Transcriptomic and proteomic analyses of Mycobacterium tuberculosis strains isolated from tuberculous meningitis patients.

Background: Tuberculous meningitis (TBM) is caused by the dissemination of Mycobacterium tuberculosis (MTB) from the primary site of infection to the central nervous system. However, the bacterial factors associated with the pathogenesis of TBM remain unclear. This study employed transcriptomic and proteomic methods to comprehensively analyze the changes in genes and proteins and their associated pathways in MTB strains isolated from cerebrospinal fluid (CSF) of TBM and sputum of pulmonary TB (PTB) cases. Methodology: Five MTB strains were subjected to OMICs (transcriptomic and proteomic) analysis. Among five MTB strains, two were isolated from CSF and sputum samples of the same patient with PTB and TBM infections, one from the sputum of a different PTB patient, and a strain obtained from the CSF of another TBM patient. H37Rv was used as a reference strain. The reliability of transcriptomic results was validated by real time polymerase chain reaction with selected genes from 100 MTB isolates (CSF, 50 and sputum, 50). Results: The transcriptomic study revealed that overlapping differentially expressed genes of MTB strains isolated from TBM patients showed featured enrichment in benzoate degradation, lysine degradation, tryptophan metabolism, fatty acid degradation, ATP binding cassette transporters, microbial metabolism in diverse environments, biosynthesis of antibiotics, and metabolic pathways. Eleven genes were upregulated, and four were downregulated in MTB strains isolated from TBM compared to PTB. From proteomic analysis, we identified three candidate proteins belonging to plasminogen binding proteins (PBP) (enolase, dnaK, and isocitrate lyase 1) that were significantly upregulated in MTB strains isolated from TBM. Conclusion: Overall, the transcriptomic and proteomic analyses provided an important base for understanding the unique feature of TBM pathogenesis. To the best of our knowledge, this is the first report highlighting the importance of PBPs on TBM pathogenesis.

Clinical Profile and Predictors of Mortality among Patients with Melioidosis.

Introduction: Melioidosis is an under-recognized but important infection with high mortality and morbidity. It is endemic along the coastal regions of the Southern part of India. The present study focuses on the varied clinical manifestations, associated risk factors, and outcomes in patients from the Southeastern part of India. Methods: Seventy patients from January 2018 to June 2021 from a Tertiary Care Hospital were included and prospectively followed up from 6 months to 3 years. Cox regression was performed to test for the association of various clinical and demographic factors with overall survival. Results: Diabetes and occupational exposure to soil and water (78.6%) followed by alcoholism (61.4%) were the most common risk factors for melioidosis. The most frequent presentation was sepsis (47.1%), followed by skin and soft tissue infection (32.9%) and pneumonia (25.7%). Mortality was 50%. Patients with sepsis had a 3.5-fold higher risk of mortality (adjusted hazard ratio = 3.50; P = 0.01) while other risk factors were not significantly associated with mortality. Conclusion: Lifestyle-dependent risk factors (diabetes, occupational exposure, and alcoholism) were most common among patients with melioidosis. Hospitalization among patients with sepsis is associated with high mortality despite the initiation of specific therapy.

Bacteriuria due to Typhoidal and Nontyphoidal Salmonella: A Report of Three Cases from South India.

Urinary tract infection (UTI) with Salmonella is uncommon, accounting for merely 0.01% to 0.1% of cases of UTIs. It is reported more frequently in the presence of predisposing factors such as structural abnormalities of the urinary tract or weakened immune system. We present a case series of three patients with Salmonella bacteriuria and their susceptibility patterns. All three patients had underlying urologic features such as neurogenic bladder, chronic kidney disease, and urethral stricture, and two presented with urinary tract involvement symptoms.

Safety and immunogenicity of SII-NVX-CoV2373 (COVID-19 vaccine) in adults in a phase 2/3, observer-blind, randomised, controlled study.

Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study. Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults. In phase 2, 200 participants were randomized 3:1 to SII-NVX-CoV2373 or placebo. In phase 3, 1400 participants were randomized 3:1 to SII-NVX-CoV2373 or NVX-CoV2373 (940 safety cohort and 460 immunogenicity cohort). Two doses of study products (SII-NVX-CoV2373, NVX-CoV2373 or placebo) were given 3 weeks apart. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 to NVX-CoV2373 in terms of geometric mean ELISA units (GMEU) ratio of anti-S IgG antibodies 14 days after the second dose (day 36) and to determine the incidence of causally related serious adverse events (SAEs) through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAb) were assessed by a microneutralization assay using wild type SARS CoV-2 in participants from the immunogenicity cohort at baseline, day 22, day 36 and day 180. Cell mediated immune (CMI) response was assessed in a subset of 28 participants from immunogenicity cohort by ELISpot assay at baseline, day 36 and day 180. The total follow-up was for 6 months. Trial registration: CTRI/2021/02/031554. Findings: Total 1596 participants (200 in Phase 2 and 1396 in Phase 3) received the first dose. SII-NVX-CoV2373 was found non-inferior to NVX-CoV2373 (anti-S IgG antibodies GMEU ratio 0.91; 95% CI: 0.79, 1.06). At day 36, there was more than 58-fold rise in anti-S IgG and nAb titers compared to baseline in both the groups. On day 180 visit, these antibody titers declined to levels slightly lower than those after the first dose (13-22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. No adverse event of special interest (AESI) was reported. No causally related SAE was reported. Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has acceptable safety profile. Funding: SIIPL, Indian Council of Medical Research, Novavax.

A Panoramic View of Patients' Beliefs and Knowledge About Chronic Respiratory Disease.

Objective Patients with chronic respiratory diseases (CRD) like asthma and chronic obstructive pulmonary disease (COPD) experience significant morbidity and mortality. The patient's quality of life deteriorates with the progression of the disease. Pharmacological treatment focuses on reducing the symptoms. The psychological impact of the disease on the patient's quality of life is not assessed by all healthcare providers. There is limited knowledge about the patient's demographic and clinical factors affecting the quality of life in CRD patients and aspects hindering or influencing the management of disease in this population. Hence we aimed to conduct a qualitative study on patients with asthma or COPD to get a view of their knowledge about the disease, the problems they encounter in their day-to-day life and the treatment. Methods Semi-structured, face-to-face interviews were conducted by the investigator in the hospital during the patient's follow-up visits. The questions focused on the patient's awareness of the disease, living with chronic respiratory disease, understanding of disease and treatment, and compliance with inhaled therapy. The interviews were audio recorded and transcribed verbatim. Content analysis of the data was done manually. Codes and themes were derived manually. Themes were formed from the codes and sub-themes. Results Five themes were generated from the data obtained: (1) misconceptions regarding the contagious nature of the disease; (2) psychological stress due to feelings of worthlessness, helplessness due to inability to work and poor understanding among family members; (3) inappropriate lifestyle modifications like avoiding fruits and vegetables due to the fear of acute attacks; (4) poor adherence to inhalers due to work timing and difficulty travelling; and (5) lack of reinforcement by the healthcare providers on inhaler technique and adherence were identified as causes of poor inhaler technique and inappropriate knowledge about drugs. Conclusion Subjective reporting by patients in this study was helpful in understanding issues concerning disease management in CRD patients. Apart from assessing the patients' symptoms and prescribing drugs, healthcare providers should take time to impart knowledge about the disease to patients. Though patient education and psychological intervention are challenging to implement daily, they are supplemental to the pharmacologic management of the disease.

Hyperglycemia and steroid use increase the risk of rhino-orbito-cerebral mucormycosis regardless of COVID-19 hospitalization: Case-control study, India.

