Lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension.

Vascular inflammation regulates endothelial pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulated lysosomal activity and cholesterol metabolism activate pathogenic inflammation, but their relevance to PAH is unclear. Nuclear receptor coactivator 7 () deficiency in endothelium produced an oxysterol and bile acid signature through lysosomal dysregulation, promoting endothelial pathophenotypes.

Abdominal visceral and subcutaneous adipose tissue associations with postmenopausal breast cancer incidence.

Background: Obesity, classified by body mass index (BMI), is associated with higher postmenopausal breast cancer (BCa) risk. Yet, the associations between abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) with BCa are unclear.

Methods: We assessed BCa associations with abdominal VAT and SAT in a prospective cohort of postmenopausal women without a history of cancer and with 27 years follow-up (N = 9950), during which all new cancers were adjudicated.

Orismilast, a PDE4B/D inhibitor, in moderate-to-severe atopic dermatitis: Efficacy and safety from a multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (ADESOS).

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by eczematous skin lesions and pruritus. There is an unmet need for effective first-line systemic therapies with good safety profiles, particularly oral medications. Orismilast is a novel first-in-class oral phosphodiesterase-4 (PDE4) B/D inhibitor under investigation for the treatment of moderate-to-severe AD.

Suggested Dosing of Select Beta-lactam Agents for the Treatment of Antimicrobial-Resistant Gram-Negative Infections in Children.

Background: The Infectious Diseases Society of America (IDSA) publishes annual guidance on the treatment of antimicrobial-resistant (AMR) gram-negative infections. Within the AMR guidance, suggested dosages of antibiotics for adults infected with AMR pathogens are provided. This document serves as a companion document to the IDSA guidance to assist pediatric specialists with dosing β-lactam agents for the treatment of AMR infections in children.

Third Proceedings of The North American Airway Collaborative (NoAAC): Consensus Statement on Trial Design for Airway Stenosis.

Importance: Airway stenosis is a rare but debilitating disorder that significantly degrades the quality of life in affected patients. Treatments are primarily surgical, and disease management lacks established medical therapies. The North American Airway Collaborative held its third symposium at The Johns Hopkins Hospital in Baltimore, Maryland, on April 15, 2024, focused on strategies to advance the care of these patients.

Short-term outcomes of low anterior resection with and without ileostomy for low, mid and upper rectal cancers.

Although the addition of an ileostomy to low anterior resection (LAR) may often be considered preventative of anastomotic leakage (AL), evidence that clearly demonstrates such benefit is lacking. This study aimed to identify the impact of adding an ileostomy upon AL and organ-space surgical site infection (SSI) rates in patients with lower, middle, or upper rectal cancer. This case-control study included rectal cancer patients who had undergone elective LAR in the American College of Surgeons-National Surgical Quality Improvement Program dataset between 2016 and 2022.

Weathering the Pain: Ambient Temperature's Role in Chronic Pain Syndromes.

Purpose Of Review: Chronic pain is highly prevalent and involves a complex interaction of sensory, emotional, and cognitive processes, significantly influenced by ambient temperature. Despite advances in pain management, many patients continue to experience inadequate pain relief. This review aims to consolidate and critically evaluate the current evidence on the impact of ambient temperature on chronic pain conditions such as fibromyalgia (FM), multiple sclerosis (MS), complex regional pain syndrome (CRPS), and osteoarthritis (OA).

Prescriptions (Rx) for Prevention: Clinical Tools for Integrating Environmental Health into Pediatric Clinical Care.

The integration of environmental health (EH) into routine clinical care for children is in its early stages. The vision of pediatric EH is that all clinicians caring for children are aware of and able to help connect families to needed resources to reduce harmful environmental exposures and increase health-enhancing ones. Environmental exposures include air pollution, substandard housing, lead, mercury, pesticides, consumer products chemicals, drinking water contaminants, industrial facility emissions and, increasingly, climate change-related extreme weather and heat events.

Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

Worsening of Heart Failure in Outpatients With Transthyretin Amyloidosis and Cardiomyopathy in the APOLLO-B Trial.

Background: Outpatient worsening heart failure (HF), defined by initiation or intensification of diuretics, is adversely prognostic for patients with either reduced or preserved ejection fraction.

Objectives: This study sought to investigate the prognostic value of outpatient worsening HF in transthyretin amyloidosis with cardiomyopathy and the effect of patisiran treatment.

Methods: Post hoc analyses of the APOLLO-B trial (NCT03997383) evaluated the associations between outpatient worsening HF (defined by oral diuretic initiation or intensification), measures of disease progression, and a composite endpoint of all-cause mortality and cardiovascular (CV) events.

Results of ICE-Guided Isolation of the Superior Vena Cava With Pulsed Field Ablation.

