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Importance Limited granular data exist on breast cancer in transgender, nonbinary, and/or gender-diverse (TGD) individuals. Objective To describe patient demographic and tumor clinicopathological variables, clinically relevant risk factors, method of breast cancer detection, treatment characteristics, and locoregional outcomes and to estimate a 5-year breast cancer–specific survival (BCSS). Design, Setting, and Participants This cohort study obtained data on patients treated from 1990 to 2023 from 22 US academic medical centers using institutional databases, electronic medical records, and tumor registries. Included participants were TGD individuals 18 years or older with stage 0 to IV breast cancer. A comparative breast cancer cohort was selected from the 2016 to 2021 Surveillance, Epidemiology, and End Results Program (SEER) breast cancer dataset. Data were analyzed from January to October 2025. Exposure Breast cancer. Main Outcomes and Measures Estimated 5-year BCSS and locoregional recurrence rates. Wilcoxon rank sum and χ 2 tests were used to compare continuous and categorical variables. Kaplan-Meier analysis was used to estimate 5-year BCSS. Results A total of 112 TGD persons (median [IQR] age at diagnosis, 42.5 [36.5-51.0] years; 104 individuals [92.9%] were assigned female at birth) with breast cancer and 1 with bilateral disease were included in the analysis. Forty-three patients (38.4%) used gender-affirming hormone therapy before diagnosis. Among the entire cohort, 58 patients (51.8%) detected their own breast cancer, 68 (60.7%) had a familial breast cancer history, and 16 (14.3%) had a pathogenic germline variant. Tumors were predominantly hormone receptor positive (96 [85.7%]) and early stage (29 [25.7%] ductal carcinoma in situ [DCIS]; 51 [45.1%] stage I). The TGD cohort, compared with patients with breast cancer in the SEER dataset (N = 480 915), was younger (median [IQR] age, 42.5 [36.5-51.0] years vs 62.0 [52.0-72.0] years), had a higher proportion of persons assigned male at birth (8 [7.1%] vs 3522 [0.7%]), more often had progesterone receptor–positive disease (89 [79.5%] vs 335 491 [69.8%]), and presented with earlier-stage disease (eg, DCIS: 29 [25.9%] vs 79 604 [16.6%]). With a median (IQR) follow-up time for the TGD cohort of 38 (24-74) months, 5-year BCSS was favorable at 96.2% (95% CI, 85.3%-99.0%). Conclusions and Relevance This cohort study of TGD patients with breast cancer found that this population was young and often detected their own tumors via self-examination, suggesting opportunities to improve early detection through screening for individuals at elevated risk. Although short-term BCSS appeared favorable, prospective research is essential to define evidence-based guidelines and elucidate long-term outcomes.

BACKGROUND: Technetium-based cardiac amyloid radionuclide imaging enables noninvasive diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM), but conventional planar and visual semiquantitative approaches have important limitations. We developed the quantitative 3-dimensional Mayo 3D Score, defined as the ratio of mean left ventricular myocardial radiotracer uptake to right atrial blood-pool uptake using computed tomography (CT)-fused single-photon emission CT (SPECT) volumes of interest, and sought to validate its diagnostic performance against myocardial pathology. METHODS: Consecutive patients who underwent 99m Tc-pyrophosphate SPECT/CT at Mayo Clinic for suspected ATTR-CM between June 2017 and January 2025 with archived myocardial tissue were included. Baseline characteristics, including demographics, echocardiogram, biomarkers, visual semiquantitative, and Mayo 3D Score metrics, were collected. Myocardial specimens underwent histopathologic confirmation of amyloid, with amyloid subtype determination and further semiquantitative grading of amyloid burden and deposition patterns. RESULTS: Among 230 patients (median age, 72 years; 78% male), 107 (47%) had ATTR-CM, of whom 9 had hereditary ATTR-CM. The Mayo 3D Score showed excellent discrimination against pathology (area under the receiver operating characteristic curve, 0.92 [0.88–0.96]), exceeding planar Perugini (0.87 [0.83–0.92]; P =0.006), and heart-to-contralateral lung ratio (0.86 [0.81–0.91]; P =0.004) and comparable to SPECT Perugini (0.90 [0.86–0.94]; P =0.12). A cutoff ≥1.0 yielded 86.0% sensitivity, 92.7% specificity, 91.1% positive predictive value, and 88.4% negative predictive value. Among ATTR-positive cases, the Mayo 3D Score correlated strongly with semiquantitative amyloid burden (Spearman ρ=0.69), was higher in pericellular than nodular deposition patterns ( P <0.001), and was not associated with vascular involvement ( P =0.42). CONCLUSIONS: In patients with suspected ATTR-CM undergoing 99m Tc-pyrophosphate SPECT/CT, the Mayo 3D Score demonstrated superior diagnostic performance compared with planar metrics and comparable to SPECT Perugini, while correlating with myocardial ATTR burden and deposition patterns on pathology. These findings support its integration as a quantitative adjunct within clinical diagnostic ATTR-CM workflows.

