Citations

Imaging biomarkers complement traditional risk assessment by enabling direct patient-specific detection and characterization of subclinical atherosclerotic cardiovascular disease, which supports earlier diagnosis, improved risk stratification, and more personalized cardiovascular prevention.

Abstract We are interested in DNA stiffness in vitro and in vivo . Classical approaches for measuring this parameter in vitro involve tedious T4 DNA ligase-mediated cyclization kinetics experiments performed for one DNA fragment length at a time to establish effective local end-end concentrations ( J -factors). Protein-mediated DNA looping is a more relevant biological reaction. An efficient approach to determine length-dependent protein-mediated DNA J - loop values in vitro has been lacking. We describe LOOP-TAG, a massively-parallel method. We leverage intramolecular DNA looping and tagmentation catalyzed by Tn5 transposase (Tnp) tethered to the terminus of a ∼1,000-bp bead-bound duplex DNA. We detected loops terminating with Tnp. Counts of the resulting DNA looping-dependent bead-bound tagmentation products from deep sequencing determine DNA loop length probabilities at single-base pair resolution for all bead-bound fragments. When normalized to DNA fragment length probabilities from tagmentation using known concentrations of free Tnp, length-dependent J - loop values are directly determined. We demonstrate LOOP-TAG for Tnp tethered in two ways and in the presence of DNA-kinking architectural DNA binding protein Nhp6A. Intermediate length J-loop values are consistent with expectations of wormlike chain theory after accounting for strong sequence-dependence of Tnp. DNA loops are shifted to smaller sizes in the presence of Nhp6A, as predicted. (200/200 words)

Abstract Varlilumab is a monoclonal antibody with agonistic activity on CD27. The efficacy of single-agent PD-1 inhibitors on aggressive B-cell non-Hodkin lymphoma is limited. Preclinical and phase 1 data suggest that Varlilumab is safe and may have synergistic activity with PD-1 inhibitors. In the DIAL study, we explored whether dual immunomodulatory therapy with Varlilumab and Nivolumab in patients with relapsed/refractory aggressive B-NHL was safe and effective. We conducted a randomized phase II clinical trial on adult patients with relapsed/refractory aggressive B-NHL. Patients were randomized to receive Nivolumab monotherapy in the control group and Varlilumab combined with Nivolumab in the experimental group. Crossover to the experimental group was allowed upon progression in the control group. The primary endpoint was the overall response rate based on the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC). 54 patients underwent randomization, and 51 received assigned intervention and were included in the intention-to-treat analysis. Objective response was observed in 6 out of 51 patients (ORR 12%). There were 4 responders (ORR 16%) in the Nivolumab group and 2 responders (ORR 7.6%) in the Nivolumab and Varlilumab combination group (p = 0.3). None of the 7 patients that crossed over to the experimental group responded to the addition of Varlilumab. The ORR of patients who were previously exposed to CAR-T cell therapy was 13% (5 out of 39) compared to 8.3% (1 out of 12) in the unexposed patients (p > 0.99). The rate of treatment emergent adverse events was similar between groups, and there was no fatal TEAE in the study. The addition of Varlilumab to Nivolumb did not improve outcomes in patients with aggressive B-NHL. Even though this trial was not designed to evaluate immunotherapy as a rescue therapy after CAR-T failure, most patients (76%) had previously received CAR-T therapy, and their outcomes were equally poor.

Purpose To compare short‐term outcomes of intratunnel anchor fixation versus transtibial pull‐through repair for meniscus root tears with a minimum of 12‐month follow‐up. Methods Patients who underwent primary meniscus root repair between 2011 and 2024 at a single institution were retrospectively reviewed. Inclusion criteria consisted of primary medial or lateral meniscus root repair using either intratunnel anchor fixation or transtibial pull‐through repair, availability of preoperative radiographs, and completion of postoperative patient‐reported outcome measures with a minimum of 12‐month follow‐up. The groups were propensity‐matched by age, sex, body mass index, operative side, root laterality, and concomitant procedures. Baseline radiographic characteristics (hip‐knee‐ankle angle and posterior tibial slope) were measured. Outcomes included Lysholm score, International Knee Documentation Committee score, Tegner activity score (preoperative and postoperative), Visual Analog Scale for pain at rest and with activity, satisfaction, subjective surgical outcome, and reoperations. Results Fifty patients who underwent intratunnel anchor fixation (mean age, 44 years) were propensity‐matched to 100 patients who underwent transtibial pull‐through repair (mean age, 41 years). Mean follow‐up was 1.5 years (range, 1.0‐2.3) in the intratunnel anchor group and 6.1 years (range, 2.7‐13.7) in the transtibial pull‐through group. Reoperation rates were 8% and 14%, respectively ( P = .43), with repair failure occurring in 4% and 6% ( P > .99). Preoperative and postoperative Tegner scores were similar between groups. Tegner minimal clinical important difference was 0.8, and 26.5% of intratunnel anchor patients achieved this compared with 0% of transtibial pull‐through patients. Patients in the intratunnel anchor cohort reported slightly lower Visual Analog Scale pain with activity (1.8 vs 2.5, P = .02). Postoperative Lysholm (87 vs 83, P = .05) and International Knee Documentation Committee scores (79 vs 76, P = .09) were comparable between groups. A greater proportion of intratunnel anchor patients achieved Patient Acceptable Symptomatic State compared with transtibial pull‐through patients for Visual Analog Scale with activity (74% vs 56%, P = .03) and Lysholm (66% vs 47%, P = .01). Most patients in both cohorts rated their outcome as “much better” or “slightly better” ( P = .49), and satisfaction scores were high. Conclusions At short‐term follow‐up, both the intratunnel anchor and transtibial pull‐through techniques showed high patient satisfaction and comparable overall clinical outcomes. There were no differences in reoperation rates between techniques. Level of Evidence Level III, retrospective comparative case series.

