Carrier Screening and Diagnosis for Spinal Muscular Atrophy Using Droplet Digital PCR Versus MLPA: Analytical Validation and Early Test Outcome.

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular life-threatening disorder. Owing to high carrier frequency, population-wide SMA screening to quantify the copy number of SMN gene is recommended by American College of Medical Genetics and Genomics. An accurate, reliable, short runaround time and cost-effective method may be helpful in mass population screening for SMA. Methods: Multiplex ligation-dependent probe amplification (MLPA) is a gold standard to estimate the copy number variation (CNV) for SMN1 and SMN2 genes. In this study, we validated droplet digital polymerase chain reaction (ddPCR) for the determination of CNV for both SMN1 and SMN2 exon 7 for a diagnostic purpose. In total, 66 clinical samples were tested using ddPCR, and results were compared with the MLPA as a reference test. Results: For all samples, CNV for SMN1 and SMN2 exon 7 was consentaneous between ddPCR and MLPA test results (κ = 1.000, p < 0.0001). In addition, ddPCR also showed a significant acceptable degree of test repeatability, coefficient of variation < 4%. Conclusion: ddPCR is expected to be utilitarian for CNV detection for carrier screening and diagnosis of SMA. ddPCR test results for CNV detection for SMN1/SMN2 exon 7 are concordant with the gold standard. ddPCR is a more cost-effective and time-saving diagnostic test for SMA than MLPA. Furthermore, it can be used for population-wide carrier screening for SMA.

A new onset drug induced diabetes mellitus presenting with diabetic ketoacidosis in a child undergoing treatment for B cell acute lymphoblastic leukemia. A case report and review of literature.

OBJECTIVES: Hyperglycemia is a known side effect of anticancer chemotherapeutic drugs. This entity known as drug-induced diabetes mellitus usually does not present with the development of diabetic ketoacidosis (DKA). We hereby report a case of drug induced diabetes mellitus in a child with acute leukemia presenting with DKA. CASE PRESENTATION: We report a case of a teenage boy diagnosed with B cell acute lymphoblastic leukemia and was started on induction phase chemotherapy as per the Indian Collaborative Childhood Leukemia group (ICICLe) acute lymphoblastic leukemia-14 protocol. On day 12 of the induction phase, he developed hyperglycemia and presented to us with severe diabetic ketoacidosis (DKA). Serum anti glutamic acid decarboxylase 65 antibody levels were negative with low serum C peptide levels. Initially, the possibility of drug-induced acute pancreatitis was kept which was ruled out. Keeping the possibility of drug-induced hyperglycemia, the child was started on subcutaneous regular insulin which was titrated as per sugar records. Continuation of remaining chemotherapy was done by PEGylated L-asparaginase with titration of insulin as per home-based sugar records. Insulin requirement increased from 0.3 unit/kg/day to a maximum of 1 unit/kg/day during consolidation phase 1 with PEGylated L-asparaginase suggesting drug-induced hyperglycemia but subsequently insulin requirement decreased and insulin was stopped. CONCLUSIONS: Drug induced diabetes mellitus can present as DKA during induction phase of acute lymphoblastic leukemia (ALL) chemotherapy. A high index of suspicion and close monitoring are required. The insulin requirements in these patients can be very fluctuant and may become nil during the course of treatment.

Cost analysis of telemedicine use in paediatric nephrology-the LMIC perspective.

BACKGROUND: The overall cost of managing chronic diseases is a significant barrier to accessing complete and timely healthcare, especially in rural and geographically isolated areas. This cost disparity becomes more pronounced in the case of children and more so in under-resourced regions of the world. In the era of COVID-19, as the need for physical distancing increased, there was a transition in approach to healthcare provision to telemedicine consultations. This study evaluates the cost saving using teleconsultations in a paediatric nephrology clinic. METHODS: This prospective cohort study was conducted at AIIMS Jodhpur, a tertiary care centre in western Rajasthan from March 2021 to October 2022. All consecutive paediatric (29 days-18 years) patients attending telemedicine services for kidney-related illness were enrolled. Basic demographic details were collected. Cost analysis was done after 6 months, regarding perceived cost savings for the patient and family by using telehealth for follow-up during 6 months starting from enrolment. RESULTS: A total of 112 patients were enrolled; 266 teleconsultations attended; 109 patients who could be followed up saved INR 457,900 during 6 months of follow-up. The average cost saving was INR - 1577/patient/visit. Patients saved 4.99% of the family income (median 2.16% (IQR 0.66-5.5)). The highest expenditure per visit was incurred for food and transport. The median distance from the residence to the clinic was 122.5 km (IQR 30-250). Over the 6-month study period, patients saved a travel distance of 83,274 km (743 km/patient). CONCLUSIONS: The use of telemedicine as a follow-up method helps save significant costs and distances travelled by patients. A higher-resolution version of the Graphical abstract is available as Supplementary information.