This JAMA Clinical Guidelines Synopsis summarizes the American College of Gastroenterology’s (ACG) 2025 clinical guideline update on management of ulcerative colitis in adults.

Abstract Background Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features. Methods Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) &lt;0.2 was used to identify associations with strong statistical evidence. Results Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend&lt;0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend&lt;0.001 and &lt;0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend&lt;0.001 and &lt;0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units. Conclusion This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.

Donation after circulatory death (DCD) liver transplants (LTs) are associated with increased risk of post-LT acute kidney injury (AKI). This retrospective study aimed to examine the effect of continuous normothermic machine perfusion (NMP) on the incidence and stage of AKI in DCD LT. The incidence of AKI within 48 hours was compared between 507 NMP-DCD and 472 static cold storage (SCS)-DCD LT transplanted between January 1, 2016, and December 31, 2024. AKI developed in 337 (34%) patients. On univariate analysis, AKI rate was lower in NMP-DCD compared with SCS-DCD (28% vs. 41%, p <0.001). Stages 2 and 3 AKI at 48 hours and renal replacement therapy (RRT) within the first 3 weeks were also lower in NMP-DCD compared with SCS-DCD ( p <0.001). After adjusting for multiple recipient, donor, and intraoperative factors using multivariate logistic regression, NMP-DCD was independently associated with a 37% lower odds of AKI (aOR: 0.63, CI: 0.46–0.85, p =0.003) and 55% lower odds of stages 2 and 3 AKI (aOR: 0.45, CI: 0.29–0.69, p <0.001) compared with SCS-DCD. To mitigate for the era effect and other unmeasured confounders, an inverse probability of treatment weighting (IPTW) analysis was performed using a propensity score model with average treatment effect (ATE). After weighting for multiple factors, NMP-DCD was associated with lower odds of AKI at 48 hours (OR: 0.65, CI: 0.53–0.81, p =0.001), stages 2 and 3 AKI at 48 hours (OR: 0.60, CI: 0.42–0.85, p =0.02), and RRT at day 7 (OR: 0.31, CI: 0.13–0.65, p =0.003) compared with SCS-DCD. In conclusion, compared with SCS-DCD, NMP-DCD was independently associated with lower odds of AKI at 48 hours, of stages 2 and 3 AKI at 48 hours from LT, and of RRT requirement at day 7 from LT, an effect that extended for the first 3 post-LT weeks.

Background Malpositioned orbital implants are an underappreciated source of significant postoperative morbidity, often necessitating revision surgery. Decision-making regarding practical frameworks to guide revision remains challenging and is not well standardized or characterized. Objective To analyze clinical presentations, radiographic failure patterns, multidisciplinary surgical strategies, and outcomes of patients undergoing revision surgery for malpositioned orbital implants. Methods A single-center retrospective consecutive case series was conducted of patients who underwent removal or replacement of malpositioned orbital implants. Patient demographics, presenting symptoms, radiographic findings, surgical approaches, implant management strategies, and postoperative outcomes were reviewed. Most cases were co-managed by plastic/reconstructive and oculoplastic surgeons. Descriptive statistics were used to summarize findings. Results Five of seven patients (71.4%) were female, with a median age of 60 years (range 29–78). Diplopia was the most common presenting symptom (5/7, 71.4%) along with pain or swelling (5/7, 71.4%) followed by globe malposition (3/7, 42.9%). CT demonstrated implant protrusion into orbital soft tissue in 4/7 patients (57.1%) and peri-implant inflammatory collections in 3/7 (42.9%). Out of our 7 revision cases, four patients (57.1%) underwent explantation alone, and three (42.9%) underwent secondary reconstruction with custom or semi-custom implants. At follow-up, diplopia improved or resolved in 4/5 affected patients (80%), and pain, swelling, and globe position improved in all symptomatic patients. Conclusion Malpositioned orbital implants demonstrate heterogeneous failure mechanisms that require individualized surgical management. A multidisciplinary approach can guide decision-making regarding implant removal versus revision of reconstruction, enabling safe revision surgery and favorable clinical outcomes. Additionally, virtual surgical planning and intraoperative navigation are enablers of safe and precise revision orbital surgery.

ABSTRACT In 567 PH‐COPD patients from the PVRI GoDeep Meta‐Registry, ACE inhibitor use was associated with improved survival only in severe PH (PVR > 5 WU), supporting prospective trials targeting this high‐risk subgroup.