Anemia and its association with glycemia and transaminitis in patients with type 2 diabetes mellitus: A cross-sectional pilot study.

Background and Aims: Anemia impairs glucose homeostasis, affects glycemic control, and predisposes to complications in diabetics. It correlates with oxidative stress and increases the risk of developing microvascular and macrovascular complications. However, it is an underrecognized comorbidity in diabetics. This study was conducted to assess the prevalence of anemia in diabetic patients and compare the metabolic profiles of anemic and non-anemic diabetics. Methods: This is a cross-sectional study, conducted among type 2 diabetes (T2DM) patients, at the outpatient clinic. Patients with chronic kidney disease (CKD), known hematological disorders, and chronic inflammatory disorders were excluded. Results: Of the 97 patients, 37 (38.14%) were found to be anemic (hemoglobin (Hb): male <13 g/dl, female <12 g/dl). The mean values of fasting blood sugar (FBS) in low and normal mean corpuscular volume (MCV) patients were 265.9 ± 43.7 mg/dl and 157.2 ± 7.2 mg/dl, respectively (P = 0.0026), and those of postprandial blood sugar (PPBS) were 370.3 ± 58.4 mg/dl and 226.3 ± 10.1 mg/dl, respectively (P = 0.0015). It was found that 6 (22.2%) of 27 patients with raised alanine aminotransferase (ALT) had anemia against 27 (45.8%) of 59 patients with normal ALT (P = 0.03). The mean Hb levels in patients with raised and normal ALT were 13.31 ± 2.3 gm% and 12.2 ± 2.0 gm% (P = 0.03), respectively. Conclusions: Blood sugar may have a direct relationship with MCV in T2DM patients. Hb tends to relate to hepatic enzymes likely due to altered dietary patterns in anemics. Further larger studies on the effect of iron supplementation and dietary habits on glycemic control and hepatic steatosis are warranted.

Understanding obesity among young adults in India: A focus group study.

INTRODUCTION: The study aims to understand the knowledge and awareness about risk factors and consequences of obesity, barriers and motivators to weight loss, and potential solutions for weight management among young adults (YAs) in India. METHOD: Six focus group discussions were conducted with an inductive approach among obese YAs (18-30 years) recruited through snowball and purposive sampling. The principle of maximum diversity was used to build a pool of varied and extensive information regarding obesity in YAs. The discussions were audio-recorded and transcribed verbatim using NVivo 1.0 by QSR International to generate codes, subthemes, and themes from the discussions. RESULT: Among the thirty recruited YAs (mean age 24.7 ± 2.84 years), nearly half were from a high-income group (56.6 %) and had postgraduate education (53.3 %). Key themes included the need for increased awareness about obesity risk factors and consequences across different societal levels. Physical appearance was the primary motivator for weight loss, followed by physical endurance and social support. Major barriers included lack of energy, time, motivation, lifestyle changes, easy access to unhealthy foods, work commitments, and workplace culture. A holistic approach involving dietary changes, physical activity, and educational and policy reforms was suggested as potential solutions. CONCLUSION: The challenges faced by YAs in developing countries regarding different aspects of the development and management of obesity are unique and different from the other population groups. Individualized weight management modules may be useful for managing obesity in this group.

Linking Non-alcoholic Fatty Liver Disease Severity With Metabolic Syndrome Features: An Integrative Study on Clinical and Radiological Fronts.

