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Objective: The objective of this study is to evaluate outcomes of fetal sacrococcygeal teratoma (SCT) from an academic tertiary center., Study Design: This is a retrospective study evaluating pregnancy and postnatal outcomes of fetal SCT management at a single institution between 2006 and 2023. Results are reported as median (range)., Results: Fourteen patients with fetal SCT were studied. Hydrops fetalis occurred in 2 (14.3%) cases. Pregnancy course included expectant management in 12 (85.7%) and palliative preterm induction in 1 patient (7.1%). Indications for delivering timing included fetal deterioration in 7 patients (50%), preeclampsia in 3 (21.4%), elective induction of delivery in 3 (21.4%), and preterm labor in 1 (7.1%). Delivery GA was 36.4 weeks (26.4-40.1 weeks), with 11 (78.5%) cesareans and 3 (21.4%) vaginal deliveries. There were 13 (92.9%) live births and 11 (78.6%) long-term survivors. Postnatal resection pathology demonstrated 7 (53.8%) mature, 3 (23.1%) immature, and 3 (23.1%) malignant SCTs. Of the 11 long-term survivors, 3 (27.3%) had teratoma recurrences, including 2 (18.2%) with metastatic disease requiring chemotherapy. Notable long-term complications involved gastrointestinal (n = 7, 63.6%), genitourinary (n = 4, 36.4%), and musculoskeletal (n = 2, 18.2%) systems., Conclusion: SCT confers significant morbidity to both the pregnant patient and neonate. Multidisciplinary prenatal and postnatal care is needed to comprehensively manage this complex condition., (© 2024 Wiley Periodicals LLC.)

Objectives: Evaluate the impact of the Dobbs vs Jackson decision on abortion care at an academic center in Oregon, a state with no legal restrictions on abortion., Study Design: Electronic health records from patients who received an abortion at Oregon's largest tertiary hospital were utilized to compare the years before and after Dobbs., Results: Monthly average abortions increased from 57.8 pre-Dobbs to 77.1 post-Dobbs (p = 0.001). This trend was associated with an increased proportion of out-of-state patients (14.3% vs 9.5%, p = 0.004) presenting with gestational duration ≥26 weeks (23.6% vs 3.7% in-state, p < 0.001)., Conclusions: The Dobbs decision resulted in increased utilization of hospital-based abortion care in a protective state., Implications: This study reflects the critical role of protective states such as Oregon in preserving access to abortion services and the need for continued support to alleviate the impact of nationwide barriers to reproductive healthcare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: The prevalence of cannabis use in pregnancy is rising and is associated with adverse perinatal outcomes. In parallel, combined prenatal use of cannabis and nicotine is also increasing, but little is known about the combined impact of both substances on pregnancy and offspring outcomes compared with each substance alone., Objective: To assess the perinatal outcomes associated with combined cannabis and nicotine exposure compared with each substance alone during pregnancy., Design, Setting, and Participants: This retrospective population-based cohort study included linked hospital discharge data (obtained from the California Department of Health Care Access and Information) and vital statistics (obtained from the California Department of Public Health) from January 1, 2012, through December 31, 2019. Pregnant individuals with singleton gestations and gestational ages of 23 to 42 weeks were included. Data were analyzed from October 14, 2023, to March 4, 2024., Exposures: Cannabis-related diagnosis and prenatal nicotine product use were captured using codes from International Classification of Diseases, Ninth Revision, Clinical Modification, and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification., Main Outcome and Measures: The main outcomes were infant and neonatal death, infants small for gestational age, and preterm delivery. Results were analyzed by multivariable Poisson regression models., Results: A total of 3 129 259 pregnant individuals were included (mean [SD] maternal age 29.3 [6.0] years), of whom 23 007 (0.7%) had a cannabis-related diagnosis, 56 811 (1.8%) had a nicotine-use diagnosis, and 10 312 (0.3%) had both in pregnancy. Compared with nonusers, those with cannabis or nicotine use diagnoses alone had increased rates of infant (0.7% for both) and neonatal (0.3% for both) death, small for gestational age (14.3% and 13.7%, respectively), and preterm delivery (<37 weeks) (12.2% and 12.0%, respectively). Moreover, risks in those with both cannabis and nicotine use were higher for infant death (1.2%; adjusted risk ratio [ARR], 2.18 [95% CI, 1.82-2.62]), neonatal death (0.6%; ARR, 1.76 [95% CI, 1.36-2.28]), small for gestational age (18.0%; ARR, 1.94 [95% CI, 1.86-2.02]), and preterm delivery (17.5%; ARR, 1.83 [95% CI, 1.75-1.91])., Conclusions and Relevance: These findings suggest that co-occurring maternal use of cannabis and nicotine products in pregnancy is associated with an increased risk of infant and neonatal death and maternal and neonatal morbidity compared with use of either substance alone. Given the increasing prevalence of combined cannabis and nicotine use in pregnancy, these findings can help guide health care practitioners with preconception and prenatal counseling, especially regarding the benefits of cessation.

