Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies.

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies.

Clinical profile and outcomes of multisystem inflammatory syndrome in children (MIS-C): Hospital-based prospective observational study from a tertiary care hospital in South India.

AIM: To study the clinical profile and outcomes in children with multisystem inflammatory syndrome in children (MIS-C). METHODS: Children aged 1 month to 15 years presenting with MIS-C (May 2020 to November 2021) were enrolled. Clinical, laboratory, echocardiography parameters and outcomes were analysed. RESULTS: Eighty-one children (median age 60 months (24-100)) were enrolled. Median duration of fever was 5 days (3-7). Twenty-nine (35.8%) had shock (severe MIS-C) including 23 (28.3%) requiring inotropes (median duration = 25 h (7.5-33)). Ten required mechanical ventilation, 12 had acute kidney injury and 1 child died. Left ventricular (LV) dysfunction was seen in 38 (46.9%), 16 (19.7%) had coronary artery abnormalities (CAA) and 13 (20%) had macrophage activation syndrome. Sixty-one (75.3%) were SARS CoV-2 positive (10 by RT-PCR and 51 by serology). Sixty-eight (83.9%) received immunomodulators. Younger age was significantly associated with CAA (P value = 0.05). Older age, LV dysfunction, SARS CoV-2 positivity, low platelet count and elevated serum ferritin were significantly associated with severe MIS-C (univariate analysis). Younger age was an independent predictor of CAA (P = 0.05); older age (P = 0.043) and low platelet count (P = 0.032) were independent predictors of severe MIS-C (multivariate logistic regression analysis). CONCLUSION: Our patients had diverse clinical manifestations with a good outcome. Younger age was significantly associated with CAA. Older age, LV dysfunction, low platelet count and elevated serum ferritin were significantly associated with severe MIS-C. Younger age is an independent predictor of CAA. Older age and low platelet count are independent predictors of severe MIS-C.

Visceral Toxocariasis Presenting as Systemic-Onset Juvenile Idiopathic Arthritis.

An 8-year-old boy presented with intermittent fever, abdominal pain and joint pain for 1 month. On examination, he had pallor, generalized lymphadenopathy, hepatomegaly and arthritis. Investigations revealed anemia, leucocytosis, hypereosinophilia and hypergammaglobulinemia, with an elevation of inflammatory markers. Initially, suspected as systemic-onset juvenile idiopathic arthritis, and on further probing, the child had geophagy and contact with dogs in the household. Ultrasonography of the abdomen showed multiple cystic lesions, and serology for Toxocara canis was positive; hence the child was diagnosed with visceral toxocariasis and managed with albendazole therapy.

Acute Motor Axonal Polyneuropathy Following Mumps Infection in a 9-Year-Old Girl.

A 9-year-old girl presented with lower motor neuron type of paralysis involving limbs, trunk and multiple cranial nerves (7, 9 and 10) with preceding history of mumps 1 week before the onset of weakness. There were no features to suggest either a meningitis or encephalitis in the child. Cerebrospinal fluid showed hypoglycorrhachia and mild protein elevation; magnetic resonance imaging of the brain was normal. Nerve conduction study showed motor axonal neuropathy. Serology for mumps IgM was positive, consistent with a diagnosis of post-mumps acute motor axonal polyneuropathy. The girl made a complete recovery within 3 weeks.

Hemophagocytic Lymphohistiocytosis in A Child With Very Severe Aplastic Anemia: Double Jeopardy Resulting in Fatality.

A 7-year-old male child with very severe aplastic anemia developed refractory disease, which was attributed to febrile hemolytic transfusion reactions and was treated with immunosuppressants, which lead to a transient improvement. However, the child worsened subsequently and succumbed to an underlying hemophagocytic lymphohistiocytosis that was recognized late due to an overlap of clinical and biochemical parameters in both the conditions. Hemophagocytic lymphohistiocytosis should be an early suspicion in children with refractory very severe aplastic anemia and the detection of underlying gene mutations can predict disease severity.

Chronic Pruritus in an 18-Month-Old Male Infant Due to Anicteric Cholestasis.

An 18-month-old male infant was referred to us with pruritus from 6 months of age. He was being managed as atopic eczema with emollients and antihistamines without any response to treatment. On examination, he was found to have extensive scratch marks, mild hepatomegaly and no icterus. Blood investigations were suggestive of anicteric cholestatic liver disease. Liver biopsy was suggestive of progressive familial intrahepatic cholestasis type 3. He showed symptomatic improvement after starting ursodeoxycholic acid and fat-soluble vitamins and is under follow up.

