Spectrum of Primary Immunodeficiency Disorders in Hospitalized Children: Multicentric Data From Kolkata.

OBJECTIVE: To evaluate the incidence and types of primary immunodeficiency diseases (PIDs) in hospitalized children with infection. METHODS: This prospective study was conducted in five tertiary-care facilities in Kolkata over two consecutive years between November 1, 2018 and October 31, 2020. We included all children aged upto 12years who were hospitalized and screened them for PID. Children were screened for suspected IPD using Jeffrey Modell Foundation (JMF) Criteria; any child who satisfied at least 2 out of 10 warning signs was further evaluated for PIDs. RESULTS: Out of 33,204 hospital admissions, 50 children satisfied JMF criteria. Out of 50 children screened during the study period, 27 were finally diagnosed with an underlying PID, with a prevalence of 1 in 1000 hospitalized children. Majority (37.03%) of them had antibody deficiency followed by phagocytic defect (33.3%). Chronic granulomatous disease was the commonest PID followed by common variable immunodeficiency. Around 62.97% children presented with respiratory infections and overall Acinetobacter baumannii was the commonest isolated organism. CONCLUSION: Our study presents the first cohort of PID from eastern India. A methodical step-wise clinical and diagnostic approach can facilitate early diagnosis and timely therapeutic interventions.

Mortality indicators with clinical profile of multisystem inflammatory syndrome in children during SARS-CoV-2 second wave in India: A tertiary referral center experience.

Background: Post-COVID-19 cases are being reported with features of hyperinflammatory state causing multiple system dysfunctions in previously healthy children. Objectives: To describe clinical characteristics, laboratory, and radiological profile of children affected with COVID-19-related multisystem inflammatory syndrome postsecond wave in India and compare them with respect to adverse outcome. Materials and Methods: This prospective, observational study was conducted in the department of pediatrics of a tertiary care center in Eastern India over a period of 3 months. Demographic data, clinical details, biochemical parameters, and treatment with clinical outcome were recorded. Children who survived the clinical course were compared with those died during hospital stay. Results: Thirty-five children with a median age of 4.8 (3.9) years were included who were admitted between June 16 and September 15, 2021. Only 17.14% had reverse transcription-polymerase chain reaction positivity previously with 77.14% had positive COVID-19 serology. Most common features were fever (100%), edema (68.6%), gastrointestinal (71.4%), mucocuteneous (65.7%), cardiovascular (57.1%), and neurological symptoms (45.7%). Twenty (57.1%) children had shock at presentation. Decreased ejection fraction (<55%) was the most common echocardiographic feature (37.14%) followed by coronary dilatation (20%). Majority (77.14%) of the patients required intensive care with inotrope requirement in 62.86% cases. Forty percent patients were intubated with mean duration of 9.94 (±10.5) days. All patients received methylprednisolone and 76% were given intravenous immunoglobulin. Tocilizumab was used in three patients. Nine patients died (25.7%) with overall median pediatric intensive care unit stay of 13 (14) days. Conclusion: Of the parameters described, we have found shock, heart failure, neurological involvement at presentation, infancy, and laboratory parameters such as C-reactive protein, CPK, D-Dimer, and lactate dehydrogenase were the predictors of mortality.

Autoimmune diseases post-COVID 19 infection in children in intensive care unit: A case series.

SARS-CoV2 primarily affects the respiratory system but a hyperinflammatory response leading to multisystem inflammatory syndrome - children (MIS-C), immune dysfunction and various autoimmune manifestations has also been noted. Autoimmunity depends on various factors, including genetic predisposition, environmental factors, immune dysregulation and infections acting as triggers like Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, hepatitis B. Molecular mimicry, bystander T-cell activation and persistence of viral infection are the main mechanisms behind these manifestations. We present here 3 cases of newly diagnosed connective tissue disease with high titers of COVID19 immunoglobulin G antibody in children. A 9-year-old girl with fever, oliguria and malar rash (prior history of sore throat) and a 10-year-old girl with fever for 2 weeks and choreoathetoid movements were diagnosed as systemic lupus erythematosus (SLE) nephritis (stage 4) and neuropsychiatric SLE, respectively as per European League Against Rheumatism / American College of Rheumatology 2019 criteria. An 8-year-old girl with fever, joint pain and respiratory distress (a recent contact with a positive COVID19 patient) presented with altered sensorium, Raynaud's phenomenon noted, and eventually diagnosed as mixed connective tissue disease as per Kusukawa criteria. The immune-mediated manifestations post-COVID infection are a de-novo phenomenon which necessitates further workup as not many studies exist in the pediatric population.