Importance: Prenatal cannabis use is rising and is a major public health issue. Cannabis use in pregnancy and during lactation has been associated with increased maternal and offspring morbidity and mortality., Objective: This review aims to summarize the existing literature and current recommendations for cannabis use during pregnancy or lactation., Evidence Acquisition: A PubMed, Cochrane Library, and Google Scholar literature search using the following terms was performed to gather relevant data: "cannabis," "cannabinoid," "delta-9-tetrahydrocannabinol," "THC," "cannabidiol," "fetal outcomes," "perinatal outcomes," "pregnancy," and "lactation.", Results: Available studies on cannabis use in pregnancy and during lactation were reviewed and support an association with increased risk of preterm birth, neonatal intensive care unit admission, low birth weight, and small-for-gestational-age infants., Conclusion and Relevance: There is a critical need for research on the effects of cannabis use in pregnancy and during lactation. This is a necessary first step before furthering patient education, developing interventions, and targeting antenatal surveillance to ameliorate the adverse impacts on maternal and fetal health.

Importance: Many states enacted 20-week abortion bans from 2011 to 2018. Such bans affect individuals who receive diagnoses of fetal anomalies and aneuploidy in the second trimester, preventing pregnant individuals from having the choice of whether or not to continue the pregnancy., Objectives: To examine the trends of neonatal Down syndrome rates and assess the association between enactment of 20-week abortion bans and rates of Down syndrome diagnosis., Design, Setting, and Participants: This population-based, historical cohort study used National Vital Statistics System data on 31 157 506 births in the US from 2011 to 2018. Statistical analysis was performed from May 2021 to February 2023., Exposure: States were categorized as those with or without a 20-week abortion ban enacted during the study period., Main Outcomes and Measures: Demographic characteristics between the ban and no-ban states were compared using χ2 tests and 2-sample t tests. Multivariable logistic regression evaluated the adjusted odds of Down syndrome among births in states that enacted 20-week abortion bans after the abortion ban enactment, adjusting for state, year of birth, maternal race and ethnicity, age, educational level, insurance, and number of prenatal visits., Results: The cohort consisted of 31 157 506 births (mean [SD] maternal age, 28.4 [5.9] years) in the United States, of whom 15 951 neonates (0.05%) received a diagnosis of Down syndrome at birth. A total of 17 states enacted 20-week abortion bans during the study period, and 33 states did not enact bans. In both states with and states without bans, the birth prevalence of neonatal Down syndrome increased over time; in states with bans, rates increased from 48.0 to 58.4 per 100 000 births; in states without bans, rates increased from 47.4 to 53.3 per 100 000 births. In multivariable logistic regression assessing the interaction of time and presence of a 20-week abortion ban, the odds of Down syndrome were higher in states that enacted 20-week abortion bans after enactment of the law compared with the years prior to enactment of the ban (adjusted odds ratio, 1.22; 95% CI, 1.11-1.35)., Conclusions and Relevance: In the US from 2011 to 2018, neonatal Down syndrome diagnoses increased more in states that enacted 20-week abortion bans compared with states that did not enact bans. Because these abortion bans were enacted throughout the study period and are known to inhibit choice in patient decision-making, it is possible that the difference in the rates of diagnosis is associated with these policies.

