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OBJECTIVE The optimal surgical treatment for lumbar spinal stenosis (LSS) with degenerative spondylolisthesis (DS) remains controversial. Posterior lumbar facet arthroplasty preserves motion after decompression and may address some of the limitations of fusion techniques. The Total Posterior Spine System (TOPS) investigational device exemption trial compared decompression with facet arthroplasty to decompression plus fusion (open with interbody). This study reports the 3-year outcomes from this trial. METHODS This randomized, controlled, multicenter trial enrolled 321 patients with LSS and grade I DS across 37 sites (2:1 randomization of arthroplasty to fusion). Eligible patients were 35–80 years old, had failed ≥ 6 months of nonsurgical treatment, and met thresholds for disability and leg pain. The primary endpoint was a composite clinical success score at 36 months, defined by four criteria: 1) no reoperation or lumbar injection, 2) no major device adverse events, 3) ≥ 15-point improvement in the Oswestry Disability Index (ODI), and 4) no new/progressive neurological deficit. Secondary outcomes included the ODI score, visual analog scale (VAS) scores for back and leg pain, the Zurich Claudication Questionnaire (ZCQ), device-related adverse events, and reoperations. RESULTS One hundred seventy-nine patients in the arthroplasty (TOPS) group and 74 in the fusion group were eligible for the 36-month analysis. The composite clinical success achievement rate was significantly higher in the arthroplasty group (76.0%) than in the fusion group (56.8%; p = 0.0038). The rate of reoperation or lumbar injection was significantly lower for the arthroplasty group (14.0%) compared to the fusion group (25.3%; p = 0.0222). Arthroplasty was associated with a significantly higher minimal clinically important difference (MCID) achievement rate for VAS back pain score compared with fusion (85.2% vs 72.2%; p = 0.041). Although there was no significant difference in ODI score, VAS leg pain score, or ZCQ component scores between groups, the arthroplasty group trended toward higher MCID achievement rates across all patient-reported outcome measures. There was no significant difference in reoperation failure rates between groups (5.8% for arthroplasty vs 9.5% for fusion; p = 0.329). CONCLUSIONS Decompression and dynamic stabilization with lumbar facet arthroplasty was associated with statistically significantly superior clinical outcomes and lower rates of secondary invasive procedures, including reoperations and injections, compared with decompression and fusion. Long-term follow-up is critical in defining the role of lumbar facet arthroplasty for the treatment of DS.

139 Background: Statins have been shown to reduce the risk of HCC in high-risk populations with metabolic diseases. However, emerging data suggests that GLP-1 RA’s may also offer hepatoprotection by reversing metabolic and inflammatory drivers contributing to HCC development. Patients with T2DM are at an increased risk of metabolic associated steatotic liver disease (MASLD) and HCC. To our knowledge, no real-world studies have directly compared the effectiveness of GLP-1 RA’s and statins for prevention of HCC in patients with T2DM. In this study, we aim to compare the incidence of HCC and hepatic decompensation events in patients with T2DM treated with GLP-1 RA’s vs statins. Methods: We performed a retrospective cohort study using data from TriNetX, a healthcare database of over 150 million patients in the United States. Adult patients with T2DM were identified and stratified by use of GLP-1 RA (semaglutide, dulaglutide, tirzepatide, exenatide, liraglutide, and lixisenatide) or statin (pitavastatin, simvastatin, fluvastatin, atorvastatin, rosuvastatin or lovastatin). Exposure groups were mutually exclusive with no overlap in GLP-1 RA or statin use. Propensity score matching was conducted between cohorts, matching for age, sex, race, tobacco use, alcohol use, hypertension, hyperlipidemia, obesity, MASLD, aspirin use, non-steroidal anti-inflammatory analgesic drug use, and other T2DM medications. Five-year incidence of HCC was compared between the GLP-1 RA and statin cohorts. In a subsequent analysis, hepatic decompensation events of ascites, hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and esophageal varices (EV) were compared. Results: We identified 1,411,022 patients with T2DM, including 254,832 GLP-1 RA users and 1,156,190 statin users. After PSM, 219,984 patients were included in the analysis. There was no significant difference in the five-year incidence of HCC between the GLP-1 RA and statin cohorts (0.14% vs 0.15%, odds ratio (OR) 0.95, 95% confidence interval (CI)0.81-1.11, p =0.5). In the subsequent analysis, GLP-1 RA use was associated with a lower incidence of ascites (0.98% vs 1.99%, OR 0.84, 95% CI 0.46-0.51, p <0.001), HE (0.18% vs 0.22%, OR 0.84, 95% CI 0.74-0.96, p =0.01), and SBP (0.05% vs 0.1%, OR 0.52, 95% CI 0.42-0.65, p <0.001). There was no difference in incidence of EV (0.33% vs 0.35%, OR 0.94, 95% CI 0.85-1.04, p =0.25). Conclusions: In patients with T2DM at elevated risk for MASLD and HCC, we found that GLP-1 RA use was associated with significantly lower incidence of hepatic decompensation events compared to statin use. However, there was no significant difference in HCC incidence between the cohorts. Prospective studies are warranted to confirm the hepatoprotective effect of GLP-1 RA medications and evaluate long-term oncologic outcomes.

