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The accurate diagnosis and classification of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) are challenging due to the overlapping pathological and molecular features of myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). We investigated the genomic landscape in different MDS/MPN subtypes, including chronic myelomonocytic leukemia (CMML; n = 97), atypical chronic myeloid leukemia (aCML; n = 8), MDS/MPN-unclassified (MDS/MPN-U; n = 44), and MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n = 12). Our study indicated that MDS/MPN is characterized by mutations commonly identified in myeloid neoplasms, with TET2 (52%) being the most frequently mutated gene, followed by ASXL1 (38.7%), SRSF2 (34.7%), and JAK2 (19.7%), among others. However, the distribution of recurrent mutations differs across the MDS/MPN subtypes. We confirmed that specific gene combinations correlate with specific MDS/MPN subtypes (e.g., TET2/SRSF2 in CMML, ASXL1/SETBP1 in aCML, and SF3B1/JAK2 in MDS/MPN-RS-T), with MDS/MPN-U being the most heterogeneous. Furthermore, we found that older age (≥65 years) and mutations in RUNX1 and TP53 were associated with poorer clinical outcomes in CMML (p < 0.05) by multivariate analysis. In MDS/MPN-U, CBL mutations (p < 0.05) were the sole negative prognostic factors identified in our study by multivariate analysis (p < 0.05). Overall, our study provides genetic insights into various MDS/MPN subtypes, which may aid in diagnosis and clinical decision-making for patients with MDS/MPN.

Abstract Introduction In November 2020, the FDA issued an emergency use authorization (EUA) for monoclonal antibody (mAb) therapy in patients with mild‐to‐moderate COVID‐19 at high risk for disease progression. Methods We retrospectively reviewed 38 adult hematology patients who received mAbs from 11/2020 to 2/2021. Results Thirty (79%) patients received bamlanivimab and 8 (21%) casirivimab‐imdevimab. Four (11%) patients were hospitalized due to COVID‐19, two (5%) progressed to severe disease and one patient (3%) died within 30 days from COVID‐19 disease. Most patients (n = 34, 89%) ultimately tested negative for SARS‐CoV‐2, with 34% (n = 13) clearing the virus within 14 days after mAb infusion. The median time to clearance of viral shedding was 25.5 days (range: 7–138). After mAb infusion, most patients with hematological malignancies (HM) (n = 10/15; 67%) resumed therapy for underlying disease with a median delay of 21.5 days (range: 12–42). We observed a significant difference in hospitalization among patients who received a HCT versus non‐HCT (0% n = 0/26 and 36% n = 4/11, respectively; p

Abstract: Busulfan combined with cyclophosphamide (BuCy) has long been considered a standard myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation (HCT), including both nonmalignant conditions and myeloid diseases. Substituting fludarabine for cyclophosphamide (BuFlu) to reduce toxicity without an increase in relapse has been increasingly performed in children, but without comparison with BuCy. We retrospectively analyzed 1781 children transplanted from 2008 to 2014 to compare the effectiveness of BuCy with BuFlu. Nonmalignant and malignant disease populations were analyzed separately. Overall mortality was comparable for children with nonmalignant conditions who received BuFlu or BuCy (relative risk [RR], 1.14, P = .52). Lower incidences of sinusoidal obstruction syndrome (P = .04), hemorrhagic cystitis (P = .04), and chronic graft-versus-host disease (P = .02) were observed after BuFlu, but the influence of the conditioning regimen could not be assessed by multivariate analysis because of the low frequency of these complications. Children transplanted for malignancies were more likely to receive BuFlu if they had higher hematopoietic cell transplantation-comorbidity index scores (P < .001) or their donor was unrelated and HLA-mismatched (P = .004). Nevertheless, there were no differences in transplant toxicities and comparable transplant-related mortality (RR, 1.2; P = .46), relapse (RR, 1.2; P = .15), and treatment failure (RR, 1.2; P = .12). BuFlu was associated with higher overall mortality (RR, 1.4; P = .008) related to inferior postrelapse survival (P = .001). Our findings demonstrated that outcomes after BuFlu are similar to those for BuCy for children, but for unclear reasons, those receiving BuFlu for malignancy may be at risk for shorter postrelapse survival.

Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P

Introduction: In November 2020, the FDA issued an emergency use authorization (EUA) for monoclonal antibody (mAb) therapy in patients with mild-to-moderate COVID-19 at high risk for disease progression. Methods: We retrospectively reviewed 38 adult hematology patients who received mAbs from 11/2020 to 2/2021. Results: Thirty (79%) patients received bamlanivimab and 8 (21%) casirivimab-imdevimab. Four (11%) patients were hospitalized due to COVID-19, two (5%) progressed to severe disease and one patient (3%) died within 30 days from COVID-19 disease. Most patients (n = 34, 89%) ultimately tested negative for SARS-CoV-2, with 34% (n = 13) clearing the virus within 14 days after mAb infusion. The median time to clearance of viral shedding was 25.5 days (range: 7-138). After mAb infusion, most patients with hematological malignancies (HM) (n = 10/15; 67%) resumed therapy for underlying disease with a median delay of 21.5 days (range: 12-42). We observed a significant difference in hospitalization among patients who received a HCT versus non-HCT (0% n = 0/26 and 36% n = 4/11, respectively; p < 0.01). Conclusions: This study demonstrates that SARS-CoV-2 specific mAb was safe and may reduce hospitalization compared to what is reported in malignant hematology patients at high risk for disease progression. Our HCT cohort patients had less hospitalization rate compared with HM cohort patients. [ABSTRACT FROM AUTHOR]

The article presents several abstracts from the 38th Annual Meeting of the Society of General Internal Medicine including on medical homes by veterans, pain management for veterans, and the care and services to older people.

In September 2010, the Cancer and Aging Research Group, in collaboration with the National Cancer Institute and the National Institute on Aging, conducted the first of three planned conferences to discuss research methodology to generate the highest quality research in older adults with cancer and then disseminate these findings among those working in the fields of cancer and aging. Conference speakers discussed the current level of research evidence in geriatric oncology, outlined the current knowledge gaps, and put forth principles for research designs and strategies that would address these gaps within the next 10 years. It was agreed that future oncology research trials that enroll older adults should include: 1) improved standardized geriatric assessment of older oncology patients, 2) substantially enhanced biological assessment of older oncology patients, 3) specific trials for the most vulnerable and/or those older than 75 years, and 4) research infrastructure that specifically targets older adults and substantially strengthened geriatrics and oncology research collaborations. This initial conference laid the foundation for the next two meetings, which will address the research designs and collaborations needed to enhance therapeutic and intervention trials in older adults with cancer. [ABSTRACT FROM PUBLISHER]

Purpose. Myelodysplastic syndromes (MDSs) are a heterogenous group of clonal hematopoietic disorders affecting approximately 60,000 people in the U.S. Little information is available regarding how aware MDS patients are of their disease severity, prognosis, and treatment outcomes. Methods. This Internet-based survey assessed patient perceptions regarding these factors, determined differences between patients with higher- and lower-risk disease and between those receiving active treatment and supportive care, and assessed patient-reported outcomes. Results. Among 358 patients (median age, 65 years), the median time since MDS diagnosis was 3 years and time from initial hematologic abnormality detection was 6 years. Many patients (55%) did not know their International Prognostic Scoring System score, 42% were unaware of their blast percentage, and 28% were unaware of their cytogenetics. Patients were unlikely to recall having their MDS described as cancer (7%), 37% felt their treatment would improve survival, and 16% felt treatment would be curative. Patients receiving active treatment were more likely to believe their therapy would prolong survival than those receiving supportive care (52% versus 31%; p < .001) or be curative (23% versus 14%; p = .03). Patients with higher-risk disease were more likely to think their therapy would be curative than those with lower-risk disease (26% versus 11%; p = .01). Patients with MDS reported poor physical or mental health on two to three times more days per month than population norms. Conclusion. Patients with MDS have a limited understanding of their disease characteristics, prognosis, and treatment goals. These results may help improve physician-patient communication and identify factors to consider when making treatment decisions. [ABSTRACT FROM AUTHOR]

Several abstracts related to biology are presented which includes one on the use of multiparametric magnetic resonance images for recognizing prostate cancer, the other on extracellular inflammatory exosomes and the third on stochastic electrotransport selectively.

Discusses the use of game theory to analyze practical problems of distributive justice. Significance of game theory for moral philosophy; Equilibrium selection problem of philosophers who use game theory; Use of game theory for insight into individuals' compliance with norms of justice and mutual aid.

Acquired vancomycin resistance in enterococci may be associated with teicoplanin susceptibility (VanB) or teicoplanin resistance (VanA). This paper characterizes the first instance of in vivo emergence of teicoplanin resistance in an Enterococcus faecium strain of VanB phenotype. Vancomvcin- resistant (MIC. 2563512 µg/mL) E. faecium was isolated intermittently from a patient's blood over 4 months. The MIC of teicoplanin for the first 5 isolates was 1.0 µ/mL; it was 64 µg/mL for the final 2. Analysis of plasmid and chromosomal DNA revealed the isolates to be of clonal origin. Conjugal transfer of vancomycin resistance was not obtained. A vanB DNA probe hybridized with both teicoplanin-susceptible and resistant isolates, but a vanA probe failed to hybridize with any isolate. SDS-PAGE of membrane proteins from a teicoplanin-resistant isolate revealed constitutive production of a normally inducible 41-kDa protein. These findings challenge the ultimate utility of teicoplanin for treatment of infections caused by vancomycin-resistant enterococci. [ABSTRACT FROM PUBLISHER]

One of the central goals of almost all politicians in democracies is to get reelected. To achieve this, they generally try to keep track of the public's desires and expectations, [...]