A study of electrocardiographic and 2D echocardiographic changes in type 2 diabetes mellitus patients without cardiovascular symptoms.

Context: Cardiovascular diseases in diabetic patients are mostly asymptomatic due to autonomic neuropathy. Many patients with left ventricular dysfunction remain undiagnosed and untreated until advance disease causes disability. This delay could be avoided if screening techniques are used to identify left ventricular dysfunction in its preclinical phase. Aims: This study was undertaken to find out the incidence of electrocardiographic (ECG) and 2D echocardiographic (2 D Echo) abnormalities in diabetic patients without cardiovascular symptoms. The correlation of control of diabetes with these abnormalities was also studied. Settings and Design: A hospital-based, cross-sectional observational study. Methods and Material: Type 2 diabetic patients (outpatient and indoor) without cardiovascular symptoms like palpitations, chest pain, syncope, and breathlessness were included in the study. Their ECG and 2D Echo findings were noted and correlated with their blood sugar levels. Statistical Analysis Used: Chi-square test. Results: Type 2 diabetic patients without cardiovascular symptoms had significant abnormal findings on ECG and 2D Echo. Control of postprandial blood sugar level was of primary importance to prevent cardiovascular abnormalities. Conclusions: Type 2 diabetics without cardiovascular symptoms must be screened for cardiovascular abnormalities so that early interventions can be done to prevent further progression to symptomatic cardiovascular abnormalities. There is a significant number of people having normal ECG but abnormal 2D Echo and vice versa, so not only ECG but also 2D Echo should be done to predict cardiovascular risk in type 2 diabetic patients without cardiovascular symptoms.

Functional Single-Nucleotide Polymorphisms in the MBL2 and TLR3 Genes Influence Disease Severity in Influenza A (H1N1)pdm09 Virus-Infected Patients from Maharashtra, India.

The clinical outcome in influenza A (H1N1)pdm09 virus-infected subjects is determined by several factors, including host genetics. In the present study, single-nucleotide polymorphisms (SNPs) in the IFITM, MBL2, TLR3, TLR8, DDX58, IFIH1, CD55, and FCGR2, genes were investigated in influenza A (H1N1)pdm09 virus-infected subjects to find out their association with disease severity. Influenza A (H1N1)pdm09 virus-infected subjects with severe disease (n = 86) and mild disease (n = 293) from western India were included in the study. The SNPs were investigated by PCR-based methods. The results revealed a higher frequency of TLR3 rs5743313 T/T genotype [odds ratio (OR) with 95% confidence interval (CI) 2.55 (1.08-6.04) p = 0.039] and TLR3 two-locus haplotype rs3775291-rs3775290 T-A [OR with 95% CI 7.94 (2.05-30.68)] in severe cases. Lower frequency of the mutant allele of MBL2 rs1800450 [OR with 95% CI 0.51 (0.27-0.87), p = 0.01] and TLR3 two-locus haplotype rs3775291-rs3775290 T-G [OR with 95% CI 0.48 (0.27-0.85)] was observed in severe cases compared with cases with mild disease. Higher frequency of TLR3 two-locus haplotype rs3775291-rs3775290 T-A was observed in severe cases [OR with 95% CI 7.9 (2.0-30.7)]. The allele and genotype frequencies of other SNPs were not different between the study categories. The results suggest that the functional SNPs in MBL2 and TLR3 are associated with severe disease in influenza A (H1N1)pdm09 virus-infected subjects.

TNFA and IL10 Polymorphisms and IL-6 and IL-10 Levels Influence Disease Severity in Influenza A(H1N1)pdm09 Virus Infected Patients.

Cytokines are key modulators of immune response, and dysregulated production of proinflammatory and anti-inflammatory cytokines contributes to the pathogenesis of influenza A(H1N1)pdm09 virus infection. Cytokine production is impacted by single nucleotide polymorphisms (SNPs) in the genes coding for them. In the present study, SNPs in the IL6, TNFA, IFNG, IL17A, IL10, and TGFB were investigated for their association with disease severity and fatality in influenza A(H1N1)pdm09-affected patients with mild disease (n = 293) and severe disease (n = 86). Among those with severe disease, 41 patients had fatal outcomes. In a subset of the patients, levels of IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17 were assayed in the plasma for their association with severe disease. The frequency of TNFA rs1800629 G/A allele was significantly higher in severe cases and survived severe cases group compared to that of those with mild infection (OR with 95% for mild vs. severe cases 2.95 (1.52-5.73); mild vs. survived severe cases 4.02 (1.84-8.82)). IL10 rs1800896-rs1800872 G-C haplotype was significantly lower (OR with 95% 0.34 (0.12-0.95)), while IL10 rs1800896-rs1800872 G-A haplotype was significantly higher (OR with 95% 12.11 (2.23-76.96)) in fatal cases group compared to that of the mild group. IL-6 and IL-10 levels were significantly higher in fatal cases compared to that of survived severe cases. IL-6 levels had greater discriminatory power than IL-10 to predict progression to fatal outcome in influenza A(H1N1)pdm09 virus-infected patients. To conclude, the present study reports the association of TNFA and IL10 SNPs with severe disease in Influenza A(H1N1)pdm09 virus-infected subjects. Furthermore, IL-6 levels can be a potential biomarker for predicting fatal outcomes in Influenza A(H1N1)pdm09 virus infected subjects.