Background: Frailty has been increasingly recognized as an important risk factor for vascular procedures. To assess the impact of frailty on clinical outcomes and resource utilization in patients undergoing carotid revascularization using a national cohort., Methods: The 2005-2017 National Inpatient Sample was used to identify patients who underwent carotid endarterectomy (CEA) or carotid stenting (CAS). Patients were classified as frail using diagnosis codes defined by the Johns Hopkins Adjusted Clinical Groups frailty indicator. Multivariable regression was used to evaluate associations between frailty and in-hospital mortality, postoperative stroke, myocardial infarction (MI), hospitalization costs, and length of stay (LOS)., Results: Of 1,426,343 patients undergoing carotid revascularization, 59,158 (4.2%) were identified as frail. Among frail patients, 79.4% underwent CEA and 20.6% underwent CAS. Compared to CEA, a greater proportion of patients undergoing CAS were frail (6.0% vs. 3.8%, P < 0.001). Compared to the nonfrail cohort, frail patients had higher rates of mortality (2.2% vs. 0.5%, P < 0.001), postoperative stroke (2.6% vs. 1.0%, P < 0.001), MI (2.2% vs. 0.8%, P < 0.001), and stroke/death (4.4% vs. 1.4%, P < 0.001). After adjustment, frailty was associated with increased odds of mortality (AOR = 1.59, 95% CI: 1.30-1.80, P < 0.001), stroke (AOR = 1.66, 95% CI: 1.38-1.83 P < 0.001), MI (AOR = 1.51, 95% CI: 1.29-1.72, P < 0.001), and stroke/death (AOR = 1.62, 95% CI: 1.45-1.81, P < 0.001). Furthermore, frailty was associated with increased hospitalization costs (β = +$5,980, 95% CI: $5,490-$6,470, P < 0.001) and LOS (β = +2.6 days, 95% CI: 2.4-2.8, P < 0.001)., Conclusions: Frailty is associated with adverse outcomes and greater resource use for those undergoing carotid revascularization. Risk models should include an assessment of frailty to guide management and improve outcomes for these high-risk patients., (Copyright © 2021. Published by Elsevier Inc.)

