Left ventricular diastolic dysfunction is prevalent but not associated with mortality in patients with septic shock.

Purpose: Prognostic impact of left ventricular diastolic dysfunction (LVDD) in septic shock patients has not been determined using current diagnostic guidelines. We assessed the relation between LVDD during the first 3 days following intensive care unit (ICU) admission for septic shock and Day-28 mortality.

Methods: This prospective, multicenter, observational study enrolled 402 patients (age: 63 ± 13 year; 59% male; SAPS II: 59 ± 20; SOFA: 9.

Myotilin gene duplication causing late-onset myotilinopathy.

Background: myotilinopathy is a very rare inherited muscle disease that belongs to the group of myofibrillar myopathies. These diseases share a common alteration of the sarcomere organization at the level of the Z disk resulting in pathological protein aggregation, autophagic abnormalities, and ultimately muscle degeneration. Most reported cases are due to dominant missense mutations in the MYOT gene, two of which are largely recurrent.

COMPOSIT study: evaluating osimertinib combination with targeted therapies in EGFR-mutated non-small cell lung cancer.

Introduction: The emergence of diverse resistance mechanisms after osimertinib therapy, including on-target epidermal growth factor receptor (EGFR) mutations and off-target alterations, warrants investigation of novel therapeutics to overcome these challenges and improve patient outcomes.

Methods: COMPOSIT was a French, retrospective, multicenter, cohort study of the effectiveness and tolerability of osimertinib in combination with other targeted therapies in patients with advanced EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC) who harbored other oncogenic drivers as primary or acquired resistance mechanisms. Real-world progression-free survival (rwPFS), overall survival (OS), and objective response rate (ORR) were the primary endpoints.

A voice-based algorithm can predict type 2 diabetes status in USA adults: Findings from the Colive Voice study.

The pressing need to reduce undiagnosed type 2 diabetes (T2D) globally calls for innovative screening approaches. This study investigates the potential of using a voice-based algorithm to predict T2D status in adults, as the first step towards developing a non-invasive and scalable screening method. We analyzed pre-specified text recordings from 607 US participants from the Colive Voice study registered on ClinicalTrials.

Cross-Cultural Adaptation and Clinical Validation of TIME Criteria to Detect Potentially Inappropriate Medication Use in Older Adults: Methodological Report from the TIME International Study Group.

Background: Various explicit screening tools, developed mostly in central Europe and the USA, assist clinicians in optimizing medication use for older adults. The Turkish Inappropriate Medication use in oldEr adults (TIME) criteria set, primarily based on the STOPP/START criteria set, is a current explicit tool originally developed for Eastern Europe and subsequently validated for broader use in Central European settings. Reviewed every three months to align with the latest scientific literature, it is one of the most up-to-date tools available.

Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma with Main Trunk and/or Contralateral Portal Vein Invasion in IMbrave150.

Introduction: Atezolizumab plus bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in IMbrave150. Efficacy and safety in patient subpopulations with Vp4 portal vein tumor thrombosis (PVTT) and other high-risk prognostic factors are reported.

Methods: IMbrave150 was a global, randomized (2:1), open-label, phase 3 study in systemic treatment-naive patients with unresectable HCC; OS and PFS were co-primary endpoints.

Burden of Cardio-Cerebrovascular and Renal Diseases Attributable to Systolic Hypertension in France in 2021.

Background: Hypertension is the most common chronic disease and a major modifiable risk factor for cardio-cerebrovascular and renal diseases. This study estimated the national burden of hypertension, defined as systolic blood pressure ≥140 mm Hg, on morbidity and mortality in 2021 in France.

Methods: For all diseases causally associated with hypertension (cardiovascular diseases, chronic kidney diseases, and dementia), the number and proportion of cases attributable to hypertension in adults aged ≥35 years were estimated using population attributable fractions.

Serum Neutrophil Biomarkers to Predict Crohn's Disease Progression and Infliximab Treatment Outcomes.

Background And Aims: Predicting the treatment outcomes of biological therapies is an unmet need in Crohn's Disease. In this study, we explored the potential of serum neutrophil-related biomarkers to predict infliximab therapeutic results and disease progression in Crohn's Disease patients, over a 2-year period, in a real-world setting.

Methods: The study included 100 asymptomatic Crohn's Disease patients in the IFX maintenance phase from the prospective, observational, multicenter DIRECT study.

Stakeholder Perspectives on Randomized Clinical Trials for Children With Poor-Prognosis Cancers.

Importance: In poor-prognosis children's cancers, new therapies may carry fresh hope for patients and parents. However, there is an absolute requirement for any new therapy to be properly evaluated to fulfill scientific, regulatory, and reimbursement requirements. Randomized clinical trials (RCTs) are considered the gold standard, but no consensus exists on how and when they should be deployed to best meet the needs of all stakeholders.

Aortic Valve Replacement vs Clinical Surveillance in Asymptomatic Severe Aortic Stenosis: A Systematic Review and Meta-Analysis.

Background: Current guidelines recommend a strategy of clinical surveillance (CS) for patients with asymptomatic severe aortic stenosis (AS) and a normal left ventricular ejection fraction.

Objectives: The aim of this study was to conduct a study-level meta-analysis of randomized controlled trials (RCTs) evaluating the effect of early aortic valve replacement (AVR) compared with CS in patients with asymptomatic severe AS.

Methods: Studies were quantitatively assessed in a meta-analysis using random-effects modeling.

Mathematical basis and toolchain for hierarchical optimization of biochemical networks.

Biological signalling systems are complex, and efforts to build mechanistic models must confront a huge parameter space, indirect and sparse data, and frequently encounter multiscale and multiphysics phenomena. We present HOSS, a framework for Hierarchical Optimization of Systems Simulations, to address such problems. HOSS operates by breaking down extensive systems models into individual pathway blocks organized in a nested hierarchy.

Dietary exposure to mixtures of chemicals in the first year of life and allergic and respiratory diseases up to 8 years in the French EDEN mother-child cohort.

Exposure to environmental chemicals has been associated with higher risk of childhood allergies. This study aimed to examine the association between infant's dietary exposure to mixtures of chemicals and allergic and respiratory multimorbidity in childhood. Dietary exposures were assessed at 8 and 12 months in 724 and 745 children of the EDEN cohort.

Validation of the Lung Immune Prognostic Index in patients with untreated advanced non-small cell lung cancer: Post hoc analysis of the IMpower 130, 131 and 150 trials.

Introduction: LIPI has been strongly correlated with immunotherapy (IT) outcomes in advanced NSCLC. Limited data is available for upfront chemotherapy (CT) + IT combinations. We aimed to study its prognostic value in 1st-line CT +/- IT +/- antiangiogenics.

Patients' psychosocial attributes and aggressiveness of cancer treatments near the end of life.

Background: While the use of chemotherapy near the end of life (EOL) has been identified as a relevant criterion for assessing quality of cancer care and has been estimated as non-beneficial, a trend of aggressiveness in cancer care during the last period of life remains. Both patients' sociodemographic characteristics and physicians' practice setting are associated with this use. The role of patients' psychosocial characteristics has however been understudied.