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Abstract Background Multiple guideline-based surgical treatment options for Peyronie’s disease (PD) exist, including penile plication and plaque incision or excision and grafting. Surgical incision type may differ depending upon location and severity of curve, planned concomitant procedures, and surgeon preference. Aim To evaluate postoperative wound complications comparing outcomes between ventral and subcoronal incisions in patients undergoing tunica albuginea plication (TAP) and plaque incision or partial excision and grafting (PG) for PD. Methods A single-surgeon, single-center retrospective chart review was conducted on all patients undergoing TAP or PG from 2019 to 2023. Patient demographics, including previous PD treatments, were recorded. A Mann–Whitney U test was utilized to determine differences in wound complication rate, median curvature improvement, and remaining postoperative curvature between ventral and subcoronal approaches. Outcomes Wound complication was classified as any dehiscence and/or wound exudate suspicious for infection within the first 3 months postoperatively. A secondary analysis was performed comparing these outcomes between TAP and PG. Results In the analysis, 189 patients were included, including PD straightening surgery, including 125 patients who underwent TAP (66%) and 64 patients (34%) who underwent PG. Among all cases, 49.7% underwent ventral incision (N = 94) and 50.3% (N = 95) underwent subcoronal incision. A total of 12 patients (6.3%) experienced a wound-related complication postoperatively (range 3-23 days), including 9/94 (9.6%) in the ventral incision cohort and 3/95 (3.2%) in the subcoronal cohort (P = 0.081). All the patients were treated with oral antibiotics and two patients required closure under local anesthesia (both in the ventral incision cohort). Secondary analysis did not reveal any significant difference in outcomes between TAP and PG cohorts with respect to wound complications. Clinical Implications While we did not identify a statistically significant difference, most of our wound complications, including infection and/or dehiscence, were seen in those undergoing a ventral penile raphe incision. Despite this, the rate of wound complications with either incisional approach as low. Strengths and Limitations Our report represents a large cohort of patients treated with surgical straightening for PD, and to our knowledge is one of the first to compare wound complications between ventral and subcoronal incisions. Limitations include the retrospective single-surgeon series without randomization, lack of power analysis, and heterogenous classification of wound complications. Conclusion Both ventral penile raphe and subcoronal (degloving) incisions can be considered for penile straightening procedures to correct PD curvature deformity with a low risk for serious wound-related complications.

PURPOSE Patients with cancer take different types of medications with varying schedules and settings. They are also sometimes instructed to stop medications due to toxicity. To measure self-reported nonadherence in this heterogeneous population, we modified and evaluated a measure originally developed to assess nonadherence to daily oral antihypertensives, the Domains of Subjective Extent of Nonadherence (DOSE-Nonadherence). METHODS The measure was refined in an iterative process incorporating feedback from patient investigators and participant interviews in English and Spanish. Branching logic was added for participant selection of medication administration setting: (1) only home, (2) only clinic, or (3) partly home/partly clinic. Participants reported their adherence to medications taken over a setting-specific reference period (1 week for home, 1 month for clinic medications). Participants who missed medications then reported on reasons for nonadherence. Adherence was dichotomized for analysis (complete adherence v any nonadherence). For participants who received clinic-administered medications, concordance between chart-abstracted and self-reported adherence was evaluated. RESULTS Seventy-three participants completed the measure (68% English; 32% Spanish; 86% female; 44% age ≥60 years). The majority had breast cancer; 64% had metastatic disease. Twenty-six percent (15/58) of participants who received medication in clinic and 24% (11/46) of those who took medication at home reported nonadherence. Participants felt able to respond accurately to both reference periods and perceived all reasons for nonadherence to be relevant. Among participants who completed the final version of the measure for clinic-administered medication, 96% (26/27) accurately reported their adherence compared with chart-abstracted data. CONCLUSION Our results support the validity of the DOSE-Nonadherence-Cancer for assessing cancer treatment nonadherence. This measure can be used to assess nonadherence in patients with cancer receiving a broad array of systemic therapies.

