AST/ALT Ratio as an indicator of functional severity in chronic heart failure with reduced left ventricular ejection fraction: A prospective cross-sectional study.

OBJECTIVE: The study was carried out to evaluate the role of the AST (Aspartate transaminase)/ALT (Alanine transaminase) ratio as an indicator of the functional severity in people with chronic heart failure (CHF) with reduced left ventricular ejection fraction. METHODS: A prospective cross-sectional study was conducted in a tertiary care centre in South India among the individuals who had left ventricular ejection fraction (LVEF) of ≤40 %. The study period was between January 2021 and December 2021. Consecutive patients with the criteria were enrolled in the study. Study participants were grouped based on their AST/ALT ratio value (ratio<1 and ratio≥1). RESULTS: In present study of 100 participants, there was a statistically significant difference between two groups with respect to ALT, AST/ALT ratio, and ALP (Alkaline phosphatase). There was a significant correlation between the APRI (AST to platelet ratio index) and FIB-4 (Fibrosis-4) with AST/ALT ratio. Diagnostic analysis of AST/ALT ratio to predict the severity of CHF with reduced EF, the area under the curve (AUC) was 0.547 (p-value = 0.5654) with a 95 % confidence interval of 0.299-0.795 with an optimal cut-off value of 0.6, sensitivity of 96.70 %, and specificity of 33.33 %. CONCLUSION: The AST/ALT ratio is increased in patients with CHF patients with reduced left ventricular ejection fraction. It is a simple predictor of left ventricular dysfunction in patients with heart failure with reduced ejection fraction.

Safety of low dose efavirenz regimen in Indian adults with HIV-1 infection: Insights from a phase 4 interventional randomised trial.

BACKGROUND: A randomized interventional phase 4 study in the Indian population confirmed the non-inferiority of the combination tenofovir/lamivudine/efavirenz (TLE)-400 to TLE600. The current manuscript describes in detail the safety profile and patient-reported safety outcomes obtained from the phase 4 study. METHODS: This investigation was part of a phase 4 non-inferiority study with a blinded assessment, conducted across 17 sites in India. The duration of the study was 24 weeks. Safety endpoints assessed included all the adverse events (AEs) related to the study treatment (TLE400 and TLE600). The depression anxiety stress 21-item scale questionnaire and efavirenz-related symptom questionnaire were also used to measure depression, anxiety, stress, and patient experience. RESULTS: A total of 68 patients (52.3%) reported 261 AEs and 87 patients (64.9%) reported 379 AEs related to study treatment in TLE400 group and TLE600 group respectively, P = .037. The reported AEs associated with central nervous system disorders were lower in the TLE400 group with 41 patients (31.5%) to 61 patients (45.5%) in the TLE600 group. The change from mean baseline value for depression anxiety stress 21-item scale at week 28 in TLE400 group and TLE600 group was -5.1 and -6.2 respectively. Similarly, the mean change from baseline score of efavirenz-related symptoms at week 28 in TLE400 group and TLE600 group were -5.1 and -4.1 respectively. CONCLUSION: The low dose efavirenz (400 mg) in combination with tenofovir and lamivudine had a better safety and tolerability profile than the standard dose of efavirenz (600 mg) in combination with tenofovir and lamivudine. Thus, low dose efavirenz should be preferred over the standard dose.

Study of Phospholipase A2 Levels and Its Comparison With Procalcitonin Levels in Patients With Sepsis Admitted in a Tertiary Care Hospital, Karnataka, India.

INTRODUCTION: Sepsis is a complicated host response to infection involving organ failure which ultimately causes death of the host. Procalcitonin (PCT) is an effective marker used to diagnose sepsis but until now, there has been no ideal marker for sepsis. Phospholipase A2 (PLA2) also increases infections; however, only a few studies have assessed its capacity as a biomarker to diagnose sepsis. Thus, we aimed to examine PLA2 and compare its diagnostic capacity and accuracy with PCT as a biomarker of sepsis. MATERIAL AND METHODS: Our study was a hospital-oriented cross-sectional study. Our study group included 80 patients of both sexes older than 18 years, meeting the quick sequential organ failure assessment (qSOFA) or systemic inflammatory response syndrome (SIRS) criteria of ≥2, hospitalized in a tertiary care hospital in Karnataka, India from January 2021 to December 2021. Out of them, 59 were found to have sepsis. Samples of all the patients were evaluated for relevant parameters, and data were statistically analyzed using SPSS v21 running on Windows 10. The statistical significance was set at p-value <0.05. RESULTS: The mean PCT and PLA2 were significantly raised in sepsis patients compared to non-sepsis patients. Out of 59 septic patients, 45.76% had positive blood cultures, and 16.95% had positive urine culture reports. In blood cultures, the most common Gram-positive organism found was Staphylococcus, and the most common Gram-negative organism was Enterobacter. In urine cultures, Escherichia coli was the most common species. PLA2 was significantly higher in patients with bacterial etiology and Gram-positive cultures. The diagnostic capability, sensitivity, specificity, and accuracy of PLA2 were demonstrably higher than those of PCT. CONCLUSION: Our study proves that PLA2 is a much better and more efficient biomarker in sepsis than PCT. The diagnostic capacity and accuracy of PLA2 clearly surpass PCT, so using PLA2 in sepsis as a biomarker can help clinicians in deciding on timely and appropriate management to speed the recovery of patients.

