Higher severe acute respiratory syndrome coronavirus 2 infection rate in pregnant patients.

BACKGROUND: During the early months of the coronavirus disease 2019 pandemic, risks associated with severe acute respiratory syndrome coronavirus 2 in pregnancy were uncertain. Pregnant patients can serve as a model for the success of clinical and public health responses during public health emergencies as they are typically in frequent contact with the medical system. Population-based estimates of severe acute respiratory syndrome coronavirus 2 infections in pregnancy are unknown because of incomplete ascertainment of pregnancy status or inclusion of only single centers or hospitalized cases. Whether pregnant women were protected by the public health response or through their interactions with obstetrical providers in the early months of pandemic is not clearly understood. OBJECTIVE: This study aimed to estimate the severe acute respiratory syndrome coronavirus 2 infection rate in pregnancy and to examine the disparities by race and ethnicity and English language proficiency in Washington State. STUDY DESIGN: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection diagnosed between March 1, 2020, and June 30, 2020 were identified within 35 hospitals and clinics, capturing 61% of annual deliveries in Washington State. Infection rates in pregnancy were estimated overall and by Washington State Accountable Community of Health region and cross-sectionally compared with severe acute respiratory syndrome coronavirus 2 infection rates in similarly aged adults in Washington State. Race and ethnicity and language used for medical care of pregnant patients were compared with recent data from Washington State. RESULTS: A total of 240 pregnant patients with severe acute respiratory syndrome coronavirus 2 infections were identified during the study period with 70.7% from minority racial and ethnic groups. The principal findings in our study were as follows: (1) the severe acute respiratory syndrome coronavirus 2 infection rate was 13.9 per 1000 deliveries in pregnant patients (95% confidence interval, 8.3-23.2) compared with 7.3 per 1000 (95% confidence interval, 7.2-7.4) in adults aged 20 to 39 years in Washington State (rate ratio, 1.7; 95% confidence interval, 1.3-2.3); (2) the severe acute respiratory syndrome coronavirus 2 infection rate reduced to 11.3 per 1000 deliveries (95% confidence interval, 6.3-20.3) when excluding 45 cases of severe acute respiratory syndrome coronavirus disease 2 detected through asymptomatic screening (rate ratio, 1.3; 95% confidence interval, 0.96-1.9); (3) the proportion of pregnant patients in non-White racial and ethnic groups with severe acute respiratory syndrome coronavirus disease 2 infection was 2- to 4-fold higher than the race and ethnicity distribution of women in Washington State who delivered live births in 2018; and (4) the proportion of pregnant patients with severe acute respiratory syndrome coronavirus 2 infection receiving medical care in a non-English language was higher than estimates of pregnant patients receiving care with limited English proficiency in Washington State (30.4% vs 7.6%). CONCLUSION: The severe acute respiratory syndrome coronavirus 2 infection rate in pregnant people was 70% higher than similarly aged adults in Washington State, which could not be completely explained by universal screening at delivery. Pregnant patients from nearly all racial and ethnic minority groups and patients receiving medical care in a non-English language were overrepresented. Pregnant women were not protected from severe acute respiratory syndrome coronavirus 2 infection in the early months of the pandemic. Moreover, the greatest burden of infections occurred in nearly all racial and ethnic minority groups. These data coupled with a broader recognition that pregnancy is a risk factor for severe illness and maternal mortality strongly suggested that pregnant people should be broadly prioritized for coronavirus disease 2019 vaccine allocation in the United States similar to some states.

Disease severity, pregnancy outcomes, and maternal deaths among pregnant patients with severe acute respiratory syndrome coronavirus 2 infection in Washington State.

BACKGROUND: Evidence is accumulating that coronavirus disease 2019 increases the risk of hospitalization and mechanical ventilation in pregnant patients and for preterm delivery. However, the impact on maternal mortality and whether morbidity is differentially affected by disease severity at delivery and trimester of infection are unknown. OBJECTIVE: This study aimed to describe disease severity and outcomes of severe acute respiratory syndrome coronavirus 2 infections in pregnancy across the Washington State, including pregnancy complications and outcomes, hospitalization, and case fatality. STUDY DESIGN: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection between March 1, 2020, and June 30, 2020, were identified in a multicenter retrospective cohort study from 35 sites in Washington State. Sites captured 61% of annual state deliveries. Case-fatality rates in pregnancy were compared with coronavirus disease 2019 fatality rates in similarly aged adults in Washington State using rate ratios and rate differences. Maternal and neonatal outcomes were compared by trimester of infection and disease severity at the time of delivery. RESULTS: The principal study findings were as follows: (1) among 240 pregnant patients in Washington State with severe acute respiratory syndrome coronavirus 2 infections, 1 in 11 developed severe or critical disease, 1 in 10 were hospitalized for coronavirus disease 2019, and 1 in 80 died; (2) the coronavirus disease 2019-associated hospitalization rate was 3.5-fold higher than in similarly aged adults in Washington State (10.0% vs 2.8%; rate ratio, 3.5; 95% confidence interval, 2.3-5.3); (3) pregnant patients hospitalized for a respiratory concern were more likely to have a comorbidity or underlying conditions including asthma, hypertension, type 2 diabetes mellitus, autoimmune disease, and class III obesity; (4) 3 maternal deaths (1.3%) were attributed to coronavirus disease 2019 for a maternal mortality rate of 1250 of 100,000 pregnancies (95% confidence interval, 257-3653); (5) the coronavirus disease 2019 case fatality in pregnancy was a significant 13.6-fold (95% confidence interval, 2.7-43.6) higher in pregnant patients than in similarly aged individuals in Washington State with an absolute difference in mortality rate of 1.2% (95% confidence interval, -0.3 to 2.6); and (6) preterm birth was significantly higher among women with severe or critical coronavirus disease 2019 at delivery than for women who had recovered from coronavirus disease 2019 (45.4% severe or critical coronavirus disease 2019 vs 5.2% mild coronavirus disease 2019; P<.001). CONCLUSION: Coronavirus disease 2019 hospitalization and case-fatality rates in pregnant patients were significantly higher than in similarly aged adults in Washington State. These data indicate that pregnant patients are at risk of severe or critical disease and mortality compared to nonpregnant adults, and also at risk for preterm birth.

