Noninvasive assessment and risk factors of liver fibrosis in patients with thalassemia major using shear wave elastography

Objectives: This study aimed to estimate the prevalence of liver fibrosis and assess the risk factors for developing significant liver fibrosis in patients with Thalassemia Major (TM).

Methods: All patients with TM over the age of 10 years were included in the study.

Results: A total of 94 eligible patients underwent 2-D SWE. The median age was 26.7 years. The median of the average 5-year serum ferritin (5yrSF) and liver iron concentration (LIC) assessed by MRI T2* were 1326?µg/L and 6.7?mg/g?dw, respectively. Hepatitis C and hepatitis B core antibodies were positive in 38% and 1% of the patients respectively. The proportion of patients with significant fibrosis was 60%. Male gender increased the risk of significant fibrosis (Odds ratio of 0.4; p?=?.0373). Additionally, the 5yrSF (p?=?.00661), the LIC (p?=?.0225) and the lowest LIC of the previous 5 years (p?=?.0211) were significant. In the multivariable logistic regression model, only 5yrSF (p?=?.0035) and gender (p?=?.00984) remained significant.

Conclusions: The risk of liver fibrosis is associated with iron overload and gender in patients with TM.     

Chronic ethanol feeding potentiates alpha1-adrenoceptor responsiveness in SHR aortas

Previous studies including ours demonstrated a hypotensive response to ethanol in spontaneously hypertensive rats (SHRs). In this study, we investigated whether this hypotensive effect of ethanol involves alterations in vascular alpha1-adrenergic receptor responsiveness. The contractile responses to the alpha1-receptor agonist phenylephrine were evaluated in aortic rings obtained from pair-fed SHRs receiving liquid diet with or without ethanol (2.5% or 5%, w/v) for 3 months. The responses were measured in aortas with and without endothelium to determine the role of the endothelium in the observed responses. The liquid diet intake was similar in the control and ethanol groups throughout the study whereas the body weight was significantly reduced by ethanol. Cumulative addition of phenylephrine (1 x 10(-9)-1 x 10(-4) M) caused concentration-related contractile responses. These responses were significantly reduced after endothelium denudation suggesting a role for the endothelium in the modulation of alpha1-receptor responsiveness. Ethanol (2.5% and 5%) caused significant and concentration-related increases in the contractile responses elicited by phenylephrine but not KCl. The maximum contraction (Emax) caused by phenylephrine in rings obtained from SHRs treated with 2.5% and 5% ethanol amounted to 413.6 +/- 26.3 and 513.0 +/- 46.7 mg tension/mg tissue, respectively, compared with 383.6 +/- 35.2 mg tension/mg tissue in control rings. The enhancement of alpha1 contractions by ethanol was virtually abolished in rings pretreated with the alpha1-receptor antagonist prazosin, suggesting upregulation of alpha1-receptors in aortas of ethanol-fed rats. Endothelium denudation also abolished ethanol-evoked increases in phenylephrine contractions. These findings suggest that chronic ethanol feeding upregulates aortic alpha1-receptors, which may be a consequence of chronic alpha1-receptor blockade by ethanol. The latter may account, at least in part, for the hypotensive response elicited by ethanol in SHRs.     

Y chromosome microdeletions in azoospermic and oligozoospermic Tunisian men

Introduction

In the present work, we aim to determine the frequency of Y microdeletions and to study the clinical and biological characteristics in idiopathic azoospermic and oligozoospermic men originating from the center of Tunisia.

Predicting early outcomes of liver transplantation in young children: The EARLY study

AIM To determine potentially modifiable predictors of early outcomes after liver transplantation in children of age 3 years.METHODS This study was a retrospective chart review including all consecutive children of age less than 3-years-old having had a liver transplant done at the Western Canadian referral center from June 2005 to June 2015.Pre-specified potential predictor variables and primary and secondary outcomes were recorded using standard definitions and a case report form. Associations between potential predictor variables and outcomes were determined using univariate and multiple logistic [odds ratio(OR); 95%CI] or linear(effect size, ES; 95%CI) regressions. RESULTS There were 65 children, of mean age 11.9(SD 7.1) mo and weight 8.5(2.1) kg, with biliary-atresia in 40(62%), who had a living related donor [LRD; 29(45%)], split/reduced [21(32%)] or whole liver graft [15(23%)]. Outcomes after liver transplant included: ventilator-days of 12.5(14.1); pediatric intensive care unit mortality of 5(8%); re-operation in 33(51%), hepatic artery thrombosis(HAT) in 12(19%), portal vein thrombosis(PVT) in 11(17%), and any severe complication(HAT, PVT, bile leak, bowel perforation, intraabdominal infection, retransplant, or death) in 32(49%) patients. Predictors of the prespecified primary outcomes on multiple regression were:(1) HAT: split/reduced(OR 0.06; 0.01, 0.76; P = 0.030) or LRD(OR 0.16; 0.03, 0.95; P = 0.044) vs whole liver graft; and(2) ventilator-days: surgeon(P 0.05), lowest antithrombin(AT) postoperative day 2-5(ES-0.24;-0.47,-0.02; P = 0.034), and split/reduced(ES-12.5;-21.8,-3.2; P = 0.009) vs whole-liver graft. Predictors of the pre-specified secondary outcomes on multiple regression were:(1) any thrombosis: LRD(OR 0.10; 0.01, 0.71; P = 0.021) or split/reduced(OR 0.10; 0.01, 0.85; P = 0.034) vs whole liver graft, and lowest AT postoperative day 2-5(OR 0.93; 0.87, 0.99; P = 0.038); and(2) any severe complication: surgeon(P 0.05), lowest AT postoperative day 2-5(OR 0.92; 0.86-0.98; P = 0.016), and split/reduced(OR 0.06; 0.01, 0.78; P = 0.032) vs whole-liver graft. CONCLUSION In young children, whole liver graft and surgeon was associated with more complications, and higher AT postoperative day 2-5 was associated with fewer complications early after liver transplantation.     

