Status of Sepsis Care in European Hospitals: Results from an International Cross-Sectional Survey.

Rationale: Early detection, standardized therapy, adequate infrastructure and strategies for quality improvement should constitute essential components of every hospital's sepsis plan.

Objectives: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute hospitals.

Methods: A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals.

Impact of Left Ventricular Size on Outcomes Following HeartMate 3 Left Ventricular Assist Device Implantation: Analysis of the European Registry for Patients With Mechanical Circulatory Support (EUROMACS).

We investigated the association of preimplant left ventricular end-diastolic diameter (LVEDD) with outcomes after HeartMate 3 (HM3) left ventricular assist device (LVAD) implantation. Patients from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) registry who underwent HM3 implantation from August 2014 to February 2023 (n = 834) were analyzed according to preoperative LVEDD: less than or equal to 65 (n = 251), 65-80 (n = 441), and greater than or equal to 80 mm (n = 142). The mean age was 54.

Increasing pesticide diversity impairs soil microbial functions.

Pesticide application is essential for stabilizing agricultural production. However, the effects of increasing pesticide diversity on soil microbial functions remain unclear, particularly under varying nitrogen (N) fertilizer management practices. In this study, we investigated the stochasticity of soil microbes and multitrophic networks through amplicon sequencing, assessed soil community functions related to carbon (C), N, phosphorus (P), and sulfur (S) cycling, and characterized the dominant bacterial life history strategies via metagenomics along a gradient of increasing pesticide diversity under two N addition levels.

Impaired macroscopic CSF flow by sevoflurane in humans - both during and after anesthesia.

Background: According to the model of the glymphatic system, the directed flow of cerebrospinal fluid (CSF) is a driver of waste clearance from the brain. In sleep, glymphatic transport is enhanced, but it is unclear how it is affected by anesthesia. Animal research indicates partially opposing effects of distinct anesthetics but corresponding results in humans are lacking.

Dynamics in zebrafish development define transcriptomic specificity after angiogenesis inhibitor exposure.

Testing for developmental toxicity is an integral part of chemical regulations. The applied tests are laborious and costly and require a large number of vertebrate test animals. To reduce animal numbers and associated costs, the zebrafish embryo was proposed as an alternative model.

Implant-based reconstruction and adjuvant radiotherapy in breast cancer patients-current status and DEGRO recommendations.

Purpose: The aim of this review is to give an overview of the results of prospective and retrospective studies using allogenic reconstruction and postmastectomy radiotherapy (PMRT) in breast cancer and to make recommendations regarding this interdisciplinary approach.

Materials And Methods: A PubMed search was conducted to extract relevant articles from 2000 to 2024. The search was performed using the following terms: (breast cancer) AND (reconstruction OR implant OR expander) AND (radiotherapy OR radiation).

C-Reactive Protein Levels and Outcomes in Infarct-Related Cardiogenic Shock: Data from the ECLS-SHOCK Trial.

Background: The impact of systemic inflammation in acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is still a matter of debate. The present ECLS-SHOCK sub-study investigates the association of C-reactive protein (CRP) levels with short-term outcomes in patients with AMI-CS.

Methods: Patients with AMI-CS enrolled in the multicenter, randomized ECLS-SHOCK trial between 2019 and 2022 were included.

Predictors and outcomes in patients undergoing surgery for acute type A aortic dissection requiring concomitant veno-arterial extracorporeal membrane oxygenation support-a retrospective multicenter cohort study.

Objectives: The study aim was to investigate the outcomes and risk factors for mortality in patients undergoing surgery for acute type A aortic dissection (ATAAD) receiving concomitant veno-arterial extracorporeal membrane oxygenation (ECMO) support.

Methods: Patients from five European centers who underwent surgery for ATAAD and received perioperative veno-arterial ECMO support were included. A multivariable binary logistic regression analysis was performed to identify risk factors for thirty-day mortality.

Intact Neural Responding to Hearing One's Own Name in Children with Autism.

