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Abstract Cholecystectomy (CCY) is the standard treatment for acute cholecystitis. For non-surgical patients, percutaneous cholecystostomy tube (PT-GBD) is recommended but is associated with high readmission rates and poor quality of life. Endoscopic gallbladder decompression techniques, including endoscopic transpapillary gallbladder drainage (ET-GBD) and endoscopic ultrasound-guided gallbladder drainage (EUS-GBD), are alternatives. Studies comparing ET-GBD and EUS-GBD have shown EUS-GBD to have superior outcomes. However, these studies assessed ET-GBD mostly via single transcystic stent placement (SSET-GBD). This study aimed to compare outcomes of dual transcystic stents (DSET-GBD) and EUS-GBD in non-surgical candidates with acute cholecystitis. A multicenter analysis was conducted on patients who underwent ET-GBD or EUS-GBD between January 2019 and January 2023. Data were extracted from electronic medical records and outcomes including technical success, success, adverse events (AEs), and recurrence rates of cholecystitis were measured. Of 129 procedures (56 EUS-GBD; 73 ET-GBD), technical success was achieved in 87.5% of EUS-GBD and 86.3% of ET-GBD attempts. Immediate clinical success was achieved in 98.1% for EUS-GBD and 100% for DSET-GBD. AE rates were similar between the groups. Recurrent cholecystitis rates were 5.3% for EUS-GBD and 8.2% for DSET-GBD (P = 0.692). This study demonstrates that DSET-GBD has similarly low rates of recurrent acute cholecystitis compared with EUS-GBD. DSET-GBD should be considered as an alternative management strategy for management of acute cholecystitis in patients who are unable to undergo CCY.

ObjectivesTo combine sonographic Murphy sign (SMS) with clinical parameters to effectively stratify patients into risk groups for acute cholecystitis.MethodsConsecutive emergency department patients from April 1, 2019 to August 31, 2022 with possible acute cholecystitis were grouped using patient age, sex, and white blood cell count to determine the rate of acute cholecystitis found in subgroups. Three distinct clinical risk groups were established and then regrouped by prospective assessment of SMS into three non‐imaging risk groups. Differences in the rate of acute cholecystitis for clinical parameters, clinical risk groups, and non‐imaging risk groups were statistically analyzed.ResultsOf 1231 patients (mean [SD] age, 51.2 [19.5]; 476 [38.7%] male), 156 had acute cholecystitis (mean [SD] age, 62.0 [15.4]; 85 [54.5%] male). Rates differed based on sex (9.4% female vs 17.9% male, P < .001), age group (1.8% for patients <30 years, 9.0% for patients 30–59 years, 22.3% for patients ≥60 years; P < .001), and white blood cell count (23.1% elevated vs 6.6% not elevated; P < .001). The low, average, and high non‐imaging risk groups had acute cholecystitis rates of 1.8%, 14.0%, and 43.1%, respectively. Relative risk (95% CI) for the low non‐imaging group compared with others was 0.07 (0.04, 0.12; P < .001); relative risk for the high non‐imaging risk group compared with others was 7.05 (5.32, 9.43; P < .001).ConclusionsSonographic Murphy sign assessment combined with patient age, sex, and white blood cell count effectively stratifies acute care patients into distinct acute cholecystitis risk groups.