Abstract The treatment patterns and clinical outcomes for patients experiencing progression of disease (POD) following CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) mantle cell lymphoma (MCL) are undefined. We identified all patients who received CD19-directed CAR T-cell therapy for R/R MCL therapy across 15 international centers, and studied those experiencing POD post–CAR T-cell therapy in detail. We extracted clinical/treatment/pathologic variables, and associated these features with survival outcomes. In total, 384 patients received CAR T-cell therapy, and 135 (35%) experienced POD. POD occurred at a median of 6 months following CAR T-cell therapy infusion, and most (64%) patients with POD had complete response as best response to CAR T-cell therapy. Tumor features at POD included blastoid/pleomorphic morphology in 29 of 78 (37%) patients, and TP53 mutation in 21 of 41 (51%) patients. Following POD, 17 patients received no further therapy, 13 underwent local therapy, and 105 received systemic therapy. The most common first-line systemic therapies were chemo(immuno)therapy (22 patients; overall response rate [ORR], 40%), pirtobrutinib (17 patients; ORR, 36%), and bispecific antibodies (13 patients; ORR, 67%). Among patients experiencing POD, the median progression-free survival and overall survival (OS) were 2.5 months and 5.4 months, respectively, from POD. Lack of response to CAR T-cell therapy and short time from CAR T-cell therapy infusion to POD (<3 vs 3-6 vs >6 months), among other factors, were associated with inferior OS after POD. In conclusion, we confirm the challenging prognosis for patients experiencing POD following CD19 CAR T-cell therapy for R/R MCL, and establish a benchmark for future investigations in this patient population.

ABSTRACT Background and Aims Steroid supplementation remains controversial in septic shock, partly due to the heterogeneity of the populations studied. Cirrhotic patients with sepsis frequently develop relative adrenal insufficiency, showing poor response to vasopressors and poor prognosis. Early administration of low‐dose hydrocortisone might facilitate shock reversal and reduce mortality in this population. Methods Double‐blind, randomised, placebo‐controlled multicentre trial, enrolling adult cirrhotic patients with septic shock. Patients were assigned to receive i.v. hydrocortisone (100 mg followed by a continuous infusion of 200 mg/24 h) or placebo, for at least 3 days, followed by a tapering period of 3–7 days, depending on the time of shock resolution. Primary endpoint was 28‐day all‐cause mortality. Results After enrolment of 83 patients the trial was stopped early due to slow inclusions. Most patients required low‐to‐moderate doses of vasopressors. There was no difference in 28‐day mortality (35% vs. 39.5%; p = 0.84) between hydrocortisone and placebo groups. Shock resolution (85% vs. 72.1%; p = 0.25) and days to shock resolution [3 days (2.2–4; IQR) vs. 4 (2–7.5; IQR)] were also similar between groups. More patients receiving placebo died of refractory shock (47.6% vs. 8.7%). No significant differences between treatment arms were observed in shock relapse, new shock episodes or bacterial or fungal superinfections during hospital stay. Hypo‐ and hyperglycaemias were more frequent in the hydrocortisone arm. Severity of ACLF at inclusion and inadequacy of empirical antibiotic therapy (HR = 6.40; 95% CI: 3.21–12.79) independently predicted 28‐day mortality. Conclusions Supplemental hydrocortisone did not improve short‐term survival in cirrhotic patients with septic shock requiring low‐to‐moderate doses of vasopressors. Trial Registration S‐number University Hospitals Leuven, Belgium: S55168; EUDRACT: 2010–024273‐38; Clinicaltrials.gov id: NCT02602210

Abstract Background and Aims Invasive coronary function testing (CFT) identifies coronary vasomotor disorders in up to 90% of patients with angina with non-obstructive coronary arteries (ANOCA). The ILIAS ANOCA trial hypothesized that routine ad hoc CFT would be feasible, safe, and effective in providing an early, comprehensive diagnosis. Additionally, it was anticipated that combining CFT with a disease-specific treatment protocol would significantly improve quality of life in ANOCA patients compared with standard care. Methods After excluding patients with obstructive coronary artery disease (CAD) during clinically indicated invasive coronary angiography (ICA), eligible patients underwent CFT and were randomized to either the standard care group, where CFT results remained blinded, or the intervention group, where CFT results were disclosed along with a tailored medical therapy protocol. The primary outcome was the mean difference in the within-subject change in Seattle Angina Questionnaire summary score (SAQSS) between groups from baseline to a follow-up of 6 months. The trial is registered with the International Clinical Trials Registry Platform (NL-OMON20739). Results A total of 255 patients consented, of whom 153 patients (60%) without CAD underwent CFT and were randomized 1:1 to the standard care (n = 76) or intervention group (n = 77). All CFT procedures were successful without adverse events. A vasomotor disorder was identified in 120 patients (78%). At 6-month follow-up, the SAQSS improved significantly in the intervention group compared with the control group, with an intervention effect of 9.4 units (95% confidence interval 3.9–14.9, P = .001). There were no major adverse cardiac events at the 6-month follow-up. Conclusions Routine CFT during the initial ICA was feasible, safe, and had high diagnostic yield. Implementing a pragmatic CFT protocol combined with a disease-specific treatment protocol significantly improved disease-related quality of life in patients with ANOCA compared with standard care.