Efficacy and safety of 400 mg efavirenz versus standard 600 mg dose when taken with tenofovir and lamivudine combination in Indian adult patients with HIV-1 infection: An open-label, interventional, randomized, non-inferiority trial.

BACKGROUND: To evaluate the non-inferiority of low dose efavirenz (400 mg) to standard dose efavirenz (600 mg), when taken in combination with tenofovir and lamivudine in Indian patients with HIV-1 infection. METHODS: An open-label, interventional phase IV study with blinded assessment was conducted across 17 sites in India. HIV-1-infected antiretroviral therapy-naive adult patients (≥18 years of age) with a plasma HIV-1 viral load of at least 1000 copies per mL were randomized to receive either tenofovir/lamivudine/efavirenz (TLE) 400 or TLE 600. The primary endpoint was the difference in the proportion of patients achieving < 200 copies per mL at the end of 24 weeks. RESULTS: A total of 265 patients were enrolled and were randomized in 1:1 ratio to TLE 400 group (130 patients) and TLE 600 group (135 patients). At week 24, the proportion of patients with a viral load of less than 200 copies per mL was 80.70% for TLE 400 and 78.95% for TLE 600 (difference 1.75%, 90% confidence interval: -7.01, 10.49) which was within the predefined margin of -10% (90% confidence interval). Significantly lower study drug-related adverse events were observed in TLE 400 group compared to TLE 600 group (52.30%, n = 68 vs 64.92%, n = 87; P = .037). The treatment discontinuation percentage was marginally higher by 2.08% in TLE 600 group. CONCLUSION: The fixed-dose combination of TLE 400 is non-inferior to TLE 600 in terms of viral suppression and has an improved safety profile over 24 weeks in adult Indian patients with HIV-1 infection.

A Phase IV Study on Safety, Tolerability and Efficacy of Dolutegravir, Lamivudine, and Tenofovir Disoproxil Fumarate in Treatment Naïve Adult Indian Patients Living with HIV-1.

Purpose: WHO recommends dolutegravir (DTG) based regimens as first-line treatment for HIV-1 infection. However, few studies have been conducted in Indian population. Hence, our study evaluated the safety, tolerability, and efficacy of DTG 50 mg with Tenofovir and Lamivudine (300/300mg) fixed dose combination in treatment naïve adult Indian patients. Methods: This was an open label, multicenter, prospective, interventional, phase IV study conducted across 14 sites between February 2019 and July 2020. 24 weeks was the treatment duration for each subject. The primary end point was to assess the incidence of adverse events (AEs) and secondary end points were to assess the proportion of patients achieving plasma HIV-1 RNA levels <50 copies/mL at week 24 and change in CD4+ cell count from the baseline. Safety analysis was conducted using Safety Analysis Set and efficacy analysis was carried out using Full Analysis Set and Per protocol set. Results: A total of 288 patients were screened; 250 were enrolled; and 229 completed the study. 389 AEs were reported from 58% of patients. Of these, 61 were related to study treatment. One event of decreased creatinine clearance led to study discontinuation. One serious event of pyrexia was reported, which was unrelated to the study drug. The most common AEs were headache (18%), pyrexia (14%), vomiting (6.4%) and upper respiratory tract infections (6%). No deaths were reported. At week 24, 86.8% of the patients achieved plasma HIV-1 RNA levels <50 copies/mL and the mean CD4 cell count increased from 350.2 (SD, 239.73) at baseline to 494.6 (SD, 261.40) with an average increase of 143.2 (SD, 226.14) cells. Conclusion: This study demonstrated the safety and efficacy of DTG based regimen in treatment naïve HIV-1 patients in Indian population and support use of DTG as first-line treatment regimen.