BACKGROUND: In the ongoing COVID-19 pandemic, an increased incidence of ROCM was noted in India among those infected with COVID. We determined risk factors for rhino-orbito-cerebral mucormycosis (ROCM) post Coronavirus disease 2019 (COVID-19) among those never and ever hospitalized for COVID-19 separately through a multicentric, hospital-based, unmatched case-control study across India. METHODS: We defined cases and controls as those with and without post-COVID ROCM, respectively. We compared their socio-demographics, co-morbidities, steroid use, glycaemic status, and practices. We calculated crude and adjusted odds ratio (AOR) with 95% confidence intervals (CI) through logistic regression. The covariates with a p-value for crude OR of less than 0·20 were considered for the regression model. RESULTS: Among hospitalised, we recruited 267 cases and 256 controls and 116 cases and 231 controls among never hospitalised. Risk factors (AOR; 95% CI) for post-COVID ROCM among the hospitalised were age 45-59 years (2·1; 1·4 to 3·1), having diabetes mellitus (4·9; 3·4 to 7·1), elevated plasma glucose (6·4; 2·4 to 17·2), steroid use (3·2; 2 to 5·2) and frequent nasal washing (4·8; 1·4 to 17). Among those never hospitalised, age ≥ 60 years (6·6; 3·3 to 13·3), having diabetes mellitus (6·7; 3·8 to 11·6), elevated plasma glucose (13·7; 2·2 to 84), steroid use (9·8; 5·8 to 16·6), and cloth facemask use (2·6; 1·5 to 4·5) were associated with increased risk of post-COVID ROCM. CONCLUSIONS: Hyperglycemia, irrespective of having diabetes mellitus and steroid use, was associated with an increased risk of ROCM independent of COVID-19 hospitalisation. Rational steroid usage and glucose monitoring may reduce the risk of post-COVID.

Estimation of seroprevalence of melioidosis among adult high risk groups in Southeastern India by indirect Hemagglutination assay.

Burkholderia pseudomallei is an environmental saprophyte known to cause melioidosis, a disease endemic in northern Australia and Southeast Asia. With the increasing number of melioidosis cases, there is a lack of data on seroprevalence rates and extent of exposure in high risk population of melioidosis from different endemic regions in India. The present cross sectional study was undertaken to estimate the seroprevalence of melioidosis in high risk populations in and around Puducherry, a coastal town in Southeastern India. Blood samples were collected from 275 diabetic individuals attending a tertiary care centre in Southern India and 275 farmers residing under the rural field practice area of our hospital. The antibody levels were estimated using an Indirect Hemagglutination Assay. The overall seropositivity was found to be 19.8% with a titer ≥1:20. Farmers were 2.8 times more likely to be seropositive than non-farmers. Rates of seroprevalence among diabetic subjects were less compared to the non-diabetic individuals. The seropositivity rates in non-diabetic farmers were higher (56/203, 27.6%) compared to diabetic farmers (34/164, 20.7%). The lowest seropositivity was seen among diabetic non-farmers at 10.4%. Multivariable logistic regression analysis revealed domicile (adjusted odds ratio-aOR: 2.32, 95% Confidence interval-CI: 1.05, 5.13) and contact with animals (aOR: 1.89, 95% CI:1.04, 3.44) as significant predictors of seropositivity. None of the other socio-demographic factors including gender and age were significantly associated with seropositivity. This study demonstrates widespread exposure to B. pseudomallei among adults residing in and around Puducherry, including those engaged in non-farming occupations.

Diagnosis of Undifferentiated Connective Tissue Disease in a Patient With Digital Gangrene and Positive Antinuclear Antibodies.

The occurrence of ischemia of the digits or digital gangrene is a well-known complication of systemic autoimmune diseases, such as systemic sclerosis, systemic lupus erythematosus, and anti-phospholipid syndrome, among others. The pathophysiological mechanisms are small vessel vasculitis, vasospasm of Raynaud's phenomenon, microthrombi due to antiphospholipid syndrome, and/or accompanying accelerated atherosclerosis. Digital ischemia can also occur in the context of disseminated bacterial infections and sepsis. We present here the case of a patient who had digital ischemia and positive antinuclear antibodies but without well-defined clinical features of a connective tissue disease. A diagnosis of undifferentiated connective tissue disease was made.

Point-of-care infrared thermal imaging for differentiating venomous snakebites from non-venomous and dry bites.

