Intratumoral or Subcutaneous MK-2118, a Non-Cyclic Dinucleotide STING Agonist, With or Without Pembrolizumab for Advanced or Metastatic Solid Tumors or Lymphomas.

Background: We evaluated the non-cyclic dinucleotide stimulator of interferon genes agonist MK-2118 ± pembrolizumab in patients with advanced solid tumors or lymphomas.

Methods: This first-in-human study (NCT03249792) enrolled patients with refractory, advanced solid tumors or lymphomas. Patients received intratumoral (IT) MK-2118 100-20,000 µg (arm 1), IT MK-2118 900-15,000 µg plus intravenous (IV) pembrolizumab 200 mg every 3 weeks (Q3W; arm 2), or subcutaneous (SC) MK-2118 5000-150,000 µg plus IV pembrolizumab 200 mg Q3W (arm 4); arm 3 (visceral injection of MK-2118) was not pursued.

The Cutaneous Pathology of Erythromelalgia and Its Role in Establishing Critical Clues Regarding Pathogenesis.

Erythromelalgia, a rare cutaneous pain syndrome, is characterized by acral burning pain and flushing, often alleviated by cold and rest. Primary erythromelalgia is caused by gain-of-function mutations of genes encoding for sodium channels, resulting in hyperexcitability of pain signaling neurons. Autoimmunity and hematologic dyscrasias such as thrombocythemia have been implicated in secondary erythromelalgia.

Benefits of Cilostazol's Effect on Vascular and Neuropathic Complications Caused by Diabetes.

Diabetes mellitus (DM) is a global health concern with a rising incidence, particularly in aging populations and those with a genetic predisposition. Over time, DM contributes to various complications, including nephropathy, retinopathy, peripheral arterial disease (PAD), and neuropathy. Among these, diabetic neuropathy and PAD stand out due to their high prevalence and significant impact on patients' quality of life.

The Evolution of Match Running Performance in the Top Two Spanish Soccer Leagues: A Comparative Four-Season Study.

: This study uniquely examines the evolution of match running performance in official matches over four consecutive seasons (2019/2020-2022/23) within Spain's top two professional soccer leagues (LaLiga). By analyzing differences between competitive league standards (First Division vs. Second Division), this research provides critical insights into how competition levels influence physical performance trends over time.

Genetic Predisposition to Hippocampal Atrophy and Risk of Amnestic Mild Cognitive Impairment and Alzheimer's Dementia.

Background: There is a paucity of evidence on the association between genetic propensity for hippocampal atrophy with cognitive outcomes. Therefore, we examined the relationship of the polygenic risk score for hippocampal atrophy (PRShp) with the incidence of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) as well as the rates of cognitive decline.

Methods: Participants were drawn from the population-based HELIAD cohort.

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.

Prescribing Psychostimulants for the Treatment of Stimulant Use Disorder: Navigating the Federal Legal Landscape.

Stimulant use disorder (StUD) is a rapidly growing concern in the United States, with escalating rates of death attributed to amphetamines and cocaine. No medications are currently approved for StUD treatment, leaving clinicians to navigate off-label medication options. Recent studies suggest that controlled prescription psychostimulants such as dextroamphetamine, methylphenidate, and modafinil are associated with reductions in self-reported stimulant use, craving, and depressive symptoms.

Tangential Versus Segmental Portomesenteric Venous Resection During Pancreatoduodenectomy for Pancreatic Cancer: An International Multicenter Cohort Study on Surgical and Oncological Outcome.

Objective: To investigate whether tangential versus segmental portomesenteric venous resection (PVR) impacts surgical and oncological outcome in patients undergoing pancreatoduodenectomy for pancreatic cancer with portomesenteric vein (PMV) involvement.

Summary Background Data: Current comparative studies on tangential versus segmental PVR as part of pancreatoduodenectomy for pancreatic cancer include all degrees of PMV involvement, including cases where tangential PVR may not be a feasible approach, limiting the clinical applicability.

Methods: International retrospective study in 10 centers from 5 countries, including all consecutive patients after pancreatoduodenectomy with PVR for pancreatic cancer with ≤180° PMV involvement on cross-sectional imaging at diagnosis (2014-2020).

Directed Acyclic Graphs in Decision-Analytic Modeling: Bridging Causal Inference and Effective Model Design in Medical Decision Making.

Our commentary proposes the application of directed acyclic graphs (DAGs) in the design of decision-analytic models, offering researchers a valuable and structured tool to enhance transparency and accuracy by bridging the gap between causal inference and model design in medical decision making.The practical examples in this article showcase the transformative effect DAGs can have on model structure, parameter selection, and the resulting conclusions on effectiveness and cost-effectiveness.This methodological article invites a broader conversation on decision-modeling choices grounded in causal assumptions.