Introduction Non-alcoholic fatty liver disease (NAFLD) has become a widespread cause of chronic liver disease, ranging from simple steatosis to severe conditions like non-alcoholic steatohepatitis (NASH) and cirrhosis. Despite its similarity to alcohol-induced liver damage, NAFLD affects individuals with no significant alcohol consumption. This study explores the association between NAFLD, bone mineral density (BMD), insulin resistance, and subclinical inflammation, focusing on the Asian Indian population. The primary objective was to investigate the relationship between NAFLD and BMD, insulin levels, and markers of subclinical inflammation, hypothesizing that patients with NAFLD exhibit lower BMD, possibly linked to insulin resistance and inflammation. Methodology A cross-sectional study with 100 subjects aged 18-50 years (50 cases with NAFLD and 50 controls) was conducted. Exclusion criteria included excessive alcohol consumption, drug-induced fatty liver, severe organ dysfunction, infections, pregnancy, and acute or chronic illness. Data were collected through clinical examinations, anthropometric measurements, biochemical investigations, ultrasound diagnosis of NAFLD, and dual-energy X-ray absorptiometry (DEXA) scans for BMD assessment. Statistical analysis employed the chi-squared tests, t-tests, and Wilcoxon rank-sum tests. Results NAFLD patients had higher body mass index (BMI), waist-to-hip ratio, and markers of insulin resistance and inflammation compared to non-NAFLD controls. DEXA scans revealed significantly lower BMD in NAFLD cases, along with a higher prevalence of osteopenia. Positive correlations were observed between BMD and insulin resistance. The study contributes to understanding the link between NAFLD and lower BMD in the Asian Indian population, emphasizing the impact of insulin resistance and inflammation on bone health. The literature review supports the relevance of exploring NAFLD as an independent risk factor for low BMD. Conclusion This case-control study underscores the significant association between NAFLD and lower BMD in the Asian Indian population. Despite limitations, the findings highlight the importance of further research with larger samples and comprehensive assessments to elucidate the interplay between NAFLD, metabolic factors, and bone health.

Development of "DiabetesSutra" a mobile application for lifestyle management of Type 2 Diabetes in India.

Background: Multiple mhealth (mobile health) interventions and mobile applications have been developed to support diabetes self-management. However, most of the apps are developed without the need for assessment and evaluation by experts in the field. This study aimed to design and develop a mobile application (app) supporting diabetes self-management for people with Type 2 Diabetes Mellitus (T2D) using a systematic approach. Methods: In this study mixed method design was used to develop the mobile application. The mhealth intervention was designed and developed in five steps: i) Extensive literature search, ii) Needs assessment of patients with T2D with the help of healthcare providers and patients (Interviews with 15 healthcare providers like clinicians, dietitians, and diabetes educators, and 2 focus group discussions with patients) iii) Ideation and content development of app based on outcomes of needs assessment; iv) content validation (by 10 healthcare providers) and v) App development on a hybrid platform. Evaluation of the app by users i.e., type 2 diabetes patients was done using the users' Mobile App rating scale (uMARS). The app was evaluated by 40 patients and rated on the uMARS questionnaire. Results: A patient-centric mobile app was developed for the nutritional management of diabetes with three modules: The patient module, the Evaluation module, and the Healthcare provider module. The patient module was the app that was provided to the patients with features like diet, physical activity, blood glucose log, education, etc., in addition to, a symptom checker, Stress meter blog, and FAQ. The evaluation module was integrated with the app it works when a user enters any log, it evaluates the entry against the standard cutoffs and flash prompts on the screen. The Healthcare provider module interacts with the server to provide them with patient data, comments, and feedback. Conclusions: The users found the app to be satisfactory. Incorporating additional features to enhance the user interface and streamline navigation could potentially enhance user engagement, thereby aiding in the management of T2D.

Hyperglycemia modulates M1/M2 macrophage polarization in chronic diabetic patients with pulmonary tuberculosis infection.

Increased susceptibility to bacterial infections like tuberculosis (TB) is one of the complications of type 2 diabetes, however the underlying mechanisms remains poorly characterized. To explore how chronic hyperglycemia in diabetes affects progression of active TB, we examined mRNA expression of M1 (proinflammatory) and M2 (anti-inflammatory) cytokines/markers, in monocyte-derived macrophages obtained from patients with PTB + DM (pulmonary TB + diabetes mellitus type 2), patients with DM alone, patients with PTB alone, and healthy individuals (controls). Our findings indicate a dysregulated cytokine response in patients with both PTB and DM, characterized by decreased expression levels of interferon-gamma (IFN-γ) and inducible nitric oxide synthase (iNOS), along with increased expression levels of interleukin-1 beta (IL-1ß) and CD206. Furthermore, we observed a positive correlation of IL-1ß and CD206 expression with levels of glycosylated hemoglobin (HbA1c) in both PTB + DM and DM groups, while IFN-γ showed a positive correlation with HbA1c levels, specifically in the PTB + DM group. Additionally, M1 cytokines/markers, IL-1ß and iNOS were found to be significantly associated with the extent of sputum positivity in both PTB and PTB + DM groups, suggesting it to be a function of increased bacterial load and hence severity of infection. Our data demonstrates that tuberculosis in individuals with PTB + DM is characterized by altered M1/M2 cytokine responses, indicating that chronic inflammation associated with type 2 diabetes may contribute to increased immune pathology and inadequate control of tuberculosis infection.

