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Background The objective of this study was to investigate whether an isolated abnormal 1-hour glucose challenge test (GCT) among patients without gestational diabetes (GDM) is associated with adverse outcomes. Methods This is a retrospective cohort study of patients who underwent GDM screening at ≥ 24 weeks’ gestation with a 1-hour GCT and delivered a singleton fetus at > 35 weeks’ gestation at an urban tertiary hospital from 1/2013 to 10/2021. Data were extracted from an electronic medical record data warehouse using standardized billing/diagnosis codes. Individuals were categorized into 3 groups: normal screening (1-hour GCT value < 140 mg/dL), intermediate screening (1-hour GCT value ≥ 140 and < 200 but normal 3-hour glucose tolerance test (GTT)), and GDM (1-hour GCT ≥ 200 mg/dL or abnormal 3-hour GTT). The primary composite perinatal morbidity outcome included any of the following: large for gestational age (LGA) birthweight, birth injury, hypoglycemia with neonatal intensive care unit (NICU) admission, respiratory distress syndrome, transient tachypnea of the newborn, apnea, NICU admission, or perinatal death. Multiple secondary outcomes were also evaluated. Bivariable analyses and multivariable logistic regression modeling were performed. Results Of 37,277 eligible patients, 29,698 (79.7%) had normal screening results, 5092 (13.7%) had intermediate screening results, and 2487 (6.6%) were diagnosed with GDM. There were significant differences in baseline characteristics between the three groups, including age, parity, race and ethnicity, payer-type, obesity, and pre-pregnancy metformin use. Compared to normal screening, intermediate screening was associated with an increased risk for the composite perinatal morbidity outcome (OR 1.23, 95% CI 1.15–1.32), cesarean (OR 1.37, 95% CI 1.28–1.46), and hypertensive disorders of pregnancy (OR 1.30, 95% CI 1.20–1.40). Associations for these outcomes were further pronounced in those with GDM compared to normal screening (OR 1.86, 95% CI 1.70–2.03; OR 1.69, 95% CI 1.56–1.84; and OR 1.57, 95% CI 1.42–1.74, respectively). After adjusting for potential confounders, increased risks for the composite perinatal morbidity outcome persisted for those with intermediate screening (aOR 1.18, 95% CI 1.10–1.26). Conclusions In addition to patients with GDM, individuals an isolated abnormal 1-hour GCT without GDM were also at increased risks for adverse pregnancy outcomes. Further investigation is needed to understand if patients with mild dysregulation may still benefit from other interventions.

BACKGROUNDThe effects of the novel coronavirus disease 2019 (COVID-19) in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic COVID-19 complicated by severe preeclampsia and placental abruption.METHODSWe analyzed the placenta for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through molecular and immunohistochemical assays and by and electron microscopy and measured the maternal antibody response in the blood to this infection.RESULTSSARS-CoV-2 localized predominantly to syncytiotrophoblast cells at the materno-fetal interface of the placenta. Histological examination of the placenta revealed a dense macrophage infiltrate, but no evidence for the vasculopathy typically associated with preeclampsia.CONCLUSIONThis case demonstrates SARS-CoV-2 invasion of the placenta, highlighting the potential for severe morbidity among pregnant women with COVID-19.FUNDINGBeatrice Kleinberg Neuwirth Fund and Fast Grant Emergent Ventures funding from the Mercatus Center at George Mason University. The funding bodies did not have roles in the design of the study or data collection, analysis, and interpretation and played no role in writing the manuscript.

Recent preclinical studies have identified three treatments that are especially promising for reducing acute lesion expansion following traumatic spinal cord injury (SCI): riluzole, systemic hypothermia, and glibenclamide. Each has demonstrated efficacy in multiple studies with independent replication, but there is no way to compare them in terms of efficacy or safety, since different models were used, different laboratories were involved, and different outcomes were evaluated. Here, using a model of lower cervical hemicord contusion, we compared safety and efficacy for the three treatments, administered beginning 4 h after trauma. Treatment-associated mortality was 30% (3/10), 30% (3/10), 12.5% (1/8), and 0% (0/7) in the control, riluzole, hypothermia, and glibenclamide groups, respectively. For survivors, all three treatments showed overall favorable efficacy, compared with controls. On open-field locomotor scores (modified Basso, Beattie, and Bresnahan scores), hypothermia- and glibenclamide-treated animals were largely indistinguishable throughout the study, whereas riluzole-treated rats underperformed for the first two weeks; during the last four weeks, scores for the three treatments were similar, and significantly different from controls. On beam balance, hypothermia and glibenclamide treatments showed significant advantages over riluzole. After trauma, rats in the glibenclamide group rapidly regained a normal pattern of weight gain that differed markedly and significantly from that in all other groups. Lesion volumes at six weeks were: 4.8±0.7, 3.5±0.4, 3.1±0.3 and 2.5±0.3 mm3 in the control, riluzole, hypothermia, and glibenclamide groups, respectively; measurements of spared spinal cord tissue confirmed these results. Overall, in terms of safety and efficacy, systemic hypothermia and glibenclamide were superior to riluzole.

