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Abstract: CD19-negative relapse is a leading cause of treatment failure after chimeric antigen receptor (CAR) T-cell therapy for acute lymphoblastic leukemia. We investigated a CAR T-cell product targeting CD19 and CD22 generated by lentiviral cotransduction with vectors encoding our previously described fast-off rate CD19 CAR (AUTO1) combined with a novel CD22 CAR capable of effective signaling at low antigen density. Twelve patients with advanced B-cell acute lymphoblastic leukemia were treated (CARPALL [Immunotherapy with CD19/22 CAR Redirected T Cells for High Risk/Relapsed Paediatric CD19+ and/or CD22+ Acute Lymphoblastic Leukaemia] study, NCT02443831), a third of whom had failed prior licensed CAR therapy. Toxicity was similar to that of AUTO1 alone, with no cases of severe cytokine release syndrome. Of 12 patients, 10 (83%) achieved a measurable residual disease (MRD)-negative complete remission at 2 months after infusion. Of 10 responding patients, 5 had emergence of MRD (n = 2) or relapse (n = 3) with CD19- and CD22-expressing disease associated with loss of CAR T-cell persistence. With a median follow-up of 8.7 months, there were no cases of relapse due to antigen-negative escape. Overall survival was 75% (95% confidence interval [CI], 41%-91%) at 6 and 12 months. The 6- and 12-month event-free survival rates were 75% (95% CI, 41%-91%) and 60% (95% CI, 23%-84%), respectively. These data suggest dual targeting with cotransduction may prevent antigen-negative relapse after CAR T-cell therapy., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: To evaluate the sleep habits of school-going children before and during school closure in the national lockdown period (called 'Circuit Breaker' or CB in Singapore) due to the COVID-19 pandemic., Methods: Cross-sectional, anonymous, online, population-based survey questionnaire was administered to parents aged 21 years and above with children aged between 3 and 16 years attending pre-school, primary or secondary school (equivalent to kindergarten, middle and-high school) and residing in Singapore. Sleep duration in relation to various daily activities including academic activities, physical exercise, and screen time was evaluated pre-CB and during CB., Results: Data from 593 participants were analyzed. Pre-CB, the overall mean (SD) sleep duration of the study population was 9.01 (1.18) hours on weekdays and 9.99 (0.94) hours on weekends. During CB, mean (SD) sleep duration overall was 9.63 (1.18) hours. Although children generally went to bed later (mean 0.65 h later), they woke up even later during CB (mean 1.27 h later), resulting in longer sleep duration (mean increase of 0.35 h). This was most evident in secondary school children (mean increase of 0.70 h). Children attending private schools (which had later start times) had increased sleep duration (mean 10.01 (SD 0.89) hours pre-CB and 10.05 (SD 0.93) hours during CB) compared to public schools (mean 9.05 (SD 0.91) pre-CB and 9.49 (SD 1.22) hours during CB)., Conclusions: School closure from the COVID-19 pandemic resulted in longer sleep duration in school-going children. Early school/academic activity start times had a significant impact on limiting children's sleep duration., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We set out to investigate whether neckties worn by doctors are more likely to be contaminated with Methicillin resistant Staphylococcus aureus (MRSA) compared to neckties worn by preclinical medical undergraduates who have never been exposed to a hospital environment. We discovered that more than half (52%) of neckties worn by doctors were contaminated with Staphylococcus and out of these, 62% of them were identified as MRSA. In contrast, none of the student's ties were contaminated with MRSA. Due to the high prevalence of staphylococcus detected on doctors' neckties, we recommend that health care workers do not wear neckties.