Background: Large language models (LLMs) are increasingly used in patient-facing clinical applications, creating a need for scalable methods to evaluate the accuracy, safety, and appropriateness of their responses. Although physician review remains the reference standard, it is resource-intensive and difficult to scale. Objective: To develop and clinically validate an LLM-as-a-judge framework for evaluating responses to patients’ periprocedural questions. Methods: We retrospectively evaluated 1285 patient–AIVA interactions from 112 patients across two Mayo Clinic sites and multiple surgical specialties. Physician reviewers classified interactions using a predefined true-positive (TP), false-negative (FN), true-negative (TN), and false-positive (FP) framework. The finalized LLM judge independently evaluated the same interactions. Agreement was assessed using four-class and category-specific agreement, Cohen’s kappa, and a secondary binary analysis of response correctness. Results: Overall, four-class agreement was 93.1% (95% CI, 91.7–94.5%), with Cohen’s κ = 0.852 (95% CI, 0.823–0.882). Category-specific agreement was 94.1% for TP, 90.7% for FN, 95.5% for TN, and 84.9% for FP classifications. In the binary correctness analysis, accuracy was 93.4% (95% CI, 92.0–94.7%), sensitivity 94.6%, specificity 90.2%, precision 96.2%, and F1-score 0.954. McNemar’s test demonstrated no significant asymmetry between paired classifications (p = 0.11). Conclusions: A clinically grounded LLM judge closely approximated physician evaluation of patient-facing AI responses. These findings support its potential as a scalable assistive monitoring tool while preserving physician oversight for uncertain or safety-sensitive interactions.

BACKGROUND Acral lentiginous melanoma (ALM) is a biologically distinct, inherently aggressive, and understudied melanoma subtype without a unified surgical approach. OBJECTIVE To provide an updated review of ALM and offer practical, surgeon-focused guidance on diagnosis, biopsy, margin-controlled excision, and Mohs micrographic surgery (MMS)-based management of ALM. METHODS & MATERIALS A PubMed/MEDLINE search of ALM, with an emphasis on articles published after 2015. RESULTS ALM demonstrates inherent biological aggressiveness characterized by extensive subclinical spread, delayed diagnosis, and higher stage-adjusted recurrence compared with nonacral cutaneous melanomas. Anatomic constraints additionally necessitate specialized surgical approaches, although current management is extrapolated from nonacral melanoma data. Retrospective data support MMS and margin-controlled excision and tissue preservation in ALM, with the benefit of digit-sparing surgery and functional preservation. No randomized trials have included ALM, highlighting a key evidence gap. CONCLUSION Margin-controlled approaches such as MMS may improve local control and tissue preservation in select ALM patients. Prospective ALM-specific research and standardized diagnostic and surgical protocols are strongly needed.

Objective To evaluate the efficacy of cytokine‐directed therapies in VEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory somatic) syndrome using previously proposed treatment response criteria. Methods All patients with genetically confirmed VEXAS syndrome who received targeted therapies with JAK inhibitors (JAKi), tumor necrosis factor α inhibitors (TNFαi), or interleukin‐1 (IL‐1) or IL‐6 inhibitors were identified. Clinical and biochemical data were recorded for patients at time of targeted therapy initiation, and at 3‐, 6‐, and 12‐month follow‐up time points. Treatment response was labeled as complete response (CR; normalization of C‐reactive protein [CRP], prednisone <10 mg/day, and resolution of disease activity), partial response (PR; >50% improvement in CRP, >50% prednisone dose reduction, improvement or resolution of disease features), treatment failure (TF; worsening CRP, increasing prednisone, worsening of disease features), or no response (not meeting criteria for CR, PR, or TF). Results Overall, 52 patients received an IL‐1i, IL‐6i, or JAKi therapy. At six‐month follow‐up, 3 of 19 IL‐6i patients experienced CR, 4 of 19 experienced PR, and 7 of 19 experienced TF. 2 of 17 patients receiving JAKi experienced CR, 3 of 17 experienced PR, and 6 of 17 experienced TF. No patients receiving IL‐1i or TNFαi experienced CR, and only 1 of 5 IL‐1i patients experienced PR. Among those still receiving biologic therapy at 12 months, only 1 of 11 receiving IL‐6i and 0 of 7 receiving JAKi experienced CR. Conclusion IL‐6i and JAKi therapies demonstrated limited, unsustained efficacy for management of VEXAS syndrome. IL‐1i and TNFαi therapies were not efficacious. Useful application of previously reported treatment response criteria was demonstrated, but future incorporation of hematologic parameters may be beneficial.