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The burden of preeclampsia, a substantial contributor to perinatal morbidity and mortality, is not born equally across the population. Although the prevalence of preeclampsia has been reported to be 3% to 5%, racial and ethnic minority groups such as non-Hispanic Black women and American Indian or Alaskan Native women are widely reported to be disproportionately affected by preeclampsia. However, studies that add clarity to the causes of the racial and ethnic differences in preeclampsia are limited. Race is a social construct, is often self-assigned, is variable across settings, and fails to account for subgroups. Studies of the genetic structure of human populations continue to find more variations within racial groups than among them. Efforts to examine the role of race and ethnicity in biomedical research should consider these limitations and not use it as a biological construct. Furthermore, the use of race in decision making in clinical settings may worsen the disparity in health outcomes. Most of the existing data on disparities examine the differences between White and non-Hispanic Black women. Fewer studies have enough sample size to evaluate the outcomes in the Asian, American Indian or Alaskan Native, or mixed-race women. Racial differences are noted in the occurrence, presentation, and short-term and long-term outcomes of preeclampsia. Well-established clinical risk factors for preeclampsia such as obesity, diabetes, and chronic hypertension disproportionately affect non-Hispanic Black, American Indian or Alaskan Native, and Hispanic populations. However, with comparable clinical risk factors for preeclampsia among women of different race or ethnic groups, addressing modifiable risk factors has not been found to have the same protective effect for all women. Abnormalities of placental formation and development, immunologic factors, vascular changes, and inflammation have all been identified as contributing to the pathophysiology of preeclampsia. Few studies have examined race and the pathophysiology of preeclampsia. Despite attempts, a genetic basis for the disease has not been identified. A number of genetic variants, including apolipoprotein L1, have been identified as possible risk modifiers. Few studies have examined race and prevention of preeclampsia. Although low-dose aspirin for the prevention of preeclampsia is recommended by the US Preventive Service Task Force, a population-based study found racial and ethnic differences in preeclampsia recurrence after the implementation of low-dose aspirin supplementation. After implementation, recurrent preeclampsia reduced among Hispanic women (76.4% vs 49.6%; P<.001), but there was no difference in the recurrent preeclampsia in non-Hispanic Black women (13.7 vs 18.1; P=.252). Future research incorporating the National Institute on Minority Health and Health Disparities multilevel framework, specifically examining the role of racism on the burden of the disease, may help in the quest for effective strategies to reduce the disproportionate burden of preeclampsia on a minority population. In this model, a multilevel framework provides a more comprehensive approach and takes into account the influence of behavioral factors, environmental factors, and healthcare systems, not just on the individual. [ABSTRACT FROM AUTHOR]

• Inorganic arsenic was measureable in all amniotic fluid specimens. • This suggest ubiquitous maternal, and thus fetal, exposure. • This expands our scope of knowledge in environmental contaminants in amniotic fluid. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hypoxia results in chromatin remodeling in the LIFR promoter. • HDAC inhibitors stimulate LIFR and other pro-dormancy factors in hypoxia. • HDAC inhibitors stimulate LIFR even when it is repressed by elevated PTHrP levels. Breast cancer cells frequently disseminate to the bone marrow, where they either induce osteolysis or enter a dormant state. Downregulation of leukemia inhibitory factor receptor (LIFR), a known breast tumor suppressor, enables otherwise dormant MCF7 human breast cancer cells to become aggressively osteolytic. Hypoxia (low oxygen tensions), which may develop in tumors as a pathological response to the metabolic demands of the proliferating cells and as a physiological state in the bone, downregulates LIFR in breast cancer cells independent of hypoxia-inducible factor (HIF) signaling. However, the mechanism by which LIFR is repressed in hypoxia is unknown. Histone deacetylase (HDAC) inhibitors stimulate LIFR by increasing histone acetylation in the proximal promoter and induce a dormancy phenotype in breast cancer cells inoculated into the mammary fat pad. We therefore aimed to determine whether hypoxia alters histone acetylation in the LIFR promoter, and whether HDAC inhibitors effectively stimulate LIFR in breast cancer cells residing in hypoxic microenvironments. Herein, we confirmed that disseminated MCF7 cells became hypoxic in the bone and that hypoxia increased the epigenetic transcriptional repressor H3K9me3 in the distal LIFR promoter while H3K9ac, which promotes transcription, was significantly reduced. Furthermore, HDAC inhibitor treatment rescued hypoxic repression and dramatically increased expression of LIFR, p38β, and p21, which regulate tumor dormancy. In a second model of LIFR repression, in which parathyroid hormone-related protein (PTHrP) suppresses LIFR expression, we found that PTHrP binds to the distal LIFR promoter, and that PTHrP suppression of LIFR protein is similarly reversed by HDAC inhibitor treatment. Together, these data suggest that HDAC inhibitors stimulate LIFR regardless of the way it is repressed by the microenvironment. [ABSTRACT FROM AUTHOR]

