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].

Right Atrial Strain in Pediatric Pulmonary Hypertension-A Prospective Observational Study.

Right ventricular (RV) afterload due to elevated pulmonary arterial (PA) pressure in pulmonary hypertension (PH) causes long-term right atrial (RA) remodeling and dysfunction. RA function has been shown to correlate with PA pressures and outcome in both adult and pediatric patients with PH. We studied the role of RA strain in estimating PA pressures in congenital heart disease (CHD)-associated PH. Children below 12 years undergoing elective repair of CHD with left-to-right shunts and echocardiographic evidence of PH were included. RA reservoir, conduit and contractile strain along with conventional measures of RV function and PA pressure were measured using transthoracic echocardiography after induction of anaesthesia. Pre-and post-repair invasive PA pressures were measured after surgical exposure. 51 children with a median age of 24 months (range 4-144 months) were included, most of whom were undergoing VSD closure. Contractile RA strain showed good correlation with pre-repair systolic PA pressure in mmHg (r = 0.59, 95%CI 0.37-0.75) or expressed as a percentage of SBP (r = 0.67, 95%CI 0.49-0.80). It also predicted persistent postoperative PH as well as pre-repair pulmonary artery acceleration time and right ventricular systolic pressure measured from tricuspid regurgitation jet. The trends of correlation observed suggest a possible prognostic role of RA strain in ACHD with PH and potential utility in its echocardiographic assessment. The observed findings merit deeper evaluation in larger cohorts.

Therapeutic high-dose vitamin D for vitamin D-deficient severe COVID-19 disease: randomized, double-blind, placebo-controlled study (SHADE-S).

BACKGROUND: efficacy of therapeutic cholecalciferol supplementation for severe COVID-19 is sparingly studied. OBJECTIVE: effect of single high-dose cholecalciferol supplementation on sequential organ failure assessment (SOFA) score in moderate-to-severe COVID-19. METHODS: participants with moderate to severe COVID-19 with PaO2/FiO2 ratio < 200 were randomized to 0.6 million IU cholecalciferol oral (intervention) or placebo. OUTCOMES: primary outcome was change in Day 7 SOFA score and pre-specified secondary outcomes were SOFA and 28-day all-cause mortality. RESULTS: in all, 90 patients (45 each group) were included for intention-to-treat analysis. 25(OH)D3 levels were 12 (10-16) and 13 (12-18) ng/ml (P = 0.06) at baseline; and 60 (55-65) ng/ml and 4 (1-7) ng/ml by Day 7 in vitamin D and placebo groups, respectively. The SOFA score on Day 7 was better in the vitamin D group [3 (95% CI, 2-5) versus 5 (95% CI, 3-7), P = 0.01, intergroup difference - 2 (95% CI, -4 to -0.01); r = 0.4]. A lower all-cause 28-day mortality [24% compared to 44% (P = 0.046)] was observed with vitamin D. CONCLUSIONS: single high-dose oral cholecalciferol supplementation on ICU admission can improve SOFA score at Day 7 and reduce in-hospital mortality in vitamin D-deficient COVID-19. ClinicalTrials.gov  id: NCT04952857 registered dated 7 July 2021. What is already known on this topic-vitamin D has immunomodulatory role. Observational and isolated intervention studies show some benefit in COVID-19. Targeted therapeutic vitamin D supplementation improve outcomes in severe COVID-19 is not studied in RCTs. What this study adds-high-dose vitamin D supplementation (0.6 Million IU) to increase 25(OH)D > 50 ng/ml is safe and reduces sequential organ failure assessment score, in-hospital mortality in moderate to severe COVID-19. How this study might affect research, practice or policy-vitamin D supplementation in vitamin D-deficient patients with severe COVID-19 is useful may be practiced.

Analysis of Predictors and Outcomes of COVID-19 Patients Requiring ICU Admission from COVID-19 Registry, India.

