Untargeted Maternal Plasma Metabolomics in Hirschsprung Disease: A Pilot Study.

Background and Aims: Hirschsprung disease (HSCR) is a congenital disorder of unknown etiology affecting the enteric nervous system (ENS). Since the early gestational development of the ENS is dependent on the prenatal maternal metabolic environment, the objective of this pilot study was to explore the role of specific maternal plasma metabolites in the etiology of HSCR. Methods: In this cross-sectional study, postnatal (as a surrogate for prenatal) plasma samples were obtained from mothers of children diagnosed with HSCR (n = 7) and age-matched mothers of normal children (n = 6). The plasma metabolome was analyzed by ultra-high-pressure liquid chromatography and mass spectrometry. Metabolites were identified by mzCloud using Compound Discoverer software. Using an untargeted metabolomics workflow, metabolites with case versus control group differences were identified. Results: A total of 268 unique plasma metabolites were identified and annotated in maternal plasma. Of these, 57 were significantly different between case and control groups (P < 0.05, t-test). Using a false discovery rate corrected cutoff of 10% to adjust for multiple comparisons, 19 metabolites were significantly different in HSCR cases, including carnitines, medium-chain fatty acids, and glutamic acid. Pathways affected were for amino acid and lipid metabolism. Conclusion: Disordered prenatal metabolic pathways may be involved in the etiopathogenesis of HSCR in the developing fetus. This is the first study to assess maternal plasma metabolomics in HSCR.

Mandatory fortification of rice in the public distribution system in India: An ethics perspective.

In response to the continuing high prevalence of anaemia recorded in the National Family Health Survey-5, the Indian government launched a policy for mandatory iron fortification of the rice provided through public nutrition programmes in India. This was done even though a rigorous evidence analysis had already concluded that rice fortification was not effective in preventing anaemia or iron deficiency at the population level. Fortification also poses a potential risk of iron toxicity over time, but there is no stated time period for the policy's implementation. The risk is particularly high in segments of the population who already have a high habitual iron intake, and who could be exposed to simultaneous fortification in different staples and food commodities along with the ongoing weekly Iron and Folic Acid tablets supplementation programme. Finally, this fortification policy also requires significant additional funding and resources to implement. It is crucial to examine such mandatory health actions, and to weigh the benefits and risks of harm, using the principles of public health ethics.

An observational study on the prevalence of choledochal cyst with pancreatitis: Geographical implications and management.

The objective of this study was to analyse the prevalence, risk factors and need for intervention in a sample of Indian children with choledochal cyst (CDC) complicated by pancreatitis with a special focus on chronic pancreatitis. A retrospective review of medical records of children admitted with CDC over 11 years was done and pancreatitis identified using INSPPIRE guidelines. Children were divided into two groups-one having choledochal cyst alone and the other choledochal cyst along with pancreatitis to determine associated risk factors. 40.2% of children with CDC had pancreatitis based on elevation of enzymes or radiological imaging. Age, total bilirubin and indirect bilirubin, requirement of intervention was significantly higher in the group with pancreatitis. 47% of those with radiological features of pancreatitis had imaging features of chronic pancreatitis. Chronic pancreatitis has not been reported previously in children with CDC and maybe peculiar to the Indian subcontinent.

Bioavailability and daily requirement of vitamin B12 in adult humans: an observational study of its colonic absorption and daily excretion as measured by [13C]-cyanocobalamin kinetics.

BACKGROUND: Clinical and biochemical vitamin B12 (B12) deficiency is lower than anticipated in vegetarians. Extraileal absorption, such as from the colon, as well as reduced daily excretion, may be adaptive mechanisms to maintain B12 homeostasis with marginal intakes. OBJECTIVE: To measure the absorption of B12 from the small and large intestine, and its daily rate of excretion from the body, using a [13C]-cyanocobalamin tracer. METHODS: Oral B12 bioavailability was measured over 12 h after administration of [13C]-cyanocobalamin tracer (2.5 µg) in normal participants. The colonic B12 bioavailability was evaluated by direct instillation of [13C]-cyanocobalamin (5 µg) into the ascending colon. Bioavailability was calculated from 2-compartmental modeling of the tracer appearance in plasma. The excretion rate of B12 was measured from [13C]-cyanocobalamin elimination from the body over 4 wk after oral dosing (5 µg). RESULTS: The oral B12 bioavailability (n = 11) was 63% ± 10% measured over 12 h. A late absorption peak, accounting for 12% of the absorption, was observed after an average lag time of 8.7 h from dosing. The colonic B12 bioavailability (n = 10) was 7% ± 5% over 4 h. The daily B12 excretion rate (n = 4) was 0.7 ± 0.2 µg/d. The minimum daily requirement of B12 in these participants was derived at 1 µg /d. CONCLUSIONS: B12 is absorbed in the human colon. This observation confirms the potential contribution of the colon in daily B12 nutriture, and along with a possible lower requirement, could explain the absence of clinical deficiency in populations with marginal B12 intakes. TRIAL REGISTRATION NUMBER: This study was registered in Clinical Trials Registry of India (CTRI) with the registration number CTRI/2018/04/012957, available from https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=49319&EncHid=&userName=029108.

