Understanding why restrictive trial eligibility criteria are inappropriate.

Background: An important difference between explanatory and pragmatic clinical trials concerns eligibility criteria. Eligibility criteria are restrictive in explanatory trials, while pragmatic trials are more inclusive or even all-inclusive.

Methods: To better understand the diverging views regarding eligibility criteria, we examine the contrast between theoretical and clinical medicine, and 3 different research contexts: laboratory research, population studies and clinical trials.

Giant metastatic mixed-type spinal ependymoma presenting with hydrocephalus.

Ependymomas are rare nervous system tumors that can arise anywhere in the neuraxis. While having a high propensity for leptomeningeal dissemination, retrograde dissemination (from the spine to the CNS) remains infrequent. We describe the case of a 31-year-old female who presented with hydrocephalus secondary to an intracranial leptomeningeal metastasis of a giant spinal ependymoma with mixed (classic and myxopapillary) histopathologic features, successfully treated with surgical resection and radiotherapy of the entire neuraxis.

Outcomes of sacral neuromodulation in male patients with overactive bladder, chronic pelvic pain, and fecal incontinence.

Introduction: Despite the growing body of literature on sacral neuromodulation (SNM) outcomes, research focusing on male patients remains limited and often represented by small cohorts nested within a larger study of mostly women. Herein, we evaluated the outcomes of SNM in a male-only cohort with overactive bladder (OAB), fecal incontinence (FI), chronic bladder pain, and neurogenic lower urinary tract dysfunction (NLUTD).

Materials And Methods: This retrospective cohort study included 64 male patients who underwent SNM insertion between 2013 and 2021 at a high-volume tertiary center.

Development of a new scale for self-reported procedural patient comfort during endovascular therapy for acute stroke.

Introduction: In stroke patients with acute large vessel occlusion, endovascular therapy (EVT) may be performed with or without sedation. Our aim is to describe self-reported intraprocedural comfort in patients undergoing EVT depending on sedation type.

Methods: We performed a prospective observational single-center study of patients undergoing EVT.

SPECT/CT to quantify early small airway disease and its relationship to clinical symptoms in smokers with normal lung function: a pilot study.

Introduction: Smokers frequently display respiratory symptoms despite the fact that their pulmonary function tests (PFTs) can be normal. Quantitative lung ventilation single-photon emission computed tomography (SPECT/CT) can provide a quantification of lung ventilatory homogeneity and could prove useful as an early marker of airway disease in smokers. We measured the effects of smoking on regional ventilation distribution in subjects with normal lung function and evaluated whether ventilation distribution in these subjects is related to lung function tests results and clinical symptoms.

A Breast Reduction Technique for the Free DIEP Flap Post Breast Reconstruction.

Breast flap remodeling is a common procedure after breast reconstruction. We present a unique approach to breast reduction using a superomedial pedicle inverted "T" technique in patients with previous free deep inferior epigastric perforator (DIEP) flap breast reconstruction, not previously reported. Breast reduction can be a valid option for reshaping breasts after free DIEP flap reconstruction.

Phylogenetic Network Analyses Reveal the Influence of Transmission Clustering on the Spread of HIV Drug Resistance in Quebec from 2002 to 2022.

Background: HIV drug resistance (HIV-DR) may jeopardize the benefit of antiretroviral therapy (ART) in treatment and prevention. This study utilized viral phylogenetics to resolve the influence of transmission networks on sustaining the spread of HIV-DR in Quebec spanning 2002 to 2022.

Methods: Time trends in acquired (ADR) and transmitted drug resistance (TDR) were delineated in treatment-experienced ( = 3500) and ART-naïve persons ( = 6011) with subtype B infections.

Leveraging PARP-1/2 to Target Distant Metastasis.

Poly (ADP-Ribose) Polymerase (PARP) inhibitors have changed the outcomes and therapeutic strategy for several cancer types. As a targeted therapeutic mainly for patients with mutations, PARP inhibitors have commonly been exploited for their capacity to prevent DNA repair. In this review, we discuss the multifaceted roles of PARP-1 and PARP-2 beyond DNA repair, including the impact of PARP-1 on chemokine signalling, immune modulation, and transcriptional regulation of gene expression, particularly in the contexts of angiogenesis and epithelial-to-mesenchymal transition (EMT).

Resting-State Functional Connectivity Profile of Insular Subregions.

The insula is often considered the fifth lobe of the brain and is increasingly recognized as one of the most connected regions in the brain, with widespread connections to cortical and subcortical structures. As a follow-up to our previous tractography work, we investigated the resting-state functional connectivity (rsFC) profiles of insular subregions and assessed their concordance with structural connectivity. We used the CONN toolbox to analyze the rsFC of the same 19 insular regions of interest (ROIs) we used in our prior tractography work and regrouped them into six subregions based on their connectivity pattern similarity.

A Randomized Trial Comparing Concurrent versus Sequential Radiation and Endocrine Therapy in Early-Stage, Hormone-Responsive Breast Cancer.

