Citations

Abstract Background The incidence of early onset breast cancers (BCs) has increased, paralleling rising trends in delayed childbearing. We hypothesize that a distinct postpartum BC (PPBC) subtype, identifiable by time since last birth (TSLB) and biomarker expression, contributes to this trend. Methods We applied GeoMx Digital Spatial Profiling (DSP) to measure associations between TSLB and 71 proteins in 640 BCs from women aged ≤40 years included in the Young Women’s Breast Cancer Study. We analyzed data using univariable linear regression and multivariable sliced inverse regression to account for higher order interactions among biomarkers. Results In keratin-rich segments, progesterone receptor (PR) (P = 1.00 × 10−4) and PTEN (P = 1.00 × 10−3) were associated with longer TSLB; multivariable analyses revealed positive associations for GZMB (P = 4.00 × 10−4), SMA (P = 1.00 × 10−4), and NF-1 (P = 1.00 × 10−3). In keratin-poor segments, univariable significant positive associations were found for PR (P = 2.00 × 10−4) and PTEN (P = 1.00 × 10−3), whereas CD20 (P = 3.00 × 10−4) and CTLA4 (P = 4.00 × 10−5) were negatively associated; multivariable significant associations were found for fibronectin (P = 3.00 × 10−5) and pan-Akt (P = 1.00 × 10−3). Associations persisted after adjustment for multiple comparisons and BC molecular subtypes. Associations including for PR, PTEN, and CD20 were strongest among women with the shortest TSLB. OPAL multiplex immunofluorescence assays for PR, PTEN, CD20, SMA, and CTLA4 replicated several DSP findings, particularly when stratified by subtype and with compartment matching. In TCGA, RNA species linked to proteins associated with TSLB correlated strongly with a T-cell exhaustion signature previously linked to poor prognosis among premenopausal women. Conclusion These data support PPBC as a biologically coherent phenotype defined by TSLB and biomarker profile, with potential implications for prevention and therapy.

Abstract Background Critical illness is a risk factor for carnitine deficiency. Carnitine deficiency may result in serious medical complications and poor clinical outcomes. This study aimed to identify the prevalence and potential predictors of carnitine deficiency. Methods This was a descriptive cross‐sectional study conducted in a convenience sample of 144 critically ill adults admitted to a surgical or cardiovascular intensive care unit at the University of Utah Hospital, with serum carnitine levels measured from January 1, 2022, to December 31, 2024. Binary and multivariable logistic regression models were constructed to explore potential predictors of carnitine deficiency, which was defined as a free serum carnitine level <36 µmol/L. Results The mean age of patients was 56.5 years; 41.7% of the sample had carnitine deficiency. For each unit decrease in body mass index, the odds of developing carnitine deficiency increased by 5% compared with maintaining normal free carnitine status (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.9–0.99). Those prescribed continuous renal replacement therapy were 2.43 times more likely to develop carnitine deficiency than those not on continuous renal replacement therapy (OR, 2.43; 95% CI, 1.12–5.25). Conclusion A high proportion of our study population had carnitine deficiency. Continuous renal replacement therapy and a lower body mass index were significant predictors in the multivariable model. Female sex and a history of chronic kidney disease may warrant further exploration based on significance in the univariable analysis.

Abstract Background Despite advancements in care, pregnant individuals with congenital heart disease (CHD) face disproportionately high risks. Objectives To address these challenges, a national consortium was established to improve maternal outcomes in CHD through multidisciplinary collaboration and patient engagement. Study design As part of a 2.5‐year multi‐phase consortium initiative, an in‐person research summit followed by three virtual focus groups (Project PHASE 3) was conducted with patients, clinicians, researchers, advocates, and policy representatives. Qualitative data were collected, and reflexive thematic analysis was performed to identify shared priorities. Results A total of 48 individuals participated in the in‐person meeting, including 18 patients (83% female; 11% Black/African American, 17% Asian, 11% Hispanic, 61% White) and 30 clinicians/researchers. An additional 19 patients (100% female; 32% rural/non‐urban; 16% Black/African American, 10% Hispanic, 74% White) participated in virtual focus groups. Key priorities identified included improved patient–healthcare provider communication, expanded access to multidisciplinary and adult CHD‐specialized care, and greater inclusion of patient voices in reproductive planning and research. Focus groups underscored racial disparities in care, limited CHD education for patients of color, and the need for culturally tailored resources. Participants emphasized the importance of representative research cohorts, integration of genetic counseling, and dissemination of research in accessible, plain‐language formats. Conclusions Findings demonstrate the value of integrating patient expertise and partnership in shaping cardio‐obstetric research, care models, and education. Addressing maternal health concerns in CHD research requires both structural changes and community‐driven, inclusive research strategies.