Tocilizumab plus standard care versus standard care in patients in India with moderate to severe COVID-19-associated cytokine release syndrome (COVINTOC): an open-label, multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: Global randomised controlled trials of the anti-IL-6 receptor antibody tocilizumab in patients admitted to hospital with COVID-19 have shown conflicting results but potential decreases in time to discharge and burden on intensive care. Tocilizumab reduced progression to mechanical ventilation and death in a trial population enriched for racial and ethnic minorities. We aimed to investigate whether tocilizumab treatment could prevent COVID-19 progression in the first multicentre randomised controlled trial of tocilizumab done entirely in a lower-middle-income country. METHODS: COVINTOC is an open-label, multicentre, randomised, controlled, phase 3 trial done at 12 public and private hospitals across India. Adults (aged ≥18 years) admitted to hospital with moderate to severe COVID-19 (Indian Ministry of Health grading) confirmed by positive SARS-CoV-2 PCR result were randomly assigned (1:1 block randomisation) to receive tocilizumab 6 mg/kg plus standard care (the tocilizumab group) or standard care alone (the standard care group). The primary endpoint was progression of COVID-19 (from moderate to severe or from severe to death) up to day 14 in the modified intention-to-treat population of all participants who had at least one post-baseline assessment for the primary endpoint. Safety was assessed in all randomly assigned patients. The trial is completed and registered with the Clinical Trials Registry India (CTRI/2020/05/025369). FINDINGS: 180 patients were recruited between May 30, 2020, and Aug 31, 2020, and randomly assigned to the tocilizumab group (n=90) or the standard care group (n=90). One patient randomly assigned to the standard care group inadvertently received tocilizumab at baseline and was included in the tocilizumab group for all analyses. One patient randomly assigned to the standard care group withdrew consent after the baseline visit and did not receive any study medication and was not included in the modified intention-to-treat population but was still included in safety analyses. 75 (82%) of 91 in the tocilizumab group and 68 (76%) of 89 in the standard care group completed 28 days of follow-up. Progression of COVID-19 up to day 14 occurred in eight (9%) of 91 patients in the tocilizumab group and 11 (13%) of 88 in the standard care group (difference -3·71 [95% CI -18·23 to 11·19]; p=0·42). 33 (36%) of 91 patients in the tocilizumab group and 22 (25%) of 89 patients in the standard care group had adverse events; 18 (20%) and 15 (17%) had serious adverse events. The most common adverse event was acute respiratory distress syndrome, reported in seven (8%) patients in each group. Grade 3 adverse events were reported in two (2%) patients in the tocilizumab group and five (6%) patients in the standard care group. There were no grade 4 adverse events. Serious adverse events were reported in 18 (20%) patients in the tocilizumab group and 15 (17%) in the standard care group; 13 (14%) and 15 (17%) patients died during the study. INTERPRETATION: Routine use of tocilizumab in patients admitted to hospital with moderate to severe COVID-19 is not supported. However, post-hoc evidence from this study suggests tocilizumab might still be effective in patients with severe COVID-19 and so should be investigated further in future studies. FUNDING: Medanta Institute of Education and Research, Roche India, Cipla India, and Action COVID-19 India.

Association of Single Nucleotide Polymorphisms in TNFA and IL10 Genes with Disease Severity in Influenza A/H1N1pdm09 Virus Infections: A Study from Western India.

Susceptibility to severe influenza A/H1N1pdm09 virus is multifactorial. The present study was carried out in 246 patients infected with A/H1N1pdm09 virus to find out whether single nucleotide polymorphisms (SNPs) in the genes coding for proinflammatory and anti-inflammatory cytokines are associated with disease severity. Among the cases, 129 had mild disease, whereas 117 had severe disease. There were 27 fatal cases. TNFA rs1800629, IFNG rs2430561, IL10 rs1800872, IL10 rs1800896, and CCL2 rs1024611 SNPs were genotyped by polymerase chain reaction-based methods. A significantly higher frequency of TNFA rs1800629 "G/A" genotype was observed in severe and fatal cases compared with mild and survived cases, respectively. In a dominant mode, IL10 rs1800896 "G" allele was significantly negatively associated with disease severity. IL10 rs1800896 "C/A" genotype was significantly associated with fatality in influenza A/H1N1pdm09 infections. The results suggest that SNPs in the IL10 and TNFA genes might be associated with disease severity in influenza A/H1N1pdm09-infected patients.

