Hyperreflective Material Boundary Remodeling in Neovascular Age-Related Macular Degeneration: A Post Hoc Analysis of the AVENUE Trial.

Objective: To describe the spatial and temporal characteristics of hyperreflective material (HRM) on spectral-domain OCT (SD-OCT) in neovascular age-related macular degeneration (nAMD) during antiangiogenic treatment and explore associations with best-corrected visual acuity (BCVA) and macular atrophy (MA).

Design: Retrospective regrading of SD-OCT-images from the multicenter, randomized controlled AVENUE trial (NCT02484690, conducted from August 2015 to September 2017).

Participants: Treatment-naive nAMD patients enrolled from 50 sites in the US.

Angiopoietin 2 and hsCRP are associated with pulmonary hemodynamics and long-term mortality respectively in CTEPH-Results from a prospective discovery and validation biomarker study.

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed disease of uncertain etiology. Altered endothelial homeostasis, defective angiogenesis and inflammation are implicated. Angiopoietin 2 (Ang2) impairs acute thrombus resolution and is associated with vasculopathy in idiopathic pulmonary arterial hypertension.

Safety and Efficacy of Tocilizumab 4 or 8 mg/kg in Hospitalized Patients With Moderate to Severe Coronavirus Disease 2019 Pneumonia: A Randomized Clinical Trial.

Background: Tocilizumab, an interleukin 6 receptor (IL-6R) antagonist monoclonal antibody, has shown efficacy in patients with coronavirus disease 2019 (COVID-19) pneumonia, but the optimal dose is unknown.

Methods: Patients hospitalized for moderate to severe COVID-19 pneumonia were randomized 1:1 to receive standard of care treatment and 1-2 doses of intravenous tocilizumab 4 mg/kg or 8 mg/kg (open-label). Primary pharmacokinetic and pharmacodynamic end points were serum concentrations of tocilizumab and soluble interleukin 6 receptor (sIL-6R), IL-6, ferritin, and C-reactive protein (CRP), from baseline to day 60.

Dosing regimen optimisation for oseltamivir in immunocompromised paediatric patients with influenza: Extrapolation of efficacy.

Aims: To optimise the dosing regimen of oseltamivir for immunocompromised (IC) paediatric patients (<18 years) with influenza, we used an extrapolation approach alongside clinical data.

Methods: Efficacy was extrapolated from adult IC patients to paediatric IC patients by leveraging existing efficacy, safety, pharmacokinetic (PK)/pharmacodynamic (PD), and disease-progression models of oseltamivir and oseltamivir carboxylate (OC). Data of IC paediatric patients from two studies (NV25719 and NV20234) were included in the population PK (n = 30), PK/PD analysis (n = 22) and disease modelling approach (n = 36).

Mid-term follow-up after aortic valve replacement with the Carpentier Edwards Magna Ease prosthesis.

Background: Approximately 250,000 heart valve operations are performed annually worldwide. An intensive research and development effort has led to progressively more advanced heart valve prostheses. The Carpentier-Edwards Perimount Magna Ease (CEPME) prosthesis represents the latest iteration of the Edwards Perimount series of aortic tissue valves.

Pharmacokinetics and Pharmacodynamics of Conventional-Dose vs Triple-Dose Oseltamivir in Severely Immunocompromised Children With Influenza.

This randomized phase 1b study evaluated the pharmacokinetics/pharmacodynamics of conventional-dose (30-75 mg twice daily [BID]) vs triple-dose (90-225 mg BID; weight-adjusted) oseltamivir for treatment of influenza in severely immunocompromised children <13 years. Oseltamivir carboxylate (OC) C and AUC were ~2-fold higher with triple-dose vs conventional-dose oseltamivir. Increased dose/exposure of oseltamivir/OC did not improve virological outcomes or reduce viral resistance.

Usefulness of the STOP-Bang Questionnaire in a Cardiac Surgical Population.

Objective: The aim of this study was to assess the predictive accuracy of the STOP-Bang questionnaire in relation to obstructive sleep apnea (OSA) detected by nocturnal oximetry, as well as postoperative outcomes, in a population undergoing cardiac surgery.

Design: A prospective observational cohort study.

Setting: The specialist cardiothoracic center at the Royal Papworth Hospital, Cambridge University Health Partners, United Kingdom.

Early Outcomes After Mitral Valve Repair versus Replacement in the Elderly: A Propensity Matched Analysis.

Background: To compare early outcomes of mitral valve repair versus replacement in elderly patients with degenerative mitral valve disease.

Methods: A retrospective review of prospectively collected clinical data of patients over 75 years of age, who underwent mitral valve surgery for degenerative disease, between 2010 and 2013, was carried out. Those undergoing mitral valve repair and replacement were propensity matched to adjust for baseline clinical differences.

Effects of Patent Foramen Ovale Closure on Obstructive Sleep Apnea Syndrome: PCOSA Study.

Background: Previous studies have shown a higher prevalence of patent foramen ovale (PFO) in patients with obstructive sleep apnea syndrome (OSAS). Right to left shunting through a PFO may be encouraged by the respiratory physiology of OSAS, contributing to the disease pathophysiology. We assessed whether PFO closure would improve respiratory polygraphy parameters compared with baseline measurements in patients with OSAS.

