important cause for morbidity and mortality in pediatric acute myeloid leukemia (AML). We therefore characterized infectious complications in children treated according to the trial AML-BFM 2004. Patients with Down syndrome were excluded from the analysis. Data were gathered from the medical records in the hospital where the patients were treated. A total of 405 patients (203 girls; median age 8.4 years) experienced 1326 infections. Fever without identifiable source occurred in 56.1% of the patients and clinically and microbiologically documented infections in 17.5% and 32.4% of the patients, respectively. In all, 240 Gram-positive (112 viridans group streptococci) and 90 Gram-negative isolates were recovered from the bloodstream. Invasive fungal infection was diagnosed in 3% of the patients. Three children each died of Gram-negative bacteremia and invasive aspergillosis, respectively. As compared with the results of AML-BFM 93 with lower dose intensity, infection-related morbidity was slightly higher in AML-BFM 2004 (3.3. versus 2.8 infections per patient), whereas infection-related mortality significantly decreased (1.5% versus 5.4% P=0.003). Specific anti-infective recommendations included in the treatment protocol, regular training courses for pediatric hematologists and increasing experience may be the reason for reduced infection-related mortality in children with AML. Further studies are needed to decrease infection-related morbidity. PMID:26771808

  18. Pulmonary manifestations in adult patients with chronic granulomatous disease.

    PubMed

    Salvator, Hélène; Mahlaoui, Nizar; Catherinot, Emilie; Rivaud, Elisabeth; Pilmis, Benoit; Borie, Raphael; Crestani, Bruno; Tcherakian, Colas; Suarez, Felipe; Dunogue, Bertrand; Gougerot-Pocidalo, Marie-Anne; Hurtado-Nedelec, Margarita; Dreyfus, Jean-François; Durieu, Isabelle; Fouyssac, Fanny; Hermine, Olivier; Lortholary, Olivier; Fischer, Alain; Couderc, Louis-Jean

    2015-06-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by failure of superoxide production in phagocytic cells. The disease is characterised by recurrent infections and inflammatory events, frequently affecting the lungs. Improvement of life expectancy now allows most patients to reach adulthood. We aimed to describe the pattern of pulmonary manifestations occurring during adulthood in CGD patients. This was a retrospective study of the French national cohort of adult patients (≥16 years old) with CGD. Medical data were obtained for 67 adult patients. Pulmonary manifestations affected two-thirds of adult patients. Their incidence was significantly higher than in childhood (mean annual rate 0.22 versus 0.07, p=0.01). Infectious risk persisted despite anti-infectious prophylaxis. Invasive fungal infections were frequent (0.11 per year per patient) and asymptomatic in 37% of the cases. They often required lung biopsy for diagnosis (10 out of 30). Noninfectious respiratory events concerned 28% of adult patients, frequently associated with a concomitant fungal infection (40%). They were more frequent in patients with the X-linked form of CGD. Immune-modulator therapies were required in most cases (70%). Respiratory manifestations are major complications of CGD in adulthood. Noninfectious pulmonary manifestations are as deleterious as infectious pneumonia. A specific respiratory monitoring is necessary. PMID:25614174

  19. Mediastinal Tuberculosis in an Adult Patient with Cystic Fibrosis▿

    PubMed Central

    Morand, Philippe C.; Burgel, Pierre-Régis; Carlotti, Agnès; Desmazes-Dufeu, Nadine; Farhi, David; Martin, Clémence; Kanaan, Reem; Mangialavori, Luigi; Palangié, Estelle; Dusser, Daniel; Poyart, Claire; Hubert, Dominique

    2011-01-01

    Tuberculosis (TB) is rarely observed in cystic fibrosis (CF) patients. We report the first case of mediastinal TB, associated with leg pain and skin rash, in an adult patient with CF, and discuss factors suggestive of TB in the course of CF. PMID:21106788

  20. Hierarchy in Gene Expression is Predictive of Risk, Progression, and Outcome in Adult Acute Myeloid Leukemia

    PubMed Central

    Tripathi, Shubham; Deem, Michael W.

    2015-01-01

    Cancer progresses with a change in the structure of the gene network in normal cells. We define a measure of organizational hierarchy in gene networks of affected cells in adult acute myeloid leukemia (AML) patients. With a retrospective cohort analysis based on the gene expression profiles of 116 acute myeloid leukemia patients, we find that the likelihood of future cancer relapse and the level of clinical risk are directly correlated with the level of organization in the cancer related gene network. We also explore the variation of the level of organization in the gene network with cancer progression. We find that this variation is non-monotonic, which implies the fitness landscape in the evolution of AML cancer cells is nontrivial. We further find that the hierarchy in gene expression at the time of diagnosis may be a useful biomarker in AML prognosis. PMID:25685944

  1. A prognostic model for survival after salvage treatment with FLAG-Ida +/- gemtuzumab-ozogamicine in adult patients with refractory/relapsed acute myeloid leukaemia.

    PubMed

    Bergua, Juan M; Montesinos, Pau; Martinez-Cuadrón, David; Fernández-Abellán, Pascual; Serrano, Josefina; Sayas, María J; Prieto-Fernandez, Julio; García, Raimundo; García-Huerta, Ana J; Barrios, Manuel; Benavente, Celina; Pérez-Encinas, Manuel; Simiele, Adriana; Rodríguez-Macias, Gabriela; Herrera-Puente, Pilar; Rodríguez-Veiga, Rebeca; Martínez-Sánchez, María P; Amador-Barciela, María L; Riaza-Grau, Rosalía; Sanz, Miguel A

    2016-09-01

    The combination of fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (FLAG-Ida) is widely used in relapsed/refractory acute myeloid leukaemia (AML). We retrospectively analysed the results of 259 adult AML patients treated as first salvage with FLAG-Ida or FLAG-Ida plus Gentuzumab-Ozogamicin (FLAGO-Ida) of the Programa Español de Tratamientos en Hematología (PETHEMA) database, developing a prognostic score system of survival in this setting (SALFLAGE score). Overall, 221 patients received FLAG-Ida and 38 FLAGO-Ida; 92 were older than 60 years. The complete remission (CR)/CR with incomplete blood count recovery (CRi) rate was 51%, with 9% of induction deaths. Three covariates were associated with lower CR/CRi: high-risk cytogenetics and t(8;21) at diagnosis, no previous allogeneic stem cell transplantation (allo-SCT) and relapse-free interval <1 year. Allo-SCT was performed in second CR in 60 patients (23%). The median overall survival (OS) of the entire cohort was 0·7 years, with 22% OS at 5-years. Four independent variables were used to construct the score: cytogenetics, FLT3-internal tandem duplication, length of relapse-free interval and previous allo-SCT. Using this stratification system, three groups were defined: favourable (26% of patients), intermediate (29%) and poor-risk (45%), with an expected 5-year OS of 52%, 26% and 7%, respectively. The SALFLAGE score discriminated a subset of patients with an acceptable long-term outcome using FLAG-Ida/FLAGO-Ida regimen. The results of this retrospective analysis should be validated in independent external cohorts. PMID:27118319

  2. Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia

    PubMed Central

    2013-01-01

    BACKGROUND Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns of mutations and epigenetic phenotypes are not yet clear. METHODS We analyzed the genomes of 200 clinically annotated adult cases of de novo AML, using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and microRNA sequencing and DNA-methylation analysis. RESULTS AML genomes have fewer mutations than most other adult cancers, with an average of only 13 mutations found in genes. Of these, an average of 5 are in genes that are recurrently mutated in AML. A total of 23 genes were significantly mutated, and another 237 were mutated in two or more samples. Nearly all samples had at least 1 nonsynonymous mutation in one of nine categories of genes that are almost certainly relevant for pathogenesis, including transcription-factor fusions (18% of cases), the gene encoding nucleophosmin (NPM1) (27%), tumor-suppressor genes (16%), DNA-methylation–related genes (44%), signaling genes (59%), chromatin-modifying genes (30%), myeloid transcription-factor genes (22%), cohesin-complex genes (13%), and spliceosome-complex genes (14%). Patterns of cooperation and mutual exclusivity suggested strong biologic relationships among several of the genes and categories. CONCLUSIONS We identified at least one potential driver mutation in nearly all AML samples and found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients. The databases from this study are widely available to serve as a foundation for further investigations of AML pathogenesis, classification, and risk stratification. (Funded by the National Institutes of Health.) PMID:23634996

  3. Defining and Treating Older Adults with Acute Myeloid Leukemia Who Are Ineligible for Intensive Therapies

    PubMed Central

    Pettit, Kristen; Odenike, Olatoyosi

    2015-01-01

    Although acute myeloid leukemia (AML) is primarily a disease of older adults (age ≥60 years), the optimal treatment for older adults remains largely undefined. Intensive chemotherapy is rarely beneficial for frail older adults or those with poor-risk disease, but criteria that define fitness and/or appropriateness for intensive chemotherapy remain to be standardized. Evaluation of disease-related and patient-specific factors in the context of clinical decision making has therefore been largely subjective. A uniform approach to identify those patients most likely to benefit from intensive therapies is needed. Here, we review currently available objective measures to define older adults with AML who are ineligible for intensive chemotherapy, and discuss promising investigational approaches. PMID:26697412

  4. Wilms Tumor: An Uncommon Entity in the Adult Patient

    PubMed Central

    Mahmoud, Fade; Allen, M Brandon; Cox, Roni; Davis, Rodney

    2016-01-01

    Wilms tumor, the most common kidney tumor in children, is rarely seen in adults, making it a challenge for the adult oncologist to diagnose and treat. Unlike with renal cell carcinoma, patients with Wilms tumor should receive adjuvant chemotherapy with or without radiation therapy. Adult oncologists may not be familiar with pediatric oncology protocols, so it is important to consult with pediatric oncologists who have more experience in this disease. Multimodal therapy based on pediatric protocols improved the outcomes of adults with Wilms tumor worldwide. We report a rare case of a 24-year-old woman with a slow-growing mass of the left kidney during a 4-year period. The mass was surgically removed and final diagnosis confirmed by pathology to be Wilms tumor. The patient received adjuvant chemotherapy and has been free of disease since 2014. PMID:27043834

  5. [Mesial temporal sclerosis syndrome in adult patients].

    PubMed

    Consalvo, D; Giobellina, R; Silva, W; Rugilo, C; Saidón, P; Schuster, G; Kochen, S; Sica, R

    2000-01-01

    Magnetic resonance imaging (MRI) has become an essential tool in the work-up of epilepsy. Since its appearance it has been possible to identify pathologies, such as hippocampal sclerosis (HS), that had previously only been detected by histopathological assays. The aim of this study was to analyze the clinical manifestations, EEG and the outcome of patients with HS as shown by MRI. We revised the clinical histories of 384 outpatients from the Epilepsy Center, Ramos Mejía Hospital, who had been studied by MRI. Thirty five of them (15.5%) had a diagnosis of HS, based on the structural changes observed on the images. Six patients were excluded because of incomplete clinical data. Therefore, we studied 29 patients including 15 men. The mean age was 32.7 +/- 10.2 years (range: 19-58). All of them had partial seizures. Ten subjects had had febrile convulsions (34.5%) in childhood. Neurological examination was normal in all subjects. Interictal EEG showed focal abnormalities that were coincident in their location with the MRI abnormalities in 16 patients (55.1%). Fourteen patients (48.3%) showed right side hippocampal lesions on MRI, thirteen on the left side (44.9%) and 2 bilateral HS (6.8%). Twenty-seven patients (93.1%) had intractable epilepsy. Anterior temporal lobectomy was performed in 3 subjects with good outcome. The identification of these patients who present certain clinical and MRI characteristics, provides an opportunity to define the mesial temporal sclerosis syndrome. This could benefit patients in their prognosis and for specific treatments. PMID:10962804

  6. Increased expression of amyloid precursor protein promotes proliferation and migration of AML1/ETO-positive leukemia cells and be inhibited by panobinostat.

    PubMed

    Wang, C L; Ding, B J; Jiang, L; Yin, C X; Zhong, Q X; Yu, G P; Li, X D; Meng, F Y

    2015-01-01

    Amyloid precursor protein (APP) is a highly conserved integral membrane protein extensively expressed in various types of cells. Previously we found that overexpression of APP in patients with AML1/ETO-positive acute myeloid leukemia (AML) associated with a higher incidence of extramedullary infiltrationin and indicate a poor prognosis. In this study, we attempted to define the roles of APP in AML1/ETO-positive leukemia cells. Western blotting and qRT-PCR analysis showed that protein levels of APP are significantly higher in Kasumi-1, a t(8;21)/ AML1/ETO-positive M2-type AML cell line. Stable knockdown of APP by lentivirus-based RNA interference (RNAi) dramatically impaired colony-formation and migration ability of Kasumi-1 cells, whereas APP knockdown had very little effect on cell viability, apoptosis, cell cycle and differentiation. We further explored whether the pan-histone deacetylase inhibitor panobinostat could deplete the protein levels of APP in Kasumi-1 cells. Treatment with panobinostat caused depletion of APP in Kasumi-1 cells. These findings indicate that overexpression of APP is involved in promoting proliferation and migration of AML1/ETO-positive leukemia cells and can be inhibited by panobinostat, which provide an attractive prospect for treatment of AML1/ETO-positive AML. PMID:26458322

  7. Frequent ASXL2 mutations in acute myeloid leukemia patients with t(8;21)/RUNX1-RUNX1T1 chromosomal translocations.

    PubMed

    Micol, Jean-Baptiste; Duployez, Nicolas; Boissel, Nicolas; Petit, Arnaud; Geffroy, Sandrine; Nibourel, Olivier; Lacombe, Catherine; Lapillonne, Helene; Etancelin, Pascaline; Figeac, Martin; Renneville, Aline; Castaigne, Sylvie; Leverger, Guy; Ifrah, Norbert; Dombret, Hervé; Preudhomme, Claude; Abdel-Wahab, Omar; Jourdan, Eric

    2014-08-28

    Acute myeloid leukemia (AML) with t(8;21) (q22;q22) is considered to have favorable risk; however, nearly half of t(8;21) patients are not cured, and recent studies have highlighted remarkable genetic heterogeneity in this subset of AML. Here we identify somatic mutations in additional sex combs-like 2 (ASXL2) in 22.7% (25/110) of patients with t(8;21), but not in patients with inv(16)/t(16;16) (0/60) or RUNX1-mutated AML (0/26). ASXL2 mutations were similarly frequent in adults and children t(8;21) and were mutually exclusive with ASXL1 mutations. Although overall survival was similar between ASXL1 and ASXL2 mutant t(8;21) AML patients and their wild-type counterparts, patients with ASXL1 or ASXL2 mutations had a cumulative incidence of relapse of 54.6% and 36.0%, respectively, compared with 25% in ASXL1/2 wild-type counterparts (P = .226). These results identify a high-frequency mutation in t(8;21) AML and identify the need for future studies to investigate the clinical and biological relevance of ASXL2 mutations in this unique subset of AML. PMID:24973361

  8. Frequent ASXL2 mutations in acute myeloid leukemia patients with t(8;21)/RUNX1-RUNX1T1 chromosomal translocations

    PubMed Central

    Micol, Jean-Baptiste; Duployez, Nicolas; Boissel, Nicolas; Petit, Arnaud; Geffroy, Sandrine; Nibourel, Olivier; Lacombe, Catherine; Lapillonne, Helene; Etancelin, Pascaline; Figeac, Martin; Renneville, Aline; Castaigne, Sylvie; Leverger, Guy; Ifrah, Norbert; Dombret, Hervé; Preudhomme, Claude; Jourdan, Eric

    2014-01-01

    Acute myeloid leukemia (AML) with t(8;21) (q22;q22) is considered to have favorable risk; however, nearly half of t(8;21) patients are not cured, and recent studies have highlighted remarkable genetic heterogeneity in this subset of AML. Here we identify somatic mutations in additional sex combs-like 2 (ASXL2) in 22.7% (25/110) of patients with t(8;21), but not in patients with inv(16)/t(16;16) (0/60) or RUNX1-mutated AML (0/26). ASXL2 mutations were similarly frequent in adults and children t(8;21) and were mutually exclusive with ASXL1 mutations. Although overall survival was similar between ASXL1 and ASXL2 mutant t(8;21) AML patients and their wild-type counterparts, patients with ASXL1 or ASXL2 mutations had a cumulative incidence of relapse of 54.6% and 36.0%, respectively, compared with 25% in ASXL1/2 wild-type counterparts (P = .226). These results identify a high-frequency mutation in t(8;21) AML and identify the need for future studies to investigate the clinical and biological relevance of ASXL2 mutations in this unique subset of AML. PMID:24973361

  9. Pre-transplant MRD predicts outcome following reduced-intensity and myeloablative allogeneic hemopoietic SCT in AML.

    PubMed

    Anthias, C; Dignan, F L; Morilla, R; Morilla, A; Ethell, M E; Potter, M N; Shaw, B E

    2014-05-01

    The presence of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) has been associated with adverse outcomes in AML patients treated with chemotherapy alone, but its impact in the setting of allogeneic hematopoietic SCT (HSCT) is less clear. We studied 88 patients who underwent myeloablative (MA) or reduced-intensity conditioned allogeneic HSCT for AML in first or subsequent remission at our center. MRD status was determined using three-color MFC on pre-HSCT BM aspirates, and patients were stratified by MRD status into MRD-negative, low-level MRD-positive (<1%) or high-level MRD-positive groups (1-4.9%). Two-year survival estimates in these groups were 66.8%, 51% and 30%, respectively (P=0.012), and 2-year estimates of relapse were 7.6, 37 and 70% (P<0.001). Pre-HSCT MRD was related to disease characteristics including secondary AML (P=0.002) and primary induction failure (P=0.005), but, despite these strong correlations, MRD remained independently associated with poorer survival in multivariate analysis (hazard ratio, 1.92; P=0.014). Pre-HSCT MRD is associated with adverse clinical outcomes in AML patients undergoing reduced-intensity or MA HSCT in first or subsequent remission and should be integrated into transplant strategies for patients with AML. PMID:24510069

  10. Acne in the adult female patient: a practical approach.

    PubMed

    Kamangar, Faranak; Shinkai, Kanade

    2012-10-01

    Acne vulgaris is a common reason why adult women present to dermatologists and can be a clinical challenge to treat. It may also be an important sign of an underlying endocrine disease such as Polycystic Ovary Syndrome (PCOS). Although standard acne therapies can be successfully used to treat acne in adult female patients, hormonal treatment is a safe and effective therapeutic option that may provide an opportunity to better target acne in this population, even when other systemic therapies have failed. In this article, a practical approach to the adult female patient with acne will be reviewed to enhance the dermatologist's ability to use hormonal acne therapies and to better identify and evaluate patients with acne in the setting of a possible endocrine disorder. PMID:22994662

  11. Practical fluoride and remineralization protocols for adult patients.

    PubMed

    Chan, Daniel C N; Wefel, James S; Caughman, W Frank

    2004-12-01

    There is a wealth of information on preventive measures and procedures that can be used to care for paediatric and adolescent patients. However, few studies have been conducted in adult or geriatric populations, and an understanding of preventive and non-surgical treatment regimens for these patients is lacking. Traditionally, caries incidence is high among risk groups of low income, low dental IQ and certain ethnic subgroups, but we are now witnessing a high incidence of caries among middle-income and healthy adult patients with an imbalance of protective factors and cariogenic factors. We will direct our attention to the adult population and attempt to address some of the most common questions. PMID:15736834

  12. New study reveals relatively few mutations in AML genomes - TCGA

    Cancer.gov

    Investigators for The Cancer Genome Atlas (TCGA) Research Network have detailed and broadly classified the genomic alterations that frequently underlie the development of acute myeloid leukemia (AML).

  13. Combination of galectin inhibitor GCS-100 and BH3 mimetics eliminates both p53 wild type and p53 null AML cells.

    PubMed

    Ruvolo, Peter P; Ruvolo, Vivian R; Benton, Christopher B; AlRawi, Ahmed; Burks, Jared K; Schober, Wendy; Rolke, James; Tidmarsh, George; Hail, Numsen; Davis, R Eric; Andreeff, Michael

    2016-04-01

    Galectin 3 (LGALS3) expression is prognostic for poor survival in acute myeloid leukemia (AML) patients. GCS-100 is a novel galectin inhibitor that may prove useful for AML therapy. In this study, we found that GCS-100 induced apoptosis in AML cells. The agent reduced MCL-1 expression suggesting that GCS-100 could be more effective when combined with a BH3 mimetic. Indeed, potent synergistic cytotoxicity was achieved when GCS-100 was combined with ABT-737 or ABT-199. Furthermore, the GCS-100/ABT-199 combination was effective against primary AML blast cells from patients with FLT3 ITD mutations, which is another prognostic factor for poor outcome in AML. This activity may involve wild-type p53 as shRNA knockdown of LGALS3 or galectin 1 (LGALS1) sensitized wild-type p53 OCI-AML3 cells to GCS-100/ABT-737-induced apoptosis to a much greater extent than p53 null THP-1 cells. Suppression of LGALS3 by shRNA inhibited MCL-1 expression in OCI-AML3 cells, but not THP-1 cells, suggesting the induced sensitivity to ABT-737 may involve a MCL-1 mediated mechanism. OCI-AML3 cells with LGALS1 shRNA were also sensitized to ABT-737. However, these cells exhibited increased MCL-1 expression, so MCL-1 reduction is apparently not required in this process. A role for p53 appears important as GCS-100 induces p53 expression and shRNA knockdown of p53 protected OCI-AML3 cells from the cytotoxic effects of the GCS-100/ABT-737 treatment combination. Our results suggest that galectins regulate a survival axis in AML cells, which may be targeted via combined inhibition with drugs such as GCS-100 and ABT-199. PMID:26704388

  14. Pyridoxine deficiency in adult patients with status epilepticus.

    PubMed

    Dave, Hina N; Eugene Ramsay, Richard; Khan, Fawad; Sabharwal, Vivek; Irland, Megan

    2015-11-01

    An 8-year-old girl treated at our facility for superrefractory status epilepticus was found to have a low pyridoxine level at 5 μg/L. After starting pyridoxine supplementation, improvement in the EEG for a 24-hour period was seen. We decided to look at the pyridoxine levels in adult patients admitted with status epilepticus. We reviewed the records on patients admitted to the neurological ICU for status epilepticus (SE). Eighty-one adult patients were identified with documented pyridoxine levels. For comparison purposes, we looked at pyridoxine levels in outpatients with epilepsy (n=132). Reported normal pyridoxine range is >10 ng/mL. All but six patients admitted for SE had low normal or undetectable pyridoxine levels. A selective pyridoxine deficiency was seen in 94% of patients with status epilepticus (compared to 39.4% in the outpatients) which leads us to believe that there is a relationship between status epilepticus and pyridoxine levels. PMID:26418265

  15. Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia.

    PubMed

    Ruggeri, A; Labopin, M; Sanz, G; Piemontese, S; Arcese, W; Bacigalupo, A; Blaise, D; Bosi, A; Huang, H; Karakasis, D; Koc, Y; Michallet, M; Picardi, A; Sanz, J; Santarone, S; Sengelov, H; Sierra, J; Vincent, L; Volt, F; Nagler, A; Gluckman, E; Ciceri, F; Rocha, V; Mohty, M

    2015-09-01

    Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared outcomes after UCBT and Haplo in adults with de novo acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Median follow-up was 24 months. Analysis was performed separately for patients with AML, n=918 (Haplo=360, UCBT=558) and ALL, n=528 (Haplo=158 and UCBT=370). UCBT was associated with delayed engraftment and higher graft failure in both AML and ALL recipients. In multivariate analysis, UCBT was associated with lower incidence of chronic graft-vs-host disease both in the AML group (hazard ratio (HR)=0.63, P=0.008) and in the ALL group (HR=0.58, P=0.01). Not statistically significant differences were observed between Haplo and UCBT for relapse incidence (HR=0.95, P=0.76 for AML and HR=0.82, P=0.31 for ALL), non-relapse mortality (HR=1.16, P=0.47 for AML and HR=1.23, P=0.23 for ALL) and leukemia-free survival (HR 0.78, P=0.78 for AML and HR=1.00, P=0.84 for ALL). There were no statistically differences on main outcomes after unmanipulated Haplo and UCBT, and both approaches are valid for acute leukemia patients lacking a HLA matched donor. Both strategies expand the donor pool for patients in need. PMID:25882700

  16. Aberrant splicing and drug resistance in AML.

    PubMed

    de Necochea-Campion, Rosalia; Shouse, Geoffrey P; Zhou, Qi; Mirshahidi, Saied; Chen, Chien-Shing

    2016-01-01

    The advent of next-generation sequencing technologies has unveiled a new window into the heterogeneity of acute myeloid leukemia (AML). In particular, recurrent mutations in spliceosome machinery and genome-wide aberrant splicing events have been recognized as a prominent component of this disease. This review will focus on how these factors influence drug resistance through altered splicing of tumor suppressor and oncogenes and dysregulation of the apoptotic signaling network. A better understanding of these factors in disease progression is necessary to design appropriate therapeutic strategies recognizing specific alternatively spliced or mutated oncogenic targets. PMID:27613060

  17. The prognostic relevance of flt3 and npm1 mutations on older patients treated intensively or non-intensively: a study of 1312 patients in the UK NCRI AML16 trial.

    PubMed

    Lazenby, M; Gilkes, A F; Marrin, C; Evans, A; Hills, R K; Burnett, A K

    2014-10-01

    Although the prognostic impact of mutations of FLT3 and NPM1 have been extensively studied in younger patients with acute myeloid leukaemia, less is known in older patients whether treated intensively or non-intensively, or in the context of existing prognostic scores. In 1312 patients 16 and 21%, respectively had an FLT3 and NPM1 mutation. An FLT3 mutation did not affect remission rate in intensively or non-intensively treated patients but was associated with an inferior survival. All patients with an NPM1c mutation had a significantly higher remission rate irrespective of treatment approach but survival was not improved, overall, or in any genotype except as in younger patients, in the FLT3 WT NPM1c mutant subgroup. When incorporated into an established multi-parameter prognostic risk score, the molecular information provided additional prognostic definition in 11% of patients. PMID:24573385

  18. [Diabetes education in adult diabetic patients].

    PubMed

    Weitgasser, Raimund; Clodi, Martin; Cvach, Sarah; Grafinger, Peter; Lechleitner, Monika; Howorka, Kinga; Ludvik, Bernhard

    2016-04-01

    Diabetes education and self management has gained a critical role in diabetes care. Patient empowerment aims to actively influence the course of the disease by self-monitoring and treatment modification, as well as integration of diabetes in patients' daily life to achieve changes in lifestyle accordingly.Diabetes education has to be made accessible for all patients with the disease. To be able to provide a structured and validated education program adequate personal as well as space, organizational and financial background are required. Besides an increase in knowledge about the disease it has been shown that structured diabetes education is able to improve diabetes outcome measured by parameters like blood glucose, HbA1c, blood pressure and body weight in follow-up evaluations. Modern education programs emphasize the ability of patients to integrate diabetes in everyday life and stress physical activity besides healthy eating as a main component of lifestyle therapy and use interactive methods in order to increase the acceptance of personal responsibility. PMID:27052242

  19. Approach to Adult Patients with Acute Dyspnea.

    PubMed

    DeVos, Elizabeth; Jacobson, Lisa

    2016-02-01

    Undifferentiated patients in respiratory distress require immediate attention in the emergency department. Using a thorough history and clinical examination, clinicians can determine the most likely causes of dyspnea. Understanding the pathophysiology of the most common diseases contributing to dyspnea guides rational testing and informed, expedited treatment decisions. PMID:26614245

  20. [Adult patients with congenital heart disease].

    PubMed

    Grabitz, R G; Kaemmerer, H; Mohr, F-W

    2013-01-01

    Unlike a few decades ago, today most patients with congenital heart disease reach adulthood after intervention or reparative surgery. As complete correction is generally not possible, a patient population with great complexity and a particular challenge to medical management is rising and a regular follow-up is mandatory. The aim of care is the timely recognition of residual or associated problems. Frequency and intensity of follow-up examinations depend on type and complexity of the lesion. The standard repertoire at follow-up consists of a specific history, clinical examination, ECG, Holter-monitoring, exercise tests, and echocardiography. Depending on the indication, cardio-MRI, CT scan, and sophisticated cardiac catheterization may become necessary. Long-term complications like rhythm disturbances, pulmonary hypertension, or heart failure are frequent, despite optimal care. Acute complications like arrhythmias, infective endocarditis, cerebral events, cerebral abscesses, aortic dissection, pulmonary embolism, and bleeding have to be recognized early and treated appropriately. Additional focus has to be placed on counseling and management of noncardiac disease and surgery, pregnancy and delivery, exercise at work and in private life, driving, and insurance issues. Training and certification of physicians as well as the establishment of specialized centers will help to ensure high quality health care for the affected patient population. PMID:23318541

  1. Peculiarities of Anxiety Score Distribution in Adult Cancer Patients.

    PubMed

    Blank, Mikhail; Blank, Olga; Myasnikova, Ekaterina; Denisova, Daria

    2015-01-01

    The goal of the present research is to investigate and analyze possible peculiarities of the psychological state of cancer patients undergoing treatment. Scores characterizing the trait and state anxiety were acquired using the Integrative Anxiety Test from four groups: adults with no appreciable disease, pregnant women, cancer patients examined during the specific antitumor treatment, and cancer patients brought into lasting clinical remission. Statistical analysis of the testing results revealed the bimodal type of the distribution of scores. The only statistically significant exception was the distribution of the state anxiety scores in cancer patients undergoing treatment that was clearly unimodal. PMID:26176239

  2. Advanced Manned Launch System (AMLS) study

    NASA Technical Reports Server (NTRS)

    Ehrlich, Carl F., Jr.; Potts, Jack; Brown, Jerry; Schell, Ken; Manley, Mary; Chen, Irving; Earhart, Richard; Urrutia, Chuck; Randolph, Ray; Morris, Jim

    1992-01-01

    To assure national leadership in space operations and exploration in the future, NASA must be able to provide cost effective and operationally efficient space transportation. Several NASA studies and the joint NASA/DoD Space Transportation Architecture Studies (STAS) have shown the need for a multi-vehicle space transportation system with designs driven by enhanced operations and low costs. NASA is currently studying an advanced manned launch system (AMLS) approach to transport crew and cargo to the Space Station Freedom. Several single and multiple stage systems from air-breathing to all-rocket concepts are being examined in a series of studies potential replacements for the Space Shuttle launch system in the 2000-2010 time frame. Rockwell International Corporation, under contract to the NASA Langley Research Center, has analyzed a two-stage all-rocket concept to determine whether this class of vehicles is appropriate for the AMLS function. The results of the pre-phase A study are discussed.

  3. Nutritional profile of adult patients with celiac disease.

    PubMed

    Abenavoli, L; Delibasic, M; Peta, V; Turkulov, V; De Lorenzo, A; Medić-Stojanoska, M

    2015-11-01

    Celiac disease (CD) is a chronic immune-mediated gluten dependent enteropathy induced by ingestion of gluten, characterized by intestinal malabsorption and subtotals or total atrophy of intestinal villi. The predominant consequence of CD in untreated patients, is malnutrition as a result of malabsorption. Moreover, several and increasing extra-intestinal clinical manifestations have been described in the CD patients. Strict adherence to a gluten-free diet (GFD) improves nutritional status, inducing an increase in fat and bone compartments, but does not completely normalize body composition and nutritional deficiencies. An early and accurate evaluation of nutritional status can be of the pivotal step in the clinical management of the adult CD patients. The aim of this review is to present the most important and recent data on nutritional and metabolic features in the CD adult patients, the related implications and the effects of the GFD on these conditions. PMID:26636515

  4. Allogeneic hematopoietic cell transplantation in patients 60 to 70 years of age with de novo high-risk MDS or secondary AML – a comparison with patients lacking donors who received azacitidine

    PubMed Central

    Platzbecker, Uwe; Schetelig, Johannes; Finke, Jürgen; Trenschel, Rudolf; Scott, Bart L.; Kobbe, Guido; Schaefer-Eckart, Kerstin; Bornhäuser, Martin; Itzykson, Raphael; Germing, Ulrich; Beelen, Dietrich; Ehninger, Gerhard; Fenaux, Pierre; Deeg, H.-Joachim; Adès, Lionel

    2015-01-01

    Standard first-line therapy for older patients with high-risk MDS consists of hypomethylating agents such as azacitidine (AZA). However, the only approach with curative potential remains allogeneic hematopoietic cell transplantation (HCT). So far no direct comparison of both strategies has been carried out. The outcomes of two well balanced cohorts of high-risk MDS patients defined by age (60–70 years), performance status (ECOG ≤2) and donor availability (yes/no) were compared including 103 patients undergoing HCT and 75 patients without this option who received AZA. The estimated 2-year overall survival (OS) after the start of treatment was 39% (95% CI, 30% to 50%) for the HCT patients and 23% (95% CI, 14 to 40%) for the AZA patients. In a multivariate Cox regression analysis of all (n=178) patients ECOG score (0 vs. 1 vs. 2, HR: 2.9/3.9, p<0.001), cytogenetics (good vs. intermediate vs. poor, HR: 1.2/1.7, p=0.026) and type of treatment (HCT vs. AZA, HR: 0.3, p=0.007) were associated with OS. This retrospective cohort analysis suggests a survival advantage with allogeneic HCT compared to treatment with AZA in medically fit high-risk MDS patients 60 to 70 years of age, Prospective controlled studies are warranted. PMID:22579634

  5. Rhabdomyosarcoma in adolescent and young adult patients: current perspectives

    PubMed Central

    Egas-Bejar, Daniela; Huh, Winston W

    2014-01-01

    Rhabdomyosarcoma (RMS), a malignant tumor of mesenchymal origin, is the third most common extracranial malignant solid tumor in children and adolescents. However, in adults, RMS represents <1% of all solid tumor malignancies. The embryonal and alveolar histologic variants are more commonly seen in pediatric patients, while the pleomorphic variant is rare in children and seen more often in adults. Advances in the research of the embryonal and alveolar variants have improved our understanding of certain genes and biologic pathways that are involved in RMS, but much less is known for the other variants. Multimodality therapy that includes surgery and chemotherapy with or without radiation therapy is the mainstay of treatment for RMS. Improvements in the risk stratification of the pediatric patients based on presurgical (primary tumor site, tumor size, regional lymph node involvement, presence of metastasis) and postsurgical parameters (completeness of resection or presence of residual disease or metastasis) has allowed for the treatment assignment of patients in different studies and therapeutic trials, leading to increases in 5-year survival from 25%–70% over the past 40 years. However, for adult patients, in great part due to rarity of the disease and the lack of consensus on optimal treatment, clinical outcome is still poor. Many factors have been implicated for the differing outcomes between pediatric RMS versus adult RMS, such as the lack of standardized treatment protocols for adult RMS patients and the increased prevalence of advanced presentations. Now that there are increased numbers of survivors, we can appreciate the sequelae from therapy in these patients, such as bone growth abnormalities, endocrinopathies, and infertility. Improvements in risk stratification have led to clinical trials using lower doses of chemotherapy or radiation therapy with the intention of decreasing the incidence of side effects without compromising survival outcome. PMID

  6. DNMT3A R882 Mutations Predict a Poor Prognosis in AML

    PubMed Central

    Yuan, Xiao-Qing; Peng, Li; Zeng, Wen-Jing; Jiang, Bin-Yuan; Li, Guan-Cheng; Chen, Xiao-Ping

    2016-01-01

    Abstract DNA (cytosine-5)-methyltransferase 3 alpha (DNMT3A) mutations were widely believed to be independently associated with inferior prognosis in acute myeloid leukemia (AML) patients. As dominant missense alterations in DNMT3A mutations, R882 mutations cause the focal hypomethylation phenotype. However, there remains debate on the influence of R882 mutations on AML prognosis. Thus, this meta-analysis aimed at further illustrating the prognostic power of DNMT3A R882 mutations in AML patients. Eligible studies were identified from 5 databases containing PubMed, Embase, Web of Science, Clinical Trials, and the Cochrane Library (up to October 25, 2015). Effects (hazard ratios [HRs] with 95% confidence interval [CI]) of relapse-free survival (RFS) and overall survival (OS) were pooled to estimate the prognostic power of mutant DNMT3A R882 in overall patients and subgroups of AML patients. Eight competent studies with 4474 AML patients including 694 with DNMT3A R882 mutations were included. AML patients with DNMT3A R882 mutations showed significant shorter RFS (HR = 1.40, 95% CI = 1.24–1.59, P < 0.001) and OS (HR = 1.47, 95% CI = 1.17–1.86, P = 0.001) in the overall population. DNMT3A R882 mutations predicted worse RFS and OS among the subgroups of patients under age 60 (RFS: HR = 1.44, 95% CI = 1.25–1.66, P < 0.001; OS: HR = 1.48, 95% CI = 1.15–1.90, P = 0.002), over age 60 (RFS: HR = 2.03, 95% CI = 1.40–2.93, P < 0.001; OS: HR = 1.85, 95% CI = 1.36–2.53, P < 0.001), cytogenetically normal (CN)-AML (RFS: HR = 1.52, 95% CI = 1.26–1.83, P < 0.001; OS: HR = 1.67, 95% CI = 1.16–2.41, P = 0.006), and non-CN-AML (RFS: HR = 1.96, 95% CI = 1.20–3.21, P = 0.006; OS: HR = 2.51, 95% CI = 1.52–4.15, P = 0.0038). DNMT3A R882 mutations possessed significant unfavorable prognostic influence on RFS and OS in AML patients. PMID:27149454

  7. Pain Assessment in Noncommunicative Adult Palliative Care Patients.

    PubMed

    McGuire, Deborah B; Kaiser, Karen Snow; Haisfield-Wolfe, Mary Ellen; Iyamu, Florence

    2016-09-01

    Palliative care patients who have pain are often unable to self-report their pain, placing them at increased risk for underrecognized and undertreated pain. Use of appropriate pain assessment tools significantly enhances the likelihood of effective pain management and improved pain-related outcomes. This paper reviews selected tools and provides palliative care clinicians with a practical approach to selecting a pain assessment tool for noncommunicative adult patients. PMID:27497016

  8. A Future for Adult Educators in Patient Education

    ERIC Educational Resources Information Center

    Fleming, Jean E.

    2014-01-01

    Adult education in healthcare comes in several forms: degree and certificate programs aimed at preparing better academic and clinical educators; and community education programs aimed at wellness, rehabilitation, or learning to live with chronic diseases. Patient-centered healthcare, however, is part of something new: coordinated and transitional…

  9. Improvement with Duloxetine in an Adult ADHD Patient

    ERIC Educational Resources Information Center

    Tourjman, Smadar Valerie; Bilodeau, Mathieu

    2009-01-01

    Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a common and disabling disorder among adults and is treated with stimulant and non stimulant medication. Objective: To report the case of a patient with ADHD showing good clinical response to duloxetine, a selective serotonin and norepinephrine reuptake inhibitor (SSNRI). Case…

  10. Medication adherence among adult patients on hemodialysis.

    PubMed

    Alkatheri, Abdulmalik M; Alyousif, Sarah M; Alshabanah, Najla; Albekairy, Abdulkareem M; Alharbi, Shemylan; Alhejaili, Fayze F; Alsayyari, Abdullah A; Qandil, Abeer Ma; Qandil, Amjad M

    2014-07-01

    Medication adherence was assessed in 89 patients on hemodialysis (HD) at the King Abdul Aziz Medical City using an Arabic version of the Morisky Medication Adherence Scale (MASS-8). The results of the study revealed that 31.46% and 40.45% of the participants showed low and medium adherence, respectively, while 28.09% showed high medication adherence. Accordingly, 71.91% of the patients visiting the dialysis unit were considered medication non-adherent. While being of older age (P = 0.012), being married (P = 0.012) increased the level of adherence, being of medium level of education (P = 0.024) decreased adherence levels. On the other hand, gender, presence of a care-giver, number of members in the household and employment status seems to have no effect on the level of medication adherence. These results call upon the practitioners in HD units to develop intervention programs that can increase the level of medication adherence. PMID:24969185

  11. Neuropsychological profile of adult patients with nonsymptomatic occipital lobe epilepsies.

    PubMed

    Bilo, Leonilda; Santangelo, Gabriella; Improta, Ilaria; Vitale, Carmine; Meo, Roberta; Trojano, Luigi

    2013-02-01

    To explore the neuropsychological and neurobehavioral profile in adult patients affected by nonsymptomatic (cryptogenic and idiopathic) occipital lobe epilepsy (OLE), with normal intelligence, we enrolled 20 adult patients with nonsymptomatic OLE and 20 age-, sex-, and education-matched healthy subjects. All participants underwent neuropsychiatric assessment scales, and standardized neuropsychological tests tapping memory, executive functions, constructional, visuospatial and visuoperceptual skills. After Bonferroni correction for multiple comparisons, patients performed significantly worse than controls on several tests tapping complex visuospatial skills and frontal lobe functions. The analysis of single patients' performance revealed that a significantly higher number of OLE patients achieved age- and education-adjusted pathological scores on three tests (Benton Judgment of Line Orientation Test, Freehand Copying of Drawings Test, color-word interference task of Stroop test) with respect to controls. Patients did not differ from control subjects on neuropsychiatric aspects. The direct comparison between OLE subtypes showed that cryptogenetic OLE patients tended to achieve lower scores than idiopathic OLE patients on most tests, but no difference between the two groups was fully significant. In summary, patients with nonsymptomatic OLE can be affected by clinically relevant impairments in selected neuropsychological domains: complex visuospatial skills and executive functions. It could be speculated that frontal and visuospatial cognitive deficits might be the result of epileptic activity spreading within a neural network that includes structures far beyond the occipital lobe. PMID:22903808

  12. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia.

    PubMed

    Gale, Rosemary E; Green, Claire; Allen, Christopher; Mead, Adam J; Burnett, Alan K; Hills, Robert K; Linch, David C

    2008-03-01

    An internal tandem duplication in the fms-like tyrosine kinase 3 gene (FLT3/ITD) is associated with poor prognosis in acute myeloid leukemia (AML), but the impact of mutant level, size, and interaction with nucleophosmin 1 (NPM1) mutations remains controversial. We evaluated these characteristics in a large cohort of young adult AML patients. There was a highly significant trend for worsening in relapse risk (RR) and overall survival (OS) with increasing FLT3/ITD mutant level (P < .001 for both), and even in the low level mutant group (1%-24% of total FLT3 alleles), RR was significantly worse than in the FLT3 wild-type (WT) group (P < .001). In multivariate analysis, mutant level was the most powerful prognostic factor for RR. Mutant size and number had no significant impact on outcome. The beneficial impact of an NPM1 mutation on RR and OS was seen in FLT3/ITD(+) as well as FLT3/WT patients; both markers were highly significant independent predictors of outcome (P < .001). Stratification using both markers identified 3 prognostic groups: good (FLT3/ITD(-)NPM1(+)), intermediate (FLT3/ITD(-)NPM1(-) or FLT3/ITD(+)NPM1(+)), and poor (FLT3/ITD(+)NPM1(-)). Patients with high FLT3/ITD mutant level (greater than 50%) or FLT3/ITD(+) in the absence of an NPM1 mutation may be good candidates for more experimental therapeutic approaches. PMID:17957027

  13. Patient-specific FDG dosimetry for adult males, adult females, and very low birth weight infants

    NASA Astrophysics Data System (ADS)

    Niven, Erin

    Fluorodeoxyglucose is the most commonly used radiopharmaceutical in Positron Emission Tomography, with applications in neurology, cardiology, and oncology. Despite its routine use worldwide, the radiation absorbed dose estimates from FDG have been based primarily on data obtained from two dogs studied in 1977 and 11 adults (most likely males) studied in 1982. In addition, the dose estimates calculated for FDG have been centered on the adult male, with little or no mention of variations in the dose estimates due to sex, age, height, weight, nationality, diet, or pathological condition. Through an extensive investigation into the Medical Internal Radiation Dose schema for calculating absorbed doses, I have developed a simple patient-specific equation; this equation incorporates the parameters necessary for alterations to the mathematical values of the human model to produce an estimate more representative of the individual under consideration. I have used this method to determine the range of absorbed doses to FDG from the collection of a large quantity of biological data obtained in adult males, adult females, and very low birth weight infants. Therefore, a more accurate quantification of the dose to humans from FDG has been completed. My results show that per unit administered activity, the absorbed dose from FDG is higher for infants compared to adults, and the dose for adult women is higher than for adult men. Given an injected activity of approximately 3.7 MBq kg-1, the doses for adult men, adult women, and full-term newborns would be on the order of 5.5, 7.1, and 2.8 mSv, respectively. These absorbed doses are comparable to the doses received from other nuclear medicine procedures.

  14. Nassi-Schneiderman Diagram in HTML Based on AML

    ERIC Educational Resources Information Center

    Menyhárt, László

    2013-01-01

    In an earlier work I defined an extension of XML called Algorithm Markup Language (AML) for easy and understandable coding in an IDE which supports XML editing (e.g. NetBeans). The AML extension contains annotations and native language (English or Hungarian) tag names used when coding our algorithm. This paper presents a drawing tool with which…

  15. Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells.

    PubMed

    Martelli, Maria Paola; Gionfriddo, Ilaria; Mezzasoma, Federica; Milano, Francesca; Pierangeli, Sara; Mulas, Floriana; Pacini, Roberta; Tabarrini, Alessia; Pettirossi, Valentina; Rossi, Roberta; Vetro, Calogero; Brunetti, Lorenzo; Sportoletti, Paolo; Tiacci, Enrico; Di Raimondo, Francesco; Falini, Brunangelo

    2015-05-28

    Nucleophosmin (NPM1) mutations represent an attractive therapeutic target in acute myeloid leukemia (AML) because they are common (∼30% AML), stable, and behave as a founder genetic lesion. Oncoprotein targeting can be a successful strategy to treat AML, as proved in acute promyelocytic leukemia by treatment with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO), which degrade the promyelocytic leukemia (PML)-retinoic acid receptor fusion protein. Adjunct of ATRA to chemotherapy was reported to be beneficial for NPM1-mutated AML patients. Leukemic cells with NPM1 mutation also showed sensibility to ATO in vitro. Here, we explore the mechanisms underlying these observations and show that ATO/ATRA induce proteasome-dependent degradation of NPM1 leukemic protein and apoptosis in NPM1-mutated AML cell lines and primary patients' cells. We also show that PML intracellular distribution is altered in NPM1-mutated AML cells and reverted by arsenic through oxidative stress induction. Interestingly, similarly to what was described for PML, oxidative stress also mediates ATO-induced degradation of the NPM1 mutant oncoprotein. Strikingly, NPM1 mutant downregulation by ATO/ATRA was shown to potentiate response to the anthracyclin daunorubicin. These findings provide experimental evidence for further exploring ATO/ATRA in preclinical NPM1-mutated AML in vivo models and a rationale for exploiting these compounds in chemotherapeutic regimens in clinics. PMID:25795919

  16. [Chemotherapy for brain tumors in adult patients].

    PubMed

    Weller, M

    2008-02-01

    Chemotherapy has become a third major treatment option for patients with brain tumors, in addition to surgery and radiotherapy. The role of chemotherapy in the treatment of gliomas is no longer limited to recurrent disease. Temozolomide has become the standard of care in newly diagnosed glioblastoma. Several ongoing trials seek to define the role of chemotherapy in the primary care of other gliomas. Some of these studies are no longer only based on histological diagnoses, but take into consideration molecular markers such as MGMT promoter methylation and loss of genetic material on chromosomal arms 1p and 19q. Outside such clinical trials chemotherapy is used in addition to radiotherapy, e.g., in anaplastic astrocytoma, medulloblastoma or germ cell tumors, or as an alternative to radiotherapy, e.g., in anaplastic oligodendroglial tumors or low-grade gliomas. In contrast, there is no established role for chemotherapy in other tumors such as ependymomas, meningiomas or neurinomas. Primary cerebral lymphomas are probably the only brain tumors which can be cured by chemotherapy alone and only by chemotherapy. The chemotherapy of brain metastases follows the recommendations for the respective primary tumors. Further, strategies of combined radiochemotherapy using mainly temozolomide or topotecan are currently explored. Leptomeningeal metastases are treated by radiotherapy or systemic or intrathecal chemotherapy depending on their pattern of growth. PMID:18253773

  17. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification.