Cryptostegia grandiflora Toxicity Manifesting as Hyperkalemia, Complete Heart Block and Thrombocytopenia.

Cardiac glycosides are widely available in botanic products and other naturally occurring substances worldwide. Accidental consumption of it leads to digitalis toxicity with varied systemic manifestations. We describe a case of consumption of extract of leaves of the Indian rubber vine plant (Crytostegia grandiflora) which led to gastrointestinal, cardiac, electrolyte, and hematological disturbances.

Foreign Body in Left Main Bronchus.

Tracheobronchial foreign body (TFB) aspiration is rare in adults, although incidence rates increases with advancing age. We report a case of foreign body in left main bronchus in an adult female who had no risk factor. She was successfully treated with removal of betel nuts by bronchoscopy. Unusual presentation and high index of suspicion can help in proper management.

Mycobacterium avium-intracellulare brain abscess in HIV-positive patient.

Mycobacterial opportunistic infections are a major cause of morbidity and mortality among patients living with HIV (PLHIV) worldwide. Nontuberculous mycobacterial (NTM) infection is one of the leading causes of opportunistic infection in patients with advanced acquired immunodeficiency syndrome i.e., with CD4 count less than 50/cu.mm. Mycobacterium avium complex (MAC) is among the most common opportunistic bacterial infections in those patients with advanced immunodeficiency apart from cryptococcal meningitis, progressive multifocal leukoencephalopathy, etc. Common presentations of mycobacterium avium complex are fever, lymphadenitis and respiratory disease. Immune reconstitution disease is also known to manifest with MAC infections in PLHIV on highly active antiretroviral therapy. Very few cases of central nervous system involvement due to NTM infection have been described. We are reporting a case of advanced acquired immunodeficiency who presented with brain abscess due to Mycobacterium avium intracellulare.

Evan's syndrome in HIV infection.

Haematological complications are common in HIV patients and it can be because of infection per se or secondary to opportunistic infections and antiretroviral therapy. Evan's syndrome, i.e., autoimmune haemolytic anaemia with thrombocytopenia is however a very rare occurrence inspite of high direct Coomb's test positivity in HIV patients. We are reporting one such rare case of Evan's syndrome in HIV patient probably first such reported case from India.

Skeletal muscle involvement in human immunodeficiency virus infection: a report of four cases.

Human immunodeficiency virus (HIV) may affect any part of the neuraxis and may affect skeletal muscle in many ways, ranging from myofiber atrophy in the wasting syndrome to inflammatory muscle disease and a host of opportunistic infections involving muscle. We report here a case series of 4 zidovudine-naοve patients with proven HIV infection with myopathy. One was a case of HIV wasting syndrome, and the three others were diagnosed as HIV polymyositis. Muscle biopsy proved invaluable in the characterization of these cases.

Mortality & clinical characteristics of hospitalized adult patients with HIV in Pune, India.

BACKGROUND & OBJECTIVE: In India, data regarding mortality and clinical characteristics of hospitalized HIV-infected patients are sparse, which may limit the effectiveness of new hospital-based HIV programmes providing antiretroviral therapy (ART). The objective of our study was to determine mortality and clinical characteristics of hospitalized HIV-infected individuals in a high HIV prevalence region of India. METHODS: A retrospective chart review was done of known HIV-infected adults admitted to the Medical Service of a large, public hospital in Pune, India, from January 2002 to November 2003. RESULTS: A total of 655 HIV-infected patients were identified; 489 (74.7%) were male and 4 (0.6%) were on ART. The most common illnesses reported were tuberculosis (55.8%), diarrhoea (4.2%), and alcoholic liver disease (3.7%) . The inpatient mortality was 172 (26.3%). The most common causes of death of the 172 people were tuberculosis (52.9%) and cryptococcal meningitis (7.6%). In multivariate analysis, factors associated with increased mortality were male sex (adjusted odds ratio (AOR) 1.92, 95% CI: 1.08-3.41), haemoglobin level < 7 g/dl (AOR 2.75, 95% CI:1.23-6.14), length of stay < 2 days (OR 5.78, 95%, CI: 1.82-18.4), and cryptococcal meningitis (OR 4.44, 95% CI:1.19-16.6). INTERPRETATION & CONCLUSION: In the era prior to widespread ART, a high inpatient mortality of 26 per cent was found among hospitalized HIV-infected individuals. Thus, while hospitalization is an important access and referral point for HIV care and treatment, earlier identification of HIV-infected persons must occur to ensure they will optimally benefit from the government's ART programme.