Citations

Diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, arises from various pathogenic mechanisms including gene translocations and fusions. Detection of gene rearrangements using fluorescence in situ hybridization (FISH) is a standard practice for DLBCL diagnosis and guides treatment decisions. High-throughput chromosome conformation capture (Hi-C) DNA sequencing is a next-generation sequencing-based technology to identify genome-wide rearrangements using a single assay. In this study, Hi-C sequencing was performed using FFPE tissues from 159 patients with DLBCL, and identified 746 cancer genes at or proximal to the rearrangement breakpoints with a total of 1903 occurrences. Focusing on clinically important rearrangements, Hi-C detected 102 rearrangements of MYC, BCL2, and/or BCL6 in 92 patients and revealed the fusion partners, including 25 rearrangements missed by FISH. Causes of FISH negative results included FISH-cryptic breakpoints, complex or faint FISH signals, low percentage of FISH positivity, and issues related to tissue fixation. Moreover, in 20 patients (12.6%), Hi-C sequencing detected 22 rearrangements characteristic of other lymphoma types, including CCND1 rearrangements that could lead to reclassification as mantle cell lymphoma. Survival analysis for genome-wide rearrangements using machine learning models identified MYC, PD-L1, CCND1, BCL2, NTRK1/PRCC, RRAS, and FANCE rearrangements with significant prognostic effects in the DLBCL cohort. In conclusion, Hi-C sequencing detects gene rearrangements crucial for diagnosis in an unbiased and molecular manner and showed high sensitivity and specificity in our study. These advantages of Hi-C sequencing offer help to improve the workflow of clinical pathology laboratories, diagnostic precision, and treatment of large B-cell lymphoma.

Purpose To assess if hospitals with high physician employment differ in risk-standardized mortality and readmission rates. Design/methodology/approach A cross-sectional evaluation of data from the 2021 Hospital Readmission Reduction program, Hospital Value-Based Purchasing Program, American Hospital Association and Area Health Resource Files was utilized. A binary variable was created to identify hospitals with ≤ 50% or >50% employed physicians. Dependent variables included 30-day mortality and readmission rates for acute myocardial infarction (AMI), congestive heart failure (CHF), pneumonia (PN), and chronic obstructive pulmonary disease (COPD) hospitalizations. Propensity score matching was utilized to compare hospitals. The final matched cohort compared 200 hospitals in each group ( ≤ 50% physicians and > 50% physicians). Findings After matching, hospitals with > 50% physician employment were associated with improved mortality scores for AMI (−0.36, 95% CI: −0.58, −0.14), COPD (−0.38, 95% CI: −0.63, −0.14), and PN (−0.71, 95% CI: −1.15, −0.27). No significant differences were noted for CHF mortality or readmission rates. Originality/value There has been a growth in hospitals employing physician in the United States. This work demonstrates that hospitals with higher physician employment levels are associated with lower mortality scores. This likely reflects a broader organizational phenotype characterized by alignment, scale and clinical integration rather than physician employment as an isolated strategy. Further research should examine organizational features to better disentangle the structure and combination of organizational characteristics underlying these associations.

Importance Currently, there are no standardized outcome domains or measures in clinical trials for facial aging. Heterogeneity in outcome domains and measurement instruments across clinical trials creates difficulty in directly comparing interventions, determining superior therapies, and developing high-quality meta-analyses. Objective To develop a core outcome set (COS) of essential domains to be reported in clinical trials evaluating the efficacy of interventions for facial aging. Evidence Review PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from September 2005 to September 2015. An updated search of the same databases was performed from September 2015 to February 2026. Studies were included if (1) they were randomized clinical trial or controlled clinical trial in design, (2) they assessed the efficacy or safety of an intervention for facial aging, (3) they were published in English, and (4) they involved human participants. Complementary sources, including patient interviews, were used to capture further relevant outcomes. Two rounds of Delphi surveys, followed by consensus meetings, were used to identify outcome domains considered most important by both patient and physician stakeholders. Findings The final COS consists of 6 outcome domains: (1) overall convenience of treatment; (2) time to return to normal work and social activity; (3) overall assessment of focused area of treatment (at the point in time when treatment is expected to provide peak benefit); (4) duration of treatment effect; (5) severity of persistent local or systemic adverse events, including pigmentary change, skin texture change, delayed healing, scarring, and serious adverse events; and (6) patient satisfaction with treatment. Conclusions and Relevance The 6 outcome domains identified through a Delphi consensus are recommended for reporting in future facial aging trials to ensure that outcomes that matter most to patients and clinicians are measured and that results are comparable across interventions.

