Characteristics and predictors of outcomes of critically Ill children with SARS-CoV-2 infection - the PICU experience

Abstract Objective To describe the clinical characteristics, laboratory parameters, treatment, and predictors of an unfavorable outcome of critically ill children with SARS-CoV-2 infection. Method This was a prospective observational study performed in a pediatric intensive care unit (PICU) of a tertiary care COVID referral hospital among critically ill children in the age group 1 month - 12 years admitted due to SARS-CoV-2 infection from June to December 2020. Demographic, clinical profile, pSOFA and PRISM III scores, laboratory parameters, treatment, and outcomes of the patients were recorded. Children who had a prolonged PICU stay (>14 days) or died were compared with those who were discharged from PICU within 14 days to assess predictors of unfavorable outcomes. Results PICU admission rate among hospitalized SARS-CoV-2 infected children was 22.1% (92/416). Infants comprised the majority of the ICU population. Invasive mechanical ventilation and inotropic support were required for 28.3% and 37% of patients, respectively. Remdesivir, IVIg, and steroids were administered to 15.2%, 26.1%, and 54.3% of the subjects, respectively. The mortality rate was 7.6 %. MIS-C patients were older, less comorbid, and required less ventilator support but more inotrope support than acute severe COVID-19 patients. Predictors of unfavorable outcomes were age < 1 year, fever duration > 5 days, respiratory distress, shock, comorbidity, elevated CRP (> 50 mg/L), procalcitonin (> 6 ng/L), D-dimer (> 6 µg/L) and arterial lactate (> 2 mmol/L). Conclusion Critically ill children with unfavorable outcomes were predominantly infants, comorbid, prolonged fever, respiratory distress, shock and elevated inflammatory markers, D-dimer and lactate. These factors may be useful for watchful monitoring and early intervention.

Clinical Characteristics of Children With SARS-CoV-2 Infection During the Third Wave of the Pandemic: Single Center Experience

Objective: To determine the clinical presentation and outcome of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the third wave of the pandemic in India. Method: A review of hospital records was done at a tertiary care hospital, for children seen between 1 and 25 January, 2022. Result: Out of total 112 SARS-CoV-2 positive patients, 17 were hospitalized and 95 were treated in the outpatient department. Among non-hospitalized children, fever was the commonest feature (72, 75.7%), followed by sneezing, and loss of appetite. The median (IQR) duration of symptoms was 2.5 (1.5) days. Among hospitalized children, 10 had co-morbidities and one-third required intensive care unit admission. MIS-C was diagnosed in four patients. Out of 4 mechanically ventilated patients, two had coronavirus disease (COVID) pneumonia. The mean (SD) length of hospital stay was 7.5 (2.5) days. One child with leukemia died during management. Conclusion: During the third wave of the pandemic, most children had symptomatic illnesses, but recovery was fast among non-hospitalized children.

Deciphering the functional role of EGR1 in Prostaglandin F2 alpha induced luteal regression applying CRISPR in corpus luteum of buffalo

