A Phase 2 Study of Sitravatinib in Combination with Nivolumab in Patients with Advanced or Metastatic Urothelial Carcinoma.

Background And Objective: Checkpoint inhibitor therapy (CPI) has demonstrated survival benefits in urothelial carcinoma (UC); however, not all patients benefit from CPI due to resistance. Combining sitravatinib, a multitargeted receptor tyrosine kinase inhibitor of TYRO3, AXL, and MERTK (TAM) receptors and VEGFR2, with CPI may improve antitumor responses. Our objective was to assess the efficacy and safety of sitravatinib plus nivolumab in patients with advanced/metastatic UC.

International Pooled Analysis of Leisure-Time Physical Activity and Premenopausal Breast Cancer in Women From 19 Cohorts.

Purpose: There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer.

Methods: We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer.

Normative Modeling of Brain Morphometry Across the Lifespan Using CentileBrain: Algorithm Benchmarking and Model Optimization.

We present an empirically benchmarked framework for sex-specific normative modeling of brain morphometry that can inform about the biological and behavioral significance of deviations from typical age-related neuroanatomical changes and support future study designs. This framework was developed using regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The Multivariate Factorial Polynomial Regression (MFPR) emerged as the preferred algorithm optimized using nonlinear polynomials for age and linear effects of global measures as covariates.

Lasofoxifene versus fulvestrant for ER+/HER2- metastatic breast cancer with an ESR1 mutation: results from the randomized, phase II ELAINE 1 trial.

Background: Acquired estrogen receptor alpha (ER/ESR1) mutations commonly cause endocrine resistance in ER+ metastatic breast cancer (mBC). Lasofoxifene, a novel selective ER modulator, stabilizes an antagonist conformation of wild-type and ESR1-mutated ER-ligand binding domains, and has antitumor activity in ESR1-mutated xenografts.

Patients And Methods: In this open-label, randomized, phase II, multicenter, ELAINE 1 study (NCT03781063), we randomized women with ESR1-mutated, ER+/human epidermal growth factor receptor 2 negative (HER2-) mBC that had progressed on an aromatase inhibitor (AI) plus a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) to oral lasofoxifene 5 mg daily or IM fulvestrant 500 mg (days 1, 15, and 29, and then every 4 weeks) until disease progression/toxicity.

Engaging Underrepresented Youth: Remote Transition of the Health Career Collaborative Program.

Introduction: Pipeline programs can help increase diversity in health care by engaging underrepresented minority groups to pursue higher education and training in medical fields. Here we describe the implementation of Health Career Collaborative, a pipeline program designed to connect high school students with health care professionals, and the transition to remote delivery of the curriculum.

Methods: This study is a retrospective, descriptive observational study where the baseline characteristics of participating students were evaluated via preparticipation surveys.

Cerebral microdialysis demonstrates improvements in brain metabolism with cerebrospinal fluid diversion in spontaneous intracerebral hemorrhage.

Background: Cerebral microdialysis (CMD) is an FDA-approved multimodal invasive monitoring technique that provides local brain metabolism measurements through continuous interstitial brain fluid sampling at the bedside. The past applications in traumatic brain injury and subarachnoid hemorrhage show that acute brain injury (ABI) can lead to a metabolic crisis reflected by changes in cerebral glucose, pyruvate, and lactate. However, limited literature exists on CMD in spontaneous intracerebral hemorrhage (ICH).

Gain-of-function and loss-of-function variants in GRIA3 lead to distinct neurodevelopmental phenotypes.

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) mediate fast excitatory neurotransmission in the brain. AMPARs form by homo- or heteromeric assembly of subunits encoded by the GRIA1-GRIA4 genes, of which only GRIA3 is X-chromosomal. Increasing numbers of GRIA3 missense variants are reported in patients with neurodevelopmental disorders (NDD), but only a few have been examined functionally.

A multi-institutional study from the US ROPE consortium examining factors associated with endocrine surgery exposure for general surgery residents.

Background: Prior analyses of general surgery resident case logs have indicated a decline in the number of endocrine procedures performed during residency. This study aimed to identify factors contributing to the endocrine operative experience of general surgery residents and compare those who matched in endocrine surgery fellowship with those who did not.

Methods: We analyzed the case log data of graduates from 18 general surgery residency programs in the US Resident Operative Experience Consortium over an 11-year period.

Biomechanics in the onset and severity of spondyloarthritis: a force to be reckoned with.

Increasing evidence suggests that there is a pivotal role for physical force (mechanotransduction) in the initiation and/or the perpetuation of spondyloarthritis; the review contained herein examines that evidence. Furthermore, we know that damage and inflammation can limit spinal mobility, but is there a cycle created by altered spinal mobility leading to additional damage and inflammation?Over the past several years, mechanotransduction, the mechanism by which mechanical perturbation influences gene expression and cellular behaviour, has recently gained popularity because of emerging data from both animal models and human studies of the pathogenesis of ankylosing spondylitis (AS). In this review, we provide evidence towards an appreciation of the unsolved paradigm of how biomechanical forces may play a role in the initiation and propagation of AS.

Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastoma.

Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumors from 465 patients, we identify circular ecDNA in 82 patients (18%). Patients with ecDNA-positive medulloblastoma were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis.

The potential impact of periodontitis on cerebral small vessel disease.

