Bhaktivedanta Hospital & Research Institute

Low or abnormal plasma concentrations of anti-tuberculosis drugs can be a major reason for treatment failure or the emergence of drug resistance. Acetylator status, which affects drug metabolism, plays a key role in determining drug bioavailability. This study aimed to perform therapeutic drug monitoring (TDM) of rifampicin and isoniazid and to evaluate the correlation between plasma drug concentrations and acetylator status among Indian patients receiving first-line antituberculosis therapy. Plasma concentrations of rifampicin and isoniazid were measured using in-house standardized high-performance liquid chromatography methods, while acetylator status was determined by conventional PCR of NAT2 gene. Peak concentrations were estimated from 125 patients on first-line tuberculosis (TB) treatment. Among these, 56% exhibited subtherapeutic rifampicin concentrations and 28% had subtherapeutic isoniazid concentrations. Conversely, above normal (potentially toxic) concentrations were seen in 2% and 21% for rifampicin and isoniazid, respectively. Despite receiving the standard TB treatment regimen, only 62% of patients improved clinically, while 38% of patients continued harboring TB signs and symptoms, among which 6 patients (5%) developed rifampicin resistance during the treatment course. About 44% were slow acetylators, followed by 40% intermediate and 16% rapid acetylators. The acetylator status significantly influenced the plasma concentrations of both drugs. Slow acetylators had significantly higher isoniazid concentrations (p = 0.004) and lower rifampicin concentrations (p = 0.01) as compared to rapid acetylators. Abnormal concentrations of rifampicin and isoniazid are prevalent and a major concern. Acetylator status influences plasma concentrations of rifampicin and isoniazid. Hence, determining acetylator status and performing TDM could be instrumental in optimizing and improving TB outcomes.

Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot surrounding the myocardium and evidence suggests its potential role in the development of cardiovascular complications in type 1 diabetes mellitus (T1DM). This systematic review and meta-analysis aimed to: (1) quantify EAT measurements (thickness and volume) in patients with T1DM, and (2) compare EAT measurements between T1DM patients and healthy controls. A comprehensive literature review was conducted using a systematic search strategy to identify studies that measured EAT thickness or volume in T1DM patients in PubMed, Embase, Cochrane Library, Web of Science, and CINAHL. Studies were included if they: (1) involved patients with T1DM, (2) reported EAT measurements using imaging techniques, and (3) were published in English. Case reports and reviews were excluded. Two independent reviewers performed study selection, data extraction, and quality assessment. Study quality was evaluated using the Newcastle-Ottawa Scale (NOS). Statistical heterogeneity was assessed using I2 statistics. Meta-analysis was performed using a random effect model. A total of nine studies involving 285 and 233 participants measuring thickness and volume with T1DM were included. The pooled mean EAT thickness was 5.81mm (95%CI: 4.30, 7.32mm), and the pooled mean EAT volume was 56.84cm3 (95%CI: 34.05, 79.63cm3). Significant heterogeneity was observed between the volume and thickness of EAT among people with T1DM (I2 = 99% for volume and 95% for thickness). Subgroup analysis revealed a mean difference of 2.12mm (95%CI: 0.82, 3.43mm) in EAT thickness between T1DM and control groups. Our findings indicate increased EAT measurements in T1DM patients compared to healthy individuals, suggesting EAT's potential involvement in T1DM-related cardiovascular issues.

e15040 Background: Liquid biopsies analyzing circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) allow minimally invasive monitoring and testing of lung cancer at different stages. It is known that 90% of patients succumb due to metastasis. However, accounting for patients with early metastatic signatures is extremely challenging. In addition, monitoring minimal residual disease (MRD) and identifying patients for recurrence is very prudent. While the role of CTCs in % prediction of survival has been established in several cancers. However, CTC's co-occurrence role with CtDNA and vice versa is not implored in monitoring the aggressiveness of the disease, response to therapies, and therapy decisions. In this study, we investigated ctDNA and CTC's combined roles in monitoring disease aggressiveness and metastasis in lung cancer patients. Methods: A cohort of 265 lung cancer patients with late-stage cancer were retrospectively analyzed for co-occurrence of dual biomarker ctDNA and CTC. The results were correlated as quadrant to assess clinical disease states, obtained from PET scans and HPE findings. Next Generation Sequencing (NGS) test was performed using OncoMonitor dual biomarker assay having CTC enumeration with PD-L1 expression. CTC count was performed using the OncoDiscover Liquid Biopsy Test, approved by CDSCO-India, in 1.5 ml of blood. Results: CTC distribution in this study ranged from 1-8 CTCs with a mean CTC distribution of 1.22. Amongst these patients, 75.47% (n = 200) showed the presence of CTCs and amongst these 200, 91.50% (n = 183) showed PD-L1 expression on their CTCs with a mean value of 0.99. While both biomarkers were positive for ctDNA and CTC (ctDNA+/CTC+) in 135 (50.94%) patients. Interestingly, only 19 (7.17%) patients were negative for both ctDNA and CTC (ctDNA-/CTC-). Similarly, 43 patients (16.23) were positive for ctDNA and negative for CTC (ctDNA+/CTC-), while 68 (25.66%) patients were negative for ctDNA and positive for CTC (ctDNA-/CTC+). The ctDNA+/CTC- cohort had the highest metastatic rate of 62.8%, with ctDNA+/CTC+ at 57.0%. Noteworthy, the ctDNA+ cohort showed the highest % of progressive disease patients with 20.2% and 18.6% along with CTC+ and CTC- status, respectively. The mutations, EGFR, TP53, and KRAS were observed in 62.64% (166/265) of patients. Only stable disease was observed in 29.4% of patients when both biomarkers ctDNA-/CTC- were absent. Conclusions: Overall, the ctDNA+ cohort showed a higher rate of MRD, progression, and metastasis with no stable disease. The quadrant that combined clinical results of the CTC-PD-L1 cells and CtDNA manifest the non-invasive monitoring of disease progression, treatment response, complete remission, and utility of early metastatic detection in lung cancer patients.

