Citations

ABSTRACT Genetic variants that impair cardiac function or predispose individuals to autoimmune diseases can influence both the risk and severity of inflammatory heart diseases, including lymphocytic myocarditis and cardiac sarcoidosis. We review recent clinical and experimental studies that describe the emerging interplay between genetic susceptibility and active myocardial inflammation. We summarize the current perspective on the mechanisms of inflammatory pathways and gene‐immune interactions, and explore the emerging therapeutic approaches aimed at targeting inflammation in genetic cardiomyopathies.

Abstract Background Native vertebral osteomyelitis (NVO) is a life-threatening spinal infection with rising incidence and significant morbidity. Despite its growing burden, long-term data on clinical characteristics, management trends, and outcomes remain limited. Methods We conducted a 26-year multicenter retrospective cohort study of adults (≥18 years) diagnosed with NVO at Mayo Clinic sites between 1999 and 2024. Demographic, microbiologic, treatment, and outcome data were analyzed across five time periods. Predictors of treatment failure were assessed using a multivariable competing risk model. Results Among 1255 patients (median age 67; 66% male), lumbosacral involvement was most common (65%), and 21% had multilevel involvement. Pathogens were identified in 77%, most commonly Staphylococcus aureus (49%; Methicillin-susceptible S. aureus 37%, methicillin-resistant S. aureus 13%). Over time from 1999–2004 to 2020–2024, Gram-negative bacilli increased from 6% to 14% (P = .048). Comorbidities including chronic kidney disease (10% to 21%), active chemotherapy (6% to 11%), and immunosuppression (8% to 17%) increased significantly. Additionally, 1-year treatment failure declined (16% to 10%). In multivariable analysis, diabetes mellitus (subdistribution hazard ratio [sHR] 1.92, 95% CI 1.18–3.13) and multilevel involvement (sHR 1.67, 95% CI 1.17–2.38) were associated with increased incidence of treatment failure, while concurrent infections (sHR 0.57, 95% CI 0.37–0.87) and higher Charlson Comorbidity Index (sHR 0.62, 95% CI 0.43–0.90) were associated with lower failure. Conclusions This large multicenter cohort highlights increasing host complexity, shifting microbiology, and predictors of failure, emphasizing the importance of early risk stratification and tailored strategies, such as multidisciplinary evaluation and close follow-up of high-risk patients to improve outcomes.

Abstract Background Mitral valve prolapse (MVP) is the most common valvular abnormality in the population. Emerging evidence suggests that MVP is associated with left ventricular (LV) remodelling and dysfunction regardless of mitral regurgitation (MR) severity mimicking an early stage of dilated cardiomyopathy. However, prior studies have provided scattered results and were limited by small sample size and poor adjustment for confounders. Purpose To assess early cardiac chamber remodelling associated with MVP in absence of significant MR. Methods This multicentre, retrospective case-control study included patients with isolated MVP without significant MR undergoing CMR including late gadolinium enhancement (LGE). Healthy controls (HC) were selected from local databases and included subjects without cardiovascular pathology or significant comorbidities, with normal CMR parameters defined as comprised within normality ranges reported in the literature. Propensity-score-matching (PSM) was performed in a 1:1 nearest neighbour without replacement method (calliper 0.1), based on age, sex, body-surface-area, hypertension, and diabetes. The impact of MVP on cardiac remodelling was quantified using absolute standardized mean differences (SMDs). Results A total of 587 MVP patients and 583 HC were included, with 517 pairs successfully matched after PSM. Compared to HC, MVP patients showed greater left atrial (LA) area (12.2 [10.5 – 14.1] vs. 11.0 [9.5 – 12.4] cm²/m²), left ventricular (LV) end-diastolic-volume (86.3 [72.4–101.4] vs. 76.3 [66.1–86.0] ml/m²), and lower LV ejection-fraction (60.0% [55.2–65.6] vs. 61.0% [58.0–66.0], all p<0.001). MVP patients also showed greater right atrial area, right ventricular end-diastolic-volume, and higher right ventricular ejection-fraction compared to HC (Figure 1). The greatest impact of MVP on remodelling was observed for LV-end-diastolic volume and left atrial size (SMD ~0.55–0.62, respectively), (Figure 2). Among patients with MVP, remodelling was most pronounced in patients with bi-leaflet MVP and LGE. Conclusions In the absence of significant MR, MVP is associated with cardiac chambers’ remodelling with a particular emphasis on LV and LA dilatation.Cardiac chamber parameters in HC vs. MVP Effect size of MVP on cardiac remodeling

This study uncovers a previously unrecognized role for NAV3 in TGF-β1-driven cardiac fibroblast activation. We show that NAV3 facilitates profibrotic remodeling through noncanonical signaling and cell cycle arrest, independently of SMAD2/3. These findings position NAV3 as a novel regulator of fibroblast phenotype and a potential modulator of cardiac fibrosis.