Brachial artery flow-mediated dilatation and carotid intima medial thickness in pediatric nephrotic syndrome: a cross-sectional case-control study.

BACKGROUND: Children with nephrotic syndrome (NS) have hyperlipidemia, which may lead to endothelial dysfunction. This study evaluated endothelial function and structural atherosclerosis in NS children with disease duration more than 2 years, by assessment of brachial artery flow-mediated dilatation (FMD) and carotid intima medial thickness (CIMT). METHODS: This is a cross-sectional case-control study recruiting 32 subjects aged 1-13 years with NS and 32 matched controls. Clinical details, FMD and CIMT were recorded. Lipid profile and oxidative stress were also analyzed in the subjects. RESULTS: The proportionate change in FMD was significantly lower in cases (5.65 ± 6.08 %) compared to controls (15.21 ± 9.41 %) (p < 0.01). No significant differences in CIMT were observed (p = 0.383). Blood malondialdehyde was significantly higher (p = 0.006) in the cases. Overall, 25 NS children (78 %) were in remission for more than 6 months, and in them, 9 (36 %) had deranged lipid profile. On stepwise linear regression, age of the patient was found to be a determinant of FMD (model R (2) = 18.9 %, p value = 0.048). CONCLUSION: The significantly low proportionate change in FMD in NS children suggests an ongoing process of endothelial dysfunction. Further studies are needed to confirm these findings. A long-term follow-up of children with NS may be required for identification of CIMT derangements.

Comparison of two empiric antibiotic regimen in late onset neonatal sepsis--a randomized controlled trial.

OBJECTIVE: To compare the effectiveness of two antibiotic regimens among neonates with late onset sepsis (LOS). METHODS: This randomized controlled trial conducted in a tertiary care teaching hospital, South India, included 90 babies with LOS. Detailed history, examination and appropriate investigations were done for all the babies. Cloxacillin + Amikacin were administered to 40 and Cefotaxime + Gentamicin to 50 babies. Outcomes including mortality, complications and treatment failure were evaluated. Chi-square test was used for categorical variables and Student's unpaired t-test for continuous variables. RESULTS: LOS had a male preponderance, and median time of onset was 13 days. Mortality was more among low birth weight babies irrespective of the antibiotics. Predominant bacteria isolated were coagulase-negative staphylococci (26.67%), Escherichia coli (13.33%) and Streptococcus pneumoniae (13.33%). Complications, mortality and cost were similar in both regimens. CONCLUSION: There was no significant difference between the two antibiotic regimens with regard to outcome of LOS.

Longitudinal Echocardiographic Follow-Up of a Pediatric Multisystem Inflammatory Syndrome Cohort.

OBJECTIVE: Significant involvement of the cardiovascular system is known in multisystem inflammatory syndrome in children (MIS-C). This study aimed to examine the recovery of affected cardiovascular parameters over a medium-term follow-up. METHODS: A cohort of 69 children was studied prospectively. Assessments of left ventricular (LV) function and coronary artery abnormalities (CAA) were conducted at admission, 1.5 months, and 3 months. Coronavirus Disease 2019 (COVID-19) antibody titers were assessed at these three time points. Echocardiographic and antibody parameters (rising/decreasing) were analyzed for correlation. Outcomes were assessed using logistic regression. RESULTS: At admission, among the 78.2% of patients who were tested, 88.9% tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). A quarter of the patients had pericardial effusion, and half had valvulitis. Decreased ejection fraction, global circumferential strain (GCS), and global longitudinal strain (GLS) were seen in 54.4%, 68.6%, and 35.8% of patients, respectively. CAAs were observed in 27.78% of patients. Systolic dysfunction was significantly associated with older age. During follow-up, severe LV dysfunction normalized within 6-7 weeks, while mild to moderate dysfunction reached normalcy by two weeks. Both GCS and GLS reached normalcy within a median of two weeks. Diastolic parameters recovered by six weeks. Most small and moderate coronary aneurysms resolved, but a giant aneurysm in an infant remained large even after 15 months. Trends in antibodies and ejection fraction (EF) at three months were significantly correlated. Admission EF, GLS (at 6 weeks) and deceleration time (at 3 months) were significantly associated with intensive care unit (ICU) admission. The median segmental strain of the cohort remained low in certain segments at three months. CONCLUSION: Smaller CAAs resolve, whereas giant CAAs persist. EF and GLS are important predictors of Pediatric Intensive Care Unit (PICU) stay. The residual impairment of median segmental strain and persistent diastolic dysfunction at three months indicate the need for long-term follow-up.