ImportanceRetrieval strategies for children, adolescents, and young adults with relapsed classic Hodgkin lymphoma (cHL) aim to maintain efficacy while minimizing long-term toxic effects. Children, adolescents, and young adults with low-risk, relapsed cHL may benefit from replacing high-dose chemotherapy and autologous stem cell transplant with less intensive involved-site radiotherapy (ISRT).ObjectiveTo evaluate a risk-stratified, response-adapted, transplant-free approach for treatment of children, adolescents, and young adults with low-risk relapsed cHL with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response and ISRT (30.0 to 30.6 Gy).Design, Setting, and ParticipantsCheckMate 744 (R1 cohort) was a phase 2, nonrandomized, single-arm study enrolling children, adolescents, and young adults aged 5 to 30 years with low-risk cHL between September 25, 2017, and December 16, 2020, across the US, Canada, and Europe. Data were analyzed from September 2017 to November 2022.ExposuresPatients received 4 cycles of nivolumab plus BV induction; patients with complete metabolic response (CMR) received an additional 2 cycles of nivolumab plus BV while patients with suboptimal response received 2 cycles of BV plus bendamustine intensification. Patients with CMR after induction or intensification received ISRT consolidation.Main Outcomes and MeasuresPrespecified coprimary end points were CMR rate (Lugano 2014 classification) any time before ISRT and 3-year event-free survival (EFS) rate, per blinded independent central review (BICR).ResultsOf 28 included patients treated in the low-risk cohort, 18 (64%) were female, and the median (range) age was 17 (6-27) years. At a median (range) follow-up of 31.9 (2.2-55.3) months, CMR per BICR any time before ISRT was 93% (26 of 28; 90% CI, 79.2-98.7; objective response rate [ORR], 100%), and 23 of 28 (82%) achieved CMR per BICR after 4 cycles of nivolumab plus BV (ORR, 96.4%). Kaplan-Meier estimates of EFS and progression-free survival rates at 3 years were 87% (3 of 18; 90% CI, 69.5-94.7) and 95% (1 of 18; 90% CI, 76.7-99.0), respectively. During induction, 22 patients (79%) had treatment-related adverse events, including 7 with grade 3 or 4 adverse events, 2 with anemia, 1 with neutropenia, and 6 with immune-mediated adverse events. Serious adverse events leading to discontinuation occurred in 2 patients.Conclusions and RelevanceThis nonrandomized clinical trial found that for children, adolescents, and young adults with low-risk, relapsed cHL, a transplant-free, risk-adapted, response-based approach with nivolumab plus BV and ISRT offered high CMR rates and high 3-year EFS rate, with a safety profile consistent with that of each agent used.Trial RegistrationClinicalTrials.gov Identifier: NCT02927769

This nonrandomized clinical trial reports outcomes for children with low-risk relapsed Hodgkin lymphoma treated with second-line chemotherapy and involved-field radiotherapy without autologous stem cell transplant.

PURPOSE In light of evolving evidence that some patients with node-positive estrogen receptor–positive (ER+) disease may receive less benefit from chemotherapy, this study reports 12-year outcomes of the C9741 trial overall, and by the sensitivity to endocrine therapy (SET2,3) test index, a biomarker measuring endocrine transcriptional activity, to identify patients most likely to benefit from dose-dense chemotherapy. METHODS In all, 1,973 patients were randomly assigned to dose-dense versus conventional chemotherapy. Hazard ratios (HRs) for prognosis and for predictive interaction with chemotherapy schedule were estimated from Cox models of long-term disease-free survival (DFS) and overall survival (OS). SET2,3 was tested on the 682 banked RNA samples from ER+ cancers. RESULTS Dose-dense chemotherapy improved DFS in the overall study population by 23% (HR, 0.77 [95% CI, 0.66 to 0.90]) and OS by 20% (HR, 0.80 [95% CI, 0.67 to 0.95]); the benefits of dose-dense therapy were seen for ER+ and ER-negative subsets, without significant interaction between treatment arm and ER status. Low SET2,3 status was highly prognostic, but also predicted improved outcomes from dose-dense chemotherapy (interaction P = .0998 for DFS; 0.027 for OS), independent of menopausal status. Specifically, low endocrine transcriptional activity predicted benefit from dose-dense chemotherapy, whereas tumor burden and proliferation-driven signatures for molecular subtype classification did not. CONCLUSION At 12-year follow-up, C9741 confirmed the sustained long-term benefit of adjuvant dose-dense chemotherapy for node-positive breast cancer. SET2,3 identified patients with ER+ breast cancer who benefited from dose-dense chemotherapy, and specifically, this benefit was predicted by low endocrine activity in the cancer, rather than tumor burden, molecular subtype, or menopausal status.

Background: Previous research has reported higher rates of both injury and illness among Paralympic athletes compared with Olympic athletes during the Winter Olympic and Paralympic Games, but no studies have directly compared injury and illness incidence between Olympic and Paralympic athletes competing in a Summer Games. Purpose: To compare injury and illness rates between Olympic and Paralympic Team USA athletes competing in the Tokyo 2020 Olympic and Paralympic Games. Study Design: Descriptive epidemiology study. Methods: All injuries and illnesses that occurred among the Team USA athletes competing in the Tokyo 2020 Summer Olympic or Paralympic Games were documented. A total of 701 Team USA athletes (53.6% female) competed in the Tokyo 2020 Summer Olympic Games, across 34 different sports. For the Tokyo 2020 Summer Paralympic Games, a total of 245 athletes (51.6% female) competed across 20 sports. Incidence rates (IRs) per 1000 athlete-days were calculated according to sex, sport, anatomic location, and illness type. IR ratios (IRRs) were calculated to compare IRs between male and female athletes and between Olympic and Paralympic athletes. Results: Overall, there were no differences in injury incidence (IRR, 1.18; 95% CI, 0.84-1.68) or illness incidence (IRR, 0.68; 95% CI, 0.41-1.15) between Olympic and Paralympic athletes. Male Paralympic athletes were less likely to sustain an illness compared with female Paralympic athletes (IRR, 0.35; 95% CI, 0.11-0.90). Conclusion: There were no differences in injury or illness rates between Olympic and Paralympic Team USA athletes competing at the Tokyo 2020 Summer Games, contrary to previous comparisons among winter sport athletes. These results challenge the prevailing notion that Summer Paralympic athletes are at greater injury and illness risk, suggesting that factors beyond Olympic or Paralympic Games participation influence health concerns.

