Rajiv Gandhi Government General Hospital is a major state-owned hospital situated in Chennai, India. The hospital is funded and managed by the state government of Tamil Nadu. Founded in 1664 by the British East India Company, it is the first modern hospital in India In the 19th century, the Madras Medical College joined it. As of 2018, the hospital receives an average of 12,000 outpatients every day.
Achieving a hermetic three-dimensional seal of the root canal system remains a primary objective of endodontic therapy, yet comparative evidence on the sealing efficacy of contemporary bioceramic and resin-based sealers remains limited. Therefore, it is interest to compare the sealing ability of three bioceramic sealers (Bio-C Sealer, CeraSeal and EndoSequence BC Sealer HiFlow) with two resin-based sealers (AH Plus and ThermaSeal Plus) using micro-computed tomography. Seventy-five extracted single-rooted human premolars were obturated using single-cone technique for bioceramic sealers and warm vertical compaction for resin-based sealers, followed by three-dimensional assessment of void volume and sealer adaptation. Bioceramic sealers demonstrated significantly lower total void percentages (0.89-1.24%) compared with resin-based sealers (1.78-2.15%) (p < 0.001), with EndoSequence BC Sealer HiFlow showing the best adaptation and lowest void volume. Thus, we show that contemporary bioceramic sealers provide superior sealing ability and canal wall adaptation compared with resin-based sealers, supporting their clinical use for predictable root canal obturation.
Obstructive sleep apnea is widely recognized for its cardiovascular and pulmonary complications, but contemporary evidence has increasingly illuminated its multifaceted neuroendocrine consequences. This review synthesizes evidence from landmark physiological investigations alongside recent genetic epidemiology, metabolomic analyses, and randomized clinical trials. Recurrent pharyngeal collapse during sleep generates two core triggers: intermittent hypoxemia and cortical sleep fragmentation. These triggers drive sustained sympathetic hypertonicity, oxidative stress, and systemic inflammation, precipitating dysfunction across the hypothalamic-pituitary-adrenal, hypothalamic-pituitary-gonadal, and hypothalamic-pituitary-thyroid axes, while also inducing profound peripheral insulin and leptin resistance. Chronic nocturnal elevation of cortisol promotes visceral fat accumulation and hepatic glucose production, establishing a feed-forward loop in which cortisol- driven pharyngeal fat deposition further increases upper airway collapsibility. Loss of slow-wave and rapid eye movement sleep blunts pulsatile luteinizing hormone secretion and Leydig cell steroidogenesis, producing functional hypogonadism in affected men, while sleep-disordered breathing contributes to reproductive and metabolic dysfunction in women. Bidirectional Mendelian randomization studies have established that primary thyroid hormone deficiency causally elevates the risk of obstructive sleep apnea, whereas genetic liability to obstructive sleep apnea does not causally produce thyroid failure. Intermittent hypoxia independently impairs glycemic regulation through catecholamine-driven hepatic glucose output, downregulation of skeletal muscle glucose transporters, and oxidative injury to pancreatic beta cells; hypoxic burden during rapid eye movement sleep appears to be the strongest independent predictor of systemic insulin resistance. Appetite regulation is likewise disrupted, with paradoxical elevation of circulating leptin alongside functional leptin resistance and heightened ghrelin-driven orexigenic drive. Continuous positive airway pressure mitigates sympathetic tone and modestly enhances metabolic parameters, but because it is essentially weight-neutral its effect on systemic obesity and long-term endocrine restoration is limited. The introduction of dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists provides a viable metabolic mechanism to reduce disease severity and improve endocrine function, with phase 3 trial data showing substantial reductions in the apnea-hypopnea index alongside weight loss. Obstructive sleep apnea therefore exerts systemic endocrine disruption across central and peripheral axes, and comprehensive management requires proactive bidirectional screening between sleep medicine, internal medicine, and endocrinology clinics.
BACKGROUND AND AIMS:Saroglitazar magnesium, a dual PPAR α/γ agonist, is approved in India for the treatment of non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated steatotic liver disease (MASLD). While controlled trials with saroglitazar have demonstrated improvements in hepatic and metabolic parameters in patients with MASLD, real-world data in populations with diverse metabolic comorbidities remain limited. METHODS:This is an ongoing, prospective, single-arm, multicenter, real-world, phase 4 study evaluating the effectiveness and safety of saroglitazar 4 mg once daily in patients with MASLD. The current interim analysis includes 500 patients who completed 24 weeks of treatment. Changes in liver stiffness measurement (LSM), hepatic steatosis (CAP and UAP), glycemic control, lipid profile, liver enzymes and non-invasive fibrosis scores were assessed. Safety was evaluated based on treatment-emergent adverse events (TEAEs). This was a non-protocol-defined, exploratory interim analysis; all statistical inferences are descriptive and p-values are nominal. RESULTS:At baseline, the mean age was 45.7 ± 11.6 years, weight 81.0 ± 13.6 kg, body mass index (BMI) 29.9 ± 4.7 kg/m2 and 42% had obesity. After 24 weeks of treatment, mean LSM ± SD decreased from 10.1 ± 3.2 kPa to 8.0 ± 3.2 kPa (-20.7%, p < 0.001) and CAP decreased by 20.3 dB/m (p < 0.001). ALT levels reduced by 33.6% (p < 0.001) and HbA1c by 4.8% (p < 0.001). Improvements were also observed in lipid profile and fibrosis scores (FIB-4, FAST, APRI, ALERT). A total of 68 patients (13.6%) reported TEAEs, the majority of which were mild (85.5%) and unrelated to the study drug. No deaths were reported. CONCLUSIONS:In this interim real-world analysis, saroglitazar 4 mg was associated with improvements in liver stiffness, hepatic steatosis, metabolic parameters and non-invasive fibrosis markers in patients with MASLD. The treatment was generally well tolerated. These findings warrant further confirmation upon completion of the 52-week analysis. IMPACT AND IMPLICATIONS:Saroglitazar 4 mg for 24 weeks was associated with improvements in surrogate markers of liver injury, steatosis, glycaemic control and lipid metabolism, with good tolerability. These interim real-world findings support further evaluation in the planned 52-week analysis. CLINICAL TRIAL NUMBER:CTRI/2023/05/053326 [Registered on: 31/05/2023].
