Citations

Purpose To evaluate implantation rates, time to implantation, and predictors of implantation following matrix‐induced autologous chondrocyte implantation (MACI) biopsy for knee chondral defects. Methods Patients undergoing MACI biopsy or implantation for symptomatic knee chondral defects from 2017 to 2024 at a single institution were reviewed. At a minimum 1‐year follow‐up, the decision to proceed with implantation, recurrent symptoms, complications, and reoperations were assessed. Kaplan‐Meier analysis estimated time to implantation, and multivariable logistic regression identified predictors of MACI implantation. Results A total of 208 knees in 202 patients (mean age 28.0 ± 10.9 years, range 11‐59) underwent MACI biopsy for 243 chondral defects (patella [38%], femoral condyle [34%], and trochlea [26%]). At a mean follow‐up of 4.3 years (range 1.0‐8.3), 64 knees (31%) proceeded to second‐stage MACI implantation. Among 144 knees not implanted, 87 (60%) reported symptom improvement, and 26 (18%) had persistent symptoms. The remaining 22% did not undergo implantation due to another cartilage procedure, insurance denial, or pending scheduling. Patients who underwent biopsy at the home institution had a shorter time from biopsy to implantation compared with those biopsied at outside institutions (6.1 vs 13.1 months, P = .001). Median time to implantation was 9.4 months (95% confidence level: 7.2‐12.2) for home biopsies. Lower body mass index was associated with progression to implantation after adjusting for covariates (odds ratios 0.92, P = .019). Patients implanted within 4 months had larger chondral defects (4.0 vs 3.0 cm 2 , P = .045). At a mean 4.1‐year follow‐up, 6 patients (8%) experienced postoperative complications, including 3 (4%) who required revision chondroplasty. Conclusions MACI biopsy for knee chondral defects resulted in approximately one‐third of patients proceeding to MACI implantation, at a median of 9.4 months after biopsy. Lower body mass index was associated with higher likelihood of progression to implantation, larger chondral defects with earlier implantation, and among patients who did not proceed to implantation, approximately 60% reported symptom improvement following concomitant chondroplasty at the time of biopsy. Level of Evidence Level IV, retrospective case series.

Abstract T-cell immune tolerance is established in part through the activity of the autoimmune regulator (AIRE) transcription factor in medullary thymic epithelial cells (mTEC) of the thymus. AIRE induces expression of peripheral tissue–specific self-antigens for presentation to naïve T cells to promote activation/deletion of autoreactive T cells. This traditional role of AIRE in mTECs is to prevent autoimmunity. Herein, we demonstrate that tumors mimic the role of AIRE in mTECs to evade immune rejection. We found that AIRE induced a profile of “selfness” at the RNA and protein levels which, when presented on major histocompatibility complexes (MHC), shielded the tumor from inherently self-tolerized T cells. Moreover, we describe an in vivo immunotherapy in which engineered changes in AIRE expression in tumor cells altered their profile of selfness, exposing both AIRE-modified and parental unmodified tumor cells to T-cell attack. Therefore, by resetting the immunologic selfness of cancer cells, this AIRE-mediated immunotherapy (i) converted a highly tolerized T-cell compartment into a tumor-reactive T-cell population; (ii) conferred upon nonimmunogenic tumors de novo sensitivity to immune checkpoint blockade; (iii) removed the need to identify potentially immunogenic tumor-associated antigens as targets for generation of T-cell responses; and (iv) lead to potent T cell–mediated rejection of aggressive, immunologically cold, nonimmunogenic tumors. Patient RNA sequencing data showed that the expression of AIRE predicted response to immune therapies with a strong correlation between AIRE expression and markers of T-cell receptor signaling, suggesting that our studies have therapeutic translational value.