Clinical profile of acute kidney injury in a pediatric intensive care unit from Southern India: A prospective observational study.

BACKGROUND: Although the term acute renal failure was replaced by acute kidney injury (AKI) recently, there is a paucity of data on the incidence and profile of AKI in critically ill children from the developing world. OBJECTIVES: The objective of this study is to determine the incidence, etiology, short term outcome and predictors of fatality in critically ill children admitted to the pediatric intensive care unit (PICU) with AKI, aged 1 month to 13 years. MATERIALS AND METHODS: In this prospective observational study, from June 2010 to March 2011, 215 children admitted to the PICU were screened for AKI, defined according to the AKI Network criteria. The patients with AKI were followed-up until discharge/death. Their clinical and biochemical data were recorded. RESULTS: The incidence of AKI among 215 patients screened was 54 (25.1%). The common etiologies were infections, [34 (62.9%)], acute glomerulonephritis (7.6%), snake envenomation (5.7%), hemolytic uremic syndrome (3.8%) and congestive cardiac failures (3.8%). Among infections, pneumonia and septicemia constituted 26.5% each, meningoencephalitis accounted for 23.5%, and dengue, scrub typhus, tuberculosis and malaria constituted 9.3% of children with AKI. 27.8% of patients required dialysis. Overall mortality was 46.3%. On logistic regression analysis, requirement of mechanical ventilation was an independent predictor of fatality in AKI. CONCLUSIONS: Besides the high incidence of AKI in critically ill-children admitted to the PICU (25.1%), the condition was associated with adverse outcomes, including high mortality (46.3%) and need for dialysis (27.8%). Infections dominated the etiological profile. Requirement of mechanical ventilation predicted an adverse outcome in our patient population.

Bacteriuria due to Typhoidal and Nontyphoidal Salmonella: A Report of Three Cases from South India.

Urinary tract infection (UTI) with Salmonella is uncommon, accounting for merely 0.01% to 0.1% of cases of UTIs. It is reported more frequently in the presence of predisposing factors such as structural abnormalities of the urinary tract or weakened immune system. We present a case series of three patients with Salmonella bacteriuria and their susceptibility patterns. All three patients had underlying urologic features such as neurogenic bladder, chronic kidney disease, and urethral stricture, and two presented with urinary tract involvement symptoms.

Osteomyelitis and pyomyositis due to Pseudomonas aeruginosa in a child with sickle ß°-thalassemia.

Sickle cell osteomyelitis is usually due to Salmonella or Staphylococcal etiology. Pseudomonas as a cause of sickle cell osteomyelitis is rare. Similarly, pyomyositis is a rare complication in children with sickle cell disease and few cases have been reported, predominantly due to Staphylococcus. We describe an 8-year-old boy who presented with high-grade fever and tender, swollen left thigh. There was a history of intramuscular injections in the left thigh. He also had severe anemia, hepatosplenomegaly, and laboratory evidence of hemolysis. Hemoglobin electrophoresis showed sickle ß-thalassemia. Magnetic resonance imaging of the left thigh showed evidence of osteomyelitis with pyomyositis. Surgical drainage of the pus was done and Pseudomonas aeruginosa was isolated. He was treated with intravenous antibiotics for 8 weeks. The child had a protracted course of illness with development of pathologic fracture of the femur. Clinicians need to be aware of Pseudomonas infection as a complication in children with sickle cell disease, as this affects therapeutic decisions, including the choice of antibiotics.

Effect of Neutralization of Gastric Aspirate on culture yield of mycobacterium tuberculosis in children with pulmonary tuberculosis.