ABSTRACT Importance Risk stratification of cutaneous squamous cell carcinoma (CSCC) is central to effective management. Despite advancements in the 8th edition of the American Joint Committee on Cancer (AJCC8) staging system, the distinctiveness of T‐stages remains limited. Objective To evaluate the effectiveness of the Brigham and Women's Hospital (BWH) and the AJCC8 staging systems in predicting poor outcomes in head and neck (HN) CSCC. Design A retrospective, multinational cohort study of CSCCs diagnosed between January 10, 1991, and December 31, 2023. Setting Twelve centers across the United States (10), Spain (1), and Brazil (1). Participants Patients with invasive CSCC who underwent curative‐intent surgical treatment. Exclusions included cases of lip CSCC, cases with prior HN cancer with associated regional disease, patients with a history of chemotherapy/radiotherapy for other HN neoplasms, and recurrent primary tumors. Exposure Tumors were staged according to both the AJCC8 TNM staging system and the BWH tumor classification. Main Outcomes and Measures Local recurrence (LR), nodal recurrence (NR), distant recurrence (DR), and disease‐specific death (DSD). Results A total of 9852 excised tumors from 3168 patients were included. The 2 systems had comparable monotonicity and homogeneity. Significant differences could be observed in 5‐year cumulative incidence for DSD in both BWH and AJCC8, and also for LR in BWH. Higher T‐stages exhibited similar curves regarding NR and DR for both AJCC8 and BWH staging systems. Overall, we observed high specificity and NPV, low sensitivity and PPV, and moderately high c‐indices for both the BWH and AJCC8 staging systems in predicting the main outcomes for HNCSCC. Conclusion and Relevance Current AJCC8 and BWH staging systems can accurately predict survival in HNCSCC, although there are still important characteristics to be addressed in future staging systems for better stratification according to the other main outcomes.

Abstract Epcoritamab and glofitamab are CD20-directed bispecific antibodies (BsAbs) approved in the United States for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Limited data exist for patients treated outside of trials. Patients with R/R DLBCL receiving commercial epcoritamab or glofitamab between 1 January 2023 and 15 October 2024 were collected from 21 United States institutions. Among 245 patients, 156 received epcoritamab and 89 received glofitamab, 113 were refractory to front-line therapy, 40 had MYC and BCL2 and/or BCL6 rearrangements, 147 received prior chimeric antigen receptor T-cell therapy, and 174 patients would have been ineligible for registrational trials. The overall response rate (ORR) for epcoritamab and glofitamab was 51% (23% complete response, [CR]) and 53% (30% CR), respectively. Median progression-free survival (PFS) was 2.6 months (95% confidence interval [CI], 2.0-3.8 months), and median overall survival (OS) was 7.8 months (95% CI, 6.2-11.0 months). The 6-month PFS was 36% (95% CI, 30-44) and the 6-month OS was 60% (95% CI, 54-67). Both trial ineligibility and undetectable CD20 pre-BsAbs portended shorter PFS and OS. Of 17 individuals with paired biopsies, 15 (88.2%) lost CD20 expression after BsAbs with a median time to progression of 3.7 months. This analysis including patients with R/R DLBCL shows the ORR to CD3/CD20 BsAbs was comparable to pivotal trials, although PFS and OS were lower. Baseline undetectable levels of CD20 were associated with poor outcomes. These results demonstrate the activity of BsAbs in R/R DLBCL, and underscore the importance of target antigen expression.

