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Objectives: Rheumatic mitral stenosis (RMS) remains a significant health challenge, particularly in low- and middle-income countries, due to limited access to preventive measures and timely treatment. Percutaneous mitral balloon valvuloplasty (PMBV) has become the preferred treatment for RMS, offering a less invasive alternative to surgical mitral valve replacement. This study aimed to evaluate the demographic, clinical, and echocardiographic characteristics of patients with RMS undergoing PMBV and to assess the procedural outcomes. Materials and Methods: This study included 52 patients who underwent PMBV RMS. Patients with non-RMS, incomplete patient files, or previous valve surgeries were excluded. Results: The procedural success rate was 87%, with better outcomes observed in patients with a Wilkins score ≤8 than in those with a score >8. PMBV resulted in a significant increase in mitral valve area (MVA) (from 1.18±0.19 cm² to 2.27±0.48 cm², p=0.001) and a decrease in both mean mitral valve gradient (from 12.82±3.5 mmHg to 5.97±2.04 mmHg, p=0.001) and maximum mitral valve gradient (from 27.12±14.0 mmHg to 12.70±3.1 mmHg, p=0.001). Although the procedure was generally safe, manageable complications, such as chordal rupture (1 case, 1.9%) and mitral regurgitation (MR) progression, were observed, particularly in patients with higher Wilkins scores. Conclusion: The significant improvements in MVA and reduced gradient observed in our study underscore the effectiveness of PMBV, even in patients with higher Wilkins scores. Although we observed manageable complications, such as chordal rupture and MR progression, the overall safety and efficacy of PMBV in our patient population highlight its value as a practical and effective treatment option for RMS in our clinical setting. These findings support the continued use of PMBV as a standard treatment approach in our region, potentially enhancing the quality of care for patients with this condition.

Abstract Alcohol use disorder (AUD) is the most prevalent substance use disorder worldwide. Acamprosate and naltrexone are anti-craving drugs used in AUD pharmacotherapy. However, molecular mechanisms underlying their anti-craving effect remain unclear. This study utilized a patient-derived induced pluripotent stem cell (iPSC)-based model system and anti-craving drugs that are used to treat AUD as “molecular probes” to identify possible mechanisms associated with alcohol craving. We examined the pathophysiology of craving and anti-craving drugs by performing functional genomics studies using iPSC-derived astrocytes and next-generation sequencing. Specifically, RNA sequencing performed using peripheral blood mononuclear cells from AUD patients with extreme values for alcohol craving intensity prior to treatment showed that inflammation-related pathways were highly associated with alcohol cravings. We then performed a genome-wide assessment of chromatin accessibility and gene expression profiles of induced iPSC-derived astrocytes in response to ethanol or anti-craving drugs. Those experiments identified drug-dependent epigenomic signatures, with IRF3 as the most significantly enriched motif in chromatin accessible regions. Furthermore, the activation of IRF3 was associated with ethanol-induced endoplasmic reticulum (ER) stress which could be attenuated by anti-craving drugs, suggesting that ER stress attenuation might be a target for anti-craving agents. In conclusion, we found that craving intensity was associated with alcohol consumption and treatment outcomes. Our functional genomic studies suggest possible relationships among craving, ER stress, IRF3 and the actions of anti-craving drugs.