Background: High hospital safety-net burden has been associated with inferior clinical outcomes. We aimed to characterize the association of safety-net burden with outcomes in a national cohort of patients undergoing carotid interventions., Methods: The 2010-2017 Nationwide Readmissions Database was used to identify adults undergoing carotid endarterectomy and carotid artery stenting. Hospitals were classified as low (LBH), medium, or high safety-net burden (HBH) based on the proportion of uninsured or Medicaid patients. Multivariable models were developed to evaluate associations between HBH and outcomes., Results: Of an estimated 540,558 hospitalizations for a carotid intervention, 28.5% were at HBH. Patients treated at HBH were more likely to be admitted non-electively (28.7% vs 20.2%, P < .001), have symptomatic presentation (11.0% vs 7.7%, P < .001), and undergo carotid artery stenting (18.7% vs 8.9%, P < .001). After adjustment, HBH remained associated with increased odds of postoperative stroke (AOR 1.19, P = .023, Ref = LBH), non-home discharge (AOR 1.10, P = .026), 30-day readmissions (AOR 1.14, P < .001), and 31-90-day readmissions (AOR 1.13, P < .001), but not in-hospital mortality (AOR 1.18, P = .27). HBH was linked to increased hospitalization costs (β +$2,169, P = .016)., Conclusion: HBH was associated with postoperative stroke, non-home discharge, readmissions, and increased hospitalization costs after carotid revascularization. Further studies are warranted to alleviate healthcare inequality and improve outcomes at safety-net hospitals., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Many factors affect access to immediate breast reconstruction (IR) after mastectomy. The present study was performed to assess trends, outcomes, and predictors of IR techniques using a nationally representative cohort., Methods: The 2009-2014 National Inpatient Sample (NIS) was used to identify adult women who underwent inpatient mastectomy with IR. Patients were compared by type of reconstruction: implant-based IR versus autologous reconstruction (AR). AR was classified as a microsurgical or pedicled flap procedure. Incidence, outcomes, and predictors were assessed using Chi squared univariate tests and multivariable logistic regression analyses., Results: Of 194,073 women who underwent IR, 136,668 (70.4%) received implant-based IR and 57,405 (29.6%) received AR. Of those who underwent AR procedures, 31,336 (54.6%) received microsurgical flaps and 26,680 (46.5%) received pedicled flaps. Utilization of deep inferior epigastric perforator (DIEP) flaps increased significantly (28.6-42.5% of AR, P < 0.001). Predictors of AR were Black race [adjusted odds ratio (AOR) = 1.46, P < 0.001], lower Elixhauser Comorbidity Index (AOR = 1.25, P < 0.001), private insurance (AOR = 1.07, P = 0.030), body mass index (BMI) ≥ 30 kg/m 2 (AOR = 1.38, P < 0.001), urban teaching hospital designation (AOR = 1.77, P < 0.001), and high hospital volume (AOR = 3.11, P < 0.001). Similar factors were associated with the use of microsurgical flaps. AR and microsurgical flaps were associated with higher rates of acute inpatient complications, resource utilization and length of stay (LOS) compared with implant-based IR and pedicled flaps, respectively., Conclusion: Implant-based IR remains the most common type of IR, although rates of microsurgical AR are on the rise. Follow-up of complications, costs, and quality-of-life measures may show that AR provides long-term high-value care despite upfront morbidity, cost, and use of hospital resources.

Motor neuron-specific microRNA-218 (miR-218) has recently received attention because of its roles in mouse development. However, miR-218 relevance to human motor neuron disease was not yet explored. Here, we demonstrate by neuropathology that miR-218 is abundant in healthy human motor neurons. However, in amyotrophic lateral sclerosis (ALS) motor neurons, miR-218 is down-regulated and its mRNA targets are reciprocally up-regulated (derepressed). We further identify the potassium channel Kv10.1 as a new miR-218 direct target that controls neuronal activity. In addition, we screened thousands of ALS genomes and identified six rare variants in the human miR-218-2 sequence. miR-218 gene variants fail to regulate neuron activity, suggesting the importance of this small endogenous RNA for neuronal robustness. The underlying mechanisms involve inhibition of miR-218 biogenesis and reduced processing by DICER. Therefore, miR-218 activity in motor neurons may be susceptible to failure in human ALS, suggesting that miR-218 may be a potential therapeutic target in motor neuron disease., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Aims/hypothesis: Adult beta cells in the pancreas are the sole source of insulin in the body. Beta cell loss or increased demand for insulin impose metabolic challenges because adult beta cells are generally quiescent and infrequently re-enter the cell division cycle. The aim of this study is to test the hypothesis that a family of proto-oncogene microRNAs that includes miR-17-92 and miR-106b-25 clusters regulates beta cell proliferation or function in the adult endocrine pancreas., Methods: To elucidate the role of miR-17-92 and miR-106b-25 clusters in beta cells, we used a conditional miR-17-92/miR-106b-25 knockout mouse model. We employed metabolic assays in vivo and ex vivo, together with advanced microscopy of pancreatic sections, bioinformatics, mass spectrometry and next generation sequencing, to examine potential targets of miR-17-92/miR-106b-25, by which they might regulate beta cell proliferation and function., Results: We demonstrate that miR-17-92/miR-106b-25 regulate the adult beta cell mitotic checkpoint and that miR-17-92/miR-106b-25 deficiency results in reduction in beta cell mass in vivo. Furthermore, we reveal a critical role for miR-17-92/miR-106b-25 in glucose homeostasis and in controlling insulin secretion. We identify protein kinase A as a new relevant molecular pathway downstream of miR-17-92/miR-106b-25 in control of adult beta cell division and glucose homeostasis., Conclusions/interpretation: The study contributes to the understanding of proto-oncogene miRNAs in the normal, untransformed endocrine pancreas and illustrates new genetic means for regulation of beta cell mitosis and function by non-coding RNAs., Data Availability: Sequencing data that support the findings of this study have been deposited in GEO with the accession code GSE126516.