Inhibition of cellular activation induced by platelet factor 4 via the CXCR3 pathway ameliorates Japanese encephalitis and dengue viral infections.

BACKGROUND: Activated platelets secrete platelet factor 4 (PF4), which contributes to viral pathogenesis. Recently, we reported the proviral role of PF4 in replication of closely related flaviviruses, Japanese encephalitis virus (JEV) and dengue virus (DENV). OBJECTIVES: This study aimed to investigate the detailed mechanism of PF4-mediated virus replication. METHODS: PF4-/- or wild-type (WT) mice were infected with JEV, and host defense mechanisms, including autophagic/interferon (IFN) responses, were assessed. WT mice were pretreated with the CXCR3 antagonist AMG487 that inhibits PF4:CXCR3 pathway. This pathway was tested in PF4-/- monocytes infected with DENV or in monocytes isolated from patients with DENV infection. RESULTS: PF4-/- mice infected with JEV showed reduced viral load and improved brain inflammation and survival. PF4-/- mice synthesized more IFN-α/ß with higher expression of phosphorylated IRF3 in the brain. PF4 treatment decreased IRF-3/7/9 and IFN-α/ß expression and suppressed autophagic LC3-II flux and lysosomal degradation of viral proteins in JEV-infected cells. PF4 increased the expression of P-mTOR, P-p38, and P-ULK1Ser757 and decreased expression of LC3-II. Decreased autophagosome-lysosome fusion in turn promoted DENV2 replication. The above processes were reversed by AMG487. Uninfected PF4-/- monocytes showed elevated LC3-II and autophagosome-lysosome fusion. Microglia of JEV-infected PF4-/- mice exhibited elevated LC3-II inversely related to viral load. Similarly, monocytes from PF4-/- mice showed reduced infection by DENV2. In patients with DENV infection, higher plasma PF4 and viral load were inversely correlated with LC3-II, LAMP-1, and lysosomal degradation of DENV-NS1 in monocytes during the febrile phase. CONCLUSION: These studies suggest that PF4 deficiency or inhibition of the PF4:CXCR3 pathway prevents JEV and DENV infection. The studies also highlight the PF4:CXCR3 axis as a potential target to develop treatment regimens against flaviviruses.

Efficacy of Rifaximin in Patients With Abdominal Bloating or Distension: A Systematic Review and Meta-analysis.

BACKGROUND: Abdominal bloating is a common complaint in patients with functional and organic bowel disease. Rifaximin, a nonabsorbable antibiotic, has been tried for the treatment of this disease. We performed a systematic review and meta-analysis to study the efficacy of rifaximin in abdominal bloating and distension in patients with functional gastrointestinal disorders (FGID). METHODS: We accessed 4 databases (MEDLINE, Embase, SCOPUS, and Web of Science) to identify randomized placebo-controlled trials that utilized rifaximin in FGID. We excluded observational studies, those including patients with organic bowel disorders such as inflammatory bowel diseases, or those in which rifaximin was given for other indications, such as hepatic encephalopathy. RESULTS: A total of 1426 articles were available, of which 813 articles were screened after removing duplicates and 34 articles were selected for full-text review. Finally, 10 trials (3326 patients) were included. Rifaximin was administered in doses ranging from 400 to 1650 mg per day for 1 to 2 weeks. Rifaximin therapy led to a higher likelihood of improvement in symptoms of bloating (44.6% vs. 34.6%, RR 1.22, 95% CI 1.11, 1.35; n=2401 patients) without significant heterogeneity. However, daily doses less than 1200 mg/day were similar to placebo ( P =0.09). Bloating was quantified subjectively in 7 studies, and rifaximin led to a greater reduction in bloating scores compared with placebo (standardized mean difference -0.3, 95% CI -0.51, -0.1, P =0.04) but carried significant heterogeneity ( I2 =61.6%, P =0.01). CONCLUSIONS: Rifaximin therapy is associated with an increased likelihood of improvement in bloating and distension, as well as reduces the subjective severity of these symptoms in patients with FGID.

Prevalence of sarcopenia and its determinants in people with type 2 diabetes: Experience from a tertiary care hospital in north India.

