A multicentre, double-blind, placebo-controlled randomized trial of Mycobacterium w in critically ill patients with COVID-19 (ARMY-2).

BACKGROUND: Mycobacterium w (Mw), an immunomodulator, resulted in better clinical status in severe coronavirus infectious disease 19 (COVID-19) but no survival benefit in a previous study. Herein, we investigate whether Mw could improve clinical outcomes and survival in COVID-19. MATERIALS AND METHODS: In a multicentric, randomized, double-blind, parallel-group, placebo-controlled trial, we randomized hospitalized subjects with severe COVID-19 to receive either 0.3 mL/day of Mw intradermally or a matching placebo for three consecutive days. The primary outcome was 28-day mortality. The co-primary outcome was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The key secondary outcomes were the change in sequential organ failure assessment (SOFA) score on days 7 and 14 compared to the baseline, treatment-emergent adverse events, and others. RESULTS: We included 273 subjects (136 Mw, 137 placebo). The use of Mw did not improve 28-day survival (Mw vs. placebo, 18 [13.2%] vs. 12 [8.8%], P = 0.259) or the clinical status on days 14 (odds ratio [OR], 1.33; 95% confidence intervals [CI], 0.79-2.3), 21 (OR, 1.49; 95% CI, 0.83-2.7) or 28 (OR, 1.49; 95% CI, 0.79-2.8) between the two study arms. There was no difference in the delta SOFA score or other secondary outcomes between the two groups. We observed higher injection site reactions with Mw. CONCLUSION: Mw did not reduce 28-day mortality or improve clinical status on days 14, 21 and 28 compared to placebo in patients with severe COVID-19. [Trial identifier: CTRI/2020/04/024846].

Eternal Hunt: Unravelling the Challenge of CRE, the Quest for Perfection Continues!

How to cite this article: Salotagi S, Kannan A, Jindal A. Eternal Hunt: Unravelling the Challenge of CRE, the Quest for Perfection Continues! Indian J Crit Care Med 2024;28(5):513-514.

Methylene Blue in Septic Shock-A Novel Weapon in Our Arsenal: Are Utility Studies Highlighting its Futility?

How to cite this article: Angadi VM, Jindal A. Methylene Blue in Septic Shock-A Novel Weapon in Our Arsenal: Are Utility Studies Highlighting its Futility? Indian J Crit Care Med 2024;28(1):89.

To C or not to C? Designing a Pragmatic Trial to Deploy a Novel Immunomodulatory Therapy to Fight Organ Dysfunction in Sepsis.

Angadi VM, Jindal A. To C or not to C? Designing a Pragmatic Trial to Deploy a Novel Immunomodulatory Therapy to Fight Organ Dysfunction in Sepsis. Indian J Crit Care Med 2024;28(3):311.

Lung Ultrasound Score: Does It Really Predict Extubation Failure?

How to cite this article: Salotagi S, Kannan A, Jindal A. Lung Ultrasound Score: Does It Really Predict Extubation Failure? Indian J Crit Care Med 2023;27(11):855-856.

Faecal calprotectin as an inflammatory biomarker to distinguish between bacterial and viral causes of childhood diarrhoea in Indian settings.

OBJECTIVES: The purpose of this study was to determine the value of faecal calprotectin (f-CP) in distinguishing between bacterial and viral aetiologies of infective diarrhoea in children attending a tertiary care hospital in Central India. METHODS: Stool samples from children aged 3 months to 10 years who had acute or persistent diarrhoea were processed for microscopy, bacterial culture, and viral antigen detection (Rotavirus and Norovirus). The remaining samples, as well as stool samples from 20 healthy controls, were tested for f-CP using the enzyme linked immunosorbent assay. RESULTS: Among 48 patients, 21 (43.7%) had bacterial diarrhoea, 14 (29.2%) had viral diarrhoea, and 13 (27.1%) had an unidentified aetiology. The median f-CP values were significantly (p â€‹= â€‹0.004) higher in children with bacterial diarrhoea (75.2 â€‹µg/g; IQR-18.75-239.15) than in children with viral diarrhoea (75.2 â€‹µg/g; IQR-123.5-1987.5). Bacterial aetiology could be reliably predicted at the optimum f-CP concentrations of >541 â€‹µg/g and >238.4 â€‹µg/g in children aged 1 and 1-4 years, with an area under the curve of 0.767 and 0.867, respectively, using receiver-operator characteristic analysis. CONCLUSIONS: Faecal calprotectin could reliably distinguish between bacterial and viral aetiologies of diarrhoea in children aged up to four years, but at relatively higher age-specified cut off values.

Profile and predictors of babies admitted to SNCUs of two tribal districts of Chhattisgarh.