BACKGROUND: PGF2α is essential for the induction of the corpus luteum regression which in turn reduces progesterone production. Early growth response (EGR) proteins are Cys2-His2-type zinc-finger transcription factor that are strongly linked to cellular proliferation, survival and apoptosis. Rapid elevation of EGR1 was observed after luteolytic dose of PGF2α. EGR1 is involved in the transactivation of many genes, including TGFß1, which plays an important role during luteal regression. METHODS: The current study was conducted in buffalo luteal cells with the aim to better understand the role of EGR1 in transactivation of TGFß1 during PGF2α induced luteal regression. Luteal cells from mid stage corpus luteum of buffalo were cultured and treated with different doses of PGF2α for different time durations. Relative expression of mRNAs encoding for enzymes within the progesterone biosynthetic pathway (3ßHSD, CYP11A1 and StAR); Caspase 3; AKT were analyzed to confirm the occurrence of luteolytic event. To determine if EGR1 is involved in the PGF2α induced luteal regression via induction of TGFß1 expression, we knocked out the EGR1 gene by using CRISPR/Cas9. RESULT: The present experiment determined whether EGR1 protein expression in luteal cells was responsive to PGF2α treatment. Quantification of EGR1 and TGFß1 mRNA showed significant up regulation in luteal cells of buffalo at 12 h post PGF2α induction. In order to validate the role of PGF2α on stimulating the expression of TGFß1 by an EGR1 dependent mechanism we knocked out EGR1. The EGR1 ablated luteal cells were stimulated with PGF2α and it was observed that EGR1 KO did not modulate the PGF2α induced expression of TGFß1. In PGF2α treated EGR1 KO luteal cell, the mRNA expression of Caspase 3 was significantly increased compared to PGF2α treated wild type luteal cells maintained for 12 h. We also studied the influence of EGR1 on steroidogenesis. The EGR1 KO luteal cells with PGF2α treatment showed no substantial difference either in the progesterone concentration or in StAR mRNA expression with PGF2α-treated wild type luteal cells. CONCLUSION: These results suggest that EGR1 signaling is not the only factor which plays a role in the regulation of PGF2α induced TGFß1 signaling for luteolysis.

Transcriptional Abundance of Myosin Light Chain 2 Gene in Cardiac Differentiated Canine Induced Pluripotent Stem Cells

Induced pluripotent stem cells (iPSCs) are promising cell source for cardiac tissue engineering and cell based therapies for heart repair as they can be expanded in vitro and differentiated into most cardiovascular cell types, including cardiomyocytes. During embryonic heart development, this differentiation occurs under the influence of internal and external stimuli that guide cells to go down the cardiac lineage. The aim of this study was to characterize the cardiac differentiation potential of a canine iPS cell. With the use of a standard embryoid body–based differentiation protocol for iPS cells were differentiated for 24 days. In vitro differentiations of canine iPSCs via embryoid bodies (EBs) were produced by ‘Hanging Drop’ method. EB’s were differentiated using 5-azacytidine (5-Aza). During differentiation, EBs were collected on day 4, 6, 8, 12, 16, 20 and 24 to evaluate the expression of cardiomyocyte specific marker. Analyses on molecular, structural, and functional levels demonstrated that iPS cell– derived cardiomyocytes show typical features of ES cell– derived cardiomyocytes. Reverse transcription polymerase chain reaction analyses demonstrated expression of marker genes. The differentiated cells expressed cardiac-specific gene myosin light chain 2 (MYL2) which started from day 8 of differentiation and highest expression was observed on day 16. Immunocytochemistry and relative expression of cardiac specific genes revealed that iPS cells differentiate into functional cardiomyocytes and allow to derivation of autologous functional cardiomyocytes for cellular cardiomyoplasty and myocardial tissue engineering

Foeto-Maternal Outcome of Obstructed Labour in a Tertiary Care Hospital of Kolkata

Obstructed labour is the situation where in spite of adequate uterine contraction the progressive decent of presenting part is arrested due to mechanical obstruction. Obstructed labour contributes to around eight percent of maternal deaths in India. It is also one of the leading causes of perinatal morbidity and mortality in developing countries. We wanted to study the risk factors and fetomaternal outcome in obstructed labour at Chittaranjan Seva Sadan College of Obstetrics, Gynaecology and Child Health. This will help us to assess obstetric near miss cases and to develop strategies to decrease the complications arising from obstructed labour.METHODSThis was a three year retrospective observational study conducted by reviewing the records of obstructed labour during the period April 2014 - March 2017. The study was approved by Institutional Ethics Committee. All the mothers who were admitted in the labour room with signs and symptoms of obstructed labour were included in this study. All the relevant information such as age, parity, socioeconomic status, risk factors, complications, mode of delivery, and fetomaternal outcome were collected.RESULTSThere were 219 cases of obstructed labour among a total of 23,815 deliveries. Most common cause for obstructed labour was cephalopelvic disproportion (77%) followed by malposition/malpresentation (17.3%). Majority of the patients (69.2%) belonged to poor socioeconomic group. Sepsis (10.6%) and pyrexia (9.6%) were the common complications. Neonatal mortality was 30.8% and maternal morbidity was 5.8%.CONCLUSIONSLack of health education, antenatal care, low socioeconomic condition, poor referral system and demographic factors are important contributory factors leading to adverse outcome of obstructed labour. This can be sorted out by proper antenatal care, improving health care delivery system and by timely referral of cases according to partograph monitoring.

