Citations

Interest in using gene therapy to treat osteoarthritis (OA) is growing and a number of clinical trials have been initiated. This commentary identifies three intersecting areas that need to be addressed for the field to move forward expeditiously. The first relates to lowering the cost of manufacturing clinical grade viral vectors, addressing various aspects of their deployment, and overcoming immune barriers to dosing and re-dosing. The second area requires an improved understanding of the pathophysiology of OA, including its stratification by endotype and phenotype. Coupled to the development of reliable biomarkers, this will enable the creation of personalized gene therapies, facilitate patient selection, and aid the identification of additional molecular targets. Moreover, progress in the early diagnosis of OA will enable administration of gene therapeutics at a stage when they are most likely to be successful. Finally, important issues with regard to financing and regulation are discussed. Top line data from two pivotal Phase III clinical trials are expected to be released this year. The findings from these trials will exercise considerable influence on the future development of the field.

Community engagement and trust are vital to medical education and improving health. The experience of national level, extramural seed grant programs to support faculty in both education and health care delivery with the focus of building trust has not been previously reported. The authors reviewed a total of four cohorts of the “Building Trust: Advancing Health Equity” grant recipients supported by the ABIM Foundation and other funding partners. Over $1.5 million was awarded from 2021 to 2024, which represented 92 grants ranging from $2,500–$40,000 each. The geographic regions receiving the most grants and funding were the middle and south Atlantic, and the Pacific regions in the United States. University programs received more grants and funding than affiliated or community programs. The majority of project types primarily focused on developing educational curricula for internal medicine residents (68%) and engaging with local communities (19%). The approach to implementation often included service-learning and community experts (29%), quality improvement and patient care delivery methods (22%), and traditional curriculum development (21%). The most common education topic themes were health equity and social determinants of health (43%) and addressing bias in care delivery and learning environment (20%). The Building Trust grant program reflects the unique needs of local communities and supported innovative practices and educational techniques. Implementation support was provided to grantees through shared experiences and mentorship. Evaluating outcomes upon completion of grants will be an imperative next step. This serves as a model that can inform institutions and other professional organizations approaching implementation of seed grant funding.

ABSTRACT Unexpected RF noise artifact “followed” a patient with an implanted spinal cord stimulator to multiple MR systems. Subsequent testing and clinical scanning showed no artifact, implying that the artifact originated from the implanted device. MR exams ( n = 173) performed over a two‐year period in patients ( n = 122) who had implanted spinal cord stimulators from the same manufacturer were reviewed for artifacts and device models. RF noise artifacts were observed in ~50% of exams in patients with a specific model of spinal cord stimulator, but only ~1%–8% of exams in other models from the same manufacturer. We hope that by describing this artifact, health care professionals can avoid service costs and scheduling delays.

Abstract Endocytosis regulates receptor trafficking and signaling, yet its role in colorectal cancer (CRC) remains unclear. We analyzed transcriptomic data from 15,025 CRC tumors to evaluate gene expression in clathrin-mediated endocytosis (CME) and the endosomal sorting complexes required for transport (ESCRT) pathway. Pathway-level signatures were compared across consensus molecular subtypes (CMS) and examined in relation to oncogenic signaling programs, while individual endocytosis-related genes were evaluated for associations with clinical outcomes in an independent randomized trial cohort. Expression of CME and ESCRT pathways varied by CMS, with the highest expression in CMS4 and the lowest in CMS3. Endocytosis signatures correlated with multiple oncogenic signaling pathways, including MAPK, TGF-β, WNT, PI3K, NOTCH, and angiogenesis, suggesting broad links between endocytic activity and tumor biology. In the randomized phase III CALGB/SWOG 80405 trial, low expression of AP2M1 —a core adaptor in the CME complex—was significantly associated with longer overall survival and progression-free survival in patients treated with anti-EGFR agents, but not in those receiving anti-VEGF agents. These findings suggest that endocytic trafficking may be associated with oncogenic signaling and differential therapeutic benefit in patients with metastatic CRC. The endocytosis pathway reflects biologically relevant heterogeneity in CRC and may help guide therapeutic stratification.