Background: The neonatal period is the crucial and vulnerable period of the human life cycle. Various research has been conducted worldwide that provide the baseline data on clinical profiles and predictors of outcomes of babies admitted to sick newborn care units (SNCUs). Nonetheless, studies on tribal areas and community outreach areas are rare. In the present study, predictors and profiles of patients admitted to SNCU, in the Dantewada and Bijapur districts of Chhattisgarh, India, were evaluated which shall help prioritize patient care and preventive approaches. Methods: This retrospective study was undertaken from January 2019 to December 2020 in the SNCUs of Dantewada and Bijapur. Neonatal and maternal characteristics, course during labor, treatment given to the neonates, and outcome data were obtained and analysed. Results: In total, 1,531 neonates were enrolled in the study. Mothers had a mean age of 25.6 years (standard deviation [SD] ±4.9) with birth spacing less than 2 years (60.3%) and antenatal care (ANC) visits less than 4 (50.4%). Neonates were low birth weight (43.75%) and were home-delivered (15.8%). One hundred forty-nine neonates died. In the multivariate regression model, extremely low birth weight babies, less than 1 kg (odds ratio [OR]: 11.59 confidence interval [CI] 4.625-31.58), gestational age less than 34 weeks (OR: 2.13 CI 1.291-3.532), central cyanosis (OR: 10.40 CI: 3.269-32.35), duration of IV fluid > 3 days (OR: 2.16 CI 0.793-0.880), duration of antibiotic >3 days (OR 0.63 CI 0.408-0.979) were found to be independent predictors of mortality among neonates. Conclusion: The prevalence of newborns aged less than 12 h is higher among the study population. Birth asphyxia, prematurity, neonatal jaundice, and sepsis were fundamental and leading causes of morbidity. Preterm birth and low birth weight babies had significantly high mortality. The government needs to focus on marginalized communities with target-based interventions and policies.

Normal Anion Gap: A Knowledge Gap.

We studied with great interest the article titled "Acute diarrhea and severe dehydration in children: Does non-anion gap component of severe metabolic acidemia need more attention?" by Takia L et al. and would express our views about the same. Normal anion gap metabolic acidosis (NAGMA) is a common entity following stool loss of bicarbonate during an acute diarrheal illness. Several studies have shown that there is a higher incidence of hyperchloremic acidosis and acute kidney injury (AKI) with normal saline (NS) when compared to balanced crystalloids like Ringer's lactate (RL) or balanced salt solutions like plasmalyte. We would like to know about the type of resuscitation fluid used in the study population as it would affect the degree of resolution of acidemia. As per the World Health Organization (WHO) guidelines, rehydration therapy for children with severe acute malnutrition (SAM) is different from other children including the fluid used for bolus, i.e., RL and oral rehydration solution (ORS), i.e., rehydration solution for malnourished (ReSoMal). We would like to know if the study population included SAM children and a subgroup analysis of the same was done as SAM is an independent risk factor for mortality and morbidity. We suggest to plan studies on cognitive outcome of these children. How to cite this article: Pratyusha K, Jindal A. Normal Anion Gap: A Knowledge Gap. Indian J Crit Care Med 2023;27(4):298.

A Curious Case of an Accented Extra Nose.

There have been about 60 cases of supernumerary nostril reported. We encountered a 38 weeker, male child with supernumerary nostril and midline congenital nevus which was later locally excised. The uniqueness of our case is the presence of an entirely well-formed nostril perched on top on the normal nose.

Effect of the Angiotensin-Converting Enzyme (ACE) (I/D) Polymorphism in COVID-19 Patients and Their Healthy Contacts.

Introduction The quest to understand the pathophysiology behind the deleterious effects of the coronavirus disease 2019 (COVID-19) outbreak took a turn when involvement of the angiotensin converting enzyme (ACE) receptors in different organs, especially the lungs, could explain all the clinical manifestations and adverse events in patients. The I/D polymorphism in the ACE gene, having been attributed in various studies, was also seen to have an effect in this pandemic. Present study aimed to analyze the effect of this I/D mutation in COVID-19 patients and in their healthy contacts. Methods Patients with past history of COVID-19 infection and their healthy contacts were enrolled in the study after obtaining ethical clearance and informed consent. The polymorphism was studied by real-time polymerase chain reaction (PCR). Data was analyzed in SPSS version 20 (IBM Corp., Armonk, NY, USA). p value less than 0.05 was taken as significant. Results The allelic distribution followed the Hardy-Weinberg equilibrium, with the wild 'D' allele being dominant in the population. Between the case and controls, the mutant 'I' allele was observed more in the controls, and the association was statistically significant. Conclusion From the results of the present study, it could be concluded that while the wild 'D' allele led to higher chances of being affected with COVID-19, the polymorphism to 'I' allele was relatively protective in nature.

Non-invasive Ventilation Failure - Predict and Protect.

