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ImportanceEtiologic heterogeneity in breast carcinogenesis needs to be well characterized for targeted prevention. Associations between menopausal hormonal therapy (MHT) and oral contraceptive (OC) use and breast cancer intrinsic-like subtypes are not well understood.ObjectiveTo examine whether exogenous hormone use is differentially associated with breast cancer subtypes and to evaluate heterogeneity by intrinsic-like subtypes.Design, Setting, and ParticipantsThis study pooled data from 31 nested and population-based case-control studies involved in the Breast Cancer Association Consortium. The study population included individuals with breast cancer and control participants from 13 case-control studies nested in prospective cohorts (recruited between 1982 and 2011) and 18 population-based case-control studies (recruited between 1990 and 2013). Data analysis was performed in June 2024.ExposureMHT use (estrogen-progestin therapy [EPT] or estrogen-only therapy [ET]) in postmenopausal women and OC use in premenopausal women (never, past use, or current use).Main Outcomes and MeasuresBreast cancer intrinsic-like subtypes (luminal A–like, luminal B–like, luminal B–ERBB2 [formerly HER2 or HER2/neu]-like, ERBB2 enriched–like, or triple-negative) were determined by immunohistochemistry of tumor sections. Polytomous logistic regression was performed to estimate the association between exogenous hormones and risk of breast cancer by intrinsic-like subtypes. Analyses by subtypes were stratified by body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]; healthy weight, 18.5-<25; overweight, 25-<30; or obesity, ≥30).ResultsThis study included 42 269 individuals with breast cancer (11 901 [28.2%] premenopausal and 30 368 [71.8%] postmenopausal; 23 353 [55.2%] had a known intrinsic-like subtype) and 71 072 control participants. The mean (SD) age of all participants was 57.9 (10.9) years. In postmenopausal women, associations between current MHT use (EPT or ET) and breast cancer differed by subtype. Current EPT users with healthy weight were more likely to be diagnosed with luminal A–like (odds ratio [OR], 2.51 [95% CI, 2.26-2.80]) or luminal B–ERBB2-like (OR, 1.95 [95% CI, 1.61-2.37]) subtypes. These associations were attenuated but remained for individuals with overweight (OR, 1.40 [95% CI, 1.02-1.92]) or obesity (OR, 1.68 [95% CI, 1.01-2.78]). EPT use increased the odds of being diagnosed with luminal B–like tumors solely in women with healthy weight (OR, 1.47 [95% CI, 1.17-1.86]). Current ET use was positively associated with luminal A–like disease in women with healthy weight only (OR, 1.16 [95% CI, 1.01-1.32]), showing inverse associations with higher BMI (obesity: OR, 0.65 [95% CI, 0.50-0.85]). In premenopausal women, recent OC use was associated with luminal B–ERBB2-like (OR, 1.50 [95% CI, 1.09-2.08]), ERBB2 enriched–like (OR, 2.33 [95% CI, 1.55-3.51]), and triple-negative (OR, 1.75 [95% CI, 1.33-2.29]; P < .04 for heterogeneity) tumors.Conclusions and RelevanceIn this study, clear differences were observed in associations between current EPT use and luminal-like breast cancer subtypes and other subtypes. EPT users with healthy weight were more likely to be diagnosed with luminal-like breast cancer compared with nonusers. Subtype heterogeneity was less apparent in associations of OC and ET use. Future studies on contemporary formulations, patterns of use, and routes of administration of exogenous hormone usage are warranted.

