Immune checkpoint inhibitors in advanced gastroesophageal adenocarcinoma: a series of patient-level meta-analyses in different programmed death-ligand 1 subgroups.

Background: While the benefit of immune checkpoint inhibitors (ICI) is well established in programmed death-ligand 1 high (PD-L1) advanced gastroesophageal adenocarcinoma (GEAC), there remains significant controversy about their benefit in PD-L1 GEAC. To elucidate the benefit of ICI in PD-L1 and PD-L1 GEAC, we conducted an analysis leveraging individual patient data (IPD) extracted from Kaplan-Meier (KM) plots of pivotal trials.

Methods: KM curves from randomized clinical trials investigating the efficacy of ICI for advanced GEAC were extracted from published articles.

Combined Distal Interphalangeal Joint Arthrodesis With Proximal Interphalangeal Joint Arthroplasty or Arthrodesis: Technical Considerations.

Combined distal interphalangeal joint (DIP) arthrodesis with proximal interphalangeal joint (PIP) arthroplasty or arthrodesis presents unique challenges. Although less common than isolated surgery for the DIP and PIP joints, with an aging population, combined DIP and PIP procedures are an increasingly encountered occurrence. Anatomical and morphological studies have provided length and width measurement standards for the middle and distal phalanges, allowing for planning to assess the compatibility of strategies.

Oligomerization-driven avidity correlates with SARS-CoV-2 cellular binding and inhibition.

Cellular processes are controlled by the thermodynamics of the underlying biomolecular interactions. Frequently, structural investigations use one monomeric binding partner, while ensemble measurements of binding affinities generally yield one affinity representative of a 1:1 interaction, despite the majority of the proteome consisting of oligomeric proteins. For example, viral entry and inhibition in SARS-CoV-2 involve a trimeric spike surface protein, a dimeric angiotensin-converting enzyme 2 (ACE2) cell-surface receptor and dimeric antibodies.

Stereotactic Magnetic Resonance-Guided Daily Adaptive Radiation Therapy for Localized Prostate Cancer: Acute and Late Patient-Reported Toxicity Outcomes.

Purpose: To report acute and late bowel, urinary, and sexual dysfunction patient-reported outcome measures, among patients with localized prostate cancer who underwent stereotactic magnetic resonance-guided daily adaptive radiation therapy (SMART).

Methods And Materials: All patients who completed a baseline 12-item Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events questionnaire, before undergoing SMART with 36.25 Gy in 5 fractions, were subsequently followed up with the same graded questionnaire at set time points.

Cardiovascular Magnetic Resonance Before Invasive Coronary Angiography in Suspected Non-ST-Segment Elevation Myocardial Infarction.

Background: In suspected non-ST-segment elevation myocardial infarction (NSTEMI), this presumed diagnosis may not hold true in all cases, particularly in patients with nonobstructive coronary arteries (NOCA). Additionally, in multivessel coronary artery disease, the presumed infarct-related artery may be incorrect.

Objectives: This study sought to assess the diagnostic utility of cardiac magnetic resonance (CMR) before invasive coronary angiogram (ICA) in suspected NSTEMI.

Dose-Dependent Association Between Body Mass Index and Mental Health and Changes Over Time.

Importance: Overweight and obesity affect 340 million adolescents worldwide and constitute a risk factor for poor mental health. Understanding the association between body mass index (BMI) and mental health in adolescents may help to address rising mental health issues; however, existing studies lack comprehensive evaluations spanning diverse countries and periods.

Objective: To estimate the association between BMI and mental health and examine changes over time from 2002 to 2018.

Three-year outcomes of valoctocogene roxaparvovec gene therapy for hemophilia A.

Background: Valoctocogene roxaparvovec transfers a human factor (F)VIII coding sequence into hepatocytes of people with severe hemophilia A to provide bleeding protection.

Objectives: To present 3-year efficacy and safety in the multicenter, open-label, single-arm, phase 3 GENEr8-1 trial.

Methods: GENEr8-1 enrolled 134 adult males with severe hemophilia A who were receiving FVIII prophylaxis.

Standardization of definition and management for bleeding disorder of unknown cause: communication from the SSC of the ISTH.

In many patients referred with significant bleeding phenotype, laboratory testing fails to define any hemostatic abnormalities. Clinical practice with respect to diagnosis and management of this patient cohort poses significant clinical challenges. We recommend that bleeding history in these patients should be objectively assessed using the International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool.

CareKnowDo-A Multichannel Digital and Telephone Support Program for People With Chronic Kidney Disease: Feasibility Randomized Controlled Trial.

Background: Chronic kidney disease (CKD) is a common, progressive condition. Lifestyle changes and antihypertensive medication can slow the progression to end-stage kidney disease, which requires renal replacement therapy. However, adherence to these recommendations is often low.

Detailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design.

Background: The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP ) receptor type 1 (IP R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood.

Cardiac Remodeling After Hypertensive Pregnancy Following Physician-Optimized Blood Pressure Self-Management: The POP-HT Randomized Clinical Trial Imaging Substudy.

Background: Hypertensive pregnancy disorders are associated with adverse cardiac remodeling, which can fail to reverse in the postpartum period in some women. The Physician-Optimized Postpartum Hypertension Treatment trial demonstrated that improved blood pressure control while the cardiovascular system recovers postpartum associates with persistently reduced blood pressure. We now report the effect on cardiac remodeling.

Repeat expansions in are a cause of spinocerebellar ataxia Type 36 in the British population.

Spinocerebellar ataxias form a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by progressive cerebellar ataxia. Their prevalence varies among populations and ethnicities. Spinocerebellar ataxia 36 is caused by a GGCCTG repeat expansion in the first intron of the gene and is characterized by late-onset ataxia, sensorineural hearing loss and upper and lower motor neuron signs, including tongue fasciculations.

Choroideremia: The Endpoint Endgame.

Choroideremia is an X-linked retinal degeneration resulting from the progressive, centripetal loss of photoreceptors and choriocapillaris, secondary to the degeneration of the retinal pigment epithelium. Affected individuals present in late childhood or early teenage years with nyctalopia and progressive peripheral visual loss. Typically, by the fourth decade, the macula and fovea also degenerate, resulting in advanced sight loss.

Investigating the impact of metabolic syndrome traits on telomere length: a Mendelian randomization study.

Objective: Observational studies have reported bidirectional associations between metabolic syndrome (MetS) traits and short leukocyte telomere length (LTL), a TL marker in somatic tissues and a proposed risk factor for age-related degenerative diseases. However, in Mendelian randomization studies, longer LTL has been paradoxically associated with higher MetS risk. This study investigated the hypothesis that shorter LTL might be a consequence of metabolic dysfunction.

A low-energy total diet replacement program demonstrates a favorable safety profile and improves liver disease severity in nonalcoholic steatohepatitis.

Objective: Low-energy diets are used to treat obesity and diabetes, but there are fears that they may worsen liver disease in patients with nonalcoholic steatohepatitis (NASH) and significant-to-advanced fibrosis.

Methods: In this 24-week single-arm trial, 16 adults with NASH, fibrosis, and obesity received one-to-one remote dietetic support to follow a low-energy (880 kcal/d) total diet replacement program for 12 weeks and stepped food reintroduction for another 12 weeks. Liver disease severity was blindly evaluated (magnetic resonance imaging proton density fat fraction [MRI-PDFF], iron-corrected T1 [cT1], liver stiffness on magnetic resonance elastography [MRE], and liver stiffness on vibration-controlled transient elastography [VCTE]).