Protocolized Sedation Utilizing COMFORT-B Scale versus Non-protocol-directed Sedation in Mechanically Ventilated Children - An Open-label, Randomized Controlled Trial.

This study aimed to determine the effect of protocolized sedation using the COMFORT-B scale on the duration of mechanical ventilation (DMV). Eighty children with anticipated Duration of mechanical ventilation (DMV) >24 h admitted to the Pediatric intensive care unit (PICU) were randomized into one group that received protocolized sedation (PS) using the COMFORT behavioural (COMFORT-B) scale, and another group that received non-protocolized sedation (NPS). The primary outcome was the impact on the DMV. The DMV was significantly lower in PS (PS: 3.5 [3-7] vs. NPS group: 8.5 [4.25-13.75] d; p = 0.008). The cumulative dose and duration of fentanyl in the PS group was significantly lower (median [IQR]; 120 [62.88-279.12] vs. 320.4 [110.88-851.52] µg/kg; p = 0.007 and 4 [2.25-7.75] vs. 8 [4-17.5] d; p = 0.009, respectively). The authors found a decrease in DMV and sedation related adverse events (SRAE) like ventilator associated pneumonia (VAP), accidental extubation, post-extubation stridor and dose and duration of sedative agents with PS.

Use of prostaglandin and cyclophosphamide for pediatric lupus with digital gangrene: Back to safety before hitting the axe!

Digital gangrene is a rare presenting feature of childhood lupus and only a reported incidence of 1.3%. We describe two cases of pediatric onset systemic lupus erythematosus (SLE), both 16 years old, presenting with digital gangrene and the successful salvage of the digits after using intravenous cyclophosphamide for immunosuppression and use of intravenous prostaglandin E1 infusions for limb reperfusion. Both of the patients responded exceptionally to the infusions with resolution of gangrene and near-total preservation of the functionality of toes.

Clinical Profile, Follow-up, and Role of Neuroimaging in Pediatric Guillain-Barré Syndrome in the COVID Era: An Ambispective Study.

Background: To define the varied presentations of Guillain-Barré syndrome in children in the COVID era and 6 months' follow-up outcome. Methods: Ambispective study of 15 months' duration involving children with Guillain-Barré syndrome aged 1 month to 18 years at a tertiary care pediatric hospital. They were categorized into groups A and B based on COVID-19 serology testing. Hughes Disability Scale was used for disability assessment. Modified Rankin scale was used for improvement assessment in follow-up. Results: Of 19 children with Guillain-Barré syndrome, 9 (47%) were females and 10 (53%) were males. Groups A and B had children with negative (8) and positive serology (11), respectively. The most common presentation in both groups was motor weakness. Post-COVID pediatric Guillain-Barré syndrome presented with variants of Guillain-Barré syndrome rather than the classical form (P = .03). In group B, patients with elevated inflammatory markers had poor response to intravenous immunoglobulin, and 5 of 11 patients had good response to pulse steroids, probably depicting an inflammation-predominant pathology. Conclusion: Post-COVID Guillain-Barré syndrome in children presented with Guillain-Barré syndrome variants rather than the classic form. Neuroimaging is of great value in both confirming Guillain-Barré syndrome diagnosis and excluding differentials. Patients with elevated inflammatory markers and residual weakness may be given a pulse steroid trial.

Post-COVID-19 Immune-Mediated Neurological Complications in Children: An Ambispective Study.