Clinical characteristics of 46 pregnant women with a severe acute respiratory syndrome coronavirus 2 infection in Washington State.

BACKGROUND: The impact of coronavirus disease 2019 on pregnant women is incompletely understood, but early data from case series suggest a variable course of illness from asymptomatic or mild disease to maternal death. It is unclear whether pregnant women manifest enhanced disease similar to influenza viral infection or whether specific risk factors might predispose to severe disease. OBJECTIVE: To describe maternal disease and obstetrical outcomes associated with coronavirus disease 2019 in pregnancy to rapidly inform clinical care. STUDY DESIGN: This is a retrospective study of pregnant patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 6 hospital systems in Washington State between Jan. 21, 2020, and April 17, 2020. Demographics, medical and obstetrical history, and coronavirus disease 2019 encounter data were abstracted from medical records. RESULTS: A total of 46 pregnant patients with a severe acute respiratory syndrome coronavirus 2 infection were identified from hospital systems capturing 40% of births in Washington State. Nearly all pregnant individuals with a severe acute respiratory syndrome coronavirus 2 infection were symptomatic (93.5%, n=43) and the majority were in their second or third trimester (43.5% [n=20] and 50.0% [n=23], respectively). Symptoms resolved in a median of 24 days (interquartile range, 13-37). Notably, 7 women were hospitalized (16%) including 1 admitted to the intensive care unit. A total of 6 cases (15%) were categorized as severe coronavirus disease 2019 with nearly all patients being either overweight or obese before pregnancy or with asthma or other comorbidities. Of the 8 deliveries that occurred during the study period, there was 1 preterm birth at 33 weeks' gestation to improve pulmonary status in a woman with class III obesity, and 1 stillbirth of unknown etiology. CONCLUSION: Severe coronavirus disease 2019 developed in approximately 15% of pregnant patients and occurred primarily in overweight or obese women with underlying conditions. Obesity and coronavirus disease 2019 may synergistically increase risk for a medically indicated preterm birth to improve maternal pulmonary status in late pregnancy. These findings support categorizing pregnant patients as a higher-risk group, particularly those with chronic comorbidities.

Cardiac Autotransplantation and Commando Operation for Complex Multivalvular Infective Endocarditis.

This report describes a patient with destructive multivalvular endocarditis with multiorgan dysfunction. Intraoperatively, severe unexpected adhesions due to pancarditis precluded the standard Commando operation. The approach of combining autotransplantation with a Commando operation was used to facilitate adequate débridement of infected tissues and reconstruction in a reasonable time and with satisfactory prosthetic valvular function. This approach may be considered in other cases of challenging destructive endocarditis with severe adhesions. We speculate that this approach may also be useful in redo surgeries.

Cesarean delivery rates and indications in pregnancies complicated by diabetes.

