Imaging Approach to Pulmonary Hypertension.

Pulmonary hypertension is a rare but important clinical problem that presents a sometimes challenging diagnostic dilemma. The diagnosis of pulmonary hypertension relies on a combination of clinical testing and radiologic imaging, with chest computed tomography (CT) often serving as the primary imaging modality for comprehensive evaluation of the chest. Chest CT can be used to evaluate for causes of pulmonary hypertension including chronic lung disease, pulmonary artery obstruction, and congenital heart disease.

Stopping of adalimumab in juvenile idiopathic arthritis-associated uveitis (ADJUST): a multicentre, double-masked, randomised controlled trial.

Background: Adalimumab is an effective treatment for juvenile idiopathic arthritis-associated uveitis. Data are scarce on the effects of discontinuing adalimumab after control of the disease had been reached. We aimed to assess efficacy and safety of discontinuing treatment in patients with juvenile idiopathic arthritis-associated uveitis.

AGA Clinical Practice Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation in At-Risk Individuals.

Background & Aims: Hepatitis B reactivation (HBVr) can occur due to a variety of immune-modulating exposures, including multiple drug classes and disease states. Antiviral prophylaxis can be effective in mitigating the risk of HBVr. In select cases, clinical monitoring without antiviral prophylaxis is sufficient for managing the risk of HBVr.

Divergent transcriptional states and kinetics of circulating tumor-infiltrating lymphocyte repertoires with highly homologous T-cell receptor sequences in a patient during immunotherapy.

Evidence has shown that T-cell receptors (TCRs) that recognize the same epitopes may not be the exact TCR clonotypes but have slightly different TCR sequences. However, the changes in the genomic and transcriptomic signatures of these highly homologous T cells during immunotherapy remain unknown. Here, we examined the evolutionary features in circulating TCR clonotypes observed in tumors (tumor-infiltrating lymphocyte (TIL)-TCRs) by combining single-cell RNA/TCR sequencing of longitudinal blood samples and TCR sequencing of tumor tissue from a patient treated with anti-cytotoxic T-lymphocyte-associated protein 4/programmed cell death protein-1 therapy.

Association of Chronic Obstructive Pulmonary Disease and Mortality following Thoracic and Complex Endovascular Aortic Repair.

Objectives: This study assessed the association between chronic obstructive pulmonary disease (COPD) severity and postoperative mortality among patients undergoing thoracic endovascular aortic repair (TEVAR) and complex endovascular aortic repair (CEVAR).

Methods: A retrospective review of the Vascular Quality Initiative database identified elective TEVAR and CEVAR cases from 2013-2022 with endograft proximal landing zone ≥2 for thoracic or complex abdominal aortic disease. Symptomatic disease, ruptures, and urgent/emergent surgeries were excluded.

Topographic corneal changes in children with moderate to severe blepharokeratoconjunctivitis.

Purpose To determine the corneal topographic characteristics of children with blepharokeratoconjunctivitis (BKC), a chronic inflammatory ocular surface disease involving the lid margin, conjunctiva, and cornea. Methods The corneal topography of 21 children diagnosed with BKC between March 2008 and June 2019 at a single institution were reviewed retrospectively. Pachymetry and asymmetry indices were also analyzed.

Implementation of An Advance Care Planning Intervention in Dialysis Clinics.

Rationale & Objective: Sharing Patient's Illness Representations to Increase Trust (SPIRIT) is an evidence-based advance care planning intervention targeting dialysis patients and their surrogate decision-makers. To address SPIRIT's implementation potential, we report on a process evaluation in our recently completed five-state cluster-randomized trial.

Study Design: A descriptive study of implementation within a randomized clinical trial.

Heterologous expression of a recombinant ACE inhibitory peptide LYPVK and its potential antihypertensive action mechanism.

Enzymatic hydrolysis approach is commonly employed for preparation of active peptides, while the limited purity and yield of produced peptides hinder further development of action mechanisms. This study presents the biotechnological approach for the efficient production of recombinant angiotensin converting enzyme (ACE) inhibitory peptide LYPVK and investigates its potential antihypertensive action mechanism. DNA encoding sequence of recombinant peptide was designed to form in tandem, which was expressed in Escherichia coli BL21 (DE3).

Feasibility and acceptability of the delivery of a group telehealth intervention for support persons of patients receiving buprenorphine for opioid use disorder.

Background: Opioid-related overdoses increased substantially during the COVID-19 pandemic, eliciting an urgent demand for accessible treatment for individuals with opioid use disorder (OUD) and those who support them (support persons). Support persons can improve treatment initiation and retention in their individuals with OUD. Additionally, support persons may have their own mental health needs related to their loved one's OUD.

Recombinant Antibodies Inhibit Enzymatic Activity of the E3 Ubiquitin Ligase CHIP via Multiple Mechanisms.

Carboxyl-terminus of Hsp70-Interacting Protein (CHIP) is an E3 ubiquitin ligase that marks misfolded substrates for degradation. Hyper-activation of CHIP has been implicated in multiple diseases, including cystic fibrosis and cancer, suggesting that it may be a potential drug target. However, there are few tools available for exploring this possibility.

Cyclosporine Treatment in Patients with Kawasaki Disease and Coronary Artery Aneurysms or Treatment Resistance.

Objective: To describe the clinical course and outcome of 33 patients with Kawasaki disease (KD) treated with cyclosporine (CSA) for coronary artery abnormalities (CAA) or treatment resistance.