Estimation of exocrine pancreatic insufficiency in children with acute pancreatitis using the 13C mixed triglyceride breath test.

BACKGROUND: /Objective: The extent of exocrine pancreatic insufficiency (EPI) in the paediatric population with acute pancreatitis (AP) is unknown. The primary objective was to use a 6 h stable-isotope breath test to determine the prevalence of EPI in children with AP. The secondary objective was to determine the diagnostic ability of a 4 h abbreviated breath test in the detection of EPI. METHODS: 13C-mixed triglyceride (MTG) breath test was used to measure fat digestibility in 12 children with AP and 12 normal children. EPI was diagnosed based on a cumulative dose percentage recovery (cPDR) cut-off value < 26.8% present in literature. To reduce the test burden, the diagnostic accuracy of an abbreviated 4 h test was evaluated, using a cPDR cut-off that was the 2.5th percentile of its distribution in control children. RESULTS: The cPDR of cases was significantly lower than that of controls (27.71 ± 7.88% vs 36.37 ± 4.70%, p = 0.005). The cPDR during acute illness was not significantly different to that at 1 month follow up (24.69 ± 6.83% vs 26.98 ± 11.10%, p = 0.52). The 4 h and 6 h breath test results correlated strongly (r = 0.93, p < 0.001) with each other. The new 4 h test had 87.5% sensitivity and 93.8% specificity for detecting EPI. CONCLUSION: Two-thirds (66.7%) of this sample of children with AP had EPI during admission, which persisted at 1 month follow up. The 4 h abbreviated 13C-MTG breath test has good diagnostic ability to detect EPI in children and may improve its clinical utility in this age group.

Maternal Vitamin A Status as a Risk Factor of Hirschsprung Disease in the Child.

INTRODUCTION: The gene-environment interaction of the REarranged during Transfection ( RET ) gene with vitamin A in the etiopathogenesis of Hirschsprung disease (HSCR) has been suggested in rodents. The aim of this study was to evaluate vitamin A status in mothers of children with HSCR and to assess its association with pathogenic variants of the RET gene in affected children. METHODS: This was a case-control study of stable isotope-based vitamin A measurement stores of mothers of children diagnosed with HSCR (within 8 months from birth, n = 7) and age-matched mothers of normal children (n = 6). Next-generation sequencing of RET exons, along with their upstream promoter region, was performed in the 7 HSCR proband-parent triads to evaluate pathogenic variants. RESULTS: Maternal vitamin A stores in the HSCR group was almost 50% that of those in controls, tending toward significance (0.50 ± 0.17 vs 0.89 ± 0.51 µmol/g respectively, P = 0.079). Two novel pathogenic de novo mutations were identified in 2 cases, and a rare single-nucleotide deletion was detected in the 3.5-kb RET upstream region, in a heterozygous state, in all 7 proband-parent triads. Low-penetrance RET haplotypes associated with HSCR were detected in 5 cases. DISCUSSION: Mothers with children with HSCR had lower vitamin A liver stores than mothers with normal children, and the children who were affected had HSCR despite having no established pathogenic RET variants. Lower maternal vitamin A status may increase the penetrance of genetic mutations in RET , and vitamin-A mediated gene-environment interactions may underpin some of the etiology of HSCR.

Central obesity in low BMI as a risk factor for COVID-19 severity in South Indians.