Reproductive and Hormonal Factors and Thyroid Cancer Risk: Pooled Analysis of Prospective Cohort Studies in the Asia Cohort Consortium.

Given the female predominance of thyroid cancer (TC), particularly in the reproductive age range, female sex hormones have been proposed as an aetiology; however, previous epidemiological studies have shown conflicting results. We conducted a pooled analysis using individual data from 9 prospective cohorts in the Asia Cohort Consortium, to explore the association between 10 female reproductive and hormonal factors and TC risk. Using Cox proportional hazards models, cohort-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated and then pooled using a random-effects model.

Association Between Cardiometabolic Comorbidity Burden and Outcomes in Heart Failure.

Background: Cardiometabolic comorbidities such as obesity, diabetes, and hypertension are highly prevalent in heart failure (HF). We aimed to examine the association between severity of cardiometabolic comorbidities and hospitalization in patients with HF.

Methods: In a retrospective electronic health record-based cohort of adults 18 with HF, we categorized individuals based on the number of severe cardiometabolic comorbidities, including hypertension, diabetes, and obesity.

Alternative driver pathways in peripheral nerve sheath tumors - including DICER1 and/or KRAS alterations.

DICER1-associated sarcoma is an emerging entity, defined by either somatic or germline dicer 1, ribonuclease III (DICER1) mutations and sharing characteristic morphologic features irrespective of the site of origin. In addition to the DICER1 driver mutation, concurrent genomic alterations, including tumor protein 53 (TP53) inactivation and RAS pathway activation, are frequently detected. Tumors that morphologically resemble malignant peripheral nerve sheath tumor (MPNST) have rarely been reported among DICER1 sarcomas and often pose diagnostic challenges.

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.

Immunotherapy-based neoadjuvant treatment and complication rates after radical cystectomy.

Objective: To assess 30- and 90-day postoperative complication rates in patients who underwent robot-assisted radical cystectomy (RARC) after receiving novel immunotherapy-based neoadjuvant treatment.

Methods: A bi-centre analysis was conducted in patients who underwent RARC with intracorporeal urinary diversion and who received an immunotherapy-based neoadjuvant regimen between 2017 and 2023. Complications were classified using the Clavien-Dindo system.

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.

A Pilot Study of the Gut Microbiota in Spine Fusion Surgery Patients.

Background: The microbiome has been identified as a contributor to bone quality. As skeletal health is critical to success of orthopedic surgery, the gut microbiome may be a modifiable factor associated with postoperative outcomes. For spine fusion surgery in particular, bone formation and sufficient bone mineral density are essential for successful outcomes.

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.

Corrigendum: Combining Charlson comorbidity and VACS indices improves prognostic accuracy for all-cause mortality for patients with and without HIV in the Veterans Health Administration.

[This corrects the article DOI: 10.3389/fmed.2023.

Identify biological Alzheimer's disease using a novel nucleic acid-linked protein immunoassay.

Blood-based biomarkers have been revolutionizing the detection, diagnosis and screening of Alzheimer's disease. Specifically, phosphorylated-tau variants (p-tau, p-tau and p-tau) are promising biomarkers for identifying Alzheimer's disease pathology. Antibody-based assays such as single molecule arrays immunoassays are powerful tools to investigate pathological changes indicated by blood-based biomarkers and have been studied extensively in the Alzheimer's disease research field.

SARS-CoV-2 transmission dynamics in Mozambique and Zimbabwe during the first 3 years of the pandemic.

The 2019 emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid spread created a public health emergency of international concern. However, the impact of the pandemic in Sub-Saharan Africa, as documented in cases, hospitalizations and deaths, appears far lower than in the Americas, Europe and Asia. Characterization of the transmission dynamics is critical for understanding how SARS-CoV-2 spreads and the true scale of the pandemic.

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.

Arv1; a "Mover and Shaker" of Subcellular Lipids.

The composition of eukaryotic membranes reflects a varied but precise amalgam of lipids. The genetic underpinning of how such diversity is achieved or maintained is surprisingly obscure, despite its clear metabolic and pathophysiological impact. The Arv1 protein is represented in all eukaryotes and was initially identified in the model eukaryote as a candidate transporter of lipids from the endoplasmic reticulum.

Principal investigator gender and clinical trial success: analysis of over 3000 obstetrics and gynecology trials.

Background: In obstetrics and gynecology (OBGYN) research, gender disparities permeate through leadership, funding, promotion, mentorship, publishing, compensation, and publicity. Few studies have investigated OBGYN clinical trial leadership as it relates to investigator gender. Thus, we undertook an investigation of principal investigator (PI) gender and clinical trial success.