Melatonin (N‑acetyl‑5‑methoxytryptamine), traditionally viewed as a pineal neurohormone regulating circadian rhythms, is now recognized as a pleiotropic molecule with significant implications for musculoskeletal (MSK) health. Its receptor‑dependent and receptor‑independent actions influence bone, cartilage, muscle, tendon, ligament, and spine biology, positioning melatonin as a potential therapeutic agent across diverse MSK pathologies. Experimental, translational, and clinical studies were surveyed to evaluate melatonin’s role in MSK medicine. The literature was analyzed for insights into molecular mechanisms, therapeutic targets, and clinical applications, with particular emphasis on receptor signaling pathways, antioxidant and mitochondrial effects, and epigenetic regulation. Evidence spanning bone, cartilage, muscle, tendon, ligament, spine, and autoimmune MSK conditions was incorporated to provide a comprehensive synthesis. Melatonin exerts its effects through MT1/MT2 receptor signaling, stabilization of Wnt/β‑catenin pathways, modulation of circadian clock genes, andreceptor‑independent mechanisms such as antioxidant activity, mitochondrial protection, and regulation via non‑coding RNAs. In bone biology, it enhances osteoblastogenesis, suppresses osteoclastogenesis, and modulates RANKL/OPG and NLRP3 inflammasome pathways, thereby mitigating osteoporosis and accelerating fracture healing through angiogenesis and callus formation, although dosing requires careful optimization to balance remodeling. In cartilage, melatonin resynchronizes disrupted circadian clocks, inhibits NF‑κB‑mediated inflammation, and preserves extracellular matrix integrity, with novel delivery systems currently under investigation. Skeletal muscle studies highlight its role in Pax7 regulation and Wnt signaling, contributing to the prevention of sarcopenia and cachexia. Evidence also supports its benefits in tendon and ligament repair, while in spinal pathologies melatonin demonstrates protective effects against intervertebral disc degeneration, spinal cord injury, and chronic back pain. Beyond structural tissues, melatonin exhibits cytoprotective roles in musculoskeletal oncology and shows therapeutic promise in systemic autoimmune conditions such as rheumatoid arthritis, lupus, gout, and fibromyalgia. Clinical trials further reveal analgesic, sedative, and sleep‑modulating effects, though translation gaps remain regarding optimal dosing strategies and bioavailability. Melatonin is a multifaceted agent bridging molecular cytoprotection with translational musculoskeletal medicine. Its diverse actions across bone, cartilage, muscle, tendon, ligament, and spine highlight therapeutic promise. However, clinical translation requires precision‑based dosing strategies, improved bioavailability, and rigorous validation in large‑scale trials to fully establish its role in MSK health.
Background- Advanced unresectable hepatocellular carcinoma (uHCC) is associated with poor prognosis and limited treatment options. Combination therapy with lenvatinib, a multikinase inhibitor, and pembrolizumab, an immune checkpoint inhibitor, has demonstrated promising antitumor activity in recent studies. However, variability in liver function status and prior systemic therapy exposure continues to influence clinical outcomes. This review evaluates the efficacy and safety profile of lenvatinib–pembrolizumab therapy in advanced uHCC. Objective- To assess the clinical efficacy, safety, and prognostic factors associated with lenvatinib plus pembrolizumab therapy in patients with advanced unresectable hepatocellular carcinoma. Methodology- A literature review was conducted using published clinical trials and real-world studies evaluating lenvatinib combined with pembrolizumab in advanced uHCC. Key outcomes analyzed included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse effects. Prognostic variables such as Child–Pugh classification, Albumin-Bilirubin (ALBI) score, and prior systemic therapy exposure were additionally reviewed. Result- Reviewed studies demonstrated favourable efficacy and acceptable tolerability of lenvatinib–pembrolizumab therapy in advanced uHCC. In a prospective cohort involving 71 patients, 81.7% were categorized as Barcelona Clinic Liver Cancer (BCLC) stage C. Disease control rates exceeded 80% in first-line settings and approached 70% in previously treated patients. Median progression-free survival was approximately 9 months. Liver function, assessed using ALBI scores, remained relatively stable during treatment. Common adverse effects included hypertension, fatigue, and hepatic dysfunction, while severe toxicities were infrequent. Conclusion- Current evidence supports lenvatinib combined with pembrolizumab as an effective and generally well-tolerated therapeutic strategy in advanced unresectable hepatocellular carcinoma. Treatment outcomes appear to be influenced by baseline liver function and prior immunotherapy exposure. Larger prospective randomized studies are required to further validate long-term efficacy and safety outcomes.