Gating interactions steer loop conformational changes in the active site of the L1 metallo-ß-lactamase.

ß-Lactam antibiotics are the most important and widely used antibacterial agents across the world. However, the widespread dissemination of ß-lactamases among pathogenic bacteria limits the efficacy of ß-lactam antibiotics. This has created a major public health crisis. The use of ß-lactamase inhibitors has proven useful in restoring the activity of ß-lactam antibiotics, yet, effective clinically approved inhibitors against class B metallo-ß-lactamases are not available. L1, a class B3 enzyme expressed by Stenotrophomonas maltophilia, is a significant contributor to the ß-lactam resistance displayed by this opportunistic pathogen. Structurally, L1 is a tetramer with two elongated loops, α3-ß7 and ß12-α5, present around the active site of each monomer. Residues in these two loops influence substrate/inhibitor binding. To study how the conformational changes of the elongated loops affect the active site in each monomer, enhanced sampling molecular dynamics simulations were performed, Markov State Models were built, and convolutional variational autoencoder-based deep learning was applied. The key identified residues (D150a, H151, P225, Y227, and R236) were mutated and the activity of the generated L1 variants was evaluated in cell-based experiments. The results demonstrate that there are extremely significant gating interactions between α3-ß7 and ß12-α5 loops. Taken together, the gating interactions with the conformational changes of the key residues play an important role in the structural remodeling of the active site. These observations offer insights into the potential for novel drug development exploiting these gating interactions.

Acute demyelination of the medulla oblongata owing to scrub typhus in a 7-year-old boy: case report.

ABBREVIATIONS: ADEM: acute disseminated encephalomyelitis; CT: computed tomography; MRI: magnetic resonance imaging; PGCS: paediatric Glasgow coma scale; PICU: paediatric intensive care unit.

Evaluation of vitamin D profile in juvenile idiopathic arthritis.

OBJECTIVE: To observe the association between serum vitamin D level and disease activity in juvenile idiopathic arthritis (JIA). METHODS: The observational study was conducted at a tertiary care hospital during 2017-2019. Patients suffered from JIA were recruited through purposive sampling which was stratified by the disease activity based on the Juvenile Arthritis Disease Activity Score 27 (JADAS27) criteria. Serum vitamin D was estimated alongside other laboratory parameters. The numerical and categorical variables were analysed with appropriate statistical tests. RESULTS: 40 subjects were studied where inactive disease was observed in nine subjects (22.5%), five subjects (12.5%) were found to be in low disease activity and moderate disease activity groups each, and twenty-one subjects (52.5%) had high disease activity. Considering the total sample size of the study, the mean (SD) JADAS27 score and serum vitamin D level were observed to be 12.02 (11.31) and 23.10 (5.93) respectively. A negative correlation was found between the JADAS27 score and serum vitamin D (r= -0.67). The corrected Chi-square test had revealed significant association between the status of serum vitamin-D and disease activity groups (=16.28; p < .001). CONCLUSIONS: In JIA, higher grade of disease activity was found to be significantly associated with lower serum vitamin D.

Performance of SNAPPE-II score in neonatal sepsis: an experience from a tertiary care center.