    PubMed

    Matutes, Estella; Pickl, Winfried F; Van't Veer, Mars; Morilla, Ricardo; Swansbury, John; Strobl, Herbert; Attarbaschi, Andishe; Hopfinger, Georg; Ashley, Sue; Bene, Marie Christine; Porwit, Anna; Orfao, Alberto; Lemez, Petr; Schabath, Richard; Ludwig, Wolf-Dieter

    2011-03-17

    The features of 100 mixed-phenotype acute leukemias (MPALs), fulfilling WHO 2008 criteria, are documented. Myeloid and T-lineage features were demonstrated by cytoplasmic myeloperoxidase and CD3; B-lineage features were demonstrated by at least 2 B-lymphoid markers. There were 62 men and 38 women; 68% were adults. Morphology was consistent with acute lymphoblastic leukemia (ALL; 43%), acute myeloid leukemia (AML; 42%), or inconclusive (15%). Immunophenotyping disclosed B + myeloid (59%), T + myeloid (35%), B + T (4%), or trilineage (2%) combinations. Cytogenetics evidenced t(9;22)/(Ph(+)) (20%), 11q23/MLL rearrangements (8%), complex (32%), aberrant (27%), or normal (13%) karyotypes. There was no correlation between age, morphology, immunophenotype, or cytogenetics. Response to treatment and outcome were available for 67 and 70 patients, respectively; 27 received ALL, 34 AML, 5 a combination of ALL + AML therapy, and 1 imatinib. ALL treatment induced a response in 85%, AML therapy in 41%; 3 of 5 patients responded to the combination therapy. Forty (58%) patients died, 33 of resistant disease. Overall median survival was 18 months and 37% of patients are alive at 5 years. Age, Ph(+), and AML therapy were predictors for poor outcome (P < .001; P = .002; P = .003). MPAL is confirmed to be a poor-risk disease. Adults and Ph(+) patients should be considered for transplantation in first remission. PMID:21228332

  18. Optimal therapy for adult patients with acute myeloid leukemia in first complete remission.

    PubMed

    Wiernik, Peter H

    2014-06-01

    Although it is absolutely clear that postremission therapy is currently necessary to obtain disease-free long-term survivorship for patients with acute myeloid leukemia (AML) in first complete remission (CR), it is not entirely clear what form that treatment should take. High-dose cytarabine is clearly effective and there definitely is a dose-response relationship for cytarabine and remission duration. High-dose cytarabine is effective for younger patients but not elderly patients. It is effective for patients with favorable cytogenetics but it is not clear whether it is effective for patients with intermediate or unfavorable cytogenetics. Furthermore, it is not clear what the most effective and least toxic dose and schedule of high-dose cytarabine is. PMID:24792016

  19. ACG Clinical Guideline: Nutrition Therapy in the Adult Hospitalized Patient.

    PubMed

    McClave, Stephen A; DiBaise, John K; Mullin, Gerard E; Martindale, Robert G

    2016-03-01

    The value of nutrition therapy for the adult hospitalized patient is derived from the outcome benefits achieved by the delivery of early enteral feeding. Nutritional assessment should identify those patients at high nutritional risk, determined by both disease severity and nutritional status. For such patients if they are unable to maintain volitional intake, enteral access should be attained and enteral nutrition (EN) initiated within 24-48 h of admission. Orogastric or nasogastric feeding is most appropriate when starting EN, switching to post-pyloric or deep jejunal feeding only in those patients who are intolerant of gastric feeds or at high risk for aspiration. Percutaneous access should be used for those patients anticipated to require EN for >4 weeks. Patients receiving EN should be monitored for risk of aspiration, tolerance, and adequacy of feeding (determined by percent of goal calories and protein delivered). Intentional permissive underfeeding (and even trophic feeding) is appropriate temporarily for certain subsets of hospitalized patients. Although a standard polymeric formula should be used routinely in most patients, an immune-modulating formula (with arginine and fish oil) should be reserved for patients who have had major surgery in a surgical ICU setting. Adequacy of nutrition therapy is enhanced by establishing nurse-driven enteral feeding protocols, increasing delivery by volume-based or top-down feeding strategies, minimizing interruptions, and eliminating the practice of gastric residual volumes. Parenteral nutrition should be used in patients at high nutritional risk when EN is not feasible or after the first week of hospitalization if EN is not sufficient. Because of their knowledge base and skill set, the gastroenterologist endoscopist is an asset to the Nutrition Support Team and should participate in providing optimal nutrition therapy to the hospitalized adult patient. PMID:26952578

  20. ELMO1 is upregulated in AML CD34+ stem/progenitor cells, mediates chemotaxis and predicts poor prognosis in normal karyotype AML.

    PubMed

    Capala, Marta E; Vellenga, Edo; Schuringa, Jan Jacob

    2014-01-01

    Both normal as well leukemic hematopoietic stem cells critically depend on their microenvironment in the bone marrow for processes such as self-renewal, survival and differentiation, although the exact pathways that are involved remain poorly understood. We performed transcriptome analysis on primitive CD34+ acute myeloid leukemia (AML) cells (n = 46), their more differentiated CD34- leukemic progeny, and normal CD34+ bone marrow cells (n = 31) and focused on differentially expressed genes involved in adhesion and migration. Thus, Engulfment and Motility protein 1 (ELMO1) was identified amongst the top 50 most differentially expressed genes. ELMO1 is a crucial link in the signaling cascade that leads to activation of RAC GTPases and cytoskeleton rearrangements. We confirmed increased ELMO1 expression at the mRNA and protein level in a panel of AML samples and showed that high ELMO1 expression is an independent negative prognostic factor in normal karyotype (NK) AML in three large independent patient cohorts. Downmodulation of ELMO1 in human CB CD34+ cells did not significantly alter expansion, progenitor frequency or differentiation in stromal co-cultures, but did result in a decreased frequency of stem cells in LTC-IC assays. In BCR-ABL-transduced human CB CD34+ cells depletion of ELMO1 resulted in a mild decrease in proliferation, but replating capacity of progenitors was severely impaired. Downregulation of ELMO1 in a panel of primary CD34+ AML cells also resulted in reduced long-term growth in stromal co-cultures in two out of three cases. Pharmacological inhibition of the ELMO1 downstream target RAC resulted in a severely impaired proliferation and survival of leukemic cells. Finally, ELMO1 depletion caused a marked decrease in SDF1-induced chemotaxis of leukemic cells. Taken together, these data show that inhibiting the ELMO1-RAC axis might be an alternative way to target leukemic cells. PMID:25360637

  1. Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism

    PubMed Central

    Rotin, Lianne E.; Gronda, Marcela; MacLean, Neil; Hurren, Rose; Wang, XiaoMing; Lin, Feng-Hsu; Wrana, Jeff; Datti, Alessandro; Barber, Dwayne L.; Minden, Mark D.; Slassi, Malik; Schimmer, Aaron D.

    2016-01-01

    Targeting Bruton's tyrosine kinase (BTK) with the small molecule BTK inhibitor ibrutinib has significantly improved patient outcomes in several B-cell malignancies, with minimal toxicity. Given the reported expression and constitutive activation of BTK in acute myeloid leukemia (AML) cells, there has been recent interest in investigating the anti-AML activity of ibrutinib. We noted that ibrutinib had limited single-agent toxicity in a panel of AML cell lines and primary AML samples, and therefore sought to identify ibrutinib-sensitizing drugs. Using a high-throughput combination chemical screen, we identified that the poly(ADP-ribose) glycohydrolase (PARG) inhibitor ethacridine lactate synergized with ibrutinib in TEX and OCI-AML2 leukemia cell lines. The combination of ibrutinib and ethacridine induced a synergistic increase in reactive oxygen species that was functionally important to explain the observed cell death. Interestingly, synergistic cytotoxicity of ibrutinib and ethacridine was independent of the inhibitory effect of ibrutinib against BTK, as knockdown of BTK did not sensitize TEX and OCI-AML2 cells to ethacridine treatment. Thus, our findings indicate that ibrutinib may have a BTK-independent role in AML and that PARG inhibitors may have utility as part of a combination therapy for this disease. PMID:26624983

  2. Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism.

    PubMed

    Rotin, Lianne E; Gronda, Marcela; MacLean, Neil; Hurren, Rose; Wang, XiaoMing; Lin, Feng-Hsu; Wrana, Jeff; Datti, Alessandro; Barber, Dwayne L; Minden, Mark D; Slassi, Malik; Schimmer, Aaron D

    2016-01-19

    Targeting Bruton's tyrosine kinase (BTK) with the small molecule BTK inhibitor ibrutinib has significantly improved patient outcomes in several B-cell malignancies, with minimal toxicity. Given the reported expression and constitutive activation of BTK in acute myeloid leukemia (AML) cells, there has been recent interest in investigating the anti-AML activity of ibrutinib. We noted that ibrutinib had limited single-agent toxicity in a panel of AML cell lines and primary AML samples, and therefore sought to identify ibrutinib-sensitizing drugs. Using a high-throughput combination chemical screen, we identified that the poly(ADP-ribose) glycohydrolase (PARG) inhibitor ethacridine lactate synergized with ibrutinib in TEX and OCI-AML2 leukemia cell lines. The combination of ibrutinib and ethacridine induced a synergistic increase in reactive oxygen species that was functionally important to explain the observed cell death. Interestingly, synergistic cytotoxicity of ibrutinib and ethacridine was independent of the inhibitory effect of ibrutinib against BTK, as knockdown of BTK did not sensitize TEX and OCI-AML2 cells to ethacridine treatment. Thus, our findings indicate that ibrutinib may have a BTK-independent role in AML and that PARG inhibitors may have utility as part of a combination therapy for this disease. PMID:26624983

  3. Survivin is highly expressed in CD34+38− leukemic stem/progenitor cells and predicts poor clinical outcomes in AML

    PubMed Central

    Qiu, Yihua; Huang, Xuelin; Diao, Lixia; Zhang, Nianxiang; Coombes, Kevin R.; Mak, Duncan H.; Konopleva, Marina; Cortes, Jorge; Kantarjian, Hagop M.; Mills, Gordon B.; Andreeff, Michael

    2012-01-01

    Survivin, a member of the inhibitors of apoptosis protein family, plays important roles in cell proliferation and survival and is highly expressed in various malignancies, including leukemias. To better understand its role in acute myeloid leukemia (AML), we profiled survivin expression in samples obtained from 511 newly diagnosed AML patients and in CD34+38− AML stem/progenitor cells using a validated reverse-phase protein array; we correlated its levels with clinical outcomes and with levels of other proteins in the same sample set. We found that survivin levels were higher in bone marrow than in paired peripheral blood leukemic cells (n = 140, P = .0001) and that higher survivin levels significantly predicted shorter overall (P = .016) and event-free (P = .023) survival in multivariate Cox model analysis. Importantly, survivin levels were significantly higher in CD34+38− AML stem/progenitor cells than in bulk blasts and total CD34+ AML cells (P < .05). Survivin expression correlated with the expressions of multiple proteins involved with cell proliferation and survival. Particularly, its expression strongly correlated with HIF1α in the stem/progenitor cell compartment. These results suggest that survivin is a prognostic biomarker in AML and that survivin, which is overexpressed in AML stem/progenitor cells, remains a potentially important target for leukemia therapy. PMID:22645176

  4. Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice.

    PubMed

    Etchin, J; Montero, J; Berezovskaya, A; Le, B T; Kentsis, A; Christie, A L; Conway, A S; Chen, W C; Reed, C; Mansour, M R; Ng, C E L; Adamia, S; Rodig, S J; Galinsky, I A; Stone, R M; Klebanov, B; Landesman, Y; Kauffman, M; Shacham, S; Kung, A L; Wang, J C Y; Letai, A; Look, A T

    2016-01-01

    Currently available combination chemotherapy for acute myeloid leukemia (AML) often fails to result in long-term remissions, emphasizing the need for novel therapeutic strategies. We reasoned that targeted inhibition of a prominent nuclear exporter, XPO1/CRM1, could eradicate self-renewing leukemia-initiating cells (LICs) whose survival depends on timely XPO1-mediated transport of specific protein and RNA cargoes. Using an immunosuppressed mouse model bearing primary patient-derived AML cells, we demonstrate that selinexor (KPT-330), an oral antagonist of XPO1 that is currently in clinical trials, has strong activity against primary AML cells while sparing normal stem and progenitor cells. Importantly, limiting dilution transplantation assays showed that this cytotoxic activity is not limited to the rapidly proliferating bulk population of leukemic cells but extends to the LICs, whose inherent drug resistance and unrestricted self-renewal capacity has been implicated in the difficulty of curing AML patients with conventional chemotherapy alone. PMID:26202935

  5. Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice

    PubMed Central

    Etchin, J; Montero, J; Berezovskaya, A; Le, BT; Kentsis, A; Christie, AL; Conway, AS; Chen, WC; Reed, C; Mansour, MR; Ng, CEL; Adamia, S; Rodig, SJ; Galinsky, IA; Stone, RM; Klebanov, B; Landesman, Y; Kauffman, M; Shacham, S; Kung, AL; Wang, JCY; Letai, A; Look, AT

    2016-01-01

    Currently available combination chemotherapy for acute myeloid leukemia (AML) often fails to result in long-term remissions, emphasizing the need for novel therapeutic strategies. We reasoned that targeted inhibition of a prominent nuclear exporter, XPO1/CRM1, could eradicate self-renewing leukemia-initiating cells (LICs) whose survival depends on timely XPO1-mediated transport of specific protein and RNA cargoes. Using an immunosuppressed mouse model bearing primary patient-derived AML cells, we demonstrate that selinexor (KPT-330), an oral antagonist of XPO1 that is currently in clinical trials, has strong activity against primary AML cells while sparing normal stem and progenitor cells. Importantly, limiting dilution transplantation assays showed that this cytotoxic activity is not limited to the rapidly proliferating bulk population of leukemic cells but extends to the LICs, whose inherent drug resistance and unrestricted self-renewal capacity has been implicated in the difficulty of curing AML patients with conventional chemotherapy alone. PMID:26202935

  6. Infective Dermatitis in an Adult Patient With HTLV-1

    PubMed Central

    Riveros, Rosalba; Medina, Raquel; Morel, Maida

    2015-01-01

    Abstract: Infective dermatitis is a chronic exudative eczematous eruption presenting in human T-lymphotropic virus type 1 (HTLV-1)–infected people. It presents with relapsing erythematous, scaly, and crusted lesions affecting simultaneously the scalp, external ear, retroauricular area, eyelid, paranasal skin, neck axilla, and groin. Superimposed Staphylococcus and Streptococcus infection are common. It mainly affects children and exceptionally adults, and there are only a few published cases. The authors present the first reported case in Paraguay of an adult patient who had symptoms of human T-lymphotropic virus type 1–associated progressive tropical spastic paraparesis, and 6 years after the onset of the neurological symptoms, the patient developed infective dermatitis lesions on the skin, with frequent exacerbations since then. PMID:26588341

  7. Incorporating measurable ('minimal') residual disease-directed treatment strategies to optimize outcomes in adults with acute myeloid leukemia.

    PubMed

    Pettit, Kristen; Stock, Wendy; Walter, Roland B

    2016-07-01

    Curative-intent therapy leads to complete remissions in many adults with acute myeloid leukemia (AML), but relapse remains common. Numerous studies have unequivocally demonstrated that the persistence of measurable ('minimal') residual disease (MRD) at the submicroscopic level during morphologic remission identifies patients at high risk of disease recurrence and short survival. This association has provided the impetus to customize anti-leukemia therapy based on MRD data, a strategy that is now routinely pursued in acute promyelocytic leukemia (APL). While it is currently uncertain whether this approach will improve outcomes in AML other than APL, randomized studies have validated MRD-based risk-stratified treatment algorithms in acute lymphoblastic leukemia. Here, we review the available studies examining MRD-directed therapy in AML, appraise their strengths and limitations, and discuss avenues for future investigation. PMID:27269126

  8. Study of inhaler technique in asthma patients: differences between pediatric and adult patients

    PubMed Central

    Manríquez, Pablo; Acuña, Ana María; Muñoz, Luis; Reyes, Alvaro

    2015-01-01

    Objective: Inhaler technique comprises a set of procedures for drug delivery to the respiratory system. The oral inhalation of medications is the first-line treatment for lung diseases. Using the proper inhaler technique ensures sufficient drug deposition in the distal airways, optimizing therapeutic effects and reducing side effects. The purposes of this study were to assess inhaler technique in pediatric and adult patients with asthma; to determine the most common errors in each group of patients; and to compare the results between the two groups. Methods: This was a descriptive cross-sectional study. Using a ten-step protocol, we assessed inhaler technique in 135 pediatric asthma patients and 128 adult asthma patients. Results: The most common error among the pediatric patients was failing to execute a 10-s breath-hold after inhalation, whereas the most common error among the adult patients was failing to exhale fully before using the inhaler. Conclusions: Pediatric asthma patients appear to perform most of the inhaler technique steps correctly. However, the same does not seem to be true for adult patients. PMID:26578130

  9. Organ doses to adult patients for chest CT

    SciTech Connect

    Huda, Walter; Sterzik, Alexander; Tipnis, Sameer; Schoepf, U. Joseph

    2010-02-15

    Purpose: The goal of this study was to estimate organ doses for chest CT examinations using volume computed tomography dose index (CTDI{sub vol}) data as well as accounting for patient weight. Methods: A CT dosimetry spreadsheet (ImPACT CT patient dosimetry calculator) was used to compute organ doses for a 70 kg patient undergoing chest CT examinations, as well as volume computed tomography dose index (CTDI{sub vol}) in a body CT dosimetry phantom at the same CT technique factors. Ratios of organ dose to CTDI{sub vol} (f{sub organ}) were generated as a function of anatomical location in the chest for the breasts, lungs, stomach, red bone marrow, liver, thyroid, liver, and thymus. Values of f{sub organ} were obtained for x-ray tube voltages ranging from 80 to 140 kV for 1, 4, 16, and 64 slice CT scanners from two vendors. For constant CT techniques, we computed ratios of dose in water phantoms of differing diameter. By modeling patients of different weights as equivalent water cylinders of different diameters, we generated factors that permit the estimation of the organ doses in patients weighing between 50 and 100 kg who undergo chest CT examinations relative to the corresponding organ doses received by a 70 kg adult. Results: For a 32 cm long CT scan encompassing the complete lungs, values of f{sub organ} ranged from 1.7 (thymus) to 0.3 (stomach). Organs that are directly in the x-ray beam, and are completely irradiated, generally had f{sub organ} values well above 1 (i.e., breast, lung, heart, and thymus). Organs that are not completely irradiated in a total chest CT scan generally had f{sub organ} values that are less than 1 (e.g., red bone marrow, liver, and stomach). Increasing the x-ray tube voltage from 80 to 140 kV resulted in modest increases in f{sub organ} for the heart (9%) and thymus (8%), but resulted in larger increases for the breast (19%) and red bone marrow (21%). Adult patient chests have been modeled by water cylinders with diameters between

  10. Vaccination of Adult Patients with Systemic Lupus Erythematosus in Portugal

    PubMed Central

    Moraes-Fontes, Maria Francisca; Antunes, Ana Margarida; Gruner, Heidi; Riso, Nuno

    2016-01-01

    In the wake of the Portuguese vaccination program 50th anniversary it seems appropriate to review vaccination in patients with systemic lupus erythematosus. Controversial issues as regards the association between autoimmune diseases, infections, and vaccines are discussed as well as vaccine safety and efficacy issues as regards chronic immunosuppressant (IS) drug therapy. After a brief overview of national policies, specific recommendations are made as regards vaccination for adult patients with SLE with a particular focus on current IS therapy and unmet needs. PMID:27069477

  11. Is it important to decipher the heterogeneity of "normal karyotype AML"?

    PubMed

    Nimer, Stephen D

    2008-03-01

    Almost half of adult acute myelogenous leukemia (AML) is normal cytogenetically, and this subgroup shows a remarkable heterogeneity of genetic mutations at the molecular level and an intermediate response to therapy. The finding of recurrent cytogenetic abnormalities has influenced, in a primary way, the understanding and treatment of leukemias. Yet "normal karyotype AML" lacks such obvious abnormalities, but has a variety of prognostically important genetic abnormalities. Thus, the presence of a FLT3-ITD (internal tandem duplication), MLL-PTD (partial tandem duplication), or the increased expression of ERG or EVI1 mRNAs confer a poor prognosis, and an increased risk of relapse. In contrast, the presence of cytoplasmic nucleophosmin or C/EBPA mutations is associated with lower relapse rates and improved survival. Although resistance to treatment is associated with specific mutations, the degree to which the leukemia resembles a stem cell in its functional properties may provide greater protection from the effects of treatment. Although usually all of the circulating leukemia cells are cleared following treatment, a small residual population of leukemic cells in the bone marrow persists, making this disease hard to eradicate. Increased understanding of the biological consequences of at least some of these mutations in "normal karyotype AML" is leading to more targeted approaches to develop more effective treatments for this disease. PMID:18342811

  12. Genomic DNA breakpoints in AML1/RUNX1 and ETO cluster with topoisomerase II DNA cleavage and DNase I hypersensitive sites in t(8;21) leukemia

    PubMed Central

    Zhang, Yanming; Strissel, Pamela; Strick, Reiner; Chen, Jianjun; Nucifora, Giuseppina; Le Beau, Michelle M.; Larson, Richard A.; Rowley, Janet D.

    2002-01-01

    The translocation t(8;21)(q22;q22) is one of the most frequent chromosome translocations in acute myeloid leukemia (AML). AML1/RUNX1 at 21q22 is involved in t(8;21), t(3;21), and t(16;21) in de novo and therapy-related AML and myelodysplastic syndrome as well as in t(12;21) in childhood B cell acute lymphoblastic leukemia. Although DNA breakpoints in AML1 and ETO (at 8q22) cluster in a few introns, the mechanisms of DNA recombination resulting in t(8;21) are unknown. The correlation of specific chromatin structural elements, i.e., topoisomerase II (topo II) DNA cleavage sites, DNase I hypersensitive sites, and scaffold-associated regions, which have been implicated in chromosome recombination with genomic DNA breakpoints in AML1 and ETO in t(8;21) is unknown. The breakpoints in AML1 and ETO were clustered in the Kasumi 1 cell line and in 31 leukemia patients with t(8;21); all except one had de novo AML. Sequencing of the breakpoint junctions revealed no common DNA motif; however, deletions, duplications, microhomologies, and nontemplate DNA were found. Ten in vivo topo II DNA cleavage sites were mapped in AML1, including three in intron 5 and seven in intron 7a, and two were in intron 1b of ETO. All strong topo II sites colocalized with DNase I hypersensitive sites and thus represent open chromatin regions. These sites correlated with genomic DNA breakpoints in both AML1 and ETO, thus implicating them in the de novo 8;21 translocation. PMID:11867721

  13. Osteosarcoma in Adult Patients Living with HIV/AIDS

    PubMed Central

    Marais, Leonard C.; Ferreira, Nando

    2013-01-01

    Background. HIV infection has reached epidemic proportions in South Africa, with an estimated prevalence of 21.5% in adults living in the province of KwaZulu-Natal. Several malignancies have been identified as part of the spectrum of immunosuppression-related manifestations of HIV infection. Very few reports, however, exist regarding the occurrence of non-AIDS-defining sarcomas in the extremities or limb girdles. Methods. A retrospective review was performed on all adult patients, between the ages of 30 and 60 years, with histologically confirmed osteosarcomas of the appendicular skeleton referred to a tertiary-level orthopaedic oncology unit. Results. Five out of the nine patients (62.5%) included in the study were found to be HIV positive. The average CD4 count of these patients was 278 (237–301) cells/mm3, indicating advanced immunological compromise. Three of the malignancies in HIV-positive patients occurred in preexisting benign or low-grade tumours. Conclusion. A heightened index of suspicion is required in HIV patients presenting with unexplained bone and joint pain or swelling. Judicious use of appropriate radiological investigation, including magnetic resonance imaging of suspicious lesions and timely referral to an appropriate specialized orthopaedic oncology unit, is recommended. PMID:23762607

  14. The blind men and the AML elephant: can we feel the progress?

    PubMed Central

    Tauro, S

    2016-01-01

    The pharmacological therapy of non-promyelocytic acute myeloid leukemia (AML) has remained unchanged for over 40 years with an anthracycline–cytarabine combination forming the backbone of induction treatments. Nevertheless, the survival of younger patients has increased due to improved management of the toxicity of therapies including stem cell transplantation. Older patients and those with infirmity that precludes treatment-intensification have, however, not benefited from improvements in supportive care and continue to experience poor outcomes. An increased understanding of the genomic heterogeneity of AML raises the possibility of treatment-stratification to improve prognosis. Thus, efforts to identify agents with non-conventional anti-leukemic effects have paralleled those aiming to optimize leukemia cell-kill with conventional chemotherapy, resulting in a number of randomized controlled trials (RCT). In the last 18 months, RCTs investigating the effects of vosaroxin, azacitidine and gemtuzumab ozogamycin and daunorubicin dose have been reported with some studies indicating a statistically significant survival benefit with the investigational agent compared with standard therapy and potentially, a new era in AML therapeutics. Given the increasing costs of cancer care, a review of these studies, with particular attention to the magnitude of clinical benefit with the newer agents would be useful, especially for physicians treating patients in single-payer health systems. PMID:27176800

  15. Drug resistance: Still a daunting challenge to the successful treatment of AML

    PubMed Central

    Shaffer, Brian C.; Gillet, Jean-Pierre; Patel, Chirayu; Baer, Maria R.; Bates, Susan E.; Gottesman, Michael M.

    2012-01-01

    Resistance to chemotherapy remains a challenging issue for patients and their physicians. P-glycoprotein (Pgp, MDR1, ABCB1), as well as a family of structurally and functionally related proteins, are plasma membrane transporters able to efflux a variety of substrates from the cell cytoplasm, including chemotherapeutic agents. The discovery of ABCB1 made available a potential target for pharmacologic down-regulation of efflux-mediated chemotherapy resistance. In patients with acute myeloid leukemia (AML), a neoplasm characterized by proliferation of poorly differentiated myeloid progenitor cells, leukemic cells often express ABCB1 at high levels, which may lead to the development of resistance to chemotherapy. Thus, AML seemed to be a likely cancer for which the addition of drug efflux inhibitors to the chemotherapeutic regimen would improve outcomes in patients. Despite this rational hypothesis, the majority of clinical trials evaluating this strategy have failed to reach a positive endpoint, most recently the Eastern Cooperative Oncology Group E3999 trial. Here we review data suggesting the importance of ABCB1 in AML, address the failure of clinical trials to support a therapeutic strategy aimed at modulating ABCB1-mediated resistance, and consider the type of research that should be conducted in this field going forward. PMID:22409994

  16. The blind men and the AML elephant: can we feel the progress?

    PubMed

    Tauro, S

    2016-01-01

    The pharmacological therapy of non-promyelocytic acute myeloid leukemia (AML) has remained unchanged for over 40 years with an anthracycline-cytarabine combination forming the backbone of induction treatments. Nevertheless, the survival of younger patients has increased due to improved management of the toxicity of therapies including stem cell transplantation. Older patients and those with infirmity that precludes treatment-intensification have, however, not benefited from improvements in supportive care and continue to experience poor outcomes. An increased understanding of the genomic heterogeneity of AML raises the possibility of treatment-stratification to improve prognosis. Thus, efforts to identify agents with non-conventional anti-leukemic effects have paralleled those aiming to optimize leukemia cell-kill with conventional chemotherapy, resulting in a number of randomized controlled trials (RCT). In the last 18 months, RCTs investigating the effects of vosaroxin, azacitidine and gemtuzumab ozogamycin and daunorubicin dose have been reported with some studies indicating a statistically significant survival benefit with the investigational agent compared with standard therapy and potentially, a new era in AML therapeutics. Given the increasing costs of cancer care, a review of these studies, with particular attention to the magnitude of clinical benefit with the newer agents would be useful, especially for physicians treating patients in single-payer health systems. PMID:27176800

  17. Experimental identification of potential falls in older adult hospital patients.

    PubMed

    Cloutier, Aimee; Yang, James; Pati, Debajyoti; Valipoor, Shabboo

    2016-05-01

    Patient falls within hospitals have been identified as serious but largely preventable incidents, particularly among older adult patients. Previous literature has explored intrinsic factors associated with patient falls, but literature identifying possible extrinsic or situational factors related to falls is lacking. This study seeks to identify patient motions and activities along with associated environmental design factors in a patient bathroom and clinician zone setting that may lead to falls. A motion capture experiment was conducted in a laboratory setting on 27 subjects over the age of seventy using scripted tasks and mockups of the bathroom and clinician zone of a patient room. Data were post-processed using Cortex and Visual3D software. A potential fall was characterized by a set of criteria based on the jerk of the upper body׳s center of mass (COM). Results suggest that only motion-related factors, particularly turning, pushing, pulling, and grabbing, contribute most significantly to potential falls in the patient bathroom, whereas only pushing and pulling contribute significantly in the clinician zone. Future work includes identifying and changing precise environmental design factors associated with these motions for an updated patient room and performing motion capture experiments using the new setup. PMID:26920507

  18. Approach to the Patient: The Adult With Congenital Adrenal Hyperplasia

    PubMed Central

    Arlt, Wiebke

    2013-01-01

    The most common form of congenital adrenal hyperplasia is steroid 21-hydroxylase deficiency (21OHD). When the nonclassical (mild) form is included, 21OHD is the most common genetic disease in human beings. With the advent of pharmaceutical preparation of glucocorticoids starting in the 1960s and newborn screening starting in the 1990s, the majority of children with 21OHD are reaching adulthood, which has yielded a cohort of patients with, in essence, a new disease. Only recently have some data emerged from cohorts of adults with 21OHD, and in some centers, experience with the management of these patients is growing. These patients suffer from poor health, infertility, characteristic tumors in the adrenal glands and gonads, and consequences of chronic glucocorticoid therapy. Their care is fragmented and inconsistent, and many stop taking their medications out of frustration. Internal medicine residents and endocrinology fellows receive little training in their care, which further discourages their seeking medical attention. Adults with 21OHD have a different physiology from patients with Addison's disease or other androgen excess states, and their needs are different than those of young children with 21OHD. Consequently, their care requires unorthodox treatment and monitoring strategies foreign to most endocrine practitioners. Our goal for this article is to review their physiology, complications, and needs in order to develop rational and effective treatment and monitoring strategies. PMID:23837188

  19. Proteomic and Genetic Approaches Identify Syk as an AML Target

    PubMed Central

    Hahn, Cynthia K.; Berchuck, Jacob E.; Ross, Kenneth N.; Kakoza, Rose M.; Clauser, Karl; Schinzel, Anna C.; Ross, Linda; Galinsky, Ilene; Davis, Tina N.; Silver, Serena J.; Root, David E.; Stone, Richard M.; DeAngelo, Daniel J.; Carroll, Martin; Hahn, William C.; Carr, Steven A.; Golub, Todd R.; Kung, Andrew L.; Stegmaier, Kimberly

    2009-01-01

    SUMMARY Cell-based screening can facilitate rapid identification of compounds inducing complex cellular phenotypes. Advancing a compound toward the clinic, however, generally requires identification of precise mechanisms of action. We previously found that epidermal growth factor receptor (EGFR) inhibitors induce acute myeloid leukemia (AML) differentiation via a non-EGFR mechanism. In this report, we integrated proteomic and RNAi-based strategies to identify their off-target anti-AML mechanism. These orthogonal approaches identified Syk as a target in AML. Genetic and pharmacological inactivation of Syk with a drug in clinical trial for other indications promoted differentiation of AML cells and attenuated leukemia growth in vivo. These results demonstrate the power of integrating diverse chemical, proteomic, and genomic screening approaches to identify therapeutic strategies for cancer. PMID:19800574

  20. Cellular Intrinsic Mechanism Affecting the Outcome of AML Treated with Ara-C in a Syngeneic Mouse Model

    PubMed Central

    Tan, Dongming; Su, Guangsong; Zheng, Yanwen; He, Chao; Mao, Zhengwei J.; Singleton, Timothy P.; Yin, Bin

    2014-01-01

    The mechanisms underlying acute myeloid leukemia (AML) treatment failure are not clear. Here, we established a mouse model of AML by syngeneic transplantation of BXH-2 derived myeloid leukemic cells and developed an efficacious Ara-C-based regimen for treatment of these mice. We proved that leukemic cell load was correlated with survival. We also demonstrated that the susceptibility of leukemia cells to Ara-C could significantly affect the survival. To examine the molecular alterations in cells with different sensitivity, genome-wide expression of the leukemic cells was profiled, revealing that overall 366 and 212 genes became upregulated or downregulated, respectively, in the resistant cells. Many of these genes are involved in the regulation of cell cycle, cellular proliferation, and apoptosis. Some of them were further validated by quantitative PCR. Interestingly, the Ara-C resistant cells retained the sensitivity to ABT-737, an inhibitor of anti-apoptosis proteins, and treatment with ABT-737 prolonged the life span of mice engrafted with resistant cells. These results suggest that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C. Incorporation of apoptosis inhibitors, such as ABT-737, into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. This work provided direct in vivo evidence that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C, suggesting that incorporation of apoptosis inhibitors into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. PMID:25314317

  1. Two methods for the quantitative analysis of surface antigen expression in acute myeloid leukemia (AML).

    PubMed

    Woźniak, Jolanta

    2004-01-01

    The expression of lineage molecules (CD13 and CD33), c-Kit receptor (CD117), CD34, HLA-DR and adhesion molecule CD49d was assessed in acute myeloid leukemia (AML) blast cells from 32 cases, using direct and indirect quantitative cytometric analysis. High correlation (r=0.8) was found between antigen expression intensity values calculated by direct analysis method (ABC) and by indirect analysis method (RFI). Moreover, the differences in expression intensity of CD13, CD117 and CD34 antigens were found between leukemic and normal myeloblasts. This may be helpful in identification of leukemic cells in the diagnostics of minimal residual disease after treatment in AML patients. PMID:15493582

  2. Celastrol Induces Cell Apoptosis and Inhibits the Expression of the AML1-ETO/C-KIT Oncoprotein in t(8;21) Leukemia.

    PubMed

    Yu, Xianjun; Ruan, Xuzhi; Zhang, Jingxuan; Zhao, Qun

    2016-01-01

    Resistance to chemotherapy is a major challenge to improving overall survival in Acute Myeloid Leukemia (AML). Therefore, the development of innovative therapies and the identification of more novel agents for AML are urgently needed. Celastrol, a compound extracted from the Chinese herb Tripterygium wilfordii Hook, exerts anticancer activity. We investigated the effect of celastrol in the t(8;21) AML cell lines Kasumi-1 and SKNO-1. We demonstrated that inhibition of cell proliferation activated caspases and disrupted mitochondrial function. In addition, we found that celastrol downregulated the AML1-ETO fusion protein, therefore downregulating C-KIT kinases and inhibiting AKT, STAT3 and Erk1/2. These findings provide clear evidence that celastrol might provide clinical benefits to patients with t(8;21) leukemia. PMID:27144550

  3. Clinical features in adult patient with Wolf-Hirschhorn syndrome.

    PubMed

    Martínez-Quintana, E; Rodríguez-González, F

    2014-06-01

    The Wolf-Hirschhorn syndrome (WHS) encompasses deletions at the distal part of the short arm of one chromosome 4 (4p16 region). Clinical signs frequently include a typical facial appearance, mental retardation, intrauterine and postnatal growth retardation, hypotonia with decreased muscle bulk and seizures besides congenital heart malformations, midline defects, urinary tract malformations and brain, hearing and ophthalmologic malformations. Pathogenesis of WHS is multigenic and many factors are involved in prediction of prognosis such as extent of deletion, the occurrence of severe chromosome anomalies, the severe of seizures, the existence of serious internal, mainly cardiac, abnormalities and the degree of mental retardation. The phenotype of adult with WHS is in general similar to that of childhood being facial dysmorphism, growth retardation and mental retardation the rule in both adults and children. Avoid long-term complications and provide rehabilitation programs and genetic counseling may be essential in these patients. PMID:24656633

  4. Clostridium difficile infections among Jordanian adult hospitalized patients.

    PubMed

    Nasereddin, Lina M; Bakri, Fares G; Shehabi, Asem A

    2009-12-01

    This prospective study investigated the important epidemiologic aspects of Clostridium difficile infections (CDIs) among Jordanian adult hospitalized patients. A total of 300 stool specimens were investigated using culture and polymerase chain reaction methods for detection of C difficile, its toxins, and fluoroquinolone resistance. C difficile-positive cultures were found in 13.7% of the patients, and 73% of the isolates carried tcdA and/or tcdB toxin genes, and all C difficile isolates were negative for binary toxin. The isolates showed moderate level of resistance to both ciprofloxacin and levofloxacin, whereas metronidazole and vancomycin were highly susceptible. This study indicates the need for early detection of CDIs and prevention of its severe disease in hospitalized patients. PMID:19712999

  5. Urinary considerations for adult patients with spinal dysraphism.

    PubMed

    Veenboer, Paul W; de Kort, Laetitia M O; Chrzan, Rafal J; de Jong, Tom P V M

    2015-06-01

    The incidence of newborns with spinal dysraphism is diminishing worldwide, although survival of individuals with this condition into adulthood continues to improve. The number of adults with spinal dysraphism will, therefore, increase in the coming years, which will pose new challenges in patient management. Urological manifestations of spinal dysraphism can include increased risks of urinary incontinence, urinary tract infection, urinary calculi, sexual dysfunction, end-stage renal disease and iatrogenic metabolic disturbances; however, the severity and incidence of these symptoms varies substantially between patients. Owing to the presence of multiple comorbidities, treatment and follow-up protocols often have to be adapted to best suit the needs of specific patients. Authors describe bladder and kidney function and long-term complications of treatments initiated in childhood, as well as the potential for improvements in quality of life through better follow-up schedules and future developments. PMID:25963964

  6. Amelogenesis imperfecta - lifelong management. Restorative management of the adult patient.

    PubMed

    Patel, M; McDonnell, S T; Iram, S; Chan, M F W-Y

    2013-11-01

    The biggest challenge restorative dentists face in rehabilitating patients with amelogenesis imperfecta (AI) is trying to restore aesthetics, function and occlusal stability while keeping the treatment as conservative as possible. The goals of treatment should be to prolong the life of the patient's own teeth and avoid or delay the need for extractions and subsequent replacement with conventional fixed, removable or implant retained prostheses. In order to achieve these goals a stepwise approach to treatment planning is required starting with the most conservative but aesthetically acceptable treatment. This article discusses the management of AI and presents the various treatment options available for restoring the adult patient who presents to the dentist with AI. PMID:24201615

  7. Asthma Economic Costs in Adult Asthmatic Patients in Tehran, Iran

    PubMed Central

    SHARIFI, Laleh; POURPAK, Zahra; FAZLOLLAHI, Mohammad Reza; BOKAIE, Saied; MOEZZI, Hamid Reza; KAZEMNEJAD, Anoushirvan; MOIN, Mostafa

    2015-01-01

    Background: High prevalence and increasing rate of asthmatic patients around the word witnesses the high burden of asthma. We have limited data on asthma burden and economic costs in Iran. This study aimed to find direct and indirect economic costs of asthma and their association with some background factors in one of the referral tertiary centers for adult patients with asthma. Methods: We surveyed asthma related economic costs of 197 adult patients who referred to Milad Hospital, Tehran, Iran from Jun 2007 to January 2010. The patients were followed up for a period of one-year ±1 month and asthma related costs and its control status were registered. Results: Patients were consisted of 125 (64.1%) females and 70 (35.9%) males. Total cost of asthma was 590.22 ±32.18 USD for one patient per one year, the cost of drug, paraclinic, doctor visit, hospitalization, emergency, transportation, and absent days were 327.02, 4.76, 35.44, 3.82, 0.26, 113.03, 105.89 USD respectively. Men showed a significant elevation in their total (P=0.009) and drug costs (P=0.028). In addition, we found significant differences between total asthma costs and asthma control status (P=0.002). Conclusions: According to the high proportion of asthma, related cost compare to Total Income of an Iranian family, the necessity of public coverage of health assurance is quite clear. We suggest that improving asthma management and accessibility to specialized treatment centers can result in decreasing asthma medication and transportation costs as major direct and indirect asthma related costs. PMID:26587495

  8. Emerging strategies for the treatment of older patients with acute myeloid leukemia.

    PubMed

    Sanz, Miguel A; Iacoboni, Gloria; Montesinos, Pau; Venditti, Adriano

    2016-10-01

    Acute myeloid leukemia (AML) is the most common acute leukemia in adults, and its incidence increases with age. Clinical outcomes in younger patients have improved over the years but, unfortunately, there is little evidence for an equivalent improvement in outcome for older patients. Approximately 50 % of older patients who are able to receive intensive chemotherapy will achieve a complete remission; however, they face a much higher relapse rate than younger patients, and survival rates for this group are low. Therefore, there is an urgent need to improve outcomes in older patients with AML. In this article, we discuss current treatment paradigms for older patients with AML including the challenges faced when determining which patients are eligible for intensive chemotherapy. We then highlight new treatments in development that may benefit this patient group. Cytotoxic agents, hypomethylating agents, molecularly targeted agents, and cell cycle kinase inhibitors are discussed, with a focus on novel agents that have achieved an advanced stage of development. Overall, the treatment of AML in older patients remains a challenge and, whenever possible, treatment should be offered in the context of clinical trials and should be planned with curative intent. PMID:27118541

  9. Establishment of xenotransplantation model of human CN-AML with FLT3-ITD (mut) /NPM1 (-) in NOD/SCID mice.

    PubMed

    Shang, Zhen; Wang, Jue; Wang, Di; Xiao, Min; Li, Tong-juan; Wang, Na; Huang, Liang; Zhou, Jian-feng

    2013-06-01

    Patients with FLT3-ITD (mut) /NPM1 (-) cytogenetically normal acute myeloid leukemia (CN-AML), as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is beneficial to generate xenotransplantation model of FLT3-ITD (mut) /NPM1 (-) CN-AML to better understand the pathogenesis and therapeutic strategies of such AML subtype. The purpose of present study was to establish the xenotransplantation model in NOD/SCID mice with FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells. The FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells from 3 of 7 cases were successfully transplanted into NOD/SCID mice, and human CD45 positive cells were detected in the peripheral blood, spleen and bone marrow of mice by using flow cytometry. Infiltration of human leukemia cells in various organs of mice was observed by using immunohistochemistry. Gene analysis confirmed sustained FLT3/ITD mutation without NPM1 mutation in mice. By performing serial transplantation, it was found that characteristics of the leukemia cells in secondary and tertiary generation models remained unchanged. Moreover, in vivo cytarabine administration could extend survival of NOD/SCID mice, which was consistent with clinical observation. In conclusion, we successfully established xenotransplantation model of human FLT3-ITD (mut) /NPM1 (-) CN-AML in NOD/SCID mice. The model was able to present primary disease and suitable to evaluate the curative effects of new drugs or therapy strategies. PMID:23771655

  10. Updates in vaccination: Recommendations for adult inflammatory bowel disease patients

    PubMed Central

    Chaudrey, Khadija; Salvaggio, Michelle; Ahmed, Aftab; Mahmood, Sultan; Ali, Tauseef

    2015-01-01

    Treatment regimens for inflammatory bowel disease (IBD) incorporate the use of a variety of immunosuppressive agents that increase the risk of infections. Prevention of many of these infections can be achieved by the timely and judicious use of vaccinations. IBD patients tend to be under-immunized. Some of the contributing factors are lack of awareness regarding the significance of vaccinating IBD patients, misperception about safety of vaccinations in immunocompromised patients, ambiguity about the perceived role of the gastroenterologist in contrast to the primary care physician and unavailability of vaccination guidelines focused on IBD population. In general, immunocompetent IBD patients can be vaccinated using standard vaccination recommendations. However there are special considerations for IBD patients receiving immunosuppressive therapy, IBD travelers and pregnant women with IBD. This review discusses current vaccination recommendations with updates for adult IBD patients. Centers for Disease Control and Prevention 2013 vaccination guidelines with 2014 updates and the Advisory Committee on Immunization Practices recommendations have been highlighted as a primary source of recommendations. PMID:25805924

  11. Embryonal Sarcoma of the Liver in an Adult Patient

    PubMed Central

    Lightfoot, Nicole; Nikfarjam, Mehrdad

    2012-01-01

    Undifferentiated embryonal sarcomas (UESs) are uncommon tumours that are seen predominantly in late childhood. Cases in adults are rare and generally present once a large mass develops and may be mistaken for other tumours. A case of an UES of the liver with an isolated peritoneal metastasis is described. The patient presented with a palpable mass with imaging findings suggestive of a cystic tumour. She had complete surgical resection of the liver mass and isolated peritoneal metastasis. She was tumour-free on imaging at 6 months without adjuvant chemotherapy. An UES should be considered in the differential of large cystic hepatic lesions, with aggressive surgical resection considered when possible. PMID:22690347

  12. Midface fracture in an unoperated adult patient with cleft palate

    PubMed Central

    Pathak, Sanyog; Baliga, Shridhar; Kotrashetti, Sharadaindu Mahadevappa; Pillai, Ajay

    2014-01-01

    In western countries, it is hard to find an unoperated cleft palate due to better healthcare services and awareness. Here, we present an unoperated adult case of cleft palate that had midfacial fractures following a road traffic accident. The patient's cleft lip was repaired when he was 2 years old but the palate was not operated because of poor follow-up. We would like to share the difficulties encountered in diagnosis and treatment planning for this rare kind of trauma case. After routine investigations, a palatal acrylic splint was constructed for fixation and an acceptable degree of function and aesthetics was achieved postoperatively. PMID:25150231

  13. PU.1 downregulation in murine radiation-induced acute myeloid leukaemia (AML): from molecular mechanism to human AML

    PubMed Central

    Verbiest, Tom; Bouffler, Simon; Nutt, Stephen L.; Badie, Christophe

    2015-01-01

    The transcription factor PU.1, encoded by the murine Sfpi1 gene (SPI1 in humans), is a member of the Ets transcription factor family and plays a vital role in commitment and maturation of the myeloid and lymphoid lineages. Murine studies directly link primary acute myeloid leukaemia (AML) and decreased PU.1 expression in specifically modified strains. Similarly, a radiation-induced chromosome 2 deletion and subsequent Sfpi1 point mutation in the remaining allele lead to murine radiation-induced AML. Consistent with murine data, heterozygous deletion of the SPI1 locus and mutation of the −14kb SPI1 upstream regulatory element were described previously in human primary AML, although they are rare events. Other mechanisms linked to PU.1 downregulation in human AML include TP53 deletion, FLT3-ITD mutation and the recurrent AML1-ETO [t(8;21)] and PML-RARA [t(15;17)] translocations. This review provides an up-to-date overview on our current understanding of the involvement of PU.1 in the initiation and development of radiation-induced AML, together with recommendations for future murine and human studies. PMID:25750172

  14. Supraphysiologic levels of the AML1-ETO isoform AE9a are essential for transformation.

    PubMed

    Link, Kevin A; Lin, Shan; Shrestha, Mahesh; Bowman, Melissa; Wunderlich, Mark; Bloomfield, Clara D; Huang, Gang; Mulloy, James C

    2016-08-01

    Chromosomal translocation 8;21 is found in 40% of the FAB M2 subtype of acute myeloid leukemia (AML). The resultant in-frame fusion protein AML1-ETO (AE) acts as an initiating oncogene for leukemia development. AE immortalizes human CD34(+) cord blood cells in long-term culture. We assessed the transforming properties of the alternatively spliced AE isoform AE9a (or alternative splicing at exon 9), which is fully transforming in a murine retroviral model, in human cord blood cells. Full activity was realized only upon increased fusion protein expression. This effect was recapitulated in the AE9a murine AML model. Cotransduction of AE and AE9a resulted in a strong selective pressure for AE-expressing cells. In the context of AE, AE9a did not show selection for increased expression, affirming observations of human t(8;21) patient samples where full-length AE is the dominant protein detected. Mechanistically, AE9a showed defective transcriptional regulation of AE target genes that was partially corrected at high expression. Together, these results bring an additional perspective to our understanding of AE function and highlight the contribution of oncogene expression level in t(8;21) experimental models. PMID:27457952

  15. Psychopharmacological options for adult patients with anorexia nervosa.

    PubMed

    Miniati, Mario; Mauri, Mauro; Ciberti, Agnese; Mariani, Michela Giorgi; Marazziti, Donatella; Dell'Osso, Liliana

    2016-04-01

    The aim of this review was to summarize evidence from research on psychopharmacological options for adult patients with anorexia nervosa (AN). Database searches of MEDLINE and PsycINFO (from January 1966 to January 2014) were performed, and original articles published as full papers, brief reports, case reports, or case series were included. Forty-one papers were screened in detail, and salient characteristics of pharmacological options for AN were summarized for drug classes. The body of evidence for the efficacy of pharmacotherapy in AN was unsatisfactory, the quality of observations was questionable (eg, the majority were not blinded), and sample size was often small. More trials are needed, while considering that nonresponse and nonremission are typical of patients with AN. PMID:26145463

  16. [Salmonella enteritidis: an unusual meningitis agent in an adult patient].

    PubMed

    Metan, Gökhan; Alp, Emine; Eşel, Duygu; Aygen, Bilgehan; Sümerkan, Bülent

    2005-10-01

    Salmonella species may cause wide spectrum of infections changing from enterocolitis to sepsis. However, Salmonella meningitis in adults is a rare but important clinical condition with a high mortality rate. In this report, a 71 years old male patient with Salmonella enteritidis meningitis who was followed-up with the diagnosis of immune thrombocytopenic purpura and had been administered azothioprin and prednisolone, has been presented and similar cases in the literature have been reviewed. The cerebrospinal fluid culture yielded S. enteritidis, and the isolate was intermediate susceptible to ampicillin, susceptible to cefotaxime, trimethoprim-sulphametoxasole, ciprofloxacin and chloramphenicol. Our patient was successfully treated with ceftriaxone (2 x 2 gr i.v.) and discharged with total cure. PMID:16544553

  17. CDKN2 Gene Deletion as Poor Prognosis Predictor Involved in the Progression of Adult B-Lineage Acute Lymphoblastic Leukemia Patients

    PubMed Central

    Xu, Na; Li, Yu-ling; Zhou, Xuan; Cao, Rui; Li, Huan; Lu, Qi-si; Li, Lin; Lu, Zi-yuan; Huang, Ji-xian; Sun, Jing; Liu, Qi-fa; Du, Qing-feng; Liu, Xiao-li

    2015-01-01

    Deletion of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) is well known in many hematologic malignancies, but only few reports have investigated this deletion effect on clinical prognosis. This study performed analysis of the CDKN2 deletion in 215 adult B- lineage acute lymphoblastic leukemia (B-ALL) patients, and related cytogenetic prognostic factors (BCR/ABL; E2A/PBXl; TEL/AML1; Mixed Lineage Leukemia (MLL) rearrangement; MYC, Immunoglobulin heavy locus (IGH) translocation). The prevalence of CDKN2 deletions in all study populations was 28.4%. There is no difference between patients with CDKN2 deletion and wild-type patients in sex, age, white blood cells (WBC) count, BM blast percentage, extra infiltration and induction complete remission (CR) rate. Analysis in relapse patients revealed that the distribution of CDKN2 deletion is higher in relapse patients (44.6%) than all patients (28.4%, P=0.006). Deletion of CDKN2 was significantly associated with poor outcomes including decreased overall survival (OS) (P<0.001), lower disease free-survival (DFS) (P<0.001), and increased cumulative incidence of relapse (P=0.002); Also, CDKN2 deletion was strongly associated with IGH translocation (P=0.021); and had an adverse effect on patients with BCR-ABL fusion gene or with MLL rearrangement. Patients with CDKN2 gene deletion benefited from allogenic hematopoietic stem cell transplantation (Allo-HSCT). Deletion of CDKN2 gene was commonly observed through leukemia progression and was poor prognostic marker in long-term outcomes. PMID:26516359

  18. Acute Myeloid Leukemia and Myelodysplastic Syndromes in Older Adults

    PubMed Central

    Klepin, Heidi D.; Rao, Arati V.; Pardee, Timothy S.