Effectiveness of beta blockers in primary prophylaxis of variceal bleeding in children with portal hypertension.

Aim: The primary aim of our study was to assess the effectiveness of beta blockers in non bleeding portal hypertensive children. The secondary objective was to evaluate whether the newer generation beta blockers were superior compared to conventional ones. Methods: Conventional propranolol and newer generation carvedilol were administered to 31 subjects each, after stratifying them into nearly equal subgroups according to etiology (sinusoidal or presinusoidal). Results: At the end of 2 years study period, 3 children (4.83%) had breakthrough bleeding. A decrease, increase and no alteration in grade of oesophageal varices was seen in 40, 9 and 13 cases respectively. Of the 9 children with associated gastroeosophageal varices (GOV), the severity of lesions was reduced in 8 of them. Both the drugs had efficacious outcome in sinusoidal as well as presinusoidal cases, having a significant coefficient of correlation (r>0.5) with time. Carvedilol was more effective than propranolol statistically (p = 0.035 and p = 0.034 respectively), only at 4 and 5 month follow-up period. Conclusion: Beta blockers are effective in preventing variceal bleed in children with portal hypertension. Long term efficacy of carvedilol and propranolol was similar.

Dorfman-Chanarin syndrome: A rare neutral lipid storage disease.

Dorfman-Chanarin syndrome is a rare neutral lipid storage disorder characterized by ichthyosis, lipid vacuolations in peripheral leucocytes, and multisystem involvement. It is an autosomal recessive disorder caused by mutations in the CGI-58 gene. A total of 42 cases have been reported worldwide till February 2009 out of which 4 have been previously reported from India. We report a case of a 20-month-old male with congenital ichthyosis, organomegaly, and bilateral cryptorchidism. Examination of the peripheral smear revealed lipid vacuoles in the leucocytes consistent with Jordan's anomaly, which was confirmed by transmission electron microscopy. Liver biopsy revealed micronodular cirrhosis with macrovesicular steatosis while skin biopsy showed ichthyosis vulgaris. Dorfman-Chanarin syndrome was diagnosed on the basis of clinical and laboratory criteria with certain unreported manifestations. Dietary modifications were instituted and followed up after 1 year with promising results. This emphasizes the importance of neonatal screening for lipid vacuolations in peripheral blood in all cases of congenital ichthyosis.

Generalized epimerase deficiency galactosemia.

Galactosemia is caused by inherited deficiencies in one of three enzymes involved in the metabolism of galactose: galactose- 1-phosphate uridyltransferase (GALT), galactokinase (GALK), and uridine diphosphate galactose-4-epimerase (GALE). The rarest and most poorly understood form of galactosemia is due to epimerase deficiency. We are reporting such a rarest form of galactosemia presenting with progressively increasing cholestatic jaundice and failure to thrive at one month of age. After confirmation of decreased epimerase level in RBC hemolysate, the patient was put on galactose restricted diet and vitamins supplementation, which reversed the clinical signs as well as altered liver function. Patient is on regular follow-up and now at 15 months of age he has no marked developmental delay.

Anti-La negative cutaneous lupus erythematosus in a newborn.

A newborn presented with erythematous lesion over face, which appeared soon after birth. Diagnosis of neonatal lupus erythematosus (NLE) was confirmed by positive anti-Ro SSA antibody and skin biopsy. But anti-La SSB antibody was negative. Her hepatic transaminases were high. But no cardiac manifestations were noted.