Avitis Institute of Medical Sciences is an Indian hospital based in Palakkad, Kerala, India. In May 2018, two of the hospital's executive directors, Santhi Promoth and Jyothy Palat, reached out to help the family of nurse Lini Puthussery. They learned nurse Lini had died within days of contracting the Nipah virus after dutifully attending to the first victim of the virus outbreak in Kerala. The executives promised they would see to it that the educational expenses of Lini's children, ages 2 and 5 at the time of her death, would be covered, beginning with the 2019 academic year and carrying forward to when they acquire a professional degree or begin a postgraduate course. In August 2018, the hospital again gained notability for their aid and rescue efforts when helping the victims of Nelliyampathy, Kerala after flooding and heavy rains caused 70 landslides making roads impossible from the upper reaches of the Nelliyampathy Mountains to the mainland.
ABSTRACT Context The management of metabolic dysfunction‐associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) presents a significant clinical challenge, with a focus on preventing progression to liver and renal complications. Objective To evaluate the liver and renal outcomes among new users of sodium‐glucose cotransporter 2 inhibitors (SGLT2i) versus glucagon‐like peptide‐1 receptor agonists (GLP‐1RA), dipeptidyl peptidase‐4 inhibitors (DPP4i) and other anti‐diabetic medications in patients with MASLD and T2DM. Design Retrospective cohort study. Setting Electronic health records. Participants A total number of 88 306 patients with MASLD and T2DM were included in a propensity score‐matched analysis comparing the effects of anti‐diabetic drugs. Intervention Patients were categorized into groups based on their initiation of anti‐diabetic medications. Main Outcome Measures The primary outcomes were the incidence of cirrhosis, hepatic decompensations, and hepatocellular carcinoma. Secondary outcomes were a progression of chronic kidney disease (CKD), severity of CKD stages, and the need for hemodialysis. Results In the SGLT2i versus DPP4i, a reduced risk of cirrhosis was observed in the SGLT2i (HR: 0.97), along with fewer hepatic decompensations (HR: 0.84) and a lower incidence of HCC (HR: 0.50). CKD progression, particularly to stages 4–5, was significantly lower in the SGLT2i (HR: 0.53), as was hemodialysis (HR: 0.38). However, SGLT2i exhibited a slightly lower risk of CKD progression (HR: 0.77) and a reduced need for hemodialysis (HR: 0.71) compared to the GLP‐1RA, while there was no difference in hepatic outcomes between the GLP‐1RA and SGLT2i. Conclusions SGLT2 inhibitors in patients with MASLD and T2DM demonstrated reduced risks of liver complications and a favorable impact on renal outcomes. These findings support the preferential consideration of SGLT2i in managing this patient population, particularly for mitigating the progression of liver and kidney diseases.
The classification of central nervous system (CNS) tumors has evolved significantly with the integration of molecular markers, particularly through DNA methylation profiling. We aimed to explore the disparity between epigenetic profiling, histomorphology, and CNS WHO grade by analyzing the therapeutic and survival duration of the patients. This retrospective study evaluated three ambiguous pediatric cases, aged 9 to 15 years, with a radiological diagnosis of high-grade glioma. A multidisciplinary approach assessed the discordance between histomorphology, epigenetic profiling, CNS WHO grade, and overall survival. Based on the 5th edition CNS WHO classification, two cases were diagnosed as diffuse pediatric-type high-grade gliomas (PHGG), H3 wild type, IDH wild type, NOS. One of the cases exhibited a BRAF V600E mutation and was classified as glioblastoma with BRAF V600E mutation. DNA methylation profiling using the Heidelberg/DKFZ Classifier classified all three cases as pleomorphic xanthoastrocytoma (PXA), despite a mean survival of only 13.7 months. The study highlights that the methylation class PXA comprises tumors which can exhibit high-grade features and a poor prognosis.