Importance Hypopigmented mycosis fungoides (HMF) is uncommon in adults, and data on clinicopathologic features and long-term outcomes remain sparse. Objective To investigate the clinicopathologic features and outcomes of adults with HMF in a large multicenter cohort. Design, Setting, and Participants This retrospective multicenter cohort study conducted from January 2011 to October 2023 at 6 US tertiary referral centers and included adults (18 years or older at diagnosis) with biopsy-confirmed HMF and hypopigmentation documented at diagnosis, with a median (range) follow-up of 39 (1-347) months. Data were analyzed from February to December 2025. Exposures Clinical variant, immunophenotype predominance, and polymerase chain reaction–based T-cell receptor ( TCR ) gene rearrangement in peripheral blood and/or skin. Main Outcomes and Measures Best overall response, defined as complete response, partial response, stable disease, or progressive disease, and progression to a higher stage. Results The cohort included 224 adults with HMF (median [range] age, 44 [18-74] years), of whom 164 (73%) were women (60 men [27%]), 5 (2%) were Asian individuals, 1 (0.4%) was a Hispanic/Latino individual, 1 (0.4%) was a Middle Eastern individual, 19 (8%) were White individuals, and 186 (83%) were Black individuals; 219 (98%) presented with early-stage disease. Most had hypopigmented lesions only (159 [71%]), whereas 65 (29%) exhibited mixed-variant mycosis fungoides; outcomes were similar between groups. Among 141 patients with available immunophenotyping, 88 (63%) had CD8-positive predominance. Among 207 treated patients, most (179 [90%]) received skin-directed therapy alone. Among 198 evaluable patients, the best overall response was complete response for 52 (26%), partial response for 101 (51%), stable disease for 34 (17%), and progressive disease for 11 (6%). Over a median (range) follow-up of 39 (1-347) months, 14 of 224 patients (6%) experienced progression to a higher stage, including 5 of 219 patients (2%) with early-stage disease at baseline who experienced progression to advanced-stage disease. Peripheral blood TCR monoclonality was detected in 23 of 85 tested patients (27%) and was associated with poorer treatment response but not with disease progression. Conclusions and Relevance The finding of this cohort study suggest that adult HMF demonstrated a generally indolent course, with favorable response to skin-directed therapy, irrespective of immunophenotype or mixed-variant presentation. Peripheral blood TCR monoclonality was associated with lower treatment response but not disease progression.