    2014-01-01

    Treatment of older adults with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is challenging because of disease morbidity and associated treatments. Both diseases represent a genetically heterogeneous group of disorders primarily affecting older adults, with treatment strategies ranging from supportive care to hematopoietic stem-cell transplantation. Although selected older adults can benefit from intensive therapies, as a group they experience increased treatment-related morbidity, are more likely to relapse, and have decreased survival. Age-related outcome disparities are attributed to both tumor and patient characteristics, requiring an individualized approach to treatment decision making beyond consideration of chronologic age alone. Selection of therapy for any individual requires consideration of both disease-specific risk factors and estimates of treatment tolerance and life expectancy derived from evaluation of functional status and comorbidity. Although treatment options for older adults are expanding, clinical trials accounting for the heterogeneity of tumor biology and aging are needed to define standard-of-care treatments for both disease groups. In addition, trials should include outcomes addressing quality of life, maintenance of independence, and use of health care services to assist in patient-centered decision making. This review will highlight available evidence in treatment of older adults with AML or MDS and unanswered clinical questions for older adults with these diseases. PMID:25071138

  19. MicroRNA-9 promotes proliferation of leukemia cells in adult CD34-positive acute myeloid leukemia with normal karyotype by downregulation of Hes1.

    PubMed

    Tian, Chen; You, M James; Yu, Yong; Zhu, Lei; Zheng, Guoguang; Zhang, Yizhuo

    2016-06-01

    Acute myeloid leukemia (AML) is a group of heterogeneous hematopoietic malignancies sustained by leukemic stem cells (LSCs) that can resist treatment. Previously, we found that low expression of Hes1 was a poor prognostic factor for AML. However, the activation status of Hes1 and its regulation in LSCs and leukemic progenitors (LPs) as well as normal hematopoietic stem cells (HSCs) in Hes1-low AML patients have not been elucidated. In this study, the expression of Hes1 in LSCs and LPs was analyzed in adult CD34(+) Hes1-low AML with normal karyotype and the upstream microRNA (miRNA) regulators were screened. Our results showed that the level of either Hes1 or p21 was lower in LSCs or LPs than in HSCs whereas the level of miR-9 was highest in LPs and lowest in HSCs. An inverse correlation was observed in the expression of Hes1 and miR-9. Furthermore, we validated miR-9 as one of the regulators of Hes1 by reporter gene analysis. Knockdown of miR-9 by lentivirus infection suppressed the proliferation of AML cells by the induction of G0 arrest and apoptosis in vitro. Moreover, knockdown of miR-9 resulted in decreased circulating leukemic cell counts in peripheral blood and bone marrow, attenuated splenomegaly, and prolonged survival in a xenotransplant mouse model. Our results indicate that the miR-9 plays an important role in supporting AML cell growth and survival by downregulation of Hes1 and that miR-9 has potential as a therapeutic target for treating AML. PMID:26678889

  20. Phase I Trial of Maintenance Sorafenib after Allogeneic Hematopoietic Stem Cell Transplantation for FLT3-ITD AML

    PubMed Central

    Chen, Yi-Bin; Li, Shuli; Lane, Andrew A.; Connolly, Christine; Del Rio, Candice; Valles, Betsy; Curtis, Morgan; Ballen, Karen; Cutler, Corey; Dey, Bimalangshu R.; El-Jawahri, Areej; Fathi, Amir T.; Ho, Vincent T.; Joyce, Amy; McAfee, Steven; Rudek, Michelle; Rajkhowa, Trivikram; Verselis, Sigitas; Antin, Joseph H.; Spitzer, Thomas R.; Levis, Mark; Soiffer, Robert

    2014-01-01

    The FLT3-ITD mutation is associated with a high relapse rate for patients with AML even after allogeneic hematopoietic stem cell transplantation (HSCT). Sorafenib is a tyrosine kinase inhibitor which inhibits the FLT3 tyrosine kinase and has shown encouraging activity in FLT3-ITD AML. We conducted a phase I trial of maintenance sorafenib after HSCT in patients with FLT3-ITD AML (ClinicalTrials.gov NCT01398501). Patients received a variety of conditioning regimens and graft sources. A dose escalation 3+3 cohort design was used to define the maximum tolerated dose (MTD) with an additional 10 patients treated at the MTD. Sorafenib was initiated between days 45 and 120 after HSCT continued for twelve 28-day cycles. Twenty-two patients were enrolled (status at HSCT: CR1=16, CR2=3, refractory=3). The MTD was established at 400 mg BID with one DLT observed (pericardial effusion). Two patients died of transplant-related causes, both unrelated to sorafenib. Two patients stopped sorafenib after relapse and 5 stopped due to attributable toxicities after the DLT period. Median follow-up for surviving patients is 16.7 months after HSCT (range, 8.1–35.0). There was one case of grade II acute GVHD after starting sorafenib and the 12-month cumulative incidence of chronic GVHD was 38% (90% CI, 21%–56%). For all patients, one-year progression-free survival (PFS) is 85% (90% CI, 66%–94%) and one-year overall survival (OS) is 95% (90% CI, 79%–99%) after HSCT. For patients in CR1 / CR2 prior to HSCT (n=19), one-year PFS is 95% (90% CI, 76%–99%) and one-year OS is 100% with only one patient who has relapsed. Sorafenib is safe after HSCT for FLT3-ITD AML and merits further investigation for the prevention of relapse. PMID:25239228

  1. Intravenous fish oil in adult intensive care unit patients.

    PubMed

    Heller, Axel R

    2015-01-01

    Omega-3 fatty acids contained in fish oils have shown efficacy in the treatment of chronic and acute inflammatory diseases due to their pleiotropic effects on inflammatory cell signalling pathways. In a variety of experimental and clinical studies, omega-3 fatty acids attenuated hyperinflammatory conditions and induced faster recovery. This chapter will shed light on the effects of intravenous fish oil in adult intensive care unit (ICU) patients and will discuss clinical data and recent meta-analyses on the topic. While significant beneficial effects on infection rates and the lengths of ICU and hospital stays have concordantly been identified in three recent meta-analyses on non-ICU surgical patients, the level of evidence is not so clear for critically ill patients. Three meta-analyses published in 2012 or 2013 explored data on the ICU population. Although the present data suggest the consideration of enteral nutrition enriched with fish oil, borage oil and antioxidants in mild to severe acute respiratory distress syndrome, only one of the three meta-analyses found a trend (p = 0.08) of lower mortality in ICU patients receiving intravenous omega-3 fatty acids. Two of the meta-analyses indicated a significantly shorter hospital stay (5.17-9.49 days), and one meta-analysis found a significant reduction in ICU days (1.92). As a result of these effects, cost savings were postulated. Unlike in surgical patients, the effects of fish oil on infection rates were not found to be statistically significant in ICU patients, and dose-effect relationships were not established for any cohort. Thus, obvious positive secondary outcome effects with intravenous fish oil have not yet been shown to transfer to lower mortality in critically ill patients. There is a need for adequately powered, well-planned and well-conducted randomized trials to give clear recommendations on the individual utility and dosage of intravenous omega-3 fatty acids in critical illness. PMID:25471809

  2. High Bad and Bax mRNA expression correlate with negative outcome in acute myeloid leukemia (AML).

    PubMed

    Köhler, T; Schill, C; Deininger, M W; Krahl, R; Borchert, S; Hasenclever, D; Leiblein, S; Wagner, O; Niederwieser, D

    2002-01-01

    The search for molecular markers in AML that allow prediction of outcome has recently focused on genes involved in the regulation of programmed cell death (PCD). The aim of our study was to determine whether mRNA levels of Mdm-2, Bcl-2, Bcl-x(L), Bad, and Bax are independent prognostic parameters for outcome. Transcript levels were analyzed by real-time quantitative RT-PCR in 232 samples collected either at diagnosis or following induction chemotherapy (ICT). Multivariate COX regression analysis adjusted for chemotherapy protocol, de novo vs secondary AML, and de novo vs relapsed AML indicated: (1) At diagnosis, high expression of Bad (P = 0.015) and even more so high Bax and Bad levels (P = 0.018) predicted adverse outcome, regardless of the response to ICT. In patients who subsequently failed to enter complete remission (CR), high levels of Bad, Bax and Bax high/Bad high were associated with an increased relative risk (RR) to die from tumor (RR = 5.0 for Bad, 3.4 for Bax and 6.14 for Bax high/Bad high). (2) Following ICT, high expression of Bax (P= 0.005) and high Bcl-2/Bax ratios (P = 0.004) were independent predictors of unfavorable outcome, regardless of response to ICT. We conclude that high levels of Bax and Bad correlate with poor outcome, particularly in patients who do not enter CR and may serve as prognostic markers in AML. PMID:11840259

  3. Co-inhibition of NF-κB and JNK is synergistic in TNF-expressing human AML.

    PubMed

    Volk, Andrew; Li, Jing; Xin, Junping; You, Dewen; Zhang, Jun; Liu, Xinli; Xiao, Yechen; Breslin, Peter; Li, Zejuan; Wei, Wei; Schmidt, Rachel; Li, Xingyu; Zhang, Zhou; Kuo, Paul C; Nand, Sucha; Zhang, Jianke; Chen, Jianjun; Zhang, Jiwang

    2014-06-01

    Leukemic stem cells (LSCs) isolated from acute myeloid leukemia (AML) patients are more sensitive to nuclear factor κB (NF-κB) inhibition-induced cell death when compared with hematopoietic stem and progenitor cells (HSPCs) in in vitro culture. However, inadequate anti-leukemic activity of NF-κB inhibition in vivo suggests the presence of additional survival/proliferative signals that can compensate for NF-κB inhibition. AML subtypes M3, M4, and M5 cells produce endogenous tumor necrosis factor α (TNF). Although stimulating HSPC with TNF promotes necroptosis and apoptosis, similar treatment with AML cells (leukemic cells, LCs) results in an increase in survival and proliferation. We determined that TNF stimulation drives the JNK-AP1 pathway in a manner parallel to NF-κB, leading to the up-regulation of anti-apoptotic genes in LC. We found that we can significantly sensitize LC to NF-κB inhibitor treatment by blocking the TNF-JNK-AP1 signaling pathway. Our data suggest that co-inhibition of both TNF-JNK-AP1 and NF-κB signals may provide a more comprehensive treatment paradigm for AML patients with TNF-expressing LC. PMID:24842373

  4. Co-inhibition of NF-κB and JNK is synergistic in TNF-expressing human AML

    PubMed Central

    Volk, Andrew; Li, Jing; Xin, Junping; You, Dewen; Zhang, Jun; Liu, Xinli; Xiao, Yechen; Breslin, Peter; Li, Zejuan; Wei, Wei; Schmidt, Rachel; Li, Xingyu; Zhang, Zhou; Kuo, Paul C.; Nand, Sucha; Zhang, Jianke; Chen, Jianjun

    2014-01-01

    Leukemic stem cells (LSCs) isolated from acute myeloid leukemia (AML) patients are more sensitive to nuclear factor κB (NF-κB) inhibition-induced cell death when compared with hematopoietic stem and progenitor cells (HSPCs) in in vitro culture. However, inadequate anti-leukemic activity of NF-κB inhibition in vivo suggests the presence of additional survival/proliferative signals that can compensate for NF-κB inhibition. AML subtypes M3, M4, and M5 cells produce endogenous tumor necrosis factor α (TNF). Although stimulating HSPC with TNF promotes necroptosis and apoptosis, similar treatment with AML cells (leukemic cells, LCs) results in an increase in survival and proliferation. We determined that TNF stimulation drives the JNK–AP1 pathway in a manner parallel to NF-κB, leading to the up-regulation of anti-apoptotic genes in LC. We found that we can significantly sensitize LC to NF-κB inhibitor treatment by blocking the TNF–JNK–AP1 signaling pathway. Our data suggest that co-inhibition of both TNF–JNK–AP1 and NF-κB signals may provide a more comprehensive treatment paradigm for AML patients with TNF-expressing LC. PMID:24842373

  5. Prosthodontic treatment of the edentulous adult cleft palate patient.

    PubMed

    Sykes, Leanne M

    2003-03-01

    Clefts of the upper lip and plate are relatively common, yet dental treatment of these patients is still very poor and many grow up suffering dental neglect. Dental practitioners should become involved in the treatment team as dental needs are present from birth to death. Adult cleft patients often need tooth replacement with obturation of any residual clefts. They are best treated with tooth-supported removable appliances including partial and complete overdentures, thus preservation of their natural dentition is desirable. Edentulous cleft palate patients present with restorative difficulties due to their compromised maxillary arches as well as the presence of scar tissue in their palates and lips. An outline of these complications and guidelines for their treatment is illustrated in the form of three case reports from members of one family all presenting with varying cleft lip and palate defects. This article highlights the need for dental students to be exposed to dentally compromised patients so that they will feel confident enough to treat them in private practice. PMID:12800267

  6. Multiple Functional Domains of AML1: PU.1 and C/EBPα Synergize with Different Regions of AML1

    PubMed Central

    Petrovick, Martha S.; Hiebert, Scott W.; Friedman, Alan D.; Hetherington, Christopher J.; Tenen, Daniel G.; Zhang, Dong-Er

    1998-01-01

    Control elements of many genes are regulated by multiple activators working in concert to confer the maximal level of expression, but the mechanism of such synergy is not completely understood. The promoter of the human macrophage colony-stimulating factor (M-CSF) receptor presents an excellent model with which we can study synergistic, tissue-specific activation for two reasons. First, myeloid-specific expression of the M-CSF receptor is regulated transcriptionally by three factors which are crucial for normal hematopoiesis: PU.1, AML1, and C/EBPα. Second, these proteins interact in such a way as to demonstrate at least two examples of synergistic activation. We have shown that AML1 and C/EBPα activate the M-CSF receptor promoter in a synergistic manner. As we report here, AML1 also synergizes, and interacts physically, with PU.1. Detailed analysis of the physical and functional interaction of AML1 with PU.1 and C/EBPα has revealed that the proteins contact one another through their DNA-binding domains and that AML1 exhibits cooperative DNA binding with C/EBPα but not with PU.1. This difference in DNA-binding abilities may explain, in part, the differences observed in synergistic activation. Furthermore, the activation domains of all three factors are required for synergistic activation, and the region of AML1 required for synergy with PU.1 is distinct from that required for synergy with C/EBPα. These observations present the possibility that synergistic activation is mediated by secondary proteins contacted through the activation domains of AML1, C/EBPα, and PU.1. PMID:9632776

  7. Systematic review of surgical treatment techniques for adult and pediatric patients with pectus excavatum

    PubMed Central

    2014-01-01

    This compares outcome measures of current pectus excavatum (PEx) treatments, namely the Nuss and Ravitch procedures, in pediatric and adult patients. Original investigations that stratified PEx patients based on current treatment and age (pediatric = 0–21; adult 17–99) were considered for inclusion. Outcome measures were: operation duration, analgesia duration, blood loss, length of stay (LOS), outcome ratings, complications, and percentage requiring reoperations. Adult implant patients (18.8%) had higher reoperation rates than adult Nuss or Ravitch patients (5.3% and 3.3% respectively). Adult Nuss patients had longer LOS (7.3 days), more strut/bar displacement (6.1%), and more epidural analgesia (3 days) than adult Ravitch patients (2.9 days, 0%, 0 days). Excluding pectus bar and strut displacements, pediatric and adult Nuss patients tended to have higher complication rates (pediatric - 38%; adult - 21%) compared to pediatric and adult Ravitch patients (12.5%; 8%). Pediatric Ravitch patients clearly had more strut displacements than adult Ravitch patients (0% and 6.4% respectively). These results suggest significantly better results in common PEx surgical repair techniques (i.e. Nuss and Ravitch) than uncommon techniques (i.e. Implants and Robicsek). The results suggest slightly better outcomes in pediatric Nuss procedure patients as compared with all other groups. We recommend that symptomatic pediatric patients with uncomplicated PEx receive the Nuss procedure. We suggest that adult patients receive the Nuss or Ravitch procedure, even though the long-term complication rates of the adult Nuss procedure require more investigation. PMID:24506826

  8. Preference for One or Two Hearing Aids among Adult Patients

    PubMed Central

    Cox, Robyn M; Schwartz, Kathryn S.; Noe, Colleen M.; Alexander, Genevieve C.

    2010-01-01

    Objectives Most practitioners believe that use of two hearing aids is the ideal fitting for adults with bilateral symmetrical hearing loss. However, previous research has consistently shown that a substantial proportion of these patients actually prefer to use only one hearing aid. The current study explored whether this pattern of preferences is seen with technologically advanced hearing aids. In addition, a selection of variables that were available pre-fitting were used to attempt to predict which patients will prefer one hearing aid rather than two. Design The study was designed as a 12-week field trial including structured and unstructured use of one and two hearing aids. Ninety-four subjects with mild to moderate bilaterally symmetrical hearing loss were bilaterally fit with 2005-2007 era hearing aids. Potential predictors included demographic, audiometric, auditory lifestyle, personality, and binaural processing variables. After the field trial, each subject stated his/her preference for one or two hearing aids and completed three self-report outcome questionnaires for their preferred fitting. Results Previous research was confirmed with modern technology hearing aids: after the field trial 46% of the subjects preferred to use one hearing aid rather than two. Subjects who preferred two hearing aids tended to report better real-world outcomes than those who preferred one. Subjects who reported more hearing problems in daily life, who experienced more binaural loudness summation, and whose ears were more equivalent in dichotic listening were more likely to prefer to use two hearing aids. Contrary to conventional wisdom (ideas that are generally accepted as true), audiometric hearing loss and auditory lifestyle were not predictive of aiding preference. However, the best predictive approach from these data yielded accurate predictions for only two-thirds of subjects. Conclusions Evidence-based practice calls for a conscientious melding of current evidence

  9. [Clinical efficacy of decitabine combined with modified CAG regimen for relapsed-refractory acute myeloid leukemia with AML1-ETO⁺].

    PubMed

    Jing, Yu; Zhu, Cheng-Ying; Zhang, Qi; Niu, Jian-Hua; Yang, Hua; Liu, Shi-Yan; Zhu, Hai-Yan; Yu, Li

    2014-10-01

    This study was aimed to investigate the clinical characteristics of relapsed-refractory acute myeloid leukemia (AML) with AML1-ETO⁺, and its therapeutic efficacy and side effects when decitabine combined with modified CAG regimen was used. Clinical data of 5 cases of AML with AML1-ETO⁺ from January 2013 to Agust 2013 were analyzed retrospectively. The analyzed data included age, sex, initial symptoms, peripheral blood and bone marrow characteristics. Meanwhile, the therapeutic effecacy and side effects of decitabine combined with modified CAG regimen were evaluated. The 5 patients were with median age of 35 (17-43) years. Among these 5 patients, 2 patients were relapsed and other 3 patients were relapsed-refractory patients, their median white blood cell count was 12.55 (7.8-66.55) × 10⁹/L, median platelets count was 44 (20-72) × 10⁹/L, median hemoglobin level was 110 (77-128) g/L, median lactate dehydrogenase level was 312.9 U/L (123.6-877.8) at the initial diagnosis. The results showed that after decitabine combined with modified CAG regimen was administered, 4 patients achieved complete remission, 1 patient did not achieve remission, the overall remission rate was 80% (4/5). The main side effects of this regimen was myelosuppression, these were no new lung infection and other serious complications, one case without complete remission treated with FLAG once again died of heart failure when being mobilized for transplantation. It is concluded that according to preliminary results of decitabine combined with modified CAG regimen for relapsed and refractory AML patients with AML1-ETO⁺ displays higher remission rate and lower side effects, which worthy to further explore for clinal application. PMID:25338566

  10. Allogeneic hematopoietic stem cell transplantation could improve survival of cytogenetically normal adult acute myeloid leukemia patients with DNMT3A mutations.

    PubMed

    Xu, Yang; Sun, Yanjun; Shen, Hongjie; Ding, Lin; Yang, Zhen; Qiu, Huiying; Sun, Aining; Chen, Suning; Wu, Depei

    2015-11-01

    DNMT3A mutations are frequent in cytogenetically normal acute myeloid leukemia (cn-AML) patients and associated with poor survival. The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in DNMT3A(mut) cn-AML patients remains unclear. In this study, we retrospectively analyzed the prognostic impact of DNMT3A mutations and explored the role of allo-HSCT in 308 cn-AML patients who received consolidation of intensive chemotherapy or allo-HSCT in our center from March 2005 to May 2014. In the whole cohort, 63 patients (20.5%) were identified with DNMT3A exon 23 mutations and R882H was the most frequent variant. DNMT3A(mut) patients had shorter overall survival (3-year OS: 31.9% vs. 52.0%, P = 0.009) and disease-free survival (3-year DFS: 21.8% vs. 40.1%, P = 0.004) compared with DNMT3A(wt) patients. Based on FLT3/NPM1/CEBPA mutations, 308 cn-AML patients were divided into favorable/intermediate group (n = 262) and unfavorable group (n = 46). There were no significant differences in 3-year OS and 3-year DFS between DNMT3A(mut) and DNMT3A(wt) patients in both favorable/intermediate and unfavorable groups. Additionally, in multivariate analysis, DNMT3A mutation remained an independent adverse prognostic factor for the survival. In the DNMT3A(mut) cohort, 23 complete remission (CR) patients received allo-HSCT consolidation and 32 CR patients received chemotherapy consolidation, dramatic differences were observed in 3-year OS (51.7% vs. 28.9%, P = 0.048) and 3-year DFS (41.6% vs. 14.9%, P = 0.024) between allo-HSCT group and chemotherapy group. Collectively, DNMT3A mutation is a poor prognostic factor for cn-AML patients and allo-HSCT could improve survival of cn-AML patients with DNMT3A mutations. PMID:26223865

  11. AGS67E, an Anti-CD37 Monomethyl Auristatin E Antibody–Drug Conjugate as a Potential Therapeutic for B/T-Cell Malignancies and AML: A New Role for CD37 in AML

    PubMed Central

    Pereira, Daniel S.; Guevara, Claudia I.; Jin, Liqing; Mbong, Nathan; Verlinsky, Alla; Hsu, Ssucheng J.; Aviña, Hector; Karki, Sher; Abad, Joseph D.; Yang, Peng; Moon, Sung-Ju; Malik, Faisal; Choi, Michael Y.; An, Zili; Morrison, Kendall; Challita-Eid, Pia M.; Doñate, Fernando; Joseph, Ingrid B.J.; Kipps, Thomas J.; Dick, John E.; Stover, David R.

    2015-01-01

    CD37 is a tetraspanin expressed on malignant B cells. Recently, CD37 has gained interest as a therapeutic target. We developed AGS67E, an antibody–drug conjugate that targets CD37 for the potential treatment of B/T-cell malignancies. It is a fully human monoclonal IgG2 antibody (AGS67C) conjugated, via a protease-cleavable linker, to the microtubule-disrupting agent mono-methyl auristatin E (MMAE). AGS67E induces potent cytotoxicity, apoptosis, and cell-cycle alterations in many non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) cell lines and patient-derived samples in vitro. It also shows potent antitumor activity in NHL and CLL xenografts, including Rituxan-refractory models. During profiling studies to confirm the reported expression of CD37 in normal tissues and B-cell malignancies, we made the novel discovery that the CD37 protein was expressed in T-cell lymphomas and in AML. AGS67E bound to >80% of NHL and T-cell lymphomas, 100% of CLL and 100% of AML patient-derived samples, including CD34+CD38− leukemic stem cells. It also induced cytotoxicity, apoptosis, and cell-cycle alterations in AML cell lines and antitumor efficacy in orthotopic AML xenografts. Taken together, this study shows not only that AGS67E may serve as a potential therapeutic for B/T-cell malignancies, but it also demonstrates, for the first time, that CD37 is well expressed and a potential drug target in AML. PMID:25934707

  12. Attachment and Parenting in Adult Patients with Anxiety Disorders

    PubMed Central

    Picardi, Angelo; Caroppo, Emanuele; Fabi, Elisa; Proietti, Serena; Gennaro, Giancarlo Di; Meldolesi, Giulio Nicolò; Martinotti, Giovanni

    2013-01-01

    Background: The literature suggests that dysfunctional parenting and insecure attachment may increase risk of anxiety-related psychopathology. This study aimed at testing the association between anxiety disorders, attachment insecurity and dysfunctional parenting while controlling for factors usually not controlled for in previous studies, such as gender, age, and being ill. Methods: A sample of 32 non-psychotic inpatients with SCID-I diagnosis of an anxiety disorder, either alone or in comorbidity, was compared with two age- and sex-matched control groups consisting of 32 non-clinical participants and 32 in-patients with drug-resistant epilepsy. Study measures included the Experience in Close Relationships questionnaire (ECR) and the Parental Bonding Instrument (PBI). Results: The patients with anxiety disorders scored significantly higher on attachment-related anxiety and avoidance than patients with drug-resistant epilepsy and non-clinical participants. These findings were independent of comorbidity for mood disorders. ECR scores did not differ among diagnostic subgroups (generalized anxiety disorder, panic disorder, other anxiety disorders). Patients with anxiety disorders scored significantly lower on PBI mother’s care and borderline significantly lower on PBI father's care than patients with drug-resistant epilepsy. Conclusions: Although limitations such as the relatively small sample size and the cross-sectional nature suggest caution in interpreting these findings, they are consistent with the few previous adult studies performed on this topic and corroborate Bowlby's seminal hypothesis of a link between negative attachment-related experiences, attachment insecurity, and clinical anxiety. Attachment theory provides a useful theoretical framework for integrating research findings from several fields concerning the development of anxiety disorders and for planning therapeutic interventions. PMID:24155770

  13. [15-year results following implantation of a stem type AML hip prosthesis].

    PubMed

    Schwerter, K; Meyenberg, A; Sander, K; Layher, F; Roth, A

    2013-06-01

    The trend in arthroplasty of the hip joint to implement new models is partly based on theoretical considerations. In order to verify to which extent the philosophy of individual models is ultimately successful, the presentation of long-term results is required. In the years 1991 and 1992, 433 patients with primary implantation of an uncemented total hip replacement in primary coxarthrosis with a stem type AML (anatomic medullary locking) were treated surgically. 283 of them got a cementless cup type Duraloc. In 311 (71.8 %) patients the mean survival rate of the prosthesis could be determined at a mean follow-up of 15.5 years. 145 (33.5 %) patients were followed up completely both clinically and radiologically. Radiographically, the stem position, changes of the periprosthetic bone of the stem and the cup, as well as the wear of the cups were examined. The cumulative survival rate of the AML stem after 15.5 years was 97.5 %, of the Duraloc cup 88.2 %. The clinical results of the hip scores according to Harris and Merle d'Aubigné were good and excellent and patient satisfaction was very high. There was no relationship between stem position, stress shielding and surrounding lyses at the femur and the acetabulum and survival of stem or cup. There was no correlation between inlay wear and survival of the Duraloc cup. A subsiding of the stem in 2 cases had no effect on the clinical symptoms and quality of life. The press-fit implanted AML stem and the Duraloc cup revealed very good results during the investigation period. Like other implants, the survival rate is limited at the presented implant mainly by the cup. PMID:23696163

  14. Primary Care for the Older Adult Patient: Common Geriatric Issues and Syndromes.

    PubMed

    Thompson, Katherine; Shi, Sandra; Kiraly, Carmela

    2016-06-01

    Older adults are the fastest growing segment of the US population and the majority of older adults are women. Primary care for the older adult patient requires a wide variety of skills, reflecting the complexity and heterogeneity of this patient population. Individualizing care through consideration of patients' goals, medical conditions, and prognosis is paramount. Quality care for the older adult patient requires familiarity with common geriatric syndromes, such as dementia, falls, and polypharmacy. In addition, developing the knowledge and communication skills necessary for complex care and end-of-life care planning is essential. PMID:27212097

  15. [Comparison of serum trace element spectrum of liver cancer patients and healthy adults].

    PubMed

    Yin, D Z

    1990-05-01

    The contents of 15 trace elements in the sera of 30 liver cancer patients and 30 healthy adults were assayed by ICP-AES method. The data obtained were analysed by routine statistical tests, multi-variate discrimination analysis, multi-variate stepwise regression analysis and non-linear mapping algorithm. The results showed that the contents of copper, vanadium, cadmium, stannum, cobalt, nickel in liver cancer patients were significantly higher than those in healthy adults. The serum trace element spectrum of liver cancer patients was different from that of healthy adults. Hence, the liver cancer patients could be differentiated from healthy adults by serum trace element spectrum. PMID:2249593

  16. Humidification during Mechanical Ventilation in the Adult Patient

    PubMed Central

    Al Ashry, Haitham S.; Modrykamien, Ariel M.

    2014-01-01

    Humidification of inhaled gases has been standard of care in mechanical ventilation for a long period of time. More than a century ago, a variety of reports described important airway damage by applying dry gases during artificial ventilation. Consequently, respiratory care providers have been utilizing external humidifiers to compensate for the lack of natural humidification mechanisms when the upper airway is bypassed. Particularly, active and passive humidification devices have rapidly evolved. Sophisticated systems composed of reservoirs, wires, heating devices, and other elements have become part of our usual armamentarium in the intensive care unit. Therefore, basic knowledge of the mechanisms of action of each of these devices, as well as their advantages and disadvantages, becomes a necessity for the respiratory care and intensive care practitioner. In this paper, we review current methods of airway humidification during invasive mechanical ventilation of adult patients. We describe a variety of devices and describe the eventual applications according to specific clinical conditions. PMID:25089275

  17. Research proposal: evaluation of ART in adult patients.

    PubMed

    Zanata, Régia Luzia

    2006-01-01

    The primary objective of the Atraumatic Restorative Treatment (ART) is to reduce the indication of tooth extraction by means of a low-cost technique. Considering the difficulties of Brazilian public services to meet the demand of care of the low-income population, with lack of care to the adult population, which usually receives only emergency care, the aim of this study is to assess the performance of high-viscosity glass ionomer cements accomplished by the modified atraumatic restorative treatment in one- and multiple-surface cavities, compared to the conventional restorative approach. It will be analyzed the clinical performance of the materials; cost (material and human resources); patient satisfaction with the treatment received; and preventive effect of treatment. PMID:19089083

  18. Adult patients with Fontan circulation: What we know and how to manage adults with Fontan circulation?

    PubMed

    Ohuchi, Hideo

    2016-09-01

    Most of patients after the Fontan operation can reach their adulthood, however, the management strategy for this complex pathophysiology has not been yet established. In general, elevated central venous pressure (CVP) and low cardiac output (CO) due to impaired ventricular preload characterize the Fontan circulation and the ideal hemodynamics could be a combination of a lower CVP with a higher CO. Thus, preserved functional systemic ventricle with low pulmonary artery resistance is thought to be crucial for better long-term outcome. However, on the other hand, because of the unique hemodynamics, these patients have significantly higher incidence of complications, sequelae, and even mortality. The major complications are supraventricular arrhythmias, heart failure, and Fontan-related problems, including protein-losing enteropathy and pulmonary arteriovenous fistulae, both of which are refractory to the treatments, and most of these "Fontan inconveniences" increase as patients age. In addition, one of the recent emerging problems is Fontan-associated liver disease that includes liver cirrhosis and hepatocellular carcinoma. Furthermore, women with Fontan circulation also reach childbearing age and there have been increasing numbers of reports showing a high incidence of pregnancy-associated complications. All these problems may be a part of "Fontan inconveniences" because most of the current Fontan patients are still "young" i.e. in their twenties or thirties and it may be not surprising that more new Fontan-associated pathophysiology emerges as patients age. Recent evidence reminds us of the concept that adult Fontan pathophysiology is not just a cardiovascular disease, rather, a multiorgan disease with many interactions between cardiovascular and non-cardiovascular organs. Therefore, a multidisciplinary approach is mandatory to take care of and anticipate the better long-term outcome. PMID:27134136

  19. Chronic GVHD induced GVL effect after unmanipulated haploidentical hematopoietic SCT for AML and myelodysplastic syndrome.

    PubMed

    Mo, X-D; Xu, L-P; Zhang, X-H; Liu, D-H; Wang, Y; Chen, H; Yan, C-H; Chen, Y-H; Han, W; Wang, F-R; Wang, J-Z; Liu, K-Y; Huang, X-J

    2015-01-01

    The aim of this study was to investigate the impact of occurrence of chronic GVHD (cGVHD) and its severity on transplantation outcomes in a consecutive cohort of AML and myelodysplastic syndrome (MDS) patients who received unmanipulated haploidentical hematopoietic SCT (haplo-HSCT; n=324). The cumulative incidence of relapse was significantly decreased in patients with cGVHD compared with the non-cGVHD group (1 year: 3.2% vs 11.9%, P=0.002; 3 years: 6.0% vs 16.3%, P=0.002), particularly in those with mild cGVHD. The cumulative incidence of non-relapse mortality was comparable between patients with and without cGVHD. The probabilities of disease-free survival (DFS) were significantly better in patients with cGVHD than in those in the non-cGVHD group (1 year: 90.5% vs 78.5%, P=0.002; 3 years: 86.5% vs 71.5%, P<0.001), particularly in those with mild or moderate cGVHD; however, no significant impact of severe cGVHD on DFS was seen. Our findings highlight the close relationship between cGVHD and the immune-mediated GVL effect in patients with AML and MDS receiving unmanipulated haplo-HSCT; however, only mild or moderate cGVHD was associated with a lower risk of relapse translating into improved DFS. PMID:25387095

  20. Achieving stringent CR is essential before reduced-intensity conditioning allogeneic hematopoietic cell transplantation in AML.

    PubMed

    Ustun, C; Wiseman, A C; Defor, T E; Yohe, S; Linden, M A; Oran, B; Burke, M; Warlick, E; Miller, J S; Weisdorf, D

    2013-11-01

    Reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (allo-HCT) can cure patients with AML in CR. However, relapse after RIC allo-HCT may indicate heterogeneity in the stringency of CR. Strict definition of CR requires no evidence of leukemia by both morphologic and flow cytometric criteria. We re-evaluated 85 AML patients receiving RIC allo-HCT in CR to test if a strict definition of CR had direct implications for the outcome. These patients had leukemia immunophenotype documented at diagnosis and analyzed at allo-HCT. Eight (9.4%) had persistent leukemia by flow cytometric criteria at allo-HCT. The patients with immunophenotypic persistent leukemia had a significantly increased relapse (hazard ratio (HR): 3.7; 95% confidence interval (CI): 1.3-10.3, P=0.01) and decreased survival (HR: 2.9; 95% CI: 1.3-6.4, P<0.01) versus 77 patients in CR by both morphology and flow cytometry. However, the pre-allo-HCT bone marrow (BM) blast count (that is, 0-4%) was not significantly associated with risks of relapse or survival. These data indicate the presence of leukemic cells, but not the BM blast count affects survival. A strict morphologic and clinical lab flow cytometric definition of CR predicts outcomes after RIC allo-HCT, and therefore is critical to achieve at transplantation. PMID:23933764

  1. Potential Harm of Prophylactic Platelet Transfusion in Adult Dengue Patients

    PubMed Central

    Lee, Tau-Hong; Wong, Joshua G. X.; Leo, Yee-Sin; Thein, Tun-Linn; Ng, Ee-Ling; Lee, Linda K.; Lye, David C.

    2016-01-01

    Background Thrombocytopenia is a hallmark of dengue infection, and bleeding is a dreaded complication of dengue fever. Prophylactic platelet transfusion has been used to prevent bleeding in the management of dengue fever, although the evidence for its benefit is lacking. In adult dengue patients with platelet count <20,000/mm3 without bleeding, we aimed to assess if prophylactic platelet transfusion was effective in reducing clinical bleeding and other outcomes. Method We conducted a retrospective non-randomised observational study of dengue patients with platelet count < 20,000/mm3 without bleeding (except petechiae) admitted to Tan Tock Seng Hospital from January 2005 to December 2008. Baseline characteristics and clinical outcomes were compared between the non-transfused vs. transfused groups. Outcomes studied were clinical bleeding, platelet increment, hospital length of stay, intensive care unit admission and death. Results Of the 788 patients included, 486 received prophylactic platelet transfusion. There was no significant difference in the presence of clinical bleeding in the two groups (18.2% in non-transfused group vs. 23.5% in transfused group; P = 0.08). Patients in the transfused group took a median of 1 day longer than the non-transfused group to increase their platelet count to 50,000/mm3 or more (3 days vs. 2 days, P <0.0001). The median duration of hospital stay in the non-transfused group was 5 days vs. 6 days in the transfused group (P< 0.0001). There was no significant difference in the proportion requiring ICU admission (non-transfused 0.66% vs. transfused 1.23%, P = 0.44) and death (non-transfused 0% vs. transfused 0.2%, P = 0.43). Conclusion Platelet transfusion in absence of bleeding in adult dengue with platelet count <20,000/mm3 did not reduce bleeding or expedite platelet recovery. There was potential harm by slowing recovery of platelet count to >50,000/mm3 and increasing length of hospitalization. PMID:27015272

  2. Population Pharmacokinetics of Benznidazole in Adult Patients with Chagas Disease

    PubMed Central

    Aldasoro, E.; Guerrero, L.; Posada, E.; Serret, N.; Mejía, T.; Urbina, J. A.; Gascón, J.

    2015-01-01

    The aim of the present study was to build a population pharmacokinetic (popPK) model to characterize benznidazole (BNZ) pharmacokinetics in adults with chronic Chagas disease. This study was a prospective, open-label, single-center clinical trial approved by the local ethics committee. Patients received BNZ at 2.5 mg/kg of body weight/12 h (Abarax, Elea Laboratory, Argentina) for 60 days. Plasma BNZ samples were taken several times during the study and analyzed by high-performance liquid chromatography with UV-visible detection (HPLC-UV). The popPK analysis was done with NONMEMv.7.3. Demographic and biological data were tested as covariates. Intraindividual, interoccasion, and residual variabilities were modeled. Internal and external validations were completed to assess the robustness of the model. Later on, simulations were performed to generate BNZ concentration-time course profiles for different dosage regimens. A total of 358 plasma BNZ concentrations from 39 patients were included in the analysis. A one-compartment PK model characterized by clearance (CL/F) and the apparent volume of distribution (V/F), with first-order absorption (Ka) and elimination, adequately described the data (CL/F, 1.73 liters/h; V/F, 89.6 liters; and Ka, 1.15 h−1). No covariates were found to be significant for CL/F and V/F. Internal and external validations of the final model showed adequate results. Data from simulations revealed that a dose of 2.5 mg/kg/12 h might lead to overexposure in most patients. A lower dose (2.5 mg/kg/24 h) was able to achieve trough BNZ plasma concentrations within the accepted therapeutic range of 3 to 6 mg/liter. In summary, we developed a population PK model for BNZ in adults with chronic Chagas disease. Dosing simulations showed that a BNZ dose of 2.5 mg/kg/24 h will adequately keep BNZ trough plasma concentrations within the recommended target range for the majority of patients. (This study has been registered at EudraCT under number 2011

  3. Metabolic aspects of adult patients with nonalcoholic fatty liver disease.

    PubMed

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-08-21

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD. PMID:27610012

  4. Metabolic aspects of adult patients with nonalcoholic fatty liver disease

    PubMed Central

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD. PMID:27610012

  5. Genetic risk factors of cisplatin induced ototoxicity in adult patients.

    PubMed

    Talach, T; Rottenberg, J; Gal, B; Kostrica, R; Jurajda, M; Kocak, I; Lakomy, R; Vogazianos, E

    2016-01-01

    Ototoxicity is an important adverse effect of using Cisplatin (cis-diamminedichloroplatinum) (CDDP) as a form of chemotherapy. The clinical picture of CDDP induced ototoxicity includes perceptive hearing impairment (reversible or permanent) and tinnitus. Ototoxicity manifests with considerable variability between patients. The objective of this prospective study was to investigate a possible genetic background to this variability. We assessed ototoxicity induced by therapeutic doses of CDDP in adult patients with germinative testicular tumors, or other tumors treated with an identical CDDP dosage scheme. Audiological examination before, during and after the treatment has shown deterioration in hearing; first in the high-frequencies and with increased CDDP cumulative doses, impairment in other frequencies as well. Occurrence of tinnitus was not dependent on the administered dose of CDDP, or the other risk factors examined in this study. The association of CDDP induced ototoxicity with genetic polymorphisms in candidate genes was examined. Our study has demonstrated an association of early onset of CDDP induced ototoxicity with the presence of two copies of GSTT1 gene (p=0,009) and with T allele of rs9332377 polymorphism in COMT gene (p=0,001). PMID:26774148

  6. Using Adult Learning Concepts To Assist Patients in Completing Advance Directives.

    ERIC Educational Resources Information Center

    Meyer, Rose Mary

    2000-01-01

    Advance directives that enable individuals to control their health care are underused due to lack of patient knowledge. Nurses can teach patients about them using adult learning principles, transformation theory, and skills for learning how to learn. (SK)

  7. Cystic Fibrosis below the Diaphragm: Abdominal Findings in Adult Patients.

    PubMed

    Lavelle, Lisa P; McEvoy, Sinead H; Ni Mhurchu, Elaine; Gibney, Robert G; McMahon, Colm J; Heffernan, Eric J; Malone, Dermot E

    2015-01-01

    Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in the white population. Mutation of the CF transmembrane conductance regulator gene on chromosome 7 results in production of abnormally viscous mucus and secretions in the lungs of patients with CF. A similar pathologic process occurs in the gastrointestinal tract, pancreas, and hepatobiliary system. Inspissated mucus causes luminal obstruction and resultant clinical and radiologic complications associated with the disease process. Pancreatic involvement can result in exocrine and endocrine insufficiency, pancreatic atrophy, fatty replacement, or lipomatous pseudohypertrophy. Acute and chronic pancreatitis, pancreatic calcification, cysts, and cystosis also occur. Hepatic manifestations include hepatic steatosis, focal biliary and multilobular cirrhosis, and portal hypertension. Biliary complications include cholelithiasis, microgallbladder, and sclerosing cholangitis. The entire digestive tract can be involved. Distal ileal obstruction syndrome, intussusception, appendicitis, chronic constipation, colonic wall thickening, fibrosing colonopathy, pneumatosis intestinalis, gastroesophageal reflux, and peptic ulcer disease have been described. Renal manifestations include nephrolithiasis and secondary amyloidosis. The educational objectives of this review are to reveal the abdominal manifestations of CF to facilitate focused analysis of cross-sectional imaging in adult patients. Life expectancy in patients with CF continues to improve because of a combination of aggressive antibiotic treatment, improved emphasis on nutrition and physiotherapy, and development of promising new CF transmembrane conductance regulator modulators. As lung function and survival improve, extrapulmonary conditions, including hepatic and gastrointestinal malignancy, will be an increasing cause of morbidity and mortality. Awareness of the expected abdominal manifestations of CF may assist radiologists in identifying

  8. Rasch Measurement in the Assessment of Growth Hormone Deficiency in Adult Patients.

    ERIC Educational Resources Information Center

    Prieto, Luis; Roset, Montse; Badia, Xavier

    2001-01-01

    Tested the metric properties of a Spanish version of the Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire through Rasch analysis with a sample of 356 adult patients in Spain. Results suggest that the Spanish AGHDA could be a useful complement of the clinical evaluation of growth hormone deficiency patients at group and…

  9. Warming up Improves Speech Production in Patients with Adult Onset Myotonic Dystrophy

    ERIC Educational Resources Information Center

    de Swart, B.J.M.; van Engelen, B.G.M.; Maassen, B.A.M.

    2007-01-01

    This investigation was conducted to study whether warming up decreases myotonia (muscle stiffness) during speech production or causes adverse effects due to fatigue or exhaustion caused by intensive speech activity in patients with adult onset myotonic dystrophy. Thirty patients with adult onset myotonic dystrophy (MD) and ten healthy controls…

  10. SIMILAR OUTCOMES USING MYELOABLATIVE VERSUS REDUCED INTENSITY ALLOGENEIC TRANSPLANT PREPARATIVE REGIMENS FOR AML OR MDS

    PubMed Central

    Luger, Selina M.; Ringdén, Olle; Zhang, Mei-Jie; Pérez, Waleska S.; Bishop, Michael R.; Bornhauser, Martin; Bredeson, Christopher N.; Cairo, Mitchell S.; Copelan, Edward A.; Gale, Robert Peter; Giralt, Sergio A.; Gulbas, Zafer; Gupta, Vikas; Hale, Gregory A.; Lazarus, Hillard M.; Lewis, Victor Anthony; Lill, Michael C.; McCarthy, Philip L.; Weisdorf, Daniel J.; Pulsipher, Michael A.

    2011-01-01

    Although reduced intensity (RIC) and nonmyeloablative (NMA) conditioning regimens have been used for over a decade, their relative efficacy versus myeloablative (MA) approaches to allogeneic hematopoietic cell transplantation (HCT) in patients with acute myelogenous leukemia (AML) and myelodysplasia (MDS) is unknown. We compared disease status, donor, graft and recipient characteristics with outcomes of 3731 MA with 1448 RIC/NMA procedures performed at 217 centers between 1997 and 2004. Five year univariate probabilities and multivariate relative risk (RR) outcomes of relapse, transplant related mortality (TRM), disease free survival (DFS) and overall survival (OS) are reported. Adjusted OS at 5 years was 34%, 33%, and 26% for MA, RIC and NMA transplants, respectively. NMA conditioning resulted in inferior DFS and OS but there was no difference in DFS and OS between RIC and MA regimens. Late TRM negates early decreases in toxicity with RIC and NMA regimens. Our data suggest higher regimen intensity may contribute to optimal survival in patients with AML/MDS, suggesting roles for both regimen intensity and graft vs. leukemia in these diseases. Prospective studies comparing regimens are needed to confirm this finding and determine the optimal approach to patients who are eligible for either MA or RIC/NMA conditioning. PMID:21441963

  11. A Phase II Study Of The Farnesyltransferase Inhibitor ZANESTRA (R115777, NSC #702818, IND #58,359) In Complete Remission Following Induction And/Or Consolidation Chemotherapy In Adults With Poor-Risk Acute Myelogenous Leukemia (AML) And High-Risk Myelodysplasia (MDS)

    ClinicalTrials.gov

    2013-01-08

    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; Secondary Myelodysplastic Syndromes

  12. Flavopiridol induces BCL-2 expression and represses oncogenic transcription factors in leukemic blasts from adults with refractory acute myeloid leukemia

    PubMed Central

    Nelson, Dwella M.; Joseph, Biju; Hillion, Joelle; Segal, Jodi; Karp, Judith E.; Resar, Linda M. S.

    2011-01-01

    Flavopiridol is a cyclin-dependent kinase inhibitor that induces cell cycle arrest, apoptosis, and clinical responses in selected patients with acute myeloid leukemia (AML). A better understanding of the molecular pathways targeted by flavopiridol is needed to design optimal combinatorial therapy. Here, we report that in vivo administration of flavopiridol induced expression of the BCL-2 anti-apoptotic gene in leukemic blasts from adult patients with refractory AML. Moreover, flavopiridol repressed the expression of genes encoding oncogenic transcription factors (HMGA1, STAT3, E2F1) and the major subunit of RNA Polymerase II. Our results provide mechanistic insight into the cellular pathways targeted by flavopiridol and suggest that blocking anti-apoptotic pathways could enhance cytotoxicity and improve outcomes in patients treated with flavopiridol. PMID:21728742

  13. Chest CT findings of influenza virus‐associated pneumonia in 12 adult patients

    PubMed Central

    Fujita, Jiro; Bandoh, Shuji; Yamaguchi, Masahiro; Higa, Futoshi; Tateyama, Masao

    2008-01-01

    Objective  In this study, we describe the chest computed tomography findings of influenza virus‐associated pneumonia in adult patients. Methods  Our retrospective study included 12 adult patients who had proven influenza virus ‐ associated pneumonia. Results  Out of 12 patients, six were diagnosed as having pure influenza virus pneumonia, five as having bronchopneumonia caused by bacteria associated with influenza A infection, and one as having a cryptogenic organizing pneumonia associated with influenza A infection. Conclusion  Radiographic findings of influenza virus pneumonia in adult patients consist of ground‐glass attenuation. Localized patchy consolidations were observed in cases of bronchopneumonia. PMID:19453425

  14. Responding to requests from adult patients for neuroenhancements

    PubMed Central

    Larriviere, Dan; Williams, Michael A.; Rizzo, Matt; Bonnie, Richard J.

    2009-01-01

    In the last decade, persons who have no diagnosed medical or mental health condition are increasingly seeking and utilizing, for the ostensible purpose of enhancing their memory or cognitive skills, prescription drugs that were originally developed to improve executive function or memory in persons diagnosed with disorders such as attention deficit hyperactivity disorder or Alzheimer disease. Evidence suggests that this practice, now known as neuroenhancement, is gathering momentum. As a result, neurologists may be encountering patients without a diagnosed illness asking for medications with the goal of improving their memory, cognitive focus, or attention span. Strong arguments have been made for and against this practice, often reflecting strongly held convictions concerning the appropriate practice of medicine. The purpose of this report is to provide neurologists with an overview of the ethical, legal, and social issues surrounding the use of pharmaceuticals prescribed to enhance or augment normal cognitive or affective functioning, as well as practical guidance for responding to an adult patient’s request for neuroenhancement. GLOSSARY ELHC = Ethics, Law and Humanities Committee; FDA = Food and Drug Administration. PMID:19776378

  15. The Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy in Acute Myeloid Leukaemia : An IndividualPatient Data Meta-analysis of Randomised Trials in Adults

    PubMed Central

    Hills, Robert K; Castaigne, Sylvie; Appelbaum, Frederick R; Delaunay, Jacques; Petersdorf, Stephen; Othus, Megan; MD, Elihu H Estey; Dombret, Hervé; Chevret, Sylvie; Ifrah, Norbert; Cahn, Jean-Yves; Récher, Christian; Chilton, Lucy; Moorman, Anthony V; Burnett, Alan K

    2014-01-01

    Summary Background Gemtuzumab Ozogamicin (GO) was the first example of antibody directed chemotherapy in cancer and developed for Acute Myeloid Leukaemia. Its role has been unclear. Five randomised trials where it was combined with standard induction chemotherapy in adults have produced different results. In an effort to clarify the level of benefit, if any, and in which patients outcomes might be improved, an individual patient data meta-analysis of these 5 trials has been undertaken. Methods All randomised trials of GO in adults (age >15), given in conjunction with the first course of intensive induction chemotherapy for AML (excluding APL) were identified. In a collaboration between the groups involved, source data concerning demographics, treatment was requested in May 2013 and collected in 3325 randomised patients (median age 58). All trials were centrally randomised and open-label, with survival as primary endpoint. Analyses are presented by standard techniques, and within standardised risk groups Results Remission rates were not increased, but by significantly reducing the risk of relapse overall survival at 5 years was improved irrespective of patient age (30.7% vs 34.6%; HR 0.90 (95% CI 0.82-0.98), p=0.01). The survival benefit was particularly clear in those with favourable cytogenetics (55.2% vs 76.3%; HR0.47 (0.31-0.73), p=0.0005), but also observed in intermediate risk patients (34.1% vs 39.4%; HR 0.84 (0.75-0.95), p=0.007) Patients with adverse karyotype did not benefit overall or within any trial. Dose levels of 3mg/m2 were associated with less toxicity and equal efficacy. Interpretation GO can be safely added to conventional induction therapy. For patients who do not have adverse cytogenetics there is a significant survival benefit. These data suggest that the use of GO should be re-evaluated and the license status of GO may need to be reviewed. Role of funding source There was no funder for this meta-analysis. PMID:25008258

  16. MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome.

    PubMed

    Stavropoulou, Vaia; Kaspar, Susanne; Brault, Laurent; Sanders, Mathijs A; Juge, Sabine; Morettini, Stefano; Tzankov, Alexandar; Iacovino, Michelina; Lau, I-Jun; Milne, Thomas A; Royo, Hélène; Kyba, Michael; Valk, Peter J M; Peters, Antoine H F M; Schwaller, Juerg

    2016-07-11

    To address the impact of cellular origin on acute myeloid leukemia (AML), we generated an inducible transgenic mouse model for MLL-AF9-driven leukemia. MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSC) in vitro resulted in dispersed clonogenic growth and expression of genes involved in migration and invasion. In vivo, 20% LT-HSC-derived AML were particularly aggressive with extensive tissue infiltration, chemoresistance, and expressed genes related to epithelial-mesenchymal transition (EMT) in solid cancers. Knockdown of the EMT regulator ZEB1 significantly reduced leukemic blast invasion. By classifying mouse and human leukemias according to Evi1/EVI1 and Erg/ERG expression, reflecting aggressiveness and cell of origin, and performing comparative transcriptomics, we identified several EMT-related genes that were significantly associated with poor overall survival of AML patients. PMID:27344946

  17. Exosomes Secreted by Apoptosis-Resistant Acute Myeloid Leukemia (AML) Blasts Harbor Regulatory Network Proteins Potentially Involved in Antagonism of Apoptosis.

