Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma.

The cytokine IL-18 has immunostimulatory effects but is negatively regulated by a secreted binding protein, IL-18BP, that limits IL-18's anticancer efficacy. A decoy-resistant form of IL-18 (DR-18) that avoids sequestration by IL-18BP while maintaining its immunostimulatory potential has recently been developed. Here, we investigated the therapeutic potential of DR-18 in renal cell carcinoma (RCC).

TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3.

Purpose: Immune checkpoint inhibitors have revolutionized the treatment of renal cell carcinoma (RCC), but many patients do not respond to therapy and the majority develop resistant disease over time. Thus, there is increasing need for alternative immunomodulating agents. The co-inhibitory molecule T-cell immunoglobulin and ITIM domain (TIGIT) may play a role in resistance to approved immune checkpoint inhibitors and is being investigated as a potential therapeutic target.

GP100 expression is variable in intensity in melanoma.

Drugs or cellular products that bind to gp100 are being investigated for treatment of cutaneous melanoma. The relative specificity of gp100 expression in melanocytes makes it an attractive target to harness for therapeutic intent. For example, Tebentafusp, a bispecific gp100 peptide-HLA-directed CD3 T cell engager, has generated significant enthusiasm in recent years due to its success in improving outcomes for uveal melanoma and is being studied in cutaneous melanoma.

Melanocortin-1 Receptor Expression as a Marker of Progression in Melanoma.

Purpose: Melanocortin-1 receptor (MC1R) plays a critical role in human pigmentation and DNA repair mechanisms. MC1R-targeting agents are being investigated in clinical trials in patients with melanoma, yet large studies investigating the rate and degree of MC1R expression in primary and metastatic human melanoma tissue are lacking.

Methods: Using tissue microarrays containing three large cohorts of 225 cases of benign nevi, 189 with primary melanoma, and 271 with metastatic melanoma, we applied quantitative immunofluorescence and immunohistochemistry to comprehensively study MC1R protein expression.

A Comparative Review of Oral Board Delivery Across Procedural Disciplines.

Objective: Despite its ubiquity in the certification process among surgical specialties, there is little data regarding oral board delivery across various procedural fields. In this study we sought to determine the specifics of oral board exam administration across surgical disciplines with the goal of highlighting common practices, differences, and areas of innovation. This comparative analysis might further serve to identify unifying principles that undergird the oral board examination process across specialties.

Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma.

Background: Desmoplastic melanoma (DM) is a rare melanoma subtype characterized by dense fibrous stroma, a propensity for local recurrence, and a high response rate to programmed cell death protein 1 (PD-1) blockade. Occult sentinel lymph node positivity is significantly lower in both pure and mixed DM than in conventional melanoma, underscoring the need for better prognostic biomarkers to inform therapeutic strategies.

Methods: We assembled a tissue microarray comprising various cores of tumor, stroma, and lymphoid aggregates from 45 patients with histologically confirmed DM diagnosed between 1989 and 2018.

Assessing the one-month mortality impact of civilian-setting prehospital transfusion: A systematic review and meta-analysis.

Background: Based on convincing evidence for outcomes improvement in the military setting, the past decade has seen evaluation of prehospital transfusion (PHT) in the civilian emergency medical services (EMS) setting. Evidence synthesis has been challenging, due to study design variation with respect to both exposure (type of blood product administered) and outcome (endpoint definitions and timing). The goal of the current meta-analysis was to execute an overarching assessment of all civilian-arena randomized controlled trial (RCT) evidence focusing on administration of blood products compared to control of no blood products.

Applications of Artificial Intelligence in Helicopter Emergency Medical Services: A Scoping Review.

Objective: Recent systematic reviews of acute care medicine applications of artificial intelligence (AI) have focused on hospital and general prehospital uses. The purpose of this scoping review was to identify and describe the literature on AI use with a focus on applications in helicopter emergency medical services (HEMS).

Methods: A literature search was performed with specific inclusion and exclusion criteria.

Nation-Wide Variation in Presence of Legislation or Protocols for EMS Care of Operational Canines.

