Citations

Objectives: The medial ulnar collateral ligament (MUCL) is the primary stabilizer of valgus forces across the elbow. Injury to the MUCL has a large impact on the throwing athlete, particularly in baseball. The incidence of MUCL injury in baseball pitchers is on the rise. Surgical treatment and rehabilitation is evolving to improve outcomes and improve return to sport time frames. The purpose of this study was to highlight the trends in MUCL repair and reconstruction in professional baseball pitchers, describe relevant outcomes such as return to any level of play (RTP) for surgical repair and reconstruction, and distinguish what factors might impact these outcomes. The authors hypothesize that primary and revision MUCL surgery is increasing with revision surgery requiring the greatest time to RTP. Methods: The Major League Baseball (MLB) Health and Injury Tracking System (MLB HITS) database was used to procure data during the targeted study period (2010 – 2023). All professional pitchers who underwent MUCL surgery within the study period were included. Variables analyzed included age, career length, and level of play. Surgical variables included date and type of procedure, RTP status, time required to RTP, return to same level of play (RTSL), career length before and after surgery, number of revision surgeries, and time between surgeries. Successful RTP was designated if a pitcher had returned in at least one professional game after index surgery. Analyses of trends over time were performed. The year 2020 was considered an outlier and omitted from the analysis of trends due to the coronavirus pandemic which limited games played. Results: A total of 2,287 pitchers underwent MUCL surgery during the study period (Table 1). The annual number of MUCL surgeries on all pitchers increased year over year (R 2 = 0.821, p < 0.001), as did the annual number of reconstructions with internal brace (IB) augmentation (R 2 = 0.896, p < 0.001) (Figure 1). The RTP rate (93%) for MLB pitchers was significantly higher compared to the RTSL rate (71%, P < 0.001). This difference was not observed in Minor League Baseball (MiLB) (RTP 76% vs. RTSL 74%, P = 0.142) (Figure 2). The percentage of players who RTP after revision surgery was significantly lower compared to primary surgery (71%vs. 80% respectively, P = 0.020). Mean time to RTP is significantly shorter (470 ± 135 days) compared to the mean time to RTSL (499 ± 153 days, P < 0.001) (Figure 3). The annual number of revision MUCL surgeries on all pitchers increased year over year as well (R 2 = 0.322, p = 0.043). Conclusions: MUCL surgery continues to increase, also leading to increasing numbers of revisions in professional pitchers. Overall, 80% of pitchers were able to RTP at a mean of 470 days (15.5 months), while only 71% were able to RTSL at a mean of 499 days (16.5 months), but this varied based on level of play. Surgical techniques continue to evolve as MUCL repairs and reconstructions with IB augmentation have increased significantly in recent years. This study will help guide athlete expectations and surgeon decision-making.

Background Intracranial occlusions in embolic stroke of undetermined source are histopathologically similar to cardiac sources of embolism. Whether patients with embolic stroke of undetermined source and intracranial occlusion benefit from anticoagulation is unknown. Methods A multicenter retrospective cohort of adults with cryptogenic stroke was queried for patients with proximal or medium/distal vessel occlusion. The primary outcome was recurrent ischemic stroke, which was assessed in unadjusted and adjusted Cox proportional hazards models and repeated following 1:1 propensity score matching and biweight kernel density matching. Results Of the 2328 patients who were followed over a median of 1.31 years (interquartile range, 0.34–2.85), 999 (42.6%) had an intracranial occlusion. When compared with patients without an intracranial occlusion, those with an occlusion had fewer atherosclerotic vascular risk factors, more severe symptoms, and less severe cerebral microvascular disease. The rate of recurrent stroke was similar between patients with versus without an intracranial occlusion (6.8%/year [95% CI, 5.7–8.2] versus 7.0%/year [95% CI 6.0–8.1]; adjusted hazard ratio [HR], 1.09 [95% CI, 0.77–1.55]). There was no association between occlusion and recurrent stroke in the adjusted propensity score matching (HR, 1.01 [95% CI, 0.64–1.59]) or kernel density models (HR, 0.95 [95% CI, 0.62–1.45]). There was no interaction between occlusion and treatment with anticoagulation, sex, age, or high‐risk sources of embolism for the primary outcome in the unmatched and matched analyses. Conclusions Intracranial occlusion in patients with embolic stroke of undetermined source is not associated with a greater risk of recurrence when compared with patients without an intracranial occlusion. There was no difference in rate of recurrent stroke with anticoagulation when stratified by presence or absence of occlusion.

