https://www.selleckchem.com/products/OSI-906.html In-vivo sensitivity to olaparib/irinotecan was seen in ATRX mutant but not wild-type xenografts. Finally, sustained responses to olaparib/irinotecan therapy were seen in an ATRX deleted neuroblastoma patient derived xenograft. ATRX LoF results in specific DNA damage repair defects that can be therapeutically exploited. In ATRX LoF models, preclinical sensitivity is demonstrated to olaparib and irinotecan, a combination that can be rapidly translated into the clinic. This work was supported by Christopher's Smile, Neuroblastoma UK, Cancer Research UK, and the Royal Marsden Hospital NIHR BRC. This work was supported by Christopher's Smile, Neuroblastoma UK, Cancer Research UK, and the Royal Marsden Hospital NIHR BRC. The contribution of substance use disorders to the burden of severe maternal morbidity in the United States is poorly understood. The objective was to estimate the independent association between substance use disorders during pregnancy and risk of severe maternal morbidity. Retrospective analysis of a weighted 53.4 million delivery hospitalizations from 2003 to 2016 among females aged>18 in the National Inpatient Sample. We constructed measures of substance use disorders using diagnostic codes for cannabis, opioids, and stimulants (amphetamines or cocaine) abuse or dependence during pregnancy. The outcome was the presence of any of the 21 CDC indicators of severe maternal morbidity. Using weighted multivariable logistic regression, we estimated the association between substance use disorders and adjusted risk of severe maternal morbidity. Because older age at delivery is predictive of severe maternal morbidity, we tested for effect modification between substance use and maternal age by age group (18-34 y vs >34 y). Pregnant women with an opioid use disorder had an increased risk of severe maternal morbidity compared with women without an opioid use disorder (18-34 years aOR 1.51; 95 % CI 1.41,1.61, >34 ye