Survodutide is a twincretin having dual glucagon-like peptide-1 and glucagon receptor agonist activity, conceptually based on endogenous peptide oxyntomodulin. This systematic review and meta-analysis (SRM) holistically analyzed the body weight lowering, glycemic efficacy, and safety of survodutide. Electronic databases were searched for RCTs involving diabetes and/or obesity patients receiving once-weekly subcutaneous survodutide in intervention arm and placebo/active comparator in control arm. Co-primary outcomes were the percent changes in body weight and HbA1c. Secondary outcomes were to evaluate absolute changes in absolute weight, blood pressure, fatty-liver disease parameters, and adverse events (AEs). Data from 3 RCTs (1088 patients) having follow-up duration ranging from 4-11 months were analyzed. Survodutide at 2.4 mg [MD (mean difference) -7.79% (95% confidence interval [CI]: -11.54, -4.07); I2 = 98%; P < 0.01] and 3.6 mg [MD - 9.08% (95% CI: -11.63, -6.54); I2 = 96%; P < 0.001] was associated with significantly greater percent reductions in body weight compared to placebo. The corresponding absolute body-weight reduction with survodutide 2.4 mg and 3.6 mg was - 9.14 kg (95% CI: -13.76, -4.53) and - 10.23 kg (95% CI: -15.43, -5.04), respectively. Survodutide of 2.4 mg was associated with significant HbA1c reduction [MD: -0.88% (95% CI - 1.72, -0.05); I2 = 99%; P = 0.040]. Survodutide of 2.4 mg [odds ratio (OR): 2.93 (95% CI: 1.66, 5.18); I2 = 0%; P < 0.001] and 3.6 mg [OR: 4.61 (95% CI: 2.33, 9.12); I2 = 0%; P < 0.001] was associated with significantly higher treatment-emergent AEs, compared to placebo, although severe AEs were not increased. Gastrointestinal AEs were the predominant AEs and were dose dependent. Treatment discontinuation due to AEs was significantly higher with survodutide and was dose dependent. Survodutide demonstrates impressive weight and glucose-lowering properties over short-term clinical use. The optimal dose for clinical use ranges from 2.4 to 4.8 mg/week.

Type 2 diabetes (T2D) is a major public health problem globally, with significant socioeconomic ramifications for healthcare systems. Diabetes unquestionably contributes to both cardiovascular disease (CVD) and chronic renal disease. Hospitalization, low quality of life, and high mortality rate are inevitable in patients with this dual burden. As a result, the emphasis in diabetes care should also be on cardiorenal health. Glycemic control, as well as optimal management of cardiorenal risk factors and comorbidities, is required to eliminate cardiovascular (CV) morbidity and mortality related to T2D. Sitagliptin is a highly efficient and selective dipeptidyl peptidase-4 inhibitor (DPP-4i) that improves glycemic control while having a low risk of hypoglycemia. It has neutral effects on body weight, low proclivity for pharmacokinetic interactions, and a favorable safety profile. Numerous clinical trials have proven that sitagliptin is CV- and renal-safe in T2D patients, even in those with obesity, old age, renal impairment (RI), and preexisting CVD. It also corrects hyperglycemia-induced osmotic diuresis and excessive filtration. In people with T2D who are at high CV risk or moderate-to-severe renal insufficiency, sitagliptin is documented as a well-tolerated treatment that does not augment the risk of CV and renal complications. Sitagliptin may effectively manage CV and renal complications in diabetes patients, considering its CV and renal safety.