Abstract Purpose: Germ cell tumors (GCTs) pose significant diagnostic challenges due to the limited sensitivity and specificity of current tumor markers. Hereby we utilize phage immunoprecipitation sequencing (PhIP-Seq) technique to develop a unique immunosignature panel (iSIGN) with high sensitivity and specificity to improve the diagnosis and differentiation of GCTs. Patients and Methods: Serum samples from patients with confirmed gonadal or extragonadal GCTs and controls were collected from Mayo Clinic repositories. Controls included benign testicular lesions, autoimmune diseases, neurodegenerative disorders, and other cancers. Samples were randomized into development and validation cohorts. PhIP-Seq identified antigen-autoantibody interactions, and enrichment scores were calculated to develop a biomarker panel distinguishing GCT from non-GCT cases. A second biomarker panel was developed to predict seminoma from nonseminoma cases. Results: A total of 427 serum samples were analyzed, including 150 from GCT patients and 277 controls. For our primary model to distinguish GCT cases (GCT-iSIGN), 24 peptides from 16 antigens were identified based on significant differential autoantibody binding enrichment in GCT patients (p &lt; 0.05), ≥2 peptides per antigen, and enrichment scores ≥ 2.5-fold. GCT-iSIGN was highly sensitive (93%) and specific (99%) for identifying GCT cases from controls with an area under curve (AUC) of 0.93 and 9% Unknown Case Rate (UCR). The secondary panel (Sem-iSIGN) included 17 peptides corresponding to 5 unique proteins with high specificity (93%), moderate sensitivity (65%) and AUC of 0.77 to distinguish seminoma from nonseminoma GCT cases. Conclusion: This study demonstrates the potential use of PhIP-Seq to identify unique immunosignature panels that can serve as reliable biomarkers for GCT. These panels address the limitations of traditional markers and other proteomic techniques. This immunosignature model represents a cost-effective, stable, and scalable approach to enhancing GCT diagnosis and management. Citation Format: M Bakri Hammami, Andrew Knight, Haidara Kherbek, Brian Costello, Silvana De Lorenzo, Bradley C. Leibovich, John C. Cheville, Yong Guo, Jessica Sagen, Janet E. Olson, Alicia Algeciras-Schimnich, Sean J. Pittock, John R. Mills, Surendra Dasari, Divyanshu Dubey. iSIGN panel identifies germ cell tumors via whole-proteome phage immunoprecipitation sequencing [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr B027.

Objective To establish a framework for validating candidate biomarkers of cerebral small vessel diseases (SVD) associated with cognitive impairment and characterize individuals enrolled by the MarkVCID2 consortium under this framework. Methods Participants age 60 to 90 years were enrolled across 17 MarkVCID2 sites. Recruitment was targeted to enrich in cognitive symptoms (mild dementia, mild cognitive impairment, subjective cognitive decline), defined risk factors (diabetes mellitus, advanced hypertension), and Black/African American, White, and Hispanic/Latino subgroups. Enrolled participants underwent baseline visits that included cognitive testing, multimodal magnetic resonance imaging (MRI), and biofluid collection. Provisional risk for SVD‐related cognitive decline was estimated primarily by baseline cognitive symptoms plus SVD risk factors. Adjudicated risk status was estimated by cognitive symptoms plus presence of moderate‐to‐severe white matter hyperintensities, microbleeds, or lacunes on baseline MRI. Results MarkVCID2 enrolled 1883 individuals age 73.4 ± 7.5 years, 65.0% female, 24.2% Hispanic, and 27.1% non‐Hispanic Black. Among enrollees, 44.8% were provisionally designated high‐risk. After baseline MRI, 48.5% were categorized as adjudicated high‐risk status, with substantial recategorization both from low‐ to high‐risk (primarily because of MRI lesions without SVD risk factors) and high‐ to low‐risk (primarily suspected cognitive impairment at screening not confirmed by baseline testing). Interpretation MarkVCID2 baseline data indicate successful enrollment of diverse individuals enriched in factors associated with SVD‐related cognitive decline. Changes over 3 years of longitudinal follow‐up will be analyzed to validate the candidate biomarkers for 2 projected contexts of use: subject selection (identifying likelihood of future SVD progression) and study outcome (efficiently measuring SVD progression). ANN NEUROL 2026;99:449–458

ABSTRACTClinicians often repeat aquaporin‐4‐immunoglobulin G (AQP4‐IgG) testing in case of possible seroconversion. Compared with older, less sensitive immunofluorescence assays (IFA), cell‐based assays (CBA) offer higher sensitivity. This study assessed the frequency of seroconversion in a retrospective Cleveland Clinic cohort (2006–2024) of 451 patients with an initial negative AQP4‐IgG result who underwent serial testing. Seroconversion occurred in 4.3% (7/170) of patients initially tested by tissue IFA, but in none (0/263) of those tested by CBA. The lack of AQP4‐IgG seroconversion after a negative CBA, with only rare cases after a negative IFA, suggests that repeat AQP4‐IgG testing is low yield unless prior testing used older methods such as IFA.

The NCCN Guidelines for Biliary Tract Cancers (BTCs) provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts is convened at least once annually to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. This manuscript focuses on the adjuvant chemotherapy and chemoradiation treatment options for BTCs as well as the systemic treatment recommendations for patients with advanced BTCs.

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.

Background: Acute disseminated encephalomyelitis (ADEM) is a demyelinating syndrome observed in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) but there are limited data on application of this definition to its cerebral attacks or in adults with this disease. Methods: We analyzed patients from the Mayo Clinic MOGAD cohort ( n = 263) with cerebral attacks. We assessed whether children (<18 years-old) and adults (⩾18 years-old) fulfilled the 2013 ADEM definition. Results: We identified 89 patients (children, 34; adults, 55) and 55/89 (62%) were of female sex. Acute magnetic resonance imaging (MRI) abnormalities included: poorly demarcated T2 lesions (white matter, 85 (96%); deep gray matter, 41 (46%); T1-hypointense lesions (42 (47%)). Forty-two patients did not fulfill the ADEM definition due to: monofocal syndrome, 9; or no encephalopathy, 33. The remaining 47 patients (53%: children, 27/34 (79%); adults, 20/55 (36%)) fulfilled the ADEM definition, and 14 had preceding attacks, and 34 had subsequent attacks relative to ADEM episode. The features in children and adults with ADEM were broadly comparable. Conclusion: Applying the ADEM definition to MOGAD cerebral attacks highlighted that an update of the 2013 ADEM definition would be beneficial and could explicitly state its application to both adults and children and allow it to be applied to attacks at any time during the disease course.