Osteoporosis is a major and growing health concern in the Asia-Pacific region, y et it remains widely underdiagnosed and undertreated due to limited access to dual-energy X-ray absorptiometry (DXA) in many areas. Artificial intelligence (AI) offers new opportunities to improve osteoporosis screening and management, but unvalidated tools pose risks of inconsistent care. This consensus was developed to provide regionally harmonized guidance on the safe, effective, and equitable use of AI in osteoporosis care. Purpose The aim of this work was to establish expert consensus recommendations on the role of AI in osteoporosis screening and management in the Asia-Pacific region. Key objectives were to define appropriate applications of AI (e.g., imaging-based bone assessment and fracture risk prediction) and specify minimum standards for validation and reporting, addressing region-specific implementation challenges and ensuring that AI use aligns with clinical guidelines and ethical principles. Methods This consensus was developed through multidisciplinary collaboration among experts across the Asia-Pacific region. Each participant reviewed draft statements, contributed feedback during virtual meetings, and provided insights based on clinical experience and current evidence. Consensus was reached iteratively until full agreement was achieved for all statements. The process integrated global best practices and regional adaptations, drawing from peer-reviewed studies, international AI guidelines, and local fracture registry data. The final recommendations emphasize the validation, transparency, and ethical implementation of AI within regional healthcare systems, ensuring compatibility with local regulations. Ultimately, twelve consensus statements were established to guide the responsible use of AI for osteoporosis screening and management in the Asia-Pacific region. Results The panel produced 12 consensus statements covering the role of AI as an adjunct for opportunistic osteoporosis screening rather than a diagnostic tool, requirements for imaging quality and AI model transparency, standards for validation and performance reporting, integration of AI with clinical risk stratification, demonstration of clinical utility in real-world settings, adherence to data protection laws and ethical AI principles, training of clinicians in AI use, strategies for implementation and monitoring (including post-market surveillance and feedback loops), and recognition of technical, clinical, and equity limitations of AI. All 12 statements give extensive recommendations for using AI to improve osteoporosis management while ensuring patient safety, accuracy, and equity. Conclusion This first Asia-Pacific consensus on AI in osteoporosis concludes that AI, when appropriately validated and implemented, can help bridge the osteoporosis care gap by identifying high-risk patients who would otherwise remain undiagnosed, thus facilitating earlier intervention. It emphasizes that AI should complement-not replace-standard diagnostic methods and clinical judgment. The guidance emphasizes validation, transparency, and ethical oversight to facilitate early intervention while minimizing risks associated with unvalidated or premature AI adoption.
Ossification of the posterior longitudinal ligament (OPLL) and diffuse idiopathic skeletal hyperostosis are debilitating conditions characterized by pain, stiffness, myelopathy, and impaired mobility due to progressive enthesopathies and spinal fractures. These disorders worsen with age and may lead to hemiplegia. The underlying mechanisms of these diseases remain poorly understood, and effective treatments are currently lacking. To elucidate the pathogenesis of OPLL, we conducted a prospective study involving plasma analyte measurement in 50 consecutive OPLL and 25 consecutive cervical osteoarthritis patients who presented for surgical correction within the same time frame, followed by exome sequencing of 19 genes associated with phosphate wasting and spinal ligament enthesopathy/ossification. Our study identified a significant association between OPLL and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) deficiency. Specifically, we observed that OPLL patients exhibited decreased plasma levels of inorganic pyrophosphate (PPi) while maintaining unaltered alkaline phosphatase levels. Additionally, 14% of OPLL patients harbored monoallelic pathogenic variants in ENPP1, the mammalian enzyme responsible for extracellular PPi. Using Enpp1-deficient mice (Enpp1asj) to model the condition, we discovered pathologic mineralization of the spine, long bones, and tendons, alongside increased long bone and spinal fracture risk by 17 wk of age. We further assessed the therapeutic potential of 2 forms of ENPP1 enzyme replacement therapies. Bone-targeted ENPP1 significantly ameliorated the spinal hyperostosis, improved or normalized spinal and long bone fragility, ameliorated tendon enthesopathies, and improved trabecular microarchitecture. Meanwhile, soluble ENPP1 prevented tendon enthesopathies, normalized cortical bone microarchitecture, and improved long bone fragility. Our findings establish a clear link between decreased plasma PPi, ENPP1 deficiency, and OPLL, unveiling additional therapeutic targets to more effectively manage this poorly treated condition.