    PubMed

    Wojtuszkiewicz, Anna; Schuurhuis, Gerrit J; Kessler, Floortje L; Piersma, Sander R; Knol, Jaco C; Pham, Thang V; Jansen, Gerrit; Musters, René J P; van Meerloo, Johan; Assaraf, Yehuda G; Kaspers, Gertjan J L; Zweegman, Sonja; Cloos, Jacqueline; Jimenez, Connie R

    2016-04-01

    Expression of apoptosis-regulating proteins (B-cell CLL/lymphoma 2 - BCL-2, Myeloid Cell Leukemia 1 - MCL-1, BCL-2 like 1 - BCL-X and BCL-2-associated X protein - BAX) in acute myeloid leukemia (AML) blasts at diagnosis is associated with disease-free survival. We previously found that the initially high apoptosis-resistance of AML cells decreased after therapy, while regaining high levels at relapse. Herein, we further explored this aspect of dynamic apoptosis regulation in AML. First, we showed that the intraindividualex vivoapoptosis-related profiles of normal lymphocytes and AML blasts within the bone marrow of AML patients were highly correlated. The expression values of apoptosis-regulating proteins were far beyond healthy control lymphocytes, which implicates the influence of microenvironmental factors. Second, we demonstrated that apoptosis-resistant primary AML blasts, as opposed to apoptosis-sensitive cells, were able to up-regulate BCL-2 expression in sensitive AML blasts in contact cultures (p= 0.0067 andp= 1.0, respectively). Using secretome proteomics, we identified novel proteins possibly engaged in apoptosis regulation. Intriguingly, this analysis revealed that major functional protein clusters engaged in global gene regulation, including mRNA splicing, protein translation, and chromatin remodeling, were more abundant (p= 4.01E-06) in secretomes of apoptosis-resistant AML. These findings were confirmed by subsequent extracellular vesicle proteomics. Finally, confocal-microscopy-based colocalization studies show that splicing factors-containing vesicles secreted by high AAI cells are taken up by low AAI cells. The current results constitute the first comprehensive analysis of proteins released by apoptosis-resistant and sensitive primary AML cells. Together, the data point to vesicle-mediated release of global gene regulatory protein clusters as a plausible novel mechanism of induction of apoptosis resistance. Deciphering the modes of communication

  18. Psychosocial Functioning of Adult Epileptic and MS Patients and Adult Normal Controls on the WPSI.

    ERIC Educational Resources Information Center

    Tan, Siang-Yang

    1986-01-01

    Psychosocial functioning of adult epileptic outpatients as assessed by the Washington Psychosocial Seizure Inventory (WPSI) was compared to that of adult multiple sclerosis (MS) outpatients and normal subjects. When only valid WPSI profiles were considered, the only significant finding was that the epilepsy group and the MS group had more…

  19. Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Münster AML-study group

    PubMed Central

    Coenen, Eva A.; Zwaan, C. Michel; Reinhardt, Dirk; Harrison, Christine J.; Haas, Oskar A.; de Haas, Valerie; Mihál, Vladimir; De Moerloose, Barbara; Jeison, Marta; Rubnitz, Jeffrey E.; Tomizawa, Daisuke; Johnston, Donna; Alonzo, Todd A.; Hasle, Henrik; Auvrignon, Anne; Dworzak, Michael; Pession, Andrea; van der Velden, Vincent H. J.; Swansbury, John; Wong, Kit-fai; Terui, Kiminori; Savasan, Sureyya; Winstanley, Mark; Vaitkeviciene, Goda; Zimmermann, Martin; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2013-01-01

    In pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical characteristics, morphology, and immunophenotypes of 62 pediatric AML patients with t(8;16)(p11;p13) from 18 countries participating in the International Berlin-Frankfurt-Münster (I-BFM) AML study group. We used the AML-BFM cohort diagnosed from 1995-2005 (n = 543) as a reference cohort. Median age of the pediatric t(8;16)(p11;p13) AML patients was significantly lower (1.2 years). The majority (97%) had M4-M5 French-American-British type, significantly different from the reference cohort. Erythrophagocytosis (70%), leukemia cutis (58%), and disseminated intravascular coagulation (39%) occurred frequently. Strikingly, spontaneous remissions occurred in 7 neonates with t(8;16)(p11;p13), of whom 3 remain in continuous remission. The 5-year overall survival of patients diagnosed after 1993 was 59%, similar to the reference cohort (P = .14). Gene expression profiles of t(8;16)(p11;p13) pediatric AML cases clustered close to, but distinct from, MLL-rearranged AML. Highly expressed genes included HOXA11, HOXA10, RET, PERP, and GGA2. In conclusion, pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features in whom spontaneous remissions occur in a subset of neonatal cases. PMID:23974201

  20. Occupational Outcome in Adult ADHD: Impact of Symptom Profile, Comorbid Psychiatric Problems, and Treatment--A Cross-Sectional Study of 414 Clinically Diagnosed Adult ADHD Patients

    ERIC Educational Resources Information Center

    Halmoy, Anne; Fasmer, Ole Bernt; Gillberg, Christopher; Haavik, Jan

    2009-01-01

    Objective: To determine the effects of symptom profile, comorbid psychiatric problems, and treatment on occupational outcome in adult ADHD patients. Method: Adult ADHD patients (N = 414) responded to questionnaires rating past and present symptoms of ADHD, comorbid conditions, treatment history, and work status. Results: Of the patients, 24%…

  1. Histopathological Characteristics of Distal Middle Cerebral Artery in Adult and Pediatric Patients with Moyamoya Disease.

    PubMed

    Takagi, Yasushi; Hermanto, Yulius; Takahashi, Jun C; Funaki, Takeshi; Kikuchi, Takayuki; Mineharu, Yohei; Yoshida, Kazumichi; Miyamoto, Susumu

    2016-06-15

    Moyamoya disease (MMD) is a unique progressive steno-occlusive disease of the distal ends of bilateral internal arteries and their proximal branches. The difference in clinical symptoms between adult and children MMD patients has been well recognized. In this study, we sought to investigate the phenomenon through histopathological study. Fifty-one patients underwent surgical procedures for treatment of standard indications of MMD at Kyoto University Hospital. Fifty-nine specimens of MCA were obtained from MMD patients during the surgical procedures. Five MCA samples were also obtained in the same way from control patients. The samples were analyzed by histopathological methods. In this study, MCA specimens from MMD patients had significantly thinner media and thicker intima than control specimens. In subsequent analysis, adult (≥ 20 years) patients had thicker intima of MCA compared to pediatric (< 20 years) patients. There is no difference in internal elastic lamina pathology between adult and pediatric patients. Our results indicated that the pathological feature of MMD in tunica media occurs in both adult and pediatric patients. However, the MMD feature in tunica intima of MCA is more prominent in adult patients. Further analysis from MCA specimens and other researches are necessary to elucidate the pathophysiology of MMD. PMID:27087193

  2. Association between prolonged neutropenia and reduced relapse risk in pediatric AML: A report from the children's oncology group.

    PubMed

    Sung, Lillian; Aplenc, Richard; Alonzo, Todd A; Gerbing, Robert B; Wang, Yi-Cheng; Meshinchi, Soheil; Gamis, Alan S

    2016-11-01

    Objective was to describe the relationship between the number of sterile site infections and duration of neutropenia during the first four cycles of chemotherapy and the risk of recurrence and overall survival in children with newly diagnosed acute myeloid leukemia (AML). AAML0531 was a Children's Oncology Group randomized phase 3 clinical trial that included 1022 children with de novo AML. For this analysis, we focused on non-Down syndrome favorable and standard risk patients who completed at least 4 cycles of chemotherapy without recurrence or withdrawal during protocol therapy. Those receiving hematopoietic stem cell transplantation in first remission were excluded. Five hundred and sixty-nine patients were included; 274 (48.2%) were favorable risk. The median cumulative time with neutropenia between Induction II to completion of Intensification II was 96 (range 54-204) days. Number of sterile site infections did not influence the risk of relapse or overall survival. However, longer duration of neutropenia was associated with a lower risk of relapse (hazard ratio 0.81 per 20 days neutropenia, p = 0.007). Longer duration of neutropenia was associated with a reduced risk of relapse for children with favorable and standard risk AML. Toxicity may be influenced by pharmacogenomics suggesting that individualized chemotherapy dosing may be an effective strategy. PMID:27312107

  3. Identification of TEL-AML1 (ETV6-RUNX1) associated DNA and its impact on mRNA and protein output using ChIP, mRNA expression arrays and SILAC

    PubMed Central

    Linka, Yvonne; Ginzel, Sebastian; Borkhardt, Arndt; Landgraf, Pablo

    2014-01-01

    The contribution of the most common reciprocal translocation in childhood B-cell precursor leukemia t(12;21)(p13;q22) to leukemia development is still under debate. Direct as well as secondary indirect effects of the TEL-AML1 fusion protein are commonly recorded by using cell lines and patient samples, often bearing the TEL-AML1 fusion protein for decades. To identify direct targets of the fusion protein a short-term induction of TEL-AML1 is needed. We here describe in detail the experimental procedure, quality controls and contents of the ChIP, mRNA expression and SILAC datasets associated with the study published by Linka and colleagues in the Blood Cancer Journal [1] utilizing a short term induction of TEL-AML1 in an inducible precursor B-cell line model. PMID:26484077

  4. Recognising falls risk in older adult mental health patients and acknowledging the difference from the general older adult population.

    PubMed

    Wynaden, Dianne; Tohotoa, Jenny; Heslop, Karen; Al Omari, Omar

    2016-01-01

    Older adults admitted to inpatient mental health units present with complex mental health care needs which are often compounded by the challenges of living with physical co-morbidities. They are a mobile population and a high risk group for falling during hospitalisation. To address quality and safety concerns around the increased risk for falls, a qualitative research study was completed to obtain an improved understanding of the factors that increase the risk of falling in this patient cohort. Focus groups were conducted with mental health professionals working across older adult mental health services in metropolitan Western Australia. Data were analysed using content analysis and three themes emerged that were significant concepts relevant to falls risk in this patient group. These themes were (1) limitations of using generic falls risk assessment and management tools, (2) assessment of falls risk not currently captured on standardised tools, and (3) population specific causes of falls. The findings demonstrate that older adult mental health patients are a highly mobile group that experience frequent changes in cognition, behaviour and mental state. The mix of patients with organic or functional psychiatric disorders within the same environment also presents complex and unique care challenges and multi-disciplinary collaboration is central to reduce the risk of falls. As this group of patients are also frequently admitted to both general inpatient and aged care settings, the findings are relevant to the assessment and management of falls risk across all health care settings. PMID:27188045

  5. Comparing illness presentation, treatment and functioning between patients with adolescent- and adult-onset psychosis.

    PubMed

    Hui, Christy Lai-Ming; Li, Adrienne Wing-Yee; Leung, Chung-Ming; Chang, Wing-Chung; Chan, Sherry Kit-Wa; Lee, Edwin Ho-Ming; Chen, Eric Yu-Hai

    2014-12-30

    Studies have shown that early- and adult-onset schizophrenia patients differ in pre-morbid traits, illness presentation, psychopathology, and prognosis. We aimed to compare adult-onset patients (age range 26-55 years) with an adolescent-onset cohort (15-25 years) in demographics, illness presentation and functioning at baseline. Participants were from two territory-wide early intervention services for adolescent-onset (n=671) and adult-onset psychosis patients (n=360) in Hong Kong. The adolescent-onset cohort had their initial psychotic episode from 2001-2003; retrospective data collection was done through systematic case note review. The adult-onset cohort was recruited for a larger interventional study from 2009-2011; information was collected via face-to-face interviews. Adult-onset psychosis was significantly associated with more females, more smokers, more non-local birth, more full-time employment, better functioning, poorer medication adherence, more psychiatric hospitalization and fewer with schizophrenia than adolescent-onset psychosis (mean age: 20.4). The effect sizes were small, except for medication adherence where a robust effect was found. No group difference in DUP was found. The finding that adult-onset patients had better functioning challenges the view that adolescent- and adult-onset psychoses share a similar prognostic trajectory. Implications for adapting intervention processes for adolescent- and adult-onset psychosis are discussed. PMID:25238985

  6. Reduced Capacity in a Dichotic Memory Test for Adult Patients with ADHD

    ERIC Educational Resources Information Center

    Dige, Niels; Maahr, Eija; Backenroth-Ohsako, Gunnel

    2010-01-01

    Objective: To evaluate whether a dichotic memory test would reveal deficits in short-term working-memory recall and long-term memory recall in a group of adult patients with ADHD. Methods: A dichotic memory test with ipsilateral backward speech distraction in an adult ADHD group (n = 69) and a control group (n = 66) is used to compare performance…

  7. Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis

    PubMed Central

    Levine, Jacob H.; Simonds, Erin F.; Bendall, Sean C.; Davis, Kara L.; Amir, El-ad D.; Tadmor, Michelle; Litvin, Oren; Fienberg, Harris; Jager, Astraea; Zunder, Eli; Finck, Rachel; Gedman, Amanda L.; Radtke, Ina; Downing, James R.; Pe’er, Dana; Nolan, Garry P.

    2015-01-01

    SUMMARY Acute myeloid leukemia (AML) manifests as phenotypically and functionally diverse cells, often within the same patient. Intratumor phenotypic and functional heterogeneity have been linked primarily by physical sorting experiments, which assume that functionally distinct subpopulations can be prospectively isolated by surface phenotypes. This assumption has proven problematic and we therefore developed a data-driven approach. Using mass cytometry, we profiled surface and intracellular signaling proteins simultaneously in millions of healthy and leukemic cells. We developed PhenoGraph, which algorithmically defines phenotypes in high-dimensional single-cell data. PhenoGraph revealed that the surface phenotypes of leukemic blasts do not necessarily reflect their intracellular state. Using hematopoietic progenitors, we defined a signaling-based measure of cellular phenotype, which led to isolation of a gene expression signature that was predictive of survival in independent cohorts. This study presents new methods for large-scale analysis of single-cell heterogeneity and demonstrates their utility, yielding insights into AML pathophysiology. PMID:26095251

  8. Paclitaxel Induced MDS and AML: A Case Report and Literature Review

    PubMed Central

    Bhatnagar, Udit Bhaskar; Singh, Daulath; Glazyrin, Alexy; Moormeier, Jill

    2016-01-01

    Therapy related acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS) have been classically linked to alkylating agents and topoisomerase inhibitors. They constitute about 1% of all AMLs. There is less evidence on association of taxanes (paclitaxel and docetaxel) with these myeloid neoplasms. We present a case of paclitaxel therapy related acute myelogenous leukemia after treatment of endometrial cancer with a regimen containing paclitaxel and carboplatin. A 63-year-old female underwent surgery followed by a total of 6 cycles of chemotherapy with carboplatin and paclitaxel. Six months after last cycle of chemotherapy, she was diagnosed with myelodysplastic syndrome with refractory anemia and excess blasts. Six weeks later, she had worsening anemia and thrombocytopenia which prompted a bone marrow biopsy which revealed acute myelomonocytic leukemia. A thorough literature review revealed 12 other case reports where taxanes have been implicated in the development of therapy related myeloid neoplasm. Based on the timeline of events in our patient, paclitaxel is the likely culprit in the pathogenesis of this myeloid neoplasm. This rare but significantly grave adverse effect should be kept in consideration when deciding on treatment options for gynecological malignancies. PMID:27057370

  9. Symptoms and socio-economic impact of ependymoma on adult patients: results of the Adult Ependymoma Outcomes Project 2.

    PubMed

    Walbert, Tobias; Mendoza, Tito R; Vera-Bolaños, Elizabeth; Acquaye, Alvina; Gilbert, Mark R; Armstrong, Terri S

    2015-01-01

    Ependymoma is a rare central nervous system tumor of adults. Reports of patient symptoms, interference patterns and costs encountered by patients and families are limited. Adult ependymoma patients completed the online Ependymoma Outcomes Questionnaire II. The survey assesses disease and functional status as well as socio-economic factors. Descriptive statistics were used to report disease characteristics as well as economic and social impact. Independent samples t test was used to test if differences exist between high- and low-income groups in terms of symptom severity. Correlations were calculated between symptoms and cost estimates. 86 international patients participated (male = 50 %). The economic analysis focused on 78 respondents from the US. 48 % were employed and 55 % earned ≥$60,000. Tumors were located in the brain (44 %), spine (44 %) or both (12 %). Spine patients compared to brain patients reported significantly worse pain (4.4 versus 2.2, p < .003), numbness (5.3 versus 2.2, p < .001), fatigue (5.1 versus 3.6, p < .03), changes in bowel patterns (3.8 versus 1.4, p < .003) and weakness (4.2 versus 2.1, p < .006). Brain patients compared with spine patients had increased lack of appetite (.4 versus 2, p < .014). Patients with lower income (≤$59,999) had more problems concentrating (p < .024) and worse cognitive module severity scores (p < .024). Estimated average monthly out-of-pocket spending was $168 for medical co-pays and $59 for prescription medication. Patients with ependymoma are highly affected by their symptoms. Spinal patients report higher severity of symptoms. Patients in the lower income group report significantly higher severity of cognitive symptoms independent of disease site. PMID:25359395

  10. Variation in Insurance Status by Patient Demographics and Tumor Site Among Nonelderly Adult Patients With Cancer

    PubMed Central

    Grant, Stephen R.; Walker, Gary V.; Guadagnolo, B. Ashleigh; Koshy, Matthew; Allen, Pamela K.; Mahmood, Usama

    2016-01-01

    BACKGROUND In the United States, an estimated 48 million individuals live without health insurance. The purpose of the current study was to explore the variation in insurance status by patient demographics and tumor site among nonelderly adult patients with cancer. METHODS A total of 688,794 patients aged 18 to 64 years who were diagnosed with one of the top 25 incident cancers (representing 95% of all cancer diagnoses) between 2007 and 2010 in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patient characteristics included age, race, sex, marital status, and rural or urban residence. County-level demographics included percent poverty level. Insurance status was defined as having non-Medicaid insurance, Medicaid coverage, or no insurance. RESULTS On multivariate logistic regression analyses, younger age, male sex, nonwhite race, being unmarried, residence in counties with higher levels of poverty, and rural residence were associated with being uninsured versus having non-Medicaid insurance (all P <.001). The highest rates of non-Medicaid insurance were noted among patients with prostate cancer (92.3%), melanoma of the skin (92.5%), and thyroid cancer (89.5%), whereas the lowest rates of non-Medicaid insurance were observed among patients with cervical cancer (64.2%), liver cancer (67.9%), and stomach cancer (70.9%) (P <.001). Among uninsured individuals, the most prevalent cancers were lung cancer (14.9%), colorectal cancer (12.1%), and breast cancer (10.2%) (P <.001). Lung cancer caused the majority of cancer mortality in all insurance groups. CONCLUSIONS Rates of insurance coverage vary greatly by demographics and by cancer type. The expansion of health insurance coverage would be expected to disproportionally benefit certain demographic populations and cancer types. PMID:25917222

  11. Transition from Pediatric to Adult Health Care in Patients with Chronic Illnesses: An Integrative Review.

    PubMed

    Lewis, Jennifer; Slobodov, Gennady

    2015-01-01

    A systematic review of the literature was performed to identify barriers, themes, or additional insight specific to the transitional care processes from a pediatric to an adult health care setting for patients with spina bifida. PMID:26630779

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

    PubMed

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

    2014-03-01

    Secondary myelodysplastic syndrome and acute myelogenous leukemia (sMDS/sAML) are the most serious secondary events occurring after immunosuppressive therapy in patients with aplastic anemia. Here we evaluate the outcome of hematopoietic stem cell transplantation (HSCT) in 17 children and young adults with sMDS/sAML after childhood aplastic anemia. The median interval between the diagnosis of aplastic anemia and the development of sMDS/sAML was 2.9 years (range, 1.2 to 13.0 years). At a median age of 13.1 years (range, 4.4 to 26.7 years), patients underwent HSCT with bone marrow (n = 6) or peripheral blood stem cell (n = 11) grafts from HLA-matched sibling donors (n = 2), mismatched family donors (n = 2), or unrelated donors (n = 13). Monosomy 7 was detected in 13 patients. The preparative regimen consisted of busulfan, cyclophosphamide, and melphalan in 11 patients and other agents in 6 patients. All patients achieved neutrophil engraftment. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and that of chronic GVHD was 70%. Relapse occurred in 1 patient. The major cause of death was transplant-related complication (n = 9). Overall survival and event-free survival at 5 years after HSCT were both 41%. In summary, this study indicates that HSCT is a curative therapy for some patients with sMDS/sAML after aplastic anemia. Future efforts should focus on reducing transplantation-related mortality. PMID:24316460

  13. Bisphosphonates and statins inhibit expression and secretion of MIP-1α via suppression of Ras/MEK/ERK/AML-1A and Ras/PI3K/Akt/AML-1A pathways.

    PubMed

    Tsubaki, Masanobu; Takeda, Tomoya; Sakamoto, Kotaro; Shimaoka, Hirotaka; Fujita, Arisa; Itoh, Tatsuki; Imano, Motohiro; Mashimo, Kenji; Fujiwara, Daiichiro; Sakaguchi, Katsuhiko; Satou, Takao; Nishida, Shozo

    2015-01-01

    Osteolytic bone disease in multiple myeloma (MM) is associated with upregulated osteoclast activity. Macrophage inflammatory protein-1α (MIP-1α) is crucially involved in the development of osteolytic bone lesions in MM. We previously reported that minodronate inhibited lipopolysaccharide-induced MIP-1α secretion in mouse myeloma cells. However, it remains unknown whether bisphosphonates and statins inhibit MIP-1α secretion by human MM cells. In present study, we investigated whether bisphosphonates and statins had any inhibitory effect on MIP-1α secretion by human myeloma cells and the mechanism underlying this effect. In this study, we found that bisphosphonates and statins inhibited MIP-1α mRNA and MIP-1α secretion and suppressed extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation by inhibiting Ras prenylation. Moreover, bisphosphonates and statins suppressed the expression of acute myeloid leukemia-1A (AML-1A) mRNA, a MIP-1α transcription factor. These results indicate that bisphosphonates and statins suppress the Ras/mitogen-activated protein kinase kinase/ERK/AML-1A and Ras/phosphatidylinositol-3 kinase/Akt/AML-1A pathways, thereby inhibiting MIP-1α secretion by MM cells. Therefore, use of MIP-1α expression inhibitors such as bisphosphonates and statins may provide a new therapeutic approach to inhibiting tumour progression and bone destruction in MM patients. PMID:25628928

  14. Sorafenib in combination with low-dose-homoharringtonine as a salvage therapy in primary refractory FLT3-ITD-positive AML: a case report and review of literature

    PubMed Central

    Xu, Gaixiang; Mao, Liping; Liu, Hui; Yang, Min; Jin, Jie; Qian, Wenbin

    2015-01-01

    The presence of internal tandem duplications (ITD) in the Fms-related tyrosine kinase 3 receptor (FLT3) has been associated with a poor prognosis in acute myeloid leukemia (AML). Over the past decade, FLT3 is a promising target in FLT3-ITD-positive AML. Sorafenib which is one of the commonly focused FLT3 inhibitors may improve outcome, but only few patients display long-term responses in previously reported cases, prompting the search for underlying resistance mechanisms and therapeutic strategies to overcome them. To the best of our knowledge, this is the first case report about sorafenib in combination with low-dose-homoharringtonine as a salvage therapy successfully administrated and got complete remission (CR) in primary refractory FLT3-ITD-positive AML. Our result demonstrates the combination of this two drugs may be a good choice for the primary refractory FLT3-ITD-positive AML patient, although cooperative studies of large numbers of these patients are needed to evaluate and optimize this combination. PMID:26884901

  15. Optimizing Management of Patients with Adult T Cell Leukemia-Lymphoma

    PubMed Central

    Yared, Jean A.; Kimball, Amy S.

    2015-01-01

    Adult T cell leukemia-lymphoma is a rare disease with a high mortality rate, and is challenging for the clinician. Early allogeneic stem cell transplant can confer durable remission. As novel therapeutic agents become available to treat T cell malignancies, it is increasingly important that medical oncologists, hematologists, and hematopathologists recognize and accurately diagnose adult T cell leukemia-lymphoma. There is no uniform standard of treatment of adult T cell leukemia-lymphoma, and clinical trials remain critical to improving outcomes. Here we present one management approach based on the recent advances in treatment for adult T cell leukemia-lymphoma patients. PMID:26610571

  16. Molecular cytogenetic investigations in a novel complex variant of t(8;21)(q22;q22) with ins(15;21)(q15;q22.2q22.3) in a patient with AML-M2 subtype.

    PubMed

    Kokate, Prajakta; Ahmad, Firoz; Dalvi, Rupa; Das, Bibhu Ranjan; Mandava, Swarna

    2008-07-01

    Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous disease characterized by the aberrant proliferation of myeloid stem cells, reduced apoptosis and blockage in cellular differentiation. The present report describes the results of hematological, cytogenetic, and fluorescence in situ hybridization (FISH) analysis in a 25-year-old man diagnosed with AML-M2. Cytogenetic as well as FISH analysis revealed a complex translocation involving four chromosomes, with the karyotype 45,-Y,der(X)t(X;8)(p21;q22),der(8)t(8;21)(q22;q22),ins(15;21)(q15;q22.2q22.3),der(21)t(8;21)(q22;q22). The breakpoints at 8q22 and 21q22 suggested a rearrangement of the RUNX1T1 (alias ETO) and RUNX1 (previously AML1) genes, respectively. Using a dual-color FISH test with RUNX1T1 and RUNX1 probes, we demonstrated an RUNX1/RUNX1T1 fusion signal on the derivative chromosome 8, establishing this translocation as a novel complex variant of t(8;21)(q22;q22). PMID:18558290

  17. Phase I study of azacitidine and bortezomib in adults with relapsed or refractory acute myeloid leukemia

    PubMed Central

    Walker, Alison R.; Klisovic, Rebecca B.; Garzon, Ramiro; Schaaf, Larry J.; Humphries, Kristina; Devine, Steven M.; Byrd, John C.; Grever, Michael R.; Marcucci, Guido; Blum, William

    2013-01-01

    We previously reported that bortezomib indirectly modulates transcription of DNA methyltransferase 1 (DNMT). We designed a phase I study of azacitidine (a direct DNMT inhibitor) plus bortezomib in acute myeloid leukemia (AML) to determine safety and tolerability. Twenty-three adults with relapsed/refractory AML received azacitidine 75mg/m2 daily on days 1-7. Bortezomib was dose escalated from 0.7mg/m2 on days 2 and 5 to 1.3mg/m2 on days 2, 5, 9, and 12. The target dose was reached without dose limiting toxicities. Infection and/or febrile neutropenia were frequent. Patients received a median of 2 cycles of therapy (range, 1-12+). Five of 23 patients achieved remission including two with morphologic and cytogenetic complete response (CR) and three with CR and incomplete count recovery (CRi). Of CR/CRi responders with cytogenetic abnormalities at baseline, three of four achieved cytogenetic CR. The combination of azacitidine and bortezomib was tolerable and active in this cohort of poor-risk previously-treated AML patients. PMID:23952243

  18. Screening for coeliac disease in adult patients with type 1 diabetes mellitus: myths, facts and controversy.

    PubMed

    Bakker, Sjoerd F; Tushuizen, Maarten E; von Blomberg, Boudewina M E; Bontkes, Hetty J; Mulder, Chris J; Simsek, Suat

    2016-01-01

    This review aims at summarizing the present knowledge on the clinical consequences of concomitant coeliac disease (CD) in adult patients with type 1 diabetes mellitus (T1DM). The cause of the increased prevalence of CD in T1DM patients is a combination of genetic and environmental factors. Current screening guidelines for CD in adult T1DM patients are not uniform. Based on the current evidence of effects of CD on bone mineral density, diabetic complications, quality of life, morbidity and mortality in patients with T1DM, we advise periodic screening for CD in adult T1DM patients to prevent delay in CD diagnosis and subsequent CD and/or T1DM related complications. PMID:27478507

  19. Rules for improving pharmacotherapy in older adult patients: part 1 (rules 1-5).

    PubMed

    Wooten, James M

    2015-02-01

    The population of older adult patients in the United States is growing each year. Appropriate pharmacotherapy has allowed many older patients to live longer and maintain healthy lives. Unfortunately, the inappropriate utilization of medications can be harmful to older adult patients. Inappropriate pharmacotherapy may lead to overusing medications and polypharmacy. Polypharmacy can contribute to a higher incidence of adverse effects, increase the risk of dangerous drug interactions, cause noncompliance with appropriate medication use, and significantly increase the cost of health care. The polypharmacy issue with geriatric patients has been described as an epidemic and this issue must be addressed. This review provides objective rules that may help prevent polypharmacy. Consideration of these rules when prescribing, dispensing, and caring for older adult patients will improve the overall pharmacotherapy regimens instituted by healthcare providers. PMID:25688894

  20. Strengthening the effectiveness of patient education: applying principles of adult education.

    PubMed

    Padberg, R M; Padberg, L F

    1990-01-01

    In spite of the recognized significance of patient education, many factors contribute to difficulties in providing effective patient teaching: diminished time from reduced hospital stays, the shortage of nursing personnel, and often, the patient's compromised physical and emotional status. With these constraints, teaching must be effective and efficient. In reviewing the literature, primary emphasis was found on providing sound clinical information with little attention to the techniques of effective methods for teaching adults. This article draws upon the principles of andragogy--the methods of teaching adults delineated by Malcolm Knowles--to provide a conceptual framework for developing effective patient education practice. Examples of both effective and ineffective practice are provided from the nursing literature. The information provided should assist nurses in understanding how adults learn and provide them with a structure to use in tailoring their teaching to meet the individual needs of their patients. PMID:2300506

  1. Prevalence of vitamin D deficiency and insufficiency among adult asthmatic patients in Karachi.

    PubMed

    Kamran, Afshan; Alam, Syed Mahboob; Qadir, Farida

    2014-11-01

    Vitamin D deficiency has assumed pandemic proportions all over the world. It has been documented as a frequent problem in studies of young adults, elderly person and children in other countries, but there is no reliable data on vitamin D status of adult asthmatic patients in Pakistan. To determine the prevalence of vitamin D deficiency and insufficiency in adult asthmatic patients with moderate to severe asthma using a cross-sectional study design in Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi.311 adult asthmatic patients with moderate to severe asthma were recruited from JPMC, tertiary care hospital in Karachi. Questionnaires were administered together demographics, height, weight, nutritional and physical activity assessment. Blood samples for vitamin D measurement were also taken. Results show high prevalence of vitamin D deficiency and insufficiency (88.10%) in adult patients with moderate to severe persistent asthma. Vitamin D deficiency and insufficiency was more frequently observed in female than in male patients.67.66% of the female patients had serum vitamin D level less than 20 ng/ml as compare to 56.1% of the male patients (p=0.01). PMID:26045376

  2. Adult Day Care for Alzheimer's Patients and Their Families.

    ERIC Educational Resources Information Center

    Sands, Dan; Suzuki, Thelma

    1983-01-01

    Harbor Area Adult Day Care Center has operated for two years with a primary purpose of providing respite care to families caring for a relative with Alzheimer's disease or related disorders. The rationale, history, program, staffing, funding, and experience for the first two years of the project are provided. (Author/RC)

  3. Low Literacy Levels in Adults: Implications for Patient Education.

    ERIC Educational Resources Information Center

    Fisher, Evelyn

    1999-01-01

    Health-education materials often require reading levels higher than that of many patients. Nurses need awareness of the prevalence of low literacy and the ability to assess reading levels so they can develop appropriate patient-education materials. (SK)

  4. Psychotherapy Interventions for Managing Anxiety and Depressive Symptoms in Adult Brain Tumor Patients: A Scoping Review

    PubMed Central

    Kangas, Maria

    2015-01-01

    Background Adult brain tumor (BT) patients and longer-term survivors are susceptible to experiencing emotional problems, including anxiety and/or depression disorders, which may further compromise their quality-of-life (QOL) and general well-being. The objective of this paper is to review psychological approaches for managing anxiety and depressive symptoms in adult BT patients. A review of psychological interventions comprising mixed samples of oncology patients, and which included BT patients is also evaluated. The review concludes with an overview of a recently developed transdiagnostic psychotherapy program, which was specifically designed to treat anxiety and/or depressive symptoms in adult BT patients. Methods Electronic databases (PsycINFO, Medline, Embase, and Cochrane) were searched to identify published studies investigating psychological interventions for managing anxiety and depressive symptoms in adult BT patients. Only four randomized controlled trials (RCTs) were identified. Results Only one of the RCTs tested a psychosocial intervention, which was specifically developed for primary BT patients, and which was found to improve QOL including existential well-being as well as reducing depressive symptoms. A second study tested a combined cognitive rehabilitation and problem-solving intervention, although was not found to significantly improve mood or QOL. The remaining two studies tested multidisciplinary psychosocial interventions in heterogeneous samples of cancer patients (included BT patients) with advanced stage disease. Maintenance of QOL was found in both studies, although no secondary gains were found for improvements in mood. Conclusion There is a notable paucity of psychological interventions for adult BT patients across the illness trajectory. Further research is required to strengthen the evidence base for psychological interventions in managing anxiety and depressive symptoms, and enhancing the QOL of distressed adults diagnosed with a BT

  5. Nutrition in adult patients with inflammatory bowel disease.

    PubMed

    Hebuterne, Xavier; Filippi, Jerome; Schneider, Stephane M

    2014-01-01

    Seventy five percent of hospitalized patients with Crohn's disease suffer from malnutrition. One third of Crohn's disease patients have a body mass index below 20. Sixty percent of Crohn's disease patients have sarcopenia. However some inflammatory bowel disease (IBD) patients are obese or suffer from sarcopenic-obesity. IBD patients have many vitamin and nutrient deficiencies, which can lead to important consequences such as hyperhomocysteinemia, which is associated with a higher risk of thromboembolic disease. Nutritional deficiencies in IBD patients are the result of insufficient intake, malabsorption and protein-losing enteropathy as well as metabolic disturbances directly induced by the chronic disease and its treatments, in particular corticosteroids. Screening for nutritional deficiencies in chronic disease patients is warranted. Managing the deficiencies involves simple nutritional guidelines, vitamin supplements, and nutritional support in the worst cases. PMID:25266810

  6. Propranolol Dosing Practices in Adult Burn Patients: Implications for Safety and Efficacy.

    PubMed

    Brown, David A; Gibbons, Janet; Honari, Shari; Klein, Matthew B; Pham, Tam N; Gibran, Nicole S

    2016-01-01

    Studies in children with burn injuries have demonstrated that propranolol improves metabolism and reduces muscle protein wasting. However, safety and efficacy in adults are less well established than in children. The purpose of this study was to determine safety of propranolol use in adult patients with burn injuries. Medical records were reviewed for burn-injured adults receiving propranolol. Patients between 18 and 65 years old and with ≥20% TBSA burn were included. Fifty-four patients met the criteria with mean age of 37 years and mean burn size of 38% TBSA. Propranolol dosages ranged from 0.1 to 3.8 mg/kg/day, with an average maximum dosage of 0.61 mg/kg/day. Mean heart rate decreased by 25% during 4 weeks. Seventy-two percent of patients experienced at least one episode of hypotension and 15% experienced bradycardia. Propranolol doses were most frequently held for low blood pressure; 32% of patients had at least one dose held for hypotension. This retrospective analysis suggests that modest dosing of propranolol results in frequent episodes of hypotension or bradycardia. Our data suggest that adults do not tolerate the higher doses reported in a pediatric population. Despite potential beneficial anti-catabolic effects of propranolol, burn care providers must recognize potential iatrogenic hemodynamic effects of this intervention. Our data support the need for prospective multicenter studies to delineate the safety and efficacy of propranolol in adult burn-injured patients. PMID:25882517

  7. Temporal Cytokine Profiles in Severely Burned Patients: A Comparison of Adults and Children

    PubMed Central

    Finnerty, Celeste C; Jeschke, Marc G; Herndon, David N; Gamelli, Richard; Gibran, Nicole; Klein, Matthew; Silver, Geoff; Arnoldo, Brett; Remick, Daniel; Tompkins, Ronald G

    2008-01-01

    A severe burn leads to hypermetabolism and catabolism resulting in compromised function and structural changes of essential organs. The release of cytokines has been implicated in this hypermetabolic response. The severity of the hypermetabolic response following burn injury increases with age, as does the mortality rate. Due to the relationship between the hypermetabolic and inflammatory responses, we sought to compare the plasma cytokine profiles following a severe burn in adults and in children. We enrolled 25 adults and 24 children who survived a flame burn covering more than 20% of total body surface area (TBSA). The concentrations of 22 cytokines were measured using the Linco multiplex array system (St. Charles, MO, USA). Large perturbations in the expression of pro- and anti-inflammatory cytokines were seen following thermal injury. During the first week following burn injury, IFN-γ, IL-10, IL-17, IL-4, IL-6, and IL-8 were detected at significantly higher levels in adults compared with children, P < 0.05. Significant differences were measured during the second week post-burn for IL-1β (higher in children) and IL-5 (higher in adults), P < 0.05. IL-18 was more abundant in children compared with adults during the third week post-burn, P < 0.05. Between post-burn d 21 and d 66, IL-1α was detected at higher concentrations in pediatric compared with adult patients, P < 0.05. Only GM-CSF expression was significantly different at all time points; it was detected at lower levels in pediatric patients, P < 0.05. Eotaxin, G-CSF, IL-13, IL-15, IP-10, MCP-1, and MIP-1α were detected at significantly different concentrations in adult compared with pediatric patients at multiple time points, P < 0.05. There were no differences in IL-12, IL-2, IL-7, or TNF levels in adult compared with pediatric burn patients at any of these time points. Following severe flame burns, the cytokine profiles in pediatric patients differ compared with those in adult patients, which may

  8. Epilepsy in Adults with Supratentorial Glioblastoma: Incidence and Influence Factors and Prophylaxis in 184 Patients

    PubMed Central

    Liang, Shuli; Zhang, Junchen; Zhang, Shaohui; Fu, Xiangping

    2016-01-01

    Aim To analyze the incidence of epilepsy in adult patients with supratentorial glioblastoma, assess the factors influencing the development of epilepsy in these cases, and evaluate patients’ response to antiepileptic drugs (AEDs) in a series of 184 patients. Methods We retrospectively analyzed the 184 adult patients diagnosed with supratentorial glioblastoma. All subjects were treated within our hospital and subsequently died between 2003 and 2013. The incidence of epilepsy was assessed before and after initial resection and reexamined every 2 months thereafter. We evaluated the efficacy of prophylactic AEDs in this patient population based on the gathered incidence data. Results Of 184 patients, 43 (23.37%) were diagnosed with epilepsy before their initial resection. The total incidence of epilepsy (both pre- and postoperative) was 68.48%. The prevalence of active epilepsy reached over 80% in patients with epilepsy and survival of greater than 13 months postoperatively. Patients with glioblastoma in the frontal and/or temporal lobes had a higher prevalence of epilepsy. In the 43 patients with preoperative epilepsy, total resection of glioblastoma resulted in significantly lower seizure frequency. Patients who received epilepsy prophylaxis with AEDs for at least 6 months had significantly fewer seizures and higher Karnofsky scores than those receiving AEDs for less than one month or not at all. Conclusion The incidence of epilepsy in adult patients with glioblastoma was high and responded poorly to AEDs in the short term. However, when taken for longer periods, AEDs can reduce the frequency of seizures in patients with glioblastoma. PMID:27438472

  9. Operative and nonoperative treatment options for ACL tears in the adult patient: a conceptual review.

    PubMed

    Bogunovic, Ljiljana; Matava, Matthew J

    2013-11-01

    Injury to the anterior cruciate ligament (ACL) is common among athletic individuals. Both nonoperative and operative treatment options exist. The optimal treatment of an adult with an ACL tear depends on several patient-specific factors, including age, occupation, and desired activity level. In less active patients with sedentary jobs, nonoperative management, consisting of physical therapy, bracing, and activity modification can yield successful results. In active patients who want to resume participation in jumping, cutting, or pivoting sports, patients who have physically demanding occupations, or patients who fail a trial of nonoperative management, ACL reconstruction is recommended. Reconstruction utilizing autograft tissue is preferred over allograft, especially in the younger athlete, but allograft tissue is a reasonable option in the older (aged > 40 years) and less active adult, as well. Successful results have been achieved with both patellar tendon and hamstring grafts. The optimal treatment in adult patients with ACL tears should be based on careful consideration of the patient's goals for return to activity, knee-specific comorbidities, such as coexistent meniscal pathology or osteoarthritis, and his or her willingness to follow a detailed rehabilitation regimen. Our article provides an overview of current nonoperative and operative treatment options for adults with ACL tears, considers the outcomes of both nonoperative and operative strategies, and provides general recommendations as to the ideal management for a given patient. PMID:24231595

  10. Effects of neurofeedback on adult patients with psychiatric disorders in a naturalistic setting.

    PubMed

    Cheon, Eun-Jin; Koo, Bon-Hoon; Seo, Wan-Seok; Lee, Jun-Yeob; Choi, Joong-Hyeon; Song, Shin-Ho

    2015-03-01

    Few well-controlled studies have considered neurofeedback treatment in adult psychiatric patients. In this regard, the present study investigates the characteristics and effects of neurofeedback on adult psychiatric patients in a naturalistic setting. A total of 77 adult patients with psychiatric disorders participated in this study. Demographic data and neurofeedback states were retrospectively analyzed, and the effects of neurofeedback were evaluated using clinical global impression (CGI) and subjective self-rating scales. Depressive disorders were the most common psychiatric disorders (19; 24.7 %), followed by anxiety disorders (18; 23.4 %). A total of 69 patients (89.6 %) took medicine, and the average frequency of neurofeedback was 17.39 ± 16.64. Neurofeedback was applied to a total of 39 patients (50.6 %) more than 10 times, and 48 patients (62.3 %) received both β/SMR and α/θ training. The discontinuation rate was 33.8 % (26 patients). There was significant difference between pretreatment and posttreatment CGI scores (<.001), and the self-rating scale also showed significant differences in depressive symptoms, anxiety, and inattention (<.001). This is a naturalistic study in a clinical setting, and has several limitations, including the absence of a control group and a heterogenous sample. Despite these limitations, the study demonstrates the potential of neurofeedback as an effective complimentary treatment for adult patients with psychiatric disorders. PMID:25740085

  11. Amount of bone marrow blasts is strongly correlated to NPM1 and FLT3-ITD mutation rate in AML with normal karyotype.

    PubMed

    Haferlach, Torsten; Bacher, Ulrike; Alpermann, Tamara; Haferlach, Claudia; Kern, Wolfgang; Schnittger, Susanne

    2012-01-01

    FLT3-ITDs are linked to higher leukocytes/blasts in acute myeloid leukemia. To evaluate the effect of NPM1 mutations, we correlated NPM1mut status with morphology in 805 adult normal karyotype AML. NPM1mut were found in 391/805 (48.6%), FLT3-ITD in 219/805 (27.2%). Frequencies of FLT3-ITD and NPM1mut cases were continuously increasing by blast decades: NPM1mut from 38/123 (30.9%) in 20-29% blast decade to 70/103 (68.0%) in 90-100% decade (p<0.001), FLT3-ITDs from 15/123 (12.2%) to 58/103 (56.3%) (p<0.001). Mean WBC count was highest in NPM1-mut/FLT3-ITD-positive and lowest in NPM1-wildtype/FLT3-ITD-negative patients (p<0.0001); similar for BM blasts. Therefore, FLT3-ITD and NPM1mut might synergistically stimulate blast proliferation. PMID:21621842

  12. Acute leukaemias in adult Ethiopians in a teaching hospital.

    PubMed

    Shamebo, M

    1994-01-01

    Eighty-two consecutive cases of acute leukaemias in adult Ethiopians were admitted to the Tikur Anbessa (Black Lion) Hospital, a teaching and referral hospital in Addis Abeba, Ethiopia, from January 1982 to December 1992. These cases were studied to describe the clinical and haematological findings, response to therapy and prognosis. The age range was 13-78 (mean 29.6) years. The male to female ratio was 1.6:1. Acute myeloblastic (AML) and acute lymphoblastic (ALL) leukaemias occurred in 53.7% and 46.3%, respectively. The commonest symptoms were anaemia, fever and bleeding tendencies. The commonest signs were pallor, fever, sternal tenderness and purpura. Splenomegaly was more commonly seen in ALL patients. The haematological findings were anaemia (mean Hgb 6.35 g%), leucocytosis (mean WBC count 88,507/mm3) and thrombocytopenia (mean platelet count 31,700/mm3). Of the patients eligible for evaluation treated with chemotherapeutic agents, only 38.4% of ALL and 6.2% of AML achieved complete remission. Twenty-seven patients with ALL died from one day to 84 (median 1.0) months after diagnosis. Ten are lost to follow-up from two weeks to 36 (median 2.5) months, one is still alive 40 months after diagnosis. Thirty-nine of the AML patients died from one day to nine (median 0.3) months after diagnosis. Five are lost to follow-up from two weeks to two and a half (median 2.0) months. The causes of death were sepsis and bleeding, separately or in combination. Increasing numbers of acute leukaemia patients are being referred to this centre. Therefore, attempts should be made to equip it for the treatment of such cases. PMID:8187778

  13. Deletion and deletion/insertion mutations in the juxtamembrane domain of the FLT3 gene in adult acute myeloid leukemia

    PubMed Central

    Deeb, Kristin K.; Smonskey, Matthew T.; DeFedericis, HanChun; Deeb, George; Sait, Sheila N.J.; Wetzler, Meir; Wang, Eunice S.; Starostik, Petr

    2014-01-01

    In contrast to FLT3 ITD mutations, in-frame deletions in the FLT3 gene have rarely been described in adult acute leukemia. We report two cases of AML with uncommon in-frame mutations in the juxtamembrane domain of the FLT3 gene: a 3-bp (c.1770_1774delCTACGinsGT; p.F590_V592delinsLF) deletion/insertion and a 12-bp (c.1780_1791delTTCAGAGAATAT; p.F594_Y597del) deletion. We verified by sequencing that the reading frame of the FLT3 gene was preserved and by cDNA analysis that the mRNA of the mutant allele was expressed in both cases. Given the recent development of FLT3 inhibitors, our findings may be of therapeutic value for AML patients harboring similar FLT3 mutations. PMID:25379410

  14. Practical review of immunizations in adult patients with cancer

    PubMed Central

    Ariza-Heredia, Ella J; Chemaly, Roy F

    2015-01-01

    Compared with the general population, patients with cancer in general are more susceptible to vaccine-preventable infections, either by an increased risk due to the malignancy itself or immunosuppressive treatment. The goal of immunizations in these patients is therefore to provide protection against these infections, and to decrease the number of vulnerable patients who can disseminate these organisms. The proper timing of immunization with cancer treatment is key to achieving better vaccine protection. As the oncology field continues to advance, leading to better quality of life and longer survival, immunization and other aspects of preventive medicine ought to move to the frontline in the care of these patients. Herein, we review the vaccines most clinically relevant to patients with cancer, as well as special cases including vaccines after splenectomy, travel immunization and recommendations for family members. PMID:26110220

  15. Anaplastic large cell lymphoma in paediatric and young adult patients.

    PubMed

    Turner, Suzanne D; Lamant, Laurence; Kenner, Lukas; Brugières, Laurence

    2016-05-01

    Anaplastic large cell lymphoma (ALCL) is a heterogeneous disease of debateable origin that, in children, is largely anaplastic lymphoma kinase (ALK) positive with aberrant ALK activity induced following the formation of chromosomal translocations. Whilst the survival rates for this disease are relatively high, a significant proportion (20-40%) of patients suffer disease relapse, in some cases on multiple occasions and therefore suffer the toxic side-effects of combination chemotherapy. Traditionally, patients are treated with a combination of agents although recent data from relapse patients have suggested that low risk patients might benefit from single agent vinblastine and, going forward, the addition of ALK inhibitors to the therapeutic regimen may have beneficial consequences. There are also a plethora of other drugs that might be advantageous to patients with ALCL and many of these have been identified through laboratory research although the decision as to which drugs to implement in trials will not be trivial. PMID:26913827

  16. Parental substance abuse, reports of chronic pain and coping in adult patients with sickle cell disease.

    PubMed Central

    Edwards, Christopher; Whitfield, Keith; Sudhakar, Shiv; Pearce, Michele; Byrd, Goldie; Wood, Mary; Feliu, Miriam; Leach-Beale, Brittani; DeCastro, Laura; Whitworth, Elaine; Abrams, Mary; Jonassaint, Jude; Harrison, M. Ojinga; Mathis, Markece; Scott, Lydia; Johnson, Stephanie; Durant, Lauren; Holmes, Anita; Presnell, Katherine; Bennett, Gary; Shelby, Rebecca; Robinson, Elwood

    2006-01-01

    There is increasing interest from a social learning perspective in understanding the role of parental factors on adult health behaviors and health outcomes. Our review revealed no studies, to date, that have evaluated the effects of parental substance abuse on reports of chronic pain and coping in adult patients with sickle cell disease (SCD). We explored the effects of parental substance (alcohol or drug) abuse on reports of the sensory, affective and summary indices of pain in 67 adult patients, mean age 38.9 (13.5), with SCD. We also explored the effects of parental substance abuse on psychopathology associated with pain and active coping. Twenty-four percent of patients reported that their parent(s) abused substances. Patients whose parent(s) were characterized as substance abusers reported greater sensory (p=0.02), affective (p=0.01) and summary (VAS; p=0.02) indices of pain as compared to their counterparts, whose parent(s) were not characterized as substance abusers. Patients did not differ in average age, education or the propensity to respond in a socially acceptable manner. There was a significant trend towards patients who characterized their parents as abusers scoring higher than their counterparts on active coping. We propose a Social Learning Theory to explain the current findings and suggest a need for additional prospective research to simultaneously explore biological (genetic) and social factors that influence the interpretation, experience and reporting of chronic pain in adult patients with chronic disease. PMID:16573309

  17. Intensive care outcomes in adult hematopoietic stem cell transplantation patients

    PubMed Central

    Bayraktar, Ulas D; Nates, Joseph L

    2016-01-01

    Although outcomes of intensive care for patients undergoing hematopoietic stem cell transplantation (HSCT) have improved in the last two decades, the short-term mortality still remains above 50% among allogeneic HSCT patients. Better selection of HSCT patients for intensive care, and consequently reduction of non-beneficial care, may reduce financial costs and alleviate patient suffering. We reviewed the studies on intensive care outcomes of patients undergoing HSCT published since 2000. The risk factors for intensive care unit (ICU) admission identified in this report were primarily patient and transplant related: HSCT type (autologous vs allogeneic), conditioning intensity, HLA mismatch, and graft-versus-host disease (GVHD). At the same time, most of the factors associated with ICU outcomes reported were related to the patients’ functional status upon development of critical illness and interventions in ICU. Among the many possible interventions, the initiation of mechanical ventilation was the most consistently reported factor affecting ICU survival. As a consequence, our current ability to assess the benefit or futility of intensive care is limited. Until better ICU or hospital mortality prediction models are available, based on the available evidence, we recommend practitioners to base their ICU admission decisions on: Patient pre-transplant comorbidities, underlying disease status, GVHD diagnosis/grade, and patients’ functional status at the time of critical illness. PMID:26862493

  18. Clonal evolution and devolution after chemotherapy in adult acute myelogenous leukemia

    PubMed Central

    Parkin, Brian; Ouillette, Peter; Li, Yifeng; Keller, Jennifer; Lam, Cindy; Roulston, Diane; Li, Cheng; Shedden, Kerby

    2013-01-01

    The frequent occurrence of persistent or relapsed disease after induction chemotherapy in AML necessitates a better understanding of the clonal relationship of AML in various disease phases. In this study, we used SNP 6.0 array-based genomic profiling of acquired copy number aberrations (aCNA) and copy neutral LOH (cnLOH) together with sequence analysis of recurrently mutated genes to characterize paired AML genomes. We analyzed 28 AML sample pairs from patients who achieved complete remission with chemotherapy and subsequently relapsed and 11 sample pairs from patients with persistent disease after induction chemotherapy. Through review of aCNA/cnLOH and gene mutation profiles in informative cases, we demonstrate that relapsed AML invariably represents re-emergence or evolution of a founder clone. Furthermore, all individual aCNA or cnLOH detected at presentation persisted at relapse indicating that this lesion type is proximally involved in AML evolution. Analysis of informative paired persistent AML disease samples uncovered cases with 2 coexisting dominant clones of which at least one was chemotherapy sensitive and one resistant, respectively. These data support the conclusion that incomplete eradication of AML founder clones rather than stochastic emergence of fully unrelated novel clones underlies AML relapse and persistence with direct implications for clinical AML research. PMID:23175688

  19. Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders.