Key Points This study demonstrates that peritoneal dialysis is a safe and feasible option for patients with autosomal dominant polycystic kidney disease, even with high cystic organ volumes. Larger organ volumes, including height-adjusted cumulative kidney and liver volume, were not associated with increased peritoneal dialysis–related complications. Background Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disorder and the fourth leading cause of kidney failure. Peritoneal dialysis (PD), preferred for its home-based convenience and cost-effectiveness, is often underutilized in ADPKD because of concerns over enlarged kidneys and heightened risk of complications. Methods This retrospective cohort study used data from the Mayo Clinic Polycystic Kidney Disease Database to evaluate individuals with ADPKD undergoing PD. We analyzed demographics, clinical parameters, and PD-related parameters. Complications were correlated with kidney and liver volumes derived from pre-kidney failure imaging. Results A total of 155 individuals with ADPKD on PD were included, of whom 45.1% were male. The mean age at PD initiation was 54.3±12.8 years, and the mean body mass index was 28.0±7.0 kg/m 2 . The median duration of PD was 24.3 months (interquartile range [IQR], 10.7–43.1), with 21.9% transitioning to hemodialysis. The most common complications were abdominal hernias (30.3%) and peritonitis (23.9%), with a peritonitis rate of 0.11 episodes per patient-year. Imaging analyses performed on a subset of 50 patients showed a median height-adjusted total kidney liver volume of 2731.9 ml/m (IQR, 2102.5–3131.1) and a median height-adjusted total kidney volume of 1303.5 ml/m (IQR, 733.1–1829.4). Kaplan–Meier analysis demonstrated no differences in complications rates on the basis of height-adjusted total kidney liver volume or height-adjusted total kidney volume (above versus below median values) or body mass index categories. Multivariate Cox regression analysis revealed that higher height-adjusted cumulative organ volume was associated with a lower risk of PD-related complications (hazard ratio=0.56, P = 0.026). Conclusions PD is a safe and feasible treatment option for patients with ADPKD, with no increased risk of PD-related complications associated with larger height-adjusted cumulative organ volumes. Infectious complication rates in this cohort were within International Society of Peritoneal Dialysis guideline thresholds, further supporting the safety of PD in this population.

BACKGROUND AND OBJECTIVES: Gynecological cancers represent 10% to 15% of cancers in women, but brain metastases (BM) are uncommon, with limited evidence regarding their management. This study investigates the role of stereotactic radiosurgery (SRS) for BM from primary gynecological cancers. METHODS: Institutions of the International Radiosurgery Research Foundation participated in this study. Inclusion criteria required histological diagnosis of epithelial ovarian, cervical, or endometrial cancer, SRS between 2000 and 2020, and at least 1 imaging or clinical follow-up. RESULTS: A total of 276 patients having SRS for 977 BM were included. Median age at SRS was 62 years (IQR, 55-70). Primary cancer origin was ovarian in 128 (46%), cervical in 43 (16%), and endometrial in 105 patients (38%). Median Karnofsky Performance Scale was 80%, and systemic disease was active in 124 (45%) of patients. A median of 1 metastasis was treated (IQR, 1-3) per patient. Median individual metastasis volume was 0.27 cc (IQR, 0.05-1.59 cc). The majority (91%) received single-fraction SRS, using a median margin dose of 18 Gy (IQR, 16-20 Gy). Actuarial overall survival was 77%, 65%, and 44% at 6, 12, and 24 months, respectively. Predictors of worsened survival included older age, cervical and endometrial primary, previous whole-brain radiation therapy (WBRT), active systemic disease, worsened Karnofsky Performance Scale, absence of subsequent surgery, and increasing number of BM. Actuarial local control was 94% at 6 months, 89% at 12 months, and 78% at 24 months. Previous SRS or WBRT, tumor bed treatment, and cervical histology increased the risk of local failure. New remote BM and leptomeningeal dissemination occurred in 44% and 11% of patients, respectively. Adverse radiation effects (ARE) occurred in 13% of cases but were symptomatic in only 3%. Previous WBRT or SRS and increased tumor diameter increased the risk of ARE. CONCLUSION: SRS is an effective management for BM from gynecological cancers with low risks of symptomatic ARE.