OBJECTIVES: Changes in skeletal muscle mass and quality are associated with type 2 Diabetes (T2D) and its complications. We evaluated the prevalence of sarcopenia in patients with T2D and its association with various anthropometric and metabolic parameters. METHODS: A total of 229 patients with T2D, ≥20-60 years, were screened for sarcopenia using handgrip strength (HGS) by dynamometer, physical performance test (by Short Physical and chair stand test), and height-adjusted appendicular skeletal muscle index (ASMI) by Dual Energy X-ray Absorptiometry (DXA) applying Asian Working Group on Sarcopenia (AWGS). Multiple logistic regressions were performed to identify the factors associated with sarcopenia. RESULTS: The mean age was 46.2 ± 7.4 years with 55% being women. The prevalence of low HGS, poor physical performance, low ASMI, possible sarcopenia, sarcopenia, and severe sarcopenia was 16.2%, 39.3%, 33%, 43%, 18.8%, and 6.1%, respectively. Age >45 years and use of >2 oral hypoglycaemic agents (OHA's) were risk factors for low HGS (OR:3.51, 95%CI = 1.5-8.3) and low ASMI (OR:2.40, 95%CI = 1.05, 5.49, p-0.04), respectively. Female sex (OR:3.3 1.8-6.1 p < 0.01), age >45 years (OR:2.12, 95% CI = 1.2-3.8 p-0.012) and liver fibrosis (OR: 2.12, 95% CI = 1.01-4.46 p-0.048) were independently associated with poor performance. No association was found with HbA1c, dyslipidaemia, albuminuria, hypertension, or duration of diabetes and sarcopenia. CONCLUSION: Sarcopenia is becoming increasingly recognized as a significant complication in younger individuals with T2D, and poor physical performance plays a vital role in its development. The prevalence of sarcopenia rises with advancing age, underscoring the importance of early intervention to address this condition.

Central Line-Associated Bloodstream Infections: Effect of Patient and Pathogen Factors on Outcome.

Introduction: Patients on central lines are often having multiple morbidities, and invasive devices provide a niche for biofilm formation, which makes central line-associated bloodstream infections (CLABSIs), a serious concern in health-care settings, as the infections difficult to treat. In this study, we evaluated the common bacteria causing CLABSI, and various patient and pathogen factors affecting the clinical outcome. Methods: In the prospective observational study, patients diagnosed with CLABSI were recruited. Extensive clinical, microbiological, and other laboratory workup was done, and observations were recorded. Congo red agar method, tube test, and microtiter plate assay were used for eliciting the biofilm-forming attributes of the bacterial pathogens. Results: Klebsiella pneumoniae was responsible for 48% of CLABSI, followed by Coagulase-negative Staphylococci (16%) and Staphylococcus aureus and Acinetobacter baumannii (12% each). Fifty-six percent of the isolates produced biofilms. The median (interquartile range) duration of hospital stay till death or discharge was 30 (20, 43) days. The all-cause mortality was 44%. Patients having a deranged liver function on the day of diagnosis (P value for total bilirubin 0.001 and for aspartate transaminase 0.02), and those infected with multidrug-resistant organisms (P value = 0.04) had significantly poor prognosis. The difference in the demographic, clinical, laboratory profile, and outcome of patients infected with biofilm producers and nonproducers was not found to be statistically significant. Conclusion: The study throws light on various host and pathogen factors determining the cause and outcome of CLABSI patients. To the best of our knowledge, this is the first study trying to decipher the role of biofilm formation in the virulence of pathogens and the prognosis of CLABSI.

Escalate: Linezolid as an add on treatment in the intensive phase of tubercular meningitis. A randomized controlled pilot trial.

Most drugs used in the treatment of Tuberculous Meningitis have limited CNS penetration thereby limiting efficacy. CSF penetration of linezolid is 80-100%.The study was a prospective, randomized, open label with blinded outcome assessment pilot trial carried out in patients with TBM. Patients were randomized in a 1:1 ratio into two treatment groups either to receive standard ATT alone or add on oral 600 mg BD Linezolid for 4 weeks along with standard four drug ATT [HRZE/S]. Primary outcome was safety and mortality at the end of one and three months measured by intention to treat analysis. 29 patients were recruited and 27 completed three months of follow up. There was no significant difference in terms of mortality with Odds ratio (95% CI) of 2 (0.161-24.87; p = 1) at one month and 0.385 (0.058-2.538; p = 0.39) at three months. There was a significant improvement in GCS in Linezolid group at one month and mRS within the Linezolid group at one and three months. No major safety concerns were observed. The sample size is underpowered to draw any definitive conclusions but improvement in mRS and GCS as well as mortality change make a case for a large sample size trial.

Hyperactive behaviour of growth differentiation factor- 15 (GDF-15) in conjunction with iron trafficking transporters and suppression of Nrf-2 gene in diabetes and metabolic syndrome.

Multiple parallel factors are frequently interrogated with various toxic radicals which are abundantly generated in the liver, heart, and pancreas in stress conditions. They are actively involved in the development of diabetes and metabolic aberrations. However, whether over-activation of GDF-15mRNA and influxes of iron-by-iron trafficking genes are directly suppressing the Nrf-2 gene in patients with diabetes and metabolic aberrations in context with undiagnosed individuals with diabetes and metabolic aberrations? Therefore, we have investigated inter and intra- related Zip8/14 mRNA, GDF-15mRNA, and Nrf-2 mRNA expressions in diabetes and metabolic syndrome as it is expected to be up to 134 million by 2045 in India. We recruited 120 subjects from the Department of Medicine, Endocrinology and Metabolic Clinic, All India Institute of Medical Sciences, New Delhi, India. Various investigations related to anthropometry, nutritional, hematological, biochemical, cytokine, and oxidative stress were measured in diabetes, metabolic syndrome, diabetes with metabolic aberration, and healthy controls. Relative expression of GDF-15, ZIP8, ZIP14, Nrf-2, and housekeeping genes was done in all subjects. Stress-responsive cytokines are highly expressed in patients with metabolic aberration with respect to body weight, IR, waist circumference, and fat mass. IL-1ß, TNF-α, and IL-6 levels were significantly higher in metabolic syndrome, whereas Adiponectin levels were profoundly lower side. MDA levels were significantly raised in diabetes with metabolic syndrome while SOD activities were lowered (p = 0.001). GDF-15 mRNA expression was 1.79-fold upregulated in group III as compared with Group I while 2-threefold down-regulation of Nrf-2 expression was observed in diabetes with metabolic aberration groups. Zip 8 mRNA expressions were downregulated (p = 0.014), and Zip 14 mRNA expressions were upregulated (p = 0.06) in diabetes and metabolic aberrations. The association of GDF-15 and Nrf-2 mRNA expression was found contradictory and highly interlinked with ROS. Zip 8/14mRNA expressions were also dysregulated in diabetes and metabolic-associated complications.

Identification of potential anti-mucor agents by targeting endothelial cell receptor glucose-regulated protein-78 using in silico approach.

Mucormycosis is a fungal infection of the sinuses, brain and lungs that is the cause of approximately 50% mortality rate despite the available first-line therapy. Glucose-Regulated Protein 78 (GRP78) is already reported to be a novel host receptor that mediates invasion and damage of human endothelial cells by Rhizopus oryzae and Rhizopus delemar, the most common etiologic species of Mucorales. The expression of GRP78 is also regulated by the levels of iron and glucose in the blood. There are several antifungal drugs in the market but they pose a serious side effect to the vital organs of the body. Therefore, there is an immediate need to discover effective drug molecules having increased efficacy with no side effects. With the help of various computational tools, the current study was attempted to determine potential antimucor agents against GRP78. The receptor molecule GRP78 was screened against 8820 known drugs deposited in DrugBank library using high-throughput virtual screening method. Total top 10 compounds were selected based on the binding energies greater than the reference co-crystal molecule. Furthermore, molecular dynamic (MD) simulations using AMBER were performed to calculate the stability of the top-ranked compounds in the active site of GRP78. After extensive computational studies, we propose that two compounds (CID439153 and CID5289104) have inhibitory potency against mucormycosis and can serve as potential drugs that can form the basis of treating mucormycosis disease.Communicated by Ramaswamy H. Sarma.

Barriers and facilitators in dietary and physical activity management of type 2 diabetes: Perspective of healthcare providers and patients.