Background: Patients admitted to intensive care units (ICUs) with severe coronavirus disease (COVID-19) are associated with high mortality. The present retrospective, multicenter study describes the predictors and outcomes of COVID-19 patients requiring ICU admission from COVID-19 Registry of Indian Council of Medical Research (ICMR), India. Materials and methods: Prospectively collected data from participating institutions were entered into the electronic National Clinical Registry of COVID-19. We enrolled patients aged >18 years with COVID-19 pneumonia requiring ICU admission between March 2020 and August 2021. Exclusion criteria were negative in RT-PCR report, death within 24 hours of ICU admission, or incomplete data. Their demographic and laboratory variables, ICU severity indices, treatment strategies, and outcomes were analyzed. Results: A total of 5,865 patients were enrolled. Overall mortality was 43.2%. Non-survivors were older (58.2 ± 15.4 vs 53.6 ± 14.7 years; p = 0.001), had multiple comorbidities (33.2% vs 29.5%, p = 0.001), had higher median D-dimer (1.56 vs 1.37, p = 0.015), higher CT severity index (16.8 ± 5.2 vs 13.5 ± 5.47, p = 0.001) and longer median hospital stay (10 vs 8 days, p = 0.001) and ICU stay (5 vs 4 days, p = 0.001), compared with survivors.On multivariate analysis, high CRP (HR 1.008, 95% CI: 1.006-1.010, p = 0.001) and high D-dimer (HR 1.089, 95% CI: 1.065-1.113, p < 0.001) were associated with invasive mechanical ventilation while older age (HR 1.19, CI: 1.001-1.038, p = 0.039) and high D-dimer (HR-1.121, CI: 1.072-1.172, p = 0.001) were independently associated with mortality and while the use of prophylactic low molecular weight heparin (LMWH) (HR 0.647, CI: 0.527-0.794, p = 0.001) lowered mortality. Conclusion: Among 5,865 COVID-19 patients admitted to ICU, mortality was 43.5%. High CRP and D-dimers were independently associated with the need for invasive mechanical ventilation while older age and high D-dimer were associated with higher mortality. The use of prophylactic LMWH independently reduced mortality. How to cite this article: Kajal K, Singla K, Puri GD, Bhalla A, Mukherjee A, Kumar G, et al. Analysis of Predictors and Outcomes of COVID-19 Patients Requiring ICU Admission from COVID-19 Registry, India. Indian J Crit Care Med 2023;27(8):552-562.

Clinicoradiological Profile of COVID-19-Associated Rhino-Orbital Cerebral Mucormycosis with a Focus on Computed Tomography: A Clinical Case Series and Review.

COVID-19-associated rhino-orbital cerebral mucormycosis (ROCM) has a rapidly evolving course with high morbidity and mortality. We describe imaging features of COVID-19-associated ROCM based on noncontrast computed tomography (NCCT). This retrospective single-center observational study included 50 patients with COVID-19 from January 1, 2021 to June 30, 2021 who subsequently developed ROCM confirmed by fungal culture studies. All patients underwent NCCT of the paranasal sinuses as the diagnostic workup. The involvement of the nasal cavity, paranasal sinuses, orbits, and intracranial cavity was identified and graded. The ethmoid sinuses were most commonly involved [right (n = 46 of 50) > left (n = 45 of 50)], followed by the maxillary, sphenoid, and frontal sinuses. Thinning and erosions of the hard palate were noted in 18% of patients (n = 9), whereas 34% (n = 17) showed dehiscence of the lamina papyracea. Retromaxillary fat stranding was noted in 68% of patients (n = 34). Severe ethmoid sinusitis was associated significantly with ipsilateral pterygopalatine fossa involvement. The extraocular muscles were involved in 64% of patients (n = 32), with 84% (n = 42) showing orbital fat stranding. Proptosis of the affected eye was seen in 66% of patients, optic nerve involvement in 52%, and irregularity of globe contour in 12% (n = 6). The cavernous sinuses were affected in 10% of patients (n = 5), with three of them having temporal infarcts. COVID-19-associated ROCM is an acute, invasive fungal disease characterized by multisinus involvement, often with orbital and intracranial extension. Bilateral involvement with rapid progression should alert one to underlying COVID-19 disease.

Ultrasonic prediction of weaning failure in children undergoing cardiac surgery: A prospective observational study.