Background: Injuries of the medial ulnar collateral ligament (MUCL) among baseball pitchers are increasing. Surgical treatment is evolving to optimize outcomes. Purpose/Hypothesis: This study’s purpose was to highlight trends in MUCL repair and reconstruction in professional pitchers, describe outcomes such as return to any level of play (RTP), and identify factors impacting these outcomes. It was hypothesized that primary and revision MUCL surgery is increasing, with revision surgery requiring greater RTP time. Study Design: Case series; Level of evidence, 4. Methods: The Major League Baseball (MLB) Health and Injury Tracking System database was used to procure data during the study period (2010-2023). All professional pitchers who underwent MUCL surgery during this period were included. RTP was defined as a pitcher returning to at least 1 professional game after index surgery. Return to the same level of play (RTSL) was defined as return to at least 1 game in the same league of play as before surgery. Because of the coronavirus pandemic, the year 2020 was considered an outlier and omitted from time-trend analysis. Results: A total of 2281 pitchers who underwent MUCL surgery during the study period were included for analysis. The number of MUCL surgeries for pitchers increased yearly ( R 2 = 0.821; P < .001), as did the number of reconstructions with internal brace augmentation ( R 2 = 0.896; P < .001). The RTP rate for MLB pitchers was significantly higher than the RTSL rate (93% vs 71%; P < .001). This difference was not observed in Minor League Baseball (MiLB) pitchers (RTP 76% vs RTSL 74%; P = .142). RTP rates after revision surgery were lower than those after primary surgery (71% vs 80%; P = .020). The mean time to RTP was shorter (470 ± 135 days) than the mean time to RTSL (499 ± 153 days; P < .001). Conclusion: The incidence of MUCL surgery and revision surgery is increasing among professional pitchers. Overall, 79% of pitchers returned to any level of play at a mean of 470 days, while 74% returned to the same level of play at a mean of 499 days, but this varied based on level of play. This study will guide athlete expectations and surgeon decision-making.

Abstract Clinicians struggle to accurately classify biliary strictures as benign or malignant. Current endoscopic retrograde cholangiopancreatography (ERCP)-based sampling modalities including brush cytology and forceps biopsy have poor sensitivity for pathologic confirmation of malignancy. Cholangioscopy allows for direct visualization and sampling of biliary pathology; however, this technology is also associated with inaccurate classification of biliary disease. Previously, an artificial intelligence (AI) system that analyzes cholangioscopy footage was found to be more accurate in diagnosing biliary malignancy than ERCP sampling techniques. The aim of this study was to validate this AI system on a new series of examinations. Three academic centers collected all available unedited cholangioscopy recordings. The videos were processed by the cholangioscopy AI system. After analyzing videos, the AI system provided predictions as to whether malignancy was present. AI performance in classifying strictures was compared with the performance of brush cytology and forceps biopsy. 112 cholangioscopy examinations (containing 4 817 081 images) were generated from 99 patients. Of those examinations, 61 (54.5%) were for investigation of biliary strictures (31 [50.8%] benign, 30 [49.2%] malignant). For the correct classification of strictures, the AI system was 80.0% sensitive and 90.3% specific. It was also significantly more accurate for stricture classification (85.2%) than brush cytology (52.5%; P<0.001), forceps biopsy (68.2%; P=0.04), and the combination of brush cytology and forceps biopsy (66.7%; P=0.02). A previously developed cholangioscopy AI system was found to continually outperform standard ERCP sampling modalities for accurate identification of malignancy, without additional retraining, in a multicenter validation cohort.

OBJECTIVE Mechanical thrombectomy (MT) is well established for large-vessel occlusion (LVO) strokes, but its safety in distal and medium-vessel occlusions (DMVOs) requires further investigation. This study analyzed the relationship between procedural approaches, petechial hemorrhage (PetH), and clinical outcomes in DMVO thrombectomy, with particular attention to technical considerations and the complex interplay between tissue injury and hemorrhagic complications. METHODS A retrospective cohort study was conducted on DMVO stroke patients treated with MT at 37 stroke centers worldwide from 2016 to 2024. Patients were categorized based on follow-up imaging into those with or without PetH. Four logistic regression models analyzed the association of PetH with favorable functional outcomes (modified Rankin Scale score ≤ 2) at 90 days, early neurological improvement (≥ 4-point National Institutes of Health Stroke Scale score decrease at 24 hours), all-cause mortality, and independent determinants of PetH. Adjusted odds ratios (aORs), 95% confidence intervals, and p values were reported. RESULTS Of 1428 patients, 439 (30.7%) developed PetH. Factors independently associated with PetH were multiple thrombectomy passes (aOR 1.58, 95% CI 1.21–2.06; p = 0.001), IV thrombolysis (aOR 1.31, 95% CI 1.01–1.69; p = 0.04), and the combined use of a stent retriever with aspiration as the first-line method compared with aspiration alone (aOR 1.66, 95% CI 1.15–2.38; p = 0.007). Conversely, general anesthesia (aOR 0.55, 95% CI 0.40–0.77; p < 0.001), higher Alberta Stroke Program Early CT Scores (aOR 0.76, 95% CI 0.69–0.83; p < 0.001), and successful recanalization (aOR 0.56, 95% CI 0.39–0.80; p = 0.002) were significantly associated with a lower odds of PetH. PetH was associated with a decreased odds of favorable functional outcomes (aOR 0.51, 95% CI 0.36–0.73; p < 0.001), reduced early neurological improvement (aOR 0.59, 95% CI 0.44–0.79; p < 0.001), and increased all-cause mortality (aOR 1.84, 95% CI 1.23–2.76; p < 0.001). CONCLUSIONS PetH is a frequent sequela following MT in DMVO strokes and is associated with poorer outcomes, likely reflecting underlying ischemic injury rather than direct causation. Procedural factors influence PetH risk, suggesting medical treatment as first-line therapy for DMVOs, with MT reserved for refractory cases using less aggressive approaches.