BACKGROUND AND OBJECTIVES: The Score for Neonatal Acute Physiology II with Perinatal Extension (SNAPPE-II) is a vital tool for prognostication in newborns. The study was conducted with the hypothesis that the performance of the SNAPPE-II score might be affected by the presence of sepsis in newborns admitted with possible early onset septicemia and whether score performance varies between culture positive and culture negative sepsis. METHODS: The prospective observational study was conducted over a period of 1 year (January 2014 to January 2015) in neonates presenting with clinical suspicion of sepsis to the Sick Newborn Care Unit (SNCU) of a tertiary care hospital in Eastern India. RESULTS: SNAPPE-II score cut-off of ≥20 offered the highest sensitivity of 74.5% with specificity 48.3%, PPV 27.6% and NPV 87.7%. Comparison of mortality proportions between the two subgroups defined by this cut-off returned p= 0.005 with OR 3.47 (95% 1.40 to 8.64). No significant association was found between SNAPPE-II score and blood culture results; mean scores for culture positive (25.16 ± 15.6) and negative groups (24.49 ± 15.6) were comparable (p= 0.920). CONCLUSIONS: At a cut-off value of ≥20 in presence of sepsis, SNAPPE-II score offers acceptable indices to predict mortality outcome. Prediction of outcome by SNAPPE-II score is not affected by positive or negative blood culture sepsis.

Ultrasound detected changes in joint cartilage thickness in juvenile idiopathic arthritis.

AIM: The purpose of this study was to investigate the changes in joint cartilage thickness in different subtypes of juvenile idiopathic arthritis (JIA) using ultrasound, comparing them with healthy children and to evaluate the relationship with disease duration and inflammatory markers. METHODS: We conducted a cross-sectional study comprising of 27 cases of JIA and 54 age- and sex-matched healthy children. Bilateral wrist, knee and ankle joint cartilage thicknesses were measured by ultrasound as per European League Against Rheumatism standard guidelines and compared them between JIA subtypes as well as between cases and control. RESULTS: Descriptive analysis of the whole cohort revealed the mean age of the study population was 8.3 ± 3.2 years with mean cartilage thicknesses at the wrist, knee and ankle being 1.40 ± 0.89 mm, 1.57 ± 0.78 mm and 1.41 ± 0.85 mm, respectively. The median cartilage thicknesses of wrist, knee and ankle joints of JIA cases (n = 27) and healthy controls (n = 54) were 1.01, 1.35, 1.05 and 1.95, 2.00, 1.95, respectively. The joint cartilage thickness was significantly reduced in JIA in comparison to the healthy cohort (P < 0.01). Diseased boys suffered greater cartilage damage in knee joints compared to girls; the polyarticular variety of cases had thinner knee cartilage in comparison to the oligoarticular subtype. Further, it was found that joint cartilage destruction is independent of inflammatory markers and disease duration. CONCLUSION: Significant cartilage thinning in addition was found in JIA children, particularly in the polyarticular subtype, and more in boys than girls, which is independent of disease duration and inflammatory markers, using ultrasound as a primary investigative tool.

Extended Sick Neonate Score (ESNS) for Clinical Assessment and Mortality Prediction in Sick Newborns referred to Tertiary Care.

OBJECTIVE: To evaluate utility of a new Extended Sick Neonate Score (ESNS). to predict 'in-hospital mortality' and compare with Score for Neonatal Acute Physiology - Perinatal Extension II (SNAPPE II) and Sick Neonate Score (SNS). DESIGN: Prospective observational study. METHODS: All extramural sick newborns transported to the neonatology unit of a tertiary care teaching hospital over a period of one year. Correlation between ESNS, SNAPPE-II and SNS scoring, and sensitivity/specificity of each score to predict mortality were determined. RESULTS: 961 newborns were enrolled in the study. ESNS, SNAPPE II and SNS were strongly correlated, even when stratified by gestation. ESNS of ≤11 had the best sensitivity (85.9%) and specificity (89.8%). For preterms, ESNS ≤12 had the best sensitivity (92.3%) and specificity (76.7%). CONCLUSION: ESNS can predict 'in-hospital mortality' outcome with satisfactory sensitivity and specificity.

Evaluation of joint cartilage thickness in healthy children by ultrasound: An experience from a developing nation.