Background and Aim: To assess the utility of ultrasonic markers like B-line score (LUS), diaphragm thickness (DT), thickening fraction (DTF), and excursion (DE) as predictors of weaning outcomes in children on mechanical ventilation (MV) after cardiac surgery. Methods: This was a prospective observational study done in postcardiac surgical intensive care unit (ICU) of a tertiary care hospital. Children aged 1 month to 18 years, on MV after cardiac surgery from January to November 2017, were included. They were extubated after satisfying institutional weaning criteria. Ultrasound for LUS, DT, DTF, and DE was performed preoperatively, during pressure support ventilation (PSV) before extubation and 4 h after extubation. Results: Patients were divided into weaning failure and success groups based on reintubation within 48 h of extubation. Of the 50 evaluated patients, 43 (86%) were weaned successfully and 7 (14%) had weaning failure. The left DTF during PSV was lower in patients weaning failure (0.00%, interquartile range (IQR) 0.00-14.28 vs 16.67%, IQR 8.33-22.20, P = 0. 012). The left DTF≤ 14.64% during PSV (area under receiver's operating curve 0.795, P = 0.014), 85% sensitivity, and 57% specificity (positive likelihood ratio 1.97, negative likelihood ratio 0.25) could predict weaning failure. Conclusion: The left DTF during PSV is a good predictor of weaning failure in children on MV in postoperative ICU after congenital cardiac surgery. Take home message: In children on mechanical ventilation after cardiac surgery, left DTF during pressure support ventilation is a good predictor of weaning failure.

Risk factors for clinically significant diffuse parenchymal lung abnormalities persisting after severe COVID-19 pneumonia.

Background & objectives: The risk factors for clinically significant diffuse parenchymal lung abnormalities (CS-DPLA) persisting after severe coronavirus disease 2019 (COVID-19) pneumonia remain unclear. The present study was conducted to assess whether COVID-19 severity and other parameters are associated with CS-DPLA. Methods: The study participants included patients who recovered after acute severe COVID-19 and presented with CS-DPLA at two or six month follow up and control group (without CS-DPLA). Adults volunteers without any acute illness, chronic respiratory illness and without a history of severe COVID-19 were included as healthy controls for the biomarker study. The CS-DPLA was identified as a multidimensional entity involving clinical, radiological and physiological pulmonary abnormalities. The primary exposure was the neutrophil-lymphocyte ratio (NLR). Recorded confounders included age, sex, peak lactate dehydrogenase (LDH), advanced respiratory support (ARS), length of hospital stay (LOS) and others; associations were analyzed using logistic regression. The baseline serum levels of surfactant protein D, cancer antigen 15-3 and transforming growth factor-ß (TGF-ß) were also compared among cases, controls and healthy volunteers. Results: We identified 91/160 (56.9%) and 42/144 (29.2%) participants with CS-DPLA at two and six months, respectively. Univariate analyses revealed associations of NLR, peak LDH, ARS and LOS with CS-DPLA at two months and of NLR and LOS at six months. The NLR was not independently associated with CS-DPLA at either visit. Only LOS independently predicted CS-DPLA at two months [adjusted odds ratios (aOR) (95% confidence interval [CI]), 1.16 (1.07-1.25); P<0.001] and six months [aOR (95% CI) and 1.07 (1.01-1.12); P=0.01]. Participants with CS-DPLA at six months had higher baseline serum TGF-ß levels than healthy volunteers. Interpretation and conclusions: Longer hospital stay was observed to be the only independent predictor of CS-DPLA six months after severe COVID-19. Serum TGF-ß should be evaluated further as a biomarker.

Utility of portal vein pulsatility fraction in patients undergoing corrective surgery for tetralogy of Fallot.

BACKGROUND: Right ventricle dysfunction is common after corrective surgery for tetralogy of Fallot and is associated with significant morbidity and mortality. We aimed to determine whether an increased portal vein pulsatility fraction (PVPF) was associated with worse clinical outcomes. METHODS: In a prospective, observational, single-centre study, PVPF and other commonly used parameters of right ventricle function were assessed in patients of all ages undergoing corrective surgery for tetralogy of Fallot intraoperatively, with transesophageal echocardiography, before and after bypass, and post-operatively, with transthoracic echocardiography, at days 1, 2, at extubation, and at ICU discharge. The correlation was tested between PVPF and mechanical ventilation duration, prolonged ICU stay, mortality, and right ventricle function. RESULTS: The study included 52 patients, and mortality was in 3 patients. PVPF measurement was feasible in 96% of the examinations. PVPF in the immediate post-operative period had sensitivity of 73.3% and a specificity of 74.3% in predicting the occurrence of the composite outcome of prolonged mechanical ventilation, ICU stay, or mortality. There was a moderate negative correlation of PVPF with right ventricle fractional area change and right ventricle global longitudinal strain (r = -0.577, p < 0.001 and r = 0.465, p < 0.001, respectively) and a strong positive correlation with abnormal hepatic vein waveform (rho = 0.749, p < 0.001). CONCLUSION: PVPF is an easily obtainable bedside parameter to assess right ventricular dysfunction and predict prolonged mechanical ventilation, prolonged ICU stay, and mortality.

Biochemical Predictors of Acute Kidney Injury in Critically Ill COVID-19 Patients.

It is estimated that 50% of patients with coronavirus disease 2019 (COVID-19) have varying degrees of renal involvement. In this clinical biomarker development research, we examined in a retrospective study design the temporal changes in biochemical laboratory parameters in relation to the development of acute kidney injury (AKI). In a sample of 399 patients admitted from May 2020 to May 2021 to a tertiary health care intensive care unit (ICU), the incidence of AKI was 27.3%, and the median time to AKI was on 7th day of ICU admission. Most common etiology of AKI was kidney hypoperfusion. Within 72 h of developmental of low blood pressure, 63.76% developed AKI. The likelihood of AKI was higher in those with elevated serum ferritin, aspartate transaminase, and thrombocytopenia (low platelet count). A cutoff value of 750.3 ng/mL [area under the ROC curve (AUC) = 0.777] for serum ferritin, and 40.05 U/L for alanine aminotransferase (AUC = 0.677) 1 day before development of AKI displayed, respectively, a sensitivity of 76.2% and 64.3%, whereas the specificity was 69.5% and 64.1%, respectively, for these two biochemical predictors. A cutoff value of platelets (152.50 × 109/L [AUC = 0.75]) measured 4 days before development of AKI, displayed 83.3% sensitivity and 16.4% specificity. Taken together, our study thoroughly examined the temporal association of various clinical and laboratory parameters with AKI and prediction models were developed as per results of the time series data. These observations in a tertiary health care setting contribute to ongoing efforts for biomarker discovery and development using routine biochemical tests so as to forecast AKI in patients with COVID-19.

Effect of breathing intervention in patients with COVID and healthcare workers.

Background: Regulated breathing facilitates ventilation and reduces breathlessness. However, the effect of Yogic breathing on patients with COVID remains unclear. We aimed to evaluate the efficacy of two breathing protocols, i.e., short breathing technique (SBT) and long duration breathing technique (LBDT). Methods: Three groups including COVID-positive patients, COVID-recovered patients, and healthcare workers (HCWs) were included in the study and segregated into Yoga and control groups. SBT was administered to COVID-positive patients. Both SBT and LBDT were administered to COVID-recovered patients and HCWs. A total of 18 biochemical parameters, a 6-min walk test (6MWT), and a 1-min sit-stand test (1MSST) were assessed on 0th, 7th, and 15th days, where biochemical parameters were the primary outcome. Pre-post estimation of neuropsychological parameters (nine questionnaires) and heart rate variability (HRV) were carried out. The paired t-test or Wilcoxon rank test was applied for pre-post comparison and the Student's t-test or Mann-Whitney U test was used for group comparison. Repeated measures test was applied for data recorded at three time points. Results: A significant elevation in white blood cell (WBC) count was observed in COVID-positive intervention (p < 0.001) and control groups (p = 0.003), indicating no role of intervention on change in WBC number. WBC count (p = 0.002) and D-dimer (p = 0.002) significantly decreased in the COVID-recovered intervention group. D-dimer was also reduced in HCWs practicing Yogic breathing as compared to controls (p = 0.01). D-dimer was the primary outcome, which remained below 0.50 µg/ml (a cutoff value to define severity) in the COVID-positive yoga group (CYG) and decreased in the COVID-recovered yoga group (RYG) and the HCW yoga group (HYG) after intervention. A 6-min walk test (6MWT) showed an increase in distance covered among the COVID-positive patients (p = 0.01) and HCWs (p = 0.002) after intervention. The high-frequency power (p = 0.01) was found to be reduced in the COVID-positive intervention group. No significant change in neuropsychological parameters was observed. Conclusion: Yogic breathing lowered D-dimer, which is helpful in reducing thrombosis and venous thromboembolism in patients with COVID-19 besides lowering the chances of vaccine-induced thrombotic thrombocytopenia in vaccinated individuals. The breathing intervention improved exercise capacity in mild to moderate cases of COVID-19. Further studies can show if such breathing techniques can influence immunity-related genes, as reported recently in a study. We suggest that Yogic breathing may be considered an integrative approach for the management of patients with COVID. Trial registration: http://ctri.nic.in/Clinicaltrials/login.php, identifier: CTRI/2020/10/028195.