Concerns exist regarding increased toxicities, including endocrine therapy toxicity, with concurrent radiation and endocrine therapy in early breast cancer (EBC). We present a pragmatic, randomized trial comparing concurrent versus sequential endocrine and radiotherapy in hormone-responsive EBC. In this multicenter trial, patients were randomized to receive adjuvant endocrine therapy concurrent with, or sequential to, radiotherapy.

Overweight and Obesity in People Living With Type 1 Diabetes: A Cross-Sectional Analysis of the BETTER Registry.

Aims: The prevalence and associations of overweight and obesity in Canadian adult people living with type 1 diabetes (PWT1D) are poorly documented. In a cohort of PWT1D patients, this study assesses (i) overweight and obesity frequencies and associated PWT1D clinicodemographic characteristics, (ii) diabetes characteristics, and (iii) the use of noninsulin adjunctive agents.

Materials And Methods: Cross-sectional analysis of self-reported data from the BETTER registry: 1091 adult PWT1D (aged 44.

A General Neurologist's Practical Diagnostic Algorithm for Atypical Parkinsonian Disorders: A Consensus Statement.

Purpose Of Review: The most common four neurodegenerative atypical parkinsonian disorders (APDs) are progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal syndrome (CBS), and dementia with Lewy bodies (DLB). Their formal diagnostic criteria often require subspecialty experience to implement as designed and all require excluding competing diagnoses without clearly specifying how to do that. Validated diagnostic criteria are not available at all for many of the other common APDs, including normal pressure hydrocephalus (NPH), vascular parkinsonism (VP), or drug-induced parkinsonism (DIP).

Inter-visit and inter-reader reproducibility of multi-parametric diffusion-weighted MR imaging in longitudinally imaged patients with metabolic dysfunction-associated fatty liver disease and healthy volunteers.

Background: Despite the widespread use of diffusion-weighted imaging (DWI) in metabolic dysfunction-associated fatty liver disease (MAFLD), MRI acquisition and quantification techniques vary in the literature suggesting the need for established and reproducible protocols. The goal of this study was to assess inter-visit and inter-reader reproducibility of DWI- and IVIM-derived parameters in patients with MAFLD and healthy volunteers using extensive sampling of the "fast" compartment, non-rigid registration, and exclusion voxels with poor fit quality.

Methods: From June 2019 to April 2023, 31 subjects (20 patients with biopsy-proven MAFLD and 11 healthy volunteers) were included in this IRB-approved study.

Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): long-term, health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial.

Background: In the European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 study, adjuvant pembrolizumab improved recurrence-free survival and distant-metastasis-free survival in patients with resected stage III melanoma. Earlier results showed no effect of pembrolizumab on health-related quality of life (HRQOL). Little is known about HRQOL after completion of treatment with pembrolizumab, an important research area concerning patients who are likely to become long-term survivors.

The gut barrier as a gatekeeper in colorectal cancer treatment.

Colorectal cancer (CRC) is highly prevalent and is a major cause of cancer-related deaths worldwide. The incidence rate of CRC remains alarmingly high despite screening measures. The main curative treatment for CRC is a surgical resection of the diseased bowel segment.

Elevated allostatic load is associated with poorer response to repetitive transcranial magnetic stimulation in treatment-resistant depression.

This cohort study investigated whether allostatic load (AL) is associated with treatment response to repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression (TRD). Pre-treatment blood samples measured AL across multiple systems. Pre- and post-treatment mood changes were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS).

Selective Enrichment of Angiomirs in Extracellular Vesicles Released from Ischemic Skeletal Muscles: Potential Role in Angiogenesis and Neovascularization.

MicroRNAs (miRs) regulate physiological and pathological processes, including ischemia-induced angiogenesis and neovascularization. They can be transferred between cells by extracellular vesicles (EVs). However, the specific miRs that are packaged in EVs released from skeletal muscles, and how this process is modulated by ischemia, remain to be determined.

Cystic fibrosis-related diabetes develops from a combination of insulin secretion defects and insulin resistance.

Aim: The relative contributions of insulin secretory defects and possible additional contribution of insulin resistance for the development of cystic fibrosis (CF)-related diabetes (CFRD) are poorly understood. We aimed to (a) determine which indices of insulin resistance predict progression to CFRD, and (b) to model the relative contributions of insulin secretory function and insulin resistance to predict the risk of CFRD.

Materials And Methods: Three hundred and three individuals living with CF underwent a 2-h oral glucose tolerance test with blood sampling every 30 min at 12-24-month intervals until they developed CFRD or until the end of follow-up (up to 15 years).

Between-Visit Reproducibility of Shear Wave Viscoelastography in Volunteers and Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease.

Objective: To assess the reproducibility of six ultrasound (US)-determined shear wave (SW) viscoelastography parameters for assessment of mechanical properties of the liver in volunteers and patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH).

Methods: This prospective, cross-sectional, institutional review board-approved study included 10 volunteers and 20 patients with MASLD or MASH who underwent liver US elastography twice, at least 2 weeks apart. SW speed (SWS), Young's modulus (E), shear modulus (G), SW attenuation (SWA), SW dispersion (SWD), and viscosity were computed from radiofrequency data recorded on a research US scanner.