Citations

Acute cholecystitis affects ∼200,000 individuals annually in the United States, with laparoscopic cholecystectomy as the gold standard treatment. However, in high-risk surgical candidates, alternative drainage methods are necessary. Percutaneous transhepatic gallbladder drainage (PT-GBD) has traditionally served as the primary alternative intervention, offering rapid decompression, but is limited by a negative impact on the patient’s quality of life, the risk of long-term or even permanent tube placement, adverse events, and high recurrence rates. Endoscopic approaches, such as endoscopic transpapillary gallbladder drainage (ET-GBD) and, more recently, endoscopic ultrasound-guided gallbladder drainage (EUS-GBD), have emerged as viable alternatives to PT-GBD. EUS-GBD, first introduced in 2007, offers technical and clinical outcomes comparable to PT-GBD with fewer adverse events, shorter hospital stays, and lower rates of recurrence. The introduction of lumen-apposing metal stents (LAMS) has revolutionized EUS-GBD, simplifying deployment and enabling subsequent internal gallbladder access, which allows additional interventions such as cholecystoscopy and stone removal. EUS-GBD is now supported by international guidelines, and 1 device has achieved FDA approval for the management of acute cholecystitis in nonsurgical candidates. Proper patient selection is essential, guided by multidisciplinary evaluation, with EUS-GBD contraindicated in specific scenarios such as gallbladder perforation, coagulopathy, and large-volume ascites. Technical considerations include choice of access site (transgastric versus transduodenal), stent type, and procedural route [direct (freehand) or wire-guided]. Postprocedural care and stent management remain variable and nonstandardized. Emerging data suggest that interval cholecystectomy can still be performed safely after EUS-GBD. As adoption of EUS-GBD with LAMS expands, structured training and standardization of practice are crucial to optimizing outcomes.

An accurate differential diagnosis for diffuse lung disease can be confidently established by using a systematic approach to identify the predominant radiographic pattern, determine the distribution of disease, and assess for architectural or volume change.

Hydrocephalus has treatment options including either temporary or permanent cerebrospinal fluid (CSF) diversion, and radiologists should be familiar with shunt components and understand the characteristic imaging features and appearances of different types of shunt malfunctions and shunt-related complications.

The study establishes the presence of a robust mitophagic response to acute mitochondrial depolarization in hASM cells mediated through the canonical PINK1-Parkin pathway. By integrating quantitative mitochondrial labeling and biochemical analyses, we demonstrate increased mitochondrial damage and remodeling, accompanied by mitochondrial PINK1 accumulation and Parkin activation, resulting in ubiquitin-dependent signaling and lysosomal engulfment. These findings identify mitophagy as a critical adaptive mechanism for maintaining mitochondrial quality control in airway smooth muscle cells during metabolic stress.

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.

Introduction: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease without approved medical therapies. We examined the efficacy and safety of oral vancomycin (OV) in those with PSC. Methods: In this phase 3, 18-month, double-blind, placebo-controlled trial, we randomly assigned adults with PSC and a serum alkaline phosphatase (SAP) greater than 1.5 times the upper limit of normal to placebo or oral vancomycin (OV) with dosages ranging from 125-375 mg four times daily pending biochemical response. The primary endpoint was normalization of SAP. Results: Of the 82 patients who underwent randomization, 73 individuals had at least one outcome assessment. Individuals who withdrew early were less likely to rate their baseline health as excellent or very good (23.4% vs 54.5%, p<0.01) despite having similar PSC prognostic features to those who completed the study. SAP normalization rates were similar (5% placebo, 6.7% OV, p=1.00) after 18 months. Those who received OV had greater reduction in SAP (+1.2% placebo, -21.9% OV, p=0.03). There were no differences in the changes in either the Mayo PSC risk score (-0.1 placebo, -0.1 OV, p=0.88) or liver stiffness values (+0.1 kPa placebo, -4.0 kPa OV, p=0.15). Discoloration of the teeth and tongue was the most common side effect of OV (17.5%). Conclusions: OV was not associated with clinically significant reductions in markers of PSC disease severity. Impairments in quality of life may influence patient retention in clinical trials.

