Real-World Experience of Patients With Multiple Myeloma Receiving Ide-Cel After a Prior BCMA-Targeted Therapy

Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior BCMA-TT cohort had a lower overall response rate (74% versus 88%; p = 0.021), median duration of response (7.4 versus 9.6 months; p = 0.03), and median progression-free survival (3.2 months versus 9.0 months; p = 0.0002) compared to the cohort without prior BCMA-TT. All five patients who received a prior anti-BCMA CAR T responded to ide-cel, and survival outcomes were best for this subgroup. In conclusion, treatment with ide-cel yielded meaningful clinical responses in real-world patients exposed to a prior BCMA-TT, though response rates and durability were suboptimal compared to those not treated with a prior BCMA-TT

CHCHD10 variants in amyotrophic lateral sclerosis: where Is the evidence?

Objective: After the initial report of a CHCHD10 mutation in mitochondrial disease with features resembling amyotrophic lateral sclerosis (ALS), CHCHD10 mutations have been considered to be a frequent cause for ALS. However, the exact pathogenicity and clinical significance of these mutations remain unclear. Here, we aimed to determine the role of CHCHD10 mutations in ALS. Methods: We analyzed 4,365 whole genome sequenced ALS patients and 1,832 controls from 7 different countries and examined all nonsynonymous single nucleotide variants in CHCHD10. These were tested for association with ALS, independently and in aggregate using several genetic burden tests (including sequence kernel association test [SKAT], optimal unified test [SKAT-O], and Firth logistic regression). Results: We identified 3 new variants in cases, but only 1 was ALS-specific. lso, 1 control-specific mutation was identified. There was no increased burden of rare coding mutations among ALS patients compared to controls (p=0.86, p=0.86, and p=0.88 for SKAT, SKAT-O, and Firth, respectively). The few carriers with potential pathogenic CHCHD10 mutations exhibited a slowly progressive ALS-like phenotype with atypical features such as myopathy and deafness. Interpretation: CHCHD10 mutations seem to be a far less prevalent cause of pure ALS than previously suggested, and instead appear related to more complex phenotypes. There appears to be insufficient evidence for the pathogenicity of most previously reported variants in pure ALS. This study shows that routine testing for CHCHD10 mutations in pure ALS is not recommended and illustrates the importance of sufficient genetic and functional evidence in establishing pathogenicity of genetic variants

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

A determinant for family planning attitudes and practices of men: marriage features

Aim: This study was conducted to determine both the use of family planning methods among married men between the ages of 20 to 50 and some marriage characteristics affecting this use. Methods: This was a descriptive and correlational study conducted in May and June 2014. The study sample included 375 males. The study data were collected using a survey form as well as the Family Planning Attitude Scale, Marital Adjustment Scale, and Marital Problem Solving Scale. The determinants of the Family Planning Attitude Scale were found using hierarchical multiple regression analysis. The risk factors for not using family planning were evaluated by logistic regression analysis. Results: According to Model 2, to which family features were added, the male himself (ß = -0.117) and his spouse (ß = -0.154) either graduated from primary school or received no formal education. They lived in an extended family (ß = -0.129), and an increasing desire for more children (ß = -0.184) decreased the family planning attitude score. The risk factors for not using family planning were evaluated using logistic regression analysis. Accordingly, the risk for not consulting family planning services is increased by older age (OR: 1.037; CI: 1.010–1.064), desiring to have more than three children (OR: 1.279; CI: 1.01.038–1.575), and not having received information about family planning (OR: 1.871; CI: 1.145–3.057) (p < 0.05). Conclusion: Marital adjustment is an important tool in making decisions about family planning. It is necessary to enable men to access to the correct information that will carry them to the relevant resources. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature

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