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.

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.

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.

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.

Antibiotic stewardship initiative in a Medicine unit of a tertiary care teaching hospital in India: A pilot study.

Background & objectives: The models for implementation of antibiotic stewardship programme (ASP) in the acute care settings of developing countries are lacking. In most of the hospitals, patient turnover is high and a proper system for recording antibiotic-related information and tracking hospital-acquired infections is not in place. This pilot study was conducted in a tertiary care teaching hospital in north India to assess the feasibility of implementation of an ASP in a Medicine unit and to evaluate the effect of implementation as per the criteria applicable in this set up. Methods: A pre-post-quasi-experimental non-randomized study was conducted in two phases. In the first phase, current practices in the Medicine wards were observed. In the second phase, the ASP was implemented in a single Medicine unit, along with prospective audit and feedback, tracking of the process, as well as outcome measures. Patient risk stratification, blood culture on day one, day 3 bundle, dose optimization, de-escalation and intravenous to oral conversion of antibiotics were the key elements focused upon. Results: There was a significant improvement in the appropriateness of antibiotic prescription (66 vs. 86%, P<0.001) and reduction in the mean number of antibiotics used per person (4.41 vs. 3.86, P<0.05) along with decrease in the duration of hospital stay (17 vs. 14 days, P<0.05). There was a significant improvement in sending of blood cultures on day one during the stewardship phase (P<0.001). Interpretation & conclusions: The ASP approach used in our pilot study may be feasible and beneficial. However, it needs further confirmation in other settings and on a large scale.

Non-alcoholic fatty liver disease is an independent risk factor for inflammation in obstructive sleep apnea syndrome in obese Asian Indians.

INTRODUCTION: Obstructive sleep apnea (OSA) has been estimated to affect 4-11% of the population and causes systemic inflammation which leads to metabolic syndrome (MS). Non-alcoholic fatty liver disease (NAFLD) is also associated with MS whether NAFLD is an additional risk factor for the systemic inflammation that occurs in OSA is unclear. OBJECTIVE: In this study, we aimed to analyze the association of OSA and NAFLD with MS and systemic inflammation in Asian Indians. METHODS: Total 240 (132 males and 108 females) overweight/obese subjects [body mass index (BMI > 23 kg/m2)] were recruited; of these, 124 subjects had OSA with NAFLD, 47 had OSA without NAFLD, 44 did not have OSA but had NAFLD and 25 had neither OSA nor without NAFLD. Severity of NAFLD was based on abdomen ultrasound and of OSA on overnight polysomnography. Clinical examinations, anthropometry, body composition, metabolic parameters, and inflammatory biomarkers were recorded. RESULTS: Serum levels of leptin, macrophage migration inhibitory factor (MIF), interleukin-6 (IL-6), high sensitive C-reactive protein (Hs-CRP), and tumor necrosis factor alpha (TNF-α) were significantly higher, and adiponectin levels were significantly lower in OSA with NAFLD subjects. Prevalence of MS was significantly increased in OSA and NAFLD subjects (p = 0.001). There was a strong association and correlation between leptin, IL-6, Hs-CRP, MIF, and TNF-α in OSA and NAFLD subjects. Multivariate logistic regression showed that OSA was positively associated with the NAFLD [odds ratio (OR), (95% confidence interval (CL) 3.12 (2.58-7.72), (P = 0.002)]. CONCLUSION: NAFLD is an additional risk factor in OSA subject which contributes to systemic inflammation in Asian Indians.

Treatment of Pulmonary Embolism with Chemotherapy in a Case of Newly Diagnosed Osteosarcoma.

A 21-year old female, recently diagnosed with osteosarcoma of right humerus, presented to the emergency with history of fever, productive cough, chest pain and progressive respiratory distress for six days. Initial investigations suggested pneumonia but she did not respond to parenteral antibiotics. CT pulmonary angiogram revealed bilateral pulmonary artery embolism. Thrombolysis was performed using alteplase, which failed to improve the clinical condition. In view of underlying malignancy, a possibility of tumour-embolism was considered and she was started on chemotherapy for osteosarcoma. There was dramatic improvement in her respiratory symptoms after the first chemotherapy cycle, along with radiological resolution of the embolism. This case highlights the importance of suspecting tumour embolism in a known case of malignancy with respiratory distress.

Compliance of WHO Guideline on Dengue Management among Indian Patients: An Interventional Quality Improvement Study.