OBJECTIVES: Musculoskeletal ultrasound (MSUS) has a crucial role in clinical assessment and monitoring of patients with rheumatologic diseases. Early detection of joint cartilage destruction is difficult. MSUS is a cheap, noninvasive, nonhazardous bedside tool that can be used for detection of cartilage damage. We aimed to generate normative data of joint cartilage thickness of children in our population using this tool. METHODS: Healthy children, aged between 2 and 12 years, not suffering from any joint disorders and not on any chronic medication were recruited. The thickness of joint cartilage at wrist, knee and ankle were measured by ultrasound as per European League Against Rheumatism standard scan criteria. The scans were done by a single observer. RESULTS: Data of 409 children revealed median cartilage thickness at right wrist, knee and ankle joints as 2.20 (interquartile range [IQR] 1.60-3.00) mm, 2.40 (1.80-3.10) mm and 2.20 (1.80-3.00) mm, respectively. The right-left differences were not statistically significant except at the knee joint. Comparison between genders showed that boys had marginally thicker cartilage than girls at all three joints; this difference was statistically significant for the knee and ankle joints, but not at the wrist. Joint cartilage thickness showed a steady decline with age. CONCLUSIONS: Measurement of joint cartilage thickness in children with MSUS and comparison with these normative values can help in better screening for joint-related disease in children.

Survey of musculoskeletal abnormalities in school-going children of hilly and foothill regions of Eastern Himalayas using the pediatric Gait, Arms, Legs, Spine screening method.

OBJECTIVE: To study the prevalence and pattern of musculosketetal abnormalities in school-going children living in the hilly and foothill regions of the Eastern Himalayas using the pediatric Gait, Arms, Legs, Spine (pGALS) screening tool. METHODS: Total of 3608 children, aged 3-12 years were enrolled from 16 schools (5 in the hills) in the eastern Himalayan region. After the three screening questions, the pGALS maneuvers were administered. Subjects were shown a video on pGALS before the actual testing. Those detected to have abnormality were probed in greater detail and referred for treatment as necessary. RESULTS: The pGALS examination was completed in 3463 children with a median time of 3 min (range 1.9-5.4 min). The abnormality pattern was in the order: growing pains (38.86%), hypermobility (25.54%), mechanical pains (24.46%) and others (11.14%). Among mechanical pain, back and neck problems occurred with a similar overall frequency of 7.61%. Similar order was observed considering only children from the pains. However, in hill children, the proportion of mechanical problems (32.28%) exceeded proportion of hypermobility (23.62%). Asymptomatic hypermobility was more common than symptomatic hypermobility. Maximum prevalence of hypermobility was in 6-9 year age group. Of the 94 children with hypermobility, 55.32% had some kind of joint pain. CONCLUSIONS: Pediatric Gait, Arms, Legs, Spine is an acceptable screening tool for musculoskeletal abnormalities in apparently healthy children. Growing pain is the commonest musculoskeletal complaint while hypermobility is the commonest physical abnormality in school-going children in the Eastern Himalayas. Asymptomatic hypermobility is more common than symptomatic hypermobility.

Childhood lupus nephritis: 12 years of experience from a developing country's perspective.

OBJECTIVE: To assess the long-term outcome of lupus nephritis in children with systemic lupus erythematosus followed up over 12 years at a tertiary care teaching hospital in Eastern India. MATERIAL AND METHODS: This is a retrospective observational study of the clinicopathological presentation, management, and outcome in 46 children with lupus nephritis over a period of 12 years at a tertiary teaching hospital in Eastern India. Mortality was compared between different lupus classes and therapy groups with Kaplan-Meier analysis and log-rank test. RESULTS: The incidence of lupus nephritis was 58.97% [95% confidence interval (CI) 48.06%-59.89%] with the mean age at presentation being 10.2±2.43 years (range 5.5-14.5) years. Majority belonged to class IV (30.43%), followed by class II (26.91%), class III (23.91), and class V (8.70%). Outcome analysis of children with lupus nephritis over 12 years revealed that 24 (52.17%) achieved complete remission of disease activity, 5 attained partial remission, 4 continued to have active disease, 5 developed end-stage renal disease (ESRD), and 8 died. Overall mortality thus observed was 17.39% with septicemia in the background of ESRD being the commonest cause. No significant difference in mortality was observed between different lupus nephritis classes or therapy arm groups. CONCLUSION: The study throws light on various aspects of lupus nephritis and their long-term outcome patterns in children from developing countries such as India.