    PubMed

    Laport, Ginna G; Sandmaier, Brenda M; Storer, Barry E; Scott, Bart L; Stuart, Monic J; Lange, Thoralf; Maris, Michael B; Agura, Edward D; Chauncey, Thomas R; Wong, Ruby M; Forman, Stephen J; Petersen, Finn B; Wade, James C; Epner, Elliot; Bruno, Benedetto; Bethge, Wolfgang A; Curtin, Peter T; Maloney, David G; Blume, Karl G; Storb, Rainer F

    2008-02-01

    Allogeneic hematopoietic cell transplantation (HCT) is the only curative strategy for patients with myelodysplastic syndrome (MDS) and myeloproliferative disorders (MPD). We report the results of 148 patients (median age = 59 years old) with de novo MDS (n = 40), acute myelogenous leukemia (AML) after antecedent MDS/MPD (n = 49), treatment-related MDS (t-MDS) (n = 25), MPD (n = 27), and chronic myelomonocytic leukemia (CMML) (n = 7) who underwent allogeneic HCT using a conditioning regimen of low-dose total body irradiation (TBI) alone (200 cGy) on day 0 (n = 5) or with the addition of fludarabine (Flu) 30 mg/m(2)/day on days -4 to -2 (n = 143). Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil (MMF). Seventy-five patients (51%) received an allograft from a matched related donor (MRD), and 73 patients (49%) were recipients of unrelated donor (URD) grafts. There was no significant difference in the incidence of acute (gr II-IV) and chronic extensive graft-versus-host disease (aGVHD, cGVHD) between the recipients of related and unrelated donor grafts. By day +28, 75% of patients demonstrated mixed T cell chimerism. Graft rejection was seen in 15% of patients. With a median follow-up of 47 (range: 6-89) months, the 3-year relapse-free survival (RFS) and overall survival (OS) are both 27% for all patients, with a relapse incidence of 41%. The 3-year RFS for the patients with de novo MDS, AML after antecedent MDS/MPD, t-MDS, MPD, and CMML were 22%, 20%, 29%, 37%, and 43%, respectively, and the 3-year OS was 20%, 23%, 27%, 43%, and 43%, respectively. The 3-year nonrelapse mortality (NRM) was 32%. Factors associated with a lower risk of relapse were the development of extensive cGVHD and having a low risk or intermediate-1 risk International Prognostic Score for the de novo MDS patients. Nonmyeloablative HCT confers remissions in patients who otherwise were not eligible for conventional HCT but for whom relapse is the leading cause of

  20. Management of Spinal Deformity in Adult Patients With Neuromuscular Disease.

    PubMed

    Protopsaltis, Themistocles S; Boniello, Anthony J; Schwab, Frank J

    2016-09-01

    A wide range of neuromuscular diseases, including Parkinson disease, cerebral palsy, multiple sclerosis, and myopathy, are associated with spinal deformities. The most common postural deformities include anterocollis, Pisa syndrome (pleurothotonus), scoliosis, and camptocormia. Nonsurgical management of spinal deformity in patients with neuromuscular disease centers on maximizing the medical management of the underlying neurodegenerative pathology before surgical intervention is contemplated. Surgical management can include decompression alone, or decompression and fusion with short or long fusion constructs. Patients with neuromuscular disease are susceptible to postoperative medical complications, such as delirium, epidural hematomas, pulmonary emboli, and cardiac events. Compared with outcomes in the typical patient with spinal deformity, postoperative outcomes in patients with neuromuscular disease have higher rates of surgical complications, such as instrumentation failure, proximal junctional kyphosis, loss of correction, and the need for revision surgery, regardless of the magnitude of surgical treatment. PMID:27471900

  1. Transfusions for anemia in adult and pediatric patients with malignancies.

    PubMed

    Shah, Neil; Andrews, Jennifer; Goodnough, Lawrence Tim

    2015-09-01

    Anemia is present in over two-thirds of patients with malignant hematological disorders. The etiology of anemia predominates from ineffective erythropoiesis from marrow infiltration, cytokine related suppression, erythropoietin suppression, and vitamin deficiency; ineffective erythropoiesis is further exacerbated by accelerated clearance due to antibody mediated hemolysis and thrombotic microangiopathy. As the anemia is chronic in nature, symptoms are generally well tolerated and often non-specific. Transfusion of red blood cells (RBCs) is a balance between providing benefit for patients while avoiding risks of transfusion. Conservative/restrictive RBC transfusion practices have shown equivalent patient outcomes compared to liberal transfusion practices, and meta-analysis has shown improved in-hospital mortality, reduced cardiac events, re-bleeding, and bacterial infections. The implications for a lower threshold for transfusion in patients with malignancies are therefore increasingly being scrutinized. Alternative management strategies for anemia with IV iron and erythropoietin stimulating agents (ESAs) should be considered in the appropriate settings. PMID:25796130

  2. Use of Patient Portals for Personal Health Information Management: The Older Adult Perspective.

    PubMed

    Turner, Anne M; Osterhage, Katie; Hartzler, Andrea; Joe, Jonathan; Lin, Lorelei; Kanagat, Natasha; Demiris, George

    2015-01-01

    The personal health information management (PHIM) practices and needs of older adults are poorly understood. We describe initial results from the UW SOARING project (Studying Older Adults & Researching Information Needs and Goals), a participatory design investigation of PHIM in older adults (60 years and older). We conducted in-depth interviews with older adults (n=74) living in a variety of residential settings about their management of personal health information. A surprising 20% of participants report using patient portals and another 16% reported prior use or anticipated use of portals in the future. Participants cite ease of access to health information and direct communication with providers as valuable portal features. Barriers to the use of patient portals include a general lack of computer proficiency, high internet costs and security concerns. Design features based on consideration of needs and practices of older adults will facilitate appeal and maximize usability; both are elements critical to adoption of tools such as patient portals that can support older adults and PHIM. PMID:26958263

  3. Use of Patient Portals for Personal Health Information Management: The Older Adult Perspective

    PubMed Central

    Turner, Anne M.; Osterhage, Katie; Hartzler, Andrea; Joe, Jonathan; Lin, Lorelei; Kanagat, Natasha; Demiris, George

    2015-01-01

    The personal health information management (PHIM) practices and needs of older adults are poorly understood. We describe initial results from the UW SOARING project (Studying Older Adults & Researching Information Needs and Goals), a participatory design investigation of PHIM in older adults (60 years and older). We conducted in-depth interviews with older adults (n=74) living in a variety of residential settings about their management of personal health information. A surprising 20% of participants report using patient portals and another 16% reported prior use or anticipated use of portals in the future. Participants cite ease of access to health information and direct communication with providers as valuable portal features. Barriers to the use of patient portals include a general lack of computer proficiency, high internet costs and security concerns. Design features based on consideration of needs and practices of older adults will facilitate appeal and maximize usability; both are elements critical to adoption of tools such as patient portals that can support older adults and PHIM. PMID:26958263

  4. Undifferentiated embryonal sarcoma of the liver in an adult patient.

    PubMed

    Lee, Kyu Ho; Maratovich, Mussin Nadiar; Lee, Kyoung-Bun

    2016-06-01

    Undifferentiated embryonal sarcoma of the liver (UESL) is rare primary hepatic sarcoma and is known to occur in pediatric patients. This case is the UESL occurred in a 51-year old male patient. Multilocular cystic lesion was composed of primitive spindle cells without specific differentiation. This rare case would help to review differential diagnosis of primary sarcoma in liver and cystic neoplasm of the liver. PMID:27377912

  5. Patient satisfaction and ethnic identity among American Indian older adults.

    PubMed

    Garroutte, Eva Marie; Kunovich, Robert M; Jacobsen, Clemma; Goldberg, Jack

    2004-12-01

    Work in the field of culturally competent medical care draws on studies showing that minority Americans often report lower satisfaction with care than White Americans and recommends that providers should adapt care to patients' cultural needs. However, empirical evidence in support of cultural competence models is limited by reliance upon measurements of racial rather than ethnic identity and also by a near-total neglect of American Indians. This project explored the relationship between ethnic identity and satisfaction using survey data collected from 115 chronically ill American Indian patients >or=50 years at a Cherokee Nation clinic. Satisfaction scores were high overall and comparable to those found in the general population. Nevertheless, analysis using hierarchical linear modeling showed that patients' self-rated American Indian ethnic identity was significantly associated with satisfaction. Specifically, patients who rated themselves high on the measure of American Indian ethnic identity reported reduced scores on satisfaction with health care providers' social skill and attentiveness, as compared to those who rated themselves lower. Significant associations remained after controlling for patients' sex, age, education, marital status, self-reported health, wait time, and number of previous visits. There were no significant associations between patients' American Indian ethnic identity and satisfaction with provider's technical skill and shared decision-making. Likewise, there were no significant associations between satisfaction and a separate measure of White American ethnic identity, although a suggestive trend was observed for satisfaction with provider's social skill. Our findings demonstrate the importance of including measures of ethnic identity in studies of medical satisfaction in racial minority populations. They support the importance of adapting care to patient's cultural needs, and they highlight the particular significance of interpersonal

  6. Undifferentiated embryonal sarcoma of the liver in an adult patient

    PubMed Central

    Lee, Kyu Ho; Maratovich, Mussin Nadiar; Lee, Kyoung-Bun

    2016-01-01

    Undifferentiated embryonal sarcoma of the liver (UESL) is rare primary hepatic sarcoma and is known to occur in pediatric patients. This case is the UESL occurred in a 51-year old male patient. Multilocular cystic lesion was composed of primitive spindle cells without specific differentiation. This rare case would help to review differential diagnosis of primary sarcoma in liver and cystic neoplasm of the liver. PMID:27377912

  7. Transition of pediatric patients to adult care: an analysis of provider perceptions across discipline and role.

    PubMed

    O'Sullivan-Oliveira, Joanne; Fernandes, Susan M; Borges, Lawrence F; Fishman, Laurie N

    2014-01-01

    The importance of successfully transitioning pediatric patients to adult care is increasingly recognized as more children with chronic diseases are living to adulthood. The aim of this study was to investigate the current state of provider perceptions across disciplines regarding transition of pediatric patients to adult care. Focus groups made up of providers of various roles and experience levels were conducted. A total of six major themes were identified. We conclude that pediatric providers share common concerns about transitioning pediatric patients to adult care. We reinforce many of the issues raised in the literature and also discuss a sense of professional ego that was identified as a barrier to successful transition, which is not widely reported in other studies. PMID:25134224

  8. Epigenetic therapy as a novel approach for GFI136N-associated murine/human AML.

    PubMed

    Botezatu, Lacramioara; Michel, Lars C; Helness, Anne; Vadnais, Charles; Makishima, Hideki; Hönes, Judith M; Robert, François; Vassen, Lothar; Thivakaran, Aniththa; Al-Matary, Yahya; Lams, Robert F; Schütte, Judith; Giebel, Bernd; Görgens, André; Heuser, Michael; Medyouf, Hind; Maciejewski, Jaroslaw; Dührsen, Ulrich; Möröy, Tarik; Khandanpour, Cyrus

    2016-08-01

    Epigenetic changes can contribute to development of acute myeloid leukemia (AML), a malignant disease of the bone marrow. A single-nucleotide polymorphism of transcription factor growth factor independence 1 (GFI1) generates a protein with an asparagine at position 36 (GFI1(36N)) instead of a serine at position 36 (GFI1(36S)), which is associated with de novo AML in humans. However, how GFI1(36N) predisposes to AML is poorly understood. To explore the mechanism, we used knock-in mouse strains expressing GFI1(36N) or GFI1(36S). Presence of GFI1(36N) shortened the latency and increased the incidence of AML in different murine models of myelodysplastic syndrome/AML. On a molecular level, GFI1(36N) induced genomewide epigenetic changes, leading to expression of AML-associated genes. On a therapeutic level, use of histone acetyltransferase inhibitors specifically impeded growth of GFI1(36N)-expressing human and murine AML cells in vitro and in vivo. These results establish, as a proof of principle, how epigenetic changes in GFI1(36N)-induced AML can be targeted. PMID:27216773

  9. Antiretroviral adherence and treatment outcomes among adult Ethiopian patients.

    PubMed

    Bezabhe, Woldesellassie M; Chalmers, Leanne; Bereznicki, Luke R; Gee, Peter; Peterson, Gregory M

    2016-08-01

    Developing appropriate strategies to sustain optimal medication adherence among the increasing number of HIV-positive patients taking antiretroviral therapy (ART) in sub-Saharan Africa is a major challenge. The objective of this study was to determine patient, regimen, disease, patient-provider, and healthcare-related factors associated with adherence with ART over a one-year period, and assess the impact of adherence on treatment outcomes. We performed a prospective, observational study among 246 patients who were initiated on ART in Ethiopia. Of 172 who completed follow-up, 130 (75.6%) had ≥95% adherence. In the multivariate analyses, a higher baseline BMI (OR, 1.2; 95% CI 1.0, 1.4) and use of reminder devices (OR, 9.1; 95% CI 2.0, 41.6) remained positively associated with adherence, while a higher HIV symptom and adverse drug reaction distress score was an independent negative predictor of adherence (OR, 0.90; 95% CI 0.9, 1.0) CD4 count increase was significantly higher in the adherent patients compared to non-adherent patients at 12 months (159 cells/µL [interquartile range (IQR), 72-324 cells/µL] vs. 132 cells/µL [IQR, 43-190 cells/µL]; p = 0.026). Our findings indicate that interventions aimed at improving adherence and thereby treatment outcomes in patients initiated on ART should promote the use of reminder devices, and monitor HIV symptoms and adverse reaction distress and nutritional status. PMID:26829232

  10. Treatment of Acute Myeloid Leukemia in Elderly Patients-A Therapeutic Dilemma.

    PubMed

    Mamdani, Hirva; Santos, Cedric Dos; Konig, Heiko

    2016-07-01

    Older adults represent the majority of approximately 20,000 new patients diagnosed with acute myeloid leukemia (AML) in the United States each year. While the treatment goal for younger patients is to achieve a cure with intensive therapeutic protocols, including standard chemotherapy and hematopoietic stem cell transplantation, these goals are less well defined in the elderly population. This is in part due to the continuous decline in treatment outcomes with increasing age secondary to a number of patient-related and disease-specific factors, ranging from the presence of comorbid conditions to the higher frequency of adverse cytogenetic and unfavorable molecular markers. Although best supportive care, low-dose cytarabine, and epigenetic drugs represent well recognized treatment concepts, no universally accepted strategy for the management of elderly patients with AML exists. Therapeutic decisions are widely based on the patient's age, general health, the disease features, as well as the patient's personal wishes. The predicament of treating AML in the elderly population is the central theme of this review. PMID:27073039

  11. Percutaneous Endovascular Treatment of Hepatic Artery Stenosis in Adult and Pediatric Patients After Liver Transplantation

    SciTech Connect

    Maruzzelli, Luigi; Miraglia, Roberto Caruso, Settimo; Milazzo, Mariapina; Mamone, Giuseppe; Gruttadauria, Salvatore; Spada, Marco; Luca, Angelo; Gridelli, Bruno

    2010-12-15

    The purpose of this study was to evaluate the efficacy of percutaneous endovascular techniques for the treatment of hepatic artery stenosis (HAS) occurring after liver transplantation (LT) in adult and pediatrics patients. From February 2003 to March 2009, 25 patients (15 adults and 10 children) whose developed HAS after LT were referred to our interventional radiology unit. Technical success was achieved in 96% (24 of 25) of patients. Percutaneous transluminal angioplasty (PTA) was performed in 13 patients (7 children), and stenting was performed in 11 patients (2 children). After the procedure, all patients were followed-up with liver function tests, Doppler ultrasound, and/or computed tomography. Mean follow-up was 15.8 months (range 5 days to 58 months). Acute hepatic artery thrombosis occurred immediately after stent deployment in 2 patients and was successfully treated with local thrombolysis. One patient developed severe HA spasm, which reverted after 24 h. After the procedure, mean trans-stenotic pressure gradient decreased from 30.5 to 6.2 mmHg. Kaplan-Meyer curve of HA primary patency was 77% at 1 and 2 years. During the follow-up period, 5 patients (20%) had recurrent stenosis, and 2 patients (8.3%) had late thrombosis. Two of 7 patients with stenosis/thrombosis underwent surgical revascularization (n = 1) and liver retransplantation (n = 1). Six (25%) patients died during follow-up, but overall mortality was not significantly different when comparing patients having patent hepatic arteries with those having recurrent stenosis/thrombosis. There were no significant differences in recurrent stenosis/thrombosis and mortality comparing patients treated by PTA versus stenting and comparing adult versus pediatric status. Percutaneous interventional treatment of HAS in LT recipients is safe and effective and decreases the need for surgical revascularization and liver retransplantation. However, the beneficial effects for survival are not clear, probably because

  12. Structure of the AML1-ETO eTAFH domain-HEB peptide complex and its contribution to AML1-ETO activity.

    PubMed

    Park, Sangho; Chen, Wei; Cierpicki, Tomasz; Tonelli, Marco; Cai, Xiongwei; Speck, Nancy A; Bushweller, John H

    2009-04-01

    AML1-ETO is the chimeric protein product of the t(8;21) in acute myeloid leukemia. The ETO portion of the fusion protein includes the eTAFH domain, which is homologous to several TATA binding protein-associated factors (TAFs) and interacts with E proteins (E2A and HEB). It has been proposed that AML1-ETO-mediated silencing of E protein function might be important for t(8;21) leukemogenesis. Here, we determined the solution structure of a complex between the AML1-ETO eTAFH domain and an interacting peptide from HEB. On the basis of the structure, key residues in AML1-ETO for HEB association were mutated. These mutations do not impair the ability of AML1-ETO to enhance the clonogenic capacity of primary mouse bone marrow cells and do not eliminate its ability to repress proliferation or granulocyte differentiation. Therefore, the eTAFH-E protein interaction appears to contribute relatively little to the activity of AML1-ETO. PMID:19204326

  13. Imaging assessment and clinical significance of pneumatosis in adult patients.

    PubMed

    Lassandro, Francesco; Valente, Tullio; Rea, Gaetano; Lassandro, Giulia; Golia, Erica; Brunese, Luca; Laghi, Andrea

    2015-01-01

    Gas detection in the bowel wall and in portomesenteric venous vessels in adults has long been related to intestinal infarction and poor outcome; many case reports have shown that pneumatosis may be associated with a large variety of pathological situations, ranging from absolutely benign and asymptomatic forms to abdominal catastrophes. Several studies have been conducted on this topic with different conclusions, probably due to differences in population so that the clinical value of these signs is still questioned. Intestinal pneumatosis, especially if presenting with a band-like pattern and if associated with portomesenteric vein gas, when observed in an acute abdominal setting should raise the suspicion of mesenteric infarct and prompt a careful search for other signs of intestinal involvement, so as not to miss cases of life-threatening intestinal infarct or allow them to further evolve into extensive necrosis with worse prognosis. In this review we illustrate the most relevant aspects of these debated but significant radiological signs. PMID:25297049

  14. Kidney transplantation in an adult patient with VACTERL association.

    PubMed

    Cimen, Sertac; Nantais, Jordan; Guler, Sanem; Lawen, Joseph

    2015-01-01

    The vertebral, anal, cardiac, tracheoesophageal, renal, and limb birth defects (VACTERL) association is a rare, non-random constellation of congenital abnormalities among which urinary tract anomalies can be included. In the presence of these anomalies, patients are suspected to have a higher rate of renal failure than average. We report a case of a 22-year-old woman with VACTERL association and consequent end stage renal failure. A live-related kidney transplant was carried out successfully and the postoperative course was uncomplicated. The patient had immediate graft function. Risk factors that may complicate kidney transplant surgery in this patient population as well as considerations relevant to peritransplant management are discussed. PMID:26106170

  15. Underdiagnosis of Attention-Deficit/Hyperactivity Disorder in Adult Patients: A Review of the Literature

    PubMed Central

    Quintero, Javier; Anand, Ernie; Casillas, Marta; Upadhyaya, Himanshu P.

    2014-01-01

    Objective: To raise awareness of attention-deficit/hyperactivity disorder (ADHD) as an underdiagnosed, undertreated, often comorbid, and debilitating condition in adults. Data Sources: PubMed was searched using combinations of keywords, including ADHD, adult, diagnosis, identify, prevalence, and comorbid, to find articles published between 1976 and 2013. Study Selection: In total, 99 articles were selected for inclusion on the basis of their relevance to the objective and importance to and representation of ADHD research, including international guidelines for adults with ADHD. Results: In a large proportion of children with ADHD, symptoms persist into adulthood. However, although adults with ADHD often experience chaotic lifestyles, with impaired educational and vocational achievement and higher risks of substance abuse and imprisonment, many remain undiagnosed and/or untreated. ADHD is usually accompanied by other psychiatric comorbidities (such as major depressive disorder, anxiety disorder, and alcohol abuse). Indeed, adults with ADHD are more likely to present to a psychiatric clinic for treatment of their comorbid disorders than for ADHD, and their ADHD symptoms are often mistaken for those of their comorbidities. Untreated ADHD in adults with psychiatric comorbidities leads to poor clinical and functional outcomes for the patient even if comorbidities are treated. Effective treatment of adults’ ADHD improves symptoms, emotional lability, and patient functioning, often leading to favorable outcomes (eg, safer driving, reduced criminality). A few medications have now been approved for use in adults with ADHD, while a multimodal approach involving psychotherapy has also shown promising results. Conclusions General psychiatrists should familiarize themselves with the symptoms of ADHD in adults in order to diagnose and manage ADHD and comorbidities appropriately in these patients. PMID:25317367

  16. A snapshot of the adult spina bifida patient – high incidence of urologic procedures

    PubMed Central

    Liu, Joceline S.; Greiman, Alyssa; Casey, Jessica T.; Mukherjee, Shubhra

    2016-01-01

    Introduction To describe the urologic outcomes of contemporary adult spina bifida patients managed in a multidisciplinary clinic. Material and methods A retrospective chart review of patients seen in our adult spina bifida clinic from January 2004 to November 2011 was performed to identify urologic management, urologic surgeries, and co-morbidities. Results 225 patients were identified (57.8% female, 42.2% male). Current median age was 30 years (IQR 27, 36) with a median age at first visit of 25 years (IQR 22, 30). The majority (70.7%) utilized clean intermittent catheterization, and 111 patients (49.3%) were prescribed anticholinergic medications. 65.8% had urodynamics performed at least once, and 56% obtained appropriate upper tract imaging at least every other year while under our care. 101 patients (44.9%) underwent at least one urologic surgical procedure during their lifetime, with a total of 191 procedures being performed, of which stone procedures (n = 51, 26.7%) were the most common. Other common procedures included continence procedures (n = 35, 18.3%) and augmentation cystoplasty (n = 29, 15.2%). Only 3.6% had a documented diagnosis of chronic kidney disease and 0.9% with end-stage renal disease. Conclusions Most adult spina bifida patient continue on anticholinergic medications and clean intermittent catheterization. A large percentage of patients required urologic procedures in adulthood. Patients should be encouraged to utilize conservative and effective bladder management strategies to reduce their risk of renal compromise. PMID:27123330

  17. Perioperative Hemoglobin Trajectory in Adult Cardiac Surgical Patients

    PubMed Central

    Scott, David A.; Tung, Hon-Ming Andrew; Slater, Reuben

    2015-01-01

    Abstract: Preoperative anemia and nadir hemoglobin (Hb) during cardiopulmonary bypass (CPB) have been identified as significant risk factors for blood transfusion during cardiac surgery. The aim of this study was to confirm the association between preoperative anemia, perioperative fluid management, and blood transfusion. In addition, the proportion of elective cardiac surgery patients presenting for surgery with anemia was identified to examine whether the opportunity exists for timely diagnosis and intervention. Data from referral until hospital discharge were comprehensively reviewed over a 12-month period for all nonemergency cardiac surgical patients operated on in our institution. Of the 342 patients identified, elective cases were referred a median of 35 days before preoperative clinic and operated on a median of 14 days subsequently. Subacute cases had a median of 3 days from referral to surgery. As per the World Health Organization (WHO) criteria for anemia, 24.2% of elective and 29.6% of subacute patients were anemic. Blood transfusion was administered to 46.2% of patients during their admission. Transfusion was more likely in patients who were female (odds ratio [OR]: 2.45, 95%confidence interval [CI]: 1.28–4.70), had a low body mass index (BMI) (OR: .89, 95% CI: .84–.94), preoperative anemia (OR: 5.15, 95% CI: 2.59–10.24), or renal impairment (OR: 5.44, 95% CI: 2.42–12.22). Hemodilution minimization strategies reduced the Hb fall during CPB, but not transfusion rates. This study identifies a high prevalence of preoperative anemia with sufficient time for elective referrals to undergo appropriate diagnosis and interventions. It also confirms that low red cell mass (anemia and low BMI) and renal impairment are predictors of perioperative blood transfusion. Perfusion strategies to reduce hemodilution are effective at minimizing the intraoperative fall in Hb concentration but did not influence transfusion rate. PMID:26543251

  18. A patient - centered approach to addressing physical activity in older adults: motivational interviewing.

    PubMed

    Letourneau, Katherine; Goodman, Janice H

    2014-11-01

    Regular physical activity reduces the burden of chronic diseases in older adults, but the majority of this population is relatively sedentary. Individuals considering a change in behavior, such as increasing exercise, often experience a mental state of ambivalence, which can lead to inaction. Ambivalence is resistant to traditional counseling methods used in medical settings, such as patient education. Motivational interviewing (MI) is a conversational style that has been shown to help overcome ambivalence by guiding patients to voice their personal reasons for change. Nurse practitioners are uniquely positioned to use MI with older adults to address ambivalence toward increasing physical activity. PMID:25199152

  19. Allogeneic hematopoietic cell transplantation in adult patients with acute lymphoblastic leukemia.

    PubMed

    Marks, David I; Alonso, Laura; Radia, Rohini

    2014-12-01

    This review discusses the use of prognostic factors, patient and donor selection, choice of conditioning regimens, and timing of transplant. It also describes the management of Philadelphia-positive acute lymphocytic leukemia (ALL) and central nervous system disease. All aggressively treated adults with ALL should be considered for allogeneic transplantation and tissue typed at diagnosis. We further suggest that eligible patients be entered into clinical trials (that incorporate transplantation); these unselected prospective outcome data are essential to evaluate the true value of allogeneic transplantation in adults with ALL. PMID:25459175

  20. [Perioperative management of adult patients with obstructive sleep apnea].

    PubMed

    Rösslein, Martin

    2015-03-01

    Obstructive sleep apnea (OSA) is a common sleep related breathing disorder with an increasing prevalence. Most surgical patients with OSA have not been diagnosed prior to surgery and are at an increased risk of developing perioperative complications. Preoperative identification of these patients is important in order to take appropriate measures concerning a safe perioperative management. While the level of scientific evidence for single measures is still low, several steps seem prudent: Preoperatively, sedating medications should only be applied with extreme caution. Anesthetic management should focus on regional anesthetic techniques and reduction of systemic opioids. In the case of general anesthesia, an increased risk of a patient presenting with a difficult airway should be appreciated. The extent and duration of postoperative continuous monitoring has to be determined on an individual basis. A preoperatively existing therapy with continuous positive airway pressure should be continued postoperatively as soon as possible. Patients with OSA may be managed on an outpatient basis if certain requirements are met. PMID:25850644

  1. Use of caries preventive agents on adult patients compared to pediatric patients by general practitioners: findings from The Dental Practice-Based Research Network

    PubMed Central

    Riley, Joseph L.; Gordan, Valeria V.; Rindal, D. Brad; Fellows, Jeffrey L.; Williams, O. Dale; Ritchie, Lloyd K.; Gilbert, Gregg H.

    2010-01-01

    Background Evidence suggests that caries prevention reduces caries in adults. This study tested the frequency of recommended caries prevention agents for children compared to adult patients. Methods This study surveyed 467 Dental Practice-Based Research Network general dentists who practice within the United States and treat both pediatric and adult patients. Dentists were asked the percentage of their patients who are administered or recommended dental sealants, in-office and at-home fluoride, chlorhexidine rinse, and xylitol gum. Results Adults were less likely to receive in-office caries preventive agents compared to pediatric patients. However, the rate of recommendation for at-home preventive regimens was very similar. Dentists with a conservative approach to caries treatment were the most likely to use caries prevention at similar rates in adults as in children. In addition, practices with a greater number of patients with dental insurance were significantly less likely to provide in-office fluoride or sealants to adult patients than to their pediatric patients. Conclusion In-office caries prevention agents are more commonly used by general dentists for their pediatric patients compared to their adult patients. Practice Implications Some general dentists should consider providing additional in-office prevention agents for their adult patients who are at increased risk for dental caries. PMID:20516100

  2. Neighborhood Socioeconomic Status, Race, and Mortality in Young Adult Dialysis Patients

    PubMed Central

    Estrella, Michelle M.; Crews, Deidra C.; Appel, Lawrence J.; Anderson, Cheryl A.M.; Ephraim, Patti L.; Cook, Courtney; Boulware, L. Ebony

    2014-01-01

    Young blacks receiving dialysis have an increased risk of death compared with whites in the United States. Factors influencing this disparity among the young adult dialysis population have not been well explored. Our study examined the relation of neighborhood socioeconomic status (SES) and racial differences in mortality in United States young adults receiving dialysis. We merged US Renal Data System patient-level data from 11,027 black and white patients ages 18–30 years old initiating dialysis between 2006 and 2009 with US Census data to obtain neighborhood poverty information for each patient. We defined low SES neighborhoods as those neighborhoods in US Census zip codes with ≥20% of residents living below the federal poverty level and quantified race differences in mortality risk by level of neighborhood SES. Among patients residing in low SES neighborhoods, blacks had greater mortality than whites after adjusting for baseline demographics, clinical characteristics, rurality, and access to care factors. This difference in mortality between blacks and whites was significantly attenuated in higher SES neighborhoods. In the United States, survival between young adult blacks and whites receiving dialysis differs by neighborhood SES. Additional studies are needed to identify modifiable factors contributing to the greater mortality among young adult black dialysis patients residing in low SES neighborhoods. PMID:24925723

  3. Clinical and histopathological results of the adult patients with unilateral cryptorchidism

    PubMed Central

    Ateş, Ferhat; Soydan, Hasan; Okçelik, Sezgin; Çırakoğlu, Abdullah; Yılmaz, İsmail; Malkoç, Ercan; Karademir, Kenan

    2016-01-01

    Objective To evaluate the clinical and histopathological results of adult unilateral cryptorchidism patients. Material and methods Data from adult unilateral cryptorchidism patients that underwent orchiectomy in our clinic between between January 2004 and March 2013 were retrospectively evaluated. Patients were divided into three groups as intra-abdominal, inguinal canal and superficial inguinal region according to the location of the undescended testes. Patients were also grouped according to their testicular volume (<4 cc, 4.1–12 cc, and >12 cc). Histopathology results of orchiectomy specimens were classified as follows: 1. Sertoli cells only, testicular atrophy and vanished testis (anorchia) 2. Hypospermatogenesis, and 3. Maturation arrest. Patients were grouped as normospermia, azoospermia and oligo/astheno/teratospermia groups according to semen analysis results. Correlations between testicular localization, testicular size, semen analysis and pathology results were evaluated. Incidental tumor detection rates were also calculated. Results Two hundred and forty-four adult unilateral cryptorchidism patients underwent orchiectomy in our clinic. There was no a significant relationship between location of the testis and testicular pathology results (p=0.707). Most common semen analysis results was normospermia in patients with high testicular volume group however azoospermia and oligoasthenospermia observed commonly in patients with low testicular volume group. There was a significant relationship between testicular volume and semen analysis results (p=0.023). No significant relationship was observed between semen analysis and pathological results (p=0.929). After an evaluation of all factors with possible effects on the semen analysis results, only testicular volume (p=0.036) was found to have a significant impact. Only one case (0.4%) was incidentally diagnosed seminoma after a review of 233 patients with available histopathological results on record

  4. Adult neuronal ceroid lipofuscinosis with palmitoyl-protein thioesterase deficiency: first adult-onset patients of a childhood disease.

    PubMed

    van Diggelen, O P; Thobois, S; Tilikete, C; Zabot, M T; Keulemans, J L; van Bunderen, P A; Taschner, P E; Losekoot, M; Voznyi, Y V

    2001-08-01

    The fluorogenic enzyme assay for palmitoyl-protein thioesterase (PPT) has greatly facilitated the diagnosis of infantile neuronal ceroid lipofuscinosis (Santavuori-Haltia disease) and the search for possible new variants with atypical clinical presentation. Here, we present the first cases of adult neuronal ceroid lipofuscinosis with onset in the fourth decade of life due to a profound deficiency of PPT. The causative mutations in the CLN1 gene were the known, deleterious mutation R151X and the novel missense mutation G108R. Patients presented at onset (31 and 38 years), with psychiatric symptoms only. At present (ages 56 and 54 years), visual, verbal, and cognitive losses have progressed and both patients have cerebellar ataxia and cannot walk without support. PMID:11506414

  5. [Neurological presentations of lysosomal diseases in adult patients].

    PubMed

    Sedel, F; Turpin, J-C; Baumann, N

    2007-10-01

    Lysosomal diseases represent a large group of genetic storage disorders characterized by a defect in the catabolism of complex molecules within the lysosome. Effective treatments are now possible for some of them given progresses in bone-marrow transplantation, enzyme replacement therapy and substrate reduction therapy. Neurologists and psychiatrists are concerned by these diseases because they can present in adolescence or adulthood with progressive neuropsychiatric signs. Here we focus on late-onset clinical forms which can be met in an adult neurology or psychiatric department. Lysosomal diseases were classified into 3 groups: (1) leukodystrophies (metachromatic leukodystrophy, Krabbe's disease and Salla's disease); (2) Neurodegenerative or psychiatric-like diseases (GM1 and GM2 gangliosidoses, Niemann Pick type C disease, sialidosis type I, ceroid-lipofuscinosis, mucopolysaccharidosis type III); (3) multisystemic diseases (Gaucher's disease, Fabry's disease, alpha and B mannosidosis, Niemann Pick disease type B, fucosidosis, Schindler/Kanzaki disease, and mucopolysaccharidosis type I and II. We propose a diagnostic approach guided by clinical examination, brain MRI, electrodiagnostic studies and abdominal echography. PMID:18033028

  6. Comparison of the Phenotype and Approach to Pediatric vs Adult Patients With Nonalcoholic Fatty Liver Disease.

    PubMed

    Nobili, Valerio; Alisi, Anna; Newton, Kimberly P; Schwimmer, Jeffrey B

    2016-06-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the main chronic noncommunicable diseases in Westernized societies; its worldwide prevalence has doubled during the last 20 years. NAFLD has serious health implications not only for adults, but also for children. However, pediatric NAFLD is not only an important global problem in itself, but it is likely to be associated with increases in comorbidities, such as metabolic syndrome and cardiovascular diseases. There are several differences between NAFLD in children and adults, and it is not clear whether the disease observed in children is the initial phase of a process that progresses with age. The increasing prevalence of pediatric NAFLD has serious implications for the future adult population requiring appropriate action. Studies of NAFLD progression, pathogenesis, and management should evaluate disease phenotypes in children and follow these over the patient's lifetime. We review the similarities and differences of NAFLD between children and adults. PMID:27003600

  7. Innovative Strategies Designed to Improve Adult Pneumococcal Immunizations in Safety Net Patient-Centered Medical Homes.

    PubMed

    Park, Nina J; Sklaroff, Laura Myerchin; Gross-Schulman, Sandra; Hoang, Khathy; Tran, Helen; Campa, David; Scheib, Geoffrey; Guterman, Jeffrey J

    2016-08-01

    Streptococcus pneumoniae is a principal cause of serious illness, including bacteremia, meningitis, and pneumonia, worldwide. Pneumococcal immunization is proven to reduce morbidity and mortality in high-risk adult and elderly populations. Current pneumococcal vaccination practices are suboptimal in part because of recommendation complexity, the high cost of provider-driven immunization interventions, and outreach methods that are not patient-centric. These barriers are amplified within the safety net. This paper identifies efforts by the Los Angeles County Department of Health Services to increase pneumococcal immunization rates for adult indigent patient populations. A 4-part approach will be used to increase vaccination rates: (1) protocol driven care, (2) staff education, (3) electronic identification of eligible patients, and (4) automated patient outreach and scheduling. The proposed analytics plan and potential for scalability are described. (Population Health Management 2016;19:240-247). PMID:26824148

  8. Characteristics of acute care utilization of a Delaware adult sickle cell disease patient population.

    PubMed

    Anderson, Nina; Bellot, Jennifer; Senu-Oke, Oluseyi; Ballas, Samir K

    2014-02-01

    Sickle cell disease (SCD) is an inherited blood disorder that is chronic in nature and manifests itself through many facets of the patient's life. Comprehensive specialty centers have the potential to reduce health care costs and improve the quality of care for patients who have chronic medical conditions such as heart failure and SCD. The purpose of this practice inquiry was to analyze de-identified data for acute care episodes involving SCD in order to create a detailed picture of acute care utilization for adult patients in Delaware with SCD from 2007 to 2009. Gaining a better understanding of acute care utilization for adults with SCD may provide evidence to improve access to high-quality health care services for this vulnerable patient population in the state of Delaware. PMID:23965046

  9. Design Considerations for Patient Portal Adoption by Low-Income, Older Adults

    PubMed Central

    Latulipe, Celine; Gatto, Amy; Nguyen, Ha T.; Miller, David P.; Quandt, Sara A.; Bertoni, Alain G.; Smith, Alden; Arcury, Thomas A.

    2016-01-01

    This paper describes the results of an interview study investigating facilitators and barriers to adoption of patient portals among low-income, older adults in rural and urban populations in the southeastern United States. We describe attitudes of this population of older adults and their current level of technology use and patient portal use. From qualitative analysis of 36 patient interviews and 16 caregiver interviews within these communities, we derive themes related to benefits of portals, barriers to use, concerns and desired features. Based on our initial findings, we present a set of considerations for designing the patient portal user experience, aimed at helping healthcare clinics to meet U.S. federally-mandated ‘meaningful use’ requirements. PMID:27077140

  10. Clinical next generation sequencing of pediatric-type malignancies in adult patients identifies novel somatic aberrations

    PubMed Central

    Silva, Jorge Galvez; Corrales-Medina, Fernando F.; Maher, Ossama M.; Tannir, Nizar; Huh, Winston W.; Rytting, Michael E.; Subbiah, Vivek

    2015-01-01

    Pediatric malignancies in adults, in contrast to the same diseases in children are clinically more aggressive, resistant to chemotherapeutics, and carry a higher risk of relapse. Molecular profiling of tumor sample using next generation sequencing (NGS) has recently become clinically available. We report the results of targeted exome sequencing of six adult patients with pediatric-type malignancies : Wilms tumor(n=2), medulloblastoma(n=2), Ewing's sarcoma( n=1) and desmoplastic small round cell tumor (n=1) with a median age of 28.8 years. Detection of druggable somatic aberrations in tumors is feasible. However, identification of actionable target therapies in these rare adult patients with pediatric-type malignancies is challenging. Continuous efforts to establish a rare disease registry are warranted. PMID:25859559

  11. Clinical next generation sequencing of pediatric-type malignancies in adult patients identifies novel somatic aberrations.

    PubMed

    Silva, Jorge Galvez; Corrales-Medina, Fernando F; Maher, Ossama M; Tannir, Nizar; Huh, Winston W; Rytting, Michael E; Subbiah, Vivek

    2015-01-01

    Pediatric malignancies in adults, in contrast to the same diseases in children are clinically more aggressive, resistant to chemotherapeutics, and carry a higher risk of relapse. Molecular profiling of tumor sample using next generation sequencing (NGS) has recently become clinically available. We report the results of targeted exome sequencing of six adult patients with pediatric-type malignancies : Wilms tumor(n=2), medulloblastoma(n=2), Ewing's sarcoma( n=1) and desmoplastic small round cell tumor (n=1) with a median age of 28.8 years. Detection of druggable somatic aberrations in tumors is feasible. However, identification of actionable target therapies in these rare adult patients with pediatric-type malignancies is challenging. Continuous efforts to establish a rare disease registry are warranted. PMID:25859559

  12. Clinical Trials of Adult Stem Cell Therapy in Patients with Ischemic Stroke

    PubMed Central

    2016-01-01

    Stem cell therapy is considered a potential regenerative strategy for patients with neurologic deficits. Studies involving animal models of ischemic stroke have shown that stem cells transplanted into the brain can lead to functional improvement. With current advances in the understanding regarding the effects of introducing stem cells and their mechanisms of action, several clinical trials of stem cell therapy have been conducted in patients with stroke since 2005, including studies using mesenchymal stem cells, bone marrow mononuclear cells, and neural stem/progenitor cells. In addition, several clinical trials of the use of adult stem cells to treat ischemic stroke are ongoing. This review presents the status of our understanding of adult stem cells and results from clinical trials, and introduces ongoing clinical studies of adult stem cell therapy in the field of stroke. PMID:26610894

  13. Multidimensional Clinical Phenotyping of an Adult Cystic Fibrosis Patient Population

    PubMed Central

    Conrad, Douglas J.; Bailey, Barbara A.

    2015-01-01

    Background Cystic Fibrosis (CF) is a multi-systemic disease resulting from mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene and has major manifestations in the sino-pulmonary, and gastro-intestinal tracts. Clinical phenotypes were generated using 26 common clinical variables to generate classes that overlapped quantiles of lung function and were based on multiple aspects of CF systemic disease. Methods The variables included age, gender, CFTR mutations, FEV1% predicted, FVC% predicted, height, weight, Brasfield chest xray score, pancreatic sufficiency status and clinical microbiology results. Complete datasets were compiled on 211 subjects. Phenotypes were identified using a proximity matrix generated by the unsupervised Random Forests algorithm and subsequent clustering by the Partitioning around Medoids (PAM) algorithm. The final phenotypic classes were then characterized and compared to a similar dataset obtained three years earlier. Findings Clinical phenotypes were identified using a clustering strategy that generated four and five phenotypes. Each strategy identified 1) a low lung health scores phenotype, 2) a younger, well-nourished, male-dominated class, 3) various high lung health score phenotypes that varied in terms of age, gender and nutritional status. This multidimensional clinical phenotyping strategy identified classes with expected microbiology results and low risk clinical phenotypes with pancreatic sufficiency. Interpretation This study demonstrated regional adult CF clinical phenotypes using non-parametric, continuous, ordinal and categorical data with a minimal amount of subjective data to identify clinically relevant phenotypes. These studies identified the relative stability of the phenotypes, demonstrated specific phenotypes consistent with published findings and identified others needing further study. PMID:25822311

  14. Home management of the adult patient with leukemia.

    PubMed

    Dwyer, J E; Held, D M

    1982-12-01

    The many changes that have occurred within the medical profession and among the public are taking long-term care out of the hospital and placing it back into the home. Attitudes toward cancer have altered, as seen by the rapid growth of the oncology specialty as well as the willingness of the community to allow those with cancer to return to a viable status. Even the individual who must face end-stage disease can now rest comfortably in the privacy of his or her own home, surrounded by loved ones. Improved nutritional efforts during periods of active therapy are reducing the side effects and improving the tolerance of highly cytotoxic drugs. Thus, acute episodes of treatment are shortened, allowing for earlier discharge. Individuals are demanding accurate information regarding their disease and its treatment. Patients are catalysts for their own recovery as they become more active participants in their care. Some are even choosing not to undergo suggested therapies and are returning home to put their lives in order and let disease processes take their natural course, even until death. As for leukemia, more supportive measures such as blood component therapy and evaluative work-ups are being offered on an outpatient basis. Patients are learning self-care measures to counteract or minimize side effects to chemotherapy or radiation therapy. Thus, overwhelming infection is of less risk and hospitalization is shortened. Infection, especially from Staphylococcus aureus, still remains a major cause of death of patients with leukemia. However, one must consider how prevalent this organism is in the hospital environment. Home care management is improving; care can be as comprehensive as one might need or receive in the hospital setting. PMID:6924785

  15. Complications and benefits of intrahospital transport of adult Intensive Care Unit patients

    PubMed Central

    Harish, M. M.; Janarthanan, S.; Siddiqui, Suhail Sarwar; Chaudhary, Harish K.; Prabu, Natesh R.; Divatia, Jigeeshu V.; Kulkarni, Atul Prabhakar

    2016-01-01

    Background: The transport of critically ill patients for procedures or tests outside the Intensive Care Unit (ICU) is potentially hazardous; hence, the transport process must be organized and efficient. Plenty of data is available on pre- and inter-hospital transport of patients; the data on intrahospital transport of patients are limited. We audited the complications and benefits of intrahospital transport of critically ill patients in our tertiary care center over 6 months. Materials and Methods: One hundred and twenty adult critically ill cancer patients transported from the ICU for either diagnostic or therapeutic procedure over 6 months were included. The data collected include the destination, the accompanying person, total time spent outside the ICU, and any adverse events and adverse change in vitals. Results: Among the 120 adult patients, 5 (4.1%) required endotracheal intubation, 5 (4.1%) required intercostal drain placement, and 20 (16.7%) required cardiopulmonary resuscitation (CPR). Dislodgement of central venous catheter occurred in 2 (1.6%) patients, drain came out in 3 (2.5%) patients, orogastric tube came out in 1 (0.8%) patient, 2 (1.6%) patients self-extubated, and in one patient, tracheostomy tube was dislodged. The adverse events were more in patients who spent more than 60 min outside the ICU, particularly requirement of CPR (18 [25%] vs. 2 [4.2%], ≤60 min vs. >60 min, respectively) with P < 0.05. Transport led to change in therapy in 32 (26.7%) patients. Conclusion: Transport in critically ill cancer patients is more hazardous and needs adequate pretransport preparations. Transport in spite being hazardous may lead to a beneficial change in therapy in a significant number of patients.

  16. Pharmacological interventions for ADHD: how do adolescent and adult patient beliefs and attitudes impact treatment adherence?