Outcome after heart transplantation from donation after circulatory-determined death donors.

Background: The requirement for heart transplantation is increasing, vastly outgrowing the supply of hearts available from donation after brain death (DBD) donors. Transplanting hearts after donation after circulatory-determined death (DCD) may be a viable additive alternative to DBD donors. This study compared outcomes from the largest single-center experience of DCD heart transplantation against matched DBD heart transplants.

Prediction of postpercutaneous coronary intervention myocardial infarction: insights from intravascular imaging, coronary flow, and biomarker evaluation.

Background: Percutaneous coronary intervention-induced myocardial infarction (PMI) has prognostic significance. Identifying patients at high risk for PMI is desirable as it may alter strategy and facilitate early preventative therapy. We therefore sought to establish whether preprocedural demographic, interventional (plaque characteristics and coronary microcirculatory function), and inflammatory, endothelial damage, and platelet-derived biomarker data could predict the risk of PMI.

Medication and patient factors associated with adherence to pulmonary hypertension targeted therapies.

The aims of this study were to investigate the medication adherence of patients on pulmonary hypertension (PH)-targeted therapies and uncover factors that might influence adherence values. Patients taking at least one specialist medicine (sildenafil, tadalafil, bosentan, ambrisentan, iloprost, epoprostenol, treprostinil) completed a Morisky Medication Adherence Scale-8 (MMAS-8) questionnaire. Participants' MMAS-8 scores were used to estimate overall medicine adherence.

Phenotypic Characterization of Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

Background: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 () are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene () are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH.

Clinical trial protocol for TRANSFORM-UK: A therapeutic open-label study of tocilizumab in the treatment of pulmonary arterial hypertension.

Our aim is to assess the safety and potential efficacy of a novel treatment paradigm in pulmonary arterial hypertension (PAH), immunomodulation by blocking interleukin-6 (IL6) signaling with the IL6 receptor antagonist, tocilizumab. Inflammation and autoimmunity are established as important in PAH pathophysiology. One of the most robust observations across multiple cohorts in PAH has been an increase in IL6, both in the lung and systemically.

Association between severity of untreated sleep apnoea and postoperative complications following major cardiac surgery: a prospective observational cohort study.

Objective: To examine whether untreated sleep apnoea is associated with prolonged Intensive Care Unit (ICU) stay and increased frequency of postoperative ICU complications, in patients undergoing major cardiac surgery.

Patients/methods: Adult patients, undergoing elective coronary artery bypass grafting with or without cardiac valve surgery, between March 2013 and July 2014, were considered. We excluded patients participating in other interventional studies, those who had a tracheostomy before surgery, required emergency surgery or were due to be admitted on the day of surgery.

Genome Wide Association Analysis Reveals New Production Trait Genes in a Male Duroc Population.

In this study, 796 male Duroc pigs were used to identify genomic regions controlling growth traits. Three production traits were studied: food conversion ratio, days to 100 KG, and average daily gain, using a panel of 39,436 single nucleotide polymorphisms. In total, we detected 11 genome-wide and 162 chromosome-wide single nucleotide polymorphism trait associations.

Vaccination of koalas with a prototype chlamydial vaccine is safe, does not increase the incidence of lymphoma-related disease and maybe associated with increased lifespan in captive koalas.

Objectives: To assess the impact of Chlamydia vaccination on survival of captive koalas, and to compare the incidence of lymphomas and neoplasias between vaccinated and unvaccinated koalas.

Methods: Survival analysis using Cox and Weibull regressions on 54 vaccinated and 52 matched unvaccinated koalas, and chi-square contingency table for incidence of lymphomas/neoplasias.

Results: Vaccination was found to have a significant positive effect on koala lifespan (P=0.

A genome-wide association analysis for porcine serum lipid traits reveals the existence of age-specific genetic determinants.

Background: The genetic determinism of blood lipid concentrations, the main risk factor for atherosclerosis, is practically unknown in species other than human and mouse. Even in model organisms, little is known about how the genetic determinants of lipid traits are modulated by age-specific factors. To gain new insights into this issue, we have carried out a genome-wide association study (GWAS) for cholesterol (CHOL), triglyceride (TRIG) and low (LDL) and high (HDL) density lipoprotein concentrations measured in Duroc pigs at two time points (45 and 190 days).

Effect of family relatedness on characteristics of estimated IBD probabilities in relation to precision of QTL estimates.

Background: A random QTL effects model uses a function of probabilities that two alleles in the same or in different animals at a particular genomic position are identical by descent (IBD). Estimates of such IBD probabilities and therefore, modeling and estimating QTL variances, depend on marker polymorphism, strength of linkage and linkage disequilibrium of markers and QTL, and the relatedness of animals in the pedigree. The effect of relatedness of animals in a pedigree on IBD probabilities and their characteristics was examined in a simulation study.

A strong quantitative trait locus for wing length on chromosome 2 in a wild population of great reed warblers.

Wing length is a key character for essential behaviours related to bird flight such as migration and foraging. In the present study, we initiate the search for the genes underlying wing length in birds by studying a long-distance migrant, the great reed warbler (Acrocephalus arundinaceus). In this species wing length is an evolutionary interesting trait with pronounced latitudinal gradient and sex-specific selection regimes in local populations.