Genetic analysis of a Fanconi anemia case revealed the presence of FANCF mutation (exon 1;469>C-T) with implications to develop acute myeloid leukemia.

BACKGROUND: Fanconi anemia (FA) is a rare genetic disorder and one of the most common inherited forms of aplastic anemia. FA is an autosomal recessive or X-linked genetic disorder that is characterized by typical physical malformations and haematopoietic anomalies. In most cases of FA, patients harbor homozygous or double heterozygous mutations in the FANCA (60-65%), FANCC (10-15%), FANCG (~ 10%), FANCD2 (3-6%) or FANCF (2%) genes in different ethnic populations, which leads to inherited bone marrow failure (IBMF). Hence, it is important to screen such mutations in correlation with clinical manifestations of FA in various ethnic populations. APPROACH: An 11 year old female pediatric patient of an East India family was presented with febrile illness, having thrombocytopenia with positive dengue IgM (Immunoglobulin M) and treated as a case of dengue hemorrhagic fever at the initial stage of diagnosis. Chromosomal breakage study was performed based on the abnormal physical examination, which showed 100% breaks, triradials, and quadrilaterals in mitomycin (MMC)-induced peripheral blood lymphocyte culture. Importantly, conventional cytogenetic assay in most of the bone marrow cells revealed an additional gain in chromosome 3q+ [46,XX,add(3)(q25)] and terminal loss in chr8p- [46,XX,del(8)(p23)], which might have a prognostic relevance in the outcomes of the FA patient. The bone marrow aspiration and biopsy were repeated and the results showed acute leukemia with 39% blast cells. Whole-genome sequencing analysis of the patient confirmed the presence of (exon 1; 496 > C-T) non-sense mutation leading to a truncated FANCF protein attributed to a stop codon at the amino acid position 166. CONCLUSION: The study reported the presence of a homozygous C-T exon 1 mutation in FANCF gene in the female pediatric patient from Odisha, India associated with FA. Furthermore, both parents were found to be carriers of FANCF gene mutation, as this allele was found to be in heterozygous state upon genome sequencing. The pathogenicity of the agent was robustly supported by the clinical phenotype and biochemical observations, wherein the patient eventually developed acute myeloid leukemia. The findings of the study infer the importance of early detection of FA and the associated mutations, which might lead to the development of acute myeloid leukemia.

Short-term outcomes in children recovered from multisystem inflammatory syndrome associated with SARS-CoV-2 infection.

Multi-system inflammatory syndrome in children (MIS-C) associated with COVID-19 is a recently recognised potentially life-threatening entity. There is limited data on post-MIS-C sequelae. 21 children fulfilling the WHO criteria for MIS-C were included in our study. Data were collected at baseline and at 12-16 weeks post-discharge to look for any persistent sequelae mainly relating to the lungs or heart including coronary arteries. Fever was the most common presentation, found in 18 (85.7%) patients. All had a marked hyper-inflammatory state. Low ejection fraction (EF) was found in 10 (47.6%), but none had any coronary artery abnormality. All received corticosteroids, while 7 (33.3%) children required additional treatment with intravenous Immunoglobulins. 20 children improved while 1 left against medical advice. At discharge, 3 children had impaired left ventricular function. At median 15 weeks' follow-up, no persistent complications were found. EF had returned to normal and no coronary artery abnormalities were found during repeat echocardiography. Chest radiographs showed no fibrosis and all biochemical parameters had normalized. The children with MIS-C are extremely sick during the acute stage. Timely and adequate management led to full recovery without any sequelae at a median follow-up of 15 weeks.

Clinico-radiological Profile of Posterior Reversible Encephalopathy Syndrome and Its Associated Risk Factors in PICU: A Single-center Experience from a Tertiary Care Hospital in Bhubaneswar, Odisha.