ABSTRACT Background Post‐transplant malignancy is a major determinant of long‐term outcomes after solid organ transplantation. Whether simultaneous pancreas–kidney (SPK) transplantation confers a differential post‐transplant cancer risk compared With kidney transplantation alone (KA) remains uncertain. Methods We conducted a retrospective propensity score–matched cohort study of adult transplant recipients at three Mayo Clinic sites between 2001 and 2017. SPK recipients ( n = 484) were matched 1:1 with KA recipients using propensity scores. The primary outcome was post‐transplant cancer incidence analyzed using Fine–Gray competing risks regression with death as a competing event. Standardized incidence ratios (SIRs) were calculated relative to the US general population. Cox proportional hazards models with cancer modeled as a time‐varying covariate evaluated associations with mortality and death‐censored graft failure. Results Over a median follow‐up of 10 years, overall cancer incidence was similar between SPK and KA recipients (subdistribution hazard ratio [sHR] 0.80, 95% CI 0.63–1.02; p = 0.07). The observed trend toward lower cancer incidence in SPK recipients was driven by a lower incidence of non‐melanoma skin cancer (NMSC) (sHR 0.72, 95% CI 0.53–0.97; p = 0.03), which was attenuated after age adjustment (sHR 0.76, p = 0.07). Incidence of other malignancies did not differ between groups. Compared with the US general population, cancer risk excluding NMSC was approximately twofold higher in both cohorts (SIR 2.18 for SPK vs. 2.23 for KA). Incident malignancy was strongly associated with increased mortality (HR 3.40 in KA and 2.07 in SPK) but not with a statistically significant increase in graft failure. Conclusions In this propensity score–matched cohort study, overall post‐transplant malignancy incidence was comparable between SPK and KA recipients. Both groups experienced substantially elevated cancer risk relative to the general population, and incident malignancy was strongly associated with mortality. These findings suggest that malignancy risk is driven primarily by shared immunologic and demographic factors rather than transplant type.

ABSTRACT Angioimmunoblastic T‐cell lymphoma (AITL) is an aggressive peripheral T‐cell lymphoma with poor outcomes, and the role of autologous stem cell transplantation (ASCT) as consolidation after frontline therapy remains controversial. We conducted a retrospective cohort study using the National Cancer Database, including adults diagnosed with AITL between 2004 and 2020 who received frontline systemic therapy. Patients were categorized as chemotherapy alone (Chemo) or chemotherapy followed by ASCT (Chemo + ASCT). To mitigate immortal time bias, prespecified landmark analyses were performed, with a 6‐month landmark analysis as the primary approach and a 9‐month landmark analysis as a sensitivity analysis. Multivariable Cox regression and propensity score weighting using inverse probability of treatment weighting for the average treatment effect were used to address measured confounding. Among 3996 patients receiving systemic therapy, 686 (17.2%) underwent ASCT. In the 6‐month landmark analysis, ASCT was associated with improved overall survival (HR, 0.53; 95% CI, 0.45–0.62; p < 0.001). Findings were consistent in the 9‐month landmark analysis (HR, 0.58; 95% CI, 0.49–0.69; p < 0.001) and IPTW‐adjusted model (HR, 0.51; 95% CI, 0.44–0.60; p < 0.001). In this large real‐world cohort, ASCT consolidation was consistently associated with improved survival in patients with AITL. Although treatment‐response data were unavailable and residual confounding cannot be excluded, these findings provide supportive real‐world evidence and warrant prospective studies with treatment‐timing and response data to better define patient selection.

ABSTRACT Ileus is a common gastrointestinal complication in critically ill patients, posing a unique management challenge due to its multifactorial etiology and impact on clinical stability. Standard therapeutic approaches often fail in the setting of metabolic derangement and hemodynamic instability. Prucalopride, a selective 5-HT 4 receptor agonist, has demonstrated efficacy in promoting colonic motility; however, its use in severe small bowel and colonic ileus or decompensated liver disease populations remains limited. We report the case of a 28-year-old man with decompensated alcoholic hepatitis who developed severe small bowel and colonic ileus refractory to standard management. Concerns for worsening illness prompted a trial of prucalopride, which was temporally associated with rapid resolution of the ileus and remarkable improvement in radiographic imaging and clinical phenotype. Prucalopride may be a potential therapeutic option for severe small bowel and colonic ileus in critically ill patients. Further studies are warranted to delineate its safety and efficacy.