Importance Friedreich ataxia (FA), a fatal, autosomal recessive disorder caused by pathogenic variants in the frataxin ( FXN ) gene, is characterized by progressive neurologic and cardiac disease, with cardiac disease being the major cause of death. Preclinical studies have demonstrated that systemic administration of AAVrh.10hFXN, an rh.10 serotype cardiotropic adenoassociated virus (AAV) vector expressing the normal human FXN coding sequence, reverses the cardiomyopathy in FXN-deficient mice. Objective To assess the safety and preliminary efficacy of administration of AAVrh.10hFXN to adults with FA cardiomyopathy. Design, Setting, and Participants This nonrandomized clinical trial evaluates the pooled data of 2 independent, open-label, dose-escalation trials that used the same gene therapy vector and similar clinical protocols among patients with FA cardiomyopathy at academic medical centers. Data were collected from February 22, 2022, to October 4, 2025, for trial 1 and from February 14, 2023, to September 10, 2025, for trial 2 and analyzed together from November 5, 2025, to March 12, 2026. Intervention AAVrh.10hFXN, administered intravenously in 3 dose cohorts (1.8 × 10 11 , 5.6 × 10 11 , and 1.2 × 10 12 vector genomes per kilogram of body weight). Main Outcomes and Measures In addition to safety as the primary outcome, multiple parameters of exploratory end points were assessed, including cardiac biopsy levels of FXN protein, cardiac magnetic resonance imaging–derived left ventricular mass index (LVMI), and serum high-sensitivity (hs) troponin I. Results Seventeen patients with FA cardiomyopathy (mean [SD] age, 25 [6] years; 11 [65%] female) were followed up for a mean (SD) of 20 (8) months. There were 4 serious adverse events, 3 possibly related to prednisone immunosuppression and 1 possibly vector-related myocarditis 12 months after therapy, all of which resolved. Other adverse events were transient, nonserious, or not treatment related. In all 8 patients with cardiac biopsy 3 months after therapy, there were higher levels of cardiac FXN (dose cohort 1, 20%; cohort 2, 81%; cohort 3, 123%). After therapy, LVMI was lower by at least 10% in 9 patients and stabilized in 8 patients. Excluding the patient with myocarditis, posttherapy values of serum hs troponin I were lower by at least 10% in 15 patients and higher by at least 10% in 2 patients. Conclusions and Relevance Findings of this nonrandomized clinical trial suggest that intravenous administration of AAVrh.10hFXN was well tolerated and may be a potential treatment for FA cardiomyopathy, as evidenced by preliminary improvement in exploratory efficacy end points. Trial Registration ClinicalTrials.gov Identifiers: NCT05302271 and NCT05445323

Abstract Objective To evaluate otolaryngology (ENT) residency match trends before and after the USMLE Step 1 transition to pass/fail. Study Design Observational longitudinal analysis of annual, publicly available specialty‐level data (2010‐2025). Setting National Resident Matching Program (NRMP). Methods Data from 2010 to 2025 were used to calculate applicants per PGY‐1 position, fill rate, and nonmatch‐in‐specialty rate. ENT was compared with plastic surgery, orthopedic surgery, neurological surgery, and general surgery. We used ordinary least squares (OLS), segmented regression with a 2023 breakpoint, and difference‐in‐differences (DID) models. Results From 2010 to 2025, ENT programs increased from 105 to 139 and positions from 280 to 394. Applicants per position ranged from 1.06 to 1.60 (mean 1.38). OLS showed no significant long‐term trend in applicants per position (+0.002/year, P = .86), fill rate (+0.03 percentage points/year, P = .68), or nonmatch‐in‐specialty rate (+0.04 percentage points/year, P = .94). Segmented regression showed no significant post‐2023 changes in applicants per position (slope change +0.03/year, P = .78), and no significant changes in applicant counts ( P = .7). ENT had the largest 2022 to 2023 decline in this cohort, in both applicants (−14.1%) and applicants per position (−16.9%). However, in two‐way fixed‐effects DID models, there was no ENT‐specific post‐transition change in applicants per position ( P > .05 in primary and sensitivity analyses). Conclusion ENT remained highly competitive but trend‐stable from 2010 to 2025. Although 2023 showed a notable drop in applicants, we found no consistent evidence of a sustained ENT‐specific competitiveness shift after the Step 1 pass/fail transition. Level of Evidence 4.

A 70-year-old woman with a past medical history of breast cancer is undergoing surveillance. She also had a history of repeated blood transfusions for refractory anemia caused by treated marrow metastatic disease. Laboratory tests showed elevated AST (50 U/L) and ALT (115 U/L). 99m Tc MDP bone scintigraphy revealed intense diffuse splenic uptake. No splenic calcifications or infarcts were found on contrast-enhanced CT. MRI demonstrated signal dropout on in-phase sequences and marked T2 hypointensity of the spleen and liver, without focal splenic lesions, suggesting transfusion-related secondary hemosiderosis. Iron overload should be considered when diffuse splenic uptake is observed on bone scintigraphy.