Neurological manifestations in children with dengue fever: an Indian perspective.

Ours was a descriptive observational cross-sectional study carried out in a tertiary care hospital in eastern India over a period of one year to study the profile of neurological involvement in paediatric dengue patients. Of 71 laboratory-confirmed cases, 20 (28.17%) had neurological involvement. Common forms observed were acute encephalopathy (40%), encephalitis (30%), pure motor weakness (15%), transverse myelitis (5%), acute disseminated encephalomyelitis (5%) and Guillain-Barré syndrome (5%). The dengue IgM antibody could be detected in the cerebrospinal fluid of only two patients with encephalitis. Neurological involvement was present in all four patients who died during the study period (two-tailed P value = 0.005).

Penile Length and Testicular Volume in Newborns.

OBJECTIVES: To measure Penile length (PL) and Testicular volume (TV) in newborn boys for assessing genital abnormalities. METHODS: In a tertiary care setting, measurements of PL and TV were recorded from 480 babies born on alternate days except the weekend, at 24 to 72 h of life by one investigator with the same set of instruments. The penis was stretched to the point of increased resistance and the distance from the tip of the glans penis to the pubic ramus was measured as the stretched PL. Testicular volume was measured by a Prader orchidometer. Improvised beads made of plasticine were used for recording volumes <1 ml. RESULTS: In the study cohort, 365 (76.04 %) were term babies. The mean PL was 34 ± 4.7 mm for the whole cohort while the corresponding value for mean TV was 0.6 ± 0.2 ml. The gestation age-wise percentile charts of PL and TV have been generated. There was modest positive correlation between PL and TV. Positive correlation was also observed between PL and TV and birth weight, body length, and head, chest and arm circumference. Both PL and TV showed statistically significant increase with gestational age. By the index data, the cut-off for suspecting abnormal penile length should be <24.5 or >45.5 mm for term babies. CONCLUSIONS: The normative values generated can serve as reference standard in the diagnosis of penile length abnormalities in Indian babies and in clarifying issues of ambiguous genitalia and maldevelopment of male external genitalia.

Clitoral Length and Anogenital Ratio in Indian Newborn Girls.

OBJECTIVE: To generate normative data on clitoris length, anogenital distance and anogenital ratio in Indian newborns. DESIGN: Cross-sectional study. SETTING: Neonatal unit of a tertiary care teaching hospital in Kolkata. PARTICIPANTS: 378 female neonates, who were hemo-dynamically stable without critical illness or chromosomal anomaly, and without any vulval hematoma or genital abnormalities. INTERVENTIONS: Measurements were recorded using a digital vernier caliper between 24-72 hours. Infant was held in position by an assistant, while the investigator measured clitoral length by gently retracting the labia majora. Anogenital distance (centre of the anus to posterior convergence of the fourchette) and anogenital ratio (anogenital distance divided by the distance from centre of the anus to base of the clitoris) was also measured. MAIN OUTCOME MEASURES: Gestational age- and birthweight-wise normative values of clitoral length, anogenital distance and anogenital ratios. RESULTS: Mean clitoral length was 3.1 (1.54) mm for the whole cohort while anogenital distance and anogenital ratio were 10.2 (2.78) mm and 0.34 (0.07) mm, respectively. The gestation age-wise percentile charts of clitoral length, anogenital distance and anogenital ratio have been generated. There was no correlation between clitoral length and gestational age, body length, head circumference and birth weight. Correlations were also weak for anogenital distance. CONCLUSION: The normative values generated can serve as reference standard in the assessment of clitoromegaly, ambiguous genitalia, virilizing effects and suspected in utero androgen exposure.