Preoperative knowledge of surgical risks can improve perioperative care and patient outcomes. However, assessments requiring clinician examination of patients or manual chart review can be too burdensome for routine use. We conducted a multicentre retrospective study of 243 479 adult noncardiac surgical patients at four hospitals within the Mass General Brigham (MGB) system in the USA. We developed a machine learning method using routinely collected coding and patient characteristics data from the electronic health record which predicts 30-day mortality, 30-day readmission, discharge to long-term care, and hospital length of stay. Our method, the Flexible Surgical Set Embedding (FLEX) score, achieved state-of-the-art performance to identify comorbidities that significantly contribute to the risk of each adverse outcome. The contributions of comorbidities are weighted based on patient-specific context, yielding personalised risk predictions. Understanding the significant drivers of risk of adverse outcomes for each patient can inform clinicians of potential targets for intervention. FLEX utilises information from a wider range of medical diagnostic and procedural codes than previously possible and can adapt to different coding practices to accurately predict adverse postoperative outcomes. [ABSTRACT FROM AUTHOR]

Select Drug Category Opiates/Opioids Topic Tolerance/Dependence Abstract Detail Clinical - Epidemiology Abstract Category Original Research Characterize the relationship between intraoperative opioid administration and postoperative pain and opioid requirements. We conducted a retrospective cohort study of 61,250 adult patients who received non-cardiac surgery under general anesthesia at a quaternary care center between 2016 and 2020. The exposure variable was intraoperative fentanyl and intraoperative hydromorphone average effect site concentration. The primary study outcomes were maximal pain score during post-anesthesia care unit (PACU) stay and cumulative opioids administered in the PACU in morphine milligram equivalents (MME). Secondary outcomes included frequency of uncontrolled pain at 24 hours, new instances of chronic pain diagnosis, total opioid use at 24 hours and in-hospital, opioid prescriptions at 30, 90, and 180 postoperative days, frequency of new persistent opioid use, maximal pain score in the first 24 hours and in-hospital, and incidence of opioid related complications in PACU. We used multivariate propensity weighting to control for confounding and estimated the counterfactual difference in outcomes after administration of an additional 100 mcg fentanyl or 500 mcg hydromorphone intraoperatively. Increased intraoperative fentanyl and intraoperative hydromorphone were both associated with reduced maximum pain scores in the PACU. Both exposures were also associated with a reduced probability and reduced total dosage of opioid administration in the PACU. We found that increased fentanyl administration in particular was associated with lower frequency of uncontrolled pain, decreased chronic pain at 3-months, fewer opioid prescriptions at 30-, 90-, and 180-days, and decreased persistent opioid use, without significant increases in side effects. Our results show that intraoperative opioid administration is significantly associated with short- and long-term effects on post-operative pain and opioid outcomes. Contrary to prevailing trends, reduced opioid administration during surgery may have the unintended consequence of increasing postoperative pain and opioid consumption. Our analysis suggests that significant improvements in long-term outcomes might be achieved by optimizing opioid administration during surgery. [ABSTRACT FROM AUTHOR]