Superior mesenteric artery syndrome in a malnourished female: A rare cause of abdominal pain

Superior mesenteric artery (SMA) syndrome is a rare cause of duodenal obstruction that can go undiagnosed, exacerbating weight loss in an already significantly malnourished patient. Diagnosis is often challenging, however, can be made by keeping a high index of suspicion based on the clinical presentation. The pathology involves a reduction in the amount of fat pad between the abdominal aorta and superior mesenteric artery (SMA) leading to a reduction of aorto-mesenteric angle and consequent compression of mostly third part of the duodenum. Management is usually conservative, however, if conservative treatment fails, surgical intervention is warranted.Our patient was a 20-year-old female who presented to us with nausea, vomiting, weight loss, and abdominal pain. The presence of obstructive symptoms along with imaging (CT scan) lead to the diagnosis of SMA syndrome and she improved with conservative management. Informed consent was obtained for this study.     

A biallelic frameshift indel in PPP1R35 as a cause of primary microcephaly

Protein phosphatase 1 regulatory subunit 35 (PPP1R35) encodes a centrosomal protein required for recruiting microtubule-binding elongation machinery. Several proteins in this centriole biogenesis pathway correspond to established primary microcephaly (MCPH) genes, and multiple model organism studies hypothesize PPP1R35 as a candidate MCPH gene. Here, using exome sequencing (ES) and family-based rare variant analyses, we report a homozygous, frameshifting indel deleting the canonical stop codon in the last exon of PPP1R35 [Chr7: c.753_*3delGGAAGCGTAGACCinsCG (p.Trp251Cysfs*22)]; the variant allele maps in a 3.7 Mb block of absence of heterozygosity (AOH) in a proband with severe MCPH (−4.3 SD at birth, −6.1 SD by 42 months), pachygyria, and global developmental delay from a consanguineous Turkish kindred. Droplet digital PCR (ddPCR) confirmed mutant mRNA expression in fibroblasts. In silico prediction of the translation of mutant PPP1R35 is expected to be elongated by 18 amino acids before encountering a downstream stop codon. This complex indel allele is absent in public databases (ClinVar, gnomAD, ARIC, 1000 genomes) and our in-house database of 14,000+ exomes including 1800+ Turkish exomes supporting predicted pathogenicity. Comprehensive literature searches for PPP1R35 variants yielded two probands affected with severe microcephaly (−15 SD and −12 SD) with the same homozygous indel from a single, consanguineous, Iranian family from a cohort of 404 predominantly Iranian families. The lack of heterozygous cases in two large cohorts representative of the genetic background of these two families decreased our suspicion of a founder allele and supports the contention of a recurrent mutation. We propose two potential secondary structure mutagenesis models for the origin of this variant allele mediated by hairpin formation between complementary GC rich segments flanking the stop codon via secondary structure mutagenesis.     

Defective T-cell response to COVID-19 vaccination in acute myeloid leukaemia and myelodysplastic syndromes

Limited data exist on COVID-19 vaccination efficacy in patients with acute myeloid leukemia and myelodysplasia with excess blasts (AML/MDS-EB2). We report results from a prospective study, PACE (Patients with AML and COVID-19 Epidemiology). 93 patients provided samples post-vaccine 2 or 3 (PV2, PV3). Antibodies against SARS-COV-2 spike antigen were detectable in all samples. Neutralization of the omicron variant was poorer than ancestral variants but improved PV3. In contrast, adequate T-cell reactivity to SARS-COV-2 spike protein was seen in only 16/47 (34%) patients PV2 and 23/52 (44%) PV3. Using regression models, disease response (not in CR/Cri), and increasing age predicted poor T cell response.     

Retroperitoneal schwannoma: Uncommon location of a benign tumor

Schwannoma is a type of nerve tumor of the nerve sheath. They are preferentially localized on the head, neck, and flexor surfaces of the extremities. Retroperitoneal schwannoma is extremely rare. The diagnosis is uncommon and based on the anatomopathological and immunochemistry examination of the surgical specimen. We herein report an uncommon location of schwannoma treated with conventional surgery in a 53‐year‐old female patient admitted to our department for chronic abdominal pain. Retroperitoneal schwannoma is a rare disease that occurs in adult females. The histopathological examination is the only reliable examination for the diagnosis after total surgical resection.     

Renewable energy management of an hybrid water pumping system (photovoltaic/wind/battery) based on Takagi–Sugeno fuzzy model

This research work presents an optimal energy management for a hybrid water pumping system driven by a photovoltaic generator (PVG) and a wind turbine. These two renewable energies are used as power generation sources, whereas a battery is added as an energy-storing system, for the purpose of controlling the power flow and providing a constant load supply. The proposed management system, serve to guarantee the pumping system autonomy in a rural region where's no access to the electrical network. As a result, a maximum power point tracking (MPPT) controller is created based on the fuzzy Takagi–Sugeno (TS) model, ensuring maximum power transfer to the moto-pump in spite of wind speed and insolation changes. The synthesis of MPPT control law involves TS fuzzy reference models which generate the desired trajectories to track. A supervisor has been developed for energy management and its major purpose is to effectively use the battery to satisfy the power load requirements, and that is by maintaining the state of charge (SOC) to extend the battery's life. Finally, simulation results have been done based on Matlab/Simulink with the aim of validating the efficiency of the proposed energy management supervisor.