Background/Objectives: Women’s wrestling is one of the fastest growing sports within the United States at the high school and collegiate level. Weight-class sports, such as wrestling, present unique challenges for female athletes, particularly in managing acute weight fluctuations associated with the menstrual cycle. However, less is known regarding how sex-specific physiology may influence weight management strategies among female wrestlers. The purpose of this review was to highlight current weight loss trends among high school and collegiate female wrestlers and summarize the physiological mechanisms driving potential menstrual-related fluid retention and subsequent changes in body mass or composition. Methods: A literature review was conducted to include studies evaluating weight loss trends in female wrestlers competing in the United States. Additional literature focused on fluid, body mass, and body composition changes throughout the menstrual cycle was also included. Results: Recent evidence has provided observational data that can be used to develop descriptive summaries of current body composition profiles and weight loss trends among female wrestlers. These data can help to quantify the typical magnitude of weight loss changes observed in female wrestlers competing at the high school and collegiate level within the United States. Conclusions: These findings help provide insight into the magnitude of weight loss wrestlers undergo in an effort to compete in their minimal weight class, thus informing practitioners of potential health risks and helping guide optimal weight management efforts.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have advanced the treatment of type 2 diabetes mellitus (T2DM), yet their association with cancer risk remains subject of ongoing research. Chronic pancreatitis (CP) is a well-established risk factor for pancreatic cancer, yet the impact of GLP-1 RA therapy in this high-risk population is unknown. In this study, we aimed to evaluate the association between GLP-1 RA use and pancreatic cancer incidence among patients with CP, and among those with CP and T2DM. Methods: We performed a retrospective cohort study using data from TriNetX, a healthcare database of over 150 million patients in the United States. In the first analysis, adult patients with pre-existing CP were identified and stratified by use of a GLP-1 RA (semaglutide, dulaglutide, tirzepatide, exenatide, liraglutide, lixisenatide, and albiglutide). Propensity score matching (PSM) was conducted between GLP1-RA users and non-users, matching for age, sex, race, tobacco use, alcohol use, hypertension, hyperlipidemia, obesity, and pancreatic cysts. Five-year incidence of pancreatic cancer was compared between GLP-1 RA users and non-users in the matched cohort between 2015 and 2025. We then restricted the cohort to patients with CP and T2DM and repeated this analysis. Results: We identified 89,596 patients with CP, including 3183 GLP-1 RA users and 86,413 non-users. After PSM, GLP-1 RA use was associated with a lower 5-year incidence of pancreatic cancer (hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.30–0.80, p < 0.005). Similarly, amongst patients with CP and T2DM, GLP-1 RA use was associated with a lower 5-year incidence of pancreatic cancer (HR 0.53, 95% CI 0.31–0.91, p < 0.05). Conclusions: GLP-1 RA use was associated with a significantly reduced incidence of pancreatic cancer in all patients with CP, as well as the subpopulation with both CP and T2DM. Given the elevated cancer risk in CP, these findings suggest a potential beneficial effect of GLP-1RA use in this high-risk population. Prospective studies will be important to further analyze and confirm this potential benefit.

Abstract Caregivers for people with neurodegenerative disease (PWNDs) often experience mental and physical health problems, especially when caring for PWNDs who have deficits in emotional functioning. We studied 65 PWNDs and their caregivers both during active caregiving and after caregiving had ended to determine: (a) how caregiver health changes after caregiving ends; and (b) whether PWNDs’ emotional functioning predicts these changes. PWND emotional functioning was assessed in the laboratory by measuring their generation of preparatory physiological activity (e.g., increased heart rate) to an upcoming emotional event (i.e., emotion eliciting films). Caregiver mental and physical health were measured using the Short-Form Health Survey (SF36) during active caregiving and again after caregiving had ended. Results indicated that, overall, caregivers reported increases in mental health, (t(36) = 2.58, p = .014, 95% CI [1.31, 10.93]) but decreases in physical health (t(36) = -2.35, p = .025, 95% CI [-7.26, -0.53]) across the two measurement periods. Using latent change score models, PWNDs’ preparatory physiological response impairments were associated with better caregiver mental health trajectories (β = -0.37, SE = 0.04, p = .003) such that smaller PWND preparatory responses predicted greater improvements in caregiver mental health (β = 9.92, SE = 2.84, p &lt; .001). There was no association with changes in caregiver physical health. Smaller preparatory physiological responses in PWNDs may indicate diminished emotional responding, which is linked with lower caregiver mental health during active caregiving. Once caregiving ends, these caregivers may be most likely to “rebound” and show improvements in mental health.