Cerebral small vessel disease (CSVD) is a term used to describe abnormalities in the intracranial microvasculature affecting small arteries, arterioles, capillaries, and venules. The etiology of these conditions is not fully understood but inflammation appears to play a significant role. Periodontal diseases have been associated with conditions such as stroke and dementia, which are clinical consequences of CSVD.

The Incidence of Urgent Tube Shunt Surgery for Diabetic Neovascular Glaucoma at a Tertiary Academic Medical Center.

Background: Diabetic neovascular glaucoma is a secondary glaucoma that may require immediate correction of elevated intraocular pressure to control pain and protect the optic nerve. While there is a seasonal trend to glucose levels, it is unknown if a seasonal trend exists for diabetic neovascular glaucoma.

Objective: This study evaluates the incidence of urgent glaucoma tube shunt implantation in diabetic neovascular glaucoma in a tertiary academic referral center in Southern California.

9-1-1 Activations from Ambulatory Care Centers: A Sicker Pediatric Population.

Background: Pediatric patients transferred by Emergency Medical Services (EMS) from urgent care (UC) and office-based physician practices to the emergency department (ED) following activation of the 9-1-1 EMS system are an under-studied population with scarce literature regarding outcomes for these children. The objectives of this study were to describe this population, explore EMS level-of-care transport decisions, and examine ED outcomes.

Methods: This was a retrospective review of patients zero to <15 years of age transported by EMS from UC and office-based physician practices to the ED of two pediatric receiving centers from January 2017 through December 2019.

When is it safe to start venous thromboembolism prophylaxis after blunt solid organ injury? A prospective American Association for the Surgery of Trauma multi-institutional trial.

Background: The optimal time to initiate venous thromboembolism (VTE) chemoprophylaxis (VTEp) after blunt solid organ injury remains controversial, as VTE mitigation must be balanced against bleeding promulgation. Evidence from primarily small, retrospective, single-center work suggests that VTEp ≤48 hours is safe and effective. This study was undertaken to validate this clinical practice.

The 2023 Model Core Content of Disaster Medicine.

Introduction: Disaster Medicine (DM) is the clinical specialty whose expertise includes the care and management of patients and populations outside conventional care protocols. While traditional standards of care assume the availability of adequate resources, DM practitioners operate in situations where resources are not adequate, necessitating a modification in practice. While prior academic efforts have succeeded in developing a list of core disaster competencies for emergency medicine residency programs, international fellowships, and affiliated health care providers, no official standardized curriculum or consensus has yet been published to date for DM fellowship programs based in the United States.

'Chip'-ing away at morphogenesis - application of organ-on-chip technologies to study tissue morphogenesis.

Emergent cell behaviors that drive tissue morphogenesis are the integrated product of instructions from gene regulatory networks, mechanics and signals from the local tissue microenvironment. How these discrete inputs intersect to coordinate diverse morphogenic events is a critical area of interest. Organ-on-chip technology has revolutionized the ability to construct and manipulate miniaturized human tissues with organotypic three-dimensional architectures in vitro.

Misdiagnosis of amyotrophic lateral sclerosis in clinical practice in Europe and the USA: a patient chart review and physician survey.

Objective: Delays in amyotrophic lateral sclerosis (ALS) diagnosis can result in compromised disease management and unnecessary costs. We examined the extent of ALS misdiagnosis in the US and Europe.

Methods: Data were collected via the Adelphi ALS Disease Specific Programme™, a cross-sectional survey of physicians and a medical chart review of their consulting patients with ALS in France, Germany, Italy, Spain, the UK (EU5), and the US.

A core outcome set for appendicitis: A consensus approach utilizing modified Delphi methodology.

Background: Appendicitis is one of the most common pathologies encountered by general and acute care surgeons. The current literature is inconsistent, as it is fraught with outcome heterogeneity, especially in the area of nonoperative management. We sought to develop a core outcome set (COS) for future appendicitis studies to facilitate outcome standardization and future data pooling.

Taxane-Based Chemotherapy Is Effective in Metastatic Appendiceal Adenocarcinoma.

Appendiceal cancer is a rare, orphan disease with no therapies currently approved by the FDA for its treatment. Given the limited data regarding drug efficacy, these tumors have historically been treated with chemotherapy designed for colon cancer. However, an overwhelming body of molecular data has demonstrated that appendiceal adenocarcinoma is a distinct entity with key molecular differences from colon cancer, notably rare APC mutation.

Assessment of cardiopulmonary point-of-care ultrasound objective structured clinical examinations in graduating anesthesiology residents across multiple residency programs.

Study Objective: To implement and assess a cardiopulmonary point-of-care ultrasound (POCUS) objective structured clinical examination (OSCE) in a large cohort of graduating anesthesia residents.

Design: Observational cohort study.

Setting: University-affiliated hospitals.

Assessing past versus present severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection: A survey of criteria for discontinuing precautions in asymptomatic patients testing positive on admission.

Infection prevention program leaders report frequent use of criteria to distinguish recently recovered coronavirus disease 2019 (COVID-19) cases from actively infectious cases when incidentally positive asymptomatic patients were identified on routine severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing. Guidance on appropriate interpretation of high-sensitivity molecular tests can prevent harm from unnecessary precautions that delay admission and impede medical care.