138 Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RA’s) have advanced the treatment of type 2 diabetes mellitus (T2DM), yet their association with cancer risk remains subject of ongoing research. Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a well-established risk factor for colorectal cancer (CRC). Studies have shown a reduced risk of CRC with GLP-1 RA use however, the impact of GLP-1 RA therapy in the high-risk IBD population is unknown. In this study, we aim to evaluate the association between GLP-1 RA use and CRC incidence among patients with IBD, and among those with IBD and T2DM. Methods: We performed a retrospective cohort study using data from TriNetX, a healthcare database of over 150 million patients in the United States. In the first analysis, adult patients with pre-existing IBD were identified and stratified by use of a GLP-1 RA (semaglutide, dulaglutide, tirzepatide, exenatide, liraglutide, and lixisenatide) or not. Propensity score matching (PSM) was conducted between GLP1-RA users and non-users, matching for age, sex, race, tobacco use, alcohol use, hypertension, hyperlipidemia, obesity, IBD subtype (CD or UC), steroid use, immunosuppressive use including biologics, and other T2DM medications. Five-year incidence of CRC was compared between GLP-1 RA users and non-users in the matched cohort between 2015 and 2025. We then restricted the cohort to patients with IBD and T2DM and repeated this analysis. Results: We identified 1,137,300 patients with IBD, including 70,303 GLP-1 RA users and 1,066,997 non-users. After PSM with all variables adequately matched, 69,221 patients were included in the analyses. GLP-1 RA use was associated with a lower 5-year incidence of CRC (0.2% vs. 0.43%, odds ratio (OR) 0.49, 95% confidence interval (CI) 0.3-0.57, p <0.001). We then identified 209,649 patients with IBD and T2DM, including 38,567 GLP-1 RA users and 171,082 non-users. After matching for all variables, 37,740 patients were included in the analyses. Among patients with IBD and T2DM, GLP-1 RA use was associated with a lower 5-year incidence of CRC (0.31% vs. 0.57%, OR 0.54, 95% CI 0.43-0.68, p <0.001). Conclusions: GLP-1 RA use was associated with a significantly reduced incidence of CRC in all patients with IBD, as well as the subpopulation with both IBD and T2DM. Given the elevated CRC risk in IBD, these findings suggest a potential protective effect of GLP-1 RA use in this high-risk population. Prospective studies will be important to further analyze and confirm this potential benefit.

Anesthesiologists are sometimes slow to adopt new technologies despite proven benefits. The authors undertook to understand community anesthesiologists’ perspectives and practices regarding neuromuscular monitoring and reversal. Specifically, they sought to generate evidence for why some guidance-congruent practices— i.e. , quantitative train-of-four monitoring, ulnar nerve stimulation, and evidence-based reversal—remain inconsistently adopted despite robust evidence of patient harm from residual neuromuscular blockade and decades of effort to improve adoption. Thirty-six U.S. community anesthesiologists underwent a detailed qualitative cognitive interview. Analysis revealed four clinician archetypes whose neuromuscular monitoring and reversal practices are shaped by identifiable individual and practice-related biases and device- and system-level barriers. Perceived confidence in sugammadex efficacy was frequently cited as a rationale for omitting quantitative neuromuscular monitoring. The authors propose a research and implementation action agenda to close the evidence-to-practice gap in neuromuscular monitoring and reversal.

