Empirical antibiotic therapy improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study.

Background: Bacterial pulmonary superinfections develop in a substantial proportion of mechanically ventilated COVID-19 patients and are associated with prolonged mechanical ventilation requirements and an increased mortality. Albeit recommended, evidence supporting the use of empirical antibiotics at intubation is weak and of low quality. The aim of this study was to elucidate the effect of empirical antibiotics, administered within 24hours of endotracheal intubation, on superinfections, duration of mechanical ventilation, and mortality in mechanically ventilated patients with COVID-19.

Association of aortic valve size with the degree of aortic valve calcification in severe high-gradient aortic stenosis.

Aims: Less pronounced calcification of the aortic valve (AVC) was observed in women with aortic stenosis (AS) as compared to men. Since women have smaller aortic valves (AV), this could explain a lower calcium load. We aimed to analyze the association of AV size with AVC independent from sex.

A comprehensive summary of the ASEV-CzeSEV joint meeting on extracellular vesicles.

This report summarizes the ASEV-CzeSEV Joint Meeting on Extracellular Vesicles (EVs), held at the Medical University of Vienna in September 2024. The conference focused on introducing and expanding EV research and infrastructure within the Czech Republic and Austria, highlighting areas for collaboration. Key sessions featured research on EV-based diagnostics, tissue regeneration, interspecies communication and therapeutic applications, with an emphasis on shared resources and cross-border partnerships.

Equivalent reduction of Escherichia coli by rinsing hands with cold and warm water.

Objective: Hand washing is considered an important public health intervention to reduce the burden of communicable diseases such as gastrointestinal and respiratory tract infections. Washbasins in public restrooms are often only equipped with cold water and it can be observed that people only rinse their hands briefly after using the toilet instead of washing them properly with soap. As there are no recommendations on the optimal water temperature for efficacy, we measured the efficacy of simple hand rinsing with cold (4°C) and warm (40°C) water for 10 and 20 seconds compared to the European Norm EN 1499 reference hand wash.

A Systematic Review of Safety and Efficacy of Factor XI/XIa Inhibitors in Patients With ESKD on Hemodialysis.

Introduction: Factor XI/XIa (FXI/XIa) has emerged as a potential target for antithrombotic therapy, driven by preclinical evidence showing the role of FXI/XIa inhibition for preventing thrombosis without impeding hemostasis. This is particularly promising for patients at high risk of both thromboembolic events and bleeding, such as patients with end-stage kidney disease (ESKD) on hemodialysis (HD).

Methods: We systematically searched Embase, MEDLINE, and ClinicalTrials.

Efficacy and Safety of Pegcetacoplan in Kidney Transplant Recipients With Recurrent Complement 3 Glomerulopathy or Primary Immune Complex Membranoproliferative Glomerulonephritis.

Introduction: Complement 3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) have high risks for disease recurrence and allograft loss in transplant kidneys. Pegcetacoplan (targeted complement 3 [C3]/C3b inhibitor) may prevent excessive deposition of C3 and complement 5 [C5] breakdown products and associated renal damage.

Methods: NOBLE (NCT04572854) is a prospective, phase 2, multicenter, open-label, randomized controlled trial evaluating the efficacy and safety of pegcetacoplan in posttransplant patients with recurrent C3G or IC-MPGN.

Higher bone cement volume in total knee arthroplasty lowers the risk of postoperative radiolucent lines.

Purpose: >The aim of this multicenter study was to analyze the potential impact of patient demographics and cementation technique towards the development of radiolucent lines (RLLs) in primary total knee arthroplasty (TKA). It was hypothesized that cementation techniques, including higher cement volume, double-layer cementation technique and hardening in full extension, reduce RLL incidence by improving stability, whereas demographic factors such as age, BMI and smoking may increase RLL risk by affecting bone quality and mechanical loading.

Methods: Altogether, 776 patients (median age: 70.

Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells.

The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.

Cytokine expression of soft tissue cells cultured with titanium discs and their respective supernatants in vitro.

Objective: Titanium surface modifications improve osseointegration in dental and orthopedic implants. However, soft tissue cells can also reach the implant surface in immediate loading protocols. While previous research focused on osteogenic cells, the early response of soft tissue cells still needs to be better understood.

SD-LayerNet: Robust and label-efficient retinal layer segmentation via anatomical priors.

Background And Objectives: Automated, anatomically coherent retinal layer segmentation in optical coherence tomography (OCT) is one of the most important components of retinal disease management. However, current methods rely on large amounts of labeled data, which can be difficult and expensive to obtain. In addition, these systems tend often propose anatomically impossible results, which undermines their clinical reliability.

Comparative Single-Cell Transcriptomics of Human Neuroblastoma and Preclinical Models Reveals Conservation of an Adrenergic Cell State.

Transgenic mice and organoid models, such as three-dimensional tumoroid cultures, have emerged as powerful tools for investigating cancer development and targeted therapies. Yet, the extent to which these preclinical models recapitulate the cellular identity of heterogeneous malignancies, like neuroblastoma (NB), remains to be validated. Here, we characterized the transcriptional landscape of TH-MYCN tumors by single-cell RNA sequencing (scRNA-seq) and developed ex vivo tumoroids.