BACKGROUND AND OBJECTIVES: South Asians are known to have excess adiposity at a lower body mass index, with truncal fat accumulation. Whether this confers higher risk to develop severe COVID-19 is not known. This study evaluated body mass index, body fat mass and waist circumference as risk factors for COVID-19 severity and its progression, in South Asian adults. METHODS AND STUDY DESIGN: Details of COVID-19 patients (19-90 years) were obtained prospectively, along with weight, height, waist circumference and body fat mass assessed by bioelectrical impedance analysis. Binomial logistic and Poisson regression were performed to test associations between waist circumference, body fat mass and body mass index to evaluate the adjusted OR or relative risk for disease severity at admission and length of stay. RESULTS: After adjusting for age, sex, height and co-morbidities, body mass index >23 kg/m2 (adjusted OR 2.758, 95% CI 1.025, 7.427), waist circumference (adjusted OR 1.047, 95% CI 1.002, 1.093) and body fat mass (adjusted OR 1.111, 95% CI 1.013, 1.219) were associated with a significant risk for disease severity at admission, while only waist circumference (adjusted relative risk 1.004, 95% CI 1.001, 1.008), and body fat mass (adjusted relative risk 1.011, 95% CI 1.003, 1.018), were associated with a significantly longer length of stay. CONCLUSIONS: Body mass index, at a lower cut-off of >23 kg/m2, is a significant risk factor for COVID-19 disease severity in the group of patients studied. The waist circumference and body fat mass are also good indicators for both severity at admission and length of stay.

Pediatric Trauma: Management and Lessons Learned.

AIM: The aim is to prospectively study 125 trauma patients admitted in the pediatric surgery ward in our institute. MATERIALS AND METHODS: Pediatric patients admitted in the ward after initial resuscitation in the triage room were included. Isolated neurosurgical and orthopedic injuries were excluded. X-ray cervical spine, hip, and chest and a focused assessment with sonography in trauma ultrasound were done for all patients. Computed tomography of the abdomen or chest was done where relevant. Injury profile and surgical intervention when needed were analyzed. RESULTS: Road traffic accidents and fall from height caused 73.6% of the injuries. School-going children were most commonly affected (60.8%). Distinctive injuries were noted such as abdominal wall hernias and delayed bladder perforation. All solid organ injury irrespective of grade treated conservatively. Forty percent of the children required surgical intervention. Five patients after laparotomy were found to have surgical conditions unrelated to trauma, whereas another 14 required delayed surgery. Five patients had injuries secondary to sexual abuse. All except two patients were discharged in a satisfactory condition and are doing well in the follow-up. CONCLUSION: In spite of extensive injuries and the need for multiple surgeries, children with trauma have a good prognosis. Close observation during admission and also in follow-up are essential, as many patients may require delayed surgery ≥1 week from injury.

Caught Off Guard with COVID-19 Bowel Gangrene: A Case Report.

BACKGROUND: Isolated and predominant gastrointestinal presentation in coronavirus disease 2019 (COVID-19) is reported less often. With evolving evidence that gastrointestinal tract can be a portal of entry, multiplication, primary site of affliction and symptomatic manifestation, and source of infectivity through prolonged fecal shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), it is essential that isolated gastrointestinal symptoms can also be a mode of presentation of this novel virus and illness. CASE DESCRIPTION: The index case is a 10-year-old female child who presented with acute onset abdominal pain. Emergency surgery showed extensive gangrenous small bowel. The small bowel had herniated into a transmesenteric defect near the mid-ileum and was obstructed. Reverse-transcription polymerase chain reaction for SARS-CoV2 sent as preoperative work-up turned positive. The histopathology showed platelet aggregate thrombus in the venules with patent adjacent arterioles. CONCLUSION: This is probably the first reported case of COVID-19-related bowel gangrene. HOW TO CITE THIS ARTICLE: Kenchappa Y, Hegde S, Kumar P, Lalitha AV, Bukelo M. Caught Off Guard with COVID-19 Bowel Gangrene: A Case Report. Indian J Crit Care Med 2020;24(12):1269-1271.

Functional and Radiological Parameters to Assess Outcome of Endoscopic Third Ventriculostomy in Shunt Failure Patients.

BACKGROUND: Placement of ventriculoperitoneal shunt is a standard treatment for hydrocephalus. The risk of shunt malfunction in the first year is 25%-40% making endoscopic third ventriculostomy (ETV) a feasible option in those patients with shunt failure. AIM: The aim of this study was to evaluate ETV as a viable option in patients with shunt malfunction and to correlate the clinical outcome following successful ETV with functional and radiological outcomes. MATERIALS AND METHODS: All patients who underwent ETV as a diversion procedure for hydrocephalus following shunt failure or malfunction over 1 year were studied. Functional outcome was evaluated by Wee function independence measure score carried out preoperatively, postoperatively, and at 6-month follow-up. Similar comparison was carried out for radiological parameters such as effacement of gyri, periventricular lucency, frontal horn diameter (maximum), Evans' index, and third ventricular diameter. RESULTS: Of 15 patients, 61.5% were shunt free after ETV. All the failures were noted in the first month following the procedure. The factors, which showed statistically significant correlation with the outcome of ETV, included age (P = 0.030), preoperative functional score (P = 0.006), and all the three components of the functional scoring, namely self-care score (P = 0.087), motor control score (P = 0.035), and neurocognitive score (P = 0.003). Parameters such as Evans' index, maximum frontal horn diameter, and third ventricular diameter showed no significant difference between preoperative and postoperative scans. In follow-up imaging, only the frontal horn diameter showed a significant improvement (P = 0.047). CONCLUSION: ETV leads to significant neurocognitive improvement and postoperative functional status making it a viable option in patients who present with shunt malfunction.

Co-Existing Pediatric Ureteropelvic Junction Obstruction and Vesicoureteric Reflux: Prevalence and Implications.

PURPOSE: The purpose of this study is to ascertain the coexistence of ipsilateral vesicoureteric reflux (VUR) with ureteropelvic junction obstruction (UPJO) and to compare postpyeloplasty outcome in patients with and without associated VUR. MATERIALS AND METHODS: Prospective study from 2014 to 2016 of consecutive children (n = 135) undergoing pyeloplasty. Data of patients without (Group 1) and with (Group 2) associated ipsilateral VUR were compared. RESULTS: Thirty-five patients (25.9%) had ipsilateral VUR along with UPJO (Group 2). This group showed the following unique features: (1) Higher percentage of infants (31/35) compared to Group 1 (62/100) (P = 0.003) (2) VUR in the contralateral (normal) kidney in 21/35 (60%) cases and nil in Group 1 (3) Significantly less preoperative differential renal function in children above 1 year (P = 0.007) (4) Presence of renal scars (18 units) and pyelonephritic changes (6 units) in Group 2 at the 1-year follow-up dimercaptosuccinic acid renal scan. Both groups showed improvement in function 3 months after pyeloplasty with no statistically significant difference. Improvement in drainage on the renal scan was better in Group 1 at 3 months postoperative (P = 0.015) as well as between 3 months and 1-year follow-up (P = 0.052). CONCLUSION: The prevalence of VUR was 25.9% in this study and 33.3% in ≤1 year age group. There was a loss of function in delayed presenters with associated ipsilateral VUR. There was delayed drainage postpyeloplasty in patients with VUR. A preoperative voiding cystourethrogram should be done in children <1 year age before pyeloplasty so that associated VUR if detected can be concurrently managed along with pyeloplasty and preserve nephrons affected by the dual pathology.

Bronchoscopic Airway Foreign Body Extraction without Using Optical Forceps.

AIM: Airway foreign body (FB) is a very common pediatric surgical emergency. On certain difficult occasions, the extraction of FB with optical forceps (OFs) is difficult. These conditions create a life-threatening scenario. We present some of the alternative methods of FB extraction for these situations. PATIENTS AND METHODS: This is a retrospective case review of patients presenting to pediatric emergency with airway FB. All patients had a chest X-ray done before the procedure. Rigid bronchoscopy was performed in all patients for retrieval. RESULTS: A total of 20 patients (6 females) were successfully scoped. The age ranged from 1.5 years to 12 years (mean 3.5 years). Bronchoscopic removal was aided by dormia basket (DB) in 13, Fogarty's catheter (FC) in 6, and magnet aided removal in 1. Complete removal was achieved in all patients. CONCLUSIONS: We recommend that DB, FC, and a magnet should form an indispensable part of bronchoscopy set. The use of these alternative methods is successful and allows ventilation during the removal in contrast to removal by OFs. These should be kept as an option if retrieval is difficult.