Cytochrome P450 1B1 ( CYP1B1 ) is involved in the activation of many carcinogens and in the metabolism of steroid hormones. We compared allele, genotype and haplotype frequencies of six single-nucleotide polymorphisms (SNPs) within CYP1B1 among non-Hispanic Caucasians (496 cases and 498 controls) and Hispanic Caucasians (153 cases and 240 controls). In the Hispanic Caucasians, the GG genotype for rs1056836 decreased the risk for prostate cancer (PCa) when compared with the CC genotype [odds ratio (OR) = 0.31, P = 0.04, 95% confidence interval (CI) = 0.10–0.96]. Among non-Hispanic Caucasian men with more aggressive PCa, the prevalence of several SNPs (rs2567206, rs2551188, rs2617266, rs10012 and rs1056836) was significantly associated with the disease status. A common C-G-C-C-G-A haplotype for rs2567206-rs2551188-rs2617266-rs10012-rs1056836-rs1800440 showed an inverse association with PCa risk in Hispanic Caucasians (OR = 0.19, P = 0.04, 95% CI = 0.04–0.95) and with aggressive disease status (i.e. Gleason score ≥7) in non-Hispanic Caucasian cases (OR = 0.64, P = 0.008, 95% CI = 0.47–0.89). In the non-Hispanic Caucasian cases, a second major haplotype T-A-T-G-C-A was positively associated with the high-grade disease status (OR = 1.77, P = 0.002, 95% CI = 1.24–2.53). Our findings suggest that genetic polymorphisms in CYP1B1 may modify the risk for PCa and support the role of CYP1B1 as a candidate gene for PCa.
Peripartum cardiomyopathy is defined by left ventricular dysfunction and development of cardiac failure without a known cause and occurring in the final month of pregnancy and up to 5 months postpartum. Peripartum cardiomyopathy is an important and steadily increasing cause of pregnancy-associated morbidity and mortality. The incidence of peripartum cardiomyopathy in the United States has been estimated recently as 1 in 2,230 births and approximately 1 in 1,000 births worldwide. The etiopathogenesis of peripartum cardiomyopathy remains elusive; however, it is generally thought to be from a two-hit hypothesis in which an underlying cardiomyocyte protein mutation results in apoptosis mediated by vascular and hormonal actions. Clinical recognition is integral to the management of this disease, because there must be careful exclusion of alternative etiologies. Although there are no disease-specific therapies, management of peripartum cardiomyopathy is based on treatment of heart failure and its symptoms, repressing neurohormonal responses, and preventing long-term sequelae. Ventricular function recovery and rates of recurrence of peripartum cardiomyopathy vary by ethnicity and geography. Mortality rates associated with peripartum cardiomyopathy range from 3% to 40%, depending on geographic location. In this review, normal cardiovascular adaptations in pregnancy are summarized and current evidence-based clinical management of the disease is discussed.
Acute fatty liver of pregnancy is a rare, but potentially fatal obstetric disorder characterized principally by varying degrees of hepatic failure with an onset typically in late pregnancy. This review outlines the etiopathogenesis and describes the multiorgan involvement that often results in a number of clinical and laboratory aberrations. These laboratory derangements provide distinct features to differentiate from other obstetric complications, such as hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Once recognized, central to the management of acute fatty liver of pregnancy is delivery planning and meticulous supportive care. One particularly dangerous complication is profound coagulopathy. After delivery, the coagulation defect resolves over 1–2 days, and hepatic and renal function are restored soon thereafter. This report offers anticipated recovery and management strategies for commonly associated complications. Application of these factors has served to decrease mortality from as high as 80% down to 10%; however, given the seriousness of this condition, severe maternal morbidities are frequently associated with this obstetric emergency.
Acute fatty liver of pregnancy (AFLP) is a rare, but potentially fatal condition, characterized by hepatic failure typically in the third trimester of pregnancy that is associated with multiorgan involvement resulting in a number of clinical and laboratory abnormalities. The cornerstone of management of AFLP includes prompt recognition, preparation for delivery, and supportive care such as reversal of coagulopathy. Early diagnosis, prompted delivery, and supportive care have resulted in improved maternal morbidity and mortality. This review focuses on the epidemiology, etiology, clinical presentation, diagnosis, management, and resolution of AFLP.
Key Points Question What is the current state of US Food and Drug Administration labeling of medications in relation to pregnancy and lactation? Findings In this cross-sectional study of 290 newly approved medications from January 2010 to December 2019, all products submitted after June 20, 2015, were in compliance with the Pregnancy and Lactation Labeling Rule (PLLR); however, of those submitted between 2010 and 2015, 32.6% were not in PLLR format by the designated date of June 30, 2019. Human data on pregnancy and lactation were available in less than 20% of new product labeling. Meaning This study found that with the implementation of PLLR in the last decade, new therapeutic products are in compliance with the new rule; however, more than one-third of labels remain out of PLLR compliance.
ImportanceExisting reports of pregnant patients with COVID-19 disease who require extracorporeal membrane oxygenation (ECMO) are limited, with variable outcomes noted for the maternal-fetal dyad.ObjectiveTo examine maternal and perinatal outcomes associated with ECMO used for COVID-19 with respiratory failure during pregnancy.Design, Setting, and ParticipantsThis retrospective multicenter cohort study examined pregnant and postpartum patients who required ECMO for COVID-19 respiratory failure at 25 hospitals across the US. Eligible patients included individuals who received care at one of the study sites, were diagnosed with SARS-CoV-2 infection during pregnancy or up to 6 weeks post partum by positive nucleic acid or antigen test, and for whom ECMO was initiated for respiratory failure from March 1, 2020, to October 1, 2022.ExposuresECMO in the setting of COVID-19 respiratory failure.Main outcome and measuresThe primary outcome was maternal mortality. Secondary outcomes included serious maternal morbidity, obstetrical outcomes, and neonatal outcomes. Outcomes were compared by timing of infection during pregnancy or post partum, timing of ECMO initiation during pregnancy or post partum, and periods of circulation of SARS-CoV-2 variants.ResultsFrom March 1, 2020, to October 1, 2022, 100 pregnant or postpartum individuals were started on ECMO (29 [29.0%] Hispanic, 25 [25.0%] non-Hispanic Black, 34 [34.0%] non-Hispanic White; mean [SD] age: 31.1 [5.5] years), including 47 (47.0%) during pregnancy, 21 (21.0%) within 24 hours post partum, and 32 (32.0%) between 24 hours and 6 weeks post partum; 79 (79.0%) had obesity, 61 (61.0%) had public or no insurance, and 67 (67.0%) did not have an immunocompromising condition. The median (IQR) ECMO run was 20 (9-49) days. There were 16 maternal deaths (16.0%; 95% CI, 8.2%-23.8%) in the study cohort, and 76 patients (76.0%; 95% CI, 58.9%-93.1%) had 1 or more serious maternal morbidity events. The largest serious maternal morbidity was venous thromboembolism and occurred in 39 patients (39.0%), which was similar across ECMO timing (40.4% pregnant [19 of 47] vs 38.1% [8 of 21] immediately postpartum vs 37.5% postpartum [12 of 32]; P > .99).Conclusions and RelevanceIn this multicenter US cohort study of pregnant and postpartum patients who required ECMO for COVID-19–associated respiratory failure, most survived but experienced a high frequency of serious maternal morbidity.
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