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BackgroundImmunocompromised patients are at increased risk of SARS-CoV-2 infections. Patients undergoing chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory B-cell malignancies are uniquely immunosuppressed due to CAR T-mediated B-cell aplasia (BCA). While SARS-CoV-2 mortality rates of 33%–40% are reported in adult CAR T-cell recipients, outcomes in pediatric and young adult CAR T-cell recipients are limited.MethodsWe created an international retrospective registry of CAR T recipients aged 0–30 years infected with SARS-CoV-2 within 2 months prior to or any time after CAR T infusion. SARS-CoV-2-associated illness was graded as asymptomatic, mild, moderate, or severe COVID-19, or multisystem inflammatory syndrome in children (MIS-C). To assess for risk factors associated with significant SARS-CoV-2 infections (infections requiring hospital admission for respiratory distress or supplemental oxygen), univariate and multivariable regression analyses were performed.ResultsNine centers contributed 78 infections in 75 patients. Of 70 SARS-CoV-2 infections occurring after CAR T infusion, 13 (18.6%) were classified as asymptomatic, 37 (52.9%) mild, 11 (15.7%) moderate, and 6 (8.6%) severe COVID-19. Three (4.3%) were classified as MIS-C. BCA was not significantly associated with infection severity. Prior to the emergence of the Omicron variant, of 47 infections, 19 (40.4%) resulted in hospital admission and 7 (14.9%) required intensive care, while after the emergence of the Omicron variant, of 23 infections, only 1 (4.3%) required admission and the remaining 22 (95.7%) had asymptomatic or mild COVID-19. Death occurred in 3 of 70 (4.3%); each death involved coinfection or life-threatening condition. In a multivariable model, factors associated with significant SARS-CoV-2 infection included having two or more comorbidities (OR 7.73, CI 1.05 to 74.8, p=0.048) and age ≥18 years (OR 9.51, CI 1.90 to 82.2, p=0.014). In the eight patients infected with SARS-CoV-2 before CAR T, half of these patients had their CAR T infusion delayed by 15–30 days.ConclusionsIn a large international cohort of pediatric and young adult CAR-T recipients, SARS-CoV-2 infections resulted in frequent hospital and intensive care unit admissions and were associated with mortality in 4.3%. Patients with two or more comorbidities or aged ≥18 years were more likely to experience significant illness. Suspected Omicron infections were associated with milder disease.

Chimeric antigen receptor-associated hemophagocytic lymphohistiocytosis (HLH)-like toxicities (LTs) involving hyperferritinemia, multiorgan dysfunction, coagulopathy, and/or hemophagocytosis are described as occurring in a subset of patients with cytokine release syndrome (CRS). Case series report poor outcomes for those with B-cell acute lymphoblastic leukemia (B-ALL) who develop HLH-LTs, although larger outcomes analyses of children and young adults (CAYAs) with B-ALL who develop these toxicities after the administration of commercially available tisagenlecleucel are not described. Using a multi-institutional database of 185 CAYAs with B-ALL, we conducted a retrospective cohort study including groups that developed HLH-LTs, high-grade (HG) CRS without HLH-LTs, or no to low-grade (NLG) CRS without HLH-LTs. Primary objectives included characterizing the incidence, outcomes, and preinfusion factors associated with HLH-LTs. Among 185 CAYAs infused with tisagenlecleucel, 26 (14.1%) met the criteria for HLH-LTs. One-year overall survival and relapse-free survival were 25.7% and 4.7%, respectively, in those with HLH-LTs compared with 80.1% and 57.6%, respectively, in those without. In multivariable analysis for death, meeting criteria for HLH-LTs carried a hazard ratio of 4.61 (95% confidence interval, 2.41-8.83), controlling for disease burden, age, and sex. Patients who developed HLH-LTs had higher pretisagenlecleucel disease burden, ferritin, and C-reactive protein levels and lower platelet and absolute neutrophil counts than patients with HG- or NLG-CRS without HLH-LTs. Overall, CAYAs with B-ALL who developed HLH-LTs after tisagenlecleucel experienced high rates of relapse and nonrelapse mortality, indicating the urgent need for further investigations into prevention and optimal management of patients who develop HLH-LTs after tisagenlecleucel.