Diminished responding to one's own name is one of the strongest and earliest predictors of autism. However, research on the neural correlates of this response in autism is scarce. Here we investigate neural responses to hearing the own name in school-aged children with and without autism.

Hospitalized upper extremity artery disease patients: treatment and long-term outcomes.

Background And Aims: Current knowledge about upper extremity artery disease (UEAD) is scarce. This study aimed to evaluate the prevalence, treatment patterns, and short- and long-term outcomes of patients suffering from UEAD.

Methods: Retrospective health claims data of patients who were hospitalized with a primary diagnosis of UEAD between 2010 and 2017 were analysed.

RAD51 testing in patients with early HER2-negative breast cancer and homologous recombination deficiency: post-hoc analysis of the GeparOla trial.

Purpose: The randomized GeparOla trial reported comparable pathological complete response (pCR) rates with neoadjuvant containing olaparib vs. carboplatin treatment. Here, we evaluate the association between functional homologous repair deficiency (HRD) by RAD51 foci and pCR, and the potential of improving patient selection by combining RAD51 and stromal tumor infiltrating lymphocytes (sTILs).

Biomarkers.

Background: Speech abnormalities are increasingly recognized as a manifestation of cognitive deficits in Alzheimer's disease (AD) and its preclinical and prodromal stages. Here, we investigated whether MRI measures of brain atrophy, specifically in the basal forebrain and cortical language areas, can predict cognitive decline and speech difficulties in older adults within the AD spectrum.

Method: The ongoing Prospect-AD study aims to develop an algorithm to automatically identify speech biomarkers in individuals with early signs of AD.

Biomarkers.

Background: The Centiloid method (CL) was introduced as a tracer-independent measure for cortical amyloid load and is now commonly used in Alzheimer's disease (AD) clinical trials. To facilitate its implementation into clinical settings, the AMYPAD consortium set out to integrate existing literature and recent work from the consortium to provide clinical context-of-use recommendations of the Centiloid scale, which has been submitted to the European Medicine Agency for endorsement as a Biomarker Qualification Opinion.

Method: Screening of the literature was performed on the 7/11/23 on PubMed to identify articles mentioning "Centiloid".

Biomarkers.

Background: Subjective cognitive decline (SCD), in the absence of objective cognitive impairment, may be the first symptomatic manifestation of Alzheimer's disease (AD). Previous studies have suggested that its combination with amyloid-positivity (Aβ+) may represent stage 2 AD, and is associated with a higher risk of future cognitive decline. Here, we aim to (1) confirm this using the plasma Aβ42/40 ratio, and (2) test whether the addition of plasma phospho-tau181 (ptau, a marker of Aβ and tau pathology) could help refine the prediction of future cognitive decline in SCD patients.

Early-Life Adversity Predicts Markers of Aging-Related Neuroinflammation, Neurodegeneration, and Cognitive Impairment in Women.

Objective: Despite the overwhelming evidence for profound and longstanding effects of early-life stress (ELS) on inflammation, brain structure, and molecular aging, its impact on human brain aging and risk for neurodegenerative disease is poorly understood. We examined the impact of ELS severity in interaction with age on blood-based markers of neuroinflammation and neurodegeneration, brain volumes, and cognitive function in middle-aged women.

Methods: We recruited 179 women (aged 30-60 years) with and without ELS exposure before the onset of puberty.

Biomarkers.

Background: Differences in task-fMRI activation have recently been found to be related to neuropathological hallmarks of AD. However, the evolution of fMRI-based activation throughout AD disease progression and its relationship with other biomarkers remains elusive. Applying a disease progression model (DPM) to a multicentric cohort with up to four annual task-fMRI visits, we hope to provide a deeper insight into these relationships.

Biomarkers.

Background: While some memory decline in old age is "normal", there are some older individuals with maintained high cognitive performance. Using a multimodal approach including neuroimaging, fitness, genetic and questionnaire data (Figure 1A), we aimed to identify factors that are related to successful cognitive aging and whether these differ between sexes.

