Citations

Importance Classifying disease based on underlying pathobiology rather than clinical phenotype has implications for the development of biomarkers and therapy development. Observations Transactive response DNA-binding protein 43 kDa (TDP-43) pathology is observed across a range of clinically defined neurodegenerative disorders including limbic predominant age-related encephalopathy (LATE), most cases of amyotrophic lateral sclerosis (ALS), inclusion body myositis, multisystem proteinopathy, and approximately half the cases of frontotemporal dementia (FTD). Despite this shared biology, the current nosology for these neurodegenerative disorders is based on their distinct clinical phenotypes. An alternative approach recognizes the central role of TDP-43 pathology in disease pathogenesis, reserving the use of clinical terms like ALS, FTD, or LATE to describe phenotypic manifestations of underlying pathobiology. This approach also recognizes the converging biomarker and neuropathological data indicating that pathology begins presymptomatically, before the overt clinical manifestations of disease appear. Conclusions and Relevance In proposing a pathobiological definition of disease, the goal is to provide a road map for developing biomarkers that accurately reflect the underlying pathobiology of disease and for advancing therapeutic candidates that effectively target fundamental disease mechanisms.

Objective Epidemiologic estimates for age of systemic lupus erythematosus (SLE) diagnosis are limited, particularly for men and racial and ethnic subpopulations in the United States. Leveraging the Centers for Disease Control and Prevention (CDC) National Lupus Registry network of population‐based SLE registries, meta‐analyses were performed estimating age‐specific incidence of SLE by sex, race, and ethnicity. Methods The CDC network of SLE registries includes five state‐based registries, plus a sixth Indian Health Service registry. Incidence periods spanned calendar years 2002‐2018. Registries provided age‐specific incidence of SLE, fulfilling the American College of Rheumatology (ACR) SLE classification criteria, per 100,000 person‐years, stratified by sex, race, and ethnicity for the meta‐analyses. Results Incidence rates among women were highest for those aged 30‐39 (12.7, 95%CI: 9.5‐16.8), while rates among men were highest for those aged 60‐69 (2.1, 95%CI: 1.3‐3.4). Black women aged 20‐39 had the highest SLE incidence rates (23.6, 95%CI: 20.7‐26.8). Among women diagnosed with SLE before age 20, incidence was highest among Asian (6.5, 95%CI: 2.8‐15.2) individuals. Among women diagnosed with SLE after age 60, incidence was highest among American Indian/Alaska Native (9.4, 95%CI: 3.4‐15.4) individuals. Weighted percentages show 10.0% of those with SLE were diagnosed before age 20, while 15.1% were diagnosed after age 60. The largest proportion of individuals with SLE, 22.1%, were diagnosed between 30‐39 years. Conclusions This study provides comprehensive sex‐ and race‐specific estimates of age at SLE diagnosis. The substantial later in life SLE incidence among men and disease burden in pediatric and older populations should raise awareness in considering SLE in the differential diagnosis in previously underrecognized groups.

Background: Several breast cancer (BC) risk prediction models have been developed to provide personal risk assessments. Though individually validated, their performance has not been systematically evaluated across a wide range of populations or ages. Methods: We harmonized individual-level baseline questionnaire data and incident BC diagnoses from 21 cohorts from North America, Europe, and Australia participating in the Breast Cancer Risk Prediction Project. Five-year absolute risk of invasive BC was estimated for five established risk prediction models using classical risk factors only. Discrimination was evaluated by area under the curve (AUC). Calibration was assessed using average and risk-decile specific expected to observed (E/O) ratios. Performance metrics were meta-analyzed across cohorts and models. Metaregression tested associations between cohort characteristics and performance metrics. Results: This analysis included 1,595,977 women aged 20-75 years, enrolled in studies between 1976-2015, with 19,062 (1.2%) invasive BC cases ascertained within 5 years from exposure assessment. Age-adjusted AUCs were similar across models and cohorts (pooled AUCs by model: 0.57-0.58), while E/O ratios varied substantially (pooled E/O ratios by model: 0.83-1.25). Overestimation was common among predicted high-risk individuals (>3%). No appreciable differences in model performance by cohort age, birth year, race, and variable missingness emerged. Calibration improved after assigning race-specific incidence rates. Conclusion: Existing BC risk prediction models provided similar risk discrimination across multiple cohorts, although there was overestimation of risk for high-risk individuals. Performance variation across cohorts was not driven by specific characteristics, which supports development of a unified risk model for diverse populations that leverages appropriate incidence rates.

The goal in selecting these recent articles was to help identify literature that may change the clinical practice of women’s health for practitioners in the primary care and general gynecology setting. Articles were identified by reviewing high-impact medical and women’s health journals, national guidelines, ACP JournalWise and NEJM Journal Watch. In this Clinical Update, we selected recent publications relevant to the sexual health of women. Specifically, we reviewed guidelines and consensus statements on hypoactive sexual desire disorder (HSDD) and genitourinary syndrome of menopause (GSM), as well as studies around the role of pelvic floor muscle training for GSM and psychological and behavioral health for sexual health in midlife women.

Abstract Health and biomedical science-related academic societies have played significant roles in the development and evolution of science and medicine, as well as the evolution of disciplines, including the diversification of medicine into specialties and subspecialties. They have also had formative roles in the development of clinical practice, professionalism, and training standards. The communities they establish promote knowledge creation and dissemination, provide career and professional development opportunities, articulate professional matters, offer networking opportunities, provide recognition, support members, and perform public engagement and advocacy work. They also play increasingly important roles in educating the public and disseminating objective, evidence-based medical and scientific information. Academic societies face challenges related to membership (recruiting new members and engaging and retaining current members), technology, hosting meetings and conferences, generational shifts (e.g., in demographics and attitudes toward working conditions, career paths, work-life integration), costs and logistics related to operations, and morale within institutions and professions. The Council of Faculty and Academic Societies of the Association of American Medical Colleges plays a unique role in supporting academic medical and related societies by providing an interprofessional forum for their interaction and dialogue, and is a vehicle for asserting their collective voice. To the extent that past is prologue, future advances in health care and science will depend, in part, on the resilience of academic societies and on the health professional workforces that they nourish.