Background & Aims: Deployment of law enforcement operational canines (OpK9s) risks injuries to the animals. This study's aim was to assess the current status of states' OpK9 (veterinary Emergency Medical Services [VEMS]) laws and care protocols within the United States.

Methods: Cross-sectional standardized review of state laws/regulations and OpK9 VEMS treatment protocols was undertaken.

Update on Biomarkers in Renal Cell Carcinoma.

Immune checkpoint inhibitors have significantly transformed the treatment paradigm for metastatic renal cell carcinoma (RCC), offering prolonged overall survival and achieving remarkable deep and durable responses. However, given the multiple ICI-containing, standard-of-care regimens approved for RCC, identifying biomarkers that predict therapeutic response and resistance is of critical importance. Although tumor-intrinsic features such as pathological characteristics, genomic alterations, and transcriptional signatures have been extensively investigated, they have yet to provide definitive, robust predictive biomarkers.

A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better.

Background: Stimulating inflammatory tumor associated macrophages can overcome resistance to PD-(L)1 blockade. We previously conducted a phase I trial of cabiralizumab (anti-CSF1R), sotigalimab (CD40-agonist) and nivolumab. Our current purpose was to study the activity and cellular effects of this three-drug regimen in anti-PD-1-resistant melanoma.

Melanocortin 1 receptor (MC1R) expression as a marker of progression in melanoma.

Melanocortin-1 receptor (MC1R) plays a critical role in human pigmentation and DNA repair mechanisms. MC1R-targeting agents are being investigated in clinical trials in melanoma patients, yet large studies investigating the rate and degree of MC1R expression in primary and metastatic human melanoma tissue are lacking. Using tissue microarrays containing three large cohorts of 225 cases of benign nevi, 189 with primary melanoma, and 271 with metastatic melanoma, we applied quantitative immunofluorescence and immunohistochemistry to comprehensively study MC1R protein expression.

Survivorship With Incrementally Faster Times to Primary Percutaneous Coronary Intervention (SWIFT-PPCI): A Systematic Review and Meta-Analysis.

In the United States, there are approximately 750,000 ST-elevation myocardial infarction cases each year. Streamlined care and rapid delivery for primary percutaneous coronary intervention (PPCI) is associated with improved survival. This systematic review and meta-analysis aimed to generate a practical estimate of mortality savings for every notional 30-minute decrease in the time to achieving PPCI.

First-Pass Success of Intubations Using Video Versus Direct Laryngoscopy in Children With Limited Neck Mobility.

Objective: It is not clear whether video laryngoscopy (VL) is associated with a higher first-pass success rate in pediatric patients with limited neck mobility when compared with direct laryngoscopy (DL). We sought to determine the association between the laryngoscopy method and first-pass success.

Methods: In this retrospective cohort study, we examined intubation data extracted from 2 prospectively collected, multicenter, airway management safety databases (National Emergency Airway Registry and the National Emergency Airway Registry for children), obtained during the years 2013-2018 in the emergency department.

Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases.

Background: The tumor microenvironment (TME) contributes to cancer progression and treatment response to therapy, including in renal cell carcinoma (RCC). Prior profiling studies, including single-cell transcriptomics, often involve limited sample sizes and lack spatial orientation. The TME of RCC brain metastases, a major cause of morbidity, also remains largely uncharacterized.

Perceived Barriers Among Underrepresented and Historically Marginalized Medical Students Pursuing a Career in Urology.

Objective: To assess perceived barriers to pursuing urology among medical students and to determine if marginalized groups identified greater challenges to entry.

Methods: The Deans of all New York medical schools were asked to disseminate a survey to their students. The survey collected demographic information to identify underrepresented minorities, students of low socioeconomic background, and lesbian, gay, bisexual, transgender, queer, intersex, and asexual individuals.

Longitudinal Changes in the Operative Experience for Junior Urology Residents.

Objective: To evaluate longitudinal trends in surgical case volume among junior urology residents. There is growing perception that urology residents are not prepared for independent practice, which may be linked to decreased exposure to major cases early in residency.

Methods: Retrospective review of deidentified case logs from urology residency graduates from 12 academic medical centers in the United States from 2010 to 2017.