    PubMed Central

    McCarthy, Suzanne

    2014-01-01

    Adherence to medication can be problematic for patients, especially so for patients with attention deficit hyperactivity disorder (ADHD). Effective medications are available for the treatment of ADHD; however, nonadherence rates for ADHD medication range from 13.2%–64%. The reasons for nonadherence can be complex. This review aims to look at how the beliefs and attitudes of adolescents and adults impact ADHD treatment adherence. PMID:25284990

  17. Orthodontic Treatment in Adult Patient with Reduced Periodontium: A Case Report.

    PubMed

    Shintcovsk, Ricardo Lima; Knop, Luegya Amorim Henriques; Pinto, Ary Santos; Gandini, Luiz Gonzaga; Martins, Lídia Parsekian

    2015-01-01

    Patients presenting reduced periodontium represent a major concern for orthodontists. The purpose of this article is to present the clinical case of an adult patient who presented sequel of periodontal disease (diastemas) compromising her dental aesthetics. She was subjected to an orthodontic treatment with the application of light forces distant from the teeth with reduced periodontium. A periodontal support therapy was successfully implemented. The final stage of the treatment indicated satisfactory occlusal and periodontal characteristics. PMID:27029099

  18. Are daily routine chest radiographs necessary after pulmonary surgery in adult patients?

    PubMed Central

    Reeb, Jeremie; Falcoz, Pierre-Emmanuel; Olland, Anne; Massard, Gilbert

    2013-01-01

    A best evidence topic was constructed according to a structured protocol. The question addressed was whether daily routine (DR) chest radiographs (CXRs) are necessary after pulmonary surgery in adult patients. Of the 66 papers found using a report search, seven presented the best evidence to answer the clinical question. Four of these seven studies specifically addressed post-cardiothoracic adult patients. Three of these seven studies addressed intensive care unit (ICU) patients and included post-cardiothoracic adult patients in well-designed studies. Six of these seven studies compared the DR CXRs strategy to the clinically indicated, on-demand (OD) CXRs strategy. Another study analysed the clinical impact of ceasing to perform the DR, postoperative, post-chest tubes removal CXRs. The authors, journal, date and country of publication, study type, group studied, relevant outcomes and results of these papers are given. We conclude that, on the whole, the seven studies are unanimously in favour of forgoing DR CXRs after lung resection and advocate OD CXRs. One study suggested that hypoxic patients could benefit from a DR CXRs strategy, while other studies failed to identify any subgroup for whom performing DR CXRs was beneficial. Indeed, DR CXRs, commonly taken after thoracic surgery, have poor diagnostic and therapeutic value. Eliminating them for adult patients having undergone thoracic surgery significantly decreases the number of CXRs per patient without increasing mortality rates, length of hospital stays (LOSs), readmission rates and adverse events. Hence, current evidence shows that DR CXRs could be forgone after lung resection because OD CXRs, recommended by clinical monitoring, have a better impact on management and have not been proved to negatively affect patient outcomes. Moreover, an OD CXRs strategy lowers the cost of care. Nevertheless, an OD CXRs strategy requires close clinical monitoring by experienced surgeons and dedicated intensivists. However

  19. Higher Rates of Misdiagnosis in Pediatric Patients versus Adults Hospitalized with Imported Malaria

    PubMed Central

    Arguin, Paul M.; Daily, Johanna P.

    2015-01-01

    Objectives Despite the availability of effective anti-malarial prophylaxis, imported adult and pediatric malaria occurs in the United States and this can pose diagnostic issues. We examined the clinical characteristics and diagnostic challenges of imported malaria requiring adult or pediatric inpatient admission at Montefiore Medical Center (MMC) in the Bronx which provides care for a large population of immigrants from malaria endemic areas. Study Design We conducted a retrospective single center review of patients admitted with a diagnosis of malaria at MMC from 2005 through 2012. We extracted historical, clinical, and laboratory values from the electronic medical record and patient charts. Results We identified 95 patients who were diagnosed and hospitalized with malaria from 2005–2012, 33 (35%) of them children and 17 (18%) with severe malaria. Most patients contracted malaria while visiting friends and relatives (VFR) in West Africa. Only 38% of travelers took prophylaxis, and fewer than half reported taking it as prescribed. Misdiagnosis by emergency room or primary care doctors was observed in almost one quarter of all of the patients. Misdiagnosis occurred significantly more frequently in children (43%) compared to adults (13%) (p=0.002). Pediatric patients were more likely to present with abdominal pain (42% vs 15%, p=0.005). Conclusions Pediatric patients admitted for imported malaria at MMC had a higher rate of misdiagnosis and presented with more gastrointestinal symptoms than hospitalized adults. By describing the clinical characteristics of patients with imported malaria, we hope to improve diagnostic accuracy by healthcare workers and raise awareness that VFRs may require more intensive pre-travel counseling. PMID:25322145

  20. Adult Patient with Novel H1N1 Infection Presented with Encephalitis, Rhabdomyolysis, Pneumonia and Polyneuropathy.

    PubMed

    Patel, Ketan K; Patel, Atul K; Shah, Shalin; Ranjan, Rajiv; Shah, Sudhir V

    2012-07-01

    Neurological complications of influenza are well known. Influenza A is commonly associated with neurological complications. Neurological complications especially encephalitis is described in the pediatric age group of patients with current pandemic novel H1N1 infection. We are describing a case of novel H1N1 infection presenting with multi-system involvement (encephalitis, bilateral pneumonia, severe rhabdomyolysis leading to renal failure and polyneuropathy) in adult patient. PMID:23055650

  1. Adult Patient with Novel H1N1 Infection Presented with Encephalitis, Rhabdomyolysis, Pneumonia and Polyneuropathy

    PubMed Central

    Patel, Ketan K; Patel, Atul K; Shah, Shalin; Ranjan, Rajiv; Shah, Sudhir V

    2012-01-01

    Neurological complications of influenza are well known. Influenza A is commonly associated with neurological complications. Neurological complications especially encephalitis is described in the pediatric age group of patients with current pandemic novel H1N1 infection. We are describing a case of novel H1N1 infection presenting with multi-system involvement (encephalitis, bilateral pneumonia, severe rhabdomyolysis leading to renal failure and polyneuropathy) in adult patient. PMID:23055650

  2. The FLT3ITD mRNA level has a high prognostic impact in NPM1 mutated, but not in NPM1 unmutated, AML with a normal karyotype.

    PubMed

    Schneider, Friederike; Hoster, Eva; Unterhalt, Michael; Schneider, Stephanie; Dufour, Annika; Benthaus, Tobias; Mellert, Gudrun; Zellmeier, Evelyn; Kakadia, Purvi M; Bohlander, Stefan K; Feuring-Buske, Michaela; Buske, Christian; Braess, Jan; Heinecke, Achim; Sauerland, Maria C; Berdel, Wolfgang E; Büchner, Thomas; Wörmann, Bernhard J; Hiddemann, Wolfgang; Spiekermann, Karsten

    2012-05-10

    The impact of a FLT3-internal tandem duplication (FLT3ITD) on prognosis of patients with acute myeloid leukemia (AML) is dependent on the ratio of mutated to wild-type allele. In 648 normal karyotype (NK) AML patients, we found a significant independent effect of the quantitative FLT3ITD mRNA level--measured as (FLT3ITD/wtFLT3)/(FLT3ITD/wtFLT3+1)--on outcome. Moreover, this effect was clearly seen in 329 patients with a mutated NPM1 gene (NPM1+), but not in 319 patients without a NPM1 mutation (wtNPM1). In a multivariate Cox regression model, the quantitative FLT3ITD mRNA level showed an independent prognostic impact on overall survival (OS) and relapse-free survival (RFS) only in the NPM1+ subgroup (OS: hazard ratio, 5.9; [95% confidence interval [CI]: 3.1-11.2]; RFS: hazard ratio, 7.5 [95% CI: 3.4-16.5]). The FLT3ITD mRNA level contributes to relapse risk stratification and might help to guide postremission therapy in NPM1-mutated AML. PMID:22374696

  3. Epidemiology of adult-onset hydrocephalus: institutional experience with 2001 patients.

    PubMed

    Bir, Shyamal C; Patra, Devi Prasad; Maiti, Tanmoy K; Sun, Hai; Guthikonda, Bharat; Notarianni, Christina; Nanda, Anil

    2016-09-01

    OBJECTIVE Adult-onset hydrocephalus is not commonly discussed in the literature, especially regarding its demographic distribution. In contrast to pediatric hydrocephalus, which is related to a primary CSF pathway defect, its development in adults is often secondary to other pathologies. In this study, the authors investigated the epidemiology of adult-onset hydrocephalus as it pertains to different etiologies and in reference to age, sex, and race distributions. METHODS The authors retrospectively reviewed the clinical notes of 2001 patients with adult-onset hydrocephalus who presented to Louisiana State University Health Sciences Center within a 25-year span. Significant differences between the groups were analyzed by a chi-square test; p < 0.05 was considered significant. RESULTS The overall mean (± SEM) incidence of adult hydrocephalus in this population was 77 ± 30 per year, with a significant increase in incidence in the past decade (55 ± 3 [1990-2003] vs 102 ± 6 [2004-2015]; p < 0.0001). Hydrocephalus in a majority of the patients had a vascular etiology (45.5%) or was a result of a tumor (30.2%). The incidence of hydrocephalus in different age groups varied according to various pathologies. The incidence was significantly higher in males with normal-pressure hydrocephalus (p = 0.03) or head injury (p = 0.01) and higher in females with pseudotumor cerebri (p < 0.0001). In addition, the overall incidence of hydrocephalus was significantly higher in Caucasian patients (p = 0.0002) than in those of any other race. CONCLUSIONS Knowledge of the demographic variations in adult-onset hydrocephalus is helpful in achieving better risk stratification and better managing the disease in patients. For general applicability, these results should be validated in a large-scale meta-analysis based on a national population database. PMID:27581317

  4. An Examination of Intimate Partner Violence and Psychological Stressors in Adult Abortion Patients

    ERIC Educational Resources Information Center

    Ely, Gretchen E.; Otis, Melanie D.

    2011-01-01

    The purpose of this article is to describe an exploratory study examining the relationship between intimate partner violence and psychological stressors in a sample of 188 adult abortion patients. Results indicate the almost 15% of respondents report a history of abuse by the coconceiving partner. In addition, women who reported having had one or…

  5. Bladder augmentation in a young adult female exstrophy patient with associated omphalocele: an extremely unusual case.

    PubMed

    Quiroz-Guerrero, Javier; Badillo, Marco; Muñoz, Norberto; Anaya, Jorge; Rico, Gazpar; Maldonado-Valadez, Rafael

    2009-08-01

    We present the case of a 20-year-old woman with uncorrected bladder exstrophy and omphalocele treated with ileocystoplasty and continent urinary stoma. To our knowledge this is the first reported case of a young adult patient presenting with both congenital anomalies. The treatment result suggests that bladder preservation is a safe and feasible therapeutic option in bladder exstrophy. PMID:19375388

  6. Adults Living with Limited Literacy and Chronic Illness: Patient Education Experiences

    ERIC Educational Resources Information Center

    King, Judy; Taylor, Maurice C.

    2010-01-01

    The purpose of this study was to investigate how Canadian adults living with limited literacy and chronic illness made meaning of their patient education experiences. The study used a hermeneutic phenomenological research design and employed three data sources over a nine-month period. Data was interpreted and analyzed as it was collected,…

  7. [Auricular perichondritis in adults. An evaluation-study of 12 hospitalized patients].

    PubMed

    Pino Rivero, V; Marcos García, M; Trinidad Ruiz, G; Pardo Romero, G; González Palomino, A; Guerra Camacho, M; Barrantes Celaya, G; Blasco Huelva, A

    2005-01-01

    Perichondritis of the auricle in adults can be secondary to traumatic agents, external otitis or surgery being Pseudomona aeruginosa the bacteria more often isolated. We have performed a retrospective study of 12 hospitalized patients with that diagnosis and these following variables have been evaluated: Age, sex, personal antecedents, clinical symptoms, affected auricle, complementary explorations, treatment, evolution and stay. PMID:15803915

  8. Lessons Learned While Providing Group Counseling for Adult Patients with Metastatic Cancer.

    ERIC Educational Resources Information Center

    Duncan, Jack A.; Cumbia, Gilbert G.

    1987-01-01

    Provides a review of lessons learned in dealing with unique problems encountered while providing group counseling for adult patients with metastatic cancer. Discusses problems, institutional policies, personal biases, and logistics associated with forming, establishing, maintaining, conducting and assessing the outcomes of group counseling with…

  9. Micronutrient deficiencies in pediatric and young adult intestinal transplant patients

    PubMed Central

    Ubesie, Agozie C; Cole, Conrad R; Nathan, Jaimie D; Tiao, Greg M; Alonso, Maria H; Mezoff, Adam G; Henderson, Carol J; Kocoshis, Samuel A

    2013-01-01

    Background Intestinal transplant recipients are at risk for micronutrient deficiency due to the slow process of post-transplant adaptation. Another contributing factor is calcineurin inhibitor-induced renal tubular dysfunction. Patients are typically supplemented with micronutrients during parenteral nutrition; however the risk of deficiency may persist even after a successful transition to full enteral nutrition. Objective To determine the prevalence of, and associated risk factors for, iron, zinc, magnesium, phosphorus, selenium, copper, folate, vitamins A, D, E and B12 deficiency in pediatric intestinal transplant recipients after successful transition to full enteral nutrition. Method A retrospective review of prospectively collected data from children who underwent intestinal transplantation at Cincinnati Children's Hospital Medical Center. Deficiencies of various micronutrients were defined using the hospital reference values. Results Twenty-one intestinal transplant recipients, aged one to 23 years that were successfully transitioned to full enteral nutrition were included in the study. The prevalence of micronutrient deficiency was 95.2%. The common deficient micronutrients were iron (94.7%) and magnesium (90.5%). Age ≤10 years (P=0.002) and tube feeding (P= 0.02) were significant risk factors for micronutrient deficiencies. Conclusion Pediatric intestinal transplant recipients have a high risk of micronutrient and mineral deficiencies. These deficiencies were more common among younger patients and those who received jejunal feeding. PMID:23919810

  10. Best Practices in Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia: A Focus on Asparaginase

    PubMed Central

    Boissel, Nicolas

    2015-01-01

    The inclusion of asparaginase in chemotherapy regimens to treat acute lymphoblastic leukemia (ALL) has had a positive impact on survival in pediatric patients. Historically, asparaginase has been excluded from most treatment protocols for adolescent and young adult (AYA) patients because of perceived toxicity in this population, and this is believed to have contributed to poorer outcomes in these patients. However, retrospective analyses over the past 12 years have shown that 2-, 5-, and 7-year overall survival of AYA patients is significantly improved with pediatric versus adult protocols. The addition of asparaginase to adult protocols yielded high rates of first remission and improved survival. However, long-term survival remains lower compared with what has been seen in pediatrics. The notion that asparaginase is poorly tolerated by AYA patients has been challenged in multiple studies. In some, but not all, studies, the incidences of hepatic and pancreatic toxicities were higher in AYA patients, whereas the rates of hypersensitivity reactions did not appear to differ with age. There is an increased risk of venous thromboembolic events, and management with anti-coagulation therapy is recommended. Overall, the risk of therapy-related mortality is low. Together, this suggests that high-intensity pediatric protocols offer an effective and tolerable approach to treating ALL in the AYA population. PMID:26421220

  11. Selective dorsal rhizotomy for spastic diplegia secondary to stroke in an adult patient

    PubMed Central

    Eppinger, Melissa Ann; Berman, Casey Melissa; Mazzola, Catherine Anne

    2015-01-01

    Background: Selective dorsal rhizotomy (SDR) is often recommended for children with spastic paraparesis and cerebral palsy. SDR reduces spasticity in the lower extremities for these children with spastic paraplegia. However, SDR is infrequently recommended for adults with spasticity. Spastic diplegia in adult patients can be due to stroke, brain or spinal cord injury from trauma, infection, toxic-metabolic disorders, and other causes. Although rarely considered, SDR is an option for adult patients with spastic diplegia as well. Case Description: The authors describe a patient who underwent a SDR with a successful postoperative outcome. This man suffered a hypertensive and hemorrhagic stroke secondary to intravenous drug abuse at age 46. A SDR was performed after two failed intrathecal baclofen pump placements due to recurrent infections, likely resulting from his immunocompromised status. The patient underwent lumbar laminectomies and dorsal rhizotomies at levels L1-S1 bilaterally. Postoperatively, the patient's spasticity was significantly reduced. His Ashworth spasticity score decreased from 4/5 to 1/5, and the reduction in tone has been durable over 3 years. Conclusion: SDR in older patients with spastic paraparesis may be considered as a treatment option. PMID:26167363

  12. Changes in Quality of Life in 7 Older Adult Patients Receiving Activator Methods Chiropractic Technique

    PubMed Central

    Russell, David G.; Kimura, Melissa N.; Cowie, Harriet R.; de Groot, Caroline M.M.; McMinn, Elise A.P.; Sherson, Matthew W.

    2016-01-01

    Objective The purpose of this case series is to report on symptomatic and quality of life (QoL) changes in 7 older adult chiropractic patients who were receiving care using Activator Methods Chiropractic Technique (AMCT). Clinical Features Seven patients were selected from 2 chiropractic offices in Auckland, New Zealand. Patients were included if they were older adults receiving AMCT care and for whom at least 2 QoL assessments had been performed. The patients, aged 69-80 years, primarily received care for a variety of musculoskeletal complaints. Intervention and Outcomes The patients reported improvements in their presenting complaints as well as a number of nonmusculoskeletal symptoms. Each patient demonstrated clinical improvements in their RAND 36-Item Short Form Health Survey (SF-36) results. The average improvement in QoL measured using a SF-36 questionnaire was 8.0 points in the physical component and 4.1 points in the mental component. Four cases had a second progress evaluation using the SF-36 and showed an overall improvement of 5.2 in the physical and 9.8 in the mental components from baseline. Conclusion This case series describes an improvement in QoL, as measured by the SF-36 instrument, as well as subjectively reported improvements in both musculoskeletal and nonmusculoskeletal symptoms in 7 older adults receiving chiropractic care. PMID:27069434

  13. Clinical next-generation sequencing reveals aggressive cancer biology in adolescent and young adult patients

    PubMed Central

    Subbiah, Vivek; Bupathi, Manojkumar; Kato, Shumei; Livingston, Andrew; Slopis, John; Anderson, Pete M.; Hong, David S.

    2015-01-01

    Background The aggressive biology of cancers arising in adolescent and young adult (AYA; ages 15–39 years) patients is thought to contribute to poor survival outcomes. Methods We used clinical next-generation sequencing (NGS) results to examine the molecular alterations and diverse biology of cancer in AYA patients referred to the Phase 1 program at UT MD Anderson Cancer Center. Results Among the 28 patients analyzed (14 female and 14 male), 12 had pediatric-type cancers, six had adult-type cancers, and ten had orphan cancers. Unique, hitherto unreported aberrations were identified in all types of cancers. Aberrations in TP53, NKX2-1, KRAS, CDKN2A, MDM4, MCL1, MYC, BCL2L2, and RB1 were demonstrated across all tumor types. Five patients harbored TP53 aberrations; three patients harbored MYC, MCL1, and CDKN2A aberrations; and two patients harbored NKX2-1, KRAS, MDM4, BCL2L2, and RB1 alterations. Several patients had multiple aberrations; a patient with wild-type gastrointestinal stromal tumor harbored five alterations (MDM4, MCL1, KIT, AKT3, and PDGRFA). Conclusions This preliminary report of NGS of cancer in AYA patients reveals diverse and unique aberrations. Further molecular profiling and a deeper understanding of the biology of these unique aberrations are warranted and may lead to targeted therapeutic interventions. PMID:26328274

  14. Interventions That Affect Gastrointestinal Motility in Hospitalized Adult Patients

    PubMed Central

    Asrani, Varsha M.; Yoon, Harry D.; Megill, Robin D.; Windsor, John A.; Petrov, Maxim S.

    2016-01-01

    Abstract Gastrointestinal (GI) dysmotility is a common complication in acute, critically ill, postoperative, and chronic patients that may lead to impaired nutrient delivery, poor clinical, and patient-reported outcomes. Several pharmacological and nonpharmacological interventions to treat GI dysmotility were investigated in dozens of clinical studies. However, they often yielded conflicting results, at least in part, because various (nonstandardized) definitions of GI dysmotility were used and methodological quality of studies was poor. While a universally accepted definition of GI dysmotility is yet to be developed, a systematic analysis of data derived from double-blind placebo-controlled randomized trials may provide robust data on absolute and relative effectiveness of various interventions as the study outcome (GI motility) was assessed in the least biased manner. To systematically review data from double-blind placebo-controlled randomized trials to determine and compare the effectiveness of interventions that affect GI motility. Three electronic databases (MEDLINE, SCOPUS, and EMBASE) were searched. A random effects model was used for meta-analysis. The summary estimates were reported as mean difference (MD) with the corresponding 95% confidence interval (CI). A total of 38 double-blind placebo-controlled randomized trials involving 2371 patients were eligible for inclusion in the systematic review. These studies investigated a total of 20 different interventions, of which 6 interventions were meta-analyzed. Of them, the use of dopamine receptor antagonists (MD, −8.99; 95% CI, −17.72 to −0.27; P = 0.04) and macrolides (MD, −26.04; 95% CI, −51.25 to −0.82; P = 0.04) significantly improved GI motility compared with the placebo group. The use of botulism toxin significantly impaired GI motility compared with the placebo group (MD, 5.31; 95% CI, −0.04 to 10.67; P = 0.05). Other interventions (dietary factors, probiotics, hormones) did

  15. Hospital utilization patterns and costs for adult sickle cell patients in Illinois.

    PubMed Central

    Woods, K; Karrison, T; Koshy, M; Patel, A; Friedmann, P; Cassel, C

    1997-01-01

    OBJECTIVES: To determine population size, demographic characteristics, hospital utilization patterns, the specialties of physicians providing care, and costs for hospitalized adult sickle cell patients in Illinois. METHODS: A statewide, administrative dataset for the two-year period from january 1992 through December 1993 was analyzed retrospectively. RESULTS: There were 8403 admissions among 1189 individual sickle cell patients for the two-year period. Eighty-five percent of patients resided in the Chicago metropolitan area. The median age of the 1189 patients was 29; two-thirds had Medicaid or Medicare coverage. Emergency departments were the primary source of admissions (85.7%). The most common admitting diagnosis was painful crisis (97.4%), and average length of stay was four days. The median number of admissions per patient was three; most patients (85%) used only one or two hospitals. A small group used more than four hospitals and accounted for 23% of statewide admissions. Primary care physicians cared for most patients, and total hospitalization charges were more than $59 million. CONCLUSIONS: In Illinois the adult sickle cell population is concentrated in major urban centers, primarily the Chicago metropolitan area. These patients accounted for approximately 8400 admissions and more than $59 million in hospital charges during the two-year study period. A small group of patients used multiple hospitals and accounted for more than 23% of total hospitalization charges. This study shows the necessity of and provides a useful framework for developing targeted programs for adult sickle cell patients as well as for training physicians to efficiently provide comprehensive health care services for this population. PMID:9018288

  16. Dietary Intake In Adult Female Coeliac Disease Patients In Slovenia

    PubMed Central

    Mičetić-Turk, Dušanka

    2016-01-01

    Abstract Objectives The aim of the study was to assess dietary intake of coeliac disease (CD) patients and to determine if they are meeting the dietary reference values for a balanced diet. Subjects/Methods 40 women with CD, aged from 23 to 76 participated in our study. Total daily intake was assessed by a three-day food diary. Resting metabolic rate (RMR) was calculated using Harris-Benedict equation. Considering physical activity level (PAL) 1.4, the recommended total energy expenditure (TEE) value was determined. The data was evaluated with professional evaluation software Prodi and statistically analysed. Results 40 participants returned the food diary. The average energy intake was significantly too low to ensure the meeting of all-day energy needs (p<0.05). The meals contained a recommended proportion of protein, but a statistically significantly higher proportion of fat (p<0.05), lower proportion of carbohydrates and a significantly lower intake of dietary fibre (p<0.05). Regarding macro-, micro- elements and vitamins, there was a significant lack in the intake of calcium and iodine, folic acid, vitamin D and vitamin A (p<0.05), meanwhile iron intake was at the lower limit of the recommended intake, whereas zinc, potassium and vitamin K intake were significantly higher according to the recommended values, but were comparable with the intake of the general population in the Central European area. Conclusion Even in subjects with adequate or low daily energy intake, their meals contained too much fat, too few carbohydrates and dietary fibre as well as inorganic substances. The patients with CD should get regular nutritional monitoring and education on the quality and balance of a gluten-free diet. PMID:27284377

  17. Mutation Analysis of IDH1/2 Genes in Unselected De novo Acute Myeloid Leukaemia Patients in India - Identification of A Novel IDH2 Mutation.

    PubMed

    Raveendran, Sureshkumar; Sarojam, Santhi; Vijay, Sangeetha; Geetha, Aswathy Chandran; Sreedharan, Jayadevan; Narayanan, Geetha; Sreedharan, Hariharan

    2015-01-01

    IDH1/2 mutations which result in alternation in DNA methylation pattern are one of the most common methylation associated mutations in Acute myeloid leukaemia. IDH1/2 mutations frequently associated with higher platelet level, normal cytogentics and NPM1 mutations. Here we analyzed IDH1/2 mutations in 200 newly diagnosed unselected Indian adult AML patients and investigated their correlation with clinical, cytogenetic parameters along with cooperating NPM1 mutation. We detected 5.5% and 4% mutations in IDH1/2 genes, respectively. Except IDH2 c.515_516GG>AA mutation, all the other identified mutations were reported mutations. Similar to reported c.515G>A mutation, the novel c.515_516GG>AA mutation replaces 172nd arginine to lysine in the active site of the enzyme. Even though there was a preponderance of IDH1/2 mutations in NK-AML, cytogenetically abnormal patients also harboured IDH1/2 mutations. IDH1 mutations showed significant higher platelet count and NPM1 mutations. IDH2 mutated patients displayed infrequent NPM1 mutations and lower WBC count. All the NPM1 mutations in the IDH1/2 mutated cases showed type A mutation. The present data suggest that IDH1/2 mutations are associated with normal cytogenetics and type A NPM1 mutations in adult Indian AML patients. PMID:25987093

  18. The Broad Anti-AML Activity of the CD33/CD3 BiTE Antibody Construct, AMG 330, Is Impacted by Disease Stage and Risk

    PubMed Central

    Laszlo, George S.; Newhall, Kathryn J.; Sinclair, Angus M.; Frankel, Stanley R.; Kischel, Roman; Chen, Guang; Walter, Roland B.

    2015-01-01

    The CD33/CD3-bispecific T-cell engaging (BiTE) antibody construct, AMG 330, potently lyses CD33+ leukemic cells in vitro. Using specimens from 41 patients with acute myeloid leukemia (AML), we studied the factors that might contribute to clinical response or resistance. For this purpose, thawed aliquots of primary AML samples were immunophenotypically characterized and subjected to various doses of AMG 330 in the presence or absence of healthy donor T-cells. After 48 hours, drug-specific cytotoxicity was quantified and correlated with CD33 expression levels, amounts of T-cells present, and other disease characteristics. AMG 330 caused modest cytotoxicity that was correlated with the amount of autologous T-cells (P = 0.0001) but not CD33 expression, as AMG 330 exerted marked cytotoxic effects in several specimens with minimal CD33 expression. With healthy donor T-cells added, AMG 330 cytotoxicity depended on the drug dose and effector:target (E:T) cell ratio. High cytotoxic activity was observed even with minimal CD33 expression, and AMG 330 cytotoxicity and CD33 expression correlated only at high E:T cell ratio and high AMG 330 doses (P<0.003). AMG 330 resulted in significantly higher cytotoxicity in specimens from patients with newly diagnosed AML than those with relapsed/refractory disease despite similar levels of CD33 on myeloblasts. AMG 330 cytotoxicity also appeared greater in specimens from patients with favorable-risk disease as compared to other specimens. Together, our data demonstrate that AMG 330 is highly active in primary AML specimens across the entire disease spectrum, while suggesting the presence of yet undefined, CD33-independent, relative resistance mechanisms in specific patient subsets. PMID:26305211

  19. Molecular Diagnostic Experience of Whole-Exome Sequencing in Adult Patients

    PubMed Central

    Posey, Jennifer E.; Rosenfeld, Jill A.; James, Regis A.; Bainbridge, Matthew; Niu, Zhiyv; Wang, Xia; Dhar, Shweta; Wiszniewski, Wojciech; Akdemir, Zeynep H.C.; Gambin, Tomasz; Xia, Fan; Person, Richard E.; Walkiewicz, Magdalena; Shaw, Chad A.; Sutton, V. Reid; Beaudet, Arthur L.; Muzny, Donna; Eng, Christine M.; Yang, Yaping; Gibbs, Richard A.; Lupski, James R.; Boerwinkle, Eric; Plon, Sharon E.

    2015-01-01

    Purpose Whole exome sequencing (WES) is increasingly used as a diagnostic tool in medicine, but prior reports focus on predominantly pediatric cohorts with neurologic or developmental disorders. We describe the diagnostic yield and characteristics of whole exome sequencing in adults. Methods We performed a retrospective analysis of consecutive WES reports for adults from a diagnostic laboratory. Phenotype composition was determined using Human Phenotype Ontology terms. Results Molecular diagnoses were reported for 17.5% (85/486) of adults, lower than a primarily pediatric population (25.2%; p=0.0003); the diagnostic rate was higher (23.9%) in those 18–30 years of age compared to patients over 30 years (10.4%; p=0.0001). Dual Mendelian diagnoses contributed to 7% of diagnoses, revealing blended phenotypes. Diagnoses were more frequent among individuals with abnormalities of the nervous system, skeletal system, head/neck, and growth. Diagnostic rate was independent of family history information, and de novo mutations contributed to 61.4% of autosomal dominant diagnoses. Conclusion Early WES experience in adults demonstrates molecular diagnoses in a substantial proportion of patients, informing clinical management, recurrence risk and recommendations for relatives. A positive family history was not predictive, consistent with molecular diagnoses often revealed by de novo events, informing the Mendelian basis of genetic disease in adults. PMID:26633545

  20. Acute myeloid leukemia in the older patient.

    PubMed

    Godwin, John E; Smith, Scott E

    2003-10-15

    Acute myeloid leukemia (AML) is an extremely heterogeneous disorder. The biology of AML is incompletely understood, but much data indicates that older patients have a more biologically diverse and chemotherapy resistant form of AML that is quite different from that seen in the younger patients. Approximately 60% of AML cases are in patients greater than 60 years of age, so the predominant burden is in older patients. This problem will be magnified in the future, because the US population is both growing and aging. When one examines the treatment outcomes of older AML patients over the last three decades, there is little progress in long-term survival. Nine major published randomized placebo controlled trials of myeloid growth factors given during induction for AML have been conducted. All of these trials with one exception demonstrated no significant impact on the clinical outcomes of complete response (CR) rate, disease-free, and overall survival. However, the duration of neutropenia was consistently and uniformly reduced by the use of growth factor in all nine of these trials. Because of the favorable impact of the colony-stimulating factors (CSFs) on resource use, antibiotic days, hospital days, etc., it can be more economical and beneficial to use CSFs in AML than to withhold use. The overall dismal outlook for the older AML patient can only be altered by clinical trials with new therapeutic agents. New cellular and molecularly targeted agents are entering clinical trials and bring hope for progress to this area of cancer therapy. PMID:14563517

  1. Glutamine-Supplemented Parenteral Nutrition and Probiotics in Four Adult Autoimmune Enteropathy Patients

    PubMed Central

    Xu, Ren-Ying; Zhou, Yi-Quan; Lu, Li-Ping; Chen, Zhi-Qi; Wu, Ying-Jie; Cai, Wei

    2014-01-01

    To evaluate the effects of glutamine-supplemented parenteral nutrition (PN) and probiotics in adult autoimmune enteropathy (AIE) patients. Four adult AIE patients were identified from April 2006 to January 2012. Clinical and nutritional data were obtained from the patients' medical records. Glutamine-supplemented PN started immediately when the AIE diagnosis was confirmed. The total PN duration was 351 days. According to the PN prescription, the average caloric intake ranged from 20 to 25 kcal/kg/day, and the protein intake ranged from 1.2 to 1.5 g/kg/day. Alanyl-glutamine (20 g/day) was administered to AIE patients for 4 weeks followed by a 2-week break, and this treatment schedule was repeated when PN lasted for more than 6 weeks. Body weight gain and an increased serum albumin level were achieved after PN, and defecation frequency and quality also improved. Each patient received oral supplements, 250 mL of Ensure and two probiotics capsules (each capsule containing 0.5×108 colonies) three times a day when enteral nutrition started. Three AIE patients were successfully weaned off PN, and one patient died of pneumonia. Glutamine-supplemented PN and probiotics show promise in managing patients with AIE and related malnutrition. PMID:24827631

  2. Bronchoscopic removal of foreign bodies in adults: experience with 62 patients from 1974-1998.

    PubMed

    Debeljak, A; Sorli, J; Music, E; Kecelj, P

    1999-10-01

    The authors reviewed their experience with therapeutic bronchoscopy for removal of tracheobronchial foreign bodies in the adult. Bronchoscopy records and collection of foreign bodies in the endoscopic department were retrospectively examined. Among 37,466 bronchoscopies performed between 1974-1998, 62 (0.2%) were performed for the removal of tracheobronchial foreign bodies. Medical history was suggestive of foreign body aspiration in 33 patients and the chest radiograph was suggestive in 10 patients. The procedure was performed with the flexible bronchoscope in 42 patients (68%), rigid bronchoscope in 4 (6%), and with both in 16 (26%) patients. Foreign bodies were found in the right bronchial tree on 42 occasions, in the left on 20 and in the trachea once. In 39 patients, inflammatory granulations were found around the foreign body. The origins of the foreign bodies included: bone fragments (n=31), vegetable (n=10), broncholith (n=8), a part of dental prosthesis (n=7), endodontic needle (n=2), a metallic (n=2), or plastic (n=1) particle, a tracheostomy tube (n=1) and a match (n=1). In one patient, 2 foreign bodies were found. The foreign bodies were successfully removed in all but 2 patients (3%). The most useful instruments for removal were alligator forceps and the wire basket. Foreign bodies in the tracheobronchial system are rare in adults. They can be successfully removed in the majority of patients under either flexible or rigid bronchoscopy. PMID:10573222

  3. Urinary tract infections in adult general practice patients.

    PubMed Central

    Hummers-Pradier, Eva; Kochen, Michael M

    2002-01-01

    Urinary tract infections (UTIs) are symptomatic infections of the urinary tract, mainly caused by the bacterium Escherichia coli. One in two women suffers from a UTI at least once in her life. The young and sexually active are particulaly affected, but it is also seen in elderly, postmenopausal women. The likelihood of recurrence is high. Diagnosis is made with regard to typical complaints and the presence of leucocytes and nitrites in the urine. A culture is unnecessary in most cases. Uncomplicated UTI should be distinguished from complicated UTI, which has a risk of severe illness. The treatment of choice--short-term therapy with trimethoprim or nitrofurantoin--is successful in over 80% of the cases. Co-trimoxazol fluoroquinolones or cephalsporins are not considered first-choice drugs. There are indications that general practitioners' (GPs') management of UTI is not always optimal, specifically concerning diagnostic tests, the application of second-choice antibiotics, and the length of prescribed treatment courses. Many points relevant to GPs requirefurther research, such as epidemiology and resistance of urinary pathogens in the community and natural history of UTI, as well as optimal management in elderly or complicated patients and men. PMID:12236281

  4. Role for c-jun N-terminal kinase in treatment-refractory acute myeloid leukemia (AML): signaling to multidrug-efflux and hyperproliferation.

    PubMed

    Cripe, L D; Gelfanov, V M; Smith, E A; Spigel, D R; Phillips, C A; Gabig, T G; Jung, S-H; Fyffe, J; Hartman, A D; Kneebone, P; Mercola, D; Burgess, G S; Boswell, H S

    2002-05-01

    A relationship was proved between constitutive activity of leukemic cell c-jun-N-terminal kinase (JNK) and treatment failure in AML. Specifically, early treatment failure was predicted by the presence of constitutive JNK activity. The mechanistic origins of this association was sought. A multidrug resistant leukemic cell line, HL-60/ADR, characterized by hyperexpression of c-jun and JNK activity, was transfected with a mutant c-jun vector, whose substrate N-terminal c-jun serines were mutated. Down-regulated expression occurred of c-jun/AP-1-dependent genes, catalase and glutathione-S-transferase (GST) pi, which participate in cellular homeostasis to oxidative stress and xenobiotic exposure. MRP-efflux was abrogated in HL-60/ADR cells with dominant-negative c-jun, perhaps because MRP1 protein expression was also lost. Heightened sensitivity to daunorubicin resulted in cells subjected to this change. Biochemical analysis in 67 primary adult AML samples established a statistical correlation between cellular expression of c-jun and JNK activity, JNK activity with hyperleukocytosis at presentation of disease, and with exuberant MRP efflux. These findings reflect the survival role for c-jun/AP-1 and its regulatory kinase previously demonstrated for yeast in homeostatic response to oxidative stress and in operation of ATP-binding cassette efflux pumps, and may support evolutionary conservation of such function. Thus, JNK and c-jun may be salient drug targets in multidrug resistant AML. PMID:11986940

  5. Giardia Assemblages A and B in Diarrheic Patients: A Comparative Study in Egyptian Children and Adults.

    PubMed

    El Basha, Noussa R; Zaki, Mayssa M; Hassanin, Omayma M; Rehan, Mohamed K; Omran, Dalia

    2016-02-01

    Giardia duodenalis is considered the most common intestinal parasite in humans worldwide. Children are especially affected, with more severe consequences than adults. The present study was designed to determine the distribution of assemblages A and B Giardia infection in children and adults, with the use of light microscopy and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) as diagnostic procedures, and to investigate its associations with clinical and epidemiological data collected from children and adult groups. This cross-sectional study was conducted from October 2012 to October 2013 by collecting fecal samples from 200 children and 200 adults complaining of diarrhea. Samples were subjected to parasitological examination by direct wet smear and formol-ether methods. Genotyping of G. doudenalis samples was conducted by PCR-RFLP analysis. Giardia duodenalis infection caused by assemblages A and B was identified in 60 samples, 34 from children and 26 from adults. Assemblage B was detected in 38 patients (63.34%), and assemblage A was detected in 22 patients (36.66%). Assemblage A was significantly more frequent in children with age range 2-8 yr, and assemblage B was higher in children with age range 6-16 yr old. Diarrhea frequency/day and recurrences per month affected patients infected with assemblage A (P value < 0.001) more frequently. Children infected with assemblage A presented significantly more severe diarrhea and dehydration than those infected with assemblage B (P value < 0.001). Although both Giardia assemblages A and B were identified in children and adults, assemblage A infected younger children more frequently and was more closely related to severe clinical manifestations than assemblage B. PMID:26509291

  6. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia.

    PubMed

    Dhédin, Nathalie; Huynh, Anne; Maury, Sébastien; Tabrizi, Reza; Beldjord, Kheira; Asnafi, Vahid; Thomas, Xavier; Chevallier, Patrice; Nguyen, Stéphanie; Coiteux, Valérie; Bourhis, Jean-Henri; Hichri, Yosr; Escoffre-Barbe, Martine; Reman, Oumedaly; Graux, Carlos; Chalandon, Yves; Blaise, Didier; Schanz, Urs; Lhéritier, Véronique; Cahn, Jean-Yves; Dombret, Hervé; Ifrah, Norbert

    2015-04-16

    Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with Philadelphia chromosome-negative ALL, we aimed to reassess the role of allogeneic stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL-2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at least 1 conventional high-risk factor were candidates for SCT in first complete remission. Among these, 282 (54%) received a transplant in first complete remission. At 3 years, posttransplant cumulative incidences of relapse, nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%, 15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a significant difference in RFS between SCT and no-SCT cohorts. However, SCT was associated with longer RFS in patients with postinduction minimal residual disease (MRD) ≥10(-3) (hazard ratio, 0.40) but not in good MRD responders. In B-cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion (hazard ratio, 0.42). This article shows that poor early MRD response, in contrast to conventional ALL risk factors, is an excellent tool to identify patients who may benefit from allogeneic SCT in the context of intensified adult ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as #NCT00222027; GRAALL-2005 was registered as #NCT00327678. PMID:25587040

  7. Novel management options for adult patients with progressive acute lymphoblastic leukemia: introduction.

    PubMed

    Wang, Eunice S

    2015-06-01

    Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic malignancy characterized by highly proliferative immature lymphoid cells in the bone marrow and peripheral blood. In adults, ALL accounts for approximately 20% of all adult leukemias. ALL carries a poor prognosis in adults. The 5-year overall survival is 24% in patients ages 40 to 59 years and 18% in patients ages 60 to 69 years. ALL can be grouped into different categories according to its cell lineage (B cell or T cell), the presence or absence of the Philadelphia chromosome, and various cytogenetic and molecular classifications. A main goal of treatment is to allow the patient to achieve a complete remission and to consolidate this remission with either a maintenance regimen or an allogeneic stem cell transplant. Although the overall rate of complete remission following frontline therapy for newly diagnosed ALL is high, the majority of patients experience a disease relapse. In general, the duration of initial complete remission impacts the patient’s prognosis and response to further therapies. Subsequent treatments must balance the goal of achieving a remission with the need for the patient to maintain or improve quality of life. Recently approved agents, such as blinatumomab and vincristine sulfate liposome injection, offer the promise of a second remission that can serve as a bridge to allogeneic stem cell transplant while still maintaining quality of life. A novel approach using adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T cells is associated with extremely robust responses. PMID:26431322

  8. Comorbidities and inhibitors in adult patients with haemophilia: issues, costs and management strategies.

    PubMed

    Berntorp, Erik; Mauser-Bunschoten, Evelien; Jiménez-Yuste, Víctor; Spears, Jeffrey B

    2015-11-01

    Along with greater life expectancy in patients with haemophilia has been an increase in associated haemophilia-related (arthropathy, osteoporosis, viral infections) and age-related (cardiovascular disease, renal disease, cancer and others) comorbidities, many of which are only just emerging as the population ages. At present, experience in managing these comorbidities is limited. As the demographic shift continues, haemophilia care centres can expect to encounter more patients with greater levels of complexity. In the absence of evidence-based information to guide the management of adult patients with haemophilia, it is important that the scientific position be reviewed on a regular basis. To this end, several topics relevant to the clinical management of adult patients with haemophilia were examined in a symposium entitled Comorbidities and inhibitors in adult patients with haemophilia: issues, costs and management strategies held on 11 February 2015 in Helsinki, Finland, in conjunction with the 8th Annual Congress of the European Association for Haemophilia and Allied Disorders. This article is a summary of that event. PMID:26492487

  9. Combined treatment with sitagliptin and vitamin D in a patient with latent autoimmune diabetes in adults

    PubMed Central

    Rapti, E; Karras, S; Grammatiki, M; Mousiolis, A; Tsekmekidou, X; Potolidis, E; Zebekakis, P; Daniilidis, M

    2016-01-01

    Summary Latent autoimmune diabetes in adults (LADA) is a relatively new type of diabetes with a clinical phenotype of type 2 diabetes (T2D) and an immunological milieu characterized by high titers of islet autoantibodies, resembling the immunological profile of type 1 diabetes (T1D). Herein, we report a case of a young male, diagnosed with LADA based on both clinical presentation and positive anti-glutamic acid decarboxylase antibodies (GAD-abs), which were normalized after combined treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4) (sitagliptin) and cholecalciferol. Learning points Anti-glutamic acid decarboxylase antibodies (GAD-abs) titers in young patients being previously diagnosed as type 2 diabetes (T2D) may help establish the diagnosis of latent autoimmune diabetes in adults (LADA). Sitagliptin administration in patients with LADA might prolong the insulin-free period. Vitamin D administration in patients with LADA might have a protective effect on the progression of the disease. PMID:27252860

  10. Clinical and MRI findings of cerebellar agenesis in two living adult patients

    PubMed Central

    Gelal, Fazıl Mustafa; Kalaycı, Tuğçe Özlem; Çelebisoy, Mehmet; Karakaş, Levent; Akkurt, Hülya Erdoğan; Koç, Feray

    2016-01-01

    Cerebellar agenesis (CA) is an extremely rare entity. We present two adult patients with CA. The 61-year-old man had ataxia, dysarthria, abnormalities in cerebellar tests, severe cognitive impairment, and moderate mental retardation. The 26-year-old woman had dysmetria, dysdiadochokinesia, and dysarthria as well as mild cognitive impairment and mild mental retardation. Magnetic resonance imaging (MRI) showed complete absence of the cerebellum with small residual vermis. Brainstem was hypoplastic and structures above tentorium were normal. Supratentorial white matter bundles were unaffected in diffusion tensor tractography. Only few adult patients with CA have so far been published. These cases show that patients with CA present with a variety of developmental, clinical, and mental abnormalities; and emphasize the role of the cerebellum in normal motor, language, and mental development. PMID:27293341

  11. Fms like tyrosine kinase (FLT3) and nucleophosmin 1 (NPM1) mutations in de novo normal karyotype acute myeloid leukemia (AML).

    PubMed

    Dunna, Nageswara Rao; Rajappa, Senthil; Digumarti, Raghunadharao; Vure, Sugunakar; Kagita, Sailaja; Damineni, Surekha; Rao, V R; Yadav, Satish Kumar; Ravuri, Rajasekhara Reddy; Satti, Vishnupriya

    2010-01-01

    Mutations in FLT3 and NPM1 are important prognostic factors in AML, influencing outcome in normal karyotype cases. We here analysed incidences of FLT3/ITD, D 835 and NPM1 mutations in patients with de novo normal karyotype AML using PCR and gene sequencing, along with laboratory parameters and treatment outcomes. There were 128 patients with a median age of 45 years (range, 19-65). FLT3/ITD mutations were detected in 26 (20.3%), FLT3/D835 in 8 (6.2%) and NPM1 in 22 (17.1%). The incidence of FLT3/ITD was higher in those with elevated lactate dehydrogenase (LDH) and peripheral blasts (p=< 0.002, < 0.001) while NPM1 mutations or both NPM1 and FLT3/ITD was more common in elevated total leukocyte counts (TLC), LDH and peripheral blasts (p=<0.0001). Complete response and disease free survival were lower in those with FLT3/ITD mutations (p=0.04, 0.03). The incidence of FLT3 and NPM1 mutations was found to be low in Indian patients with normal karyotype AML. PMID:21338238

  12. Two Patients Diagnosed with Juvenile Myoclonic Epilepsy by First-Ever Status Epilepticus in Adult Life

    PubMed Central

    Jeong, Hye Seon; Moon, Jeong Soo; Oh, Eung Seok; Kim, Jae Moon

    2011-01-01

    Juvenile myoclonic epilepsy (JME) is an idiopathic, age-related generalized epileptic syndrome. Status epilepticus (SE) in JME is very rare, and little is known about its etiology. We report 2 cases of adult patients, retrospectively diagnosed as JME by non convulsive status epilepticus which occurred for the first time. One patient was a 52-year-old woman who was presented with confusion and brief generalized tonic-clonic seizure (GTCS) for the first time. The other patient, a 39 year-old woman, visited the ER with transient LOC following confused mental state. Electroencephalograms of both patients repetitively showed generalized polyspikes and slow waves which were disappeared after IV injection of lorazepam. With careful history taking, both of them the patients were diagnosed as JME, and the seizures stopped just after sodium valproate medication. NCSE in patients with JME is rare but detailed history taking and suspicion of the disorder is helpful for diagnosis. PMID:24649443

  13. Voice Onset Time for Turkish Stop Consonants in Adult Cochlear Implanted Patients.

    PubMed

    Dalgic, Abdullah; Kandogan, Tolga; Aksoy, Gokce

    2015-09-01

    The voice onset time is a temporal acoustic parameter defined as the time between the release of the oral constriction for plosive production and the onset of vocal fold vibrations. Hearing impairment is one of the factors that can effect the magnitude of voice onset time. Since voice onset time is a useful, noninvasive method for documenting the articulatory-phonatory aspects of vocal training during speech, we investigated voice onset time values for Turkish stop consonants in adult cochlear implanted patients in order to clarify the effect of CI and sequential hearing rehabilitation over voice onset time values. The CI patients were divided into two groups according to duration of CI usage. We looked for relations between results of the study and average voice onset time values in Turkish language for adults. Mean VOT values for for both males and females in the first and second group are shown in Tables 1, 2, 3, and 4. Most syllables both in males and females statistically significant differ from average VOT values, e.g. They did not reach to normal hearing adults level. These acoustic results indicated that VOT may be an effective measure for examining the effect of cochlear implantation over the articulatory accuracy. As far as we know, this is the first publication using voice onset time values for the efficiency of cochlear implantation in adult patients. [Table: see text] [Table: see text] [Table: see text] [Table: see text]. PMID:26405669

  14. Management of subcondylar mandible fractures in the adult patient.

    PubMed

    Hackenberg, Berit; Lee, Cameron; Caterson, E J

    2014-01-01

    the patient with multiple injuries who cannot tolerate closed reduction. PMID:24406572

  15. Effect of therapy-related acute myeloid leukemia on the outcome of patients with acute myeloid leukemia

    PubMed Central

    ESPíRITO SANTO, ANA ESPÍRITO; CHACIM, SÉRGIO; FERREIRA, ISABEL; LEITE, LUÍS; MOREIRA, CLAUDIA; PEREIRA, DULCINEIA; DANTAS BRITO, MARGARIDA DANTAS; NUNES, MARTA; DOMINGUES, NELSON; OLIVEIRA, ISABEL; MOREIRA, ILÍDIA; MARTINS, ANGELO; VITERBO, LUÍSA; MARIZ, JOSÉ MÁRIO; MEDEIROS, RUI

    2016-01-01

    Therapy-related acute myeloid leukemia (t-AML) is a rare and almost always fatal late side effect of antineoplastic treatment involving chemotherapy, radiotherapy or the two combined. The present retrospective study intended to characterize t-AML patients that were diagnosed and treated in a single referral to an oncological institution in North Portugal. Over the past 10 years, 231 cases of AML were diagnosed and treated at the Portuguese Institute of Oncology of Porto, of which 38 t-AML cases were identified. Data regarding the patient demographics, primary diagnosis and treatment, age at onset of therapy-related myeloid neoplasm, latency time of the neoplasm, cytogenetic characteristics, AML therapy and outcome were collected from medical records. A previous diagnosis with solid tumors was present in 28 patients, and 10 patients possessed a history of hematological conditions, all a lymphoproliferative disorder. Breast cancer was the most frequent solid tumor identified (39.5% of all solid tumors diagnosed). The mean latency time was 3 years. In the present study, t-AML patients were older (P<0.001) and more frequently carried cytogenetic abnormalities (P=0.009) compared with de novo AML patients. The overall survival time was observed to be significantly poorer among individuals with t-AML (P<0.001). However, in younger patients (age, <50 years) there was no difference between the overall survival time of patients with t-AML and those with de novo AML (P=0.983). Additionally, patients with promyelocytic leukemia possess a good prognosis, even when AML occurs as a secondary event (P=0.98). To the best of our knowledge, the present study is the first to evaluate t-AML in Portugal and the results are consistent with the data published previously in other populations. The present study concludes that although t-AML demonstrates a poor prognosis, this is not observed among younger patients or promyelocytic leukemia patients. PMID:27347135

  16. Acute respiratory distress syndrome in an adult patient with a myelodysplastic disorder.

    PubMed

    Pentimone, F; Cini, G; Meola, N; Ferrannini, E

    1983-01-01

    A 58-year-old man was diagnosed to have refractory anaemia with excessive blasts. After 3 1/2 years of relative control on periodic blood transfusions, the patient developed an acute leukaemia. Although the blastic crisis was not extreme (WBC counts less than 100 X 10(9)/l), a severe, intractable respiratory distress syndrome set in and brought the patient to the exitus in a few days. Overt signs of septic shock were absent, as was evidence of any other known cause of adult respiratory distress. Acute pulmonary failure can be the cause of death in leukaemic patients even in the absence of overwhelming sepsis or hyperleucocytosis. PMID:6404107

  17. The safe practice of CT coronary angiography in adult patients in UK imaging departments.

    PubMed

    Harden, S P; Bull, R K; Bury, R W; Castellano, E A; Clayton, B; Hamilton, M C K; Morgan-Hughes, G J; O'Regan, D; Padley, S P G; Roditi, G H; Roobottom, C A; Stirrup, J; Nicol, E D

    2016-08-01

    Computed tomography coronary angiography is increasingly used in imaging departments in the investigation of patients with chest pain and suspected coronary artery disease. Due to the routine use of heart rate controlling medication and the potential for very high radiation doses during these scans, there is a need for guidance on best practice for departments performing this examination, so the patient can be assured of a good quality scan and outcome in a safe environment. This article is a summary of the document on 'Standards of practice of computed tomography coronary angiography (CTCA) in adult patients' published by the Royal College of Radiologists (RCR) in December 2014. PMID:27207375

  18. Screening adult tuberculosis patients for diabetes mellitus in Ebeye, Republic of the Marshall Islands

    PubMed Central

    Brostrom, R.; Ram, S.; Kumar, A. M. V.; Seremai, J.; Hauma, M.; Paul, I. A.; Langidrik, J. R.