Development of a cost-effective ex vivo lung perfusion system for lung transplantation in India.

Background & objectives: Standard donor lung preservation with cold flush and storage allows up to six hours between retrieval of lungs from the donor and transplantation in the recipient. Ex vivo lung perfusion (EVLP) systems mimic physiological ventilation and perfusion in the donor lungs with potential for prolonged lung preservation and donor lung reconditioning. In this study, it was aimed to perform EVLP on discarded donor lungs using a locally developed EVLP system. Methods: Equipment that are routinely used for cardiac surgeries were collected and a functional EVLP system was assembled. This system was used on five pairs of lungs retrieved from brain-dead organ donors. The lungs were ventilated and pulmonary circulation was continuously perfused with a solution containing oxygen and nutrients for four hours. The system was tested without red blood cells (RBCs) added to the solution (acellular group; n=3; A1, A2 and A3) and also with RBCs added to the solution (cellular group; n=2; C1 and C2). Results: The EVLP system was successfully used in four (A1, A2, A3 and C2) of the five lung pairs. Mechanical and gas exchange functions of the lungs were preserved in these lung pairs. One lung pair (C1) worsened and developed pulmonary oedema. Histopathological examination of all five lung pairs was satisfactory at the end of the procedure. Major challenges faced were leakage of solution from the system and obstruction to drainage of RBCs containing solution from the lungs. Interpretation & conclusions: The results of the present study suggest that, it is possible to maintain the lungs retrieved for transplantation in a physiological condition using a locally prepared EVLP system and a solution without RBCs.

Clinical characteristics & outcome of SARS-CoV-2 infected neonates presenting to paediatric emergency.

Background & objectives: Data on neonatal COVID-19 are limited to the immediate postnatal period, with a primary focus on vertical transmission in inborn infants. This study was aimed to assess the characteristics and outcome of COVID-19 in outborn neonates. Methods: All neonates admitted to the paediatric emergency from August 1 to December 31, 2020, were included in the study. SARS-CoV-2 reverse transcription- (RT)-PCR test was done on oro/nasopharyngeal specimens obtained at admission. The clinical characteristics and outcomes of SARS-CoV-2 positive and negative neonates were compared and the diagnostic accuracy of a selective testing policy was assessed. Results: A total of 1225 neonates were admitted during the study period, of whom SARS-CoV-2 RT-PCR was performed in 969. The RT-PCR test was positive in 17 (1.8%). Mean (standard deviation) gestation and birth weight of SARS-CoV-2-infected neonates were 35.5 (3.2) wk and 2274 (695) g, respectively. Most neonates (11/17) with confirmed COVID-19 reported in the first two weeks of life. Respiratory distress (14/17) was the predominant manifestation. Five (5/17, 29.4%) SARS-CoV-2 infected neonates died. Neonates with COVID-19 were at a higher risk for all-cause mortality [odds ratio (OR): 3.1; 95% confidence interval (CI): 1.1-8.9, P=0.03]; however, mortality did not differ after adjusting for lethal malformation (OR: 2.4; 95% CI: 0.7-8.7). Sensitivity, specificity, accuracy, positive and negative likelihood ratios (95% CI) of selective testing policy for SARS-CoV-2 infection at admission was 52.9 (28.5-76.1), 83.3 (80.7-85.6), 82.8 (80.3-85.1), 3.17 (1.98-5.07), and 0.56 (0.34-0.93) per cent, respectively. Interpretation & conclusions: SARS-CoV-2 positivity rate among the outborn neonates reporting to the paediatric emergency and tested for COVID-19 was observed to be low. The selective testing policy had poor diagnostic accuracy in distinguishing COVID-19 from non-COVID illness.