BACKGROUND: The neurological manifestation following a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is varied, and till now, only a few studies have reported the same. METHODS: We used retrospective data from May to July 2021 and prospective study data from August to September 2021, including that from children aged between one month and 18 years who presented to a tertiary care referral center with the neurological manifestation and had a history of coronavirus disease 2019 (COVID-19) infection or exposure and positive SARS-CoV-2 serology. The neuroradiological manifestations were further categorized as in a predesigned proforma. RESULTS: Case records of the 18 children who fulfilled the criteria were included in the study; among them, seven (38.8%) were male and 11 (61.1%) were female. Predominant presentation in our study group was status epilepticus (six of 18) and Guillain-Barré syndrome (five of 18). Other manifestations included stroke (two of 18), demyelinating syndromes (three of 18), and autoimmune encephalitis (two of 18). Most of the children had favorable outcomes except for one mortality in our cohort. CONCLUSIONS: Delayed complications following SARS-CoV-2 infection are seen in children. A temporal correlation was noted between the COVID-19 infection and the increasing number of neurological cases after the second wave. Steroids could be beneficial while treating such patients, especially in the presence of high inflammatory markers. Testing for SARS-CoV-2 serology during the pandemic can give a clue to the underlying etiology. Further multicentric studies are required to understand the varied neurological manifestations following SARS-CoV-2 infection in children.

Paediatric acute haemorrhagic leukoencephalitis.

We report a case of a preschool age girl, previously healthy, referred to our hospital on ventilatory support with a history of vomiting, headache, and rapid neurological worsening within 24 hours in the form of seizures, encephalopathy and loss of consciousness. On presentation, she was deeply comatose with dilated non-reactive pupils, absent brainstem reflexes and flaccid quadriplegia. Diagnosis of acute haemorrhagic leukoencephalitis was considered based on laboratory and neuroimaging findings. MRI of the brain showed fluffy white matter hyperintensities and microhaemorrhages in bilateral cerebral hemispheres and thalami. Aggressive treatment with methylprednisolone, plasmapheresis and intravenous immunoglobulin showed dramatic improvement with no neurological sequelae. Our case is unique in a way that despite the hyperacute onset and rapid deterioration, with a fulminant course in the intensive care unit, the child recovered dramatically with aggressive management.

Guardian-Reported Impact of the COVID-19 Pandemic on the Lifestyle of Children with Diabetes Mellitus.

INTRODUCTION: The coronavirus disease-2019 (COVID-19) pandemic has had an unprecedented impact on the lives and lifestyles of people of all ages worldwide. Lifestyle has an essential role in the management of diabetes mellitus in children. METHODS: The study was carried out at a tertiary care centre in India. A telehealth survey was conducted among the parents/guardians of children with diabetes to study the impact of the COVID-19 pandemic. The survey evaluated the effects on lifestyle, diabetes management and challenges in connecting to a new telemedicine programme. RESULTS: The survey was completed by guardians of 91 patients. The mean age of the patients was 13.0 ± 3.8 years in boys and 11.9 ± 4.5 years in girls. Fifty-seven per cent of them were boys, and 63.7% stayed in rural areas. The pandemic has resulted in a significant increase in screen time and sleep duration. The median non-educational screen time has gone up from 1.00 (0.5-2.0) to 2.50 (1.0-4.0) h. The mean sleep duration in children increased from 9.1 ± 1.4 to 9.7 ± 1.4 h. Telemedicine services have been established with minimum resources, but they have limitations, and awareness about them is also limited. CONCLUSION: The COVID-19 pandemic has made the lifestyle of children with diabetes more sedentary. Some of them have also faced challenges with regard to diabetes-related supplies and management. It would be fair to anticipate more complications related to this sedentary lifestyle in the future and work towards identifying and treating them.

A Composite Study of Coagulation Milieu in Covid-19: Experience from a Tertiary Care Centre from India.

BACKGROUND: The understanding of pathogenesis is necessary for the development of effective treatment for COVID-19. Various studies have postulated that there is a complex interplay of mediators of coagulation and inflammation responsible for the pathogenesis of COVID-19. We did this study on coagulation parameters and inflammatory markers and their effect on outcome in patients with COVID-19. METHODS: This was a single centre observational cross-sectional study. Procoagulants [Prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, lupus anticoagulant (LA), fibrinogen, factor-VIII (F-VIII)]; anticoagulants [protein-C (PC), protein-S (PS), antithrombin] and inflammatory markers [interleukin-6 (IL-6) and highly sensitive - C-reactive protein (hs-CRP)] were measured at the time of hospitalization and correlated with the severity of the disease. RESULTS: A total of 230 patients were enrolled, of which 61.3%, 20.0%, and 18.7% had asymptomatic/ mild, moderate, or severe disease, respectively. COVID-19 disease severity was associated with rising trends with coagulation parameters (PT, APTT, D-Dimer; p value 0.01, <0.0001, <0.0001, respectively). Falling trends of anticoagulant (PC, Antithrombin; p value <0.0001, 0.003 respectively) and rising trends of procoagulant (fibrinogen, F-VIII; p value 0.004, <0.0001 respectively) were observed with increasing COVID-19 disease severity. Multivariate logistic regression analysis found that advanced age, high D-Dimer, and high hs-CRP (p value 0.035, 0.018, <0.0001 respectively) were independent predictors of mortality in COVID-19. Procoagulant parameters (D-dimer, APTT, Factor VIII) were positively correlated with anticoagulant parameters (PC and PS) and inflammatory parameters (hs-CRP). CONCLUSION: This study revealed increased levels of coagulation and inflammatory parameters, which correlated with the severity of COVID-19. Age, D-dimer, IL-6, hs-CRP, APTT, fibrinogen, and Factor VIII were significantly higher in patients with moderate and severe disease as compared to asymptomatic/mild disease. Advanced age, high D-dimer, and high hs-CRP were significantly associated with poor outcomes.

