Assessing Liver Fibrosis in Type 2 Diabetes Mellitus Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: The Role of Non-invasive Scoring Systems and Associated Factors.

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) constitutes a significant cause of chronic liver disease globally. Type 2 diabetes mellitus (T2DM) is a crucial risk factor for MASLD. This investigation is aimed at assessing hepatic fibrosis in T2DM patients with MASLD. Methods This cross-sectional study focused on T2DM patients with MASLD attending a tertiary care center in eastern India. Exclusion criteria were chronic alcohol intake (more than 21 units/week for males and more than 14 units/week for females), other chronic liver diseases, and pregnancy. The study utilized abdominal ultrasonography and transient elastography, complemented by calculating the BARD score, nonalcoholic fatty liver disease (NAFLD) fibrosis score, aspartate aminotransferase to platelet ratio index (APRI) score, and fibrosis 4 (FIB-4) index. The prevalence of advanced fibrosis in patients with T2DM and MASLD was assessed using transient elastography. Results Among the 149 T2DM patients with MASLD studied, 59.7% were female, with an average age of 49.09 years and a T2DM duration of 7.3 years. Transaminitis was detected in 9.4% of the subjects. The risk assessment of hepatic fibrosis revealed that 14.1% of patients had a high risk of hepatic fibrosis on BARD scoring, the NAFLD fibrosis score was in the range of F3-F4 in 8.7% of patients, the FIB-4 index showed a high risk of fibrosis in 5.4% of patients, and the APRI scoring showed severe fibrosis in 3.4% of patients. The prevalence of advanced fibrosis in patients with T2DM and MASLD was 7.4% (95% confidence interval (CI) 3.7 to 12.8), while 75.8% (95% CI 68.2 to 82.5) of participants had at least some level of hepatic fibrosis as measured by transient elastography. Notably, there was a significant positive correlation between these scores and the duration of diabetes and serum bilirubin levels, as corroborated by concordant transient elastography findings. On multivariate logistic regression, systolic blood pressure, serum total bilirubin level, and serum aspartate aminotransferase level had significant predictive value for advanced hepatic fibrosis. Conclusion The significant predictive value of systolic blood pressure, serum total bilirubin level, and serum aspartate aminotransferase level for hepatic fibrosis emphasizes the importance of integrated monitoring for these patients.

Prevalence of polymorphisms in marker genes associated with antimalarial drug resistance in Plasmodium falciparum following 10 years of artemisinin-based combination therapy implementation in urban Kolkata.

Context: Resistance to antimalarial drugs is one of the major challenges for malaria elimination. In India, artemisinin combination therapy (artesunate-sulfadoxin pyrimethamine) was introduced in place of chloroquine (CQ) for the treatment of uncomplicated falciparum malaria in 2010. Periodical monitoring of polymorphisms in antimalarial drug resistance marker genes will be useful for assessing drug pressure, mapping and monitoring of drug resistance status; and will be helpful for searching alternative treatments. Objectives: This study was conducted to study the polymorphisms in antimalarial drug resistance marker genes among clinical Plasmodium falciparum isolates collected from Kolkata after 10 years of artemisinin-based combination therapie (ACT) implementation. Materials and Methods: Blood samples were collected from P. falciparum mono-infected patients and polymorphisms in P. falciparum CQ resistance transporter (pfcrt), P. falciparum multidrug resistance (pfmdr-1), P. falciparum dihydrofolate reductase (pfdhfr), P. falciparum dihydropteroate synthetase (pfdhps), pfATPase6 and pfK-13 propeller genes were analysed by polymerase chain reaction and DNA sequencing. Results: In pfcrt gene, C72S, and K76T mutation was recorded in 100% isolates and no mutations was detected in any of the targeted codons of pfmdr-1 gene. A double mutant pfcrt haplotype SVMNT and wildtype haplotype NYD in pfmdr-1 were prevalent in 100% of study isolates. Triple mutant pfdhfr-pfdhps haplotype ANRNI-SGKAA was recorded. No polymorphism in pfK13 gene was documented in any of the isolates. Conclusions: Observed wild codon N86 along with Y184 and D1246 of pfmdr-1 gene might be an indication of the reappearance of CQ sensitivity. The absence of quadruple and quintuple haplotypes in pfdhfr-pfdhps gene along with the wild haplotype of pfK13 is evidence of ACT effectivity. Hence, similar studies with large sample size are highly suggested for monitoring the drug resistance status of P. falciparum.

A Randomized, Double-Blind, Parallel-Group Phase III Trial Investigating the Glycemic Efficacy and Safety Profile of Fixed-Dose Combination Dapagliflozin and Linagliptin Over Linagliptin Monotherapy in Patients with Inadequately Controlled Type 2 Diabetes with Metformin.