Study Design: Single-center, retrospective study of patients with KD treated from 2013 through 2023 for CAA or treatment resistance. Demographics, laboratory studies, medications, adverse events, and echocardiographic data were analyzed.

Long Term Results of a Comparative Study of Percutaneous and Surgically Created Proximal Forearm Arteriovenous Fistulae.

Objective: This retrospective, single centre, comparative effectiveness study aimed to compare the long term outcomes of percutaneous arteriovenous fistulae (pAVF) and surgically created arteriovenous fistulae (sAVF) created in the proximal forearm for haemodialysis access.

Methods: Data were reviewed from a prospectively maintained database on patients who underwent pAVF or sAVF creation from September 2017 to September 2023. A total of 217 pAVFs (61 WavelinQ and 156 Ellipsys) and 158 sAVFs were analysed.

Trends in Neurosurgeons Signing Medicare Opt-Out Affidavits.

Objective: In recent decades, many physicians have chosen to opt out of Medicare, allowing them to set their own pricing models for their patients. Characterization of Medicare opt-outs has not been thoroughly studied in any surgical specialty, including Neurosurgery. Our study characterizes the factors that may influence a neurosurgeon's decision to opt out of Medicare acceptance and contextualizes them both within the field and across various surgical specialties.

Six-month safety and efficacy outcomes from the randomized-controlled arm of the WRAPSODY Arteriovenous Access Efficacy (WAVE) trial.

Stenosis within the arteriovenous fistula (AVF) of hemodialysis patients leads to vascular access dysfunction and inadequate hemodialysis. Percutaneous transluminal angioplasty (PTA) is the standard therapy for stenosis. However, rates of restenosis and loss of access patency remain high.

Nutrient control of splice site selection contributes to methionine addiction of cancer.

Objectives: Many cancer cells depend on exogenous methionine for proliferation, whereas non-tumorigenic cells can divide in media supplemented with the metabolic precursor homocysteine. This phenomenon is known as methionine dependence of cancer or methionine addiction. The underlying mechanisms driving this cancer-specific metabolic addiction are poorly understood.

Development of a transdermal gel for reversible male contraception.

While there are several easy-to-use reversible female contraceptives, little is available for men. Introduction of novel, cost-effective male contraceptives could have important downstream global health and economic benefits. Currently, nearly half of all pregnancies globally are unintended, with many resulting in unsafe abortions, a significant burden for women and families in many countries.

Therapeutic outcomes and safety of radiofrequency ablation for primary papillary thyroid carcinoma: A game-changing meta-analysis.

Background: Radiofrequency ablation (RFA) is an emerging treatment option for small, low-risk papillary thyroid carcinoma (PTC). This systematic review and meta-analysis aimed to evaluate and compare the efficacy and safety profiles of RFA for primary T1a vs. T1b PTC.

Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial.

Background: No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia.

Safety and efficacy of satralizumab in patients with generalised myasthenia gravis (LUMINESCE): a randomised, double-blind, multicentre, placebo-controlled phase 3 trial.

Background: Evidence from preclinical studies suggests that IL-6 signalling has the potential to modulate immunopathogenic mechanisms upstream of autoantibody effector mechanisms in patients with generalised myasthenia gravis. We aimed to assess the safety and efficacy of satralizumab, a humanised monoclonal antibody targeting the IL-6 receptor, in patients with generalised myasthenia gravis.

Methods: LUMINESCE was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study at 105 sites, including hospitals and clinics, globally.

Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection.

More than 50% of families with suspected rare monogenic diseases remain unsolved after whole-genome analysis by short-read sequencing (SRS). Long-read sequencing (LRS) could help bridge this diagnostic gap by capturing variants inaccessible to SRS, facilitating long-range mapping and phasing and providing haplotype-resolved methylation profiling. To evaluate LRS's additional diagnostic yield, we sequenced a rare-disease cohort of 98 samples from 41 families, using nanopore sequencing, achieving per sample ∼36× average coverage and 32-kb read N50 from a single flow cell.

Ligand interaction landscape of transcription factors and essential enzymes in E. coli.

Knowledge of protein-metabolite interactions can enhance mechanistic understanding and chemical probing of biochemical processes, but the discovery of endogenous ligands remains challenging. Here, we combined rapid affinity purification with precision mass spectrometry and high-resolution molecular docking to precisely map the physical associations of 296 chemically diverse small-molecule metabolite ligands with 69 distinct essential enzymes and 45 transcription factors in the gram-negative bacterium Escherichia coli. We then conducted systematic metabolic pathway integration, pan-microbial evolutionary projections, and independent in-depth biophysical characterization experiments to define the functional significance of ligand interfaces.

Cross-Sectional Study Gender Pay Gap in Industry General Payments to U.S. General and Fellowship-Trained Surgeons.

Introduction: Gender disparities exist in nonresearch industry payments to U.S. physicians, but detailed analyses specific to surgeons are limited.

The Anatomy of Gossip: Dissecting Dynamics and Impacts in Surgical Residency.

Background: Gossip, defined by social scientists as "evaluative talk about an absent third party," is anecdotally pervasive yet poorly understood in surgical residency programs. Gossip is known to have both positive and negative impacts. This study sought to deconstruct the role of gossip in surgical residency and evaluate its impact through the lens of surgical residents.