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Importance Inherited pathogenic variants (PVs) in known predisposition genes can greatly increase breast cancer risk, but the combined impact of PV status, family history, and other factors on breast cancer risk in the general US population has not been well described. Objective To evaluate population-based breast cancer risk estimates for those with established PVs overall and stratified by first-degree family history of breast cancer and other factors. Design, Setting, and Participants This study used pooled data from 13 US-based breast cancer case-control studies participating in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Enrollment for individual studies occurred between 1976 and 2013, and results are based on data released March 2023, with analyses conducted from June 2022 to July 2025. Exposures PVs, breast cancer family history, self-reported race and ethnicity, and established risk factors. Main Outcomes and Measures Breast cancer rate ratios for PVs in 7 genes were estimated from the CARRIERS consortium. PV status and incidence and mortality statistics were combined using the Individualized Coherent Absolute Risk Estimation (iCARE) model to estimate conditional cumulative breast cancer risks and 95% CIs, stratified by family history and standardized to the US population. Models that incorporated population-based data and published estimates for established epidemiologic risk factors were also evaluated. Results A total of 67 692 women were studied, including 33 841 who were diagnosed with breast cancer. PVs in ATM , BRCA1 , BRCA2 , CHEK2 , and PALB2 were strongly associated with breast cancer risk, with BRCA1 and PALB2 PVs showing evidence of heterogeneity by family history. In models considering PVs, family history, and established risk factors, the estimated cumulative risks of breast cancer by age 50 years ranged from 2.4% (95% CI, 2.4-2.4) in women with no PVs and no family history to 35.5% (95% CI, 21.6-55.1) in PALB2 PV carriers with a family history. Among women who have not been diagnosed with breast cancer by age 50 years, the cumulative risk of breast cancer by age 80 years ranged from 11.1% (95% CI, 11.0-11.2) in noncarriers with no family history to 70.5% (95% CI, 52.8-83.5) for PALB2 carriers with a family history. PV-specific cumulative risk estimates varied across subgroups defined by race and ethnicity and potentially modifiable epidemiologic risk factors. Conclusions and Relevance In this study, population-based estimates of cumulative breast cancer risk for established PVs, as informed by the CARRIERS case-control sample, varied by family history and potentially modifiable risk factors. These estimates provide guidance for identifying individuals who will most benefit from enhanced screening and prevention strategies.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hematopoietic Cell Transplantation (HCT) provide expert, multidisciplinary recommendations for autologous and allogeneic HCT based on current evidence. The NCCN Guidelines focus on pretransplant recipient evaluation, hematopoietic cell mobilization, conditioning, and the diagnosis and management of graft-versus-host disease (GVHD), a common complication of allogeneic HCT that is associated with significant morbidity. This selection from the NCCN Guidelines for HCT focuses on the diagnosis, workup, and management of acute and chronic GVHD, as well as important supportive care considerations.

In women with dense breasts, adding molecular breast imaging to digital breast tomosynthesis (DBT) increased both overall and invasive cancer detection rates, while modestly raising the recall rate compared with DBT alone.

A 33-year-old female presented with finger pain, swelling, and erythema was diagnosed with cellulitis and treated with antibiotics. Persistent symptoms led to further evaluation including a point-of-care ultrasound revealing a cystic structure, concerning for abscess. Incision and drainage yielded a solid mass rather than fluid. Pathological examination revealed a schwannoma, a benign peripheral nerve sheath tumor. This case highlights the rare presentation of a schwannoma mimicking an infectious process and emphasizes the importance of considering peripheral nerve tumors in the differential diagnosis of soft tissue masses, especially when the clinical course is atypical. It also underscores the value of pathological examination in establishing a definitive diagnosis and preventing misdiagnosis, which can have implications for patient management.

ABSTRACTWe describe a case of a 56‐year‐old male who developed severe, refractory hypotension after an intentional ingestion of clozapine and who became hemodynamically stable after one session of therapeutic plasma exchange (TPE). The patient, who presented after an ingestion of clozapine, was found to have altered mental status and hypotension in the emergency department. Escalating catecholamine vasoactive agents were necessary to maintain adequate hemodynamics. Angiotensin II was added and rapidly up titrated in efforts to maintain adequate blood pressure. Due to persistent hemodynamic instability despite four vasoactive agents, TPE was attempted to enhance the elimination of the highly protein bound medication. Within 2 h of completing TPE, the catecholamines and vasopressin were stopped, and angiotensin II dosing was significantly decreased. This is the first report of utilizing TPE as a method of enhanced elimination of a toxic clozapine ingestion resulting in severe hemodynamic compromise. Further study is necessary to determine if TPE should be incorporated into the care of patients experiencing clozapine toxicity.