ABSTRACT Background and Objectives Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal, but the contribution of nonbiological factors to long‐term survival is unclear. We evaluated demographic, socioeconomic, clinical, treatment, and care‐delivery factors associated with 3‐year survival and whether these associations persisted at 5 years. Methods National Cancer Database patients with stage I–III PDAC diagnosed from 2012 to 2022 were analyzed using multivariable logistic regression adjusted for treatment pathway. Results Among 57,053 patients, 51,071 were eligible for a 3‐year analysis, and 12,205 (23.9%) survived. Compared with chemotherapy alone, surgery with chemotherapy (OR, 7.12; 95% CI, 6.64–7.63) and surgery alone (OR, 3.84; 95% CI, 3.49–4.23) had the strongest associations with survival. Younger age, lower comorbidity, Asian race, Spanish/Hispanic ethnicity, private insurance, lower grade, body or tail location, and lower nodal burden were independently associated with survival. Black race and treatment timing were not significant after adjustment. Findings were directionally consistent at 5 years. Conclusion Demographic, socioeconomic, and clinical factors independently influence 3‐year survival in PDAC. These findings underscore the need to complement biologic and therapeutic advances with structural interventions, such as insurance expansion and improved access to high‐quality centers, to mitigate disparities and improve outcomes in this highly lethal cancer.

Background: Dancers are at risk of femoroacetabular impingement (FAI) owing to supraphysiologic range of motion and associated demands placed on their hips. There remains a paucity of literature on midterm outcomes in dancers who undergo primary arthroscopy and labral repair for FAI. Purpose: To determine the rate of return to dance and patient-reported outcome measures in competitive dancers after hip arthroscopy with labral repair for FAI with minimum 2-year follow-up. Study Design: Case series; Level of evidence, 4. Methods: This study included dancers with FAI undergoing primary hip arthroscopy with labral repair from 2010 to 2022. Patient-reported outcome measures were collected at 2-year minimum follow-up: modified Harris Hip Score (overall, activities of daily living, gait, pain), Hip Outcome Score (activities of daily living, sports-specific subscale), Tegner Activity Scale, visual analog scale for pain, and surgery satisfaction. Patients were evaluated for preoperative radiographic measurements, postoperative return to sport, and revision surgery. Return to dance was evaluated. Results: Thirty-seven dancers were followed for a mean 7.4 years (range, 3.2-12.2) postoperatively (36 female and 1 male; mean ± SD age, 21 ± 7 years; mean body mass index, 23.3 ± 4.5). All outcome scores significantly improved postoperatively as compared with preoperatively ( P ≤ .037). Twenty dancers (71%) returned to dance. Of those who returned to dance, 17 (85%) returned to sport at the same or higher level as compared with the preoperative level. At final follow-up, 45% of dancers who initially returned to dance continued to dance. Of the dancers who no longer participated in dance at final follow-up, 7 (65%) quit dancing for nonhip-related reasons. Mean surgery satisfaction (0-10) at final follow-up was 7.1. Four patients (10%) underwent revision hip arthroscopy with revision labral repair. Conclusion: Hip arthroscopy with labral repair in dancers results in sustained improvements in function and pain at minimum 2-year follow-up. Most dancers return to their prior levels of dance, and nearly half remain active several years later. Notably, discontinuation of dance was often unrelated to hip symptoms, underscoring the importance of counseling patients on clinical and lifestyle factors influencing return to sport.