Cognitive Deficits in Patients with COVID-19 Infection during Their Hospital Stay: An Exploratory Study.

Background The literature on presence of cognitive deficits in patients recovered from coronavirus disease 2019 (COVID-19) infection is emerging. However, the data on whether cognitive deficits have its onset during the acute phase of illness has not been evaluated extensively. Aim This article estimates the level of cognitive functioning of patients with COVID-19 while they were admitted to COVID-designated wards. Secondary objectives were to assess the influence of medical comorbidities, severity of COVID-19 infection, and depressive and anxiety symptoms on cognitive functioning in patients with COVID-19 infection. Methods Sixty-six clinically stable patients with COVID-19 infection were evaluated during their inpatient stay on Hindi Montreal Cognitive Assessment scale (H-MoCA), Hindi Mini-Mental State Examination (HMSE) scale, Patient Health Questionnaire-9, and Generalized Anxiety Disorder Questionnaire -7. Results The mean age of the study participants was 39.85 (standard deviation [SD] 16.89) years and the participants were evaluated after 9.34 (SD 4.98; median 9.0) days of being diagnosed with COVID-19 infection. About one-fourth (28.8%; n = 19) of the participants had cognitive impairment on HMSE and about two-fifths ( n = 26; 39.39%) had cognitive impairment as per the cutoff used for H-MoCA. A higher level of cognitive deficits were seen among participants who were older, diagnosed with diabetes mellitus, and those who required oxygen support during their hospital stay prior to assessment. Conclusion Low cognitive score was found in one-fourth (28.8%) to two-fifths (39.9%) of the persons, depending on the assessment scale among those with acute COVID-19 infection. Low cognitive score was more prevalent among the elderly, those with diabetes mellitus, and those who required oxygen support prior to the assessment.

COVID-19-related dynamic coagulation disturbances and anticoagulation strategies using conventional D-dimer and point-of-care Sonoclot tests: a prospective cohort study.

OBJECTIVES: Coagulation changes associated with COVID-19 suggest the presence of a hypercoagulable state with pulmonary microthrombosis and thromboembolic complications. We assessed the dynamic association of COVID-19-related coagulation abnormalities with respiratory failure and mortality. DESIGN: Single-centre, prospective cohort study with descriptive analysis and logistic regression. SETTING: Tertiary care hospital, North India. PARTICIPANTS: Patients with COVID-19 pneumonia requiring intensive care unit (ICU) admission between August 2020 and November 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: We compared the coagulation abnormalities using standard coagulation tests like prothrombin time, D-dimer, platelet count, etc and point-of-care global coagulation test, Sonoclot (glass beaded(gb) and heparinase-treated(h)). Incidence of thromboembolic or bleeding events and presence of endogenous heparinoids were assessed. Cox proportional Hazards test was used to assess the predictors of 28-day mortality. MEASUREMENT: All patients underwent Sonoclot (glass beaded) test at admission apart from the routine investigations. In patients at risk of thromboembolic or bleeding phenomena, paired tests were performed at day 1 and 3 with Sonoclot. Activated clotting time (ACT) <110 s and peak amplitude >75 units were used as the cut-off for hypercoagulable state. Presence of heparin-like effect (HLE) was defined by a correction of ACT ≥40 s in h-Sonoclot. RESULTS: Of 215 patients admitted to ICU, we included 74 treatment naive subjects. A procoagulant profile was seen in 45.5% (n=5), 32.4% (n=11) and 20.7% (n=6) in low-flow, high-flow and invasive ventilation groups. Paired Sonoclot assays in a subgroup of 33 patients demonstrated the presence of HLE in 17 (51.5%) and 20 (62.5%) at day 1 and 3, respectively. HLE (day 1) was noted in 59% of those who bled during the disease course. Mortality was observed only in the invasive ventilation group (16, 55.2%) with overall mortality of 21.6%. HLE predicted the need for mechanical ventilation (HR 1.2 CI 1.04 to 1.4 p=0.00). On multivariate analysis, the presence of HLE (HR 1.01; CI 1.006 to 1.030; p=0.025), increased C reactive protein (HR 1.040; CI 1.020 to 1.090; p=0.014), decreased platelet function (HR 0.901; CI 0.702 to 1.100 p=0.045) predicted mortality at 28days. CONCLUSION: HLE contributed to hypocoagulable effect and associated with the need for invasive ventilation and mortality in patients with severe COVID-19 pneumonia. TRIAL REGISTRATION: NCT04668404; ClinicalTrials.gov.in. Available from https://clinicaltrials.gov/ct2/show/NCT04668404.

