Jagadish Ramasamy

Hepatitis C Virus (HCV) infection promotes insulin resistance, and metabolic dysfunction-associated fatty liver disease (MAFLD). HCV per se leads to impairment in host lipid metabolism and causes a deranged lipid profile. This study aims to analyze the prevalence of MAFLD and determine the levels of lipid profile parameters, surrogate markers of insulin resistance, liver fibrosis, and steatosis in patients with HCV infection. This study used data from the Centers for Disease Control – National Health and Nutritional Examination Survey (CDC-NHANES) 2017-2020. Those who tested positive on HCV RNA PCR were included in HCV group (n=89). Propensity score-based age- and gender-matching was done among those tested negative for HCV to select controls (n=89). Homeostatic Model Assessment of Insulin Resistance (HOMAIR), Homeostatic Model Assessment of Beta-cell Function (HOMAB), and the lipid-based insulin resistance markers such as Visceral Adiposity Index (VAI), Lipid Accumulation Product (LAP), Triglyceride-Glucose Index (TyG) were calculated using the standard formulae. Serum triglycerides, total cholesterol and low-density lipoprotein cholesterol were significantly lower in HCV. HOMAIR, HOMAB were similar, and the lipid-based insulin resistance markers such as VAI, LAP and TyG index were significantly lower in HCV. FibroScan showed less steatosis, but increased fibrosis in the HCV patients. The surrogate markers of insulin resistance showed a significant association with the presence of MAFLD. HCV patients showed hypocholesterolemia, hypotriglyceridemia and the levels of lipid-based insulin resistance markers were significantly lower. TyG index showed a strong positive association with the presence of MAFLD. These observations could be due to association between HCV replication and host lipid metabolism.

A young adult female patient presented with complaints of jaundice, intermittent vomiting, and weight loss. Upon examination, pedal oedema and abdominal distension were observed. Laboratory investigations indicated macrocytic anaemia, hemolysis, prolonged prothrombin time, mixed hyperbilirubinemia, elevated aspartate/alanine transaminase (AST/ALT), and a normal alkaline phosphatase (ALP). The investigations repeated showed an increase in bilirubin, AST, and ALT. However, the levels of ALP and the ALP: total bilirubin ratio (ALP:TB ratio) were found to be very low. This raised the suspicion of Wilson disease, and further laboratory workup was initiated. Urine (24-hour) and serum copper levels were elevated, while serum ceruloplasmin levels were lower. Based on this, the diagnosis of acute on chronic liver failure (ACLF) related to Wilson disease was made. The levels of ALP and the ALP:TB ratio remained low until the sixth day. This report demonstrates the clinical relevance of low levels of ALP and ALP: TB ratio and its diagnostic utility in establishing the diagnosis of Wilson disease.

The latest guidelines proposed by International Expert Consensus are used for the clinical diagnosis of Metabolic Associated Fatty Liver Disease (MAFLD). The new definition takes hepatic steatosis (determined by elastography or histology or biomarker-based fatty liver index) as a major criterion. In addition, race, gender, body mass index (BMI), waist circumference (WC), fasting plasma glucose (FPG), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), homeostatic model assessment of insulin resistance (HOMAIR), high sensitive c-reactive protein (HsCRP) for the diagnosis of MAFLD. Each parameter has to be interpreted based on the proposed cut-offs, making the diagnosis slightly complex and error-prone. This package is developed by incorporating the latest international expert consensus guidelines, and it will aid in the easy and quick diagnosis of MAFLD based on FibroScan in busy healthcare settings and also for research purposes. The new definition for MAFLD as per the International Consensus Statement is described by Eslam M et al (2020). .

Hospital waste management is crucial in preventing needle stick injuries and exposure to hazards. Adequate knowledge, appropriate safety measure, and methods of handling the wastes are more important in waste management. : The objective of this project is to study the impact of multi-modal training workshops in improving the knowledge and awareness on biomedical waste management among healthcare workers.An eight-hour onsite training workshop was conducted in Ahmedabad, Kolkata, Indore, and Hyderabad from July to September 2023. A validated pre and post-test questionnaire was used to assess the impact of the workshop. At the end of each workshop, responses were analyzed to study the effectiveness of the workshop and to do a gap analysis on the areas that require strategic learning. Analysis was conducted on data aggregated using the Chi-square test.In the above analysis, the pre-test scoring of these participants was 66%. After the workshop, the post-test scoring was 83% with a significant improvement (p < 0.0001). The pre-test and post-test scores in individual regions were 63% and 78% at Ahmedabad, 71% and 86% at Kolkata, 60% and 86% at Indore, and 68% and 83% at Hyderabad respectively.In healthcare facilities, training plays a key role in preventing health hazards for both employees and patients. Training must involve different types of learning methods tailored to the needs and capability of understanding of the participants. The effectiveness of training must be measured using appropriate tools to study the impact of the learning methods.

