Ocular manifestations and clinical profile of multisystemic inflammatory syndrome in children during COVID-19 pandemic

Background: Multisystemic inflammatory syndrome in children (MIS-C) is a new childhood disease, which is associated with Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). To evaluate ocular manifestations and clinical characteristics of MIS-C during COVID-19 pandemic.Methods: A cross-sectional observational study was conducted among 48 MIS-C patients (≤19 years) at Burdwan Medical college and hospital in West Bengal, India from April 2021 to June 2021. History taking, clinical examination and necessary investigations of all the patients were done.Results: Out of 48 patients, 18 patients (37.5%) presented with conjunctivitis, 4 (8.3%) with eyelid swelling, 2 (4.2%) with episcleritis, 2 (4.2%) with papilledema, 1 (2.1%) with subconjunctival haemorrhage, 1 (2.1%) with uveitis, 1 (2.1%) with retinitis and 4 (8.3%) with decreased vision. Other clinical manifestations included fever, skin rash, loose stool, vomiting, abdominal pain, cough, peripheral oedema, myalgia, breathlessness, altered sensorium, cervical lymphadenopathy, shock, oliguria, chest discomfort and joint swelling. Serum inflammatory, coagulation and cardiac markers were deranged.Conclusions: Ocular and other clinical manifestations in MIS-C were due to post-COVID immuno-dysregulation resulting in “cytokine storm” and hyper-inflammatory response. Conjunctivitis was the most common ocular manifestation. There was a positive correlation between severity of the conjunctival hyperaemia and level of serum inflammatory markers.

A Perspective on the Success and Failure of BCG

TB continues to be one of the major public health threats. BCG is the only available vaccine against TB and confers significant protection against the childhood disease. However, the protective efficacy of BCG against adult pulmonary TB, which represents a larger burden of disease, is highly variable. It has been suggested that prior exposure to environmental mycobacteria (EMb) mitigates the anti-TB efficacy of BCG by blocking its duplication or masking its immunogenicity. However, its effectiveness against childhood TB and failure of repeated administration to provide additional benefit against pulmonary TB, suggest of some other mechanisms for the variable efficacy of BCG against the pulmonary disease. Importantly, TB is a heterogeneous disease occurring in different forms and having distinct mechanisms of pathogenesis. While inability of the immune system to contain the bacilli is responsible for TB pathogenesis in infants, an aggravated immune response to Mtb has been blamed for the development of adult pulmonary TB. Available data suggest that EMb play a key role in heightening the immune response against Mtb. In this article, differential efficacy of BCG against childhood and adult TB is explained by taking into account the heterogeneity of TB, mechanisms of TB pathogenesis, and the effect of EMb on anti-Mtb immunity. It is believed that a refined understanding of the success and failure of BCG will help in the development of effective anti-TB vaccines.

Kawasaki Syndrome in Germany: Historical Aspects and Current Update

Through his analytical powers of observation, the Japanese physician Kawasaki became aware of a rare childhood disease that his colleagues mistook for scarlet fever. Even more than five decades later, there is only conjecture as to the cause, despite intensive research. Kawasaki syndrome even made it into the American blockbuster medical series Dr. House. For the Japanese pediatrician Tomisaku Kawasaki, who was regarded as very modest, it must have come as a great surprise when his name became established in medical circles worldwide at the end of the 1970s as the term for the acute inflammatory disease of the blood vessels in young children that he discovered

ALK inhibitors for treatment of adult-onset neuroblastoma.

2001 Background: Neuroblastoma (NB), a rare malignancy of the sympathetic nervous system, is a tumor of early childhood with > 90% of cases diagnosed before 5 years of age. Adult-onset NB (AON) is extremely rare and differs significantly from childhood disease. AON, while more indolent, is usually metastatic at diagnosis, generally chemotherapy-resistant, and almost invariably lethal. Additionally, standard therapies for NB such as dose-intensive chemotherapy and anti-GD2 antibody are poorly tolerated by adults. Prior studies have shown AON is enriched for genomic aberrations especially ALK (Suzuki et al 2018). Although ALK inhibitors (ALKi) are effective for therapy of lymphoma and non-small cell lung cancer, their use in AON has not previously been reported. Methods: Retrospective review of patients > 18 years old at diagnosis seen at Memorial Sloan Kettering Cancer Center (MSKCC) was performed after IRB approval. Response to ALKi was evaluated using International Neuroblastoma Response Criteria; objective responses were also noted. Progression-free (PFS) and overall survival (OS) was calculated using Kaplan-Meier methods. Results: Since 1979, 52 patients with AON were seen at MSKCC. Of 23 patients evaluated, 14 (61%), harbored somatic ALK mutations. Seven were treated with FDA-approved ALKi. One patient initially diagnosed at 12 years of age was treated with ALKi following a relapse 15 years later. Overall, all ALKi were well-tolerated; reported adverse events included grade 1-2 nausea and vomiting (n = 6), and neurologic symptoms including hallucinations, drowsiness, and dizziness (n = 1 patient each) which resolved after stopping ALKi. Four patients received > 1 ALKi either due to progressive disease or intolerance. Most patients responded to the first ALKi with objective though partial response (n = 5) while one had progressive disease (PD). Median time to progression for initial ALKi was 15.5 months (10-45). One patient with no evaluable disease after four prior relapses was treated with alectinib for 36 months without PD. Of the patients treated with a second ALKi (n = 4), 1 had CR and 2 had PR after not having progressed previously, while the other had stable disease. Median OS from beginning treatment with first ALKi was 46.5 (17-74) months. Conclusions: AON is a rare disease which is a therapeutic challenge. Enrichment of ALK mutations permits consideration of targeted therapy. ALKi were well tolerated, often associated with significant responses, and treatment with serial ALKi led to ongoing benefit. Given this, ALKi should be considered for treatment in future AON cases.