Genome-encoded microRNAs (miRNAs) provide a post-transcriptional regulatory layer that is important for pancreas development. However, how specific miRNAs are intertwined into the transcriptional network, which controls endocrine differentiation, is not well understood. Here, we show that microRNA-7 (miR-7) is specifically expressed in endocrine precursors and in mature endocrine cells. We further demonstrate that Pax6 is an important target of miR-7. miR-7 overexpression in developing pancreas explants or in transgenic mice led to Pax6 downregulation and inhibition of α- and β-cell differentiation, resembling the molecular changes caused by haploinsufficient expression of Pax6. Accordingly, miR-7 knockdown resulted in Pax6 upregulation and promoted α- and β-cell differentiation. Furthermore, Pax6 downregulation reversed the effect of miR-7 knockdown on insulin promoter activity. These data suggest a novel miR-7-based circuit that ensures precise control of endocrine cell differentiation.

microRNAs (miRNAs) play important roles in pancreas development and in regulation of insulin expression in the adult. Here we show that loss of miRNAs activity in beta-cells during embryonic development results in lower beta-cell mass and in impaired glucose tolerance. Dicer1-null cells initially constitute a significant portion of the total beta-cell population. However, during postnatal development, Dicer1-null cells are depleted. Furthermore, wild-type beta cells are repopulating the islets in complex compensatory dynamics. Because loss of Dicer1 is also associated with changes in the distribution of membranous E-cadherin, we hypothesized that E-cadherin activity may play a role in beta cell survival or islet architecture. However, genetic loss of E-cadherin function does not impair islet architecture, suggesting that miRNAs likely function through other or redundant effectors in the endocrine pancreas.

Genome-encoded microRNAs (miRNAs) provide a posttranscriptional regulatory layer, which is important for pancreas development. Differentiation of endocrine cells is controlled by a network of pancreatic transcription factors including Ngn3 and NeuroD/Beta2. However, how specific miRNAs are intertwined into this transcriptional network is not well understood. Here, we characterize the regulation of microRNA-7 (miR-7) by endocrine-specific transcription factors. Our data reveal that three independent miR-7 genes are coexpressed in the pancreas. We have identified conserved blocks upstream of pre-miR-7a-2 and pre-miR-7b and demonstrated by functional assays that they possess promoter activity, which is increased by the expression of NeuroD/Beta2. These data suggest that the endocrine specificity of miR-7 expression is governed by transcriptional mechanisms and involves members of the pancreatic endocrine network of transcription factors.

MicroRNAs (miRNAs) were shown to be important for pancreas development, yet their roles in differentiated β-cells remain unclear. Here, we show that miRNA inactivation in β-cells of adult mice results in a striking diabetic phenotype. While islet architecture is intact and differentiation markers are maintained, Dicer1-deficient β-cells show a dramatic decrease in insulin content and insulin mRNA. As a consequence of the change in insulin content, the animals become diabetic. We provide evidence for involvement of a set of miRNAs in regulating insulin synthesis. The specific knockdown of miR-24, miR-26, miR-182 or miR-148 in cultured β-cells or in isolated primary islets downregulates insulin promoter activity and insulin mRNA levels. Further, miRNA-dependent regulation of insulin expression is associated with upregulation of transcriptional repressors, including Bhlhe22 and Sox6. Thus, miRNAs in the adult pancreas act in a new network that reinforces insulin expression by reducing the expression of insulin transcriptional repressors.