OBJECTIVE: Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiographic entity of heterogeneous etiologies having similar clinical and neuroimaging features. Pediatric data are sparse, making early diagnosis challenging, which needs a high index of suspicion. So, we conducted this study to evaluate clinico-radiological features, associated risk factors, etiology, and outcome in children. MATERIALS AND METHODS: This is a retrospective case series of patients, diagnosed as having PRES and followed up at a tertiary care hospital in Eastern India between September 2016 and December 2019. RESULTS: Among 16 patients with a median age of 9.5 years [interquartile range (IQR) 8-13.75] and a male preponderance (75%), common underlying diseases were post-streptococcal glomerulonephritis (56.3%) and renovascular hypertension (12.5%). Acute elevation of blood pressure was found in all patients (n = 16). The neurological symptom was seizure (87.5%), mental changes (68.75%), headache (43.8%), vomiting (31.3%), and visual disturbances (31.3%). The most common triggering factor was hypertension (100%), use of mycophenolate mofetil and prednisolone (12.5%), and hemodialysis (12.5%). Anemia was present in 15 (93.4%) patients at the time of admission. All showed abnormal neuroimaging with 55% having atypical involvement. The most common site was the parietal-occipital cortex (88%), frontal and temporal lobe (44% cases each), and the cerebellum (13%). Clinical recovery was followed by a radiological resolution in all survived except in one, who developed visual impairment. CONCLUSION: Posterior reversible encephalopathy syndrome should be considered in the differential diagnosis of patients who present with acute neurological disturbances and underlying diseases such as renal disorders, vasculitis, malignancy, and use of immunosuppressant accompanied by hypertension. Early diagnosis and treatment of comorbid conditions are of paramount importance for the early reversal of the syndrome. HOW TO CITE THIS ARTICLE: Behera CK, Jain MK, Mishra R, Jena PK, Dash SK, Sahoo RK. Clinico-radiological Profile of Posterior Reversible Encephalopathy Syndrome and Its Associated Risk Factors in PICU: A Single-center Experience from a Tertiary Care Hospital in Bhubaneswar, Odisha. Indian J Crit Care Med 2020;24(12):1223-1229.

Dilemmas and Challenges in Treating Seronegative Autoimmune Encephalitis in Indian Children.

OBJECTIVE: The main objective is to assess the challenges in diagnosis and treatment while managing seronegative cases of autoimmune encephalitis (AIE) in Indian children. METHODS: A cohort study of patients with AIE was done where clinical presentations, investigations, management were analyzed and these patients were followed up to assess the evolution of the disease. RESULTS: Nine patients were included in the study. Four patients presented with super-refractory status epilepticus (SRSE). Other presentations were behavioral change, hemiplegia, and autonomic dysfunction. Initial magnetic resonance imaging brain was suggestive of AIE in two patients. Only two were seropositive for cerebrospinal fluid (CSF) autoimmune panel. Five patients responded to the first-line immunotherapy and four required the second-line immunotherapy. CONCLUSION: The possibility of autoimmune encephalitis should be considered in patients with super-refractory status epilepticus. A large proportion of children with suspected AE may be "seronegative." A trial of immunotherapy should be given to these children when there is a strong clinical suspicion of autoimmune encephalitis even in the absence of cerebrospinal fluid autoantibodies.

Kaleidoscopic Hues of Antiepileptics in Pediatric Population: Comparison of Prevailing Antiepileptics.