INTRODUCTION: Dengue fever management is guided by WHO guideline, the recent one being 2009; however, compliance to the guideline is difficult to assess and in India there is no data on it. The present study, a longitudinal pre-post interventional quality improvement study, was done to determine the compliance to the guideline on dengue patients before and after resident physicians' training during two peak seasons and their impact on survival. METHODS: This study was conducted in a tertiary health care centre in North India over 18 months. Data of hospitalized patients who admitted with dengue fever diagnosis in a peak season was collected in the form of quality indicators as described by the WHO-2009 guideline on dengue. Resident physicians were then given appropriate training about the guideline during the off season. Data of new dengue patients in next peak season after resident training was collected and compared with the baseline by standard statistical tests. RESULTS: The post-intervention compliances of all components increased (total mean score by giving one point to each of the quality indicators reached 7.9 from 6.4). The compliance to individual indicator also increased: the admission criteria (baseline, 44% to post-intervention, 52%, p = 0.37), classification criteria (91.7% to 96%, p = 0.33), correct staging/triage (42.9% to 86%, p <0.001), vitals monitoring (85.7% to 92%, p = 0.28), correct usage of bolus fluids (34.3% to 69.5%, p <0.001), crystalloid as choice of fluid (100% in both groups), proper fluid titration (26.2% to 56%, p <0.001), hematocrit monitoring (95.2% to 98%, p = 0.42), platelet transfusion when indicated (65.5% to 58%, p = 0.39), antibiotic use when required (61.5% to 80%, p = 0.03), and discharge criteria (100% in both groups). The mortality decreased from 7.1% (baseline) to zero (post-intervention). The median duration of hospital stay also reduced by 1 day. CONCLUSION: The study affirms that the compliance to WHO guideline on dengue management in India can be further improved by regular physician training on the guideline. Simultaneously, this educational intervention not only improves patient outcomes but also direct proper resource utilization especially platelet transfusion and antibiotic use. Furthermore, every hospital/institute should have an internal quality improvement program like this to improve the management of dengue patients. Future studies are needed to understand various barriers to 100% implementation of the guideline.

Prevalence, clinical & biochemical correlates of non-alcoholic fatty liver disease in overweight adolescents.

BACKGROUND & OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) characterized by excessive accumulation of fat in the liver, which can progress to inflammation, and cirrhosis, has emerged as an important complication of obesity in adults as well as children. This study was undertaken to assess the prevalence of NAFLD and its correlation with clinical and biochemical parameters in overweight Indian adolescents. METHODS: In this cross-sectional study, 218 overweight adolescents aged 10 to 16 yr and their parents were included. Measurements included anthropometry, ultrasonography to diagnose NAFLD, fasting glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lipids for adolescents and parents, and additional parameters of blood pressure, body fat percentage (BF%), fasting insulin, apolipoprotein C3, tumour necrosis factor-α and adiponectin for adolescents. The variables were compared between adolescents with and without NAFLD, and logistic regression analysis was performed. RESULTS: Mean age and body mass index (BMI)SD score (SDS) were 11.9±1.6 yr and 2.3±1.1, respectively. NAFLD was seen in 62.5 per cent of the adolescents. The prevalence of NAFLD in the parents was similar among the adolescents with and without NAFLD, while BMI and waist circumference SDS, BF per cent, blood pressure (BP), ALT, AST, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were significantly higher in the adolescents with NAFLD. On multiple logistic regression, abdominal obesity, HOMA-IR and BF per cent were independently associated with NAFLD with odds ratios (95% confidence interval) of 2.77 (1.40-5.47), 2.21 (1.16-4.21) and 2.17 (1.12-4.22), respectively. INTERPRETATION & CONCLUSIONS: NAFLD was noted among nearly two-thirds of the overweight adolescents. An independent association was observed between abdominal obesity, HOMA-IR and body fat percentage and NAFLD in overweight adolescents.

Hypereosinophilia with Multi-organ Dysfunction - A Diagnostic Conundrum.

Eosinophils are predominantly tissue-dwelling cells (spleen, lymph nodes, thymus, digestive tract) and counts <500/mm3 in the peripheral blood are considered to be normal. The functions of eosinophils are not completely understood, however there can be a significant rise in their levels in the peripheral blood and/or tissues in a variety of disease states. Hypereosinophilic syndromes (HES) are a group of disorders characterised by blood eosinophilia greater than 1500/mm3 on at least two occasions and eosinophilic infiltration and damage to multiple organs. Eosinophils on activation release substances that can lead to tissue damage. However, it is important to note that the degree of tissue damage is not directly proportional to the level of eosinophilia. A significant number of cases of HES are commonly missed and therefore a systematic approach is necessary for all such patients. Through our case, we have tried to summarise how to systematically approach a case of HES and manage it.

An Unusual Case of Intractable Vomiting: Unravelling the Present, Through the Past!

A 54 year old lady presented to our institute with a history of low grade fever for one week associated with occasional loose stools, vomiting and severe malaise. Initial evaluation revealed low serum sodium. An initial diagnosis of acute gastroenteritis with secondary hyponatremia was made. Work up for infective causes of gastroenteritis was however negative. ENT evaluation and review of drug history did not contribute towards a diagnosis. The patient's symptoms persisted and did not respond to symptomatic treatment. Ultrasound of abdomen revealed cholelithiasis with no evidence of cholecystitis. Further evaluation revealed hypotonic hyponatremia with normal levels of urinary sodium excretion. With other causes of hyponatremia ruled out, an endocrinopathy was suspected as the likely culprit. Follow up hormonal studies revealed hypopituitarism and MRI of brain revealed a partially empty sella. On reviewing the case, a past history of amenorrhea immediately after the birth of her third child (almost 20 years ago!) was elicited. Intractable vomiting is quite an unusual presentation for Sheehan's syndrome, but a thorough case history coupled with a high index of suspicion can contribute towards identifying the cause among a series of confounding clinical and radiological findings, as in our case.

CRAB Manifestations in a Middle-Aged Female: A Diagnostic Dilemma.

A 56 year old lady, presented to our institute with six months history of low grade fever, generalized weakness, decreased food intake and fluctuating sensorium. Initial investigations revealed hypercalcemia, renal dysfunction and anemia. Initial working diagnosis of likely underlying hematological malignancy such as lymphoma or multiple myeloma (MM) was kept after hyperparathyroidism was ruled out. Her skeletal survey revealed lytic lesions in the skull, bone marrow aspirate showed 12% plasma cells and beta-two microglobulin level was markedly elevated. However, the criterion for MM was not fully satisfied. In view of persistent altered sensorium, MRI brain was done which suggested the diagnosis of disseminated tuberculosis and was further confirmed through MR spectroscopy, bone marrow biopsy (showing granulomas) and whole body PET. She was started on anti-tubercular therapy along with steroids with marked response within a week. We describe the details of this interesting case through a systematic approach to the various features.

Outcomes of Implementing the Central Venous Catheter Bundle at a Tertiary Care Hospital in North India, at AIIMS, New Delhi.

INTRODUCTION: Central venous catheter (CVC) associated infection are many times higher in India compared to western countries. A group of interventions called as CVC bundle, if implemented effectively prevents CVC related complication. METHODOLOGY: Our study was a prospective quasi-experimental study. The study evaluated the level of compliance with the central venous catheter bundle in the management of patients in our Medicine wards and Intensive care unit (ICU). RESULTS: :In the study, the incidence of central line associated bloodstream infection (CLABSI) was zero and the incidence of pneumothorax was 5%. Most of the patients had higher Acute physiology and chronic health evaluation (APACHE II) at baseline and multi organ dysfunction. The compliance with whole CVC bundle improved from 0% at baseline to 10% in post-intervention phase. Compliance of many components increased significantly in the post intervention period. These were Hand washing before insertion (15% to 72.5%, p<0.001), Maintenance (0% to 52.5%, p<0.001), Prompt removal of catheters (40% to 70%, p=0.007), Skin antisepsis with chlorhexidine increased approaching significance (0% to 12.5%, p=0.055). Avoidance of femoral catheters was done in more than 95% of the cases. The predictors of mortality were higher APACHE II (OR 1.23 [CI 1.03-1.47], p=0.020) and duration of hospital stay (OR 0.87 [CI 0.78-0.97], p=0.022). CONCLUSION: This study done at All India Institute of Medical Sciences showed improved outcome in terms of catheter infection and mechanical complications. CVC bundle compliance increased significantly though adherence to full bundle was less. In future, with rectification of barriers to bundle completion, the compliance with CVC bundle can be further improved.

Development and validation of visceral fat quantification as a surrogate marker for differentiation of Crohn's disease and intestinal tuberculosis.