Background This study aimed to evaluate outcomes of different antibiotic durations in patients with severe diverticulitis. Methods Initial electronic medical record review identified 2437 adult patients who underwent sigmoid colectomy. Manual chart review identified 133 patients who underwent sigmoid resection and proximal diversion for Hinchey stage 3 or 4 diverticulitis. Patients who received a short antibiotic course (SAC, ≤5 days) were compared with those who received a long antibiotic course (LAC, >5 days). The primary composite outcome included superficial, incisional, organ-space infections or death within 30 days post procedure. Results A total of 53 SAC patients and 55 LAC patients were identified. The composite outcome occurred more frequently in LAC patients than in SAC patients (40% vs 15%; P = .005). Organ-space infection occurred more frequently in LAC patients than in SAC patients (31% vs 13%; P = .04). Conclusions Extended duration of antibiotics after adequate source control does not improve outcomes even in the setting of extensive intra-abdominal contamination.

Aims Total elbow arthroplasty (TEA) has shown favourable outcomes in the management of severely comminuted distal humeral fractures in low-demand elderly patients, leading to its increased use in recent years. Less is known about the outcomes of TEA when used for the failure of either internal fixation or conservative management, particularly whether not performing TEA acutely influences the options for further management if fixation fails. This systematic review aimed to assess the clinical and functional outcomes following TEA when used for the post-traumatic sequelae of a distal humeral fracture, and to compare these outcomes with those in patients with a distal humeral fracture who undergo TEA acutely. Methods MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus databases were searched from January 2000 to September 2024 for studies reporting complications, reoperations, the range of motion of the elbow, or functional outcomes following the use of TEA in the management of the post-traumatic sequelae of distal humeral fractures, including those due to failed fixation, nonunion, and post-traumatic arthritis. Demographic and clinical data were collected, descriptive statistics were summarized, and meta-analyses were undertaken to compare the outcomes between salvage and acute TEA. Results A total of 16 studies were included, with a total of 380 patients who underwent salvage TEA and 251 who underwent TEA as the initial management. Salvage TEA was associated with a significantly higher overall risk of complications (odds ratio (OR) 2.5 (95% CI 1.0 to 5.9)), though the rate of reoperations did not differ from those who underwent TEA acutely (OR 1.4 (95% CI 0.8 to 2.4)). Pooled analyses revealed a similar postoperative range of flexion (mean difference (MD) -2.4° (95% CI -9.1 to 4.3)) and extension of the elbow (MD 1.1° (95% CI -2.3 to 4.5)) and pronation (MD 0.0° (95% CI -1.1 to 1.1)) and supination (MD -0.0° (95% CI -1.0 to 0.9)) of the forearm. However, salvage TEA showed significantly inferior functional outcomes, as assessed by the Mayo Elbow Performance Score (MD 9.7 (95% CI -18.8 to -0.6)). Conclusion These findings indicate that salvage TEA represents a viable option for the management of post-traumatic sequelae following the teatment of a distal humeral fracture, although patients who underwent salvage TEA had a significantly increased rate of complications and significantly inferior functional outcomes compared with those who underwent TEA acutely. Cite this article: Bone Joint J 2026;108-B(1):21–29.

Abstract Background Primary progressive apraxia of speech (PPAOS) is a frontotemporal lobar degeneration spectrum disorder characterized by progressive speech motor planning/programming decline. Patients often develop neurological symptoms, frequently evolving into progressive supranuclear palsy (PSP)/corticobasal syndrome (CBS) overlap syndromes. Requests for information about disease progression and causes of death are common amongst our clinical and research encounters; however, empiric evidence to guide these discussions is lacking. Understanding causes of death may enhance counseling and support targeted interventions to delay fatal outcomes. This study aimed to describe causes of death in PPAOS. Methods Data from 29 deceased PPAOS patients (16 males) seen in research studies (July 2010–May 2023) were reviewed. Causes of death were established from medical charts and family reports. Fifteen had prosodic and 12 had phonetic‐predominant PPAOS; two had no clear predominance. Median age at onset was 67.08 years, disease duration 9.78 years, and age at death 76.25 years. 28 patients were white and one was Asian Indian. Results Overall, fifteen (52%) patients died from overall deterioration (cachexia/dehydration), nine (31%) from aspiration pneumonia, and the remainder from falls (10%), asphyxiation (3%), or medical aid in dying (3%). There was no clear association with AOS subtype and cause of death. Conclusions Most deaths in PPAOS resulted from systemic failure or dysphagia‐related complications. Half of the patients died without a clear precipitating event, described by family members as “shutting down,” similar to other prior studies that have shown central nervous system deterioration associated with dementia as cause of death. Aspiration pneumonia caused 34% of deaths, highlighting the need for early swallowing management, including assessments, dietary adjustments, and caregiver education. Falls underscore the importance of addressing balance and motor impairments through proactive prevention strategies. Other factors, such as access to healthcare and medical and psychiatric comorbidities were not analyzed but may influence outcomes. Future research should validate these findings in larger, diverse cohorts and compare outcomes to motor‐onset presentations of PSP and CBS. A comprehensive, multidisciplinary approach addressing motor speech impairments, dysphagia, and fall risks is essential to improve care and potentially extend survival for patients with PPAOS.