Modified heart rate, acidosis, consciousness, oxygenation and respiratory rate (HACOR) score takes into consideration pneumonia, cardiogenic pulmonary edema, pulmonary acute respiratory distress syndrome (ARDS), immunosuppression, septic shock, and the sequential organ failure assessment (SOFA) score prior to non-invasive mechanical ventilation (NIV) that would impact the success of NIV and are commonly seen in patients presenting to the emergency. Propensity score matching could have been done for similar distribution of baseline characteristics. Specific objective criteria are needed to define respiratory failure requiring intubation. How to cite this article: Pratyusha K, Jindal A. Non-invasive Ventilation Failure - Predict and Protect. Indian J Crit Care Med 2023;27(2):149.

Paroxysmal Sympathetic Hypertension: An Underdiagnosed Entity or a Diagnostic Difficulty?

How to cite this article: Pratyusha K, Jindal A. Paroxysmal Sympathetic Hypertension: An Underdiagnosed Entity or a Diagnostic Difficulty? Indian J Crit Care Med 2023;27(2):151.

Predisposition, Insult, Response, and Organ Dysfunction: A Well-constructed Score!

How to cite this article: Kannan A, Jindal A. Predisposition, Insult, Response, and Organ Dysfunction: A Well-constructed Score! Indian J Crit Care Med 2023;27(2):150.

Coronavirus-19 and its Epidemiology in Children - An Ambispective Observational Study from Central India.

This ambispective observational study, was conducted at a tertiary care centre in Central India. Children aged <16 y who tested positive for SARS-CoV2 between 1st April 2020 to 30th April 2022 were included. The prevalence of coronavirus disease-19 (COVID-19) infection was 1.2%. Of 525 children, median age was 60 mo; 88 (16.7%) were infants. Comorbidities were noted in 89 (16.9%) children. About 59% (n=309) were asymptomatic. Among symptomatic (n=216) children, fever (57.9%) was the most common symptom followed by cough (37%), running nose (21.3%) and shortness of breath (13.9%). Forty-three (8.2%) children required pediatric intensive care unit (PICU) admission, among which 21 required invasive ventilation. Patients with comorbidities were independently associated with need for invasive mechanical ventilation. Among PICU admitted children, 20 patients died. In multivariate logistic regression, children presenting with fever, shortness of breath and vasoactive requirement were found to be significantly associated with mortality. As the number of waves progressed, number of admissions were less but severity, association with comorbidities, need of ICU, mechanical ventilation and death rate increased.

Predictors of Mortality among Patients Hospitalized with COVID-19 during the First Wave in India: A Multisite Case-Control Study.

Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused more than 6 million deaths globally. Understanding predictors of mortality will help in prioritizing patient care and preventive approaches. This was a multicentric, unmatched, hospital-based case-control study conducted in nine teaching hospitals in India. Cases were microbiologically confirmed COVID-19 patients who died in the hospital during the period of study and controls were microbiologically confirmed COVID-19 patients who were discharged from the same hospital after recovery. Cases were recruited sequentially from March 2020 until December-March 2021. All information regarding cases and controls was extracted retrospectively from the medical records of patients by trained physicians. Univariable and multivariable logistic regression was done to assess the association between various predictor variables and deaths due to COVID-19. A total of 2,431 patients (1,137 cases and 1,294 controls) were included in the study. The mean age of patients was 52.8 years (SD: 16.5 years), and 32.1% were females. Breathlessness was the most common symptom at the time of admission (53.2%). Increasing age (adjusted odds ratio [aOR]: 46-59 years, 3.4 [95% CI: 1.5-7.7]; 60-74 years, 4.1 [95% CI: 1.7-9.5]; and ≥ 75 years, 11.0 [95% CI: 4.0-30.6]); preexisting diabetes mellitus (aOR: 1.9 [95% CI: 1.2-2.9]); malignancy (aOR: 3.1 [95% CI: 1.3-7.8]); pulmonary tuberculosis (aOR: 3.3 [95% CI: 1.2-8.8]); breathlessness at the time of admission (aOR: 2.2 [95% CI: 1.4-3.5]); high quick Sequential Organ Failure Assessment score at the time of admission (aOR: 5.6 [95% CI: 2.7-11.4]); and oxygen saturation < 94% at the time of admission (aOR: 2.5 [95% CI: 1.6-3.9]) were associated with mortality due to COVID-19. These results can be used to prioritize patients who are at increased risk of death and to rationalize therapy to reduce mortality due to COVID-19.

Serial Ultrasonographic-measurement of Gastric Residual Volume in Critically Ill Patients for Prediction of Gastric Tube Feed Intolerance: Views.

How to cite this article: Pratyusha K, Jindal A. Serial Ultrasonographic-measurement of Gastric Residual Volume in Critically Ill Patients for Prediction of Gastric Tube Feed Intolerance: Views. Indian J Crit Care Med 2023;27(1):79.

COVID-19 and T Cells: Do T Cells Really Matter?

How to cite this article: Gajjala C, Jindal, A. COVID-19 and T Cells: Do T Cells Really Matter? Indian J Crit Care Med 2023;27(1):75.