Benchmarking the Efficacy of Salvage Systemic Therapies for Recurrent Meningioma: A RANO Group Systematic Review and Meta-analysis to Guide Clinical Trial Design.

Background: Despite advances in our understanding of the molecular underpinnings of meningioma progression and innovations in systemic and local treatments, recurrent meningiomas remain a substantial therapeutic challenge. The objective of this systematic review and meta-analysis is to provide a historical baseline, contemporary analysis, and propose a "rate of probable interest" to inform future clinical trial design and development on behalf of the RANO meningioma group.

Methods: PubMed, ClinicalTrials.

Lateralization of Neural Speech Discrimination at Birth Is a Predictor for Later Language Development.

Newborns are able to neurally discriminate between speech and nonspeech right after birth. To date it remains unknown whether this early speech discrimination and the underlying neural language network is associated with later language development. Preterm-born children are an interesting cohort to investigate this relationship, as previous studies have shown that preterm-born neonates exhibit alterations of speech processing and have a greater risk of later language deficits.

Do national cancer control plans address care and research for children, adolescents, and young adults? A review of status, priorities, and recommendations across 41 European countries.

Paediatric cancers, although rare, are the leading cause of disease-related mortality in European children above one year. A key pillar of the European Health Union, Europe's Beating Cancer Plan (EBCP) puts a spotlight on childhood cancer. National Cancer Control Plans (NCCPs) have a key role but did not address childhood cancers sufficiently previously.

Elevated Hepatic Copper Content in Porto-Sinusoidal Vascular Disorder (PSVD): Leading Down a Wrong Track.

Background And Aims: Porto-sinusoidal vascular disorder (PSVD) is a rare vascular liver disorder characterised by specific histological findings in the absence of cirrhosis, which is poorly understood in terms of pathophysiology. While elevated hepatic copper content serves as diagnostic hallmark in Wilson disease (WD), hepatic copper content has not yet been investigated in PSVD.

Methods: Patients with a verified diagnosis of PSVD at the Medical University of Vienna and available hepatic copper content at the time of diagnosis of PSVD were retrospectively included.

Improvement in Serum Eosinophilia is Observed in Clinical Responders to Ustekinumab but not Adalimumab in Inflammatory Bowel Disease.

Introduction: In inflammatory bowel disease (IBD), the number of eosinophils increases in the lamina propria of the intestinal tract, but their specific patho-mechanistic role remains unclear. Elevated blood eosinophil counts in active IBD suggest their potential as biomarkers for predicting response to biologic therapies. This study evaluates blood eosinophil count trends and their predictive value for clinical response and endoscopic improvement in patients with IBD receiving ustekinumab or adalimumab induction therapy.

Managing depression in the elderly: real-world clinical considerations and perspectives.

This study aims to elucidate current trends in clinical practice for managing depression in elderly patients, focusing on the utilization of pharmacotherapeutics and integrated care models to improve patient outcomes. A comprehensive survey was conducted among physicians from various European countries to gather insights into prescribing habits, treatment patterns, and the impact of comorbidities on therapeutic choices, with a focus on trazodone. The participants included psychiatrists, general practitioners, and neurologists actively involved in elderly depression care.

Usability, efficacy, and safety of candidate tocilizumab biosimilar CT-P47 self-administration via auto-injector and pre-filled syringe in patients with rheumatoid arthritis: a single-arm, open-label, phase 3 study.

Background: CT-P47 is a candidate tocilizumab biosimilar that is currently in clinical development. We assessed the usability of CT-P47 self-administration via auto-injector (AI) in patients with rheumatoid arthritis (RA).

Research Design And Methods: This was a 12-week, single-arm, open-label, multiple-dose, Phase 3 study.

Bilateral foot drop as presenting feature of facioscapulohumeral muscular dystrophy type 1.

•FSHD1 may present with bilateral foot drop in adulthood.•Clinical examination, EMG and muscle MRI may additionally guide genetic testing.•Targeted genetic testing is crucial in atypical cases, particularly in light of new therapies.

A new fluorescent oxaliplatin(iv) complex with EGFR-inhibiting properties for the treatment of drug-resistant cancer cells.

Platinum chemotherapy is part of every second anticancer treatment regimen. However, its application is limited by severe side effects and drug resistance. The combination of platinum-based chemotherapeutics with EGFR inhibitors has shown remarkable synergism in clinical treatment.

Early Change in C-Reactive Protein and Venous Thromboembolism in Patients Treated With Immune Checkpoint Inhibitors.

Background: Patients with cancer treated with immune-checkpoint inhibitors (ICIs) have a substantial risk of venous thromboembolism (VTE). The association between ICI-induced inflammation and hypercoagulability is unclear, and no biomarkers currently exist to stratify VTE risk.

Objectives: The authors sought to determine the association between the early changes in C-reactive protein (CRP) after ICI initiation and the risk of VTE.

Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry.

Background And Aims: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear.

Methods: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD.