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Introduction: The clinical outcomes of COVID-19 infection in children with cancer have been variable worldwide. Therefore, we aimed to collect data from all regions in India through a national collaborative study and identify factors that cause mortality directly related to COVID-19 infection. Methods: Data was collected prospectively on children across India on cancer therapy and diagnosed with COVID-19 infections from 47 centers from April 2020 to October 2021. Information was recorded on the demographics, the number of children that required intervention, and the outcome of the infection. In addition, we analyzed the impact of the delta variant in 2021. Results: A total of 659 children were studied, of whom 64% were male and 36% were female. The data from the eastern region was sparse, and this was a collection bias. COVID-19 infection was predominantly seen in children less than five years. The delta variant had a higher impact in the southern region, and this was statistically significant. Of the 659 children, 30 children died (4.5%), however only 7 of the deaths were directly attributed to COVID-19 infection (1%). Conclusion: The study reports the largest nationally representative cohort of children with cancer and COVID-19 to date in India. We identified demographic and clinical factors associated with increased all-cause mortality in patients with cancer. Complete characterization of the cohort has provided further insights into the effects of COVID-19 on cancer outcomes. The low mortality allows us to recommend that specific cancer treatments be continued without delays in therapy.

Background: Krabbe's disease is a neurodegenerative condition caused by a deficiency of a lysosomal enzyme, galactocerebrosidase (GALC), found mainly in the brain. There are four variants based on the age of onset: Infantile, late infantile, juvenile, and adult. Hematopoietic stem cell transplants can be curative as the GALC-positive donor cells migrate to the brain and provide GALC, thus correcting the deficiency. However, this is most effective when performed in the asymptomatic or mildly symptomatic phase. Maximum experience is in infantile-onset disease. The types of transplants usually used are matched sibling donor transplant or umbilical cord blood transplant. Clinical Description: A 5-year-old girl, the only child of a nonconsanguineous marriage, presented with complaints of frequent falls and progressive visual deterioration for 2 months. After evaluation, the clinical phenotype was ascertained to be that of a juvenile-onset (>5 years) neurodegenerative disorder with neuro-axis involvement of the brain (predominantly, white motor involvement-because of gait abnormalities and visual involvement) and absence of organomegaly or any other systemic involvement. Krabbe's disease was suspected. Supportive evidence was found on neuroimaging and confirmed by a homozygous mutation in the GALC gene that was consistent with Krabbe's disease. Management: The patient was treated with a matched unrelated bone marrow transplant, a modality that is generally not used in the management of Krabbe's disease. The clinical, neurophysiological, and neuroradiological profiles are compared during a 2-year follow-up. Currently, 2 years' posttransplant, she has not deteriorated further neurologically, and though legally blind is attending a special school for the visually impaired and performing most activities of daily living independently. Conclusion: Early matched unrelated donor transplant can be beneficial in juvenile-onset Krabbe's disease.

Abstract Background Children diagnosed with haematological and oncology conditions spend long periods of time undergoing treatments in hospital. Treatments are intensive and may include combinations of chemotherapy, radiation, surgery and bone marrow transplants. This often means that they have prolonged hospital stays away from family, friends and familiar environments. Aim We aimed at starting an activity group and learning centre based in the hospital setting for children undergoing treatment for haematological and oncology conditions. Methods The activity group and learning centre was set up in a tertiary care hospital under the department of Paediatric Haematology, Oncology and Bone Marrow Transplantation with the support of a local NGO called ‘Samiksha Foundation’ in Bangalore, India. Children who participated in the programme engaged in learning through participation in the activity groups which engaged in academic and non‐academic activities. The activity group and learning centre was piloted in April and May of 2019. During the pilot sessions, 156 children participated in the group. Children of all ages were welcome to attend and were given activities based on their age and learning levels. Until March 2020, the group has seen over 600 children in attendance. Results This methods report examines various aspects of the activity group such as setting up of the activity groups, how they are run, the activities conducted in the groups and the effects the group has had on children and their families as reported by them while undergoing treatment. Conclusion The overall response to the activity groups was positive and widely accepted among our patient community. The intervention proved to be effective, easy to implement and relatively inexpensive. We hope that by sharing data from our centre, more paediatric units may be able to implement such groups for children.

With the recent Pandemic of Covid-19 affecting more than 180 countries across the globe, services to children with blood disorders and cancers are likely to be affected. Children, in general, are at lesser risk of developing severe diseases and mortality, and mostly recover from it; fortunately, till date, very few cases have been reported in children with cancers. However, since this is an unprecedented pandemic, there is a felt need for guidance on the challenges faced in providing care to children with cancers and various blood disorders including those requiring Hematopoietic Stem Cell Transplantation (HSCT). This document will provide guidance on how to maintain continuity of care for children with blood disorders & cancers during the COVID-19 pandemic while exercising all precautions to reduce the risk of Covid-19 in this vulnerable group and if infected, what optimum care should be provided to these children.

The outbreak of rapidly spreading COVID-19 pandemic in December 2019 has witnessed a major transformation in the health care system worldwide. This has led to the re-organization of the specialty services for the effective utilization of available resources and ensuring the safety of patients and healthcare workers. Suspension of oncology services will have major implications on cancer care due to delayed diagnosis and treatment leading to irreversible adverse consequences. Therefore various oncology organizations have called for a continuation of cancer care during this crisis with diligence. The COVID-19 pandemic has forced the clinicians to transform the components of care from screening to outpatient care and primary management. The purpose of this article is to establish guidelines and recommendations for ocular oncology in the management of ocular tumors set by a multidisciplinary team of experts including ocular, medical and radiation oncologists, and pathologists. As the pandemic is evolving fast, it will require constant updates and reformation of health strategies and guidelines for safe and quality health care.

The permanency of highly-reliable power supply is a core trait of an electric power transmission network. A transmission line is the main part of this network through which power is transmitted to the utility. These lines are often damaged by accidental breakdowns owing to different random origins. Hence, researchers are trying to detect and identify these failures at the earliest to avoid financial losses. This paper offers a new real-time fast mathematical morphology-based fault feature extraction scheme for detection and classification of transmission line faults. The morphological median filter is exploited to wrest unique fault features which are then fed as an input to a decision tree classifier to classify the fault type. The acquired graphical and numerical results of the extracted features affirm the potency of the offered scheme. The proposed scheme is verified for different fault cases simulated on high-voltage transmission line modelled using ATP/EMTP with varying system constraints. The performance of the stated technique is also validated for fault detection and classification on real-field transmission lines. The results state that the proposed method is capable of detecting and classifying the faults with adequate precision and reduced computational intricacy, in less than a quarter of a cycle.

The most often used motor in commercial drives is the induction motor. While the induction motor is operating, electrical, thermal, mechanical, magnetic, and environmental stresses can result in defects. Therefore, many researchers who are involved in condition monitoring have been interested in the development of reliable and efficient fault diagnostic technologies. This paper’s goal is to provide an overview of available fault detection methods for the broken rotor bar problem, one of several defects associated to induction motors. Despite the fact that it is less common than bearing or insulator failure, this fault may cause electrical machines to fail catastrophically. It can be quite harmful, especially in large motors, and it can develop as a result of manufacturing faults, repeated starting of the machine, mechanical stress, and thermal stress. Hence, a review on rotor defect diagnosis was conducted. In order to confirm rotor bar fracture, this research provides probable defect signatures that can be extracted from the current signal. Each defect signature is reported according to (a) loading level, (b) the number of BRBs, (c) validation, and (d) methodologies.

This study examines the conceptual features of Fault Detection, Isolation, and Restoration (FDIR) following an outage in an electric distribution system.This paper starts with a discussion of the premise for distribution automation, including its features and the different challenges associated with its implementation in a smart grid paradigm. Then, this article explores various concepts, control schemes, and approaches related to FDIR. Service restoration is one of the main strategies for such distribution automation, through which the healthy section of the power distribution network is re-energized by changing the topology of the network. In a smart grid paradigm, the presence of intelligent electronic devices can facilitate the automatic implementation of the service restoration scheme. The concepts of service restoration and various approaches are thoroughly presented in this article. A comparison is made among various significant approaches reported for distribution automation. The outcome of our literature survey and scope for future research concludes this review.

Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in the IFN-γ mediated immunity lead to an increased susceptibility to intracellular pathogens like mycobacteria including attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains and non-tuberculous environmental mycobacteria (NTM), Salmonella, fungi, parasites like Leishmania and some viruses, in otherwise healthy individuals. Mutations in the IL12RB1 gene are the commonest genetic defects identified. This retrospective study reports the clinical, immunological, and molecular characteristics of a cohort of 55 MSMD patients from 10 centers across India. Mycobacterial infection was confirmed by GeneXpert, Histopathology, and acid fast bacilli staining. Immunological workup included lymphocyte subset analysis, Nitro blue tetrazolium (NBT) test, immunoglobulin levels, and flow-cytometric evaluation of the IFN-γ mediated immunity. Genetic analysis was done by next generation sequencing (NGS). Disseminated BCG-osis was the commonest presenting manifestation (82%) with a median age of presentation of 6 months due to the practice of BCG vaccination at birth. This was followed by infection with Salmonella and non-typhi Salmonella (13%), Cytomegalovirus (CMV) (11%), Candida (7%), NTM (4%), and Histoplasma (2%). Thirty-six percent of patients in cohort were infected by more than one organism. This study is the largest cohort of MSMD patients reported from India to the best of our knowledge and we highlight the importance of work up for IL-12/IL-23/ISG15/IFN-γ circuit in all patients with BCG-osis and suspected MSMD irrespective of age.

BackgroundHematopoietic stem cell transplantation (HSCT) is the curative option for many primary immune deficiency disorders (PID). In the last 5 years, increased awareness, availability of diagnostics based on flow cytometry, genetic testing, improved supportive care, use of reduced toxicity conditioning, and success of haploidentical donor HSCT have improved access to HSCT for children with PID in India. We present results on children with PID who underwent HSCT across India and the factors that influenced outcome.Patients and MethodsWe collected retrospective data on the outcome of HSCT for PID from seven centers. We analyzed the impact of the type of PID, conditioning regimen, time period of HSCT- before or after January 2016, graft versus host disease prophylaxis, cause of mortality and overall survival.ResultsA total of 228 children underwent HSCT for PID at a median age of 12 months (range, 1 to 220 months) with a median follow up of 14.4 months. Infants accounted for 51.3% of the cohort and the male female ratio was 3:1. SCID (25%) and HLH (25%) were the more frequent diagnoses. Matched family donor was available in 36.4% and 44.3% children had a haploidentical HSCT. Reduced and myeloablative conditioning regimens were used with 64% children receiving a treosulfan based conditioning regimen. Peripheral blood stem cells were the predominant graft source at 69.3%. The survival in infants (60.2%) was inferior to children aged over 1 year (75.7% p value = 0.01). Children with Wiskott Aldrich syndrome (74.3%) and chronic granulomatous disease (82.6%) had the best outcomes. The survival was superior in children receiving HSCT from a matched sibling (78%) versus an alternate donor HSCT (61% p value = 0.04). In the cohort transplanted after January 2016 survival improved from 26.8% to 77.5% (p value = 0.00). Infection remains the main cause of mortality at in over 50% children. The 5-year overall survival rate was 68%.ConclusionSurvival of children with PID undergoing HSCT in India has improved dramatically in last 5 years. Alternate donor HSCT is now feasible and has made a therapeutic option accessible to all children with PID.