    2014-01-01

    A retrospective cohort study was conducted to evaluate the screening of adult TB patients for diabetes (DM) using glycated haemoglobin (HbA1C) in Ebeye, Republic of the Marshall Islands. Of 62 patients registered between July 2010 and December 2012, 28 (45%) had DM. The only significant difference in baseline characteristics between those with and those without DM was higher age in those with DM. Two-month sputum smears and cultures were also not different between the two groups. Despite the limited sample size, this study shows that screening TB patients for DM in Ebeye is feasible and worthwhile and that it should be continued. PMID:26477288

  19. Rasch Analysis of the Adult Strabismus Quality of Life Questionnaire (AS-20) among Chinese Adult Patients with Strabismus

    PubMed Central

    Wang, Zonghua; Zhou, Juan; Luo, Xingli; Xu, Yan; She, Xi; Chen, Ling; Yin, Honghua; Wang, Xianyuan

    2015-01-01

    Background The impact of strabismus on visual function, self-image, self-esteem, and social interactions decrease health-related quality of life (HRQoL).The purpose of this study was to evaluate and refine the adult strabismus quality of life questionnaire (AS-20) by using Rasch analysis among Chinese adult patients with strabismus. Methods We evaluated the fitness of the AS-20 with Rasch model in Chinese population by assessing unidimensionality, infit and outfit, person and item separation index and reliability, response ordering, targeting and differential item functioning (DIF). Results The overall AS-20 did not demonstrate unidimensional; however, it was achieved separately in the two Rasch-revised subscales: the psychosocial subscale (11 items) and the function subscale (9 items). The features of good targeting, optimal item infit and outfit, and no notable local dependence were found for each of the subscales. The rating scale was appropriate for the psychosocial subscale but a reduction to four response categories was required for the function subscale. No significant DIF were revealed for any demographic and clinical factors (e.g., age, gender, and strabismus types). Conclusion The AS-20 was demonstrated by Rasch analysis to be a rigorous instrument for measuring health-related quality of life in Chinese strabismus patents if some revisions were made regarding the subscale construct and response options. PMID:26544048

  20. Severe chronic primary neutropenia in adults: report on a series of 108 patients.

    PubMed

    Sicre de Fontbrune, Flore; Moignet, Aline; Beaupain, Blandine; Suarez, Felipe; Galicier, Lionel; Socié, Gérard; Varet, Bruno; Coppo, Paul; Michel, Marc; Pautas, Cécile; Oksenhendler, Eric; Lengline, Etienne; Terriou, Louis; Moreau, Philippe; Chantepie, Sylvain; Casadevall, Nicole; Michot, Jean Marie; Gardembas, Martine; Michallet, Mauricette; Croisille, Laure; Audrain, Marie; Bellanné-Chantelot, Christine; Donadieu, Jean; Lamy, Thierry

    2015-10-01

    Severe chronic primary neutropenia (CPN) is a rare entity, and long-term outcome and risk factors for infections in severe CPN adults have not been described to date. We report the characteristics and outcomes of 108 severe adult CPN patients enrolled in a multi-institutional observational study. Severe CPN adults were mostly female (78%), and median age at diagnosis was 28.3 years. Diagnosis was fortuitous in 62% of cases. The median absolute neutrophil count (ANC) at diagnosis was 0.4 × 10(9)/L, and median ANC without granulocyte colony-stimulating factor (G-CSF) during follow-up was 0.5 × 10(9)/L. Twenty-three of 66 (34.8%) evaluable patients had neutrophil autoantibodies, and 6 of 47 (12.8%) a T-cell clone. The presence of neutrophil autoantibodies or T-cell clone was not associated with any specific clinical or biological characteristics. No death or hematologic malignancies occurred, and 44 severe bacterial infections were reported in 27 patients with a median follow-up of 8.3 years. Fifty patients received G-CSF either sporadically (n = 24) or continuously (n = 26) and responded (96%). Nineteen patients received immunosuppressive therapies: overall response (OR) was 41%, and median duration of response was 3 months. At diagnosis, the only predictive factor for the occurrence of severe bacterial infections was an ANC count below 0.2 × 10(9)/L (OR, 0.76). Severe CPN in adults is characterized by a female predominance and a benign outcome with a low rate of severe bacterial infections and no secondary malignancies. G-CSF is efficient and well tolerated but is not required in a majority of patients. PMID:26261239

  1. Brain morphological changes in adolescent and adult patients with anorexia nervosa.

    PubMed

    Seitz, J; Herpertz-Dahlmann, B; Konrad, K

    2016-08-01

    Gray matter (GM) and white matter (WM) volume loss occur in the brains of patients with acute anorexia nervosa (AN) and improve again upon weight restoration. Adolescence is an important time period for AN to begin. However, little is known about the differences between brain changes in adolescents vs adults. We used a meta-analysis and a qualitative review of all MRI studies regarding acute structural brain volume changes and their recovery in adolescents and adults with AN. 29 studies with 473 acute, 121 short-term weight-recovered and 255 long-term recovered patients with AN were included in the meta-analysis. In acute AN, GM and WM were reduced compared to healthy controls. Acute adolescent patients showed a significantly greater GM reduction than adults (-8.4 vs -3.1 %), the difference in WM (-4.0 vs -2.1 %) did not reach significance. Short-term weight-recovered patients showed a remaining GM deficit of 3.6 % and a non-significant WM reduction of 0.9 % with no age differences. Following 1.5-8 years of remission, GM and WM were no longer significantly reduced in adults (GM -0.4 %, WM -0.7 %); long-term studies for adolescents were scarce. The qualitative review showed that GM volume loss was correlated with cognitive deficits and three studies found GM regions, cerebellar deficits and WM to be predictive of outcome. GM and WM are strongly reduced in acute AN and even more pronounced in adolescence. Long-term recovery appears to be complete for adults while no conclusions can be drawn for adolescents, thus caution remains. PMID:27188331

  2. Low 25(OH) Vitamin D3 Levels Are Associated with Adverse Outcome in Newly-Diagnosed Intensively-Treated Adult Acute Myeloid Leukemia Patients

    PubMed Central

    Lee, Hun Ju; Muindi, Josephia R.; Tan, Wei; Hu, Qiang; Wang, Dan; Liu, Song; Wilding, Gregory E.; Ford, Laurie A.; Sait, Sheila N.J.; Block, Annemarie W.; Adjei, Araba A.; Barcos, Maurice; Griffiths, Elizabeth A; Thompson, James E.; Wang, Eunice S.; Johnson, Candace S; Trump, Donald L.; Wetzler, Meir

    2013-01-01

    Background Several studies suggest that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in acute myeloid leukemia (AML). Methods VD levels were evaluated in 97 consecutive newly diagnosed, intensively-treated AML patients. MicroRNA-expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome. Results Thirty-four (35%) patients had normal 25(OH) vitamin D3 levels (32–100 ng/ml), 34 (35%) insufficient (20–31.9 ng/ml) and 29 (30%) deficient levels (<20 ng/ml). Insufficient/deficient 25(OH) vitamin D3 levels were associated with worse relapse-free survival (RFS) compared to normal vitamin D3 levels. In multivariate analyses, deficient 25(OH) vitamin D3, smoking, European LeukemiaNet Genetic Groups and white blood cell count retained their statistical significance for RFS. A number of microRNAs and SNPs were found to be associated with 25(OH) vitamin D3 level, although none remained significant after multiple test corrections; one 25(OH) vitamin D3 receptor SNP, rs10783219, was associated with lower complete remission rate (p=0.0442), shorter RFS (p=0.0058) and overall survival (p=0.0011). Conclusions It remains to be determined what role microRNA and SNP profiles play in contributing to low 25(OH) vitamin D3 level and/or outcome and whether supplementation will improve AML outcome. PMID:24166051

  3. Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients?

    PubMed

    Franceschi, E; Bartolotti, M; Paccapelo, A; Marucci, G; Agati, R; Volpin, L; Danieli, D; Ghimenton, C; Gardiman, M P; Sturiale, C; Poggi, R; Mascarin, M; Balestrini, D; Masotto, B; Brandes, A A

    2016-06-01

    The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm(2)) and no metastatic disease (M0). Main inclusion criteria were: age >16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8-13), median survival was 18 years (95 % CI 9-28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0-97.2 %) and 60.2 % (95 % CI 36.9-83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group). PMID:26940908

  4. Nutritional Status and Nosocomial Infections among Adult Elective Surgery Patients in a Mexican Tertiary Care Hospital

    PubMed Central

    Rodríguez-García, Judith; Gamiño-Iriarte, Astrid; Rodea-Montero, Edel Rafael

    2015-01-01

    Background Controversy exists as to whether obesity constitutes a risk-factor or a protective-factor for the development of nosocomial Infection (NI). According to the obesity-paradox, there is evidence that moderate obesity is a protective-factor. In Mexico few studies have focused on the nutritional status (NS) distribution in the hospital setting. Objectives The aim of this study was to estimate the distribution of NS and the prevalence of nosocomial infection NI among adult elective surgery (ES) patients and to compare the clinical and anthropometric characteristics and length of stays (LOS) between obese and non-obese patients and between patients with and without NI. Methods We conducted a cross-sectional study with a sample (n = 82) adult ES patients (21–59 years old) who were recruited from a tertiary-care hospital. The prevalences of each NS category and NI were estimated, the assessments were compared between groups (Mann-Whitney, Chi-squared or the Fisher's-exact-test), and the association between preoperative risk-factors and NI was evaluated using odds ratios. Results The distribution of subjects by NS category was: underweight (3.66%), normal-weight (28.05%), overweight (35.36%), and obese (32.93%). The prevalence of NI was 14.63%. The LOS was longer (p<0.001) for the patients who developed NI. The percentages of NI were: 33.3% in underweight, 18.52% in obese, 17.39% in normal-weight, and 6.90% in overweight patients. Conclusion The prevalence of overweight and obesity in adult ES patients is high. The highest prevalence of NI occurred in the underweight and obese patients. The presence of NI considerably increased the LOS, resulting in higher medical care costs. PMID:25803860

  5. Prevalence of celiac disease in adult type 1 patients with diabetes

    PubMed Central

    Dogan, Burcu; Oner, Can; Bayramicli, Oya Uygur; Yorulmaz, Elif; Feyizoglu, Guneş; Oguz, Aytekin

    2015-01-01

    Objectives: Celiac disease, an autoimmune disease, is related to immune mediated intolerance to gluten. Some studies suggest that Celiac Disease was 20 times more frequent in type 1 patients with diabetes. The objective of our study was to evaluate the prevalence of celiac disease in hospital based type 1 diabetic adults. Methods: Our study was carried out retrospectively in Medeniyet University Goztepe Training and Educational Hospital in Istanbul between 2012–2013. The cohort comprised 482 type 1 patients with diabetes attending the diabetes outpatient clinic. The data were analyzed by SPSS 10.5 package program. Student’s t tests is used for comparative analyses. A p-value less than 0.05 was considered statistically significant. Results: The cohort included 482 type 1 patients with diabetes. Fifty seven of them were not evaluated for Endomysium antibody positivity. Fifteen of the remaining 425 patients were positive for anti endomysial antibody (3.5%). The prevalence of biopsy proven celiac disease was 2.3% (10/425). There was no significant difference between Endomysial antibody positive and negative groups in regard of age, sex, or duration of the disease. Conclusion: This study confirms that the celiac disease is common in type 1 diabetic patients. Since a small proportion of celiac patients are symptomatic this disorder should be screened in all adult type 1 patients with diabetes by antiendomysium antibody. PMID:26430419

  6. Staphylococcal superantigens and toxins are detectable in the serum of adult burn patients.

    PubMed

    Prindeze, Nicholas J; Amundsen, Bethany M; Pavlovich, Anna R; Paul, Dereck W; Carney, Bonnie C; Moffatt, Lauren T; Shupp, Jeffrey W

    2014-07-01

    Bacterial infection in burn patients is still a devastating contributor to morbidity and mortality. Little is known regarding the presence of staphylococcal toxins in the burn-injured patient. The aim of this study was to characterize the prevalence of several of these toxins and their relationship to clinical metrics and mortality in burn patients. Levels of exotoxins staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B, toxic shock syndrome toxin 1 (TSST-1), and α-hemolysin were assayed from the serum of 207 adult burn patients aged 16-92 years. Clinical, demographic, and microbiological data from these patients were then compared to toxin levels. Staphylococcal exotoxins α-hemolysin and SEA were present in 45% and 25% of the population, respectively. Bacterial cultures concomitantly showed a high prevalence of Staphylococcus aureus in 48% of patients, of which 59% were methicillin resistant. Several metrics may be predictive of high toxin concentrations of α-hemolysin and TSST-1 and SEA including burn size, length of stay, and bacteremia. Mortality associations indicated that burn size, bacteremia, age, and the presence of α-hemolysin and SEA may be predictors of mortality. A high prevalence of staphylococcal toxin α-hemolysin and superantigens TSST-1 and SEA can be found in the circulation of the adult burn population. The presence of these toxins may contribute to the morbidity and mortality of the burn patient. PMID:24809857

  7. Clinical Profiles and Short-Term Outcomes of Acute Disseminated Encephalomyelitis in Adult Chinese Patients

    PubMed Central

    Yang, Hong-Qi; Zhao, Wen-Cong; Yang, Wei-Min; Li, Yong-Li; Sun, Zhi-Kun; Chen, Shuai

    2016-01-01

    Background and Purpose Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disorder that predominantly affects children. Previous studies have mostly involved children in Western developed countries. Methods This study retrospectively reviewed the clinical profiles of ADEM in adult Chinese patients. Results ADEM occurred during summer and autumn in about two-thirds of the 42 included patients. Prior infection was found in five patients and no preimmunization was recorded. The most frequent clinical presentations were alterations in consciousness (79%) and behavior changes (69%), followed by motor deficits (64%) and fever (50%). About one-quarter (26%) of the patients showed positive results for oligoclonal bands, and about half of them exhibited increases in the IgG index and 24-hour IgG synthesis rate. Magnetic resonance imaging showed white- and gray-matter lesions in 83% and 23% of the patients, respectively. Steroids were the main treatment, and full recovery occurred in 62% of the patients, with residual focal neurological deficits recorded in a few patients. After a mean follow-up period of 3.4 years, two patients exhibited recurrence and one patient exhibited a multiphasic course. One patient was diagnosed with multiple sclerosis (MS). Conclusions With the exception of the seasonal distribution pattern and prior vaccine rate, the clinical profiles of ADEM in adult Chinese patients are similar to those in pediatric populations. No specific markers are available for distinguishing ADEM from MS at the initial presentation. Careful clinical evaluations, cerebrospinal fluid measurements, and neuroradiological examinations with long-term follow-up will aid the correct diagnosis of ADEM. PMID:27449911

  8. Congenital intestinal malrotation in adolescent and adult patients: a 12-year clinical and radiological survey.

    PubMed

    Husberg, Britt; Salehi, Karin; Peters, Trevor; Gunnarsson, Ulf; Michanek, Margareta; Nordenskjöld, Agneta; Strigård, Karin

    2016-01-01

    Congenital intestinal malrotation is mainly detected in childhood and caused by incomplete rotation and fixation of the intestines providing the prerequisites for life-threatening volvulus of the midgut. The objective of this study was to evaluate a large cohort of adult patients with intestinal malrotation. Thirty-nine patients, 15-67 years, were diagnosed and admitted to a university setting with congenital intestinal malrotation 2002-2013. The patients were divided into three age groups for stratified evaluation. Medical charts were scrutinized, and clinical outcome of surgery was reviewed. Twelve patients presented as emergency cases, whereas 27 were admitted as elective cases. Diagnosis was established in 33 patients who underwent radiological investigation and in the remaining 6 during surgery. A Ladd's operation was performed in 31 symptomatic patients; a conservative strategy was chosen in eight cases. Volvulus was more common in the younger age group. Twenty-six surgically treated patients were available for telephone interview, 1-12 years after surgery. All patients, except one, regarded their general condition improved to a high degree (n = 18) or with some reservation (n = 7). Twelve patients suffered remaining abdominal pain of a chronic and diffuse character. Due to recurrence of malrotation six patients were reoperated. Symptomatic malrotation occurs in both children and the adult population. Improved awareness and an accurately performed CT scan can reveal the malformation and enable surgical treatment. A Ladd's procedure relieved most patients from their severe complaints even when a history of several years of suffering existed. PMID:27026938

  9. Assessing Quality of Life in Older Adult Patients with Skin Disorders

    PubMed Central

    Farage, Miranda A.; Miller, Kenneth W.; Sherman, Susan N.; Tsevat, Joel

    2012-01-01

    Significance for Public Health The global population is aging. In the industrial world, adults over 65 outnumber children and comprise almost 20% of the population in some countries. Older adults experience a number of skin diseases and disorders that substantially affect their quality of life. Opportunity exists for developing and validating health-related quality of life (HRQoL) measures specifically for dermatological conditions most pertinent to older patients. Older adults experience a number of skin diseases and disorders that substantially affect quality of life. In the last two decades, a number of instruments have been developed for use among general dermatology patients to assess the effects of treatment and disease progression, perceptions of well-being, and the value that patients place on their dermatologic state of health. This chapter reviews some health-related quality of life (HRQoL) (HRQoL) measures developed and validated specifically for dermatological conditions. However, opportunity exists for developing and validating HRQoL measures specifically for dermatological conditions most pertinent to older patients. PMID:22980159

  10. Lipids for intravenous nutrition in hospitalised adult patients: a multiple choice of options.

    PubMed

    Calder, Philip C

    2013-08-01

    Lipids used in parenteral nutrition provide energy, building blocks and essential fatty acids. Traditionally, these lipids have been based on n-6 PUFA-rich vegetable oils particularly soyabean oil. This may not be optimal because soyabean oil may present an excessive supply of linoleic acid. Alternatives to use of soyabean oil include its partial replacement by medium-chain TAG, olive oil or fish oil, either alone or in combination. Lipid emulsions containing these alternatives are well tolerated without adverse effects in a wide range of hospitalised adult patients. Lipid emulsions that include fish oil have been used in parenteral nutrition in adult patients' post-surgery (mainly gastrointestinal). This has been associated with alterations in patterns of inflammatory mediators and in immune function and, in some studies, a reduction in length of intensive care unit and hospital stay. These benefits are emphasised through recent meta-analyses. Perioperative administration of fish oil may be superior to post-operative administration. Parenteral fish oil has been used in critically ill adults. Here, the influence on inflammatory processes, immune function and clinical endpoints is not clear, since there are too few studies and those that are available report contradictory findings. However, some studies found reduced inflammation, improved gas exchange and shorter length of hospital stay in critically ill patients if they receive fish oil. More and better trials are needed in patient groups in which parenteral nutrition is used and where fish oil may offer benefits. PMID:23663322

  11. Childhood trauma and adult interpersonal relationship problems in patients with depression and anxiety disorders

    PubMed Central

    2014-01-01

    Introduction Although a plethora of studies have delineated the relationship between childhood trauma and onset, symptom severity, and course of depression and anxiety disorders, there has been little evidence that childhood trauma may lead to interpersonal problems among adult patients with depression and anxiety disorders. Given the lack of prior research in this area, we aimed to investigate characteristics of interpersonal problems in adult patients who had suffered various types of abuse and neglect in childhood. Methods A total of 325 outpatients diagnosed with depression and anxiety disorders completed questionnaires on socio-demographic variables, different forms of childhood trauma, and current interpersonal problems. The Childhood Trauma Questionnaire (CTQ) was used to measure five different forms of childhood trauma (emotional abuse, emotional neglect, physical abuse, physical neglect, and sexual abuse) and the short form of the Korean-Inventory of Interpersonal Problems Circumplex Scale (KIIP-SC) was used to assess current interpersonal problems. We dichotomized patients into two groups (abused and non-abused groups) based on CTQ score and investigated the relationship of five different types of childhood trauma and interpersonal problems in adult patients with depression and anxiety disorders using multiple regression analysis. Result Different types of childhood abuse and neglect appeared to have a significant influence on distinct symptom dimensions such as depression, state-trait anxiety, and anxiety sensitivity. In the final regression model, emotional abuse, emotional neglect, and sexual abuse during childhood were significantly associated with general interpersonal distress and several specific areas of interpersonal problems in adulthood. No association was found between childhood physical neglect and current general interpersonal distress. Conclusion Childhood emotional trauma has more influence on interpersonal problems in adult patients with

  12. A scoring system for assessing the severity of acute diarrhea of adult patients

    PubMed Central

    Xiao, Hong-li; Ma, Su-xia; Qi, Hai-yu; Li, Xiaoli; Wang, Yan; Yin, Cheng-hong

    2016-01-01

    BACKGROUND: Diarrhea is frequently seen in developed and developing countries, and severe diarrhea is characterized by the high risk of death. Thus, it is very important to assess the severity of diarrhea early. We conducted a multi-center study to identify risk factors for the severity of diarrhea in adult patients and formulate an adult diarrhea state score (ADSS) for out-patient clinicians. METHODS: A total of 219 adult patients with acute diarrhea were divided into two groups: 132 patients with mild diarrhea and 87 with severe diarrhea. Logistic regression was used to determine risk factors for the severity of diarrhea. The risk factors were assessed and an ADSS was formulated. Receiver operating characteristic (ROC) analysis was made to evaluate the diagnostic accuracy of ADSS, and the Kappa test was used to confirm the diagnostic reliability. RESULTS: Five risk factors for evaluating the severity of diarrhea in adults included age (P<0.05), axillary temperature (P<0.01), mean arterial pressure (P<0.01), white blood cell count (WBC; P<0.01), and WBC in stool (P<0.01). The area under the ROC curve for ADSS was 0.958 when the cut off value was 4 (a sensitivity of 0.909; a specificity of 0.874), and the Kappa value was 0.781 (P<0.05). CONCLUSION: The risk factors associated with the pathogenic condition of diarrhea were identified, quantified and formulated into an ADSS, which has high diagnostic accuracy and reliability for the early identification of patients with severe acute diarrhea. PMID:27313808

  13. What If the Leukemia Doesn't Respond or Comes Back After Treatment? (AML)

    MedlinePlus

    ... about acute myeloid leukemia? What if acute myeloid leukemia doesn’t respond or comes back after treatment? For most types of acute myeloid leukemia If acute myeloid leukemia (AML) doesn’t go ...

  14. Dysphagia among adult patients who underwent surgery for esophageal atresia at birth

    PubMed Central

    Huynh-Trudeau, Valérie; Maynard, Stéphanie; Terzic, Tatjana; Soucy, Geneviève; Bouin, Mickael

    2015-01-01

    BACKGROUND: Clinical experiences of adults who underwent surgery for esophageal atresia at birth is limited. There is some evidence that suggests considerable long-term morbidity, partly because of dysphagia, which has been reported in up to 85% of adult patients who undergo surgery for esophageal atresia. The authors hypothesized that dysphagia in this population is caused by dysmotility and/or anatomical anomalies. OBJECTIVE: To determine the motor and anatomical causes of dysphagia. METHODS: A total of 41 adults, followed at the Esophageal Atresia Clinic at Hôpital Saint-Luc (Montreal, Quebec), were approached to particpate in the present prospective study. Evaluation was completed using upper endoscopy, manometry and barium swallow for the participants who consented. The medical charts of respondents were systematically reviewed from the neonatal period to 18 years of age to assess medical and surgical history. RESULTS: All 41 patients followed at the clinic consented and were included in the study. Dysphagia was present in 73% of patients. Esophagogastroduodenoscopy was performed in 32 patients: hiatal hernia was present in 62% (n=20); esophageal diverticulum in 13% (n=4); macroscopic Barrett esophagus in 31% (n=10); and esophagitis in 19% (n=6). Histological esophagitis was present in 20% and intestinal metaplasia in 10%. There were no cases of dysplagia or adenocarcinoma. Esophageal manometry was performed on 56% of the patients (n=23). Manometry revealed hypomotility in 100% of patients and included an insufficient number of peristaltic waves in 96%, non-propagating peristalsis in 78% and low-wave amplitude in 95%. Complete aperistalsis was present in 78%. The lower esophageal sphincter was abnormal in 12 (52%) patients, with incomplete relaxation the most common anomaly. Of the 41 patients, 29 (71%) consented to a barium swallow, which was abnormal in 13 (45%). The anomalies found were short esophageal dilation in 28%, delay in esophageal emptying in 14

  15. Phospho-MEK1/2 and uPAR Expression Determine Sensitivity of AML Blasts to a Urokinase-Activated Anthrax Lethal Toxin (PrAgU2/LF)1

    PubMed Central

    Bekdash, Amira; Darwish, Manal; Timsah, Zahra; Kassab, Elias; Ghanem, Hadi; Najjar, Vicky; Ghosn, Marwan; Nasser, Selim; El-Hajj, Hiba; Bazerbachi, Ali; Liu, Shihui; Leppla, Stephen H.; Frankel, Arthur E.; Abi-Habib, Ralph J.

    2015-01-01

    In this study, we attempt to target both the urokinase plasminogen activator and the mitogen-activated protein kinase pathway in acute myeloid leukemia (AML) cell lines and primary AML blasts using PrAgU2/LF, a urokinase-activated anthrax lethal toxin. PrAgU2/LF was cytotoxic to five out of nine AML cell lines. Cytotoxicity of PrAgU2/LF appeared to be nonapoptotic and was associated with MAPK activation and urokinase activity because all the PrAgU2/LF-sensitive cell lines showed both uPAR expression and high levels of MEK1/2 phosphorylation. Inhibition of uPAR or desensitization of cells to MEK1/2 inhibition blocked toxicity of PrAgU2/LF, indicating requirement for both uPAR expression and MAPK activation for activity. PrAgU2/LF was also cytotoxic to primary blasts from AML patients, with blasts from four out of five patients showing a cytotoxic response to PrAgU2/LF. Cytotoxicity of primary AML blasts was also dependent on uPAR expression and phos-MEK1/2 levels. CD34+ bone marrow blasts and peripheral blood mononuclear cells lacked uPAR expression and were resistant to PrAgU2/LF, demonstrating the lack of toxicity to normal hematological cells and, therefore, the tumor selectivity of this approach. Dose escalation in mice revealed that the maximal tolerated dose of PrAgU2/LF is at least 5.7-fold higher than that of the wild-type anthrax lethal toxin, PrAg/LF, further demonstrating the increased safety of this molecule. We have shown, in this study, that PrAgU2/LF is a novel, dual-specific molecule for the selective targeting of AML. PMID:26500025

  16. Autoantibody profile and clinical characteristics in a cohort of Chinese adult myasthenia gravis patients.

    PubMed

    Hong, Yu; Li, Hai-Feng; Skeie, Geir Olve; Romi, Fredrik; Hao, Hong-Jun; Zhang, Xu; Gao, Xiang; Owe, Jone Furlund; Gilhus, Nils Erik

    2016-09-15

    Myasthenia gravis (MG) is an autoimmune disorder with heterogeneity. Antibodies against acetylcholine receptor (AChR), muscle-specific kinase (MuSK), titin and ryanodine receptor (RyR) were examined in 437 adult Chinese MG patients. The AChR, MuSK, titin and RyR antibodies were found in 82.2%, 2.3%, 28.4% and 23.8% of all patients. Autoantibody profiles vary among different MG subgroups. Thymoma MG patients had high frequencies of AChR (99.2%), titin (50.8%) and RyR antibodies (46.9%). The titin and RyR antibodies also showed high frequencies in late onset patients (54.4% and 33.3%, respectively). These two antibodies may indicate an underlying thymoma when combined. The patients with titin and RyR antibodies tend to have more severe disease and worse outcome, and may need more active immunosuppressive treatment. PMID:27609275

  17. Impact of Cranial Irradiation Added to Intrathecal Conditioning in Hematopoietic Cell Transplantation in Adult Acute Myeloid Leukemia With Central Nervous System Involvement

    SciTech Connect

    Mayadev, Jyoti S.; Douglas, James G.; Storer, Barry E.; Appelbaum, Frederick R.; Storb, Rainer

    2011-05-01

    Purpose: Neither the prognostic importance nor the appropriate management of central nervous system (CNS) involvement is known for patients with acute myeloid leukemia (AML) undergoing hematopoietic cell transplantation (HCT). We examined the impact of a CNS irradiation boost to standard intrathecal chemotherapy (ITC). Methods and Materials: From 1995 to 2005, a total of 648 adult AML patients received a myeloablative HCT: 577 patients were CNS negative (CNS-), and 71 were CNS positive (CNS+). Of the 71 CNS+ patients, 52 received intrathecal chemotherapy alone (CNS+ITC), and 19 received ITC plus an irradiation boost (CNS+RT). Results: The CNS-, CNS+ITC, and CNS+RT patients had 1- and 5-year relapse-free survivals (RFS) of 43% and 35%, 15% and 6%, and 37% and 32%, respectively. CNS+ITC patients had a statistically significant worse RFS compared with CNS- patients (hazard ratio [HR], 2.65; 95% confidence interval [CI], 2.0-3.6; p < 0.0001). CNS+RT patients had improved relapse free survival over that of CNS+ITC patients (HR, 0.45; 95% CI, 0.2-0.8; p = 0.01). The 1- and 5-year overall survivals (OS) of patients with CNS-, CNS+ITC, and CNS+RT, were 50% and 38%, 21% and 6%, and 53% and 42%, respectively. The survival of CNS+RT were significantly better than CNS+ITC patients (p = 0.004). After adjusting for known risk factors, CNS+RT patients had a trend toward lower relapse rates and reduced nonrelapse mortality. Conclusions: CNS+ AML is associated with a poor prognosis. The role of a cranial irradiation boost to intrathecal chemotherapy appears to mitigate the risk of CNS disease, and needs to be further investigated to define optimal treatment strategies.

  18. A novel variant three-way translocation of inversion 16 in a case of AML-M4eo following low dose methotrexate therapy.

    PubMed

    Li, S; Couzi, R J; Thomas, G H; Friedman, A D; Borowitz, M J

    2001-02-01

    We report a case of acute myelomonocytic leukemia with eosinophilia (AML-M4eo) in a 65-year-old man following low dose methotrexate treatment for pemphigus vulgaris. Cytogenetic studies at diagnosis revealed a complex karyotype including a reciprocal translocation between 11q14.2 and 16q22, an inversion of chromosome 16(p13.1q22), and an apparently terminal deletion of 7q31. The presence of inv(16) was confirmed by reverse transcription-polymerase chain reaction which demonstrated a Type A fusion transcript derived from the core binding factor (CBF) beta and the smooth muscle myosin heavy chain (MYH11) genes. The patient was in complete hematologic and cytogenetic remission 6 months following intensive chemotherapy. Because AML-M4eo with inv(16) has a favorable prognosis, molecular studies should be performed in case the identification of inv(16) by conventional cytogenetics is difficult due to a complex karyotype. PMID:11297772

  19. HLA-E upregulation on IFN-gamma-activated AML blasts impairs CD94/NKG2A-dependent NK cytolysis after haplo-mismatched hematopoietic SCT.

    PubMed

    Nguyen, S; Beziat, V; Dhedin, N; Kuentz, M; Vernant, J P; Debre, P; Vieillard, V

    2009-05-01

    Natural killer (NK) cells generated after haploidentical hematopoietic SCT in patients with AML are characterized by specific phenotypic features and impaired functioning that may affect transplantation outcome. We show that IFN-gamma produced by immature CD56(bright) NK cells upregulates cell surface expression of HLA-E on AML blasts and that this upregulation protects leukemic cells from NK-mediated cell lysis through the mediation of CD94/NKG2A, an inhibitory receptor overexpressed on NK cells after haploidentical SCT. Two years after transplantation, however, maturing NK cells were functionally active, as evidenced by high cytotoxicity and poor IFN-gamma production. This implies that maturation of NK cells is the key to improved immune responses and transplantation outcome. PMID:19011664

  20. Retrosigmoid Craniotomy for Auditory Brainstem Implantation in Adult Patients with Neurofibromatosis Type 2.

    PubMed

    Puram, Sidharth V; Herrmann, Barbara; Barker, Fred G; Lee, Daniel J

    2015-12-01

    Objective To report our technique and experience using a retrosigmoid craniotomy approach for auditory brainstem implantation (ABI) placement in adult neurofibromatosis type 2 (NF2) patients. Design Retrospective case series. Setting Single-center study, Boston, Massachusetts, United States. Participants All NF2 patients who underwent evaluation at Massachusetts Eye and Ear Infirmary and surgery at Massachusetts General Hospital from 2009 to 2013 were reviewed. Six cases of retrosigmoid craniotomy for ABI surgery in five adult NF2 patients were identified. The clinical history, operative course, and outcomes in these patients were reviewed. Main Outcome Measures Postoperative complications and audiological outcomes. Results Indications for ABI surgery were profound hearing loss associated with growth or treatment of bilateral vestibular schwannomas. In all cases, a retrosigmoid craniotomy was performed for tumor resection and ABI placement without complication. Electrode placement was confirmed intraoperatively using electrical-evoked auditory brainstem responses. The ABI was activated in the awake patient 4 to 6 weeks postoperatively. Audiological testing was used to evaluate sound detection and speech perception with the ABI. There were no cases of cerebrospinal fluid leak. Conclusion Retrosigmoid craniotomy is a safe and effective means to provide access to the cochlear nucleus for ABI placement following tumor resection in the adult NF2 patient. Preliminary data indicate that this approach has few complications while offering benefits for hearing. The retrosigmoid craniotomy should be considered a reasonable alternative to the traditional translabyrinthine approach for placement of the ABI in deaf patients who are not candidates for the cochlear implant. PMID:27054058

  1. Diagnostic value of symptoms and laboratory data for pertussis in adolescent and adult patients

    PubMed Central

    2013-01-01

    Background Several symptoms are classically thought to be suggestive of pertussis in children, but the diagnostic value of these symptoms in adolescent and adult patients is unclear. We evaluated the accuracy of the clinical findings for the early presumptive diagnosis of pertussis in adolescent and adult patients. Furthermore, we measured fractional exhaled nitric oxide (FeNO) with regard to whether we could distinguish eosinophilic inflammation of the airway and pertussis. FeNO is not expected to be associated with pertussis. Methods We compared 183 cases with laboratory-confirmed pertussis using serology and polymerase chain reaction and 1,132 cases without laboratory-confirmed pertussis. Results Among pertussis patients, paroxysmal cough was common with 90% sensitivity, but the specificity was low (25%). Posttussive vomiting and whoop were less common (sensitivity 25% and 19%, respectively), but both showed greater specificity for pertussis (80% and 86%, respectively). Posttussive gagging was observed with intermediate frequency and provided greater specificity (49% and 77%, respectively). Pertussis cases were most frequent between May and August with a peak in June. The mean FeNO value for the pertussis patients was 18.2 ± 9.2 ppb, which was significantly lower than that in asthma patients (56.9 ± 20.3 ppb, p <0.001). The most useful definition was posttussive vomiting and/or gagging, and a plus normal FeNO value, which had a sensitivity of 72% and a specificity of 70%. Conclusions Clinical symptoms and laboratory data are of limited value in making the diagnosis of pertussis, and it was clinically difficult to differentiate adolescent and adult patients with or without pertussis. However, pertussis should be considered if patients have posttussive vomiting and/or gagging and a normal FeNO concentration. PMID:23496900

  2. Quality of life related to urinary continence in adult spina bifida patients

    PubMed Central

    Dong, Caroline; Casey, Jessica T.; Greiman, Alyssa; Mukherjee, Shubhra; Kielb, Stephanie J.

    2015-01-01

    Introduction To analyze the correlations of bladder management technique, ambulatory status and urologic reconstruction on quality of life (QOL) as affected by urinary symptoms in adult spina bifida (SB) patients. Material and methods Sixty–six adult SB patients completed the RAND 36–Item Health Survey (mSF–36) and Incontinence Quality of Life (I–QOL). Demographic information, history of urinary reconstruction, and bladder management techniques were reviewed and analyzed with respect to survey scores. Results Mean age of patients was 32.3 (SD ±7.2) years and 44 patients (66.7%) were female. Forty–five patients (68.2%) were mainly ambulatory, 21 (31.8%) use a wheelchair and 10 (15.2%) had urologic reconstruction, while 56 (83.3%) did not. Twelve patients (18.2%) void, 42 (63.6%) perform clean intermittent catheterization (CIC), 4 (6.1%) use an indwelling catheter, 3 (4.5%) have an ileal conduit (IC) and 5 (7.6%) mainly use diapers. Mean mSF–36 General Health score was 56.5 (SD ±22.9) and mean I–QOL Sum score was 50.9 (SD ±21.7), where lower scores reflect lower QOL. mSF–36 and I–QOL scores did not significantly correlate with bladder management technique, ambulatory status or urologic reconstruction. A correlation was noted between I–QOL scales and most mSF–36 scales (all p <0.02). Conclusions In our cohort study of adult SB patients, bladder management technique and urologic reconstruction did not correlate with urinary (I–QOL) or general health (mSF–36) domains, although I–QOL and mSF–36 scores correlated closely, suggesting urinary continence is significantly related to general QOL. However, we are unable to identify a single factor that improves either urinary or general QOL. PMID:25914840

  3. Screening and risk factors of exocrine pancreatic insufficiency in critically ill adult patients receiving enteral nutrition

    PubMed Central

    2013-01-01

    Introduction Malnutrition is a frequent problem associated with detrimental clinical outcomes in critically ill patients. To avoid malnutrition, most studies focus on the prevention of inadequate nutrition delivery, whereas little attention is paid to the potential role of exocrine pancreatic insufficiency (EPI). In this trial, we aim to evaluate the prevalence of EPI and identify its potential risk factors in critically ill adult patients without preexisting pancreatic diseases. Methods In this prospective cross-sectional study, we recruited 563 adult patients with critical illnesses. All details of the patients were documented, stool samples were collected three to five days following the initiation of enteral nutrition, and faecal elastase 1 (FE-1) concentrations were assayed using an enzyme-linked immunosorbent assay kit. Blood samples were also taken to determine serum amylase and lipase activity. Results The percentages of recruited patients with EPI (FE-1 concentration <200 μg/g) and severe EPI (FE-1 concentration <100 μg/g) were 52.2% and 18.3%, respectively. The incidences of steatorrhea were significantly different (P < 0.05) among the patients without EPI, with moderate EPI (FE-1 concentration = 100 to 200 μg/g) and severe EPI (FE-1 concentration < 100 μg/g). Both multivariate logistic regression analysis and z-tests indicated that the occurrence of EPI was closely associated with shock, sepsis, diabetes, cardiac arrest, hyperlactacidemia, invasive mechanical ventilation and haemodialysis. Conclusions More than 50% of critically ill adult patients without primary pancreatic diseases had EPI, and nearly one-fifth of them had severe EPI. The risk factors for EPI included shock, sepsis, diabetes, cardiac arrest, hyperlactacidemia, invasive mechanical ventilation and haemodialysis. Trial registration NCT01753024 PMID:23924602

  4. A Systematic Review of Music Therapy Practice and Outcomes with Acute Adult Psychiatric In-Patients

    PubMed Central

    Carr, Catherine; Odell-Miller, Helen; Priebe, Stefan

    2013-01-01

    Background and Objectives There is an emerging evidence base for the use of music therapy in the treatment of severe mental illness. Whilst different models of music therapy have been developed in mental health care, none have specifically accounted for the features and context of acute in-patient settings. This review aimed to identify how music therapy is provided for acute adult psychiatric in-patients and what outcomes have been reported. Review Methods A systematic review using medical, psychological and music therapy databases. Papers describing music therapy with acute adult psychiatric in-patients were included. Analysis utilised narrative synthesis. Results 98 papers were identified, of which 35 reported research findings. Open group work and active music making for nonverbal expression alongside verbal reflection was emphasised. Aims were engagement, communication and interpersonal relationships focusing upon immediate areas of need rather than longer term insight. The short stay, patient diversity and institutional structure influenced delivery and resulted in a focus on single sessions, high session frequency, more therapist direction, flexible use of musical activities, predictable musical structures, and clear realistic goals. Outcome studies suggested effectiveness in addressing a range of symptoms, but were limited by methodological shortcomings and small sample sizes. Studies with significant positive effects all used active musical participation with a degree of structure and were delivered in four or more sessions. Conclusions No single clearly defined model exists for music therapy with adults in acute psychiatric in-patient settings, and described models are not conclusive. Greater frequency of therapy, active structured music making with verbal discussion, consistency of contact and boundaries, an emphasis on building a therapeutic relationship and building patient resources may be of particular importance. Further research is required to

  5. Prognostic impact of persistent cytogenetic abnormalities at complete remission in adult patients with acute lymphoblastic leukemia.

    PubMed

    Short, Nicholas J; Kantarjian, Hagop M; Jabbour, Elias J; O'Brien, Susan M; Faderl, Stefan; Burger, Jan A; Garris, Rebecca; Qiao, Wei; Huang, Xuelin; Jain, Nitin; Konopleva, Marina; Kadia, Tapan M; Daver, Naval; Borthakur, Gautam; Cortes, Jorge E; Ravandi, Farhad

    2016-06-01

    In acute myelogenous leukemia, the persistent detection of abnormal cytogenetics at complete remission (ACCR) is associated with inferior outcomes. However, the prognostic significance of ACCR in adult patients with acute lymphoblastic leukemia (ALL) is unknown. We evaluated 272 adult patients with ALL and abnormal cytogenetics at baseline who were treated with frontline induction chemotherapy, achieved complete remission (CR) and had cytogenetic analysis performed at the time of CR. ACCR was observed in 26 patients (9.6%). Median relapse-free survival was 22 months (95% CI, 12 months to not reached) for patients with ACCR vs. 48 months (range, 30-125 months) in patients with normal cytogenetics at CR (NCCR; P = 0.31). Median overall survival also did not differ significantly between the ACCR (99 months [range, 17 months to not reached]) and NCCR groups (67 months [range, 47 months to not reached], P = 0.86). The specificity of ACCR for minimal residual disease (MRD) positivity by multi-parameter flow cytometry (MFC) was 43%, and there was overall poor correlation between these two methods for the detection of residual disease. When patients were stratified by MRD status, the presence or absence of persistent cytogenetic abnormalities at CR did not add additional prognostic information. This study suggests that there is poor association between MRD assessment by MFC and the presence or absence of cytogenetic abnormalities at CR in adult patients with ALL. ACCR was not associated with adverse outcomes in ALL and did not add additional prognostic information when MRD status by MFC was known. PMID:26800008

  6. The complexity of ADHD: diagnosis and treatment of the adult patient with comorbidities.

    PubMed

    Newcorn, Jeffrey H; Weiss, Margaret; Stein, Mark A

    2007-08-01

    Attention-deficit/hyperactivity disorder (ADHD) is an impairing but usually treatable condition. Popular culture propagates the myth that ADHD recedes with age; this is not the case. Although it is common, <20% of adults with ADHD are diagnosed or treated. Adults with ADHD show significant comorbidities with depressive disorders, anxiety disorders, substance use, oppositional defiant disorder, personality disorders, sleep problems, and learning disabilities. However, symptoms that result from ADHD, such as mood symptoms or lability, are often mistaken for comorbid disorders. Comorbidity with ADHD impacts treatment compliance, treatment response, and patient insight. Insufficient data on the interaction between ADHD and comorbidities impedes proper diagnosis and treatment. Better clinical tools for assessing these conditions are needed. Food and Drug Administration-approved pharmacologic treatments for adult ADHD include stimulants, dexmethylphenidate, and the nonstimulant atomoxetine. Effect sizes of approved medicines at approved doses are half those seen in children. Adults may also need longer duration of medication effects than children. Short-acting stimulants are likely to result in poorer adherence and have a higher risk for diversion or abuse. Risk of abuse is a major concern; stimulant treatments are controlled substances, and children with ADHD show increased risk of substance abuse. Psychosocial interventions may be beneficial in treating both ADHD and comorbidities.In this expert roundtable supplement, Margaret Weiss, MD, PhD, presents a comprehensive overview of complications surrounding differential diagnosis in adults with ADHD. Next, Mark A. Stein, PhD, reviews evaluation, comorbidity, and development of a treatment plan in this population. Finally, Jeffrey H. Newcorn, MD, provides a discussion on the pharmacologic options available for adults with ADHD, considering dosages specific to adults and common comorbidities. PMID:17667893

  7. Molecular detection and characterization of Aichivirus A in adult patients with diarrhea in Thailand.

    PubMed

    Saikruang, Wilaiporn; Khamrin, Pattara; Suantai, Boonpa; Ushijima, Hiroshi; Maneekarn, Niwat

    2014-06-01

    Viral gastroenteritis is a common public health problem that causes morbidity and mortality worldwide. Recently, new viruses causing gastroenteritis have been identified. Among these, Aichivirus has also been proposed as a causative agent of gastroenteritis in human. Most studies have been conducted in infants and children, the information in adults is limited. Therefore, the purpose of this study was to investigate the epidemiology and molecular characterization of Aichivirus in adult patients with diarrhea. A total of 332 fecal specimens collected from January to December 2008 were screened for the presence of Aichivirus by reverse transcription-PCR (RT-PCR) method. Out of 332 fecal specimens tested, Aichivirus was detected with the prevalence of 0.9% (3/332). The data indicate that the prevalence of Aichivirus in adults was as low as those reported in children in Thailand. Phylogenetic analysis of the VP1 sequence revealed that one Aichivirus belonged to genotype A, while other two Aichiviruses were genotype B. In conclusion, this study provided the molecular epidemiological data of Aichivirus circulating in adult patients with diarrhea at low prevalence and the viruses were genetically variable as both genotypes A and B were found in this population. PMID:24536026

  8. Adult life with Duchenne muscular dystrophy: observations among an emerging and unforeseen patient population.

    PubMed

    Rahbek, Jes; Werge, Birgit; Madsen, Anny; Marquardt, John; Steffensen, Birgit Fynbo; Jeppesen, Joergen

    2005-01-01

    The knowledge of adult life with Duchenne muscular dystrophy (DMD) is sparse. The purpose of this study was to review existing information and describe body functional, social participatory and quality of life profiles of the ordinary adult Danish DMD patient. Sixty-five study subjects aged 18-42 years were included in a cross-sectional survey based on data from a semi-structured questionnaire comprising 197 items. The ordinary adult DMD patient states his quality of life as excellent; he is worried neither about his disease nor about the future. His assessment of income, hours of personal assistance, housing, years spent in school and ability to participate in desired activities are positive. Despite heavy immobilization, he is still capable of functioning in a variety of activities that are associated with normal life. He lacks qualifying education and he is in painful need of a love life. The frequency of pains is surprisingly high; nearly 40% has pains daily. The nature, magnitude, consequence and possible cure of these reported pains must be scrutinized. Parents and professionals, paediatricians not the least, must anticipate in all measures taken that the DMD boy grows up to manhood and will need competences for adult social life in all respects. PMID:15799132

  9. Peripheral blood lymphocyte to monocyte ratio identifies high-risk adult patients with sporadic Burkitt lymphoma.

    PubMed

    Wang, Liang; Wang, Hua; Xia, Zhong-Jun; Huang, Hui-Qiang; Jiang, Wen-Qi; Lin, Tong-Yu; Lu, Yue

    2015-10-01

    Adult sporadic Burkitt lymphoma (BL) is a rare subtype of lymphoma. In this retrospective study, we investigated the prognostic value of pretreatment lymphocyte to monocyte ratio (LMR) in a cohort of 62 patients. Using LMR <2.6 as the optimal cutoff point, 24 patients (38.7 %) had LMR <2.6. The complete response rates in high-LMR group and low-LMR group were 90.9 and 65.0 %, respectively (P = 0.019). At a median follow-up time of 41 months, the 3-year progression-free survival (PFS) rate and overall survival (OS) rates were 76 and 80 %, respectively. In a multivariate Cox regression model, it was found that the presence of bone marrow infiltration and low LMR were independently adverse prognostic factors for both PFS and OS. In the whole group, the addition of rituximab to treatment did not benefit patients significantly in PFS and OS. In subgroup analysis, in patients with high LMR, addition of rituximab can significantly improve survival outcomes (P = 0.046). In conclusion, we firstly found that low LMR (<2.60) was an independently adverse prognostic factor in adult patients with sporadic BL. Intensive chemotherapy could cure the majority of patients in our study, and the pretreatment LMR might predict the value of rituximab in this age population. PMID:26082333

  10. Prevalence of subclinical anterior uveitis in adult patients with inflammatory bowel disease

    PubMed Central

    Verbraak, F; Schreinemachers, M; Tiller, A; van Deventer, S J H; de Smet, M D

    2001-01-01

    AIM—To assess the prevalence of subclinical anterior uveitis in adult patients with inflammatory bowel disease.
METHODS—In 179 consecutive patients (96 with Crohn's disease, 55 with ulcerative colitis, and 28 with inflammatory bowel disease of undetermined nature) without previous or concurrent ocular complaints, quantitative flare measurements were obtained with the Kowa FC laser flare to detect the presence of subclinical uveitis.
RESULTS—The mean flare value was 3.9 (SD 1.1) ph/ms in patients younger than 30 years of age, rising to 5.8 (2.5) ph/ms in those over 60 years of age. No measurement performed in this patient population fell outside the mean observed value plus or minus SD of the normal controls within the same age category.
CONCLUSION—In an adult population of 179 consecutive patients with inflammatory bowel disease the presence of a form of subclinical uveitis, as described by Hofley et al in a group of juvenile patients, is highly unlikely.