Pediatric onset lupus nephritis in western India-is it different from the rest of the country?

AIM: To determine the clinicopathological characteristics and outcomes of children diagnosed with lupus nephritis in a tertiary hospital in western Rajasthan and compare it with the data available from other parts of India. MATERIAL AND METHODS: A retrospective review of children presenting to a tertiary care center in western Rajasthan, India, with a diagnosis of pediatric Systemic Lupus Erythematosus (p SLE), between July 2017 and July 2020 was done. Comparisons of pediatric lupus in western India to other parts of country were done. RESULTS: 19 children with SLE with Renal involvement were enrolled and followed up. The median age at presentation was 15 years (IQR-16-9.5) (73% females). 8/19 (42%) children presented with AKI, of which 62% children presented as rapidly progressive renal failure. Six (37.5%) patients required dialysis at presentation. 84.21% of children were evaluated with renal biopsy, 16 biopsies were done in 19 children, among which class II, III, and IV lupus nephritis were reported in 21%,42%, and 35% respectively(4 crescentic). Antiphospholipid antibodies were positive in 8/15(53%), children which is much higher than a reported incidence of 30% in other Indian studies. Ten patients (52%) had neurological involvement, with seizures being the most common form of presentation (60%). Seven patients (36%) developed hepatitis. We noted many uncommon presentations in the small group like Autoimmune Pancreatitis, Mononeuritis multiplex, and peripheral digital gangrene. Cyclophosphamide was used in 10 out of 19 patients for inducing remission with class 3 and 4 nephritis and MMF in 8 children. 55% patients attained remission (after completing induction), of which 4 relapsed during the follow up. Four patients were lost to follow-up. A total of 27% patients died and 10% patients developed end stage renal failure. It was seen that those who died had more cardiac and neurological involvement at presentation, higher grade of proteinuria, lower GFR, and need for dialysis at admission. CONCLUSION: We found a more severe form of clinical manifestation in pediatric SLE patients at the time of the first presentation in the form of severe renal and extrarenal manifestation compared to other parts of the country.

Intracerebral Haemorrhage in an Adolescent With COVID-19 With Acute Kidney Injury: Is the Virus to Blame?

Neurological manifestations in COVID-19 are well described. We describe a 15-year-old girl with acute focal deficit with altered sensorium due to massive right intracerebral hemorrhage following a hypertensive emergency and acute on chronic kidney disease. She was found to be COVID positive by reverse transcription-polymerase chain reaction (RT-PCR). She gradually improved although her neurological deficit in the form of left hemiparesis persisted at discharge. There might be a possible association between intracerebral hemorrhage and COVID-19, although the causation is still not well established.

Concurrent Longitudinally Extensive Transverse Myelitis and Guillain-Barré Syndrome in a Child Secondary to COVID-19 Infection: A Severe Neuroimmunologic Complication of COVID-19.

Neurologic manifestation of coronavirus disease 2019 (COVID-19) in children is evolving with time. We are reporting a young girl who presented to us with acute febrile illness followed by acute onset severe flaccid paralysis requiring prolonged intensive care unit stay and ventilator support. She was evaluated extensively and found to be positive for COVID serology, and neuroimaging revealed features of longitudinally extensive transverse myelitis (LETM) with enhancing cauda equina nerve roots, suggesting Guillain-Barré Syndrome (GBS). She failed to respond to immune suppressive therapy and needed plasma exchange for recovery. Like other common viral illnesses, COVID-19 can also act as a trigger for GBS-like illness and LETM, and we need to suspect these diagnoses in the cases with COVID-19 infection in compatible cases. This is probably the first pediatric case with concurrent GBS and LETM secondary to COVID-19 infection.