Objective Age of symptom onset is highly variable in familial frontotemporal lobar degeneration (f‐FTLD). Accurate prediction of onset would inform clinical management and trial enrollment. Prior studies indicate that individualized maps of brain atrophy can predict conversion to dementia in f‐FTLD. We used a Bayesian linear mixed‐effect (BLME) prediction method for identifying accelerated brain volume loss to predict conversion to dementia. Methods Participants included 234 asymptomatic or prodromal carriers of C9orf72 , GRN , or MAPT mutations (including 21 dementia converters) with ≥3 longitudinal magnetic resonance imaging (MRI) T1‐weighted scans. The BLME models established individual voxel‐wise gray matter trajectories using the first 2 scans. Person‐specific clusters of accelerated volume loss were estimated in subsequent scans and tested as predictors of dementia conversion compared with other approaches in time‐varying Cox proportional hazard models covarying for age. Receiver‐operating characteristic (ROC) curves estimated utility of cluster volume in discriminating which participants converted to dementia within 24 months. Results The BLME cluster volume predicted conversion to dementia in f‐FTLD mutation carriers overall and separately in C9orf72 , GRN , and MAPT , with comparable hazard ratios observed for atrophy W‐maps and regional volumes. Within a 24‐month timeframe, BLME cluster volume discriminated dementia converters from non‐converters with larger areas under the curve (AUCs) than other approaches. Interpretation Bayesian‐modeled individualized atrophy scores predict dementia progression among asymptomatic f‐FTLD mutation carriers and may have increased utility compared with other structural imaging methods when studying individuals over shorter timeframes that align with clinical trial design. ANN NEUROL 20269999:n/a–n/a

Abstract Background & Aims Central reading of endoscopy and histopathology is the current standard for disease activity assessment in inflammatory bowel disease (IBD) clinical trials but is limited by interreader and intrareader variability, operational delays, and cost. Artificial intelligence (AI) and machine learning (ML) offer the potential to improve accuracy, efficiency, and reproducibility. The International Organization for the Study of IBD (IOIBD) developed consensus statements on AI/ML use for endoscopic and histologic endpoint assessment in IBD trials. Methods As part of the IOIBD endpoints cluster initiative, a narrative, evidence-informed review with literature searches of Medline and Embase (January 2018-February 2025) identified studies applying AI/ML to endoscopy or histology in IBD. Relevant evidence informed 36 survey statements formulated by a steering committee. Seventy-two IOIBD members were invited to vote online; consensus required ≥80% agreement (score: 7-10 on a 10-point scale). Results Forty-five members completed the survey. Consensus was reached for 28 statements related to endoscopy, pathology, and trial design. Experts agreed that AI-based central reading could improve diagnostic accuracy, expedite processes, reduce costs, and enhance reproducibility. Combining human and AI assessments was favored over AI replacement. The key limitations identified included insufficient validation, generalizability concerns, and dependence on human-annotated training datasets. Conclusions This IOIBD consensus supports the integration of AI/ML into central reading for IBD clinical trials to improve objectivity, efficiency, and consistency, while maintaining human oversight. Further research should address validation, regulatory frameworks, and multimodal integration to enable broader adoption in both trials and clinical practice.

ABSTRACT Objective With regulatory approval of HPV‐specific immunotherapy for recurrent respiratory papillomatosis (RRP) and growing experience with systemic bevacizumab, a management algorithm incorporating these medical treatments is warranted. Data Sources and Methods RRP Foundation (RRPF) Key Opinion Leaders offer a proposed management algorithm for adults with RRP considering published literature and commercial drug availability. Results Preventative HPV vaccination should be considered for all patients. Determination of HPV type and pulmonary imaging are important for contemporary RRP patient care and assist in decision making. Risks and benefits of papilloma debulking as needed versus medical management of RRP must be deliberated on a patient case‐by‐case basis. HPV ‐specific immunotherapy that induces an HPV ‐specific T cell response to target the underlying HPV infection that is the cause of RRP is safe, offers the possibility of durable disease control following a short treatment course and is the recommended first‐line medical treatment for patients who wish to avoid the risks of repeat procedural management. Papilloma disease control with systemic bevacizumab, which carries defined risks and must be continued for clinical benefit is the recommended second‐line medical treatment for patients who do not achieve a complete response with immunotherapy and wish to continue medical management. For patients who elect to be treated with debulking procedures as needed, use of locally‐administered adjuvant should be considered. Conclusion This proposed management algorithm from the RRPF serves as a contemporary resource and information guide for adult patients with RRP and their physicians considering treatment options. Level of Evidence 5

