Effect of Implanted Defibrillator on Mortality in Patients With Chronic Kidney Disease.

The beneficial role of implantable cardioverter defibrillators (ICDs) in patients with chronic kidney disease (CKD) is controversial. This meta-analysis aimed to evaluate the effect of ICD on mortality in patients with CKD. A literature search was conducted for studies reporting the effect of ICD on all-cause mortality in patients with CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2). The search was not restricted to time or publication status. The search included the following databases: Ovid MEDLINE, EMBASE, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL. The primary end point was all-cause mortality. The minimum duration of follow-up required for inclusion was 1 year. The literature search identified 834 studies, of which 14 studies with 70,661 patients were included. Mean follow-up was 39 months (12 to 81 months). For all patients with CKD, ICD was associated with lower all-cause mortality (log hazard ratio [HR] -0.247, standard error [SE] 0.101, p = 0.015). Heterogeneity: degree of freedom = 13 (p <0.01), I2 = 97.057; test for overall effect: Z = -2.431 (p = 0.015). When further stratified based on dialysis, patients with CKD without the need for dialysis had significantly lower mortality (log HR -0.211, SE 0.095, p = 0.026), with a similar trend in patients who underwent dialysis (log HR -0.262, SE 0.134, p = 0.051). ICD implantation is associated with a significant mortality benefit in patients with CKD.

Effect of gender on atrial fibrillation ablation outcomes using a propensity score-matched analysis.

Background: Previous studies have shown that women with atrial fibrillation (AF) have a higher incidence of recurrence and non-pulmonary vein (non-PV) triggers. However, there remains an incomplete understanding of the impact of gender on AF ablation strategies and outcomes. Objective: The purpose of this study was to evaluate the impact of gender on AF ablation outcomes. Methods: We analyzed 1568 AF ablations in 1412 patients (34% female) performed at a single tertiary care center between January 2013 and July 2021. Patients were followed for at least 6 months (mean 34 months) for detection of AF recurrence, complications, and emergency department visits/hospitalizations. The effect was assessed by multivariate logistic regression analysis using propensity score matching (PSM). Results: Mean age was 64 years, and mean body mass index (BMI) was 31 kg/m2. Seventy-seven percent of patients underwent de novo ablations. Twenty-seven percent of patients had persistent AF, with a recurrence rate of 37%. There was no difference in AF recurrence when stratified by gender (hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.92-1.43; P >.05) and age. After PSM gender 1:1 (criteria: age, type of AF, hypertension, diabetes mellitus, and BMI; n = 888 patients), there was no difference in AF recurrence or procedure-related complications. Having a history of persistent AF (HR 1.54; 95% CI 1.18-1.99; P = .001) predisposed to recurrence of AF. Persistent AF (HR 2.99; 95% CI 1.94-4.78; P <.001) and age >70 years (HR 1.03; 95% CI 1.02-1.05; P <.001) were associated with the need for additional substrate modification with no difference based on gender. Conclusion: There was no difference in overall safety or efficacy outcomes between genders after AF ablation.

Transcriptome and toxin family analysis of the paralysis tick, Ixodes holocyclus.

The Australian paralysis tick (Ixodes holocyclus) secretes neuropathic toxins into saliva that induce host paralysis. Salivary glands and viscera were dissected from fully engorged female I. holocyclus ticks collected from dogs and cats with paralysis symptoms. cDNA from both tissue samples were sequenced using Illumina HiSeq 100 bp pair end read technologies. Unique and non-redundant holocyclotoxin sequences were designated as HT2-HT19, as none were identical to the previously described HT1. Specific binding to rat synaptosomes was determined for synthetic HTs, and their neurotoxic capacity was determined by neonatal mouse assay. They induced a powerful paralysis in neonatal mice, particularly HT4 which produced rapid and strong respiratory distress in all animals tested. This is the first known genomic database developed for the Australian paralysis tick. The database contributed to the identification and subsequent characterization of the holocyclotoxin family that will inform the development of novel anti-paralysis control methods.

Tick holocyclotoxins trigger host paralysis by presynaptic inhibition.

Ticks are important vectors of pathogens and secreted neurotoxins with approximately 69 out of 692 tick species having the ability to induce severe toxicoses in their hosts. The Australian paralysis tick (Ixodes holocyclus) is known to be one of the most virulent tick species producing a flaccid paralysis and fatalities caused by a family of neurotoxins known as holocyclotoxins (HTs). The paralysis mechanism of these toxins is temperature dependent and is thought to involve inhibition of acetylcholine levels at the neuromuscular junction. However, the target and mechanism of this inhibition remain uncharacterised. Here, we report that three members of the holocyclotoxin family; HT-1 (GenBank AY766147), HT-3 (GenBank KP096303) and HT-12 (GenBank KP963967) induce muscle paralysis by inhibiting the dependence of transmitter release on extracellular calcium. Previous study was conducted using extracts from tick salivary glands, while the present study is the first to use pure toxins from I. holocyclus. Our findings provide greater insight into the mechanisms by which these toxins act to induce paralysis.

The protective effect of glibenclamide in a model of hemorrhagic encephalopathy of prematurity.

We studied a model of hemorrhagic encephalopathy of prematurity (EP) that closely recapitulates findings in humans with hemorrhagic EP. This model involves tandem insults of 20 min intrauterine ischemia (IUI) plus an episode of elevated venous pressure induced by intraperitoneal glycerol on post-natal day (P) 0. We examined Sur1 expression, which is upregulated after focal ischemia but has not been studied after brief global ischemia including IUI. We found that 20 min IUI resulted in robust upregulation of Sur1 in periventricular microvessels and tissues. We studied tandem insult pups from untreated or vehicle-treated dams (TI-CTR), and tandem insult pups from dams administered a low-dose, non-hypoglycemogenic infusion of the Sur1 blocker, glibenclamide, for 1 week after IUI (TI-GLIB). Compared to pups from the TI-CTR group, pups from the TI-GLIB group had significantly fewer and less severe hemorrhages on P1, performed significantly better on the beam walk and accelerating Rotarod on P35 and in tests of thigmotaxis and rapid learning on P35-49, and had significantly greater body and brain weights at P52. We conclude that low-dose glibenclamide administered to the mother at the end of pregnancy protects pups subjected to IUI from post-natal events of elevated venous pressure and its consequences.

Management of hypertension in liver transplant patients.

Hypertension is a common co-morbidity and a frequent complication in liver transplant patients. The aim of this paper is to concisely review available clinical data and propose a hypertension treatment algorithm in liver transplant patients. Calcium channel blockers are mainstay of the treatment due to their potent vasodilatory effects. Dihydropyridine calcium channel blockers are preferable due to their least interaction with cytochrome P450 enzyme system and, therefore, minimal risk of potential disruption of immunosuppressive drug levels. Beta-blockers may be considered first line drugs in patients with resting tachycardia and in those with high cardiac outputs. Data support the use of beta-blockers for patients intolerant or unresponsive to calcium channel blockers. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers have little value when used early after liver transplant but may have a more pronounced role during the later periods. Diuretics may be of value in combination with other drugs, especially to counteract the potassium-retaining effects of calcineurin inhibitors. Treatment of post liver transplantation hypertension in patients with co-morbid conditions such as coronary artery disease, diabetes mellitus, congestive heart failure, and renal disease will likely require combination therapy.