BACKGROUND: Local envenomation following snakebites is accompanied by thermal changes, which could be visualized using infrared imaging. We explored whether infrared thermal imaging could be used to differentiate venomous snakebites from non-venomous and dry bites. METHODS: We prospectively enrolled adult patients with a history of snakebite in the past 24 hours presenting to the emergency of a teaching hospital in southern India. A standardized clinical evaluation for symptoms and signs of envenomation including 20-minute whole-blood clotting test and prothrombin time was performed to assess envenomation status. Infrared thermal imaging was done at enrolment, 6 hours, and 24 hours later using a smartphone-based device under ambient conditions. Processed infrared thermal images were independently interpreted twice by a reference rater and once by three novice raters. FINDINGS: We studied 89 patients; 60 (67%) of them were male. Median (IQR) time from bite to enrolment was 11 (6.5-15) hours; 21 (24%) patients were enrolled within 6 hours of snakebite. In all, 48 patients had local envenomation with/without systemic envenomation, and 35 patients were classified as non-venomous/dry bites. Envenomation status was unclear in six patients. At enrolment, area of increased temperature around the bite site (Hot spot) was evident on infrared thermal imaging in 45 of the 48 patients with envenomation, while hot spot was evident in only 6 of the 35 patients without envenomation. Presence of hot spot on baseline infrared thermal images had a sensitivity of 93.7% (95% CI 82.8% to 98.7%) and a specificity of 82.9% (66.3% to 93.4%) to differentiate envenomed patients from those without envenomation. Interrater agreement for identifying hot spots was more than substantial (Kappa statistic >0.85), and intrarater agreement was almost perfect (Kappa = 0.93). Paradoxical thermal changes were observed in 14 patients. CONCLUSIONS: Point-of-care infrared thermal imaging could be useful in the early identification of non-venomous and dry snakebites.

Circulating Secretory Phospholipase A2 Activity following Snakebites and Its Relationship with Envenomation Status and Progression of Local Swelling.

We studied whether circulating secretory phospholipase A2 (sPLA2) activity reliably distinguished patients with snakebite envenomation from those with nonvenomous/dry snakebites, and whether patients with progressive local swelling had persistence of circulating sPLA2 activity despite antivenom treatment. We prospectively enrolled adults presenting to the emergency with a history of snakebite in the past 24 hours. We estimated circulating sPLA2 activity at baseline before antivenom administration and after 48 hours in those with envenomation. We enrolled 52 patients with snakebites (mean age 39.3 ± 12.6 years; 35 [67%] men), and 16 patients with infective cellulitis as controls. Thirty patients had local ± systemic envenomation; 15 were classified as dry/nonvenomous bites; and envenomation status was unclear in seven patients. Baseline sPLA2 activity was significantly higher in snakebite patients than that in those with infective cellulitis (4.64 [3.38-5.91] versus 3.38 [1.69-4.01] nmol/minute/mL; P = 0.005). Among patients with snakebites, sPLA2 activity in the highest quartile was significantly associated with envenomation (12 of 27 versus two of 22; P = 0.010). However, median sPLA2 activity did not differ significantly between patients with envenomation and the rest. Baseline sPLA2 activity was significantly associated with the maximum extent of limb swelling (P = 0.031 for trend). In envenomed patients, circulating sPLA2 activity significantly decreased after 48 hours compared with the baseline (5.49 [3.38-8.86] versus 3.38 [2.53-4.64]; P = 0.003) including those with progressive swelling. Although circulating sPLA2 activity was elevated following snakebites, its sensitivity to diagnose envenomation appears to be limited. Administration of more antivenom after systemic manifestations had reversed might not benefit patients with progressive local swelling.

Reevaluating the true diagnostic accuracy of dipstick tests to diagnose urinary tract infection using Bayesian latent class analysis.

OBJECTIVE: Previous studies on diagnostic accuracy of dipstick testing for leukocyte esterase (LE) and nitrite to diagnose urinary tract infection (UTI) had used urine culture, which is an imperfect gold standard. Estimates of diagnostic accuracy obtained using the classical gold standard framework might not reflect the true diagnostic accuracy of dipstick tests. METHODS: We used the dataset from a prospective, observational study conducted in the emergency department of a teaching hospital in southern India. Patients with a clinical suspicion of UTI underwent dipstick testing for LE and nitrite, urine microscopy, and urine culture. Based on the results of urine microscopy and culture, UTI was classified into definite, probable, and possible. Patients with microscopic pyuria and a positive urine culture were adjudicated as definite UTI. Unequivocal imaging evidence of emphysematous pyelonephritis or perinephric collections was also considered definite UTI. We estimated the diagnostic accuracy of LE and nitrite tests using the classical analysis (assuming definite UTI as gold standard) and two different Bayesian latent class models (LCMs; 3-tests in 1-population and 2-tests in 2-populations models). RESULTS: We studied 149 patients. Overall, 64 (43%) patients had definite, 76 (51%) had probable, and 2 (1.3%) had possible UTI; 7 (4.6%) had alternate diagnoses. In classical analysis, LE was more sensitive than nitrite (87.5% versus 70.5%), while nitrite was more specific (24% versus 58%). The 3-tests in 1-population Bayesian LCM indicated a substantially better sensitivity and specificity for LE (98.1% and 47.6%) and nitrite (88.2% and 97.7%). True sensitivity and specificity of urine culture as estimated by the model was 48.7% and 73.0%. Estimates of the 2-tests in 2-populations model were in agreement with the 3-tests in 1-population model. CONCLUSIONS: Bayesian LCMs indicate a clinically important improvement in the true diagnostic accuracy of urine dipstick testing for LE and nitrite. Given this, a negative dipstick LE would rule-out UTI, while a positive dipstick nitrite would rule-in UTI in our study setting. True diagnostic accuracy of urine dipstick testing for UTI in various practice settings needs reevaluation using Bayesian LCMs.

Comparison of two Anti Snake Venom protocols in hemotoxic snake bite: A randomized trial.

The dose of Anti Snake Venom (ASV) in hemotoxic snake bite depends on the amount of venom injected and species of snake. All trials in South East Asia have studied different doses of ASV, wherein the ASV in high dose group itself was lower than the dose that is recommended in Indian National protocol. These studies favored low dose protocol, as there was no difference in mortality and morbidity between the groups. So, this study intended to assess the efficacy of National protocol in reducing morbidity and mortality in hemotoxic snake bite in comparison to current protocol followed in institution. This was an open label randomized trial of 140 hemotoxic snakebite patients. Group A received national protocol: initial dose of 100 ml followed by 100 ml 6th hourly till 20-min Whole Blood Clotting Time (20WBCT) was negative or 300 ml of ASV was given, whichever was earlier. Group B received 70 ml followed by 30 ml every 6th hourly until two consecutive 20WBCT were negative. There was no statistical difference in the amount of ASV required in both the groups. Mortality and acute kidney injury were higher in group A (statistically not significant), probably due to sicker patients in that group. There was no relapse of clotting time abnormality in both the groups. In a significant number of patients (12%), clotting time was persistently prolonged till death. We found that the use of National ASV dosing protocol did not decrease the mortality and morbidity.

Aetiology and short-term outcome of acute respiratory distress syndrome: a real-world experience from a medical intensive care unit in southern India.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a highly fatal syndrome especially in resource constrained settings. In this study we prospectively studied the aetiology of ARDS and its short-term outcome. METHODS: Consecutive adults with suspected ARDS were screened. ARDS was diagnosed by the Berlin criteria. Aetiology was determined clinically, and by imaging and microbiological investigations. Patients presenting with fever, prominent cough and expectoration had a throat swab tested for influenza H1N1 virus. Outcome was discharge from hospital or death. RESULTS: A total of 42 patients, mean age 42.6 years, were studied. All received mechanical ventilation. Thirteen (31%) had pulmonary ARDS: H1N1 virus infection (n = 5), pneumonia (n = 7) and tuberculosis (n = 1). Twenty nine (69%) had extrapulmonary ARDS: sepsis (n = 16) and scrub typhus (n = 8). Thirty three (79%) died, of the nine survivors scrub typhus was diagnosed in seven patients. CONCLUSION: The aetiology of ARDS in tropical medical setting is infection related. ARDS due to scrub typhus appeared to be mild with good outcome.

Bilateral subretinal abscess in community-acquired meticillin-susceptible Staphylococcus aureus infection.

