Citations

The effect of chronic exogenous testosterone (T) treatment on neuromuscular transmission in the diaphragm (Dia) muscle of adult male rats was determined. The contribution of neuromuscular transmission failure (NTF) to Dia fatigue was evaluated by superimposing intermittent direct muscle stimulation on repetitive nerve stimulation of isometric contraction in vitro. T treatment significantly reduced the contribution of NTF to Dia fatigue by ∼20% ( P < 0.001). Fiber type-specific effects on NTF were determined by measuring Dia fiber glycogen levels subsequent to repetitive nerve or muscle stimulation. T treatment had no effect on glycogen depletion in Dia type I and IIa fibers regardless of stimulation route. In the control group, type IIx fibers demonstrated significantly less glycogen depletion after nerve stimulation compared with direct muscle stimulation ( P < 0.05), suggesting the presence of NTF. In contrast, T treatment increased glycogen depletion of type IIx fibers during nerve stimulation to levels similar to those after direct muscle stimulation. These data indicate that testosterone treatment substantially improves neuromuscular transmission in the Dia.

It has been found that maximum specific force (Fmax; force per cross-sectional area) of rat diaphragm muscle doubles from birth to 84 days (adult). We hypothesize that this developmental change in Fmax reflects an increase in myosin heavy chain (MHC) content per half-sarcomere (an estimate of the number of cross bridges in parallel) and/or a greater force per cross bridge in fibers expressing fast MHC isoforms compared with slow and neonatal MHC isoforms (MHCslow and MHCneo, respectively). Single Triton 100-X-permeabilized fibers were activated at a pCa of 4.0. MHC isoform expression was determined by SDS-PAGE. MHC content per half-sarcomere was determined by densitometric analysis and comparison to a standard curve of known MHC concentrations. MHC content per half-sarcomere progressively increased during early postnatal development. When normalized for MHC content per half-sarcomere, fibers expressing MHCslow and coexpressing MHCneoproduced less force than fibers expressing fast MHC isoforms. We conclude that lower force per cross bridge in fibers expressing MHCslow and MHCneo contributes to the lower Fmax seen in early postnatal development.

AbstractWaldenström macroglobulinemia (WM) is an immunoglobulin M‐associated lymphoma, with majority of cases demonstrating MYD88 locus alteration, most commonly, MYD88L265P. Owing to low prevalence of the wild‐type (WT) MYD88 genotype in WM, clinically relevant data in this patient population are sparse, with one study showing nearly a 10‐fold increased risk of mortality in this subgroup compared to patients with MYD88L265P mutation. We studied a large cohort of patients with MYD88L265P and MYD88WT WM, evaluated at Mayo Clinic, Rochester, between 1995 and 2016, to specifically assess the impact of these genotypes on clinical course. Of 557 patients, MYD88L265P mutation status, as determined by allele‐specific polymerase chain reaction, was known in 219, and 174 (79%) of those exhibited MYD88L265P, 157 of 174 patients had active disease. Of 45 (21%) patients with MYD88WT genotype, 44 had active disease. The estimated median follow‐up was 7.0 years; median overall survival was 10.2 years (95% CI: 8.4‐16.5) for MYD88L265P versus 13.9 years (95% CI: 6.4‐29.3) for the MYD88WT (P = 0.86). The time‐to‐next therapy from frontline treatment and the presenting features were similar in the two patient populations. For patients with smoldering WM at diagnosis, the median time‐to‐progression to active disease was 2.8 years (95% CI: 2.2‐3.8) in the MYD88L265P cohort and 1.9 years (95% CI: 0.7‐3.1) in the MYD88WT cohort (P = 0.21). The frequency of transformation to high‐grade lymphoma, or the development of therapy‐elated myelodysplastic syndrome was higher in the MYD88WT cohort (16% versus 4% in the MYD88L265P, P = 0.009). In conclusion, MYD88L265P mutation does not appear to be a determinant of outcome, and its presence may not be a disease‐defining feature in WM. Our findings warrant external validation, preferably through prospective studies.

We surveyed multiple apheresis centers represented by the authors for their clinical approach to the management of anticoagulation issues during therapeutic plasma exchange (TPE). We present the results of their practices and a review of the pertinent literature. As plasma is removed during TPE, replacement with all or partial non‐plasma‐containing fluids (eg, 5% albumin) may lead to significant changes in hemostasis. These changes are amplified in patients who are receiving anticoagulation. We discuss various anticoagulants as well as the monitoring and adjustment of anticoagulation before, during, and after TPE. No single guideline can be applied, but rather, patients must be monitored individually, taking into account their often complex clinical conditions and medication profiles.

This article is linked to Tye‐Din and Fang et al papers. To view these articles visit https://doi.org/10.1111/apt.14287 and https://doi.org/10.1111/apt.14250.

Background and Aim: Data are scanty on allocating simultaneous liver kidney (SLK) based on model for end-stage disease (MELD) score. Diabetes mellitus (DM) and hypertension (HTN) are frequent in cirrhosis patients. We analyzed transplant recipients with DM and/or HTN to compare MELD-based outcomes of SLK to liver transplantation alone (LTA). Materials and Methods: Of 13,584 first deceased donor liver transplantation among patients with DM and/or HTN (1530 or 11.2% SLK), MELD score predicted SLK [1.02 (1.01-1.03)]. SLK was beneficial for 5-year patient survival at MELD score ≥43 (78.6% vs. 62.6%, P=0.017), but not at MELD score <29 (74.8% vs. 76.2%, P=0.63). Among 11,405 recipients (976 SLK) at MELD score <29, SLK (n=816) was beneficial compared with 706 LTA [75% vs. 64%, P<0.001; 0.71 (0.55-0.91)] at serum creatinine (SC) ≥2 but not at SC<2 [73% vs. 76%, P=0.32; 0.85 (0.60-1.2)]. Among patients with MELD score 29 to 42, SLK (n=484) and LTA (n=1403) had similar survival [69% vs. 69%, P=0.58; 0.9 (0.7-1.5)]. Among patients with MELD score ≥43, SLK (n=70) was associated with 35% improved patient survival at 5 years compared with 222 LTA [0.65 (0.46-0.93)]. Conclusions: Among patients with DM and/or HTN, SLK is useful at: (a) MELD score <29 and SC≥2 and (b) MELD score ≥43. Prospective studies are needed to confirm these findings as basis to optimize use of SLK.