BACKGROUND AND OBJECTIVES: Currently, we have a shortage of comprehensive information about newer antiepileptic drugs (AEDs) in the pediatric population. This might explain the discrepancies among pediatricians' preferences in this regard. Therefore, it is crucial to study the multifaceted impacts of these drugs on children. The endpoints of our study were non-AED predictors of the requirement of combination therapy for seizure management, seizure-free period >6 months and >12 months, change in Quality of Life in Childhood Epilepsy Questionnaire - 55 (QOLCE-55), and incidence of adverse events. METHODS: This prospective, observational study was conducted in KIMS, Bhubaneswar, India, from January 2021 to November 2022. Children of 2-12 years of age were treated with monotherapy of either newer antiepileptics, e.g., levetiracetam, topiramate, and oxcarbazepine or older antiepileptics, e.g., valproic acid, phenytoin, phenobarbital, and carbamazepine. Univariate and multivariate analyses were performed for the assessment of predictors. We used R software (version 4.1.1) for data analysis. RESULTS: One hundred and ninety-eight (91.7%) of 216 enrolled participants completed this study. The mean age of the study population was 5.2 years and 117 (59%) of them were males. The univariate analysis showed that male gender, low birth weight, preterm birth, assisted vaginal delivery and site-specific epilepsy, and maternal history of epilepsy were significant predictors of combination therapy and reduced seizure-free period. There was a non-significant difference regarding the improvement of QOLCE-55 scores. None of the adverse events were serious. CONCLUSIONS: Perinatal complications and maternal history of epilepsy contribute significantly toward the efficacy of antiepileptics. However, multivariate analysis did not yield statistically significant results.

Role of neonatal cerebrospinal fluid cytology in correlation to C-reactive protein, blood culture, risk factors and clinical outcomes in neonatal intensive care.

Introduction: The number of neonatal cerebrospinal fluid (CSF) samples sent from the neonatal intensive care unit (NICU) for cytologic examination is rising, warranting accurate analysis and interpretation of the same. This study was taken up to assess the usefulness of CSF cell count and cytology in NICU settings, as it can be used even in a resource-limited setting. Aim and Objective: 1) To study the prevalence of cell count and cytologic changes in CSF from NICU and assess their usefulness in correlation to C-reactive protein, CSF neutrophil percentage, blood, CSF culture, and other biochemical parameters. 2) To correlate cell counts and cytology with age, period of gestation, presence, and absence of sepsis, seizures, intracranial hemorrhage, and their clinical follow-up. Materials and Methods: A retrospective study was done on neonatal CSF samples submitted for cytology over one year (January-December 2016) in the Department of Pathology. CSF cell counts were retrieved, and cytosmears were reviewed for cellularity, cell type, proportion, and background and correlated with the biochemical, microbiological, and clinicoradiological findings. Results: A total of 213 samples were included with 140 males and 73 females with an age range of 0-28 (mean: 7.3) days. The mean CSF cell count was 5.48/cu.mm (0-90 cells/cu.mm). The most frequent cytologic finding was occasional lymphocytes or acellular CSF (63.9%). The CSF leucocyte count and protein levels showed a significant correlation with s C-reactive protein. The CSF cytology showed a significant correlation between the age of the neonate and blood neutrophil percentage (P = 0.0158). History of intracranial hemorrhage showed a significantly higher frequency of the presence of red blood cells (P = 0.0147). Conclusion: Accurate cell counts, cytology of neonatal CSF, and biochemical and microbiological workup can help diagnose and manage neonates in intensive care.

Atypical Presentation of Cystic Fibrosis in An Infant.

Dermatitis as an initial manifestation of cystic fibrosis (CF) is unusual. The eruption is usually first noted in the perineum anywhere from several days to few months after birth. It subsequently spreads to the extremities and trunk. We report a 2-month-old male baby who presented with failure to thrive, hypoproteinemia, anemia, and a cutaneous eruption resembling acrodermatitis enteropathica. Oral zinc supplementation resulted in temporary resolution of the dermatitis. A further workup revealed the diagnosis of CF. The rash was responsive to nutritional and pancreatic enzyme supplementation.

Tracheostomy in Pediatric Intensive Care Unit: Experience from Eastern India.