Subretinal abscesses due to endogenous staphylococcal blood stream infection is a rare occurrence. A young adult male presented with subretinal abscesses, necrotising pneumonia, pleural empyema, skin and soft tissue infection, muscle abscesses and deep vein thrombosis. Aspirate from one of the abscesses and blood culture revealed meticillin-susceptible Staphylococcus aureus. We present here a case of probable Panton-Valentine leucocidin (PVL) syndrome. PVL is a cytotoxin produced by S. aureus. Infection with PVL-positive S. aureus produces a clinical disease that is characterised by necrotising pneumonia and disseminated infection that often carries a high mortality. Our patient showed prompt clinical response to cloxacillin that was given for a total duration of 6 weeks. At the end of 6 weeks vision also recovered. The successful outcome in our patient was likely due to early and appropriate antibiotic therapy.

Expression Pattern of Selected Toll-like Receptors (TLR's) in the PBMC's of Severe and Non-severe Dengue Cases.

Objective: The role of TLR's in the pathogenesis of dengue is not explored well. Differential expression of TLR2 and TLR4 was reported in dengue cases. In the present study in order to understand the expression pattern of various TLR's, including TLR2, TLR3, TLR4 and TLR9, mRNA levels were determined in various dengue study groups compared to control groups, at the time of admission and around defervescence using quantitative real-time PCR (RT-PCR).Methods: A total of 88 dengue cases with 32 severe and 56 non-severe cases were involved in the study. Gene expression pattern of the study groups was compared with 31 other febrile illness (OFI) cases and 63 healthy controls. Transcript levels of the target genes were estimated from the peripheral blood mononuclear cells (PBMC) samples collected from cases and controls using quantitative real-time PCR.Results: We have noted a significant alteration in the levels of all TLR's in dengue and OFI cases compared to healthy controls at the time of admission. Interestingly we have noted a significant alteration in the levels of TLR9 in severe and non-severe cases during defervescence. The same was not detected in the OFI group.Conclusion: The present study found a change in TLR's during dengue infection. This suggests us to explore the TLR's as therapeutic candidate for anti-dengue virus strategies. However, in order to ascertain the involvement of TLR's in the disease pathology and its role as biomarkers for prognosis, a complete dynamics of TLR's expression needs to be studied.

Altered Platelet Fatty Acids in Dengue Cases by Gas Chromatography-Mass Spectrometry Analysis.

BACKGROUND: The role of dengue virus in altering the functional properties of platelets remains poorly understood. Few studies have observed that changes in fatty acids are found to have an effect on platelet activation and aggregation. Also, platelet fatty acids have not been extensively studied in dengue so far. So, we aimed to study the fatty acids of platelet membranes in patients with dengue. METHODS: Gas chromatography-mass spectrometry (GC-MS) method was used to analyze fatty acids in the lipid extracts of platelets isolated from the study participants. RESULTS: GC-MS analysis of platelet lipids identified and quantified nearly 23 unique lipid molecules on platelet membrane. We observed significant alterations with some of the fatty acids in patients with dengue compared to controls. Within dengue cases, increase in unsaturated fatty acids in severe dengue was observed compared to non-severe dengue. From baseline to defervescence, no difference in fatty acids was observed in dengue platelets. This indicates that in dengue, platelet physiology remains altered even after the febrile phase. CONCLUSION: To the best of our knowledge, this is the first study characterizing the differential expression of platelet fatty acids in dengue infection. However, further studies are warranted to expound the underlying cause for thrombocytopenia and platelet dysfunction in dengue.

Effect of Curcuma longa on vascular function in native Tamilians with type 2 diabetes mellitus: A randomized, double-blind, parallel arm, placebo-controlled trial.

Diabetes mellitus is characterized by increased central arterial stiffness and endothelial dysfunction leading to increased risk of cardiovascular complications. The aim of this study is to evaluate the effect of Curcuma longa on arterial stiffness and endothelial dysfunction in patients with type 2 diabetes mellitus. This randomized controlled trial was conducted in 136 patients of type 2 diabetes. Among them, 114 completed at least one follow-up visit and included for data analysis. Arterial stiffness parameters were measured at baseline and every month for 3 months and endothelial dysfunction markers at baseline and after 3 months of treatment with C. longa or placebo. These parameters were compared between the two groups. Both C. longa and placebo groups were comparable at baseline. After 3 months of treatment, C. longa produced significant reduction from baseline in carotid-femoral pulse wave velocity (p = .002), left brachial-ankle pulse wave velocity (p = .001), aortic augmentation pressure (p = .007), aortic augmentation index (p = .007), and aortic augmentation index at heart rate 75 (p = .018) as compared with the placebo group. Three months treatment with C. longa significantly decreases arterial stiffness as compared with placebo in type 2 diabetes mellitus patients.