Purpose To prospectively investigate subjective anterior groin pain, patient‐reported outcome measures, complications, reoperation rates, and hip flexion strength after arthroscopic iliopsoas fractional lengthening. Methods From 2023 to 2025, patients with persistent groin pain after total hip arthroplasty refractory to conservative management undergoing arthroscopic iliopsoas fractional lengthening were prospectively identified at 2 tertiary referral centers. Pre‐ and postoperative outcomes at a minimum 6‐month follow‐up including the Visual Analog Scale, Tegner activity scale, Single Assessment Numeric Evaluation, and subjective anterior groin pain and hip flexion strength were analyzed. Results Fifty‐nine hips in 56 patients were included (age: 64.9 ± 9.8 years, 59% women, body mass index: 30.0 ± 5.8 kg/m 2 ) and followed for 10.0 ± 6.9 months postoperatively (range: 4‐25 months). Patients experienced significant ( P < .001) postoperative improvements in the Visual Analog Scale at rest (1.4 ± 2.2 vs 2.8 ± 2.1), Visual Analog Scale with use (3.0 ± 2.9 vs 7.8 ± 1.8), Tegner activity scale (2.8 ± 1.2 vs 2.0 ± 1.0), and Single Assessment Numeric Evaluation score (73.8 ± 22.5 vs 47.7 ± 22.2). Postoperative surgical satisfaction was 8.0 ± 2.7 (scale: 0‐10). Nearly 90% of patients reported feeling much or slightly better regarding their anterior groin pain postoperatively at 2‐week (91%), 6‐week (88%), 3‐month (91%), and final follow‐up (92%). Regarding hip flexion strength, ≥66% reported feeling much or slightly better at 2‐week (73%), 6‐week (95%), 3‐month (89%), and final follow‐up (66%). Three hips (6%) underwent reoperation at the final follow‐up (1 acetabular screw removal with open revision release, 1 revision total hip arthroplasty for loosening, and 1 two‐stage exchange for nonacute periprosthetic joint infection). Conclusions Nearly 90% of patients who underwent arthroscopic iliopsoas fractional lengthening after primary total hip arthroplasty reported improved anterior groin pain, whereas two‐thirds reported increased subjective hip flexion strength throughout the follow‐up. Of note, clinically meaningful improvement in pain at rest was achieved by 50% of patients based on cohort‐specific minimal clinically important difference criteria. Level of Evidence Level IV, retrospective therapeutic case series.

Abstract Objective Surgery is an effective, yet underutilized treatment for children with drug‐resistant epilepsy. Although predictors of surgical outcomes are well described, the decision to recommend surgery varies by institution. We aim to evaluate the rates of not recommending surgery, identify associated patient characteristics, and quantify variability across centers. Methods We queried the Pediatric Epilepsy Research Consortium Surgery database, a prospective multicenter cohort of children (0–18 years) undergoing initial evaluation for epilepsy surgery. Patients with documented surgical decisions were included. Demographic, clinical, and presurgical evaluation variables were compared by surgical recommendation status. Logistic regression identified factors associated with not recommending surgery. Mixed‐effects models quantified between‐center variability. Results Among 2480 patients across 29 centers, 532 (21%) were not recommended epilepsy surgery (median center rate 17%, interquartile range [IQR] 10%–28%). After accounting for patient characteristics associated with surgical candidacy, substantial variation in decision‐making remained across centers, with a median twofold difference in the odds of not recommending surgery between otherwise similar patients evaluated at different institutions (Median Odds Ratio = 2.25; Intraclass Correlation Coefficient = .18). The clinical characteristics most strongly associated with not recommending surgery included monthly or less frequent seizures (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.75–2.69), non‐structural etiology (OR 2.02, 95% CI 1.56–2.61), and taking ≤2 anti‐seizure medications (ASMs) (OR 1.67, 95% CI 1.34–2.08, all p 's < .01). These characteristics showed minimal clustering across centers (ICCs < .05). Significance One in five children evaluated for epilepsy surgery are not recommended to pursue surgical treatment. Although clinical factors influence decision‐making, they do not explain the substantial variation in recommendations across pediatric epilepsy centers. Similar children evaluated at different institutions had significant differences in the odds of not being recommended surgery, suggesting that institutional decision‐making contributes importantly to surgical candidacy.