INTRODUCTION: The aim of the study was to evaluate the efficacy and safety of fixed-dose combination (FDC) of dapagliflozin (10 mg) and linagliptin (5 mg) in comparison to linagliptin 5 mg (Trajenta) in patients with insufficiently controlled type 2 diabetes mellitus (T2DM) on metformin monotherapy. METHODS: The double-blind, randomized, multicentric, parallel-group phase III trial screened 287 adult patients with T2DM (age 18-65 years) from 16 sites across India. The recruited subjects were undergoing metformin monotherapy ≥ 1000 mg/day for at least 28 days. Patients with HbA1c of 7.5-10.5% (58-91 mmol/l) (n = 232) after 2 weeks of run-in period with linagliptin monotherapy and placebo dapagliflozin/linagliptin on metformin monotherapy were randomized (1:1) in parallel to once daily dapagliflozin/linagliptin 10/5 mg or linagliptin 5 mg for 16 weeks. Patients were stratified on the basis of HbA1c (≤ 9.0% and > 9.0%; ≤ 75 mmol/l and > 75 mmol/l)). A total of 225 subjects completed 16 weeks of treatment, 115 patients in the test group and 110 patients in the reference group. RESULTS: Dapagliflozin/linagliptin (p = 0.0003) exhibited a greater change in HbA1c from baseline than linagliptin (p < 0.0001) in 16 weeks (mean reduction, - 1.28% vs - 0.83%). Test group showed a significant decrease in fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and body weight compared to the reference group. The FDC was well tolerated with adverse events being more frequent in the reference group. No serious adverse events (SAEs) were reported in the study. CONCLUSION: Dapagliflozin/linagliptin combination is a novel dipeptidyl peptidase 4 (DPP4)/sodium-glucose co-transporter 2 (SGLT2) inhibitor FDC approved in India for patients with T2DM. Potential limitations of this study are a small dose of dapagliflozin (10 mg) in the FDC, a short study duration (30 weeks) and a high minimum threshold for HbA1c (≤ 7.5%; ≤ 53 mmol/l). Results indicate the FDC to be a superior therapeutic option over linagliptin for patients with T2DM on metformin monotherapy. TRIAL REGISTRATION: CTRI/2022/08/044563; 01/08/2022.

Impact of meteorological parameters on soil radon at Kolkata, India: investigation using machine learning techniques.

The daily soil radon activity has been measured continuously over a year with BARASOL BMC2 probe at a measuring site of Jadavpur University Campus in Kolkata, India. The dependency of soil radon activity with different atmospheric parameters such as soil temperature, soil pressure, humidity, air temperature, and rainfall has been also analyzed. The whole study period is divided in four seasons as proposed by the Indian Meteorological Department (IMD). Minimum soil radon level has been observed during the winter season (December-February). On the other hand, higher soil radon level has been observed both for summer and monsoon. Except soil pressure, all other variables have shown positive correlation with soil radon activity. Among five variables, soil temperature has been the most significant variable in terms of correlation with soil radon level whereas maximum humidity has been the least significant correlated variable. It has been observed that considerable reduction of soil radon level occurred after four heavy rainfall events during the study period. The combined effect of these multi-parameters on soil radon gas has been evaluated using machine learning methods like principal component regression (PCR), support vector regression (SVR), random forest regression (RF), and gradient boosting machine (GBM). In terms of performances, RF and GBM have performed much better than SVR and PCR. More robust and consistent results have been obtained for GBM during both training and testing periods.

Elevated radon level in drinking water of Ajodhya Hill Area of West Bengal, India: probable health impact on lung and stomach.

A screening survey has been carried out to measure the radon concentration in drinking water at various locations of Ajodhya hill and surrounding areas in Purulia district of West Bengal, India, using AlphaGUARD radon monitor. The obtained 222Rn concentration in ground water varies from 5.71 ± 0.29 to 579.47 ± 23.18 Bq/l with an average of 110.00 ± 6.61 Bq/l. Comparison between our results with the internationally recommended reference levels reveals that drinking of water from the majority of these tube-wells can pose significant health risks to the local people. Correlation study indicates that tube-well depth has significant influence on the radon level in water samples. Using 60 l/yr and 1642.50 l/yr water consumption estimated annual effective radon doses for most of the samples (almost 70% and 96%, respectively) are high compared to the World Health Organization (WHO) and the European Union (EU) Commission prescribed reference dose limit of 100 µSv/yr. Also, the evaluated Excess Lifetime Cancer Risk (ELCR) values associated with the tube-wells are showing serious threat to the health of the locals.The primary goal of this work is to develop a radon profile map of this area and to find out the possible reasons behind the elevated radon level in ground water. This type of work may play a very crucial role to aware the locals in perspective of human exposure to radon. The local health officials and the water quality regulators of India are requested to take necessary steps for protecting the local people from water radon hazard.

Water radon risk in Susunia hill area: an assessment in terms of radiation dose.