BACKGROUND AND AIM: Crohn's disease (CD) and intestinal tuberculosis (ITB) have close phenotypic resemblance. Mesenteric fat (a component of visceral fat [VF]) hypertrophy and fat wrapping, which is visible radiologically as fibrofatty proliferation, is seen more commonly in CD than in ITB. AIM: The present study was conducted to study the role of VF in differentiating CD and ITB. METHODS: Visceral fat area and subcutaneous (SC) fat area were measured on computed tomography in two cohorts (development and validation). VF/SC ratio was also calculated for all patients. In the development cohort, retrospective data collection was carried out for 75 patients with CD and ITB who were on follow-up from January 2012 to November 2014. In the validation cohort, 82 patients were recruited prospectively from December 2014 to December 2015 and were diagnosed as CD or ITB according to standard diagnostic criteria. RESULTS: Visceral fat area and VF/SC ratio were significantly higher in CD patients (n = 42: development, n = 46: validation) than in ITB patients (n = 33: development, n = 36: validation) in both the development (106.2 ± 63.5 vs 37.3 ± 22, P = <0.001; 1.1 ± 0.57 vs 0.43 ± 0.24, P = <0.001) and validation cohorts (102.2 ± 69.8 vs 55.8 ± 44.9, P = 0.01; 1.2 ± 0.68 vs 0.56 ± 0.33, P = <0.001). A cut-off of 0.63 for VF/SC ratio in the development cohort had a high sensitivity (82%) and specificity (81%) in differentiating CD and ITB. Similar sensitivity (81%) and specificity (78%) were seen when this cut-off was applied in the validation cohort. CONCLUSION: The VF/SC ratio is a simple, cost-effective, non-invasive and single objective parameter with a good sensitivity and specificity to differentiate CD and ITB.

Glucose tolerance & insulin secretion & sensitivity characteristics in Indian children with cystic fibrosis: A pilot study.

Background & objectives: Cystic fibrosis (CF) is a life-limiting genetic condition resulting in chronic respiratory infections, pancreatic enzyme insufficiency and associated complications. This pilot study was undertaken to assess the glucose tolerance and insulin secretion and sensitivity among Indian children with CF. Methods: Children with CF under regular follow up at the Paediatric Pulmonology Clinic of a tertiary care hospital in New Delhi, India, were enrolled. Children who had a history of acute exacerbation or intake of systemic steroids within the last two weeks were excluded. Anthropometry, pulmonary function and disease severity (Shwachman) score were assessed. Fasting venous sample was drawn to assess glucose, insulin, haemoglobin and calcium. Oral glucose tolerance test was performed, and blood glucose and insulin were assessed at 30, 60, 90 and 120 min. Insulin secretion and sensitivity indices were calculated. Results: Twenty nine patients with a mean age of 11.2±4.1 yr were enrolled. Stunting, thinness, anaemia and hypocalcaemia were present in 31.0, 13.8, 37.0 and 48.3 per cent of the patients, respectively. Abnormal glucose tolerance (AGT) was present in 21.4 per cent. Insulin secretion was similar in individuals with AGT and normal glucose tolerance (NGT), but insulin sensitivity index was lower (0.12±0.02 vs 0.15±0.01, P<0.001) and homeostatic model assessment of insulin resistance higher [1.63 (0.53-1.76) vs 0.83 (0.28-4.43), P<0.05] in individuals with AGT compared to NGT. Interpretation & conclusions: AGT was observed in 21.4 per cent of children with CF. The CF patients with AGT had significantly lower insulin sensitivity compared to patients with NGT. Future multicentric studies with a large sample should be conducted to assess insulin secretion and sensitivity indices in CF patients compared to healthy controls.

Vitamin D status of adult females residing in Ballabgarh health and demographic surveillance system: A community-based study.

BACKGROUND: Vitamin D deficiency (VDD) is widespread, yet it is the most underdiagnosed and undertreated nutritional deficiency in the world. The prevalence of VDD is estimated to affect over 1 billion people worldwide. OBJECTIVES: The present study was conducted to estimate the prevalence of VDD among adult females aged 20-60 years residing in a rural community of North India, and to find its association with various sociobehavioral risk factors. METHODS: The present study is an analytical cross-sectional study conducted among females aged 20-60 years in rural Ballabgarh. Four hundred women were randomly selected from one of the villages of the Health and Demographic Surveillance System. Semi-structured, pretested interview schedule was administered to the study participants. Fasting venous blood sample was collected for the measurement of plasma sugar level and Vitamin D (25-hydroxyvitamin D). RESULTS: The prevalence of VDD was 90.8% (95% confidence interval [CI] - 87.5-93.3), while that of Vitamin D insufficiency was 8.9% (95% CI - 6.4-12.2). On logistic regression analysis, 24 h calorie intake, protein intake, and prediabetes status of the participants were significantly associated with VDD. CONCLUSION: Very high prevalence of VDD was observed among the females (20-60 years) residing in rural Ballabgarh.

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.

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.

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.