Citations

Abstract To present our clinical experience with a volar scapholunate (SL) ligament reconstruction using a strip of the long radiolunate ligament. This was a single-institution observational study (2004–2022) of SL ligament injuries with evidence of a torn volar component on arthroscopy that received volar capsulodesis with/without a dorsal repair. The postoperative range of motion (ROM), grip strength, complications, and secondary surgery (e.g., four-corner fusion or total wrist fusion), and radiographic changes were reported. Disabilities of arm, shoulder, and hand/patient-rated wrist evaluation (DASH/PRWE) scores were prospectively collected. Patients were stratified by static versus dynamic/predynamic SL diastasis and by isolated volar versus volar and dorsal ligament injury. Twenty-eight patients (15 females and 13 males) with a mean age of 35.1 years (± 15.7) met the inclusion criteria. The follow-up was 86.3 months (± 53.4; minimum 11 months). Most (26/28) patients were right-handed. The majority (20/28) of the patients presented ≥ 6 weeks postinjury. Few (4/28) used tobacco. Most (20/28) patients had dynamic/predynamic injuries. Postoperatively, the mean pronation/supination was 83 degrees/83 degrees, flexion/extension was 56 degrees/61 degrees, ulnar deviation was 30 degrees, and radial deviation (RD) was 19 degrees (n = 13). The mean grip strength was 78.8% (± 30.4) of the contralateral normal side (n = 14). Except for increased RD in patients with dynamic/predynamic injuries (p = 0.02), there were no other ROM differences. SL widening (>3 mm) postoperatively was observed in 33.3% (2/6) of static versus none of the dynamic/predynamic injuries (p = 0.165). There were only two postoperative complications, both surgical site infections. Two patients had persistent pain and required secondary surgery at a median of 48 months. At 86.9 months, patients reported a mean DASH of 16.4 (± 17.8) and a PRWE of 24.6 (± 23.6), and 78.9% (15/19) returned to prior work. We report long-term functional outcomes after a volar capsulodesis for volar SL injuries. This appears to be a safe procedure with an acceptable complication rate and low disability after 7 years. Most (approximately 79%) patients returned to their previous employment. A larger comparative study will be required to prove superiority to other types of repairs. Level IV, Case series.

Abstract Current discussion surrounding the clinical capabilities of generative language models (GLMs) predominantly center around multiple-choice question-answer (MCQA) benchmarks derived from clinical licensing examinations. While accepted for human examinees, characteristics unique to GLMs bring into question the validity of such benchmarks. Here, we validate four benchmarks using eight GLMs, ablating for parameter size and reasoning capabilities, validating via prompt permutation three key assumptions that underpin the generalizability of MCQA-based assessments: that knowledge is applied, not memorized, that semantic consistency will lead to consistent answers, and that situations with no answers can be recognized. While large models are more resilient to our perturbations compared to small models, we globally invalidate these assumptions, with implications for reasoning models. Additionally, despite retaining the knowledge, small models are prone to answer memorization. All models exhibit significant failure in null-answer scenarios. We then suggest several adaptations for more robust benchmark designs more reflective of real-world conditions.

Abstract Objective: Electronic Health Record (EHR) data are critical for advancing translational research and AI technologies. The ENACT network offers access to structured EHR data across 57 CTSA hubs. However, substantial information is contained in clinical narratives, requiring natural language processing (NLP) for research. The ENACT NLP Working Group was formed to make NLP-derived clinical information accessible and queryable across the network. Methods: We established the ENACT NLP Working Group with 13 sites selected based on criteria including clinical notes access, IT infrastructure, NLP expertise, and institutional support. We divided sites into five focus groups targeting clinical tasks within disease contexts. Each focus group consisted of two development sites and two validation sites. We extended the ENACT ontology to standardize NLP-derived data and conducted multisite evaluations using the Open Health Natural Language Processing (OHNLP) Toolkit. Results: The working group achieved 100% site retention and deployed NLP infrastructure across all sites. We developed and validated NLP algorithms for rare disease phenotyping, social determinants of health, opioid use disorder, sleep phenotyping, and delirium phenotyping. Performance varied across sites (F1 scores 0.53–0.96), highlighting data heterogeneity impacts. We extended the ENACT common data model and ontology to incorporate NLP-derived data while maintaining Shared Health Research Informatics NEtwork (SHRINE) compatibility. Conclusion: This demonstrates feasibility of deploying NLP infrastructure across large, federated networks. The focus group approach proved more practical than general-purpose approaches. Key lessons include the challenge of data heterogeneity and importance of collaborative governance. This work also provides a foundation that other networks can build on to implement NLP capabilities for translational research.