 PMID:11159490

  11. The views of patients, mentors and adult field nursing students on patients' participation in student nurse assessment in practice.

    PubMed

    McMahon-Parkes, Kate; Chapman, Linda; James, Jayne

    2016-01-01

    In recent years, changes to undergraduate nursing curricula in the United Kingdom have been coupled with increasing expectations that service users be involved in assessment of student nurses. These factors lead to the development of a tool to facilitate gathering of feedback from patients/carers on the competency of adult field student nurses in practice. This study evaluated experiences of those involved in the process of using the feedback tool. Using an exploratory qualitative research design, four patients, four mentors and five pre-registration adult field nursing students were interviewed. Thematic analysis of the data identified three interconnecting themes; value of the patient's voice, caring and protection, and authenticity of feedback. A sub-theme of timing of giving feedback was also identified. Patients felt they should be involved in giving feedback, were comfortable in doing so, and felt best placed to judge students' performance in several aspects of care. Students and mentors shared these opinions. Additionally they felt service user feedback potentially helped improve students' competence and confidence, and facilitated mentors in their assessment of students' professional values, communication and interpersonal skills. However, mentors were more reticent about the possibility of receiving feedback from service users on their own practice. PMID:26347448

  12. Estimated mortality of adult HIV-infected patients starting treatment with combination antiretroviral therapy

    PubMed Central

    Yiannoutsos, Constantin Theodore; Johnson, Leigh Francis; Boulle, Andrew; Musick, Beverly Sue; Gsponer, Thomas; Balestre, Eric; Law, Matthew; Shepherd, Bryan E; Egger, Matthias

    2012-01-01

    Objective To provide estimates of mortality among HIV-infected patients starting combination antiretroviral therapy. Methods We report on the death rates from 122 925 adult HIV-infected patients aged 15 years or older from East, Southern and West Africa, Asia Pacific and Latin America. We use two methods to adjust for biases in mortality estimation resulting from loss from follow-up, based on double-sampling methods applied to patient outreach (Kenya) and linkage with vital registries (South Africa), and apply these to mortality estimates in the other three regions. Age, gender and CD4 count at the initiation of therapy were the factors considered as predictors of mortality at 6, 12, 24 and >24 months after the start of treatment. Results Patient mortality was high during the first 6 months after therapy for all patient subgroups and exceeded 40 per 100 patient years among patients who started treatment at low CD4 count. This trend was seen regardless of region, demographic or disease-related risk factor. Mortality was under-reported by up to or exceeding 100% when comparing estimates obtained from passive monitoring of patient vital status. Conclusions Despite advances in antiretroviral treatment coverage many patients start treatment at very low CD4 counts and experience significant mortality during the first 6 months after treatment initiation. Active patient tracing and linkage with vital registries are critical in adjusting estimates of mortality, particularly in low- and middle-income settings. PMID:23172344

  13. Management of the pediatric nuclear medicine patient (or children are not small adults)

    SciTech Connect

    Kieffer, C.T.; Suto, P.A.

    1983-03-01

    The first of a four-part continuing education series on pediatric nuclear medicine is presented. Included are: (1) clinical indications for performing nuclear medicine studies in children; (2) comparison of nuclear medicine procedures for adult and pedicatric patients; (3) appropriate radiopharmaceuticals for performing pediatric studies; (4) radiation protection techniques (5) the principles of pediatric radiopharmaceutical dose calculation and common calculation methods; (6) possible injection sites and administration methods (7) radiopharmaceutical clearance times and imaging times in adults and children; (8) the collimators of choice for most procedures performed in children; (9) certain behaviors exhibited by children according to their stage of emotional development and children's response to the hospital setting; and (10) patient immobilization techniques and advantages of physical restraint over sedation. (JMT)

  14. Wandering spleen with gastric volvulus and intestinal non-rotation in an adult male patient.

    PubMed

    Ooka, Minako; Kohda, Eiichi; Iizuka, Yuo; Nagamoto, Masashi; Ishii, Tomotaka; Saida, Yoshihisa; Shimizu, Norikazu; Gomi, Tatsuya

    2013-01-01

    We report an extremely rare case of wandering spleen (WS) complicated with gastric volvulus and intestinal non-rotation in a male adult. A 22-year-old man who had been previously treated for Wilson disease was admitted with severe abdominal pain. Radiological findings showed WS in the midline of the pelvic area. The stomach was mesenteroaxially twisted and intestinal non-rotation was observed. Radiology results did not show any evidence of splenic or gastrointestinal (GI) infarction. Elective emergency laparoscopy confirmed WS and intestinal non-rotation; however, gastric volvulus was not observed. It was suspected that the stomach had untwisted when gastric and laparoscopic tubes were inserted. Surgery is strongly recommended for WS because of the high risk of serious complications; however, some asymptomatic adult patients are still treated conservatively, such as the patient in this study. The present case is reported with reference to the literature. PMID:24349711

  15. Wandering spleen with gastric volvulus and intestinal non-rotation in an adult male patient

    PubMed Central

    Kohda, Eiichi; Iizuka, Yuo; Nagamoto, Masashi; Ishii, Tomotaka; Saida, Yoshihisa; Shimizu, Norikazu; Gomi, Tatsuya

    2013-01-01

    We report an extremely rare case of wandering spleen (WS) complicated with gastric volvulus and intestinal non-rotation in a male adult. A 22-year-old man who had been previously treated for Wilson disease was admitted with severe abdominal pain. Radiological findings showed WS in the midline of the pelvic area. The stomach was mesenteroaxially twisted and intestinal non-rotation was observed. Radiology results did not show any evidence of splenic or gastrointestinal (GI) infarction. Elective emergency laparoscopy confirmed WS and intestinal non-rotation; however, gastric volvulus was not observed. It was suspected that the stomach had untwisted when gastric and laparoscopic tubes were inserted. Surgery is strongly recommended for WS because of the high risk of serious complications; however, some asymptomatic adult patients are still treated conservatively, such as the patient in this study. The present case is reported with reference to the literature. PMID:24349711

  16. First Case of Lung Abscess due to Salmonella enterica Serovar Abony in an Immunocompetent Adult Patient.

    PubMed

    Pitiriga, Vassiliki; Dendrinos, John; Nikitiadis, Emanuel; Vrioni, Georgia; Tsakris, Athanassios

    2016-01-01

    In healthy individuals, nontyphoidal Salmonella species predominantly cause a self-limited form of gastroenteritis, while they infrequently invade or cause fatal disease. Extraintestinal manifestations of nontyphoidal Salmonella infections are not common and mainly occur among individuals with specific risk factors; among them, focal lung infection is a rare complication caused by nontyphoidal Salmonella strains typically occurring in immunocompromised patients with prior lung disease. We describe the first case of a localized lung abscess formation in an immunocompetent healthy female adult due to Salmonella enterica serovar Abony. The patient underwent lobectomy and was discharged after full clinical recovery. This case report highlights nontyphoidal Salmonellae infections as a potential causative agent of pleuropulmonary infections even in immunocompetent healthy adults. PMID:27429814

  17. Nonmetastatic Ewing's Sarcoma of the Lumbar Spine in an Adult Patient

    PubMed Central

    Iacoangeli, Maurizio; Dobran, Mauro; Di Rienzo, Alessandro; di Somma, Lucia Giovanna Maria; Alvaro, Lorenzo; Moriconi, Elisa; Nocchi, Niccolò; Gladi, Maurizio; Scerrati, Massimo

    2012-01-01

    Although the spine is frequently involved in metastatic Ewing's sarcoma, primary involvement of the spine, beside sacrum, is much less frequent, especially in adult patients. Because of the low incidence of these tumors, there are currently no clinical guidelines outlining their management and a multitude of therapeutic strategies have been employed with varying success. The definitive management of Ewing's sarcoma of the spine, as in other locations, could include the combination of three main modalities: aggressive surgery, radiotherapy, and combined chemotherapy. Whenever possible, en bloc spondylectomy or extralesional resection is preferable, providing a better oncological result with a longer survival and a better preservation of the spine biomechanics. This is the lesson we learned about the case, we present here, of nonmetastatic lumbar localization by Ewing's sarcoma in as adult patient. PMID:23133768

  18. First Case of Lung Abscess due to Salmonella enterica Serovar Abony in an Immunocompetent Adult Patient

    PubMed Central

    Dendrinos, John; Nikitiadis, Emanuel; Vrioni, Georgia; Tsakris, Athanassios

    2016-01-01

    In healthy individuals, nontyphoidal Salmonella species predominantly cause a self-limited form of gastroenteritis, while they infrequently invade or cause fatal disease. Extraintestinal manifestations of nontyphoidal Salmonella infections are not common and mainly occur among individuals with specific risk factors; among them, focal lung infection is a rare complication caused by nontyphoidal Salmonella strains typically occurring in immunocompromised patients with prior lung disease. We describe the first case of a localized lung abscess formation in an immunocompetent healthy female adult due to Salmonella enterica serovar Abony. The patient underwent lobectomy and was discharged after full clinical recovery. This case report highlights nontyphoidal Salmonellae infections as a potential causative agent of pleuropulmonary infections even in immunocompetent healthy adults. PMID:27429814

  19. IQ, handedness, and pedophilia in adult male patients stratified by referral source.

    PubMed

    Blanchard, Ray; Kolla, Nathan J; Cantor, James M; Klassen, Philip E; Dickey, Robert; Kuban, Michael E; Blak, Thomas

    2007-09-01

    This study investigated whether the previously observed association of pedophilia with lower IQs is an artifact of heterogeneity in referral source. The subjects were 832 adult male patients referred to a specialty clinic for evaluation of their sexual behavior. The patients' erotic preferences for prepubescent, pubescent, or adult partners were assessed with phallometric testing. Full scale IQ was estimated using six subtests from the WAIS-R. The results showed that the relations between pedophilia and lower IQ, lesser education, and increased rates of non-right-handedness were the same in homogeneous groups referred by lawyers or parole and probation officers as they were in a heterogeneous group referred by a miscellany of other sources. Those results, along with secondary analyses in the study, supported the conclusion that the relation between pedophilia and cognitive function is genuine and not artifactual. The findings were interpreted as evidence for the hypothesis that neurodevelopmental perturbations increase the risk of pedophilia in males. PMID:17634757

  20. Use of the adult attachment projective picture system in psychodynamic psychotherapy with a severely traumatized patient

    PubMed Central

    George, Carol; Buchheim, Anna

    2014-01-01

    The following case study is presented to facilitate an understanding of how the attachment information evident from Adult Attachment Projective Picture System (AAP) assessment can be integrated into a psychodynamic perspective in making therapeutic recommendations that integrate an attachment perspective. The Adult Attachment Projective Picture System (AAP) is a valid representational measure of internal representations of attachment based on the analysis of a set of free response picture stimuli designed to systematically activate the attachment system (George and West, 2012). The AAP provides a fruitful diagnostic tool for psychodynamic-oriented clinicians to identify attachment-based deficits and resources for an individual patient in therapy. This paper considers the use of the AAP with a traumatized patient in an inpatient setting and uses a case study to illustrate the components of the AAP that are particularly relevant to a psychodynamic conceptualization. The paper discusses also attachment-based recommendations for intervention. PMID:25140164

  1. Variability of ICU Use in Adult Patients With Minor Traumatic Intracranial Hemorrhage

    PubMed Central

    Nishijima, Daniel K.; Haukoos, Jason S.; Newgard, Craig D.; Staudenmayer, Kristan; White, Nathan; Slattery, David; Maxim, Preston C.; Gee, Christopher A.; Hsia, Renee Y.; Melnikow, Joy A.; Holmes, James F.

    2013-01-01

    Study objective Patients with minor traumatic intracranial hemorrhage are frequently admitted to the ICU, although many never require critical care interventions. To describe ICU resource use in minor traumatic intracranial hemorrhage, we assess (1) the variability of ICU use in a cohort of patients with minor traumatic intracranial hemorrhage across multiple trauma centers, and (2) the proportion of adult patients with traumatic intracranial hemorrhage who are admitted to the ICU and never receive a critical care intervention during hospitalization. In addition, we evaluate the association between ICU admission and key independent variables. Methods A structured, historical cohort study of adult patients (aged 18 years and older) with minor traumatic intracranial hemorrhage was conducted within a consortium of 8 Level I trauma centers in the western United States from January 2005 to June 2010. The study population included patients with minor traumatic intracranial hemorrhage, defined as an emergency department (ED) Glasgow Coma Scale (GCS) score of 15 (normal mental status) and an Injury Severity Score less than 16 (no other major organ injury). The primary outcome measure was initial ICU admission. The secondary outcome measure was a critical care intervention during hospitalization. Critical care interventions included mechanical ventilation, neurosurgical intervention, transfusion of blood products, vasopressor or inotrope administration, and invasive hemodynamic monitoring. ED disposition and the proportion of ICU patients not receiving a critical care intervention were compared across sites with descriptive statistics. The association between ICU admission and predetermined independent variables was analyzed with multivariable regression. Results Among 11,240 adult patients with traumatic intracranial hemorrhage, 1,412 (13%) had minor traumatic intracranial hemorrhage and complete ED disposition data (mean age 48 years; SD 20 years). ICU use within this

  2. Urticaria and dermographism in patients with adult-onset Still's disease.

    PubMed

    Criado, Paulo Ricardo; de Carvalho, Jozélio Freire; Ayabe, Liliane Akemi; Brandt, Hebert Roberto Clivati; Romiti, Ricardo; Maruta, Celina W

    2012-08-01

    Adult-onset Still's disease (AOSD) patients typically present with arthralgia, fever, lymphadenopathy and a transient salmon maculopapular rash. Only approximately 25 cases of AOSD with urticaria were described in the literature. In this article, the authors report three additional cases of AOSD with urticarial and dermographic lesions who had a good clinical response to glucocorticoid and antihistamines. A review of the literature concerning this issue is also herein written. PMID:21785958

  3. A systematic review of hospitalization resulting from medicine-related problems in adult patients

    PubMed Central

    Al Hamid, Abdullah; Ghaleb, Maisoon; Aljadhey, Hisham; Aslanpour, Zoe

    2014-01-01

    Aims Medicine-related problems (MRPs) represent a major issue leading to hospitalization, especially in adult and elderly patients. The aims of this review are to investigate the prevalence, causes and major risk factors for MRPs leading to hospitalization in adult patients and to identify the main medicine classes involved. Methods Studies were identified through electronic searches of Medline, Embase, Scopus and International Pharmaceutical Abstracts between January 2000 and May 2013. A systematic review was conducted of both retrospective and prospective studies. Studies included were those involving hospitalization resulting from MRPs in adults (≥18 years old), whereas studies excluded were those investigating drug misuse and abuse and studies investigating MRPs in hospitalized patients. Data analysis was performed using SPSS version 20. Results Forty-five studies were identified, including 21 that investigated hospitalization resulting from adverse drug reactions, six studies that investigated hospitalization due to adverse drug events and 18 studies that investigated hospitalization due to MRPs. The median prevalence rates of hospitalization resulting from adverse drug reactions, adverse drug events and MRPs were 7% (interquartile range, 2.4–14.9%), 4.6% (interquartile range, 2.85–16.6%) and 12.1% (interquartile range, 6.43–22.2%), respectively. The major causes contributing to MRPs were adverse drug reactions and noncompliance. In addition, the major risk factors associated with MRPs were old age, polypharmacy and comorbidities. Moreover, the main classes of medicines implicated were medicines used to treat cardiovascular diseases and diabetes. Conclusions Hospitalization due to MRPs had a high prevalence, in the range of 4.6–12.1%. Most MRPs encountered were prevalent among adult patients taking medicines for cardiovascular diseases and diabetes. PMID:24283967

  4. Clinical presentations and biochemical profile in adult celiac disease patients in Hyderabad: Pakistan

    PubMed Central

    Masood, Naila; Ali Shaikh, Imran

    2014-01-01

    Objective: To see the various clinical presentations and biochemical profile in adult celiac disease patients of Hyderabad Sindh. Methods: A total 60 suspected cases of adult celiac disease, both males and females were screened out from Liaquat University of Medical and Health Sciences hospital and private clinics at Sadar Hyderabad Sind by non probability purposive sampling during a period from July 2011 to December 2012.Age ranged between 18 to 55 Years. A detailed history and clinical examination was done. Patients already on gluten free diet, age <12years, tuberculosis or cancer of intestine/colon and patients of diabetes and thyroid disorder were excluded, while patients having positive ant tTG (value >15 iu/ml detected by ELISA) were included. The biochemical profile including serum albumin, calcium ,ferritin, SGPT, Alkaline phosphatase and Haemoglobin were estimated in central Diagnostic laboratory LUMHS by taking 10 cc centrifuged blood sample. The data was plotted on SPSS 16, mean and percentages were calculated. Results: All patients were divided in to three groups according to age. The most common group was 18-30 years; (mean, 23.5±5.6) comprised 56.6%. The commonest clinical presentation was diarrhoea in 50%, menstrual irregularity in 21%, walking problems 21%, undue fatigue in 15% and edema in 15%. P values calculated in quantitative variable of males and females. The p value was significant in between serum calcium (p 0.004), haemoglobin (p 0,004), serum ferritin (<0.005) and alkaline phosphatise (<0.005). Conclusion: This study showed that Adult celiac disease was present with entirely different clinical and biochemical profile in patients in this region. PMID:24772128

  5. Differences of Sagittal Lumbosacral Parameters between Patients with Lumbar Spondylolysis and Normal Adults

    PubMed Central

    Yin, Jin; Peng, Bao-Gan; Li, Yong-Chao; Zhang, Nai-Yang; Yang, Liang; Li, Duan-Ming

    2016-01-01

    Background: Recent studies have suggested an association between elevated pelvic incidence (PI) and the development of lumbar spondylolysis. However, there is still lack of investigation for Han Chinese people concerning the normal range of spinopelvic parameters and relationship between abnormal sagittal parameters and lumbar diseases. The objective of the study was to investigate sagittal lumbosacral parameters of adult lumbar spondylolysis patients in Han Chinese population. Methods: A total of 52 adult patients with symptomatic lumbar spondylolysis treated in the General Hospital of Armed Police Force (Beijing, China) were identified as the spondylolysis group. All the 52 patients were divided into two subgroups, Subgroup A: 36 patients with simple lumbar spondylolysis, and Subgroup B: 16 patients with lumbar spondylolysis accompanying with mild lumbar spondylolisthesis (slip percentage <30%). Altogether 207 healthy adults were chosen as the control group. All patients and the control group took lumbosacral lateral radiographs. Seven sagittal lumbosacral parameters, including PI, pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), L5 incidence, L5 slope, and sacral table angle (STA), were measured in the lateral radiographs. All the parameters aforementioned were compared between the two subgroups and between the spondylolysis group and the control group with independent-sample t-test. Results: There were no statistically significant differences of all seven sagittal lumbosacral parameters between Subgroup A and Subgroup B. PI, PT, SS, and LL were higher (P < 0.05) in the spondylolysis group than those in the control group, but STA was lower (P < 0.001) in the spondylolysis group. Conclusions: Current study results suggest that increased PI and decreased STA may play important roles in the pathology of lumbar spondylolysis in Han Chinese population. PMID:27174324

  6. Reduced transcription of TCOF1 in adult cells of Treacher Collins syndrome patients

    PubMed Central

    2009-01-01

    Background Treacher Collins syndrome (TCS) is an autosomal dominant craniofacial disorder caused by frameshift deletions or duplications in the TCOF1 gene. These mutations cause premature termination codons, which are predicted to lead to mRNA degradation by nonsense mediated mRNA decay (NMD). Haploinsufficiency of the gene product (treacle) during embryonic development is the proposed molecular mechanism underlying TCS. However, it is still unknown if TCOF1 expression levels are decreased in post-embryonic human cells. Methods We have estimated TCOF1 transcript levels through real time PCR in mRNA obtained from leucocytes and mesenchymal cells of TCS patients (n = 23) and controls (n = 18). Mutational screening and analysis of NMD were performed by direct sequencing of gDNA and cDNA, respectively. Results All the 23 patients had typical clinical features of the syndrome and pathogenic mutations were detected in 19 of them. We demonstrated that the expression level of TCOF1 is 18-31% lower in patients than in controls (p < 0.05), even if we exclude the patients in whom we did not detect the pathogenic mutation. We also observed that the mutant allele is usually less abundant than the wild type one in mesenchymal cells. Conclusions This is the first study to report decreased expression levels of TCOF1 in TCS adult human cells, but it is still unknown if this finding is associated to any phenotype in adulthood. In addition, as we demonstrated that alleles harboring the pathogenic mutations have lower expression, we herein corroborate the current hypothesis of NMD of the mutant transcript as the explanation for diminished levels of TCOF1 expression. Further, considering that TCOF1 deficiency in adult cells could be associated to pathologic clinical findings, it will be important to verify if TCS patients have an impairment in adult stem cell properties, as this can reduce the efficiency of plastic surgery results during rehabilitation of these patients. PMID:20003452

  7. Marital Status and Fertility in Adult Iranian Patients with β-Thalassemia Major.

    PubMed

    Miri-Aliabad, Ghasem; Fadaee, Mahsoumeh; Khajeh, Ali; Naderi, Majid

    2016-03-01

    Expecting a family is an important component and a great goal for better quality of life for most of adults with β-thalassemia major. The aim of the present study was to examine the marital status of adults with β-thalassemia major. This cross-sectional study examined the marital status of patients with transfusion-dependent β-thalassemia aged over 15 years. Patients' demographic characteristics including age, gender, marital status, duration of marriage, divorce, having or not having children and spouse's health status were recorded. Information about the disease including cardiac and endocrine complications, ferritin level, splenectomy and viral hepatitis were also recorded. Of 228 patients with transfusion-dependent β-thalassemia major aged over 15 years who were treated at this medical center, 32 (14 %) were married. The mean age of married patients was 25.18 ± 4.74 years. Among the married patients, 8 (25 %) were females and 24 (75 %) patients were males. The mean age of marriage was 22.76 ± 4.16 years. The minimum and maximum marriage age was 15 and 33 years, respectively. The median duration of marriage was one year with the range from 3 months to 11 years. Only 8 (25 %) patients (one female and seven males) had children. Therapeutic advances have led to significantly increased survival and improved quality of life and fertility of patients with β-thalassemia major. According to the results, 14 % of patients over 15 years were married which was slightly higher as compared with other similar studies. PMID:26855517

  8. Quality Measures for the Care of Adult Patients with Restless Legs Syndrome

    PubMed Central

    Trotti, Lynn Marie; Goldstein, Cathy A.; Harrod, Christopher G.; Koo, Brian B.; Sharon, Denise; Zak, Rochelle; Chervin, Ronald D.

    2015-01-01

    The American Academy of Sleep Medicine (AASM) commissioned several Workgroups to develop quality measures for the care of patients with common sleep disorders, including adults with restless legs syndrome (RLS). Using the AASM process for quality measure development, the RLS Work-group developed three target outcomes for RLS management, including improving the accuracy of diagnosis, reducing symptom severity, and minimizing treatment complications. Seven processes were developed to support these outcomes. To achieve the outcome of improving accuracy of diagnosis, the use of accepted diagnostic criteria and assessment of iron stores are recommended. To realize the outcome of decreasing symptom severity, routine assessment of severity and provision of evidence-based treatment are recommended. To support the outcome of minimizing treatment complications, counseling about potential side effects and assessing for augmentation and impulse control disorders, when indicated, are recommended. Further research is needed to validate optimal practice processes to achieve best outcomes in adult patients with RLS. Citation: Trotti LM, Goldstein CA, Harrod CG, Koo BB, Sharon D, Zak R, Chervin RD. Quality measures for the care of adult patients with restless legs syndrome. J Clin Sleep Med 2015;11(3):293–310. PMID:25700882

  9. Adolescents and adults affected by Cornelia de Lange syndrome: A report of 73 Italian patients.

    PubMed

    Mariani, Milena; Decimi, Valentina; Bettini, Laura Rachele; Maitz, Silvia; Gervasini, Cristina; Masciadri, Maura; Ajmone, Paola; Kullman, Gaia; Dinelli, Marco; Panceri, Roberto; Cereda, Anna; Selicorni, Angelo

    2016-06-01

    Cornelia de Lange syndrome (CdLS) is a rare genetic condition related to mutation of various cohesion complex related genes. Its natural history is quite well characterized as regard pediatric age. Relatively little information is available regarding the evolution of the disease in young-adult age. In medical literature, only one specific study has been published on this topic. We report on our experience on 73 Italian CdLS patients (40 males and 33 females) with and age range from 15 to 49 years. Our results confirm the previous study indicating that gastroesophageal reflux disease (GERD) is the main medical problem of these patients in childhood and young-adult age. Other medical features that should be considered in the medical follow-up are tendency to overweight/frank obesity, constipation, discrepancy of limbs' length, epilepsy, hearing, and visual problems. Behavioral problems are particularly frequent as well. For this reason, every source of hidden pain should be actively searched for in evaluating a patient showing such a disorder. Finally, recommendations for medical follow-up in adult age are discussed. © 2016 Wiley Periodicals, Inc. PMID:27164219

  10. Congenital Intratympanic Cholesteatoma in an Adult Patient: A Case Report and Review of the Literature.

    PubMed

    Pedruzzi, Barbara; Mion, Marta; Comacchio, Francesco

    2016-04-01

    Congenital cholesteatoma within the tympanic membrane is an uncommon entity, with only few cases being documented. The aetiopathogenesis of this lesion is still unknown; however, when cholesteatoma develops in subjects without any history of previous ear inflammation, as in the case we report here, an embryologic origin is deeply suspected. An acquired origin is hypothesized in patients with a previous history of an inflammatory process of the external or middle ear because of the proliferation of the basal cell layer of the tympanic membrane epithelium. We report a rare case of congenital cholesteatoma of the tympanic membrane in an adult patient and review the literature. PMID:27340998

  11. Role of preoperative screening for adult patients for obstructive sleep apnea.

    PubMed

    Selim, Bernardo J; Surani, Salim R; Ramar, Kannan

    2014-12-01

    Obstructive sleep apnea (OSA) is a chronic disease with increasing prevalence. Underdiagnosed in the surgical population, OSA can reach a prevalence of up to 70% in bariatric surgery, and be associated with difficult airways and postoperative cardiopulmonary adverse events. Despite its association with escalation of care, increased health care resource utilization, and length of hospital stay, < 25% of health care institutions in the United States have OSA perioperative protocols to improve patient safety. This is explained in part by a lack of studies that support a widely accepted systematic approach to preoperative screening and risk stratification. This review evaluates the role of preoperative screening tools for adult patients with suspected OSA. PMID:25485922

  12. Contemporary Concepts in the Young Adult Hip Patient: Periacetabular Osteotomy for Hip Dysplasia.

    PubMed

    Coobs, Benjamin R; Xiong, Ao; Clohisy, John C

    2015-07-01

    The Bernese periacetabular osteotomy, as originally described by Dr. Reinhold Ganz, is an effective treatment for symptomatic acetabular dysplasia in the pre-arthritic young adult hip. This technique has experienced several recent modifications in an attempt to optimize the clinical outcomes of these patients. We will review the clinical presentation of acetabular dysplasia, indications for surgery, contemporary refinements in technique and clinical results following periacetabular osteotomy. In well-selected patients, this reconstructive osteotomy should be considered safe and effective in alleviating pain and improving hip function. PMID:25865812

  13. Evaluation and Surgical Management of the Overcorrected Clubfoot Deformity in the Adult Patient.

    PubMed

    Burger, Dawid; Aiyer, Amiethab; Myerson, Mark S

    2015-12-01

    Adult patients presenting with an overcorrected clubfoot often have had a posteromedial release. They present later in life and have compensated quite well despite the development of deformity. Minor trauma may lead to the onset of acute symptoms. A spectrum of deformity exists. Key features include a dorsally subluxated navicular, a dorsal bunion from overpull of the tibialis anterior tendon, valgus of the ankle or hindfoot or both, and a flattop talus. This article details the diagnostic approach to the overcorrected clubfoot patient and options for management of the various components of the deformity. PMID:26589080

  14. Epidemiological features of influenza in Canadian adult intensive care unit patients.

    PubMed

    Taylor, G; Abdesselam, K; Pelude, L; Fernandes, R; Mitchell, R; McGeer, A; Frenette, C; Suh, K N; Wong, A; Katz, K; Wilkinson, K; Mersereau, T; Gravel, D

    2016-03-01

    To identify predictive factors and mortality of patients with influenza admitted to intensive care units (ICU) we carried out a prospective cohort study of patients hospitalized with laboratory-confirmed influenza in adult ICUs in a network of Canadian hospitals between 2006 and 2012. There were 626 influenza-positive patients admitted to ICUs over the six influenza seasons, representing 17·9% of hospitalized influenza patients, 3·1/10,000 hospital admissions. Variability occurred in admission rate and proportion of hospital influenza patients who were admitted to ICUs (proportion range by year: 11·7-29·4%; 21·3% in the 2009-2010 pandemic). In logistic regression models ICU patients were younger during the pandemic and post-pandemic period, and more likely to be obese than hospital non-ICU patients. Influenza B accounted for 14·2% of all ICU cases and had a similar ICU admission rate as influenza A. Influenza-related mortality was 17·8% in ICU patients compared to 2·0% in non-ICU patients. PMID:26384310

  15. Extracorporeal life support for 100 adult patients with severe respiratory failure.

    PubMed Central

    Kolla, S; Awad, S S; Rich, P B; Schreiner, R J; Hirschl, R B; Bartlett, R H

    1997-01-01

    OBJECTIVE: The authors retrospectively reviewed their experience with extracorporeal life support (ECLS) in 100 adult patients with severe respiratory failure (ARF) to define techniques, characterize its efficacy and utilization, and determine predictors of outcome. SUMMARY BACKGROUND DATA: Extracorporeal life support maintains gas exchange during ARF, providing diseased lungs an optimal environment in which to heal. Extracorporeal life support has been successful in the treatment of respiratory failure in infants and children. In 1990, the authors instituted a standardized protocol for treatment of severe ARF in adults, which included ECLS when less invasive methods failed. METHODS: From January 1990 to July 1996, the authors used ECLS for 100 adults with severe acute hypoxemic respiratory failure (n = 94): paO2/FiO2 ratio of 55.7+/-15.9, transpulmonary shunt (Qs/Qt) of 52+/-22%, or acute hypercarbic respiratory failure (n = 6): paCO2 84.0+/-31.5 mmHg, despite and after maximal conventional ventilation. The technique included venovenous percutaneous access, lung "rest," transport on ECLS, minimal anticoagulation, hemofiltration, and optimal systemic oxygen delivery. RESULTS: Overall hospital survival was 54%. The duration of ECLS was 271.9+/-248.6 hours. Primary diagnoses included pneumonia (49 cases, 53% survived), adult respiratory distress syndrome (45 cases, 51 % survived), and airway support (6 cases, 83% survived). Multivariate logistic regression modeling identified the following pre-ECLS variables significant independent predictors of outcome: 1) pre-ECLS days of mechanical ventilation (p = 0.0003), 2) pre-ECLS paO2/FiO2 ratio (p = 0.002), and 3) age (years) (p = 0.005). Modeling of variables during ECLS showed that no mechanical complications were independent predictors of outcome, and the only patient-related complications associated with outcome were the presence of renal failure (p < 0.0001) and significant surgical site bleeding (p = 0

  16. Blueprint for Implementing New Processes in Acute Care: Rescuing Adult Patients With Intraosseous Access.

    PubMed

    Chreiman, Kristen M; Kim, Patrick K; Garbovsky, Lyudmila A; Schweickert, William D

    2015-01-01

    The intraosseous (IO) access initiative at an urban university adult level 1 trauma center began from the need for a more expeditious vascular access route to rescue patients in extremis. The goal of this project was a multidisciplinary approach to problem solving to increase access of IO catheters to rescue patients in all care areas. The initiative became a collaborative effort between nursing, physicians, and pharmacy to embark on an acute care endeavor to standardize IO access. This is a descriptive analysis of processes to effectively develop collaborative strategies to navigate hospital systems and successfully implement multilayered initiatives. Administration should empower nurse to advance their practice to include IO for patient rescue. Intraosseous access may expedite resuscitative efforts in patients in extremis who lack venous access or where additional venous access is required for life-saving therapies. Limiting IO dwell time may facilitate timely definitive venous access. Continued education and training by offering IO skill laboratory refreshers and annual e-learning didactic is optimal for maintaining proficiency and knowledge. More research opportunities exist to determine medication safety and efficacy in adult patients in the acute care setting. PMID:26352658

  17. Prevalence of human norovirus and Clostridium difficile coinfections in adult hospitalized patients

    PubMed Central

    Stokely, Janelle N; Niendorf, Sandra; Taube, Stefan; Hoehne, Marina; Young, Vincent B; Rogers, Mary AM; Wobus, Christiane E

    2016-01-01

    Objective Human norovirus (HuNoV) and Clostridium difficile are common causes of infectious gastroenteritis in adults in the US. However, limited information is available regarding HuNoV and C. difficile coinfections. Our study was designed to evaluate the prevalence of HuNoV and C. difficile coinfections among adult patients in a hospital setting and disease symptomatology. Study design and setting For a cross-sectional analysis, 384 fecal samples were tested for the presence of C. difficile toxins from patients (n=290), whom the provider suspected of C. difficile infections. Subsequent testing was then performed for HuNoV genogroups I and II. Multinomial logistic regression was performed to determine symptoms more frequently associated with coinfections. Results The final cohort consisted of the following outcome groups: C. difficile (n=196), C. difficile + HuNoV coinfection (n=40), HuNoV only (n=12), and neither (n=136). Coinfected patients were more likely to develop nausea, gas, and abdominal pain and were more likely to seek treatment in the winter season compared with individuals not infected or infected with either pathogen alone. Conclusion Our study revealed that patients with coinfection are more likely to experience certain gastrointestinal symptoms, in particular abdominal pain, suggesting an increased severity of disease symptomatology in coinfected patients. PMID:27418856

  18. Violent behaviour from young adults and the parents of paediatric patients in the emergency department.

    PubMed

    Pich, Jacqueline; Hazelton, Michael; Kable, Ashley

    2013-07-01

    Violence in healthcare is a significant issue and one that is increasing in prevalence globally. Nurses have been identified as the professional group at most risk, with patients the main source of this violence. The aim of this study was to describe the experiences of Australian ED nurses with episodes of patient-related violence from young adults (16-25years of age) and the parents of paediatric patients. Data analysis of semi-structured interviews led to the identification of antecedents to episodes of violence and behaviours specific to these two groups of interest. These behaviours included: "performing" and attention-seeking behaviours and violent behaviours including both verbal and physical abuse. Antecedents discussed by participants included: parental emotions and alcohol and substance abuse. Overall the results speak to a working environment where participants regularly feel unsafe. Violence in the ED is perceived to occur frequently and to such an extent that participants have become resigned to expect and accept it as part of their job. The role played by distinct groups such as young adults and the parents of paediatric patients must be acknowledged and this knowledge used along with other known risk factors to help identify patients at risk of potential violence. PMID:23063841

  19. The use of arts and crafts in the rehabilitation of the adult burn patient.

    PubMed

    Sanford, S L; Cash, S H; Nelson, C

    1995-01-01

    The purpose of this study was to gain insight into one small aspect of occupational therapy: the use of arts and crafts in the rehabilitation of the adult burn patient. While burn care literature is plentiful, that related specifically to occupational therapy treatment of burn patients is scarce. A survey was mailed to occupational therapists in 165 burn units across the United States. Responses to survey questions indicate that a majority of respondents (73%%) do not use arts and crafts in the rehabilitation of adult burn patients, while 26%% do use these modalities. Those respondents who do use arts and crafts stated that they use leatherwork, painting, and woodworking most frequently. Therapists who do not use arts and crafts indicated that their primary reasons for not doing so were the acutely ill status of the patients and wound drainage/sterility issues. The entire scope of occupational therapy treatment of burn patients deserves greater attention as it is a challenging and rapidly-evolving area of practice. PMID:23947587

  20. Patients with Acute Myeloid Leukemia Admitted to Intensive Care Units: Outcome Analysis and Risk Prediction

    PubMed Central

    Braess, Jan; Thudium, Johannes; Schmid, Christoph; Kochanek, Matthias; Kreuzer, Karl-Anton; Lebiedz, Pia; Görlich, Dennis; Gerth, Hans U.; Rohde, Christian; Kessler, Torsten; Müller-Tidow, Carsten; Stelljes, Matthias; Büchner, Thomas; Schlimok, Günter; Hallek, Michael; Waltenberger, Johannes; Hiddemann, Wolfgang; Berdel, Wolfgang E.; Heilmeier, Bernhard; Krug, Utz

    2016-01-01

    Background This retrospective, multicenter study aimed to reveal risk predictors for mortality in the intensive care unit (ICU) as well as survival after ICU discharge in patients with acute myeloid leukemia (AML) requiring treatment in the ICU. Methods and Results Multivariate analysis of data for 187 adults with AML treated in the ICU in one institution revealed the following as independent prognostic factors for death in the ICU: arterial oxygen partial pressure below 72 mmHg, active AML and systemic inflammatory response syndrome upon ICU admission, and need for hemodialysis and mechanical ventilation in the ICU. Based on these variables, we developed an ICU mortality score and validated the score in an independent cohort of 264 patients treated in the ICU in three additional tertiary hospitals. Compared with the Simplified Acute Physiology Score (SAPS) II, the Logistic Organ Dysfunction (LOD) score, and the Sequential Organ Failure Assessment (SOFA) score, our score yielded a better prediction of ICU mortality in the receiver operator characteristics (ROC) analysis (AUC = 0.913 vs. AUC = 0.710 [SAPS II], AUC = 0.708 [LOD], and 0.770 [SOFA] in the training cohort; AUC = 0.841 for the developed score vs. AUC = 0.730 [SAPSII], AUC = 0.773 [LOD], and 0.783 [SOFA] in the validation cohort). Factors predicting decreased survival after ICU discharge were as follows: relapse or refractory disease, previous allogeneic stem cell transplantation, time between hospital admission and ICU admission, time spent in ICU, impaired diuresis, Glasgow Coma Scale <8 and hematocrit of ≥25% at ICU admission. Based on these factors, an ICU survival score was created and used for risk stratification into three risk groups. This stratification discriminated distinct survival rates after ICU discharge. Conclusions Our data emphasize that although individual risks differ widely depending on the patient and disease status, a substantial portion of critically ill patients with AML benefit

  1. [Nursing diagnoses for family members of adult burned patients near hospital discharge].

    PubMed

    Goyatá, Sueli Leiko Takamatsu; Rossi, Lídia Aparecida; Dalri, Maria Célia Barcellos

    2006-01-01

    This study aimed to identify the nursing diagnoses for family members of adult burned patients in the period near hospital discharge. We evaluated 10 family members of burned patients through interviews and observation. The nursing diagnoses were established on the basis of the NANDA International Taxonomy II and on Carpenito's interpretation of the NANDA Taxonomy I. We identified 11 different diagnosis categories, all of which were real. The most frequent diagnoses among the family members under analysis were knowledge deficit and anxiety. The former was characterized by the family members' need for information about care for the burned areas and infection prevention. The feeling of anxiety was mainly related to the changes in the appearance, structure or function of the burned patient's body and to the family members' expectations with respect to the patient's return to the family and work environment, accompanied by some physical, psycho-emotional or social consequence. PMID:16532246

  2. Atypical course of Henoch-Schonlein purpura in an adult patient

    PubMed Central

    Górnikiewicz-Brzezicka, Bożena; Brzezicki, Jan; Rymko, Marcin; Jeka, Sławomir

    2015-01-01

    Henoch-Schonlein purpura is vasculitis of small blood vessels characterized by deposits of IgA immune complexes and also non-thrombocytopenic purpura, abdominal pain, arthritis and renal involvement. It affects people of all ages, but most cases occur in children between 2 and 11 years old, more frequently in boys. The disease is much less common in adults, who often have a more severe course of the disease. The paper presents the case of a 38-year-old female patient with insidious course of the disease, initially dominant skin symptoms and joint pain without signs of inflammation. Symptoms of the disease were initially uncharacteristic and mild, and did not suggest severe and rapid course of the disease. The patient required hospitalization in several departments before final diagnosis of Henoch-Schonlein purpura. The patient was treated with corticosteroids and immunosuppression. Despite the rapid course of the disease, treatment was effective. The patient was discharged in good condition. PMID:27407252

  3. Increased pulmonary alveolar-capillary permeability in patients at risk for adult respiratory distress syndrome

    SciTech Connect

    Tennenberg, S.D.; Jacobs, M.P.; Solomkin, J.S.; Ehlers, N.A.; Hurst, J.M.

    1987-04-01

    Two methods for predicting adult respiratory distress syndrome (ARDS) were evaluated prospectively in a group of 81 multitrauma and sepsis patients considered at clinical high risk. A popular ARDS risk-scoring method, employing discriminant analysis equations (weighted risk criteria and oxygenation characteristics), yielded a predictive accuracy of 59% and a false-negative rate of 22%. Pulmonary alveolar-capillary permeability (PACP) was determined with a radioaerosol lung-scan technique in 23 of these 81 patients, representing a statistically similar subgroup. Lung scanning achieved a predictive accuracy of 71% (after excluding patients with unilateral pulmonary contusion) and gave no false-negatives. We propose a combination of clinical risk identification and functional determination of PACP to assess a patient's risk of developing ARDS.

  4. Psychometric evaluation of the Sheehan Disability Scale in adult patients with attention-deficit/hyperactivity disorder.

    PubMed

    Coles, Theresa; Coon, Cheryl; DeMuro, Carla; McLeod, Lori; Gnanasakthy, Ari

    2014-01-01

    Inattention and impulsivity symptoms are common among adults with attention-deficit/hyperactivity disorder (ADHD), which can lead to difficulty concentrating, restlessness, difficulty completing tasks, disorganization, impatience, and impulsiveness. Many adults with ADHD find it difficult to focus and prioritize. Resulting outcomes, such as missed deadlines and forgotten engagements, may ultimately impact the ability to function at work, school, home, or in a social environment. The European Medicines Agency guidelines for evaluating medicinal products for ADHD recommend inclusion of both functional outcomes, such as school, social, or work functioning, and outcomes related to symptoms of ADHD in clinical studies of novel medication primary efficacy endpoints. Due to its performance in other disease areas and the relevance of its items as evidenced by content validity analyses, the Sheehan Disability Scale (SDS) was chosen to assess functional impairment in ADHD. The aim of this study was to investigate the psychometric properties of the SDS, used as a brief measure of functional impairment in a number of psychiatric disorders, in adult patients with ADHD. To the authors' knowledge, this is the first study to evaluate the reliability of the SDS (based on Cronbach's coefficient alpha and test-retest reliability), its validity (construct and known-groups validity), and its ability to detect change in this patient population. This study also established a preliminary responder definition for the SDS in this study population to determine when change can be considered clinically beneficial in a clinical trial setting. The psychometric results support the use of the SDS subscales (items 1-3) and total score (sum of items 1-3) in an ADHD population. In addition, the evaluation provides evidence for a three-point preliminary responder definition for the SDS and further evidence of its responsiveness in adults with ADHD. Altogether, the results indicate that the SDS is a

  5. Long-Term Outcome of Critically Ill Adult Patients with Acute Epiglottitis

    PubMed Central

    Hernu, Romain; Baudry, Thomas; Bohé, Julien; Piriou, Vincent; Allaouchiche, Bernard; Disant, François; Argaud, Laurent

    2015-01-01

    Background Acute epiglottitis is a potentially life threatening disease, with a growing incidence in the adult population. Its long-term outcome after Intensive Care Unit (ICU) hospitalization has rarely been studied. Methodology and Principal Findings Thirty-four adult patients admitted for acute epiglottitis were included in this retrospective multicentric study. The mean age was 44±12 years (sex ratio: 5.8). Sixteen patients (47%) had a history of smoking while 8 (24%) had no previous medical history. The average time of disease progression before ICU was 2.6±3.6 days. The main reasons for hospitalization were continuous monitoring (17 cases, 50%) and acute respiratory distress (10 cases, 29%). Microbiological documentation could be made in 9 cases (26%), with Streptococcus spp. present in 7 cases (21%). Organ failure at ICU admission occurred in 8 cases (24%). Thirteen patients (38%) required respiratory assistance during ICU stay; 9 (26%) required surgery. Two patients (6%) died following hypoxemic cardiac arrest. Five patients (15%) had sequelae at 1 year. Patients requiring respiratory assistance had a longer duration of symptoms and more frequent anti inflammatory use before ICU admission and sequelae at 1 year (p<0.05 versus non-ventilated patients). After logistic regression analysis, only exposure to anti-inflammatory drugs before admission was independently associated with airway intervention (OR, 4.96; 95% CI, 1.06-23.16). Conclusions and Significance The profile of the cases consisted of young smoking men with little comorbidity. Streptococcus spp. infection represented the main etiology. Outcome was favorable if early respiratory tract protection could be performed in good conditions. Morbidity and sequelae were greater in patients requiring airway intervention. PMID:25945804

  6. Novel Munc13–4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis

    PubMed Central

    Santoro, A; Cannella, S; Bossi, G; Gallo, F; Trizzino, A; Pende, D; Dieli, F; Bruno, G; Stinchcombe, J C; Micalizzi, C; De Fusco, C; Danesino, C; Moretta, L; Notarangelo, L D; Griffiths, G M; Aricò, M

    2006-01-01

    Familial haemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous disorder characterised by constitutive defects in cellular cytotoxicity resulting in fever, hepatosplenomegaly and cytopenia, and the outcome is fatal unless treated by chemoimmunotherapy followed by haematopoietic stem‐cell transplantation. Since 1999, mutations in the perforin gene giving rise to this disease have been identified; however, these account only for 40% of cases. Lack of a genetic marker hampers the diagnosis, suitability for transplantation, selection of familial donors, identification of carriers, genetic counselling and prenatal diagnosis. Mutations in the Munc13–4 gene have recently been described in patients with FHL. We sequenced the Munc13–4 gene in all patients with haemophagocytic lymphohistiocytosis not due to PRF1 mutations. In 15 of the 30 families studied, 12 novel and 4 known Munc13–4 mutations were found, spread throughout the gene. Among novel mutations, 2650C→T introduced a stop codon; 441del A, 532del C, 3082del C and 3226ins G caused a frameshift, and seven were mis sense mutations. Median age of diagnosis was 4 months, but six patients developed the disease after 5 years of age and one as a young adult of 18 years. Involvement of central nervous system was present in 9 of 15 patients, activity of natural killer cells was markedly reduced or absent in 13 of 13 tested patients. Chemo‐immunotherapy was effective in all patients. Munc13–4 mutations were found in 15 of 30 patients with FHL without PRF1 mutations. Because these patients may develop the disease during adolescence or even later, haematologists should include FHL2 and FHL3 in the differential diagnosis of young adults with fever, cytopenia, splenomegaly and hypercytokinaemia. PMID:16825436

  7. Clinical trials of an intravenous oxygenator in patients with adult respiratory distress syndrome.

    PubMed

    High, K M; Snider, M T; Richard, R; Russell, G B; Stene, J K; Campbell, D B; Aufiero, T X; Thieme, G A

    1992-11-01

    In patients with severe adult respiratory distress syndrome, mechanical ventilation may not be able to ensure gas exchange sufficient to sustain life. We report the use of an intravenous oxygenator (IVOX) in five patients who were suffering from severe adult respiratory distress syndrome as a result of aspiration, fat embolism, or pneumonia. IVOX was used in an attempt to provide supplemental transfer of CO2 and O2 and thereby reduce O2 toxicity and barotrauma. All patients were tracheally intubated, sedated, and chemically paralyzed and had a PaO2 < 60 mmHg when the lungs were ventilated with an FIO2 = 1.0 and a positive end expiratory pressure of > or = 5 cmH2O. The right common femoral vein was located surgically, and the patient was systemically anticoagulated with heparin. A hollow introducer tube was inserted into the right common femoral vein, and the furled IVOX was passed into the inferior vena cava and advanced until the tip was in the lower portion of the superior vena cava. IVOX use ranged from 2 h to 4 days. In this group of patients, IVOX gas exchange ranged from 21 to 87 ml x min-1 of CO2 and from 28 to 85 ml x min-1 of O2. One of the five patients survived and was discharged from the hospital. The IVOX transferred up to 28% of metabolic gas-exchange requirements. One patient with a small vena cava showed signs of caval obstruction. Three other patients demonstrated signs of a septic syndrome after the device was inserted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1443737

  8. A t(16;21)(p11;q22) in Acute M