Background: Earlier studies have documented the risk for sinoatrial node injury and phrenic nerve paralysis as complications following radiofrequency catheter ablation for electrical isolation of the superior vena cava (SVCI).

Objectives: The aim of this study was to assess the safety and feasibility of SVCI in patients with atrial fibrillation undergoing pulsed field ablation (PFA) METHODS: Six hundred sixteen consecutive patients undergoing PFA for pulmonary vein isolation plus SVCI were included in this multicenter analysis. Superior vena cava (SVC) ablation was performed under the continuous guidance of intracardiac echocardiography.

A nuanced scrutiny of the segmental renal artery spectral Doppler in "Pickering" the right diagnosis.

Approximately 5-10% of patients with hypertension have secondary hypertension. We describe a case of secondary hypertension from bilateral renal artery stenosis (RAS): "Pickering syndrome." This is a case of hypertension secondary to bilateral RAS which provides an opportunity to review secondary hypertension with a specific focus on RAS, in terms of when to consider work up, causes of secondary hypertension, diagnostic testing, and treatment.

Interest in Injectable and Oral PrEP for HIV Prevention Among Women and Men Who Inject Drugs.

Background: People who inject drugs (PWID) are at increased risk for human immunodeficiency virus (HIV). Women who inject are a particularly vulnerable group. Preexposure prophylaxis (PrEP) is effective, but access and uptake has been limited.

Long-term safety and efficacy of ritlecitinib in adults and adolescents with alopecia areata and at least 25% scalp hair loss: Results from the ALLEGRO-LT phase 3, open-label study.

Background: ALLEGRO-LT is an ongoing, long-term, open-label, multicentre, phase 3 study of ritlecitinib in adults and adolescents with alopecia areata (AA).

Objectives: To evaluate ritlecitinib safety and efficacy through Month 24 in patients with AA and ≥25% scalp hair loss.

Methods: ALLEGRO-LT enrolled rollover patients who previously received study intervention in either ALLEGRO phase 2a or 2b/3 studies and de novo patients who had not received treatment in either study.

Genomic sequencing in diverse and underserved pediatric populations: parent perspectives on understanding, uncertainty, psychosocial impact, and personal utility of results.

Purpose: Limited evidence evaluates parents' perceptions of their child's clinical genomic sequencing (GS) results, particularly among individuals from medically underserved groups. Five Clinical Sequencing Evidence-Generating Research (CSER) consortium studies performed GS in children with suspected genetic conditions with high proportions of individuals from underserved groups to address this evidence gap.

Methods: Parents completed surveys of perceived understanding, personal utility, and test-related distress after GS result disclosure.

Annular Closure Device Reduces Symptomatic Reherniation Rates: Results of a Meta-analysis.

The scope of existing annular closure device (ACD) studies examining long-term follow-up data is limited. There is a paucity of studies that report and analyze recent outcomes data following ACD use. We sought to summarize the available long-term follow-up data on postoperative outcomes of the Barricaid (Intrinsic Therapeutics) ACD.

Exploring the presence and roles of humility when experiencing situations of uncertainty.

Background: Uncertainty is a pervasive challenge in clinical practice. Whereas the importance of humility in navigating uncertainty has been discussed, empirical research on how humility is practiced or expressed (i.e.

Murine model of cross-IgE sensitization and cross-anaphylactic reactions among multiple group food allergens.

Rationale: Approximately 32 million people in the United States suffer from food allergies. Some food groups, such as legumes - peanuts, tree nuts, fish, and shellfish, have a high risk of cross-reactivity. However, the murine model of multiple food group cross-reactivity is limited.

Social determinants of financial stress and association with psychological distress among young adults 18-26 years in the United States.

Introduction: Financial stress (FS) during young adulthood may have lasting effects on financial security, physical health, and overall wellbeing. This study examines the burden, social determinants and mental health consequences of experienced FS among young adults in the United States, based on objective measures of financial stress.

Methods: We studied young adults aged 18-26 years using pooled data from the 2013-18 National Health Interview Survey.

Indications and outcomes of liver transplantation for liver tumors in the United States.

Background: While hepatocellular carcinoma (HCC) remains the leading cause of liver transplant (LT) for liver tumors, indications have broadened over the years. Data regarding patient characteristics and outcomes of LT for liver tumors are limited.

Methods: From Jan-2002 to March-2022, 14,406 LT recipients for various liver tumors were identified in United Network for Organ Sharing database.

Achieving reliable patient reported outcomes collection to measure health care improvement in a learning health network: lessons from pediatric rheumatology care and outcomes improvement network.

Introduction: Data from the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) registry suggests that reliable collection of patient-reported outcomes (PROs) varies across sites. The objective of this study was to better understand the practices of collecting PROs at PR-COIN sites.

Methods: A REDCap survey was sent to the lead representative for each PR-COIN site.