INTRODUCTION: Conventionally gastric aspirates are neutralized with sodium bicarbonate to improve the culture yield of MTB. However, only limited data is there to support this practice. The aim of this study was to compare the contamination rate, culture yield and time to detection of Mycobacterium tuberculosis (MTB) in neutralized and non-neutralized gastric aspirate samples and report the drug resistance. MATERIALS AND METHODS: A total of 336 neutralized and non-neutralized gastric aspirate samples were simultaneously cultured by both LJ culture and MGIT 960 to compare the difference in isolation rate, time to detection and contamination rate. First line drug susceptibility testing was performed using MGIT 960 SIRE kit. RESULTS: MTB was isolated from 8.6% (29/336) of GA samples by one or more of the culture methods. The isolation rate of MTB from neutralized and non-neutralized GA samples by combined LJ and MGIT 960 culture was 7.1% (24/336) and 6.8% (23/336), respectively. Both of them detected 18 MTB isolates in common. However, the neutralized and non-neutralized GA samples detected additional 6 and 5 MTB isolates, respectively. The mean time to detection of MTB were similar. In MGIT 960 culture, contamination rate of non-neutralized samples (17%) was significantly lower when compared to neutralized samples (21.1%) (P = 0.044). Drug susceptibility testing of MTB isolates revealed that, out of 26 isolates, 2 were resistant to ethambutol, one each was resistant to isoniazid and rifampicin. CONCLUSION: The findings of this study suggest that non-neutralized samples should be routinely processed in addition to the neutralized samples for optimum isolation of MTB from gastric aspirate samples.

Epinephrine Plus Vasopressin vs Epinephrine Plus Placebo in Pediatric Intensive Care Unit Cardiopulmonary Resuscitation: A Randomized Double Blind Controlled Clinical Trial.

OBJECTIVE: To compare the efficacy of epinephrine plus vasopressin vs epinephrine plus placebo in the pediatric intensive care unit (PICU) cardiopulmonary resuscitation (CPR). DESIGN: Randomized, double-blind controlled clinical trial. SETTING: PICU in a tertiary care institute from February, 2019 to May, 2020. PARTICIPANTS: Children aged one month to 13 years who required CPR during PICU stay. Patients in whom vascular access was not available or return of spontaneous circulation (ROSC) was achieved by defibrillation without epinephrine were excluded. INTERVENTION: Patients were randomized to receive vasopressin 0.1 mL per kg (=0.8 unit per kg) or placebo (0.1 mL per kg normal saline) in addition to epinephrine (1:10000) 0.1 mL per kg. The drugs were given as bolus doses every three minutes until the ROSC or up to a maximum of five doses, whichever was earlier. OUTCOME MEASURE: The primary outcome was the proportion of patients who achieved ROSC. The secondary outcomes were survival rate and functional status (at 24-hour, PICU, hospital, and 90-day post-discharge), need for organ supports, length of stay (PICU and hospital), and adverse effect(s) of the study drugs. RESULTS: 90 patients (epinephrine plus vasopressin group, n=45 and epinephrine plus placebo group, n=45) were analyzed on intention-to-treat basis. There was no significant difference in the primary outcome between epinephrine plus vasopressin (n=25, 55.5%) and epinephrine plus placebo groups (n=24, 53.3%) (Relative risk 1.04, 95% CI 0.71 to 1.52). There was no significant difference in survival rate at 24-hour (n=7, 15.6% vs. n=8, 17.8%), at PICU, hospital, and 90-day post-discharge (n=1, 2.2% vs n=1, 2.2%). There was no difference in other secondary outcomes. No trial drug-related serious adverse events were observed. CONCLUSIONS: A combination of epinephrine plus vasopressin did not improve the rate of return of spontaneous circulation in the pediatric intensive care unit cardiopulmonary resuscitation as compared with epinephrine plus placebo.

Respiratory infections: Role of Vitamin D and surfactant proteins A and D.

Respiratory tract infection is the common viral infection and the principal cause of death among children under 5 years of age. It damages lung epithelium and increases mucus production and inflammation, leading to dyspnea. The sunshine vitamin (Vitamin D) and surfactant protein (SP) A and D along with their usual function play an important role in host defense. This article reviews with immune role of Vitamin D and SP A and D which aids excessive cytokines production, boosts phagocytosis, hinders inflammatory activity, and thus acts as a first-line defense against lung pathogens.

Vitamin D Status at Admission and Its Association With Mortality in Children Admitted to the Pediatric Intensive Care Unit.