Primary immunodeficiency (PID) refers to a group of heterogeneous genetic disorders with a weakened immune system. Mendelian susceptibility to mycobacterial disease (MSMD) is a subset of PID in which patients exhibit defects in intrinsic and innate immunity. It is a rare congenital disorder characterized by severe and recurrent infections caused by weakly virulent mycobacteria or other environmental mycobacteria. Any delay in definitive diagnosis poses a major concern due to the confounding nature of infections and immune deficiencies. Here, we report the clinical, immunological, and genetic characteristics of two siblings (infants) with recurrent infections. There was a history of death of two other siblings in the family after BCG vaccination. Whole exome sequencing of the two affected surviving infants along with their consanguineous parents identified a novel, homozygous single nucleotide splice acceptor site variant in intron 2 of the interferon gamma receptor 2 (IFNGR2) gene. Sanger sequencing of DNA obtained from blood and fibroblasts confirmed the variant. The patients underwent bone marrow transplantation from their father as a donor. RT-PCR and Sanger sequencing of the cDNA of patients from blood samples after transplantation showed the expression of both wild type and mutant transcript expression of IFNGR2. To assess partial or complete expression of IFNGR2 mutant transcripts, fibroblasts were cultured from skin biopsies. RT-PCR and Sanger sequencing of cDNA obtained from patient fibroblasts revealed complete expression of mutant allele and acquisition of a cryptic splice acceptor site in exon 3 that resulted in deletion of 9 nucleotides in exon 3. This led to an in-frame deletion of three amino acids p.(Thr70-Ser72) located in a fibronectin type III (FN3) domain in the extracellular region of IFNGR2. This illustrates individualized medicine enabled by next generation sequencing as identification of this mutation helped in the clinical diagnosis of MSMD in the infants as well as in choosing the most appropriate therapeutic option.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder of uncontrolled cytotoxic T-lymphocyte and macrophage activation associated with extreme inflammation, which if left untreated is invariably fatal. HLH can be classified either as primary (familial) or secondary (acquired). Genetic mutations underlie primary HLH which typically occurs in young children, while secondary HLH is associated with infections, metabolic disease, and malignancies and manifests later in life. Both categories of HLH affect the function of T-lymphocytes and natural killer (NK) cells. Homozygous null mutations in several genes including PRF1, UNC13D (MUNC13-4), STX11, and STXBP2 (MUNC18-2) have been described in cases of primary HLH, where consanguinity has been shown to play a role. These mutations contribute to an uncontrolled inflammatory response, over production of interferon gamma (IFNγ) and pro-inflammatory cytokines leading to macrophage activation and eventually to tissue and organ damage. While no known genetic mutations have been described in patients with acquired HLH, an underlying genetic predisposition has been suggested. In an effort to better understand the genetic and clinical correlates of this disease, we performed retrospective analyses of 60 suspected HLH cases that were submitted by physicians for genomic analysis to our diagnostic laboratory. High throughput exome sequencing of the 60 HLH samples was carried out on an Illumina HiSeq 2500 platform, followed by bioinformatics analysis. Our data showed that 1) 34% of the patients had homozygous mutations in known HLH-associated genes, the majority of which were in the Perforin1 (PRF1) gene (70%) followed by mutations in the UNC13D (20%) and STXBP2 (10%) genes. Most patients with homozygous PRFI mutations were products of consanguineous marriages. The parents of these patients while being carriers, however, remained unaffected. 2) 18% of our patients had mutations in other congenital immune deficiency syndromes that are known to lead to HLH. 3) The remaining 48% of the patients lacked any known HLH-associated mutation. Our data suggest that heterozygous mutations in novel genes may contribute to predisposing patients to secondary HLH, particularly since most of these genes are associated with T-lymphocyte activation, which plays a vital role in the etiology of this devastating disease.