Study Design Retrospective cohort analysis. Objective (1) Develop a novel computed tomography (CT)-based assessment of endplate bone density (EP-HU), (2) Determine if EP-HU was a stronger predictor than trabecular HU for subsidence after transforaminal lumbar interbody fusion (TLIF). Methods All adult patients who underwent single-level TLIF for lumbar degenerative conditions at an academic center between 2017-2022 were retrospectively identified. EP-HU was calculated from a 2 mm superior and inferior endplate region on the preoperative mid sagittal CT scans, accounting for surface undulations. Lumbar vertebral HUs (trabecular region) were determined in a standard fashion on axial CT. EP-HU + vertebral HU served as an aggregate bone quality metric. Interbody subsidence (≥2 mm threshold) was directly measured on the endplate-facing surface of 1 year CT scans. Univariate and multivariate analysis compared subsidence based on CT bone metrics. Results A total of 114 patients met the inclusion/exclusion criteria. There was no significant difference in fusion or reoperation rate based on subsidence occurrence. Both vertebral HU ( P = .012) and EP-HU ( P < .001) were associated with subsidence. In receiver operating curves, EP-HU was more optimal for subsidence prediction than vertebral HU, but the aggregate metric further optimized the specificity and total area under the curve. In a predictive logistic regression model EP-HU + vertebral HU (aggregate HU < 515 odds ratio: 7.82, P < .001) was a strong independent predictor of subsidence. Conclusion Preoperative calculation of EP-HUs in addition to vertebral HUs may enhance prediction of TLIF subsidence where aggregate endplate and vertebral HU < 515 can be used to identify high risk patients.

Three-dimensional radiomic analysis of digital breast tomosynthesis outperformed two-dimensional measures in breast cancer risk assessment.

Purpose To develop an expert consensus statement on the diagnosis, management, and rehabilitation of medial meniscal root tears (MMRTs) using a modified Delphi technique. Methods A working group developed statements on MMRT diagnosis, nonoperative management, surgical indications, surgical management, alignment, and rehabilitation using modified Delphi techniques. Fifty‐six experts were surveyed over 3 rounds to reach consensus, with agreement measured on a 5‐point Likert scale. Statements were included, revised, or excluded on the basis of predefined thresholds (≥75% agreement, <20% disagreement). Experts suggested revisions or new statements in the first 2 rounds, and final consensus statements were included. Results All 56 experts completed 3 survey rounds. Experts agreed that root tears may occur with no known history of trauma, typically in older patients, and that it should be diagnosed with an magnetic resonance imaging. In symptomatic patients with MMRTs without advanced osteoarthritis should be repaired using an anatomic transtibial pull‐out technique (performing a pie‐crusting technique can be helpful for visualization). Nonoperative management is advised for patients with advanced osteoarthritis. High tibial osteotomy may be considered for significant varus malalignment during MMRT repair. The only statement without consensus was the management of asymptomatic MMRTs with mild medial compartment cartilage wear, indicating ongoing debate. Conclusions Overall, 98% of statements reached consensus. There is agreement that magnetic resonance imaging is the gold standard for diagnosis. Symptomatic MMRTs without advanced osteoarthritis should be repaired early using an anatomic transtibial pull‐out technique. End‐stage knee osteoarthritis warrants nonoperative management of MMRTs, and a structured postoperative protocol with limited weightbearing and range of motion is essential after repair. No agreement was reached on managing asymptomatic MMRTs in patients without significant medial compartment degeneration. Meniscal centralization sutures may help in cases of substantial extrusion, but their routine use is debated. Level of Evidence Level V, consensus of expert opinion.