Introduction This study aims to evaluate the prevalence of vitamin D deficiency and the correlation between serum 25-hydroxyvitamin D (25(OH)D) and mortality. Materials and methods A prospective observational study was conducted among 522 children admitted to the Pediatric Intensive Care Unit in the Pediatrics Department of the Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India. After measuring vitamin D levels, children were assigned into three groups based on their serum 25(OH)D levels: a sufficient group (25(OH)D level ≥ 30 ng/mL), an insufficient group (25(OH)D level = 20-29.9 ng/mL), and a deficient group (25(OH)D level < 20 ng/mL). Each group was again divided into two sub-groups (survivors and non-survivors if death was the outcome), and then each sub-group was again divided into two groups (sepsis and all non-septic causes). Results were evaluated for an association with mortality. Results A majority (66.6%) of patients who died had low levels of 25(OH)D (deficient = 37.9%; insufficient = 28.7%). Mortality was higher in children with 25(OH)D deficiency (P = 0.03). In univariate analysis, 25(OH)D deficiency was strongly associated with sepsis in children according to our observation, with 51% from the deficient group, 38% from the insufficient group, and 27.5% from the sufficient group (P ≤ 0.01). Mortality is not associated with 25(OH)D deficiency or insufficiency in multilogistic regression analysis. A serum vitamin D level of 20 ng/mL can predict higher mortality, with a specificity of 62.1%. Conclusions Vitamin D supplementation may be recommended for PICU-admitted cases to decrease the risk of sepsis. This association can be explored more in the future among the community population for further recommendations.

Association Between Vitamin D Deficiency and Duration of Hospital Stay, Pediatric Intensive Care Unit Stay, and Ventilation; Pediatric Risk of Mortality Score; and Rate of Readmission: A Prospective Observational Study.

Introduction The study aims to evaluate the association between a deficiency of Vitamin D level with the duration of hospital stay, pediatric intensive care unit (PICU) stay, and ventilation; the pediatric risk of mortality (PRISM) score, and the rate of readmission. Materials and methods This prospective observational study was conducted from November 2014 to October 2015, and the study population consisted of children admitted to the pediatric intensive care unit (PICU) in a tertiary care hospital of Puducherry. After measuring vitamin D levels, children were allotted into three categories depending on their serum 25(OH)D levels as the sufficient group (25[OH]D level ≥ 30 ng/mL), insufficient group (25[OH]D level = 20 - 29.9 ng/mL), and deficient group (25[OH]D level < 20 ng/mL). Among these three groups, the duration of hospital stay, PICU stay, and ventilation; the PRISM score, and the rate of readmission were compared. Results A total of 522 patients were included in the study. Based on their 25(OH)D level, 222 patients (42.5%) were in the sufficient category, 153 patients (29.3%) were in the deficient category, and 147 patients (28.2%) were in the insufficient category. Vitamin D deficiency state is not statistically significantly associated with the duration of hospital stay (P = .84), duration of PICU stay (P = .69), duration of ventilation (P = .48), PRISM score (P = .63), and rate of readmission (P = .91). Conclusions Longer hospital stay, prolonged PICU stay, longer duration of ventilation, and higher PRISM III score were independent risk factors for higher mortality in the PICU. However, lower vitamin D levels are not statistically significant to predict mortality among the study population.

Respiratory Morbidity Following Foreign Body Aspiration Among South Indian Children: A Descriptive Study.

Aim Our work aimed to study the clinical features and radiological signs of foreign body aspiration in South Indian children. Materials and methods We conducted this prospective cross-sectional study for one year in the Department of Paediatrics, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India in 56 cases. Our study included children younger than 14 years attending our hospital with a history of foreign body aspiration with or without respiratory distress, suspected cases of foreign body aspiration showing evidence of unilateral hyperinflation with or without evidence of collapse of the opposite lungs on chest X-ray (posterior-anterior view), and unexplained cough associated with X-ray evidence of unilateral hyperinflation or bronchiectasis. Emergency and elective rigid bronchoscopy were performed as per the clinical scenario, and patients were discharged from the hospital after stabilization. They were asked to return for two-week, three-month, and six-month follow-up evaluations. Results The most common age group of patients with foreign body aspiration was six to 18 months old. A definite history of foreign body aspiration was obtained in only 32 patients (57%). Most patients (n = 22; 68.75%) presented to the hospital within one to seven days of the foreign body aspiration. Respiratory distress was the most common clinical feature, present in 96% of our patients. The most common radiographic feature in our study was obstructive emphysema, seen in 33 patients (58.9%). Foreign bodies were retrieved from 40 patients (71.4%), and no foreign body could be found via bronchoscopy in 16 patients. The most common foreign body was groundnut (n = 27; 67.5%). Only four patients had inorganic foreign bodies. The most common site of aspirated foreign bodies was the right main bronchus (n = 14; 35%). Only two patients (3.57%) had persistent pneumonia that cleared up radiologically after three months and was culture negative for bacteria. Conclusions Strong clinical suspicion of foreign body aspiration based on history and early bronchoscopy can reduce the morbidity and mortality due to foreign body aspiration in children.