Abstract Anti-IgLON5 disease is an autoimmune encephalitis that presents with a heterogenous clinical phenotype, including sleep disorders, movement abnormalities and bulbar involvement. It is characterized by autoantibodies against IgLON5, 85% association with HLA-DQB1*05:∼ and a brainstem-dominant tauopathy. Cellular and murine models report pathogenic effects of the autoantibodies, and neurodegenerative factors suggest progressive atrophy as a common sequela. However, evidence from in vivo patient data and long-term follow-up is limited, and the degree of progression remains elusive. In this multicentre study, clinical and brain MRI data were collected from 127 patients across 12 countries to investigate the relationships between clinical presentations and the development of distinct brain atrophy patterns. Our data show that most patients develop a complex multisystem phenotype as the disease progresses; however, neuromuscular manifestations rarely emerge at later disease stages. By comparison to healthy controls, this disease presents with severe substructure-specific atrophy, especially affecting the hypothalamus, brainstem, accumbens and basal ganglia, which, in age-independent analyses, show significant ventricular enlargement and also suggest progression of brainstem atrophy over the disease course. Moreover, the focality of atrophy was functionally linked to specific symptoms, with more severe involvement of the basal ganglia in patients with movement disorders, and greater atrophy in the hippocampus and thalamus in patients with cognitive impairment. Taken together, our results provide evidence of distinct atrophy patterns in anti-IgLON5 disease, which closely mirror sites of pathophysiologic processes, including autoantibody binding and tau deposition. Our data emphasize the brainstem as the pathophysiological hub of the disease and provide normative data for the incorporation of atrophy measurements into routine clinical assessments and future treatment studies to monitor disease trajectory and evaluate future treatment strategies.

Importance Tumor-infiltrating lymphocytes (TILs) are a provocative biomarker in melanoma, influencing diagnosis, prognosis, and immunotherapy outcomes; however, traditional pathologist-read TIL assessment on hematoxylin and eosin–stained slides is prone to interobserver variability, leading to inconsistent clinical decisions. Therefore, development of newer TIL scoring approaches that produce more reliable and consistent readouts is important. Objective To evaluate the analytical and clinical validity of a machine learning algorithm for TIL quantification in melanoma compared with traditional pathologist-read methods. Design, Setting, and Participants This multioperator, global, multi-institutional prognostic study compared TIL scoring reproducibility between traditional pathologist-read methods and an artificial intelligence (AI)-driven approach. The study was conducted using retrospective cohorts of patients with melanoma between January 2022 and June 2023 across 45 institutions, with tissue evaluated by participants from academic, clinical, and research institutions. Participants were selected to ensure diverse expertise and professional backgrounds. Main Outcomes and Measures Intraclass correlation coefficient (ICC) values were calculated for the manual and AI-assisted arms using log-transformed data. Kendall W values were calculated for Clark scores (brisk = 3, nonbrisk = 2, and sparse = 1). Reliabilities of ICC and W values were classified as moderate (0.40-0.60), good (0.61-0.80), or excellent (>0.80). AI TIL measurements were dichotomized using the 16.6 and median cutoffs. Univariable and multivariable Cox regression analyses assessed the prognostic value of TIL scores adjusted for clinicopathologic variables. Results There were 111 patients with melanoma in the independent testing cohort (median [range] age at diagnosis, 61.0 [25.0-87.0] years; 56 [50.5%] male) who contributed melanoma whole tissue sections. A total of 98 participants evaluated TILs on 60 hematoxylin and eosin–stained melanoma tissue sections. All 40 participants in the manual arm were pathologists, while the AI-assisted arm included 11 pathologists and 47 nonpathologists (scientists). The AI algorithm demonstrated superior reproducibility, with ICCs higher than 0.90 for all machine learning TIL variables, significantly outperforming manual assessments (ICC, 0.61 for AI-derived stromal TILs vs Kendall W , 0.44 for manual Clark TIL scoring). AI-based TIL scores showed prognostic associations with patient outcomes (n = 111) using the median cutoff approach with a hazard ratio (HR) of 0.45 (95% CI, 0.26-0.80; P = .005), and using the cutoff of 16.6, with an HR of 0.56 (95% CI, 0.32-0.98; P = .04). Conclusions and Relevance In this prognostic study of TIL quantification in melanoma, the AI algorithm demonstrated superior reproducibility and prognostic associations compared with traditional methods. Although the retrospective nature of the cohorts limits demonstration of clinical utility, the publicly available dataset and open-source AI tool offer a foundation for future validation and integration into melanoma management.