Objectives Cervical spine (c-spine) X-ray (XR) remains an important tool for pediatric trauma patients. XR is a low radiation alternative to multidetector CT (MDCT). Our primary aims were to analyze the sensitivity of a negative c-spine XR and to analyze what factors lead to additional imaging after a negative c-spine XR. Methods A retrospective cohort study was conducted at a level 1 pediatric trauma center from 2012 to 2021. We compared the group with negative c-spine XR and no additional imaging to the group with negative c-spine XR followed by additional c-spine MDCT and/or MRI. Results There were 2,081 negative XRs and 1,974 (95%) had their c-spines cleared without additional imaging. No patient required an operation for a clinically significant c-spine injury in this group, and we consider this no missed injuries. The remaining 108 patients had additional c-spine imaging after negative c-spine XR for c-spine clearance (24 MDCT, 76 MRI, 8 MDCT and MRI). Indications for additional c-spine imaging were pain (48.1%), Glasgow Coma Scale (GCS) score ≤14 (43.5%), and paresthesia (8.3%). Patients who received additional imaging were more likely to have a GCS score ≤12 (25.4% vs 4.1%), Injury Severity Score >15 (21.9% vs 8.1%), Level 1 Trauma activation (21% vs 5%), Abbreviated Injury Scale head score of 4 or 5 (29% vs 5%), be intubated (30% vs 2%), and have non-accidental trauma as their mechanism of injury (20% vs 1%) (p value<0.0001, for all). Five patients who received additional imaging were treated with a cervical collar, but no operative intervention. Conclusions In this cohort, screening XR had a sensitivity of 100% for clinically significant c-spine injuries. GCS was the most significant predictor of obtaining additional imaging. A negative XR combined with a normal physical examination in an evaluable pediatric patient is a safe way of clearing the c-spine. Level of evidence Study contains level III evidence.

Abstract INTRODUCTION African American (AA) individuals are underrepresented in biomarker studies for Alzheimer's disease (AD). Biomarkers that reflect the heterogeneity of AD and achieve the greatest accuracy across populations are sorely needed. METHODS Untargeted proteome measurements were obtained using the SomaScan 7k platform to identify novel plasma biomarkers for AD in AA participants with clinical diagnoses of AD dementia ( n = 181) and cognitively unimpaired (CU, n = 142). Machine learning was used to identify a set of plasma proteins that yielded the best classification accuracy. RESULTS A set of 36 proteins achieved an area under the curve (AUC) of 0.94 to classify AD dementia versus CU, a 16% improvement over age, sex, and apolipoprotein E ( APOE) . This finding was replicated in multiple plasma and brain datasets (AUCs 0.73–0.97). Our findings underscore the importance of matrisome and cerebrovascular dysfunction in AD pathophysiology. DISCUSSION This study demonstrates the potential of biomarker discovery through untargeted plasma proteomics and machine learning. Highlights Conducted large‐scale plasma proteomics in Alzheimer's disease (AD) versus cognitively unimpaired controls. Machine learning biomarker discovery was replicated in an independent cohort. Novel set of proteins distinguishes AD versus controls with high accuracy (area under the curve [AUC] = 0.94). Achieved reproducibility across multiple replication cohorts (AUC = 0.73–0.97). Network analyses implicates matrisome biology and cerebrovascular dysfunction.

Key Points In individuals undergoing bariatric surgery, the magnitude of decline in GFR postbariatric surgery is directly associated with presurgery GFR. Reductions in GFR postsurgery were only weakly correlated with weight loss. In obese individuals, GFR-estimating equations performed best when deindexed and when applied in people with reduced kidney function. Background Important questions remain about how bariatric ( i.e ., weight loss) surgery affects measured GFR (mGFR) and eGFR as well as what factors influence change in mGFR postsurgery. Methods Data were pooled from all seven available studies (dates: 2004–2018) measuring GFR prebariatric and postbariatric surgery using gold standard methods. Change in postsurgery mGFR, factors that could influence change in mGFR, and effects on five GFR-estimating equations were analyzed using standard statistical methods. Results The cohort included 105 individuals from the United States and Europe. Sixty-eight percent were female, 97% were White, the mean age was 50 years (range, 24–70), and the mean body mass index was 46±8 kg/m 2 . The mean presurgery mGFR of 107 ml/min (range, 31–215) fell to 92 ml/min (−14%; 95% confidence interval, −21 to −10) postsurgery, with a strong linear relationship existing between presurgery mGFR and % change in GFR ( r =−0.51; −0.64 to −0.35). Individuals with presurgery mGFR ≥90, 60 to <90, and<60 ml/min had −25 (−32 to −19), 1 (−11 to 13), and 7 (0 to 14) ml/min mean postoperative changes in mGFR. Change in weight was significantly correlated with change in mGFR ( r =0.22; 0.03 to 0.40). After adjusting for sex, changes in mGFR postsurgery were associated with higher presurgical age (−0.6 ml/min per year; −1.1 to −0.2), mGFR (−0.5 ml/min per 1 ml/min; −0.6 to −0.4), and change in systolic BP (−0.3 ml/min per 1 mm Hg; −0.6 to 0.0). All GFR-estimating equations significantly underestimated postsurgical GFR reductions in people with preserved kidney function and had improved bias, precision, and accuracy when deindexed and applied to individuals with mGFR <90 ml/min. Conclusions In individuals with obesity undergoing bariatric surgery, the magnitude of postsurgical decline in mGFR was directly associated with presurgery GFR and weakly correlated with weight loss. In addition, GFR-estimating equations' performance improved when deindexed and used in people with reduced kidney function, with the combined creatinine/cystatin C equations having the best overall performance.