BACKGROUND AND AIMS: Type 2 diabetes (T2DM) is a chronic disease that requires continuous management and daily self-care activities. The purpose of the study was to identify the barriers and facilitators in dietary and physical activity management of T2DM by patients. METHOD: Two focus group discussions with patients with T2DM (n = 12) and interviews with healthcare providers (HCPs, n = 15) were done, to identify the barriers and facilitators experienced by patients towards lifestyle management in T2DM. Data were analyzed using qualitative data analysis software Atlas ti. version 8. RESULT: Three major themes were identified as barriers and facilitators viz., Personal barriers and facilitators, social barriers and facilitators, and barriers and facilitators related to the healthcare provider. Major barriers were denial of illness, low level of knowledge of the disease, excess use of gadgets, poor infrastructure, gender issues, and lack of time. Major facilitators identified were patient education and motivation, continuous counseling and regular follow-up, family and peer support, and recreational and indoor activities. CONCLUSION: Based on the findings of the study, a multifaceted approach is required to address these barriers and facilitators. These findings will help in developing novel intervention strategies and making policy-level changes, which are required to improve diabetes self-management practices in people with T2DM.

Seroprevalence of Strongyloides infection among steroid recipients in a tertiary care centre in North India.

Background: Strongyloides stercoralis (S. stercoralis), a unique parasite, can cause mortal disease even years after the exposure. Iatrogenic use of steroids can complicate asymptomatic infections to a life-threatening hyperinfection and/or disseminated infection. Data regarding seroprevalence of strongyloidiasis remains scarce and this knowledge gap needs due attention in many endemic countries including India. Aim: The present study is aimed at assessing the seroprevalence of Strongyloides infection and the need for routine screening among individuals receiving steroid therapy. Methodology: Eighty patients receiving steroid therapy and thirty healthy volunteers who had not received any immunosuppressive drugs and/or anthelminthic therapy in last six months were enrolled as cases and controls respectively and they were screened by Strongyloides IgG ELISA. Results: Among the 80 patients on steroids, the mean cumulative prednisolone equivalent dose received was 8.2 g (±11.2 g) for a mean duration of 184 days, 16 patients (20%, 95% CI 11.9-30) had a positive Strongyloides IgG serology. Only 4 controls (4/30, 13.3%, CI 3.8-30.7) tested positive (p=0.4). Conclusions: Our study demonstrated a Strongyloides seroprevalence of 20% in the study population emphasizing the need for screening for Strongyloides infection prior to immunosuppressive therapy in order to prevent hyperinfection or possible dissemination.

How Indian obese population managed their lifestyle during first and second lockdown during COVID-19 pandemic? - A comparative study.

Background: People from all over the world have been affected by the COVID-19 (SARS-CoV-2) pandemic. The lockdown during the pandemic has impacted the lifestyle of most of the population. The aim of the present study is to compare the effect of COVID lockdown-1 and lockdown-2 on the lifestyle of the obese Indian population. Methods: This was a cross-sectional study conducted during the COVID-19 lockdown on obese adults. A well-structured questionnaire was developed and administered among the study population. The study was conducted in two phases (lockdown-1 and lockdown-2). A total of 390 subjects were included in the study (260 subjects in the lockdown-1 phase and 130 subjects in the lockdown-2 phase). Data on diet, sleep, stress, and physical activity were obtained and analyzed. Results: The mean age of the participants of phase-1 in the study was 41.7 ± 10.2 years and the participants of phase-2 were 44.5 ± 9.2 years. Statistically significant differences were observed between lockdown-1 and lockdown-2 in terms of monitoring of weight and other comorbid conditions, changes in the consumption of refined flour and processed foods, sugar and sugar-sweetened foods, oils and ghee, duration of physical activity, changes in the duration of sleep, and the stress levels related to COVID-19 (P < 0.001). Conclusion: The impact of the lockdowns on health was very significant and different areas of lifestyle were affected in both the lockdowns. Weight gain was reported in both phases of the lockdown. The monitoring of health parameters, eating frequency, diet, and stress levels were affected during lockdown-1, whereas during lockdown-2, sleep duration and physical activity were affected. A comprehensive lifestyle modification plan is required to be developed to avoid these effects in the future.

Chronic hyperglycemia drives alterations in macrophage effector function in pulmonary tuberculosis.