Abstract Background A unified definition of prosthetic joint infection outcomes (PJI) is crucial for consistent data, study comparisons, and better care. This study systematically reviews how PJIs outcomes are defined, building on our prior research on native vertebral osteomyelitis and postoperative spinal infection.Figure 1Network plot illustrating the co-occurrence of outcome criteria in prosthetic joint infection studies. Edge thickness reflects the frequency of the co-occurrence of each criterion. Each plot highlights one criterion, namely (1) clinical signs, (2) imaging, (3) microbiology, (4) histopathology, (5) antibiotics-related, (6) surgical-related, (7) mortality. Methods We conducted a comprehensive search of the Cochrane, Embase, Medline, and Scopus databases for studies published after 2005 that clearly defined outcomes for PJI. Eligible studies included randomized controlled trials and cohort studies with a minimum of 10 patients diagnosed with PJI. Our methodology adhered closely to the PRISMA guidelines. Using a saturation approach, we extracted and grouped explicit definitions of PJI outcomes into thematic criteria. A network plot (Figure 1) was used to visualize how frequently these criteria appeared and how they co-occurred across the included studies. Results Out of 7,584 screened studies, 552 (7.3%) met the inclusion criteria. This pilot analysis included 49 randomly selected studies (8,162 patients), mostly retrospective (48/49, 98%), focusing on mixed joint replacements (25/49, 51%), two-stage exchanges (15/49, 31%), or mixed surgeries (24/49, 49%). Only 6/49 (12.2%) applied a society-endorsed definition, and 13/49 (26.5%) cited a reference for their outcome definitions. Overall, 32/49 (65.3%) explicitly defined "success," 35/49 (71.4%) defined "failure," and 16/49 (32.7%) defined both. Most studies (25/49, 51%) had follow-up periods over two years, and 14/49 (28.6%) included patient-reported outcomes, identifying 14 unique PROMs (most commonly UCLA, HHS, and KSS scores). Functional outcomes were assessed in 13/49 (26.5%) studies. We identified 16 distinct outcome criteria across seven categories: clinical signs, microbiology, imaging, histopathology, antibiotics-related, surgical-related, and mortality. Network analysis revealed strong links among clinical signs, microbiology, surgical factors, mortality, and imaging. Conclusion Our pilot study found major variation in PJI outcome definitions, with few standardized criteria. A consensus-driven approach is needed to strengthen evidence synthesis and advance patient care in PJI. Disclosures All Authors: No reported disclosures

Study Design Narrative Review. Objectives To summarize the scientific contributions generated from the AO Spine Knowledge Forum Tumor (AOSKFT) databases, focusing on primary spine tumors, and highlight key findings, research trends, and future directions. Methods Data from the Primary Tumor Retrospective (PT-Retro) and Primary Tumor Research Outcome Network (PTRON) registries were analyzed. The nineteen studies included were peer-reviewed manuscripts focused on primary spine tumors, excluding abstracts, book chapters, systematic reviews, and metastatic studies. Results The PT-Retro registry compiled data from 1495 patients across 18 primary tumor histologies, offering insights into recurrence, survival, and treatment paradigms. Key findings emphasize the importance of Enneking-appropriate (EA) resection in improving survival and reducing recurrence in tumors such as chordoma, chondrosarcoma, and osteosarcoma. Genetic markers, including hTERT promoter mutations and rs2305089 SNP, were linked to prognosis in specific histologies. Benign tumors, such as giant cell tumors and aneurysmal bone cysts, demonstrated variable outcomes with different surgical approaches and selective arterial embolization. Conclusions The AOSKFT registries have significantly advanced knowledge in primary spine tumor management, emphasizing preoperative staging, surgical margins, and multidisciplinary approaches. International, multicentric registries are essential for studying rare diseases like primary spine tumors, enabling robust data collection, improved statistical power, and broader applicability of findings across diverse clinical settings. Ongoing prospective data collection through PTRON will further refine evidence-based care for these rare and challenging conditions.