BACKGROUNDSpinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. METHODSWe conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. RESULTSIn the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants [51%] vs. 0 of 37 [0%]), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P = 0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P = 0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONSAmong infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074.)

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. Keywords Follow-up • MIS-C • Multi-inflammatory syndrome • Outcomes • Paediatric COVID-19 Abbreviations MIS-C Multi-system inflammatory syndrome in children EF Ejection fraction KD Kawasaki disease PAI-1 Plasminogen activator inhibitor-1 CRP C-reactive protein LDH Lactate dehydrogenase LMWH Low molecular weight heparin Rheumatology INTERNATIONAL

A 14-month-old male child presented with recurrent generalized seizures, spastic hemiplegia, microcephaly and had developmental delay in motor and speech domains. CT of the brain revealed characteristic features diagnostic of infantile type of cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome.

Background: In developing countries, there is scarce data on paediatric critical care. This makes modification of practices to improve outcome, difficult. The above study was done to highlight the lack of facilities and concept of pediatric critical in the eastern part of India so that modification of management can lead to better outcome of critically ill children.Methods: A retrospective study of the demography, clinical profile, diagnosis, treatment and outcome of children admitted to the PICU of Kalinga Institute of Medical Sciences from January 2014 to December 2015 was done. Results: A total of 848 children were admitted to the PICU with male and female children being 61.3% and 38.7% respectively. Diagnoses included infectious diseases (20.7%), respiratory disease (19.1%), central nervous system diseases (14.3%), cardiovascular diseases (10.8%), gastrointestinal diseases (7%), surgical problems (4.7%) haematological (4%), renal (3.3%), poisonings (1.4%), and others (14.3%). Out of 848 admitted children, 4.1% died and (1.4%) left against medical advice (8.5%) children received mechanical ventilation, among which (62.5%) improved, 34.7% died and 2.8% children left against medical advice. Multiorgan dysfunction syndrome (MODS) and co-morbidity were present in 25% and 22% respectively. The proportion of death among patients admitted to PICU was 4.1%.Conclusions: The leading cause of admission was infectious and respiratory diseases. Children with MODS and co-morbidity had higher mortality. The overall mortality rate in our PICU was low. We conclude, a well-equipped intensive care unit with modern and innovative facilities leads to a good outcome.

The global pandemic of SARS-CoV-2, the causative viral pathogen of COVID-19, has driven the biomedical community to action &ndash; to uncover and develop anti-viral interventions. One potential therapeutic approach currently being evaluated in numerous clinical trials is the agent remdesivir, which has endured a long and winding developmental path. Remdesivir is a nucleotide analog prodrug that perturbs viral replication, originally evaluated in clinical trials to thwart the Ebola outbreak in 2014. Subsequent evaluation by numerous virology laboratories demonstrated the ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2. Here, we provide an overview of its mechanism of action, discovery, and the current studies exploring its clinical effectiveness.

Acquired methemoglobinemia is an uncommon blood disorder induced by exposure to certain oxidizing agents and drugs. Although parents may not give any history of toxin ingestion; with the aid of pulse-oximetry and blood gas analysis, we can diagnose methemoglobinemia. Prompt recognition of this condition is required in emergency situations to institute early methylene blue therapy. We report an unusual case of severe toxic methemoglobinemia, which did not respond to methylene blue, but was successfully managed with exchange transfusion.

Pseudomonas aeruginosa , an ESKAPE pathogen causes many fatal clinical diseases in humans across the globe. Despite an increase in clinical instances of Pseudomonas infection, there is currently no effective vaccine or treatment available. The major membrane protein candidate of the P. aeruginosa bacterial cell is known to be a critical component for cellular bacterial susceptibility to antimicrobial peptides and survival inside the host organisms. Therefore, the current computational study aims to examine P. aeruginosa’s major membrane protein, OprF, and OprI, in order to design linear B-cell, cytotoxic T-cell, and helper T-cell peptide-based vaccine constructs. Utilizing various immune-informatics tools and databases, a total of two B-cells and twelve T-cells peptides were predicted. The final vaccine design was simulated to generate a high-quality three-dimensional structure, which included epitopes, adjuvant, and linkers. The vaccine was shown to be nonallergenic, antigenic, soluble, and had the best biophysical properties. The vaccine and Toll-like receptor 4 have a strong and stable interaction, according to protein-protein docking and molecular dynamics simulations. Additionally, in silico cloning was employed to see how the developed vaccine expressed in the pET28a (+) vector. Ultimately, an immune simulation was performed to see the vaccine efficacy. In conclusion, the newly developed vaccine appears to be a promising option for a vaccine against P. aeruginosa infection. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s10989-021-10356-z.

STRUCTURED ABSTRACTINTRODUCTIONFollowing an asymptomatic or mildly symptomatic Corona virus disease (COVID 19), otherwise healthy children, may develop serious manifestations in form of cardiac, neurological, respiratory, gastrointestinal and dermatologic dysfunction. Many such cases were being observed in Odisha, an eastern state of India and 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.METHODSThis retrospective observational study was carried out in three tertiary care centres: Kalinga Institute of Medical Sciences, Bhubaneswar, MKCG Medical college Berhampur and Jagannath Hospital, Bhubaneswar between July to September of year 2020. Study population include all children from 1 month to 15 years admitted to hospital with MIS-C according to WHO Diagnostic Criteria. All the data were analyzed by SPSS.RESULTSA total of 21 children were included in our study. Maximum number of cases were male (76.2%), predominate age group was 6-10 yrs (47.6%). Predominate symptoms /signs in our observation were fever, pain abdomen, seizure and hypotension. Most of these cases were positive for SARS CoV antibody (80.95%). Response to immunotherapy was dramatic. Mortality (9%) of our study is higher to 1.8–3% from western literature. None of our patient had coronary abnormality while 2 had mild cardiac dysfunction at discharge comparable to other studies.CONCLUSIONMIS-C following exposure to COVID 19 infection in children is a clinical syndrome which needs early suspicion and appropriate intervention to prevent mortality.