The research investigates the influence of food aesthetics on the satisfaction and loyalty of customers in the gastronomic scene of the state of Uttar Pradesh. A structured questionnaire was the means used to collect the opinions of the diners on the influence of visual presentation, plating, and overall aesthetic appeal on their quality of food perception, satisfaction with the dining experience, and intention to return. It was found that the aesthetics of food have an extraordinarily strong effect on the perception of the customers, but the effect on satisfaction and loyalty is only slight (R² = 0.058-0.071) in some cases where the relationships are negative. Highly elaborate or very stylized presentations may result in a drop in satisfaction; hence, it is important to not only present the food attractively but also to concentrate on the areas of authenticity, taste, and emotional involvement. The study points out that there is a weak but statistically significant negative correlation (r = -0.226, p< 0.05), which indicates that loyalty eventually is more about consistency, comfort, and emotional connection than visual novelty. The incorporation of aesthetics with service quality, food excellence, and cultural storytelling can, the study asserts, create unforgettable dining experiences and thus offer practical guidance to restaurateurs looking to enhance customer retention and brand value.

Type 2 Diabetics have elevated risk for acute coronary syndrome (ACS). The current management algorithm focuses on atherosclerotic cardiovascular (ASCVD) risk score to stratify this risk. However, in medically managed subjects, this algorithm may not be accurate. This study compares the ASCVD risk score in an Indian population with T2DM under medical supervision and the actual incidence of ACS. It also compared the ASCVD risk scores in cases with T2DM who developed ACS to controls and tried to estimate whether the ASCVD risk score is different in the two subsets, evaluating the utility of the ASCVD risk score in predicting ACS. This is an electronic medical record (EMR) based case-control study. Only records of subjects with T2DM where details of age, sex, body mass index, blood pressure, duration of diabetes, family history of ACS, lipid profile, renal and liver function tests were included. The incidence of ACS was calculated in the selected records, and the records of subjects with ACS were compared with age and sex-matched subjects without ACS. Data are summarized as median and interquartile range (IQR). Wilcoxon rank-sum test was used for checking differences in continuous variables and Pearson's Chi-squared test for categorical data. Univariate and multivariate logistic regression analyses were used to check the effect of ASCVD scores and other variables on the occurrence of ACS.Statistical data analyses were performed using JASP, version 0.16.4 (JASP Team [2022]) for MS Windows. Of the 1226 EMRs included in the analysis, 207 had ACS. The actual incidence of ACS was 16.85% in 6 years, higher than the mean predicted 10-year incidence of 14.56 percent (p <0.05). The cases were age and sex-matched with controls and the ASCVD incidence was estimated in the two groups. The mean ASCVD score in the cases was 14.565 ± 8.709 (Min: 1.5, Max: 38.3) and controls 13.114 ± 8.247 (Min: 1.4, Max: 45). The chance of development of ACS increases with elevated systolic blood pressure (per mmHg rise OR: 1.04, 95% CI: 1.03, 1.06; p <0.001), positive family history (OR: 5.70, 95% CI: 3.41, 9.77; p <0.001), statin use (OR: 2.26, 95% CI: 1.46, 3.52; p <0.001), and longer duration of diabetes (for every year increase OR: 1.19, 95% CI: 1.13, 1.25; p <0.001). The ASCVD risk score underestimates the ACS risk in subjects with T2DM under medical supervision and may not differ in those who developed and did not develop ACS. We also conclude that factors like a negative family history (30% less risk), longer duration of diabetes, and higher SBP are relevant in those who developed ACS.

BackgroundIron deficiency is a common comorbidity in heart failure (HF) and is independently associated with a worse quality-of-life and exercise capacity, as well as increased risk of hospitalization, regardless of anemia status. Although international guidelines have provided recommendations for the management of iron deficiency in patients with HF, guidelines in Asia are less established, and practical use of guidelines for management of iron deficiency is limited in the region. MethodsA panel comprising cardiologists from China, Hong Kong, India, Japan, Malaysia, Pakistan, Philippines, Singapore, South Korea, Taiwan, and Thailand convened to share insights and provide guidance for the optimal management of iron deficiency in patients with HF, tailored for the Asian community. ResultsExpert opinions were provided for the screening, diagnosis, treatment and monitoring of iron deficiency in patients with HF. It was recommended that all patients with HF with reduced ejection fraction should be screened for iron deficiency, and iron-deficient patients should be treated with intravenous iron. Monitoring of iron levels in patients with HF should be carried out once or twice yearly. Barriers to the management of iron deficiency in patients with HF in the region include low awareness of iron deficiency amongst general physicians, lack of reimbursement for screening and treatment, and lack of proper facilities for administration of intravenous iron. ConclusionsThese recommendations provide a structured approach to the management of iron deficiency in patients with HF in Asia.

Rickettsial diseases are a re-emerging group of illnesses that are known to show a good response to treatment if diagnosed in time. Here we report a case of Scrub Typhus-related Meningoencephalitis in a young gentleman and the importance of high clinical suspicion with early empirical treatment in patients with consistent epidemiological context.