Citations

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.

ABSTRACT The role of DNA topoisomerase II beta (TOP2B) in cardiomyocyte differentiation is poorly understood. To address this, human induced pluripotent stem cells (hiPSC) were differentiated into cardiomyocytes (CM) that were wild type (WT) or contained a genomic deletion of Topoisomerase 2B (BKO). Both WT and BKO hiPSC could be induced to differentiate into sheets of beating cardiomyocytes. BKO hiPSC take slightly longer to differentiate into sheets of beating CM than WT iPSC. RNA was prepared from both undifferentiated and differentiated WT and BKO hiPSC. RNA-seq was used to examine gene expression changes when the WT and BKO hiPSC were differentiated into CM. Gene expression changes following differentiation of BKO cells were largely similar to those in WT cells. In addition, the differentiated WT CM were treated with dexrazoxane (ICRF-187), a TOP2 catalytic inhibitor that targets both TOP2A and TOP2B, or topobexin, a new TOP2B selective catalytic inhibitor. Topobexin inhibition partially phenocopied a TOP2B deletion and thereby providing an alternative to TOP2B gene knockout in many cell lines. In future, hiPSC derived CM with and without TOP2B and inhibition by topobexin ex vivo CM could be used to study anthracycline-induced cardiotoxicity and to screen for cardioprotectants.

Background Reliable biomarkers of inflammatory activity in multiple sclerosis (MS) are needed to complement clinical and MRI assessments. Circulating microRNAs (miRNAs) are promising candidates due to their serum stability and involvement in MS-related biological pathways. Objectives To evaluate whether selected serum miRNAs can discriminate relapse from remission in treatment-naive patients with relapsing-remitting MS (RRMS). Methods In this prospective paired study, newly diagnosed, untreated RRMS patients were sampled during clinical relapse and subsequent remission. A targeted miRNA panel was quantified using quantitative PCR. Differential expressions were assessed using paired statistical testing with multiple comparison correction. Diagnostic performance was evaluated using ROC analysis and multivariate logistic regression. Pathway enrichment analysis was performed using Ingenuity Pathway Analysis. Results Twenty patients (40 paired samples) were included. Eight miRNAs were differentially expressed between relapse and remission after Benjamini–Hochberg correction. hsa-miR-122-5p showed the largest fold change (fold change = 3.0; adjusted p = 0.043). A three-miRNA panel (hsa-miR-122-5p, hsa-miR-15b-5p, hsa-miR-30e-5p) demonstrated high discriminative accuracy (area under the curve = 0.88; 95% CI 0.79–0.96). Pathway analysis highlighted inflammatory, metabolic, and hypoxia-related processes. Conclusions Circulating miRNAs distinguished relapse from remission in treatment-naive RRMS patients, suggesting their potential as complementary biomarkers of disease activity. These findings should be considered exploratory and require validation in an independent, larger cohort.

BACKGROUND AND OBJECTIVES: This study proposes and assesses the validity of postoperative dysphagia severity categories based on patients' Eating Assessment Tool-10 (EAT-10) scores and quality-of-life patient-reported outcome measures (PROMs) collected before and after cervical spine surgery. METHODS: A prospectively collected multi-institutional quality registry including 2003 patients was retrospectively reviewed. Patients were categorized based on EAT-10 score severities, with thresholds determined by existing literature and significant differences in PROMs: none (0-2), mild (3-4), moderate (5-15), and severe (16-40). Correlations between EAT-10 severity and established PROMs were assessed at baseline, 3-, and 12-month follow-ups. The Dunn test using Bonferroni adjustment was used to identify differences in PROMs between EAT-10 severities. Multivariate linear regression assessed how EAT-10 severity affects PROMs at baseline, 3-, and 12-month follow-ups. RESULTS: Among 1659 patients with 3-month EAT-10 data, there were 1183 no, 149 mild, 245 moderate, and 82 severe dysphagia patients. Neck Disability Index and EuroQol 5-Dimension scores were significantly different between none vs mild ( P < .001; P = .001), mild vs moderate ( P < .001; P < .001), and moderate vs severe ( P = .035; P = .024) at 3 months. Among 1405 patients with 12-month EAT-10 data, there were 1044 no, 100 mild, 194 moderate, and 67 severe dysphagia patients. Neck Disability Index scores were significantly different between none vs mild ( P < .001) and moderate vs severe ( P = .004) but not for mild vs moderate ( P > .9) at 12 months. EuroQol 5-Dimension scores were significantly different between none vs mild ( P = .004) and mild vs moderate ( P = .005) but not for moderate vs severe ( P = .08). In multivariate regression, EAT-10 severity categories independently predicted worse PROMs at all time points. CONCLUSION: We propose none (0-2), mild (3-4), moderate (5-15), and severe (16-40) dysphagia categories based on EAT-10 scores. Evidence from univariate and multivariate analyses strengthens the validity of our proposed EAT-10 severity categories, providing statistical justification for their incorporation into clinical practice.