Diabetes mellitus (DM) alters immune responses and given the rising prevalence of DM in tuberculosis (TB) endemic countries; hyperglycemia can be a potential risk factor for active TB development. However, the impact of hyperglycemia on TB-specific innate immune response in terms of macrophage functions remains poorly addressed. We assessed macrophage effector functions in uncontrolled DM patients with or without TB infection (PTB+DM and DM), non-diabetic TB patients (PTB), and non-diabetic-uninfected controls. Phagocytic capacity against BCG and surface expression of different pattern recognition receptors (PRRs) (CD11b, CD14, CD206, MARCO, and TLR-2) were measured via flow cytometry. Effector molecules (ROS and NO) required for bacterial killing were assessed via DCFDA and Griess reaction respectively. A systematic dysregulation in phagocytic capacity with concurrent alterations in the expression pattern of key PRRs (CD11b, MARCO, and CD206) was observed in PTB+DM. These altered PRR expressions were associated with decreased phagocytic capacity of macrophages. Similarly, ROS was aberrantly higher while NO was lower in PTB+DM. These altered macrophage functions were positively correlated with increasing disease severity. Our results highlight several key patterns of immune dysregulation against TB infection under hyperglycemic conditions and highlight a negative impact of hyperglycemia with etiology and progression of TB.

Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study.

Introduction: The objective of the study was to evaluate the clinical profile and outcome of patients with secondary hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. Materials and methods: A prospective observational study was conducted where critically ill adult patients presenting with fever and bicytopenia were evaluated according to the HLH-2004 diagnostic criteria for the presence of secondary HLH. The underlying trigger, clinical profile, treatment, and outcome of patients with HLH were analyzed. Results: Of the 76 critically ill patients with fever and bicytopenia, 33 (43%) patients were diagnosed with HLH. The following triggers for HLH were identified: bacterial infections (23%), fungal infections (10%), viral infections (10%), parasitic infections (10%), autoimmune diseases (13%), and malignancy (8%). A total of 78% of the HLH cases received steroids, but the use of steroids was not associated with improvement in mortality. Conclusion: There is a high prevalence of HLH in patients presenting with fever and bicytopenia in critically ill adult patients. Infections were identified as the most common trigger of HLH. How to cite this article: Fazal F, Gupta N, Soneja M, Mitra DK, Satpathy G, Panda SK, et al. Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study. Indian J Crit Care Med 2022;26(5):564-567.

Neuroleptic malignant syndrome in a case of extra-pontine myelinolysis: On the horns of dilemma.

Osmotic demyelination syndrome (ODS) and neuroleptic malignant syndrome (NMS) lead to severe neurological sequalae. Though currently thought to be different syndromes, literature suggests a relation between the two. We present the case of a 45-year-old male who was found to have chronic severe hyponatremia and underwent rapid correction of sodium and developed parkinsonism features. Magnetic resonance imaging (MRI) confirmed extrapontine myelinolysis (a type of ODS). The patient received haloperidol for agitated behavior and developed new features of rigidity, fever, tachycardia and elevated creatine phosphokinase (CPK) levels and thus neuroleptic malignant syndrome was suspected to overlap with ODS. We report this case highlighting the difficulty in differentiating the between ODS and NMS and their relationship.

Validation of Tools to Assess Predictors of Successful Weight Loss Outcome in Individuals With Overweight and Obesity.

OBJECTIVE: To develop and validate questionnaires to assess the behavioral, psychosocial, and environmental predictors of successful weight loss outcomes. DESIGN: Mixed method study. Questionnaires were developed using 5 steps: item generation by literature review and preexisting questionnaires, expert evaluation, pilot testing, factor analysis, and internal consistency. SETTING: Adults with obesity recruited via web-based survey hyperlink. PARTICIPANTS: One hundred participants with a mean body mass index of 28.7 ± 4.4 kg/m2. VARIABLES MEASURED: The questionnaires were generated using 221 items. Establishing content, face and construct validity, and internal consistency. ANALYSIS: Content validity was analyzed using content validity index and content validity ratio, internal consistency through Cronbach α (CA), and structural validity by factor analysis via principal varimax rotation. RESULTS: All three questionnaires had good content validity. The Behavioral Predictor Questionnaire had good internal consistency (CA, 0.7) and excellent structural validity (69.7%). Psychosocial Predictors Questionnaire (CA, 0.8, 67.5%) and Environmental Predictors Questionnaire (CA: 0.8, 72.2%) had excellent internal consistency and structural validity. CONCLUSION AND IMPLICATION: Questionnaires seem to be practical, valid, and reliable tools for baseline assessment of individual-specific factors related to weight loss success.