Evaluation of indigenously developed closed-loop automated blood pressure control system (claps): a preliminary study.

Closed-loop systems have been designed to assist anesthetists in controlling anesthetic drugs and also maintaining the stability of various physiological variables in the normal range. In the present study, we describe and clinically evaluated a novel closed-loop automated blood pressure control system (CLAPS) in patients undergoing cardiac surgery under cardiopulmonary bypass. Forty ASA II-IV adult patients undergoing elective cardiac surgery were randomly allocated to receive adrenaline, noradrenaline, phenylephrine and nitroglycerine (NTG) adjusted either through CLAPS (CLAPS group) or manually (Manual group). The desired target mean arterial blood pressure (MAP) for each patient in both groups was set by the attending anesthesiologist. The hemodynamic performance was assessed based on the percentage duration of time the MAP remained within 20% of the set target. Automated controller performances were compared using performance error criteria of Varvel (MDPE, MDAPE, Wobble) and Global Score. MAP was maintained a significantly longer proportion of time within 20% of the target in the CLAPS group (79.4% vs. 65.5% p < 0.001, 't' test) as compared to the manual group. Median absolute performance error, wobble, and Global score was significantly lower in the CLAPS group. Hemodynamic stability was achieved with a significantly lower dose of Phenyepherine in the CLAPS group (1870 µg vs. 5400 µg, p < 0.05, 't' test). The dose of NTG was significantly higher in the CLAPS group (3070 µg vs. 1600 µg, p-value < 0.05, 't' test). The cardiac index and left ventricular end-diastolic area were comparable between the groups. Automated infusion of vasoactive drugs using CLAPS is feasible and also better than manual control for controlling hemodynamics during cardiac surgery. Trial registration number and date This trial was registered in the Clinical Trial Registry of India under Registration Number CTRI/2018/01/011487 (Retrospective; registration date; January 23, 2018).

Presence of diarrhea associated with better outcomes in patients with COVID-19 - A prospective evaluation.

PURPOSE: Gastrointestinal (GI) manifestations have been well documented in patients with coronavirus disease 2019 (COVID-19), but its clinical impact on the course of the disease is debatable. Majority of the available data is retrospective, and hence this prospective study was planned to study the impact of GI symptoms on COVID-19 outcome. METHODS: All COVID-19 patients admitted in a tertiary care centre from August-October 2020 were screened and patients without pre-existing GI diseases were included. A detailed history of the various symptoms including duration was documented. Various baseline laboratory investigations and inflammatory markers were conducted as per the protocol. Patients with and without diarrhea were compared for the various disease outcome parameters. RESULTS: Of the 244 patients screened, 203 patients (128 males; 63.1%) were included. Respiratory symptoms alone were present in 49 (24.1%), GI symptoms alone in 20 (9.9%) and 117 (57.6%) had both. Overall GI symptoms was noted in 137 (67.5%) cases with the commonest being diarrhea (61; 30.0%). Patients with both respiratory and any GI symptoms showed a lower trend towards need for mechanical ventilation (12.2% vs 7.7%; p â€‹= â€‹0.35) and mortality (10.2% vs 4.3%; p â€‹= â€‹0.14) compared to respiratory symptoms alone, although not statistically significant. Patients with diarrhea (n â€‹= â€‹61) had no mortality (0% vs 7.7%; p â€‹= â€‹0.036) or need for mechanical ventilation and shorter hospital stay compared to those who did not have diarrhea. CONCLUSION: GI symptoms are frequent in patients with SARS-CoV-2 infection and the commonest is diarrhea. Diarrhea is a harbinger of better outcome with lower mortality among COVID-19 positive patients.

Utility of Transfontanelle Ultrasound in Predicting the Fluid Responsiveness in Children After Repair of Congenital Heart Diseases: A Prospective Observational Study.