This study presents the design of a stair climbing cart to address the problem of lifting the heavy goods up to the stairs conveniently. A detailed design, mechanism and its analysis are presented. Design may be cost effective and affordable compared to human efforts for lifting the objects up to the stairs particularly for heavy loads. It works for a range of steps with step size range of less than 16 cm in height. Our proposed design and its characterisation ensure its functioning in any environmental conditions (such as dusty surface, etc.) and also on tiles/frictionless surface.

Ethambutol (EMB) is one of the first-line drugs in the treatment of tuberculosis. EMB induces ocular toxicity which is a rare side-effect that is either dose-related or duration-related effect and is often reversible on therapy discontinuation. The toxicity has been reported at 4 to 12 months of the initiation of the therapy. We reported a rare case of EMB-induced optic neuritis after 1 month of initiation of the therapy. After the withdrawal of the drug, there was complete recovery of the patient. This case description would improve the understanding of the clinical presentation as well as the treatment of ethambutol optic neuritis, especially in recourse-limited settings. It would also enrich the knowledge regarding the prevention strategies and timely recognition of the side effect. Keywords: Ethambutol, Optic neuritis, Isoniazid.

Synovial sarcoma (SS) primary to the pleura is an extremely rare tumor. So far, only nine cases have been reported in pediatric patients. However, none of these patients was found to have a conglomeration of tumors. Here, we report a case of 16-year-old female with monophasic SS and synchronous occurrence of left paraspinal ganglioneuroma and a right paraovarian cystadenoma. A next-generation sequencing genetic panel revealed a novel variant of unknown significance in the MET gene. The occurrence of multiple different tumors in a young patient with a novel genetic variant in a known oncogene (MET) may suggest a possibility of a hitherto unknown cancer predisposition syndrome. We also present a brief review of primary pleural SS reported in pediatric patients.

Background Intraplacental choriocarcinoma (ICC) is a rare form of gestational trophoblastic disease that has been documented as complicating near-term pregnancies with massive fetomaternal haemorrhage (FMH), intrauterine fetal demise, neonatal anaemia, and disseminated disease of both mother and child. Case A 31-year-old woman at 38 weeks of gestation underwent caesarean section due to reduced fetal movements. The caesarean section was complicated by disseminated intravascular coagulopathy (DIC). Massive FMH and choriocarcinoma were diagnosed after delivery. Discussion Review of the literature demonstrated this to be the first published case of DIC associated with choriocarcinoma, a rare complication. The literature suggests post-partum serial measurement of beta human chorionic gonadotropin (β-HCG) in women with unexplained massive FMH. This case demonstrates the potential to reduce morbidity and mortality by earlier diagnosis of choriocarcinoma by means of surveillance of serial β-HCG levels in patient and child. Outcome The patient underwent 4-agent chemotherapy after methotrexate alone failed to achieve remission. β-HCG levels were undetectable at the time of publishing this case report and the child is healthy with no complications., Highlights • Unexplained massive FMH may be secondary to ICC. • ICC are typically small lesions and may be missed on histopathology. • Serial BHCG surveillance may aid in diagnosis of unexplained massive FMH.

Lymphoid interstitial pneumonia (LIP) is a rare disease characterized by benign reactive polyclonal proliferation of bronchus-associated lymphoid tissue after exposure to inhaled or circulating antigen(s), leading to a disease symptomatology similar to idiopathic interstitial pneumonia. Its association with diseases that are caused due to immune dysregulation (autoimmune diseases, congenital/acquired immunodeficiency, and allogeneic bone marrow transplant) and response to immunomodulatory/suppressive medications suggests an immunologic pathophysiology. Although LIP has been reported in association with lymphoproliferative diseases like Castleman disease, it has never been described in patients with leukemia. We report the first case of LIP in a patient with juvenile myelomonocytic leukemia (JMML) who was found to have a novel germline mutation of unknown significance in additional sex combs-like-1 (ASXL1) gene and a pathogenic somatic mutation of protein tyrosine phosphatase, nonreceptor type 11 (PTPN11) gene at diagnosis. The patient underwent a matched unrelated bone marrow transplant for JMML with complete resolution of JMML and LIP with no recurrence to date. We also emphasize the importance of considering LIP in differential diagnosis of pulmonary lesions seen in conjunction with hematologic malignancies and distinguishing it from malignant infiltration of the lung.