Abstract Purpose: Around 10% to 15% of prostate cancers harbor recurrent aberrations in the Forkhead Box A1 gene, FOXA1, whereby the alteration type and the effect on the forkhead (FKH) domain affect protein function. We developed a FOXA1 classification system to inform clinical management. Experimental Design: A total of 5,014 prostate cancer samples were examined using whole-exome and -transcriptome sequencing from the Caris Life Sciences database. We denoted class 1 FOXA1 alterations as missense and in-frame insertions/deletions with subclasses oriented with respect to the FKH domain. These were in the first part of the FKH domain [class 1A: amino acids (AA) 168–246], within the Wing2 region of FKH (class 1B: AA 247–269), or outside FKH (class 1C: AA 1–167, 270+). Two hotspot missense mutations at R219 were denoted class 2. Class 3 included predicted truncating mutations with subclasses partitioned based on the FKH domain (class 3A: AA 1–269 and class 3B: AA 270+). Class 4 represented FOXA1 amplifications. Real-world overall survival and therapy outcomes were determined from insurance claims. Results: FOXA1 alterations did not influence survival when considered in aggregate but had distinct prognostic effects when stratified by class. In primary prostate samples, class 1A alterations were associated with overall improved survival (HR, 0.57; P = 0.03); a similar trend was seen in metastatic biopsies with class 1B (HR, 0.84; P = 0.09). Conversely, in primary specimens, class 1C exhibited worse survival upon second-generation androgen receptor signaling inhibitor treatment (HR, 1.93; P &lt; 0.001). Class 2 mutations (R219C/S) were enriched in neuroendocrine prostate cancers and were associated with overall poor survival (HR, 2.05; P &lt; 0.001) and worse outcomes to first-line androgen-deprivation therapies (HR, 2.5; P &lt; 0.001). Class 3A alterations indicated improved survival (HR, 0.70; P = 0.01), whereas class 3B alterations portended poor outcomes (HR, 1.50; P &lt; 0.001). Amplifications (class 4) indicated poor outcomes in metastatic samples (HR, 1.48; P = 0.02). Molecularly, different FOXA1 alteration classes harbored distinct mutational and immunologic features as well as unique transcriptional programs. Finally, relative to European Americans, African Americans had increased class 1C alterations, whereas Asian/Pacific Islander patients had increased class 1B alterations. Conclusions: FOXA1 alterations should not be interpreted in aggregate, as different classes are associated with divergent molecular features and clinical outcomes. Our revised classification schema facilitates clinical decision-making for patients with prostate cancer and uncovers important racial differences.

Purpose of review Peyronie's disease characterizes a condition in which there is angular curvature of the penis. We know that the most patients with Peyronie's disease will not have spontaneous resolution of their penile curvature. As such, patients who desire treatment can elect for either surgical or nonsurgical therapy. Herein, we discuss the contemporary nonsurgical management options for Peyronie's disease. Recent findings Nonsurgical management options for Peyronie's disease include oral therapy, intra-lesional injections, and penile traction therapy. At the time of this review, there is essentially no high-level evidence demonstrating any benefit for oral therapy. Penile traction therapy has evolved over the past decade with second-generation devices demonstrating strong efficacy and more convenient treatment regimens. Intra-lesional options include collagenase Clostridium histolyticum (CCH), verapamil, and interferon alpha-2b. The IMPRESS trial garnered the strongest level of evidence (two randomized, double-blind, placebo-controlled trials) to support the safety and efficacy of CCH. Verapamil is an option supported by several urological societies; however, the evidence supporting its efficacy is inconsistent between several notable series and randomized studies. IFN alpha 2b can produce modest improvement in curvature, however, is not available for use in North America. Summary Herein, we will discuss notable advances in nonsurgical management of Peyronie's disease.