Abstract Background: Fibrillary glomerulonephritis (FGN) is a rare immune-mediated glomerular disease characterized by glomerular fibrillar deposits and historically associated with poor kidney outcomes. Despite recent diagnostic advances, including DNAJB9 immunohistochemistry, the clinical spectrum, prognostic factors, and optimal management of FGN remain incompletely defined. Methods: We conducted a retrospective cohort study of patients with biopsy-proven FGN identified through the Cleveland Clinic Kidney Biopsy Epidemiology Project between January 2015 and March 2023. Results: Thirty patients met inclusion criteria. The cohort was predominantly female (70%) and white (86%), with a median age of 64 years. At the time of kidney biopsy, all patients had hypertension and acute or chronic kidney disease. Additional features included hematuria (76%), proteinuria (60%), and nephrotic syndrome (48%). Monoclonal protein was detected in 20% of cases. During a mean follow-up of 24 months (range 0–70 months; n = 13), 23% achieved partial remission, 23% had persistent disease, and 53% progressed to end-stage kidney disease (ESKD). Higher serum creatinine at biopsy was the only variable associated with progression to ESKD. Conclusion: FGN remains a rare glomerular disease with substantial risk of progression to kidney failure. This single-center cohort highlights the heterogeneous clinical presentation and generally poor kidney outcomes of FGN in the modern diagnostic era. Larger, multicenter studies are needed to refine prognostic stratification and guide evidence-based management strategies.

Abstract Background The multicentre ALaCaRT and ACOSOG Z6051 randomized trials were unable to demonstrate non-inferiority of laparoscopic versus open surgery for rectal cancer with respect to a composite pathology metric indicating successful resection. Neither trial was individually powered to detect differences in long-term recurrence or survival. This planned meta-analysis determined long-term oncological outcomes of laparoscopic versus open proctectomy for rectal adenocarcinoma. Methods This prospective meta-analysis included individual patient data from patients with cT1–3 N0–2 M0 rectal adenocarcinoma enrolled in the ALaCaRT and ACOSOG Z6051 trials. Pathologically successful resection was defined as complete or near-complete total mesorectal excision, a clear circumferential resection margin (CRM; > 1 mm), and a clear distal resection margin (> 1 mm). The non-inferiority margin for disease-free survival (DFS) was an absolute difference of 5% at least 3 years after surgery. Results The combined data set included 935 patients (65.6% men, mean age 60.7 years, mean body mass index 26.7 kg/m2) randomized to open (457 patients) or laparoscopic (478 patients) proctectomy. Pathologically successful resection was lower in the laparoscopic than open group (85.1% versus 89.9%, respectively; pooled estimate 4.6% difference; 95% confidence interval (c.i.) −8.6% to −0.5%). The median follow-up was 60.2 (interquartile range 49.9–61.1) months. Three-year DFS was 75.2% (95% c.i. 71.1% to 79.2%) and 76.5% (95% c.i. 72.5% to 80.6%) for the laparoscopic and open groups, respectively (pooled estimate difference −1.5%; 95% c.i. −7.2% to 4.2%). Non-inferiority of laparoscopic surgery was not demonstrated because the lower one-sided 95% c.i. (−6.3% to 100%) crossed −5%. Three-year locoregional recurrence was higher in laparoscopic than open group (5.4% (95% c.i. 3.3% to 7.5%) versus 2.0% (95% c.i. 0.7% to 3.4%), respectively; pooled estimate 3.1% difference (95% c.i. 0.6% to 5.6%)). A clear CRM was the most significant and only pathological predictor of both DFS (P < 0.0001) and overall survival (P < 0.0001). Conclusion Laparoscopic proctectomy led to a lower rate of pathologically successful resection and a higher rate of locoregional recurrence at 3 years. The possibility of subsequent poorer DFS or overall survival rate requires further evaluation, because this analysis was not specifically powered for these endpoints.

Objective To evaluate patient satisfaction with the experience of using an autonomous wheelchair to transport patients in a large outpatient clinical environment. Methods The autonomous wheelchair pilot was approved as a feasibility pilot by the institutional committees and deemed a quality improvement project by the Institutional Review Board (IRB). A total of 409 adult patients using an autonomous wheelchair at a large academic medical center who volunteered to complete a paper survey were included. The survey was administered immediately after autonomous wheelchair use, using a cross-sectional, anonymous survey, between 15 Oct 2025 and 14 Jan 2026. Of 409 completed surveys, six were excluded because participants did not identify their endpoint for stratification purposes. Descriptive analysis included frequencies and percentages of responses. Results No collisions or adverse events were observed during the pilot, and the system operated reliably within the predefined routes. Most survey respondents were first-time users (335/402 [83.3%]). A majority reported they would use the autonomous wheelchair again (341/395 [86.3%]) and would recommend it to others (364/397 [91.7%]). Overall, the experience was rated better than expected by 293 of 393 participants (74.6%). When given a choice, 271 of 379 respondents (71.5%) preferred the autonomous wheelchair over a staff-operated wheelchair. Conclusion These findings suggest that autonomous wheelchairs are feasible and acceptable to patients in a controlled outpatient setting and support continued piloting and prospective evaluation.