Real-World Treatment Patterns and Clinical Outcomes in Patients With Multiple Myeloma Previously Treated With Lenalidomide and an Anti-CD38 Monoclonal Antibody.

Background: This analysis explored real-world characteristics, treatment patterns and clinical outcomes in patients with relapsed or refractory multiple myeloma (RRMM) previously treated with lenalidomide and an anti-CD38 monoclonal antibody (mAb) and requiring subsequent treatment.

Materials And Methods: The PREAMBLE and Connect MM prospective registries of patients with multiple myeloma (MM), and the US nationwide Flatiron Health electronic health record-derived de-identified database were analysed. MM-specific treatment patterns (prior/index therapies) and outcomes (progression-free survival [PFS]/overall survival [OS]) were assessed.

A Mutant Complement Factor H (W1183R) Enhances Proteolytic Cleavage of von Willebrand Factor by ADAMTS13 Under Shear.

Background: A loss-of-functional mutation (W1183R) in human complement factor H (CFH) is associated with complement-associated hemolytic uremic syndrome; mice carrying a similar mutation (W1206R) in CFH also develop thrombotic microangiopathy but its plasma von Willebrand factor (VWF) multimer sizes were dramatically reduced. The mechanism underlying such a dramatic change in plasma VWF multimer distribution in these mice is not fully understood.

Objective And Methods: To determine the VWF and CFH interaction and how CFH proteins affect VWF multimer distribution, we employed recombinant protein expression, purification, and various biochemical and biophysical tools.

Optimized mammalian expression system for the ubiquitin E3 ligase E6AP/UBE3A.

E6AP/UBE3A is the founding member of the HECT (Homologous to the E6-AP Carboxyl Terminus) ubiquitin E3 ligase family, which add ubiquitin post-translationally to protein substrates. E6AP has been structurally defined in complex with human papillomavirus (HPV) oncoprotein E6 and its gain-of-function substrate tumor suppressor p53; however, there is currently no report of E6AP being expressed and purified from mammalian cells, as studies to date have isolated E6AP from E. coli or insect cells.

Shoulder and Elbow Surgery Fellowship Applicants with Greater Research Productivity During Residency are Ranked Higher by Fellowship Programs.

Introduction: Shoulder and elbow surgery fellowships in the United States are recognized for their academic emphasis, yet the correlation between an applicant's research productivity and fellowship match results remains unclear. This study (1) analyzed temporal trends in research productivity among matched fellowship applicants, (2) evaluated the influence of quantity of publications and first authorships on match positions, and (3) investigated program variations in research productivity.

Methods: This is a retrospective analysis of data from the San Francisco (SF) Match Database for shoulder and elbow surgery applicants matched between 2017 and 2024.

Default mode network functional connectivity as a transdiagnostic biomarker of cognitive function.

The default mode network (DMN) is intricately linked with processes such as self-referential thinking, episodic memory recall, goal-directed cognition, self-projection, and theory of mind. Over recent years, there has been a surge in examining its functional connectivity, particularly its relationship with frontoparietal networks (FPN) involved in top-down attention, executive function, and cognitive control. The fluidity in switching between these internal and external modes of processing-highlighted by anti-correlated functional connectivity-has been proposed as an indicator of cognitive health.

Associations of maternal per- and polyfluoroalkyl substance plasma concentrations during pregnancy with offspring polycystic ovary syndrome and related characteristics in Project Viva.

Background: Per- and polyfluoroalkyl substances (PFAS) may impact ovarian folliculogenesis and steroidogenesis, but whether prenatal exposure may impact offspring reproductive health is unknown. This study examines the extent to which maternal PFAS plasma concentrations during pregnancy are associated with polycystic ovary syndrome (PCOS) and related characteristics in female offspring.

Methods: We studied 322 mother-daughter pairs in Project Viva, a Boston-area longitudinal pre-birth cohort enrolled 1999-2002.

Suture Anchor Fixation of the Pediatric Posteromedial and Posterolateral Menisco-Tibial Ligament Complex Matches or Exceeds Native Tissue Strength: A Cadaveric Study.

Objectives: To compare the biomechanical strength and stiffness of the native posteromedial and posterolateral meniscotibial ligament complex (MTLC) to suture anchor repair of the MTLC.

Methods: Biomechanical testing was performed on 24 fresh-frozen pediatric human knees. Four conditions were tested: native posteromedial MTLC (n=14), native posterolateral MTLC (n=14), posteromedial MTLC repair (n=5), and posterolateral MTLC repair (n=5).

Risk of SARS-CoV-2 infection and adverse outcomes among vaccinated patients with tuberculosis.

Objectives: Limited data are available to assess breakthrough SARS-CoV-2 infections, medical utilization, and mortality in patients with tuberculosis (TB). The aim of this study was to examine the risk of COVID-19 and severe outcomes in patients with TB between January 2020 and March 2022.

Study Design: US electronic medical records were used to identify TB and non-TB patients who completed the primary series of vaccination and had no prior COVID-19.

Neurogenic inflammation and itch in barrier tissues.

Once regarded as distinct systems, the nervous system and the immune system are now recognized for their complex interactions within the barrier tissues. The neuroimmune circuitry comprises a dual-network system that detects external and internal disturbances, providing critical information to tailor a context-specific response to various threats to tissue integrity, such as wounding or exposure to noxious and harmful stimuli like pathogens, toxins, or allergens. Using the skin as an example of a barrier tissue with the polarized sensory neuronal responses of itch and pain, we explore the molecular pathways driving neuronal activation and the effects of this activation on the immune response.

