The role of graft reperfusion sequence in the development of non-anastomotic biliary strictures following orthotopic liver transplantation: A meta-analysis

Background

Liver transplant is a potential cure for liver failure and hepatic malignancy but there are many techniques which have been described for vascular reconstruction. This study was to compare the prevalence of non-anastomotic biliary stricture and other surgical complications based on Clavien-Dindo scoring system, in initial portal reperfusion (sequential) versus simultaneous or initial artery reperfusion.

Disease-modifying effects of edasalonexent,an NF-κB inhibitor,in young boys with Duchenne muscular dystrophy: Results of the MoveDMD phase 2 and open label extension trial

Chronic activation of NF-κB is a key driver of muscle degeneration and suppression of muscle regeneration in Duchenne muscular dystrophy. Edasalonexent (CAT-1004) is an orally-administered novel small molecule that covalently links two bioactive compounds (salicylic acid and docosahexaenoic acid) that inhibit NF-κB. This placebo-controlled, proof-of-concept phase 2 study with open-label extension in boys ≥4-<8 years old with any dystrophin mutation examined the effect of edasalonexent (67 or 100 mg/kg/day) compared to placebo or off-treatment control. Endpoints were safety/tolerability, change from baseline in MRI T₂ relaxation time of lower leg muscles and functional assessment, as well as pharmacodynamics and biomarkers. Treatment was well-tolerated and the majority of adverse events were mild, and most commonly of the gastrointestinal system (primarily diarrhea). There were no serious adverse events in the edasalonexent groups. Edasalonexent 100 mg/kg was associated with slowing of disease progression and preservation of muscle function compared to an off-treatment control period, with decrease in levels of NF-κB-regulated genes and improvements in biomarkers of muscle health and inflammation. These results support investigating edasalonexent in future trials and have informed the design of the edasalonexent phase 3 clinical trial in boys with Duchenne.     

Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning

STUDY OBJECTIVES: Evidence suggests that, to maintain treatment effects, nasal continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA) needs to be used every night. What remains unknown is the nightly duration of use required to normalize functioning. This study, employing probit analyses and piecewise regression to estimate dose-response functions, estimated likelihoods of return to normal levels of sleepiness and daily functioning relative to nightly duration of CPAP. DESIGN: Multicenter, quasi-experimental study. SETTING: Seven sleep centers in the United States and Canada. PARTICIPANTS: Patients with severe OSA (total cohort n = 149; the numbers of included participants from 85 - 120, depending on outcome analyzed.) Interventions: CPAP. MEASUREMENTS AND RESULTS: Before treatment and again after 3 months of therapy, participants completed a day of testing that included measures of objective and subjective daytime sleepiness and functional status. There were significant differences in mean nightly CPAP duration between treatment responders and nonresponders across outcomes. Thresholds above which further improvements were less likely relative to nightly duration of CPAP were identified for Epworth Sleepiness Scale score (4 hours), Multiple Sleep Latency Test (6 hours), and Functional Outcomes associated with Sleepiness Questionnaire (7.5 hours). A linear dose-response relationship (P < 0.01) between increased use and achieving normal levels was shown for objective and subjective daytime sleepiness, but only up to 7 hours use for functional status. CONCLUSIONS: Our analyses suggest that a greater percentage of patients will achieve normal functioning with longer nightly CPAP durations, but what constitutes adequate use varies between different outcomes.     

Stabilized tetraether lipids based particles guided prophyrins photodynamic therapy

Photodynamic therapy (PDT) that involves ergonomically delivered light in the presence of archetypical photosensitizer such as Protoporphyrin IX (PpIX) is a time-honored missile strategy in cancer therapeutics. Yet, the premature release of PpIX is one of the most abundant dilemma encounters the therapeutic outcomes of PDT due to associated toxicity and redistribution to serum proteins. In this study, ultrastable tetraether lipids (TELs) based liposomes were developed. PpIX molecules were identified to reside physically in the monolayer; thereby the inherent π-π stacking that leads to aggregation of PpIX in aqueous milieu was dramatically improved. TEL_29.9?mol% and TEL_62mol% based liposomes revealed PpIX sustained release diffusion pattern from spherical particles as confirmed by converged fitting to Baker &; Lonsdale model. Stability in presence of human serum albumins, a key element for PDT accomplishment was emphasized. The epitome candidates were selected for vascular photodynamic (vPDT) in in-Ovo chick chorioallantoic membrane. Profoundly, TEL_62mol% based liposomes proved to be the most effective liposomes that demonstrated localized effect within the irradiated area without eliciting quiescent vasculatures damages. Cellular photodynamic therapy (cPDT) revealed that various radiant exposure doses of 134, 202, 403 or 672?mJ.cm^?2 could deliberately modulate the photo-responses of PpIX in TEL-liposomes.     

Physical and hormonal profile of male sexual development in epilepsy

PURPOSE: This study was designed to investigate the effect of epilepsy and antiepileptic drugs (AEDs) on both the physical and hormonal aspects of the sexual development of male patients with epilepsy. METHODS: One hundred thirty male subjects with epilepsy, their age ranging between 8 and 18 years (mean, 14 +/- 2.9 years), entered the study; all were taking AEDs. Anthropometric measurements [height, weight, and body mass index (BMI)], testicular volume, penile length, and pubarche were assessed in the studied groups, as well as measurement of the levels of testosterone (T), free testosterone (FT), estradiol (E2), lutenizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL), and the results were compared with those of a control group. RESULTS: In this study, male patients older than 16 years were significantly shorter than their matched controls. The mean values of testicular volume and penile length were significantly lower in the patients in the different age subgroups, and the pubic hair staging (pubarche) was delayed in the patients older than 16 years. The mean values of total testosterone, estradiol, LH, and FSH serum levels were significantly higher, whereas the mean values of free testosterone, total-T/E2, total. T/LH, and FT/E2 ratios were lower in the patient subgroups compared with their age-matched controls. There were no significant changes in the mean basal PRL serum levels in the patients compared with the controls. The present study demonstrated a reduction in the testicular volume and penile length, significantly lower mean values of free testosterone and total-T/E2, and a higher mean value of E2 in the patients receiving polytherapy in the age subgroup older than 16 years compared with those on monotherapy; however, there was no demonstrable effect of seizure control or the duration of illness in any of the studied parameters. CONCLUSIONS: There is a delay in the sexual development of male patients with epilepsy in the different age subgroups, with endocrine changes in the form of increase in the total testosterone, but the free testosterone is lower, and an increase in estradiol, with lower T/LH levels. Patients receiving polytherapy, especially those older than 16 years, were more likely to have delayed gonadarch and disturbances in their hormonal profile.