OBJECTIVES: Postoperative fluid management in children undergoing cardiac surgery requires a balanced optimization. The blood flow velocity variation in the internal carotid artery (ΔICA) measured through transfontanelle ultrasound has been shown to predict fluid responsiveness during cardiac surgery. It may provide an excellent window to study fluid responsiveness in infants during the postoperative period when the intensivist is faced with the challenges of poor echocardiographic window. The authors aimed to observe the correlation between ΔICA measured on transfontanelle ultrasound with the respiratory variability of peak aortic blood flow velocity (ΔVpeak) on transthoracic echocardiography as a marker of fluid responsiveness in infants on mechanical ventilation during the postoperative period after cardiac surgery. DESIGN: A prospective observational study. SETTING: The postcardiac surgery intensive care unit (ICU) of a tertiary care hospital. PARTICIPANTS: Thirty infants undergoing congenital cardiac surgery. INTERVENTIONS: A fluid bolus of 10 mL/kg administered over 10 minutes at 1 and 6 hours after ICU admission. Patients were categorized into fluid responders and nonresponders based on >15% increase in the indexed stroke volume. MEASUREMENTS AND MAIN RESULTS: A total of 50 fluid boluses were administered in 30 patients. Among these, 22 (73.33%) were responders and 8 (26.67%) were nonresponders. There was moderate correlation between ΔICA and peak aortic blood flow velocity variation (ΔVpeak) (r = 0.59, p ≤ 0.001). The ΔVpeak >14.74% had 68% sensitivity and 75% specificity to predict fluid responsiveness (area under the receiver operating characteristic [AUROC], 0.749; p = 0.001; positive likelihood ratio, 2.71; negative likelihood ratio, 0.43). The ΔICA >9.85% could predict fluid responsiveness in infants (AUROC, 0.728; p = 0.003; 75% sensitivity; 60% specificity; positive likelihood ratio, 1.85; negative likelihood ratio, 0.42). Among children younger than 6 months, ΔICA >9.85% was a better predictor of fluid responsiveness (AUROC, 0.889; p = 0.009) than ΔVpeak >15% (AUROC, 0.778; p = 0.061). CONCLUSION: The ICA variability >9.85% measured via transfontanelle ultrasound is a good predictor of fluid responsiveness in infants, especially those younger than 6 months on mechanical ventilation after cardiac surgery.

Hydroxychloroquine in Treatment of Asymptomatic and Mildly Symptomatic COVID-19: A Multi-Centre Cohort Study.

BACKGROUND: Although hydroxychloroquine (HCQ) lacks benefit in patients with moderate-to-severe COVID-19, its role in asymptomatic and mildly symptomatic disease needs better elucidation. METHODS: This multi-centre cohort study included asymptomatic and mildly symptomatic, RT-PCR confirmed COVID-19 cases between 30 March and 20 May, 2020. Patients were categorized into two groups (HCQ-treated and untreated) based on exposure to HCQ. Dose of HCQ used was 400 mg twice daily (day one) followed by once daily for seven days. HCQ-untreated patients were managed supportively without any active antiviral or immunomodulatory therapy. Nasopharyngeal SARS-CoV-2 clearance by RT-PCR (primary outcome) was compared between HCQ-treated and untreated patients using Kaplan-Meier analysis and Cox proportional-hazards regression. Clinical efficacy and safety profile of HCQ were assessed (secondary outcomes). RESULTS: 162 patients [84 (51·9%) males; mean age 38·2 (15·2) years] were included. Forty-four (27·2%) patients had mild disease, rest 118 (72·8%) were asymptomatic. Seventy-five (46·3%) patients received HCQ. Median time to virological negativity was lesser in HCQ-treated (13 days) versus untreated patients (15 days) (logrank<0·001) in both asymptomatic and mildly symptomatic patients. Treatment with HCQ was the only independent predictor of virological negativity (hazardratio=2·24; adjusted p-value<0·001). Two (5·4%) mildly symptomatic patients progressed to severe disease within 24 hours (two doses) of HCQ initiation, compared to none in the HCQ-untreated group. Five HCQ-treated patients developed minor gastrointestinal side effects, not requiring drug discontinuation. CONCLUSION: HCQ reduced the time to virologic negativity (by 2 days) in asymptomatic and mildly symptomatic COVID-19, without any serious adverse events. However, no obvious clinical benefit was noted.