Method: We analyzed 165 cognitively normal older adults age ≥ 60 years from an ongoing study (SFB1436) (age=71±8years, 43% female).

Biomarkers.

Background: Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) patients, are prevalent and clinically meaningful in this group of older adults.

Method: To uncover atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to structural MRI data from 813 participants (mean ± SD age = 70.

Biomarkers.

Background: Different patterns of atrophy exist in the dementia stage of AD. However, little is known about the heterogeneity of atrophy patterns and the mechanisms that drive subsequent propagation of the disease in the preclinical stages.

Method: From the AMYPAD-PNHS cohort, we included a total of 1323 non-demented individuals, including 1094 amyloid-negative, and 229 amyloid-positive participants (Table 1).

A weight of evidence review on the mode of action, adversity, and the human relevance of xylene's observed thyroid effects in rats.

Xylene substances have wide industrial and consumer uses and are currently undergoing dossier and substance evaluation under Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) for further toxicological testing including consideration of an additional neurotoxicological testing cohort to an extended one-generation reproduction toxicity (EOGRT) study. New repeated dose study data on xylenes identify the thyroid as a potential target tissue, and therefore a weight of evidence review is provided to investigate whether or not xylene-mediated changes on the hypothalamus-pituitary-thyroid (HPT) axis are secondary to liver enzymatic induction and are of a magnitude that is relevant for neurological human health concerns. Multiple published studies confirm xylene-mediated increases in liver weight, hepatocellular hypertrophy, and liver enzymatic induction the oral or inhalation routes, including an increase in uridine 5'-diphospho-glucuronosyltransferase (UDP-GT) activity, the key step in thyroid hormone metabolism in rodents.

Biomarkers.

Background: Training studies report beneficial effects of physical (PP) on cognitive performance (COG) in older adults, but are often accompanied by potentially biased parameters, conclusions, and lack of directionality. To address these issues, we used a dynamic Bayesian approach to analyse the dynamic session-to-session change and coupling of PP and COG over time.

Methods: We used two studies (N = 17 each): Study 1 contained 24-weeks (72 sessions) of training of older adults with suspected Alzheimer's disease (AD).

Biomarkers.

Background: For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussion about their coupled temporal dynamics (Garnier-Crussard et al. 2023). Longitudinal evidence supporting this hypothesis remains nonetheless scarce (Ter Telgte et al.

Biomarkers.

Background: Perivascular spaces (PVS) can become large enough to be visible in magnetic resonance imaging (MRI). The exact aetiology of PVS enlargement in humans remains, however, elusive and under continuous debate [1-5]. Here, we tracked PVS volumes longitudinally over three years in 525 individuals along AD syndromal cognitive stages, namely cognitively unimpaired (CU), mild cognitive impairment (MCI), and Alzheimer's disease (AD), to pinpoint conditions related to PVS enlargement.

Biomarkers.

Background: Amyloid PET imaging is an established diagnostic tool for Alzheimer's disease, but its successful integration into clinical practice requires a comprehensive understanding of its impact on patients and the healthcare system. In 2022, the coverage with evidence development (CED) ENABLE study has been approved by the German Federal Joint Committee (trial registration: DRKS00030839). The study is scheduled to start in early 2024.

CT-P39 Compared With Reference Omalizumab in Chronic Spontaneous Urticaria: Results From a Double-Blind, Randomized, Active-Controlled, Phase 3 Study.

Background: This study compared the therapeutic equivalence of CT-P39 (an omalizumab biosimilar) and EU-approved reference omalizumab (ref-OMA) in patients with chronic spontaneous urticaria.

Methods: This double-blind, randomized, active-controlled Phase 3 study (NCT04426890) included two 12-week treatment periods (TPs). In TP1, patients received CT-P39 300 mg, ref-OMA 300 mg, CT-P39 150 mg, or ref-OMA 150 mg.