Connecting Active-Site Loop Conformations and Catalysis in Triosephosphate Isomerase: Insights from a Rare Variation at Residue†96 in the Plasmodial Enzyme.

Despite extensive research into triosephosphate isomerases (TIMs), there exists a gap in understanding of the remarkable conjunction between catalytic loop-6 (residues 166-176) movement and the conformational flip of Glu165 (catalytic base) upon substrate binding that primes the active site for efficient catalysis. The overwhelming occurrence of serine at position 96 (98% of the 6277 unique TIM sequences), spatially proximal to E165 and the loop-6 residues, raises questions about its role in catalysis. Notably, Plasmodium falciparum TIM has an extremely rare residue--phenylalanine--at this position whereas, curiously, the mutant F96S was catalytically defective. We have obtained insights into the influence of residue 96 on the loop-6 conformational flip and E165 positioning by combining kinetic and structural studies on the PfTIM F96 mutants F96Y, F96A, F96S/S73A, and F96S/L167V with sequence conservation analysis and comparative analysis of the available apo and holo structures of the enzyme from diverse organisms.

Animal Bites and Rabies Prophylaxis in Rural Children: Indian Perspective.

A prospective observational study was conducted in a tertiary care hospital to study clinicoepidemiological profile of potentially rabid animal bite cases from rural India. Total of 308 children (median age 6 years) admitted to hospital, were recruited over 1 year and followed up till completion of antirabies vaccine course. Dog was the commonest (77.27%) offending animal. Of the exposures, 66.88% were scratches, 88.96% were unprovoked and 27.27% were categorized as Class III. The median times to wound toileting and reporting to health facility were 1 and 6 h, respectively. Majority received prompt PEP in hospital, and RIG was administered in 34.55% of Class II and 90.48% of Class III exposures. Compared with their older counterparts, children aged <5 years suffered more bites on face and trunk and more Class III exposures. The rabies prophylaxis scenario is encouraging, when compared with earlier studies, but there are gaps to be addressed.

Normative blood pressure data for Indian neonates.

OBJECTIVE: To establish the normative blood pressure (BP) values in healthy Indian neonates using oscillometric method, and to develop BP percentile charts. DESIGN: Prospective observational study. SETTING: Neonatal unit of a teaching hospital in Eastern India. PARTICIPANTS: 1617 hemodynamically stable inborn neonates without birth asphyxia, major congenital anomaly, maternal complications (e.g. preeclampsia, hypertension, diabetes) or critical neonatal illness. PROCEDURE: Quite state measurements of systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) were recorded by oscillometric method on day 4, 7 and 14 of postnatal life. The averages of three readings at 2-minute intervals were used. RESULTS: Percentile charts (providing 5th, 10th, 25th, 50th, 75th, 95th, and 99th percentile values) have been developed. SBP, DBP and MAP showed a steady rise from day 4 to day 14, and were comparable between males and females, but were significantly lower in preterms than in term neonates. CONCLUSIONS: Normative neonatal BP data along with gestational age-wise percentile charts shall be of help for decision-making and planning for sick newborns.

Blood pressure variation with gestational age and birth weight in Indian newborn.

Prospective observational study was conducted in a tertiary care hospital of India over 8 months to measure blood pressure (BP) in healthy term and preterm neonates using oscillometric method and explore the associations with gestational age and birth weight. Consecutive BP measurements were taken by standard oscillometric method on 1617 neonates on day 4, 7 and 14 of life. Mean birth weight was 2.7 ± 0.46 kg, and mean gestational age was 38.2 ± 2.12 weeks. The mean arterial pressure (MAP) on day 4, 7 and 14 were 59.3 ± 7.33, 63.2 ± 6.55 and 66.4 ± 6.13 mmHg, respectively. Larger and mature newborns had significantly higher BP than those who were smaller and premature. Birth weight more strongly correlated with MAP than gestational age. Predictive equations linking MAP with gestational age and birth weight were deduced, which can be used for judicious fluid inotrope management.