Fatal case of necrotising fasciitis due to Vibrio vulnificus in a patient with alcoholic liver disease and diabetes mellitus.

Vibrio vulnificus is a halophilic Vibrio found globally. They are thought to be normal microbiome in the estuaries along the coasts associated with seawater and seashells. Infection usually results from consumption of raw oysters or shellfish or exposure of broken skin or open wounds to contaminated salt or brackish water. Clinical manifestations range from gastroenteritis to skin and subcutaneous infection and primary sepsis. Pathogen has the ability to cause infections with significant mortality in high-risk populations, including patients with chronic liver disease, immunodeficiency, diabetes mellitus and iron storage disorders. There is often a lack of clinical suspicion in cases due to Vibrio vulnificus leading to delay in treatment and subsequent mortality. Herein we report a case of necrotising fasciitis in a diabetic patient with alcoholic liver disease caused by Vibrio vulnificus which ended fatally.

Cardiac arrhythmias, electrolyte abnormalities and serum cardiac glycoside concentrations in yellow oleander (Cascabela thevetia) poisoning - a prospective study.

BACKGROUND: Consumption of yellow oleander (Cascabela thevetia) is a popular method of intentional self-harm in South India. OBJECTIVES: The objectives of this study were to identify the cardiac arrhythmias and electrolyte abnormalities in yellow oleander poisoning and to identify the association between electrolyte abnormalities, cardiac glycoside concentrations at admission and the severity of cardiotoxicity. This study was also designed to identify clinical and biochemical parameters at presentation which predict serious arrhythmias and determinants of mortality. MATERIALS AND METHODS: This was a prospective study among 192 patients who attended our Emergency department after consuming yellow oleander seeds. Patients were monitored with serial ECGs. Serious cardiac arrhythmias included sinus bradycardia <40/min, sinus arrest/exit block, second or third degree AV block, atrial tachyarrhythmias and ventricular tachyarrhythmias. Serum sodium, potassium, magnesium, total calcium and cardiac glycoside concentrations were measured at presentation for all 192 patients. Serial estimation of cardiac glycoside concentration was done in 43 patients who presented within 24 hours of consuming at least five seeds. RESULTS: At presentation, 46 patients had serious arrhythmias and on follow-up, 11 developed new-onset serious arrhythmia. Sinus bradycardia (27%) was the most common arrhythmia followed by second-degree AV block (17%); multiple arrhythmias were observed in 18%. Digoxin effect in ECG correlated significantly with hyperkalemia. Mortality rate was 5%. Serum sodium, total calcium and magnesium levels did not correlate with cardiotoxicity. Cardiac glycoside concentration was of relatively modest clinical utility to discriminate patients with serious dysrhythmias (AUC: 0.719, 95% CI: 0.63-0.81). Prolonged PR interval and digoxin effect in ECG were significantly associated with an increased likelihood of serious dysrhythmias. Increase in 0.4 number of seed intake increased the odds of mortality by 1.5 times when all other independent variables were kept constant. CONCLUSION: Cardiac glycoside concentration at the time of presentation predicted the development of new-onset serious arrhythmias. Although serum potassium correlated significantly with cardiac glycoside concentration at admission and overall serious dysrhythmias, it did not predict the development of new-onset serious arrhythmia. On the whole, serious dysrhythmias were significantly associated with higher number of seeds ingested, hypotension at admission, PR interval prolongation, presence of digoxin effect in ECG, hyperkalemia and higher cardiac glycoside concentration. The independent determinants of mortality were larger number of seeds ingested and hypotension at admission. Cardiac glycoside concentration and hyperkalemia failed to be independent markers of serious dysrhythmias as well as mortality.