Abstract Background and Aims Primary sclerosing cholangitis (PSC) increases the risk of developing cholangiocarcinoma (CCA), which is the leading cause of premature death in these patients. Current diagnostic methods for early detection of either condition remain largely suboptimal. This study investigates serum metabolites as potential non-invasive diagnostic biomarkers. Methods This multicenter international study analyzed 459 serum samples from 13 international centers, including patients with PSC (n = 216), PSC who developed CCA during follow-up (PSC to CCA; n = 24), PSC with concomitant CCA (PSC-CCA; n = 88), ulcerative colitis (UC; n = 14), and healthy individuals (n = 79). Serum metabolomics was evaluated by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) and the accuracy of the single candidate metabolite biomarkers was further assessed. Machine learning was used to generate the best diagnostic and predictive algorithms. Results Fifty-two serum metabolites were identified as markers of PSC, independent of age, biological sex, cirrhosis, UC, or ursodeoxycholic acid (UDCA) treatment. A diagnostic model based on only six lipids distinguished PSC patients from healthy controls with high accuracy (AUC 0.952 discovery, 0.918 validation), independently of the levels of transaminases or cholestasis markers (i.e., GGT, AP, bilirubin) in blood. Subgroup analyses were performed in PSC patients with and without inflammatory bowel disease (IBD), confirming the model’s consistent performance across both subgroups when compared with their respective control groups – UC and healthy controls (AUC 0.959 and 0.939, respectively). The PSC model also confirmed its diagnostic performance in patients with established PSC-CCA or progression to CCA within 2 years, when compared to UC and healthy controls, showing AUC values ranging from 0.911 to 0.976. Additionally, 20 metabolites were significantly altered in PSC patients with CCA (PSC-CCA), regardless of demographics, cirrhosis, UDCA treatment, IBD status, or CCA subtype, and independently of serum transaminases and cholestatic markers levels. A model incorporating six lipids accurately identified PSC-CCA cases compared to PSC patients (AUC = 0.912 discovery; 0.896 validation), showing excellent performance in early-stage tumor detection (AUC 0.921) and outperforming CA19-9 (AUC 0.708). Importantly, the model retained high accuracy even in CCA patients with low CA19-9 levels (AUC 0.905) and in PSC patients who developed CCA within a year of clinical diagnosis (AUC 0.792). Conclusion The PSC and PSC-CCA blood tests provide a non-invasive approach for diagnosing PSC and PSC-CCA, addressing an important need in this population. Their integration into clinical practice could enhance risk stratification, early detection, personalized surveillance, and treatment decision-making in PSC patients.

Abstract Myelodysplastic syndromes (MDS) are clinically and biologically diverse disorders, emphasizing the need for personalized treatment approaches. The International Working Group for Prognostication of MDS (IWG_PM) recently introduced a molecular classification, referred to as the MDS taxonomy, that categorizes patients into 16 subgroups based on 21 gene mutations, 6 cytogenetic abnormalities, and loss of heterozygosity (LOH) at TP53 and TET2 loci. This study sought to validate and enhance the clinical relevance of the MDS taxonomy by analyzing a large retrospective cohort ( n = 5136) and transcriptomic data from a prospective cohort ( n = 477). The taxonomy successfully identified subgroups with distinct clinical characteristics and disease progression patterns. However, incorporating gene interactions from taxonomy subgroups did not improve the prognostic performance of the Molecular International Prognostic Scoring System (IPSS‐M). We further assessed whether the taxonomy could guide management in patients receiving disease‐modifying therapies. Except for the “ TP53 ‐complex” subgroup, taxonomy classifications were not predictive of hypomethylating agent response or transplant outcomes. Nonetheless, they correlated with overall survival, suggesting that while both IPSS‐M and the taxonomy capture disease biology, other non‐genetic factors may influence treatment response. RNA sequencing confirmed the biological distinctiveness of the taxonomy groups. Transcriptomic profiling of CD34+ bone marrow cells revealed unique, homogeneous gene expression patterns, particularly within the AML‐like, bi TET2 , SF3B1 , and TP53 ‐complex subgroups. Further integration of multi‐omics data may refine MDS classification, improving clinical decision‐making and guiding the development of targeted therapies.