OBJECTIVE: Rates of pregestational (PGDM) and gestational diabetes (GDM), and their associated pregnancy complications, are rising. Pregnancies complicated by diabetes have increased cesarean delivery (CD) rates; however, there are limited data regarding the current rates of, and contributing factors to, these deliveries. The Robson Ten Group Classification System (TGCS) is a clinically relevant, standardized framework that can be used to evaluate and analyze cesarean rates. The objective of this study was to evaluate rates of, and indications for, intrapartum, unplanned CD among pregnancies complicated by diabetes, compared to normoglycemic (NG) pregnancies, in a large United States birth cohort. METHODS: This retrospective cohort study used chart-abstracted data on births between 24 and 42 weeks' gestation at 17 hospitals that contributed to the Obstetrical Care Outcome Assessment Program database between 01/2016 and 03/2019. The CD rate for NG pregnancies, and pregnancies complicated by gestational and PGDM was calculated and compared using the Robson TGCS. The indications for intrapartum CD in patients with term, singleton, vertex gestations without a prior cesarean were then analyzed. Univariate and multivariate logistic regression models were used to compare the cesarean rate and indications for CD, between the diabetic groups and the NG group. Results were adjusted for maternal age, BMI, neonatal birth weight, and insurance status, as well as clustering by hospital. RESULTS: A total of 86,381 pregnant people were included in the study cohort. Of these 76,272 (88.3%) were NG, 8591 (9.9%) had GDM, and 1518 (1.8%) had PGDM. Compared to NG patients, overall cesarean rates were higher in patients with GDM (40.3% vs. 29.7%; aOR 1.25, 95%CI 1.18-1.31) and PGDM (60.0% vs. 29.7%; aOR 2.53, 95%CI 2.04-3.13). This finding remained true when the cohort was restricted to term, singleton, vertex laboring patients without a prior cesarean; compared to NG patients, the cesarean rate was higher in patients with GDM (17.4% vs. 12.2%, aOR 1.37, 95%CI 1.29-1.45) and PGDM (26.0% vs. 12.2%, aOR 2.55, 95%CI 2.00-3.25). The cesarean rate for fetal indications was similar in the GDM (5.7%) and NG (4.4%) groups, while those patients with PGDM had a significantly higher rate (10.4%; aOR 2.01, 95%CI 1.43-2.83). Similarly, the rate of cesarean for labor dystocia in patients with PGDM was significantly higher than in NG patients (16.9% vs. 7.0%, and aOR 2.28, 95%CI 1.66-3.13) while patients with GDM had an intermediate rate (10.6% vs. 7.0%, aOR 1.49, 95%CI 1.40-1.57). CONCLUSIONS: The CD rate is significantly higher in pregnancies complicated by diabetes, particularly pregestational, compared to NG pregnancies. Despite controlling for maternal factors and birth weight, pregnancies complicated by diabetes are more likely to undergo an unplanned intrapartum cesarean secondary to labor dystocia than their NG counterparts, but only pregnancies complicated by PGDM have an increased risk of cesarean for fetal indications. More research is needed to understand whether this higher cesarean rate is due to factors intrinsic to diabetes in laboring patients or is due to a difference in the way clinicians manage diabetics in labor.

Validation of the Eighth Edition TNM Lung Cancer Staging System.

INTRODUCTION: We performed a validation study at our institution, the International Union Against Cancer (Union for International Cancer Control latest version of TNM Classification of Malignant Tumors Eighth Edition). METHODS: Data were collected from the Queensland Oncology Online registry of NSCLC or SCLC cases between 2000 and 2015 and validated against the Queensland Integrated Lung Cancer Outcomes Project registry using case identification number, first name, last name, and date of birth. Where data were available, cases were classified according to the Union for International Cancer Control TNM seventh edition stage groupings and then compared with the eighth edition groupings. Kaplan-Meier curves were plotted, and the log-rank test of survival differences was performed with SPSS version 25 (IBM Corp, Armonk, NY). RESULTS: Of the 3636 cases, 3352 and 1031 had complete clinical and pathologic staging, respectively. Median survival time was found to reduce with increasing clinical stage: seventh edition (IA: 88, IB: 44, IIA: 31, IIB: 18, IIIA: 15, IIIB: 8, and IV: 5 mo) versus eighth edition TNM stage (IA1: not reached, IA2: 88, IA3: 53, IB: 56, IIA: 36, IIB: 22, IIIA: 14, IIIB: 9, IIIC: 8, IVA: 6, and IVB: 3 mo). A similar overall pattern was reflected in the pathologic stage: seventh edition (IA: 124, IB: 110, IIA: 48, IIB: 42, IIIA: 26, IIIB: 31, and IV: 27 mo) versus eighth edition (IA1: not reached, IA2: 122, IA3: 125, IB: 144, IIA: 98, IIB: 57, IIIA: 31, IIIB: 24, and IVA: 7 mo). The log-rank test for survival curves was significant at p < 0.001. CONCLUSIONS: Our external validation study confirms the prognostic accuracy of the eighth edition TNM lung cancer classification. Our analyses also indicated that IIIB, IIIC, and IVA stage groups had similar survival outcomes and suggest further research for refinement.

Progenitor cell maintenance requires numb and numblike during mouse neurogenesis.

Neurons in most regions of the mammalian nervous system are generated over an extended period of time during development. Maintaining sufficient numbers of progenitors over the course of neurogenesis is essential to ensure that neural cells are produced in correct numbers and diverse types. The underlying molecular mechanisms, like those governing stem-cell self-renewal in general, remain poorly understood. We report here that mouse numb and numblike (Nbl), two highly conserved homologues of Drosophila numb, play redundant but critical roles in maintaining neural progenitor cells during embryogenesis, by allowing their progenies to choose progenitor over neuronal fates. In Nbl mutant embryos also conditionally mutant for mouse numb in the nervous system, early neurons emerge in the expected spatial and temporal pattern, but at the expense of progenitor cells, leading to a nearly complete depletion of dividing cells shortly after the onset of neurogenesis. Our findings show that a shared molecular mechanism, with mouse Numb and Nbl as key components, governs the self-renewal of all neural progenitor cells, regardless of their lineage or regional identities.