Immunology in corneal transplantation-From homeostasis to graft rejection.

Immunology depends on maintaining a delicate balance within the human body, and disruptions can result in conditions such as autoimmune diseases, immunodeficiencies, and hypersensitivity reactions. This balance is especially crucial in transplantation immunology, where one of the primary challenges is preventing graft rejection. Such rejection can lead to organ failure, increased patient mortality, and higher healthcare costs due to the limited availability of donor tissues relative to patient needs.

Rising cardiovascular mortality among obstructive sleep apnea patients: United States epidemiological trends (1999-2019).

Background: Obstructive sleep apnea (OSA) prevalence has risen significantly, affecting millions globally and posing a major healthcare burden. OSA is strongly associated with cardiovascular diseases (CVD) such as heart failure, stroke, and ischemic heart disease. However, trends in CVD-related mortality among individuals with OSA remain underexplored.

Sewing the SEAMs: Surgical Education in the Art Museum.

Objective: The field of surgery is highly visual and technical. Yet, there is a paucity of data evaluating how a mandatory visual arts-based workshop may benefit surgical trainees. We report upon the feasibility of and short-term outcomes of a novel, visual art-based curriculum for surgery residents.

Disparities in cervical cancer elimination timeframes in the United States: a comparative modeling study.

Population-level estimates in timeframes for reaching cervical cancer (CC) elimination (ie, <4 cases per 100,000 women) in the United States may mask potential disparities in achieving elimination among sub-populations. We used three independent Cancer Intervention and Surveillance Modeling Network (CISNET) models to estimate differences in the time to CC elimination across seven strata of correlated screening and human papillomavirus vaccination uptake, based on national survey data. Compared to the average population, elimination was achieved ≥22 years earlier for the high-uptake strata and ≥27 years later for the most extreme low-uptake strata.

The Last Decade in Cardiac Amyloidosis: Advances in Understanding Pathophysiology, Diagnosis and Quantification, Prognosis, Treatment Strategies, and Monitoring Response.

Cardiac amyloidosis represents a unique disease process characterized by amyloid fibril deposition within the myocardial extracellular space. Advances in multimodality cardiac imaging enable accurate diagnosis and facilitate prompt initiation of disease-modifying therapies. Furthermore, rapid advances in multimodality imaging have enriched understanding of the underlying pathogenesis, enhanced prognostication, and resulted in the development of imaging-based markers that reflect the amyloid burden, which is of increasing importance when assessing the response to treatment.

Defining the Optimal Dose for 3-Dimensional Conformal Accelerated Partial Breast Irradiation: 15-Year Follow-Up of a Dose-Escalation Trial.

Purpose: Randomized trials have demonstrated similar local tumor control in patients treated with accelerated partial-breast irradiation (APBI) compared with whole-breast irradiation. However, the optimal APBI dose for maximizing tumor control and minimizing toxicity is uncertain.

Methods And Materials: We enrolled patients ≥18 years of age with grade 1 or 2 ductal carcinoma in situ or stage I invasive breast cancer and resection margins ≥2 mm between 2003 and 2011 to a sequential dose-escalation trial using 3-dimensional conformal external beam APBI giving twice daily 4 Gy fractions with total doses of 32 Gy, 36 Gy, and 40 Gy.

Growth Differentiation Factor-15 Is Associated With Congestion-Related Anorexia and Weight Loss in Advanced Heart Failure.

Background: Growth differentiation factor (GDF)-15 is a pleiotropic cytokine that is associated with appetite-suppressing effects and weight loss in patients with malignancy.

Objectives: This study aims to investigate the relationships between GDF-15 levels, anorexia, cachexia, and clinical outcomes in patients with advanced heart failure with reduced ejection fraction (HFrEF).

Methods: In this observational, retrospective analysis, a total of 344 patients with advanced HFrEF (age 58 ± 10 years, 85% male, 67% NYHA functional class III), underwent clinical and echocardiographic examination, body composition evaluation by skinfolds and dual-energy x-ray absorptiometry, circulating metabolite assessment, Minnesota Living with Heart Failure Questionnaire, and right heart catheterization.

Digital Solutions for the Optimization of Pharmacologic Therapy for Heart Failure.

Data from large-scale, randomized, controlled trials demonstrate that contemporary treatments for heart failure (HF) can substantially improve morbidity and mortality. Despite this, observed outcomes for patients living with HF are poor, and they have not improved over time. The are many potential reasons for this important problem, but inadequate use of optimal medical therapy for patients with HF, an important component of guideline-directed medical therapy, in routine practice is a principal and modifiable contributor.

Variations in Revascularization Strategies for Chronic Limb-Threatening Ischemia: A Nationwide Analysis of Medicare Beneficiaries.

Background: Recent data support both surgical-first and endovascular-first revascularization approaches for chronic limb-threatening ischemia (CLTI), but hospital-based practices are poorly described.

Objectives: This aim of this study was to characterize contemporary variations and outcomes associated with each strategy among U.S.

Inpatient Hospitalizations for COVID-19 Among Patients With Prader-Willi Syndrome: A National Inpatient Sample Analysis.

Prader-Willi syndrome (PWS) is a genetic disorder associated with baseline respiratory impairment caused by multiple contributing etiologies. While this may be expected to increase the risk of severe COVID-19 infections in PWS patients, survey studies have suggested paradoxically low disease severity. To better characterize the course of COVID-19 infection in patients with PWS, this study analyses the outcomes of hospitalizations for COVID-19 among patients with and without PWS.