Abstract Background Immune checkpoint inhibitors (ICIs) improve outcomes across malignancies but can cause immune-related adverse events (irAEs), notably myocarditis, with case-fatality up to 50% Methods We retrospectively reviewed five patients with potential ICI-associated myocarditis treated at Mayo Clinic Florida (2019–2024) and summarize the existing literature. Cases were retrospectively categorized as definite, probable, or possible myocarditis according to cardiac magnetic resonance (CMR) findings and histopathology when available. Results The median age was 74 years, and four of the five patients were male. Myocarditis developed between 5 and 30 days after initiation of anti–PD-1 therapy. Presentations included dyspnea (three patients), chest pain (one patient), and asymptomatic troponin elevation detected on routine monitoring (one patient). Troponin T elevation above the 99th percentile was seen in all five cases (normal <= 15 ng/L). Electrocardiograms (ECG) demonstrated conduction abnormalities or ventricular ectopy in each patient. Left ventricular ejection fraction was preserved in four patients and severely reduced in one. CMR provided findings supportive of myocarditis in two of the five cases, while one endomyocardial biopsy (EMB) was performed and did not demonstrate active inflammation. Based on predefined criteria, one case was classified as definite myocarditis, one as probable, and three as possible ICI-associated myocarditis. All five patients received corticosteroid therapy. Two required escalation of immunosuppression. One patient developed concurrent myasthenia gravis, consistent with myocarditis–myositis–myasthenia (MMM) overlap, and underwent plasmapheresis for the neuromuscular component. Three patients recovered. Two patients died during follow-up; in both cases, myocarditis was considered a contributing factor, although direct causality could not be definitively established.

Abstract The Tau Global Conference 2025, hosted by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation, convened international experts from academia, industry, government, and philanthropy to explore advances and challenges in tauopathy research. The meeting highlighted progress across tau biology, including emerging models of tau regulation, degradation, and propagation; advances in biomarker development for the diagnosis and staging of tauopathies; and evolving therapeutic strategies targeting diverse aspects of tau pathophysiology. Discussions also emphasized the importance of cross‐sector collaboration, and global initiatives to address disparities in tau research. This report synthesizes key insights from the conference and underscores the critical role of interdisciplinary, biomarker‐driven, and globally inclusive approaches in accelerating the translation of tau research into effective clinical applications.

Background The wide reach and unique short audiovisual nature of TikTok make it a potential modality for disseminating information about orthopaedic surgery to both patients and medical professionals. However, only a few recent studies have assessed the purpose and creators of orthopaedic surgery content on TikTok. Methods The top 100 most-liked TikTok videos about orthopaedic surgery topics were included for analysis. Data reflecting video and creator account characteristics were collected. Video validity was determined by three reviewers according to the DISCERN criteria and Kruskal-Wallis H tests were performed to correlate validity to creator and video type. Results The majority of videos were created by orthopaedic surgeons (n=57/100) and for entertainment purposes (n=82/100). Orthopaedic surgeons had the highest DISCERN score (34.7) and greater video reliability compared to all other creator types (H = 59.0-67.1, all p<0.001). Videos made for educational and procedural purposes had the highest DISCERN scores (38.9 and 40.5, respectively) while entertainment videos had lower reliability (H=-56.7 to -113.5, all p<0.05). Conclusion The most popular orthopaedic surgery-related videos on the TikTok platform are primarily being created by orthopaedic surgeons for entertainment purposes. Less frequently were videos made to educate, describe procedures, and explain the lifestyle of an orthopaedic surgeon. Potential applications of utilizing the platform by orthopaedic surgeons include case or research discussions, educational videos on different pathologies, recruitment of prospective students to the field, and entertainment highlighting a day in the life of an orthopaedic surgeon.