Radiological impact of radon in air is a global issue whereas radon in water has local consequences. Considering its importance, we have conducted a study on radon activity measurements in 316 tube-well water samples collected from Susunia hill area in Bankura district of West Bengal, India during the period of 25th December 2018-2nd February 2020. Radon contents are measured using AlphaGUARD radon monitor. The obtained radon activities in drinking water samples lie between 1.78 ± 0.07 and 3213.50 ± 77.32 Bq/l with an average of 128.30 ± 14.09 Bq/l. This study reveals that 93% of the samples have radon levels in excess of the USEPA proposed maximum contamination level (MCL) of 11.1 Bq/l while radon levels of 40% samples have exceeded the WHO and EU Council Directive recommended reference level of 100 Bq/l. The total annual effective dose of the samples have been estimated by considering the per day water intake of 3 l. The calculated total annual effective dose widely fluctuates between 10.39 and 18649.55 µSv/year with an average value of 744.59 µSv/year. 269 water samples have exceeded the WHO and EU Council Directive recommended reference level of 100 µSv/year. However, if we consider the UNSCEAR prescribed annual water intake of 60 l, the average dose becomes 279.82 µSv/year. The situation demands attention of the local authorities. Local people are advised to take some easy preventive measures for their radiological protection against such contamination.

Socio-demographic and Clinico-Epidemiological Study of Scrub Typhus in Two Tertiary Care Hospitals of Kolkata.

Background and Aims: Scrub typhus is the commonest of the rickettsial diseases in India and is difficult to diagnose. Untreated cases have fatality rates of 30-45%. Eschar is present in 7-97% cases. Pneumonia and acute respiratory distress syndrome (ARDS) are frequent complications. Serum immunoglobulin M capture ELISA is the most sensitive test. Doxycycline is the drug of choice. Our objectives were to study the socio-demographic and clinic-epidemiological profiles of scrub typhus cases in two tertiary care hospitals in Kolkata, India. This was the first study of scrub typhus in Southern West Bengal and its neighboring areas. . Methods: Study was conducted over 16 months and all fever cases of Tropical Medicine / Medicine outpatients' clinics were evaluated. Results: Fourteen cases were diagnosed. 78.6% were from rural areas and 35.7% were farmers. Headache and fever were the commonest presenting complaints while eschar was found in only 21.4%. Serum IgM scrub typhus antibody was positive in all cases . Conclusion: Scrub typhus should be a differential diagnosis in acute febrile illness cases, as early diagnosis and therapy prevents complications.

A cross-sectional study on renal involvement among HIV-infected patients attending a tertiary care hospital in Kolkata.

Background and objectives: The HIV-associated renal diseases represent a spectrum. Indian data on this is sparse. This study was undertaken to find out the prevalence and clinicopathological spectrum of renal involvement in HIV among antiretroviral therapy (ART) naïve patients (Group 1) and among those on ART (Group 2). Methods: Systematic random sampling was undertaken to select 109 patients each from virology outpatient department (VOPD) and ART centre of a tertiary care hospital. They were screened and further investigated if renal involvement was found. Results: Renal involvement was present in 25/109 (22.94%) and 15/109 (13.76%) patients of Groups 1 and 2, respectively. Among patients of Groups 1 and 2, 9/24 (37.5%) and 2/13 (15.4%), respectively, had clinically significant proteinuria, but none in the nephrotic range. Statistically significant relationships of renal involvement were observed with CD4 count <100/µl and with low BMI. Of the patients of Group 2, 20% of those on a tenofovir-based regimen had renal involvement with tubular changes, while only 4.6% of those on other regimens had renal involvement. This difference was statistically significant (p<0.05; OR=5.25). Conclusion: Renal involvement was less common among those on ART. Low CD4 count and body mass index (BMI) were associated with renal dysfunction. Patients on a tenofovir-based regimen had more renal involvement compared with not on a tenofovir-based regimen.

Therapeutic efficacy of artemisinin combination therapies and prevalence of S769N mutation in PfATPase6 gene of Plasmodium falciparum in Kolkata, India.

OBJECTIVE: To study the in vivo efficacy of these two ACTs in the treatment of Plasmodium falciparum (P. falciparum malaria) in Kolkata and to determine the prevalence of mutant S769N codon of the PfATPase6 gene among field isolates of P. falciparum collected from the study area. METHODS: A total of 207P. falciparum positive cases were enrolled randomly in two study arms and followed up for 42 days as per WHO (2009) protocol. A portion of PfATPase6 gene spanning codon S769N was amplified and sequenced by direct sequencing method. RESULTS: It was observed that the efficacy of both the ACT regimens were highly effective in the study area and no mutant S769N was detected from any isolate. CONCLUSIONS: The used, combination AS+SP is effective and the other combination AM+LF might be an alternative, if needed.