Abstract Purpose: Germline pathogenic variants (PV) in ATM increase the risk of pancreatic ductal adenocarcinoma (PDAC), but the underlying tumor biology of PDAC associated with germline PV in ATM has not been adequately explored. Experimental Design: Whole-genome, whole-exome, and RNA sequencing were performed on PDAC tumors from 25 germline ATM PV carriers diagnosed at Mayo Clinic between 2007 and 2017. Somatic and copy-number alterations, mutational signatures, transcriptomic subtypes, and the immune landscape were evaluated. Results: High-quality whole-exome and whole-genome sequencing were obtained from 21 and 15 tumors, respectively. Biallelic inactivation of ATM was observed in 87%, KRAS PV in 90%, CDKN2A homozygous loss in 60%, and TP53 alterations in <10% of these tumors. A predominant clock-like mutational signature was present in all samples. Whole-transcriptome analysis identified that the aberrantly differentiated endocrine exocrine subtype accounted for 18% of PDAC and was consistently associated with >5-year overall survival. In addition, a 28-gene expression–based signature associated with overall survival was identified and further validated in The Cancer Genome Atlas cohort. Immune landscape analysis through CODEX identified enriched CD4 T-helper cell/tumor interactions and reduced B7H3-high cell/tumor interactions in ATM PV carriers compared with noncarriers. Conclusions: The observed absence of TP53 PV and enrichment for CDKN2A alterations in ATM tumors, along with differences in the mutational signatures, transcriptomic subtypes and immune landscape, improve our understanding of the mechanistic pathways involved in PDAC development in germline ATM PV carriers and help identify potential targeted therapeutic strategies.

Abstract Changes in the clinical symptoms of acute graft-versus-host disease (GVHD) are currently used to assess treatment responses. The Mount Sinai Acute GVHD International Consortium (MAGIC) consortium has recently revealed that the integration of serum biomarkers with clinical symptoms at the onset of treatment in a MAGIC composite score (MCS) more accurately predicts treatment response and 6-month nonrelapse mortality (NRM) than clinical symptoms alone. In this study, we evaluated whether the integration of serum biomarkers and clinical symptoms on day 28 (D28) would also better predict NRM than clinical response only (CRO). We analyzed data from 1135 patients receiving systemic treatment for acute GVHD and created a fourth MCS category for patients with complete resolution of symptoms and low-risk clinical biomarkers on D28. Using a classification and regression tree model with 6-month NRM as the end point, we identified status of MCS 0 or MCS 1 at D28 as responses, which we termed the MAGIC composite response (MCR). In the validation cohort (n = 309), MCR more accurately predicted 6-month NRM than CRO (area under the curve: 0.77 vs 0.69; P = .014) and demonstrated higher negative and positive predictive values. MCR correctly reclassified both clinical nonresponders and responders: 28 of 213 clinical responders (13%) became nonresponders with fivefold higher NRM (34.3% vs 6.8%, P < .001) and a larger group (29/96, 30%) of clinical nonresponders became responders with sixfold lower NRM (7.6% vs 50.7%, P < .001). These findings support the use of MCR as a superior surrogate end point for long-term GVHD control and survival in future clinical trials.

We describe the first use of phage therapy in Canada for the treatment of a life-threatening periprosthetic joint infection (PJI), with successful outcome. PJI is a devastating complication of joint replacement surgery, with high morbidity and mortality. Our patient presented with early sepsis from a chronic recalcitrant multidrug-resistant (MDR) Staphylococcus epidermidis hip PJI which had repeatedly failed standard therapy. She had previously undergone 10 operations of the right hip, and only three weeks after completing a prolonged course of daptomycin following her most recent hip revision, she developed a draining sinus tract. Given the high burden of disease, inability to achieve surgical source control, and lack of antibiotic treatment options for long-term suppressive therapy, bacteriophage (phage) therapy was pursued. The patient underwent irrigation and debridement with complex flap reconstruction: intraoperative tissue cultures again yielded MDR S. epidermidis. We developed a novel phage therapy protocol for this patient, with twice daily, intra-articular and intravenous (7 × 109 PFU/dose) phage delivery over a planned 14-day course. Complete healing of the wound with cessation of drainage occurred within one month after treatment. A marked improvement in right hip pain and mobility occurred within three months after treatment. Twelve months following phage treatment, there is normalization of serum inflammatory markers with diminished pain, increased mobility, and no recurrent surgery. Our patient continues to improve and is currently living independently at home, with sustained clinical control of infection.

Introduction: Mitral valve transcatheter edge-to-edge repair (M-TEER) has emerged as a minimally invasive option for high-risk surgical candidates with severe and symptomatic mitral regurgitation (MR), but post-procedure residual mitral valve (MV) dysfunction remains a significant concern. This study evaluates the clinical utility of combining artificial intelligence applied to electrocardiograms (ECG-AI) for diastolic dysfunction (DD) grading and the echocardiography-derived velocity time integral of the MV and left ventricular outflow tract ratio (VTIMV/LVOT) in predicting prognosis in patients post-M-TEER. Methods: A retrospective analysis of patients who underwent M-TEER between 2014 and 2021 was conducted. Patients were categorized based on VTIMV/LVOT and ECG-AI scores into three groups: both normal parameters, either abnormal parameter, or both abnormal parameters to compare outcomes (mortality, major adverse cardiovascular events [MACE], and the need for subsequent MV reintervention) using Kaplan–Meier analysis, multivariable Cox regression models, and net reclassification improvement. Results: Overall, 250 patients were included; the median age was 79.5 (IQR: 73.1, 84.6) and 66.4% were male. The combined abnormal VTIMV/LVOT (≥2.5) and ECG-AI score for DD (>1) was associated with higher risk of one-year mortality (adjusted HR: 4.56 [1.04–19.89], p = 0.044) and MACE (adjusted HR: 3.72 [1.09–12.72], p = 0.037) compared to patients with both normal parameters. Conclusions: This study highlights the potential additive value of integrating VTIMV/LVOT and ECG-AI scores as a prognostic tool for a personalized approach to the post-operative evaluation and risk stratification in M-TEER patients.