Defibrotide improves COVID-19-related acute respiratory distress syndrome in myeloma patients after chimeric antigen receptor T-cell treatment without compromising virus-specific and anti-myeloma T-cell responses

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Testosterone Is Associated with Erectile Dysfunction: A Cross-Sectional Study in Chinese Men

Testosterone is essential for the regulation of erectile physiology, but the relationship between low testosterone and erectile dysfunction (ED) has not been firmly established.To examine the association between serum total, free and bio-available testosterone and ED in a population-based sample.A consecutive series of 1776 men aged 20–77 participated in the routine physical examination from September 2009 to December 2009 in Guangxi, China. ED was assessed using the five-item International Index of Erectile Function (IIEF-5) questionnaire. Total testosterone (TT), sex hormone binding globulin (SHBG) and other biochemical profiles were measured. Free testosterone (FT) and bio-available testosterone (BT) were calculated based on Vermeulen’s formula. Data were collected with regard to smoking, alcoholic drinking, physical activity and metabolic syndrome.The prevalence of ED (IIEF-5<22) was 47.6%. Men with ED were significantly older, and more prone to smoke cigarettes (≥20 cigarettes/day) or drink alcohol (≥3 drinks/week), and more likely to have elevated blood pressure (P = 0.036) or hyperglycemia (P<0.001) compared with those without ED. The significant increase in SHBG with age was parallel to its increase with increasing severity of ED (P<0.001). The obscure increase in TT across the ED status was detected without significance (P = 0.418), but TT was positively associated with ED after adjustment for age [odds ratio (OR)  = 1.02, 95% CI (confidence internal): 1.00–1.04]. FT and BT were inversely associated with ED (OR = 0.14, 95%CI: 0.06–0.33; OR = 0.92 (95%CI: 0.89–0.96, respectively) in the univariate analysis, and this inverse association appeared to be independent of smoking status, alcoholic drinking, physical activity, hyper-triglyceridemia and hyperglycemia.FT and BT are inversely related to worsening ED, whereas the positive association between TT and ED is most likely due to the increase in SHBG

Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/ refractory multiple myeloma: US Myeloma Immunotherapy Consortium real world experience

While response rates and survival outcomes have been very promising for idecabtagene vicleucel (ide-cel), a proportion of patients do not respond or relapse early after this B-cell maturation antigen (BCMA) targeted chimeric antigen receptor (CAR) T-cell therapy. Understanding the characteristics of these patients is important for patient selection and development of novel strategies to improve outcomes. We evaluated factors associated with early progression (progression or death due to myeloma ≤3 months after CAR T-cell infusion) in patients treated with standard of care ide-cel at 11 US academic centers. Among 211 patients that received ide-cel, 43 patients had a progressive event ≤3 months of infusion. Patients with a history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, use of bridging therapy, Hispanic ethnicity, plasma cell leukemia and t(4;14) were more likely to progress ≤3 months of infusion (P<0.05). Of these risk factors for early progression identified in univariate analyses, history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, plasma cell leukemia, and t(4;14) were associated with worse progression-free survival (PFS) in multivariable analysis. Presence of three or more of these factors had a significant negative impact on PFS (P<0.001; median PFS for ≥3 factors, 3.2 months vs. 0 factors, 14.1 months). This study helps identify patients at high risk of early progression after CAR T-cell therapy who may benefit from specific interventions pre and post CAR T-cell therpy to improve outcomes

Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma with renal impairment

We evaluated patients with relapsed multiple myeloma with renal impairment (RI) treated with standard of care idecabtagene vicleucel (ide-cel), as outcomes with chimeric antigen receptor (CAR) T-cell therapy are unknown in this population. RI was defined as creatinine clearance (CrCl) <50 mL/min. CrCl of <30 mL/min or dialysis dependence were defined as severe RI. The study cohort included 214 patients, 28 (13%) patients with RI, including 11 patients severe RI (dialysis, N=1). Patients with RI were older, more likely to be female and had higher likelihood of having Revised International Staging System stage 3 disease. Rates and severity of cytokine release syndrome (89% vs. 84%, grade ≥3: 7% vs. 2%) and immune effector cell-associated neurotoxicity syndrome (23% vs. 20%) were similar in patients with and without RI, respectively. Patients with RI had higher incidence of short-term grade ≥3 cytopenias, although cytopenias were similar by 3 months following CAR T-cell therapy. Renal function did not worsen after CAR T-cell therapy in patients with RI. Response rates (93% vs. 82%) and survival outcomes (median progression-free survival: 9 vs. 8 months; P=0.26) were comparable in patients with and without RI, respectively. Treatment with ide-cel is feasible in patients with RI, with a comparable safety and efficacy profile as patients without RI, with notable exception of higher short-term high-grade cytopenias

Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort

NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) mutations are known to cause hereditary spastic paraplegia type 6, a neurodegenerative disease that phenotypically overlaps to some extent with amyotrophic lateral sclerosis (ALS). Previously, a genomewide screen for copy number variants found an association with rare deletions in NIPA1 and ALS, and subsequent genetic analyses revealed that long (or expanded) polyalanine repeats in NIPA1 convey increased ALS susceptibility. We set out to perform a large-scale replication study to further investigate the role of NIPA1 polyalanine expansions with ALS, in which we characterized NIPA1 repeat size in an independent international cohort of 3955 patients with ALS and 2276 unaffected controls and combined our results with previous reports. Meta-analysis on a total of 6245 patients with ALS and 5051 controls showed an overall increased risk of ALS in those with expanded (>8) GCG repeat length (odds ratio = 1.50, p = 3.8×10-5). Together with previous reports, these findings provide evidence for an association of an expanded polyalanine repeat in NIPA1 and ALS

Investigation of the variation in weak-link profile of YBa 2Cu3-xAgxO7-? superconductors by Ag doping concentration

The effect of Ag doping concentration on the microstructure, transport properties and weak-link profile of YBa2Cu3-xAg xO7-? bulk superconducting compound was investigated through resistance-temperature (R-T), ac magnetic susceptibility (?-T), scanning electron microscope (SEM), X-ray diffraction (XRD) and the critical current density (Jc) versus applied magnetic field (Jc-B) measurements. We used the additive method with cationic ratio of x=0.1-0.4 for the YBCO-Ag system. The change in the silver doping concentration slightly affected the transition temperatures (Tc,zero), whereas, the critical current densities (Jc) of the samples and their magnetic field (B) dependencies were noticeably affected. The improvement on the microstructural properties of YBCO bulk superconductors was observed in SEM analysis, the J c values increased and their magnetic field dependencies decreased with the increasing of Ag concentration up to x=0.2. As well as the current transport properties. Ag doping up to a certain amount produces texturing that gives rise to a modification in the weak-link profile resulting in an enhanced strength of flux pinning which causes an increase in the current carrying capacity. © 2004 Elsevier Ltd

Pretreatment with stellate ganglion blockade before ischemia reduces infarct size in rat hearts

Objectives: To investigate the role of stellate ganglion blockade (SGB) in cardio-protection against ischemia reperfusion injury. Methods: This prospective randomized, experimental study was carried out between August and October 2008 in the Department of Anesthesia, Abant Izzet Baysal University, Bolu, Turkey. Twenty-one rats were randomly divided into 3 groups; group 1 - SGB group (rats with percutaneous ganglion blockade), group 2 - preconditioned (P) group (rats that were subjected to ischemia and then reperfusion periods for 5 minutes), and group 3 - control group (rats that were injected with normal saline). Results: During the ligation period, the length of arrhythmia was significantly shorter in group 2 compared with group 3 (p0.05). But the arrhythmia score was significantly lower both in group 1 and group 3, compared with group 2 (p<0.02). Both in the ischemic and reperfusion periods, the incidence of arrhythmia was lowest in group 1. The infarct size was measured significantly less in groups 1 and 2 compared with group 3 (p<0.001). Conclusion: Pretreatment with the left SGB leads to lower arrhythmia scores and reduced infarct size in the Langendorff-perfused rat hearts compared with group 3, but not with group 2