Repeat stereotactic radiosurgery (SRS) is a treatment option for residual brain arteriovenous malformations (AVMs) following incomplete response to an initial SRS, and this study aimed to clarify the long-term outcomes. Patients who underwent repeat SRS between 1990 and 2022 were retrospectively analyzed. Primary outcome was a favorable patient outcome, defined as AVM obliteration without post-SRS hemorrhage or symptomatic T2 signal change/late radiation-induced complications (LRICs). Fifty-eight patients with a median follow-up of 97 months were analyzed. Six patients (10.3
Background Only a minority of patients with advanced gastric cancer (GC) or esophagogastric junction (EGJ) adenocarcinoma derive durable benefit from anti-programmed cell death 1 (PD-1) therapy. However, reliable biomarkers for real-world clinical decision-making remain limited. Objective To identify tumor site-specific genomic alterations associated with outcomes of nivolumab monotherapy in a nationwide real-world cohort. Methods We conducted a retrospective nationwide analysis using Japan's Center for Cancer Genomics and Advanced Therapeutics (C-CAT) registry, including patients with GC and EGJ cancer adenocarcinoma treated with nivolumab monotherapy (July 2019-April 2024). Primary endpoints were time to treatment failure (TTF) and overall survival (OS), defined as the interval from nivolumab initiation to death from any cause; objective response rate (ORR) was secondary. Gene-level alteration indicators were derived from vendor-reported tumor-only panel calls across multiple platforms and filtered for clonal hematopoiesis of indeterminate potential (CHIP)-like variants (variant allele frequency < 0.05). Multivariable models adjusted for age and sex were fitted separately for GC and EGJ cancer. Variant pathogenicity was based on available panel annotations; therefore, gene-level results should be interpreted as exploratory findings. Results Among 798 patients with GC and 114 patients with EGJ cancer adenocarcinoma, median TTF/OS/ORR were 3.98 months/20.2 months/11.7% in GC and 4.80 months/24.7 months/14.9% in EGJ cancer adenocarcinoma. In GC, ASXL1 mutation remained independently associated with longer TTF (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.37-0.94) after adjustment and CHIP filtering. For OS, microsatellite instability-high [MSI-H] (HR 0.16, 95% CI 0.04-0.70) and FANCG (HR 0.37, 95% CI 0.16-0.87) were associated with longer OS, whereas CDH1 (HR 1.51, 95% CI 1.10-2.05) was associated with shorter OS. In EGJ cancer adenocarcinoma, NTRK1 mutation correlated with longer TTF (HR 0.31, 95% CI 0.10-0.98) and MUTYH with shorter OS (HR 5.68, 95% CI 2.04-15.81), both exploratory. Conclusions In this large Japanese real-world cohort, genomic associations with nivolumab outcomes differed by tumor site. In gastric cancer, ASXL1 mutation was associated with prolonged treatment benefit under PD-1 blockade, while CDH1 and FANCG showed exploratory associations with OS. These findings warrant further validation in prospective and platform-controlled analyses.
Coronary artery disease (CAD) is a major risk factor for the development of heart failure (HF) with preserved ejection fraction (HFpEF) and is associated with increased mortality. However, an optimal strategy to screen for HFpEF among patients with CAD has not yet been established. The HFpEF-ABA score was introduced to estimate the pretest probability of HFpEF and was shown to predict adverse HF events. This retrospective multicenter cohort study included patients registered in the Clinical Deep Data Accumulation System database who underwent percutaneous coronary intervention from April 2013 to March 2019. Patients with a left ventricular (LV) ejection fraction ≥ 50