Comparative Study of Sofa, Apache Ii, Saps Ii, as a Predictor of Mortality in Patients of Sepsis Admitted in Medical ICU.

Sepsis is a life-threatening organ dysfunction with high mortality and morbidity. Various mortality prediction scores are currently in use for prediction of mortality. Although combination of various scores have not been used before. The aim of the study was to compare SOFA, APACHE II, SAPS II, as a predictor of mortality and to assess the usefulness of combination of different scores. MATERIAL: A one-year hospital based prospective study conducted from 1st January 2020 to 31st December 2020 in medical ICU, where 100 patients of sepsis admitted in ICU with evidence of organ dysfunction were included in the study and various scores like SOFA, APACHE II, and SAPS II were calculated at 24 and 48 hours of admission, using laboratory results and clinical examination. and an attempt to access for predictive accuracy of combination of scores was undertaken. OBSERVATION: Majority of the patients (37%) were in the age group of 60-79 years with maximum mortality in this age group of (39.22 %). Mortality rate was 51%, with higher mortality in the female group being 68.63%. Diabetes was most common comorbid in our study (41%). No significant difference was observed in physiological variable over 24 and 48 hours, however decrease in WBC and platelet count was noted at the end of 48 hours; Mean SOFA, APACHE II, SAPS II were significantly higher in the mortality group than the recovery group; All three scores had good diagnostic performance, with max sensitivity at 24 and 48 hours with APACHE II being 64.10% and 78.79% respectively, max specificity at 24 and 48 hours was noticed with SAPS II being 96.97% and 87.88% respectively. On further combination of scores, maximum sensitivity was seen with SOFA plus APACHE II at 48 hours of 74.36%, maximum specificity was seen at 24 hours with SOFA plus SAPS II of 93.94%. Upon application of Youden's index to the combination of scores, best diagnostic performance was seen with SOFA plus SAPS II at 48 hours. CONCLUSION: All the three scores showed good mortality prediction rate but among the scores higher sensitivity was seen with APACHE II score at 24 and 48 hours and higher specificity was seen with SAPS II at 24 and 48 hours. Combination of scores did show a slightly better predictability with combination of SAPS II and SOFA showing maximum Youden's index at 48 hours. Mortality was comparatively higher among the females and elderly group with most common risk factor being diabetes.

Coxsackie Myocarditis with Severe Methicillin-resistant Staphylococcus aureus Sepsis, Multi-organ Dysfunction Syndrome, and Posterior Epidural Spinal Abscess: A Case Report.

AIM: The aim of this paper is to present an interesting case of viral myocarditis complicated by sepsis, its sequelae, including multi-organ dysfunction syndrome, and the approach to manage it successfully. BACKGROUND: Viral myocarditis is an inflammatory disease of myocardium, often leading to residual heart disease. Commonly, dengue and Coxsackie B viruses are the causative agents. Patients usually present with dyspnea, fever, and signs of heart failure. A possibility of bacterial sepsis should not be overlooked, given similar presentations may occur. CASE DESCRIPTION: A 21-year-old male presented with acute onset breathlessness, fever, chills, and severe neck pain. On a detailed workup, he was found to have features suggestive of viral myocarditis, bacterial sepsis, with bilateral pleural loculations, a posterior epidural spinal abscess. Elimination of infectious foci, along with a decision to stick to the ongoing antibiotics, instead of stepping up to the last available ones proved beneficial. Meticulous balance of diuretics and inotropes saved the patient's life from what turned out to be coxsackie myocarditis. CONCLUSION: Here, we present the case of a young male who came in with congestive heart failure due to Coxsackie myocarditis and his condition complicated by severe sepsis. CLINICAL SIGNIFICANCE: Up to 10% of the cases of coxsackie myocarditis progress to chronic dilated cardiomyopathy. The management is usually conservative, and antiviral agents have shown no role in speedy recovery. Elimination of infectious foci aggressively is of prime importance in the treatment of bacterial sepsis. A careful balance of inotropes, diuretics, and fluid management is needed to get the patient into remission in such cases. HOW TO CITE THIS ARTICLE: Morkar DN, Agarwal R, Patil RS. Coxsackie Myocarditis with Severe Methicillin-resistant Staphylococcus aureus Sepsis, Multi-organ Dysfunction Syndrome, and Posterior Epidural Spinal Abscess: A Case Report. Indian J Crit Care Med 2020;24(1):73-76.