Targeting unique ligand binding domain structural features downregulates DKK1 in Y537S ESR1 mutant breast cancer cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable.

Protocol to study neuronal membrane proteasome function in mouse peripheral sensory neurons.

Neuronal membrane proteasomes (NMPs) are expressed on a subset of somatosensory dorsal root ganglion (DRG) neurons and influence mechanical and pain sensitivity. Here, we present a protocol for studying NMP function in mouse peripheral sensory neurons. We describe steps for procuring and culturing primary DRG neurons.

High Rate of Complications With Early Conversion Hip Arthroplasty Following Fracture Treatment.

Background: Conversion total hip arthroplasty (THA) is associated with higher rates of complications compared with primary THA, with prior surgical fixation of fractures in the ipsilateral hip shown to further increase these rates. There is a scarcity of literature on the effect of timing of conversion THA on complication rates. In this study, we evaluated early (≤6 months of index surgery) and late (>6 months of index surgery) conversion to THA following prior fixation of the proximal femur or acetabulum.

Airway associated inflammation in post-transplant cystic fibrosis patients as a predictor of chronic lung allograft dysfunction (CLAD).

Aims: In cystic fibrosis lung transplant recipients (LTRs), graft dysfunction due to acute infections, rejection or chronic lung allograft dysfunction (CLAD) is difficult to distinguish. Characterisation of the airway inflammatory milieu could help detect and prevent graft dysfunction. We speculated that an eosinophil or neutrophil-rich milieu is associated with higher risk of CLAD.

Immune Checkpoint Inhibitors in Glioblastoma IDHwt Treatment: A Systematic Review.

Purpose: A glioblastoma (GBM) is a primary brain tumor with significant unmet therapeutic needs. Immune checkpoint inhibitors (ICIs) have marked therapeutic benefits in many different cancers but have yet to show benefit for most GBM patients in phase III trials.

Methods: A systematic review querying ClinicalTrials.

Quality of Cancer Recurrence Data in the National Cancer Database: A Reappraisal of Reporting Readiness.

Background: This study evaluated the quality of cancer recurrence data in the National Cancer Database (NCDB) to determine if missingness and reporting consistency have improved enough to support national research.

Methods: This multi-methods study included NCDB analyses and a cancer registry staff survey. Trends in recurrence data missingness from 2004 to 2021 and multivariable analyses of factors associated with missingness from 2017 to 2021 were evaluated for 4,568,927 patients with non-metastatic cancer.

Air Hunger Far Exceeds Dyspnea Sense of Effort During Mechanical Ventilation and a Weaning Trial.

Rationale: No systematic investigation into dyspnea in patients receiving prolonged ventilation (>21 days) after recovering from critical-illness has been published.

Objectives: To determine magnitude, nature and pathophysiological basis of dyspnea during an unassisted-breathing trial in prolonged-ventilation patients.

Methods: Dyspnea intensity and descriptor selection were investigated in 27 prolonged-ventilation patients during a 60-min unassisted-breathing trial.

Self-Reducible Painless and Recurrent Prosthetic Hip Dislocation: A Case Study.

Prosthetic hip dislocations following total hip arthroplasty can significantly impact patient quality of life and functional capabilities. Early dislocations typically occur within the first three months post-surgery, while delayed dislocations arise after three months. Notably, patients may experience implant instability and dislocation for years, even decades, after the initial procedure due to a variety of underlying issues.

Case Reports in Education: A Virtual Orthopaedic Surgery Summit Enhances Medical Student Confidence in Preparedness for Orthopaedic Surgery Subinternships.

Introduction: Medical school curricula offer limited exposure to orthopaedic surgery, and few national initiatives aim to prepare students for orthopaedic surgery subinternships, which are critical for success in matching into orthopaedic residency. In this study, we evaluated the effectiveness of a single-day virtual "Subinternship Summit" for medical students in 2 key areas: 1) enhancing participants' confidence in their preparedness for orthopaedic subinternship rotations and 2) mitigating any disparities based on student characteristics, such as race/ethnicity, gender, or whether or not the student's school is affiliated with a "home" orthopaedic program.

Methods: In March 2024, a single-day national virtual summit was held, featuring panels on topics relevant to performance during orthopaedic subinternships.

The Relationship Between Travel Distance for Treatment and Outcomes in Patients Undergoing Radiation Therapy: A Systematic Review.

Purpose: Although recent technological advances in radiation therapy have significantly improved treatment outcomes, the global distribution of radiation therapy is unbalanced, making access especially challenging for patients in rural or low-resource settings because of travel burden. This systematic review aimed to explore the impact of geographic distance to treatment facilities on survival, as well as other treatment outcomes, among patients undergoing radiation therapy.

Methods And Materials: A search of four databases (PubMed, Embase, CINAHL, and Web of Science) was performed.

An optimized Langendorff-free method for isolation and characterization of primary adult cardiomyocytes.

Isolation of adult mouse cardiomyocytes is an essential technique for advancing our understanding of cardiac physiology and pathology, and for developing therapeutic strategies to improve cardiac health. Traditionally, cardiomyocytes are isolated from adult mouse hearts using the Langendorff perfusion method in which the heart is excised, cannulated, and retrogradely perfused through the aorta. While this method is highly effective for isolating cardiomyocytes, it requires specialized equipment and technical expertise.

Complications following total knee arthroplasty in patients with prior extensor mechanism dysfunction: A retrospective review.

Background: Extensor mechanism disruption following total knee arthroplasty (TKA) is a rare, yet serious complication. While previous patellar abnormalities are a theoretical risk factor for this complication, there is a scarcity of literature describing the impact of prior extensor mechanism dysfunction (EMD) on this and other complications following TKA. In this study, we describe our institutional experience with complications following TKA after EMD.

Glycemic laboratory values are associated with increased length of stay and 90-day revision risk following surgical management of adult spinal deformity.

Background Context: Diabetes mellitus (DM) is a common comorbidity among patients undergoing spinal fusion for adult spinal deformity (ASD) surgery. An elevated Hemoglobin A1c (HbA1c) and elevated postoperative glucose have been shown to increase the risk of complications following spine and other orthopedic surgeries; however, data is limited for ASD.

Purpose: To investigate glycemic control and ASD surgery to inform surgical decision making, medical optimization, and patient education.

Who breaks their hip? A decade of traumatic hip fracture data.

Aims & Objectives: Hip fractures lead to significant morbidity, mortality, and healthcare costs, particularly in elderly populations. Understanding the mechanisms underlying these fractures is crucial for developing targeted prevention strategies and counseling patients.

Methods: The National Electronic Injury Surveillance System (NEISS) was utilized to identify a cohort of 25,068 hip fractures from 2013 to 2022.

Outcomes and Cost-Effectiveness of an EHR-Embedded AI Screener for Identifying Hospitalized Adults at Risk for Opioid Use Disorder.

Unlabelled: Hospitalized adults with opioid use disorder (OUD) are at high risk for adverse events and rehospitalizations. This pre-post quasi-experimental study evaluated whether an AI-driven OUD screener embedded in the electronic health record (EHR) was non-inferior to usual care in identifying patients for Addiction Medicine consults, aiming to provide a similarly effective but more scalable alternative to human-led ad hoc consultations. The AI screener analyzed EHR notes in real-time with a convolutional neural network to identify patients at risk and recommend consultation.

Preterm Birth in African American Women: A Multi-Omic Pilot Study in Early Pregnancy.

Preterm birth (PTB; <37 weeks completed gestation) is a devastating problem affecting over 13 million live births worldwide. In the U.S.