Background & objectives: Isolation of functional pancreatic islets for diabetes research and clinical islet transplantation stands as a big challenge despite the advancements in the field. In this context, the non-availability of human/animal tissues is one of the major impediments to islet-based research, which has tremendous scope for translation. The current study explores the feasibility of using the bovine pancreas as an alternative source to isolate pancreatic islets and assess its functionality for in vitro studies. Methods: The bovine pancreas was collected from a registered slaughterhouse and transported in an ice-cold medium – Hank’s Balanced Salt Solution (HBSS) to the laboratory. Islets were isolated by sequential collagenase digestion followed by a two-step filtration and purification by density gradient separation method. After isolation, islets were identified with dithizone staining and the islet function was assayed in vitro for assessing the dynamic insulin secretory function by monitoring the glucose-stimulated insulin secretion (GSIS), in response to low and high glucose. Staining techniques were also used to understand the cytoarchitecture of the bovine pancreas. Results: The islet yield was 157±23 islets per gram of pancreas and was viable. The cold ischaemia time was reduced to 60-75 min. The islets released insulin with glucose stimulation. The insulin release was observed more with high glucose (28 mM) than with low glucose (2.8 mM). Dithizone staining confirmed the presence of islets after isolation and the size of islets ranged from 50 to 600 µm size. The mantled islets (islets with acinar tissue) were also noted with the pure islets in culture. Hematoxylin and eosin (H&E) and aldehyde- fuchsin showed islets interspersed in the acinar tissue of the bovine pancreas. Special stain defined the islets better than regular staining. Fluorescent and diaminobenzidine (DAB) staining with insulin, glucagon and somatostatin revealed the arrangement of the cells in each islet. The beta cells were majorly found in the islet core with alpha cells interspersed with the delta cells in the periphery. Interpretation & conclusions: The isolation procedure described in this study yielded viable islets for in vitro studies which showed a differential response to glucose challenge, confirming their viability. We provide a simple and reproducible method for small-scale isolation of functional islets from the bovine pancreas. This model proffers the beginner a hands-on in islet experiments and helps to re-iterate the process that could be extrapolated to other pancreatic tissues as well as to expand on diabetes research.

Background: Insulin resistance (IR), a hallmark feature of diabetes and metabolic syndrome, is characterized by chronic low-grade inflammation. Pan-immune-inflammation value (PIV), an emerging immune cell count-based inflammatory index, is the global quantifier of the cellular compartment of systemic inflammation. This study determines the association of PIV with various markers of IR. Methods: This retrospective, cross-sectional study was done using the data obtained from the Center for Disease Control-National Health and Nutritional Examination Survey (CDC-NHANES) pre-pandemic data from 2017–2020. Data from 4620 survey participants was included after screening. Homeostasis model assessments of insulin resistance (HOMA-IR) and beta-cell function (HOMA-B), triglyceride glucose (TyG) index, visceral adiposity index (VAI), and lipid accumulation product (LAP) were used as markers of IR. The receiver operating characteristic (ROC) curve and multiple logistic regression are carried out to determine the association between PIV and IR. Results: PIV levels were significantly higher in obesity, diabetes, and metabolic syndrome. HOMA-IR, HOMA-B, LAP, VAI, and TyG were significantly different across PIV quartiles. PIV showed a significant positive association with IR (based on the HOMA-IR cut-off). However, the AUC of ROC for PIV is 0.58, suggesting it may not be useful as a marker to predict IR. Conclusion: In our study, PIV had a significant positive association with IR. However, the ability of PIV to predict IR is not optimal. Hence, large-scale prospective studies are needed to ascertain the role of PIV as a marker for IR.

Non-alcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver disease worldwide. There are conflicting reports on the association of serum ferritin levels and its utility in discriminating various stages of liver fibrosis in patients with NAFLD. This study is done to address the conflicts by analysing the National Health and Nutritional Examination Survey 2017–2020 (NHANES 2017–2020) data. The survey data was screened, and the eligible participants (n = 5901) were categorized based on the controlled attenuation parameter (CAP) obtained from Vibration Controlled and Transient Elastography (VCTE) scan into 2 groups, NAFLD (CAP ≥ 274 dB/m, n = 2528) and non-NAFLD (CAP < 274 dB/m, n = 3373). The NAFLD group had a significantly higher proportion of obese, diabetic, and metabolic syndrome participants. Serum ferritin levels were significantly higher in the NAFLD group, and the levels showed an upward trend from simple steatosis to significant fibrosis. Multivariate regression analysis showed that ferritin has a significant positive association with the median liver stiffness parameter (LSM), which is the index of liver fibrosis. Receiver operator characteristic curve (ROC) analysis showed that serum ferritin levels are a poor predictor of fibrosis (LSM > 8 kPA) in those with NAFLD (AUC = 0.59, Sensitivity = 53.5%, Specificity = 60.3%). To conclude, serum ferritin levels were positively associated and it trended upward as the disease progressed from simple steatosis to fibrosis in NAFLD. However, its diagnostic utility in discriminating liver fibrosis in patients with NAFLD is limited.