Abstract Background Personalized meal planning by registered dietitian nutritionists (RDNs) is time‐intensive. Large language models (LLMs) may automate drafting meal plans, but their nutritional accuracy in clinical practice is uncertain. Methods In this proof‐of‐concept study, five outpatient RDNs and four LLMs (Gemini, CoPilot, ChatGPT 4.0, and customized ChatGPT 4.0) each generated 3‐day meal plans for five validated clinical scenarios. Effectiveness was defined as accuracy in meeting pre‐specified energy, protein, carbohydrate, fat, and sodium targets. Time to create plans and RDN comfort (self‐rated confidence in nutritional accuracy and clinical appropriateness on 1–5 Likert scale) were recorded. Three independent RDNs, blinded to source, analyzed nutrient content using Nutritionist Pro. Group differences were assessed with t ‐test and ANOVA. Results All LLMs and RDNs produced feasible meal plans. LLMs generated meal plans in under 1 min, whereas RDNs required a mean of 44 min per scenario. RDNs reported comfort levels ranging from 3.8 to 4.8. Across most scenarios, LLM plans delivered a smaller proportion of requested energy than RDN plans, which more consistently approached energy targets. Both groups performed similarly for the Mediterranean diet scenario. Overall, protein accuracy did not differ. However, in chronic kidney disease, LLMs undershot the guideline‐based protein target, while RDNs tended to modestly exceed it. Accuracy for low‐carbohydrate, fat, and sodium diets was comparable. Conclusion LLMs can rapidly generate clinically plausible meal plans but are less reliable than RDNs in achieving prescribed energy and selected macronutrient goals. Prompt precision is essential for nutrient‐specific targets. A hybrid model in which RDNs refine LLM‐generated drafts may leverage efficiency without sacrificing clinical accuracy.

The kinesin-5 motor protein KIF11 is crucial for mitotic spindle assembly, driving the separation of spindle poles through microtubule sliding. Src-family kinases phosphorylate KIF11 at multiple tyrosine residues within its motor domain, but the mechanistic consequences of these modifications remain unclear. Here, we dissect the role of phosphorylation at Y211 using phospho-mimetic (Y211E) and nonphosphorylatable mutants (Y211F) in biochemical, biophysical, and cellular assays. Optical trapping and Förster resonance energy transfer analyses reveal that Y211 phosphorylation slows neck-linker docking, reducing motor velocity and force generation under load. In human cells, Y211E expression impairs bipolar spindle formation and decreases spindle pole separation velocity, while Y211F shortens steady-state spindle length. Fluorescence recovery after photobleaching analyses show that Y211E accelerates motor turnover on spindle microtubules, consistent with the mutant motor’s heightened load sensitivity. Together, these findings support a model in which Src-mediated phosphorylation at Y211 acts as a rheostat to tune KIF11 mechanochemistry and spindle assembly dynamics, linking cancer-relevant kinase signaling to mitotic force generation.

Background: Whether robot-assisted cholecystectomy reduces bile duct injury compared with laparoscopic cholecystectomy remains uncertain because prior studies have inadequately accounted for disease severity and have rarely classified injury severity using standardized criteria. This study compared perioperative outcomes after robot-assisted and laparoscopic cholecystectomy across a large healthcare system while adjusting for operative complexity. Study Design: Adults undergoing robot-assisted or laparoscopic cholecystectomy within the Mayo Clinic Enterprise (2014–2025) were retrospectively evaluated. Propensity score weighting adjusted for demographics, surgeon case volume, learning curve, and disease severity using the Tokyo Guidelines and Parkland grading system in patients with acute cholecystitis. The primary outcome was bile duct injury; secondary outcomes included general and procedure-specific complications. Results: Among 23,513 patients (19,998 laparoscopic; 3,515 robotic), robot-assisted cholecystectomy was used more frequently for Parkland grade ≥3 disease. Overall, 227 bile duct injuries occurred (204 laparoscopic; 23 robotic), corresponding to absolute risks of 1.02% and 0.65%, respectively (absolute risk difference −0.37%, 95% CI −0.72% to −0.02%; number needed to treat, 273). Robot-assisted cholecystectomy was associated with lower odds of conversion to open surgery, 30-day readmission, and mortality, shorter hospital stay (β −0.56, 95% CI −0.66 to −0.45; P<0.001), and a 5-minute longer median operative time. In acute cholecystitis, robot-assisted cholecystectomy was associated with lower adjusted odds of bile duct injury (aOR 0.29, 95% CI 0.07–0.78; P=0.011). Conclusions: After adjustment for disease severity and surgeon-related factors, robot-assisted cholecystectomy was associated with lower odds of bile duct injury in acute cholecystitis and improved perioperative outcomes, including shorter hospitalization and lower conversion rates, despite greater use in more complex cases.