Translocation t(4;14) is an independent prognostic factor for adverse outcome in multiple myeloma (MM). However, reports concerning the therapeutic effects of novel drugs on t(4;14) MM are few. We retrospectively investigated the clinical and prognostic significance of symptomatic MM cases with t(4;14) treated with novel therapies. Ninety-three patients (IgG, 56; IgA, 23; BjP, 14) newly diagnosed with MM were included (median age, 71 years; median observation period, 27.8 months). t(4;14) MM was diagnosed in 17 (IgG, 7; IgA, 9; BjP, 1) patients (18%). An association between t(4;14) and the IgA isotype was confirmed (p = 0.02). Overall survival (OS) at 3 years was lower in the t(4;14) patients than without t(4;14) group (81.2% vs 66.7%, p = 0.04). Multivariate analysis showed that t(4;14) was an independent predictor of OS (hazard ratio [HR], 7.58; 95.0% confidence interval [CI], 1.43-39.9; p = 0.0017). The ORR after autologous blood stem cell transplantation (ASCT) did not differ with or without t(4;14); progression-free survival tended to be prolonged in the group without t(4;14) (p = 0.088). Thus, even in the era of novel drugs, t(4;14) MM still has a poor prognosis, and triplet consolidation therapy should be continued.Although the estimated incidence of acquired haemophilia A (AHA) in Singapore is similar to those reported in the literature, we have observed differences in the frequency of their associated diseases, particularly bullous pemphigoid (BP). We investigated the actual incidence of BP among our AHA cohort, their clinical characteristics and treatment outcomes. 6 out of 37 (16%) patients with AHA had BP, making it the most common underlying disorder in our cohort. The median age at diagnosis of AHA was 76 years old with a female preponderance. Most patients had their AHA diagnosed after BP with the median time between BP to AHA diagnosis being 107.5 days. Initial haemostasis was achieved, and factor VIII inhibitor was eliminated in all patients with a median time of disappearance being 52 days. Two patients had recurrence of their factor VIII inhibitor during the tapering of their immunosuppression. There was no relationship between the relapse of BP and AHA. This study suggests that BP is a common association with AHA. These patients respond well to bypassing agent and immunosuppression. However, they have a higher recurrence of factor VIII inhibitor and should be monitored closely for relapse during the tapering period of their immunosuppression.We retrospectively analyzed nationwide records of 163 Fanconi anemia (FA) patients [aplastic anemia (AA), n = 118; myelodysplastic syndrome (MDS), n = 30; acute leukemia, n = 15] who underwent first allogeneic hematopoietic stem cell transplantation (HSCT) between 1987 and 2015 in Japan. An alternative donor was used in 119 (73%) patients, and 160 (98%) patients received a non-T-cell-depleted graft. With an 8.7-year median follow-up, 5-year overall survival (OS) was 81%. The 5-year OS was significantly higher in AA patients than in MDS and acute leukemia patients (89%, 71%, and 44%, respectively). In the MDS/leukemia group, factors associated with poor outcome in univariate analysis were older age at HSCT (≥ 18 years), conditioning regimen without anti-thymocyte or lymphocyte globulin, and grade II-IV acute graft-versus-host disease. After 1 year, of 137 survivors, 15 developed subsequent malignancies, of whom 12 were diagnosed with head and neck (HN)/esophageal cancer. this website An irradiation regimen and older age were associated with the risk of HN/esophageal cancer. Five of seven deaths were attributed to subsequent malignancies more than 5 years after HSCT. On the basis of the risk factors for HSCT in MDS/leukemia patients and subsequent malignancies, a more effective HSCT approach is required.

Both levetiracetam (LEV) and brivaracetam (BRV) eliminate the electroencephalogram photoparoxysmal response (PPR) in the human phase IIa photosensitivity model of epilepsy. The physiochemical properties of BRV differ from those of LEV, having higher potency and lipophilicity plus 10- to 15-fold greater affinity for synaptic vesicle glycoprotein 2A.

We compared the rapidity of the effects of both drugs in the central nervous system (CNS) of patients with photosensitive epilepsy using time to PPR elimination post-intravenous infusion as a pharmacodynamic endpoint.

Using a randomized, double-blind, two-period, balanced, crossover design, we tested patients with photosensitive epilepsy with equipotent milligram doses of intravenous LEV 1500mg versus BRV 100mg post-15-min intravenous infusion (part 1) and post-5-min intravenous infusion (part 2, same doses). Eight patients per part were deemed sufficient with 80% power to determine a 70% reduction for intravenous BRVLEV intrapatient time ratio to PPR elimina≤ 2min in 11 patients with BRV and in four patients with LEV. No period or carryover effects were seen. No serious or severe adverse effects occurred. At PPR elimination (n = 16), median plasma [BRV] was 250ng/mL (range 30-4100) and median plasma [LEV] was 28.35μg/mL (range 1-86.7).

Outcome studies directly comparing LEV and BRV are needed to define the clinical utility of the response with BRV, which was several minutes faster than that with LEV.

ClinTrials.gov Identifier = NCT03580707; registered 07-09-18.

ClinTrials.gov Identifier = NCT03580707; registered 07-09-18.

Reactive oxygen species (ROS) generation specifically in cancer cells may be a promising strategy for their selective killing. The synthetic chalcone derivative (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (DPP23) exerts antitumor activity through ROS-mediated apoptosis in cancer cells but not in healthy cells. However, the mechanism underlying ROS generation by DPP23 remains unknown.

The current study aims to identify possible DPP23 target genes responsible for ROS generation through the mining of microarray data stored in NCBI’s Gene Expression Omnibus (GEO).

A comprehensive expression profile of genes modulated by DPP23 was examined by gene ontology analysis. DPP23-modulated genes in Mia-PaCa2 pancreatic cells were validated by reverse transcription-PCR.

Multiple genes were up and downregulated by DPP23 treatment in MiaPaCa2 pancreatic cancer cells. Genes with absolute fold-change (FC) of > 2 were selected as the cut-off criteria and grouped into 10 clusters to analyze expression patterns systematically.