OBJECTIVE: Tracheostomy is one of the most commonly used surgical intervention in sick children in the intensive care unit. The literature in the pediatric population is limited, therefore, we conducted this study to evaluate the indications, timing, complications, and outcomes of tracheostomy among the children at our center. METHODS: This retrospective study was conducted from January 2016 through December 2019. Data was collected from the patients' records and analyzed. RESULTS: During this study period, 283 children were ventilated, of which 26 (9.1%) required tracheostomy. Among this 73% were boys. The median age of the children who underwent tracheostomy was 6.32 y. The most common indication for tracheostomy was prolonged mechanical ventilation [24 cases (92%)] followed by upper airway obstruction [2 cases (8%)]. The average time of tracheostomy was 11.65 d, range (1-21 d). Complications were seen in 14 patients (55%). The most common complications were accidental decannulation, occlusion, pneumothorax, and granulation tissue. Twenty one (80%) patients were successfully discharged, out of which 16 (61%) patients were discharged after decannulation and 5 (21%) were sent home with a tracheostomy tube in situ. Overall mortality in present study was 11.5%; none was directly related to tracheostomy. CONCLUSIONS: The indication for tracheostomy has been changed from emergency to more elective one. Prolonged mechanical ventilation is the most common indication for tracheostomy. Although the timing of tracheostomy is not fixed, two weeks time is reasonable and it can be done safely at the bedside in pediatric intensive care.

Clinical Profile and Immediate Outcome of Multisystem Inflammatory Syndrome in Children Associated with COVID-19: A Multicentric Study.

INTRODUCTION: Following an asymptomatic or mildly symptomatic coronavirus disease (COVID-19), otherwise healthy children may develop serious manifestations in the form of cardiac, neurological, respiratory, gastrointestinal, and dermatologic dysfunction. Many such cases were being observed in Odisha, an eastern state of India, and have been reported from different health-care facilities. We related these unexplained serious manifestations to multisystem inflammatory syndrome associated with COVID-19 (MIS-C) and planned this study. METHODS: This retrospective observational study was carried out at the following three tertiary care centers: Kalinga Institute of Medical Sciences, Bhubaneswar; MKCG Medical College, Berhampur; and Jagannath Hospital, Bhubaneswar. The study population included all children aged from 1 month to 18 years admitted to the hospitals with MIS-C according to the WHO diagnostic criteria. All the data were analyzed by SPSS software. RESULTS: A total of 21 children were included in our study. Majority of the cases were male (76.2%), and the predominant age group was 6-10 years (47.6%). Common symptoms and signs in our observation included fever, pain abdomen, seizure, and hypotension. Most of these cases were positive for severe acute respiratory syndrome coronavirus antibody (80.95%). Response to immunotherapy was dramatic. Mortality (9%) of our study was higher than 1.8%-3% from that of Western literature. None of our patients had coronary abnormality, while two patients had mild cardiac dysfunction at discharge comparable to that of other studies. CONCLUSION: MIS-C following exposure to COVID-19 infection in children is a clinical syndrome, which needs early suspicion and appropriate intervention to prevent mortality.

Heart rate variability and its correlation with pulmonary function test of smokers.

CONTEXT: Though many studies have been conducted on the effect of chronic smoking on pulmonary function test (PFT) and heart rate variability (HRV), no study has found a correlation between the pulmonary function test and heart rate variability parameters so far. AIM: The aim was to study if there was a correlation, if any, between PFT and HRV. SETTINGS AND DESIGN: Thirty male subjects who were chronic smokers of at least 10 pack years and another 30 nonsmoking healthy males were included in the study and were matched for age, height, weight, and body surface area. MATERIALS AND METHODS: PFT and HRV were performed on these subjects and a correlation was statistically derived. STATISTICAL ANALYSIS USED: Spearman's correlation coefficient was used for the analysis of HRV and PFT. Multiple stepwise regression analysis was used subsequently. RESULTS: HF and LF showed correlation coefficients of 0.378 and-0.383 with forced expiratory volume in the first second (FEV 1) and peak expiratory flow rate (PEFR), respectively. It was found that only FEV 1/FVC was having a statistically significant regression coefficient with HF the R-value was found to be 0.425 while with other parameters, it was not significant. CONCLUSION: We conclude that smoking affects all the parameters of PFT and HRV. Since there is a correlation between PFT parameters (PEFR and FEV1) and HRV parameter (LF and HF), this can help us in predicting cardiac morbidity in chronic smokers. So HRV should be included as a routine test along with PFT in chronic smokers for early diagnosis of cardiac involvement.