Abstract Background Immigrant women experience disproportionate psychosocial stress driven by acculturation, socioeconomic hardship, discrimination, and transnational responsibilities. Despite evidence supporting culturally tailored stress‑management interventions, limited formative research has examined program preferences across diverse immigrant communities. Methods Using a community‑based participatory research (CBPR) approach, we conducted three language‑concordant focus groups (Somali, Spanish, English; n = 18) and a mixed‑methods survey (n = 88) with immigrant women in southeast Minnesota. Qualitative data were analyzed using constant comparative methods; quantitative data were summarized descriptively. Results Participants described intersecting stressors including caregiving burdens, financial insecurity, immigration‑related fears, bicultural identity strain, and transnational obligations (e.g., “Every day you are being told of problems back at home”). Barriers to discussing stress included stigma, limited culturally concordant care, religious norms discouraging emotional disclosure, and structural constraints such as lack of insurance (e.g., “How are you gonna pay for a therapist if you don't have health insurance?”). Coping strategies varied culturally but consistently emphasized social support, spirituality, and practical stress‑reduction techniques. Survey findings indicated strong preference for education on stress, stigma reduction, culturally and linguistically aligned support groups, and flexible delivery formats (in‑person, hybrid). Conclusions Immigrant women experience multifaceted stress shaped by minority stress processes and structural inequities. Findings highlight the need for culturally responsive, community‑informed stress‑management interventions that integrate education, social support, and flexible delivery modalities. These results directly inform adaptation of a stress‑management program for Somali, Spanish‑, and English‑speaking immigrant women.

BACKGROUND AND OBJECTIVES Neonatal tracheal intubation is a high-risk procedure, and multiple attempts are associated with adverse events. At our tertiary neonatal intensive care unit, the baseline first-attempt success rate was 45%, which we aimed to increase to over 55% through a quality improvement (QI) initiative. METHODS A multidisciplinary team conducted a QI project using the define-measure-analyze-improve-control framework. Root cause analysis identified poor glottic visualization and patient instability as primary drivers of failure. Plan-do-study-act cycles were carried out (April 2023–July 2024), followed by a sustainability phase (August 2024–May 2025). Key interventions included the phased implementation of video laryngoscopy (VL) as the primary intubation device and the standardization of oxygenation during laryngoscopy using nasal high flow. First-attempt success was tracked using statistical process control, and bimonthly VL use was monitored as a process measure. RESULTS A total of 642 intubations were analyzed. By control chart analysis, the first-attempt success rate increased from a baseline of 45% to a sustained process mean of 61% during the intervention and sustainability phases. VL use increased from 0% at baseline to 70% to 90% during the sustainability phase. Success rates improved across all clinician types and locations. Notably, first-attempt success in infants weighing less than 1000 g increased from 38% at baseline to 62% during the intervention phase. CONCLUSION A systematic QI initiative focused on VL and standardized oxygenation improved and sustained neonatal intubation success rates, exceeding the project aim. The maintenance of high-success rates confirms the durability of these safety improvements.

Background: Telomeres are repetitive sequences at the end of linear chromosomes that preserve genetic information. Patients with telomere biology disorders (TBDs) are subject to multiorgan manifestations, which include the liver. However, due to the rare nature of the disorder, these manifestations are not fully characterized. Methods: Here, we describe the hepatic manifestations of patients with TBD at a large tertiary center within a specialized TBD clinic; 121 consecutive patients with TBD seen from 2017 to 2024 were included. The median age of the TBD diagnosis was 43 years old, with 60% male. The most common pathogenic/likely pathogenic variant was TERT (25%), followed by RTEL1 (10%) and TERC (7%). Results: Evidence of hepatic involvement in TBD was observed in 60% of patients (73 of 121), as determined by imaging studies or abnormal liver chemistries. Hepatic steatosis was the most prevalent imaging finding (56%), while a cholestatic pattern of liver injury was the predominant laboratory abnormality (73%). Biopsy-proven portosinusoidal vascular disorder was present in 4 patients. Findings of portal hypertension were observed in 25 patients (34%), with decompensation observed in 12 patients (16%). Traditional liver imaging modalities (computer tomography, ultrasound, and MRI) were compared with magnetic resonance elastography in 41 patients. Of these, 7 patients had abnormal magnetic resonance elastography with normal traditional imaging (17%), indicating higher sensitivity of magnetic resonance elastography to detect liver involvement. Conclusions: This study describes the liver manifestations within a cohort of patients with TBD with findings of portosinusoidal vascular disorder and hepatopulmonary syndrome similar to other cohorts and a noted higher prevalence of hepatic steatosis as compared with the general population. Liver stiffness measurements, integrated with imaging and laboratory testing, further improve characterization of hepatic manifestations in TBD.

This study examines the patient- and hospital-level variation in time to initiation of inpatient management among patients admitted to general medical services.

The NCCN Guidelines for Survivorship offer guidance for health care providers who care for survivors of adult-onset cancer. These guidelines include screening, evaluation, and treatment recommendations for common physical and psychosocial problems resulting from cancer and its treatment and provide a framework for care coordination. They also present guidance for helping cancer survivors to enhance their wellness and maintain a healthy lifestyle. This article summarizes the panel’s current recommendations and recent updates regarding anxiety, depression, distress, and trauma in cancer survivors.