BACKGROUND:Acute pancreatitis (AP) ranges clinically from mild, self-limiting inflammation to severe disease with multi-organ failure. Visceral adipose tissue (VAT), a key contributor to systemic inflammation and metabolic dysfunction, may therefore influence AP severity, yet its prognostic value in the Indian population remains limited in the literature. AIM:The aim of this study is to assess whether VAT and the VAT/SMT (skeletal muscle tissue) ratio can predict clinical severity and short-term prognosis of AP in a tertiary care hospital in Chennai. MATERIALS AND METHODS:This cross-sectional study included 62 patients aged 18-60 years diagnosed with AP at ACS Medical College and Hospital from December 2023 to February 2025. Contrast-enhanced CT scans obtained within 24 hours were used to quantify VAT, subcutaneous adipose tissue, SMT, and VAT/SMT ratios at the L3-L4 vertebral level. Severity grading was performed using APACHE II (Acute Physiology and Chronic Health Evaluation), modified computed tomography severity index (MCTSI), and the Revised Atlanta Classification. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 26 (Released 2018; IBM Corp., Armonk, New York, United States). RESULTS:Higher VAT values and elevated VAT/SMT ratios showed significant associations with increased APACHE II and MCTSI scores (p < 0.001). Patients with VAT >180 cm² and VAT/SMT >1.5 exhibited more severe disease patterns. The MCTSI demonstrated strong concordance with the Revised Atlanta Classification. Male sex with alcohol consumption was significantly associated with higher severity, while age showed no significant impact. CONCLUSION:CT-derived VAT and VAT/SMT ratios are useful early markers associated with increased severity. Integrating CT-based VAT assessment with the MCTSI may enhance early risk stratification and guide timely clinical management.
Perforated peptic ulcer remains a major surgical emergency associated with significant morbidity and mortality, particularly when diagnosis is delayed or complicated by atypical presentation and systemic complications. We report a rare and challenging case of a 44-year-old male who presented with acute epigastric pain and initially misleading radiological findings. An outside computed tomography report suggested pyloric thickening with features of gastritis, while repeated erect abdominal radiographs failed to demonstrate pneumoperitoneum. The patient initially improved symptomatically with conservative management; however, he subsequently developed worsening abdominal pain, diffuse tenderness, guarding, and rigidity suggestive of evolving peritonitis. Ultrasonography demonstrated free pelvic fluid, and emergency contrast-enhanced computed tomography later confirmed pneumoperitoneum with features of hollow viscus perforation. While being shifted for emergency exploratory laparotomy, the patient suddenly developed palpitations, breathlessness, and electrocardiographic evidence of acute inferior wall myocardial infarction, creating a major perioperative challenge. Despite the high operative risk, emergency surgery was undertaken with heparin infusion and intensive cardiology support. Intraoperatively, approximately 1.5 liters of toxic intraperitoneal fluid and a 2 × 1 cm perforation in the first part of the duodenum were identified. An incidental congenital intestinal malrotation with abnormal bowel orientation was also noted. Graham’s omental patch repair, extensive peritoneal lavage, appendectomy, and drain placement were performed successfully. Postoperatively, the patient required intensive care monitoring but recovered satisfactorily without major surgical complications. This case represents an unusual “triple-threat” emergency involving occult perforated duodenal ulcer with deceptive imaging, adult congenital midgut malrotation, and acute perioperative myocardial infarction. The case highlights the limitations of plain radiography in early perforation, the importance of serial clinical examination and computed tomography in suspicious cases, and the need for rapid multidisciplinary coordination in managing critically ill surgical patients with concurrent cardiovascular instability. Early recognition and timely surgical intervention remain crucial for improving outcomes in atypical presentations of perforation peritonitis.
Background: Spinal anaesthesia remains a cornerstone technique for lower-limb surgeries, and optimizing the balance between rapid onset, prolonged analgesia, and hemodynamic stability continues to be an important area of clinical research. Objective: To compare the onset, duration, and quality of sensory and motor blockade, along with hemodynamic stability and adverse effects, between 0.75% hyperbaric ropivacaine alone and 0.75% hyperbaric ropivacaine with clonidine in patients undergoing lower-limb surgeries under spinal anaesthesia. Methods: This single-centre, prospective, randomized controlled study was conducted in the Department of Anaesthesia, ACS Medical College and Hospital, Chennai, from April 2023 to April 2025, after obtaining IHEC approval (Ref: 816/2023/IEC/ACSMCH). Results: Both groups (n=60 each) were demographically and hemodynamically comparable at baseline, with similar age (38.7 ± 10.1 vs 39.3 ± 7.6 years), BMI (25.4 ± 4.4 vs 26.3 ± 5.1 kg/m²), and vitals (p > 0.05). After spinal anaesthesia, both groups showed transient reductions in heart rate and systolic blood pressure that returned to near-baseline by surgery end. Heart rate declined to 71.4 bpm in Group A and 75.5 bpm in Group B, while SBP reached nadirs of 109.0 mmHg and 103.5 mmHg, respectively. Group B exhibited significantly faster onset of sensory (4.1 min) and motor block (5.1 min), whereas Group L showed markedly longer sensory (263.8 min) and motor block (248.9 min) durations (both p < 0.001). Adverse events were more frequent in Group L (30.0% vs 8.3%, p = 0.007), mainly nausea, pruritus, and bradycardia, indicating a trade-off between prolonged analgesia and tolerability. Conclusion: Adding clonidine to 0.75% hyperbaric ropivacaine under spinal anaesthesia significantly prolonged sensory and motor blockade and delayed analgesic requirement but increased adverse events, whereas ropivacaine alone achieved a faster onset with fewer side effects, supporting regimen selection based on the desired balance between duration and tolerability.