Metabolic-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease, is an increasing global health challenge with substantial implications for metabolic and cardiovascular health (CVH). A recent study by Fu et al investigated the relationship between CVH metrics, specifically Life's Simple 7 and Life's Essential 8, and the prevalence of MAFLD. While this study offered important insights into the relationship between CVH and MAFLD, several methodological limitations, unaddressed confounding factors, and potential biases that could impact the interpretation of their findings should be considered. The study's cross-sectional nature restricted the ability to draw causal conclusions, and it did not fully account for potential confounding factors such as dietary habits, genetic predispositions, and medication use. Furthermore, relying on transient elastography to diagnose MAFLD introduces certain diagnostic limitations. Longitudinal study designs, advanced statistical modeling techniques, and diverse population groups should be utilized to strengthen future research. Exploring the mechanistic pathways that link CVH metrics to MAFLD through multi-omics approaches and interventional studies will be essential in formulating targeted prevention and treatment strategies. Structural equation modeling and machine learning techniques could provide a more refined analysis of these interrelated factors. Additionally, future research should employ longitudinal study designs and explore genetic and epigenetic influences to enhance our understanding of CVH and MAFLD interactions.
Ketamine and psilocybin show potential as therapies for various mental illnesses, including major depressive disorder. However, further investigation into their neural mechanisms is required to understand their effects on the brain. By combining computational modelling with electroencephalography (EEG), we examine the effects of ketamine and psilocybin on hierarchical sensory pwPE learning in the context of the auditory mismatch negativity, an event-related potential consistently shown to be reduced under psychotomimetic interventions. We employed a Bayesian framework and re-analyzed a previously acquired EEG dataset (Schmidt et al., 2012) by modelling single-trial EEG data using the Hierarchical Gaussian Filter. Using a placebo-controlled within-subject crossover design, healthy subjects were administered either S-ketamine or psilocybin during an auditory roving paradigm of pure sinusoidal tones. Our findings elucidate distinct neural impacts of ketamine and psilocybin on sensory learning: ketamine led to a larger reduction in the effect of sensory precision compared to placebo from 207 to 316 ms peaking at 277 ms in the frontal central channels, while psilocybin showed no significant effect. Both drugs reduced the expression of belief precision between 160 to 184 ms, peaking at 172 ms. For higher-level volatility pwPEs, ketamine reduced the expression at 312 ms while psilocybin had a null effect. For perception of elementary imagery, ketamine had a greater effect than psilocybin on sensory and volatility precision, while psilocybin had a greater effect on volatility pwPEs. Our findings suggest hallucinogens have distinct effects on sensory learning that could inform tailored therapies for major depression. ### Competing Interest Statement The authors have declared no competing interest. Schweizerischer Nationalfonds zur FM-CM-6rderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) - P1BSP3-200054 [Hauke], P1BSP3-200054 Schweizerischer Nationalfonds zur FM-CM-6rderung der Wissenschaftlichen Forschung (Swiss National Science Foundation), PZ00P3-167952 Centre for Addiction and Mental Health and Mental Health, CAMH Discovery Fund Swiss Neuromatrix Foundation - Stiftung fM-CM-<r Bewusstseinsforschung
A recent study by Lu et al examined the potential benefits of postoperative combined therapy (PCT) using anti-programmed cell death protein-1/PD-ligand-1 and anti-vascular endothelial growth factor agents for patients with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). At the same time, the findings offer important insights; however, several methodological and statistical limitations should be noted. These limitations include selection bias from the study's retrospective design, variability in treatment regimens, a small sample size, and inadequate monitoring of hepatitis B virus (HBV) reactivation. The study's conclusions about PCT efficacy warrant cautious interpretation due to unresolved biases. Prospective trials with biomarker stratification are critical to confirm these preliminary findings. These findings underscore the need for prospective, biomarker-driven trials to validate the efficacy of PCT. Future research should prioritize standardized regimens, HBV reactivation monitoring, and global collaborations to optimize therapeutic strategies for HBV-HCC.
