Recently, encouraging data provided long-awaited hope for gene therapy as a cure for sickle cell disease (SCD). Nevertheless, the suspension of the bluebird bio gene therapy trial (ClinicalTrials.gov NCT02140554) after participants developed acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) is concerning. Potential possibilities for these cases include busulfan, insertional mutagenesis, both or neither. Busulfan was considered the cause in the first reported case, as the transgene was not present in the AML/MDS. However, busulfan is unlikely to have contributed to the most recent case. The transgene was present in the patient's malignant cells, indicating they were infused after busulfan treatment. Several lines of evidence suggest an alternative explanation for events in the bluebird bio trial, including that SCD population studies show an increased relative, but a low absolute, risk of AML/MDS. We propose a new hypothesis after gene therapy for SCD, the stress of switching from homeostatic to regenerative hematopoiesis by transplanted cells drives clonal expansion and leukemogenic transformation of pre-existing premalignant clones, eventually resulting in AML/MDS. Evidence validating our hypothesis will support pre-screening individuals with SCD for pre-leukemic progenitors before gene therapy. Until a viable, safe strategy has been implemented to resume gene therapy in adults with severe SCD, reasonable alternative curative therapy should be considered for children and adults with severe SCD. Currently, open multi-center clinical trials are incorporating nonmyeloablative conditioning, related haploidentical donors, and post-transplantation cyclophosphamide. Preliminary results from these trials appear promising and NIH-sponsored trials are ongoing in pediatric and adult individuals with SCD using this platform.
  Venous thromboembolism (VTE) is a common complication of COVID-19. It is not well understood how hospitals have managed VTE prevention and the effect of prevention strategies on mortality.
 
  To characterize frequency, variation across hospitals, and change over time in VTE prophylaxis and treatment-dose anticoagulation in patients hospitalized for COVID-19, as well as the association of anticoagulation strategies with in-hospital and 60-day mortality.
 
  This cohort study of adults hospitalized with COVID-19 used a pseudorandom sample from 30 US hospitals in the state of Michigan participating in a collaborative quality initiative. Data analyzed were from patients hospitalized between March 7, 2020, and June 17, 2020. Data were analyzed through March 2021.
 
  Nonadherence to VTE prophylaxis (defined as missing ≥2 days of VTE prophylaxis) and receipt of treatment-dose or prophylactic-dose anticoagulants vs no anticoagulation during hospitalization.
 
  The effect of nonadherence and anticoagulation strategies ons may be optimal for patients hospitalized with COVID-19.
  While the 2016 US Centers for Disease Control and Prevention (CDC) guideline for prescribing opioids for chronic pain was not intended to address postoperative pain management, observers have noted the potential for the guideline to have affected postoperative opioid prescribing.
 
  To assess changes in postoperative opioid dispensing after vs before the CDC guideline release in March 2016.
 
  This cross-sectional study included 361 556 opioid-naive patients who received 1 of 8 common surgical procedures between March 16, 2014, and March 15, 2018. Data were retrieved from a private insurance database, and a retrospective interrupted time series analysis was conducted.  https://www.selleckchem.com/products/cpypp.html  Data analysis was conducted from March 2014 to April 2018.
 
  Outcomes were measured before and after release of the 2016 CDC guideline.
 
  The primary outcome was the total amount of opioid dispensed in the first prescription filled within 7 days following surgery in morphine milligram equivalents (MMEs); secondary outcomes included the total amoibed for surgery remained high during the study period, supporting the need for further efforts to improve postoperative pain management.
  Additional sources of pediatric epidemiological and clinical data are needed to efficiently study COVID-19 in children and youth and inform infection prevention and clinical treatment of pediatric patients.
 
  To describe international hospitalization trends and key epidemiological and clinical features of children and youth with COVID-19.
 
  This retrospective cohort study included pediatric patients hospitalized between February 2 and October 10, 2020. Patient-level electronic health record (EHR) data were collected across 27 hospitals in France, Germany, Spain, Singapore, the UK, and the US. Patients younger than 21 years who tested positive for COVID-19 and were hospitalized at an institution participating in the Consortium for Clinical Characterization of COVID-19 by EHR were included in the study.
 
  Patient characteristics, clinical features, and medication use.
 
  There were 347 males (52%; 95% CI, 48.5-55.3) and 324 females (48%; 95% CI, 44.4-51.3) in this study's cohort. There was a bimodal age distriection. Large-scale informatics-based approaches to integrate and analyze data across health care systems complement methods of disease surveillance and advance understanding of epidemiological and clinical features associated with COVID-19 in children and youth.
  The associations of levels of diverse serum carotenoids ascertained via repeated measurements with all-cause, cancer, and cardiovascular disease (CVD) mortality risk have not been considered in previous prospective studies.
 
  To investigate the association between repeated measurement of serum carotenoid levels and all-cause and cause-specific mortality risk.
 
  This cohort study's baseline data were collected using information from physical examinations from 1990 to 1999. Eligible participants were followed up until December 2017, with a median (interquartile range) follow-up period of 22.3 (15.5-25.3) years. Included individuals were age 40 years or older at the baseline data collection, were residents of the study site in the town of Yakumo, Hokkaido, Japan, and participated in a physical examination at least once from 1990 to 1999. Among eligible participants, after excluding 332 individuals, 3116 individuals were included in the analysis. Data analysis was conducted in April 2020.
 
  Repeated measurements of 6 serum carotenoid levels and 4 associated indices.