IntroductionInduction of labour (IOL) is a commonly performed obstetric intervention, particularly when delivery is deemed more beneficial than continuing the pregnancy due to maternal or fetal indications. When the cervix is unfavourable for delivery, cervical ripening is performed prior to IOL. A wide variety of mechanical, pharmacological and combination methods are used, but the optimal approach balancing efficacy, safety and patient experience remains uncertain. Conventional aggregate data (AD) meta-analyses lack individual-level data, limiting exploration of patient-level factors for personalised medicine and do not address concerns about the trustworthiness of data presented in peer-reviewed randomised controlled trials (RCTs). This protocol describes an individual participant data (IPD) network meta-analysis (NMA) designed to evaluate and rank cervical ripening methods for IOL using only high quality, trustworthy data.Methods and analysisWe will identify eligible parallel-group RCTs enrolling pregnant women with a singleton, cephalic fetus at ≥34 weeks’ gestation requiring cervical ripening, through comprehensive searches of Ovid MEDLINE, Embase, Emcare, Scopus, Cochrane Pregnancy and Childbirth Register, WHO International Clinical Trials Registry Platform, clinicaltrials.gov and reference lists of prior reviews. The interventions we consider will be selected via Delphi consensus with international clinical experts. Eligible trial investigators will be invited to contribute de-identified IPD; AD will be used if IPD is unavailable. Trials will be assessed for trustworthiness using the Trustworthiness in RAndomised Clinical Trials checklist and the IPD Integrity Tool, with only eligible studies included in the primary analysis. All statistical analyses will follow a pre-specified statistical analysis plan (SAP) finalised before any analyses are conducted. A two-stage, contrast-based, frequentist IPD-NMA will compare cervical ripening methods for three co-primary outcomes: vaginal birth, composite adverse perinatal outcomes and composite adverse maternal outcomes. Subgroup analyses will assess effect modifiers (eg, parity, age and previous caesarean), with treatment rankings presented using the surface under the cumulative ranking curve and rank-heat plots. Sensitivity analyses will examine the impact of bias, missing data and population criteria.Ethics and disseminationThis study has been approved by the Monash University Human Research Ethics Committee (No. 48189). IPD will be de-identified and securely transferred for storage on a Monash University-hosted shared network drive. Findings will be disseminated via peer-reviewed publications, conference abstracts and the Cervical Ripening for Induction of Labour Collaborative Evidence Network Meta-Analysis (CIRCLE-NMA) website (https://circlenma.com). Patient and public involvement will guide the communication and interpretation of results.PROSPERO registration numberCRD420251077464.

Background: Microprolactinomas are typically benign tumors that rarely become macroprolactinomas. We present a rare case of a microprolactinoma that, after discontinuation of dopamine agonist (DA) therapy, transformed into a macroprolactinoma over a period of 6 years.Clinical Case: A 16-year-old woman initially presented for evaluation of galactorrhea without menstrual irregularities and was found to have elevated prolactin (68 ng/ml, normal range: 0-20), and a 4 mm pituitary microadenoma on MRI imaging. The patient was otherwise asymptomatic and other pituitary hormone levels were normal. She was treated with DA therapy (cabergoline 0.50 mg/week) which normalized her PRL level and improved but did not completely resolve the galactorrhea. She was then lost to follow up for 6 years. During that time, she discontinued cabergoline, but was still able to conceive, delivering a healthy baby after 2 years and breastfed briefly. She re-presented to her gynecologist 4 years after delivery for galactorrhea and secondary amenorrhea, both persistent since childbirth. Re-evaluation at that time revealed a much higher PRL level (432 ng/ml) and significant interval growth of the previous microadenoma to a 2.6 cm macroadenoma, now with extension into the left cavernous sinus, suprasellar cistern, with mass effect on the optic chiasm. The patient was retreated with cabergoline up to 3 mg/week, with a near-normal PRL level being achieved at 9 months (28 ng/ml). Repeat MRI revealed modest decrease of the adenoma to 2.4 cm. Galactorrhea resolved with reduction in PRL. However, amenorrhea persisted. Estradiol (30 pg/mL, 19-357 pg/mL) was low normal with normal withdrawal bleeding to medroxyprogesterone (MPA) challenge indicating reasonable estrogenization. She was treated with MPA to achieve regular cyclic bleeding every 3 months. Conclusion: This is an unusual case demonstrating significant growth of a microprolactinoma, which is typically a stable/indolent neoplasm, to a macroprolactinoma with invasive features. Previous studies of untreated microprolactinomas have shown that they undergo only subtle to minimal growth over 3 to 6 years and none transformed to a macroprolactinoma despite significant rises in PRL levels. In this clinical case, given the 6 intervening years that had elapsed in between MRIs, we cannot determine whether this represented moderate, progressive growth during that period after the discontinuation of DA therapy or whether the tumor had grown during pregnancy with its known stimulatory effects from hyperestrogenemia. The patient will require close follow-up to ensure ongoing shrinkage or at least stability of the adenoma and ongoing control of her hyperprolactinemia.References:1. Fertility and sterility39, 753-760 (1983). 2. Dietemann, J.L et al. Neuroradiology25, 133-138 (1983). 3. Garcia, M.M et al. Journal of endocrinological investigation18, 450-455 (1995).

BACKGROUND. The effects of the novel coronavirus disease 2019 (COVID-19) in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic COVID-19 complicated by severe preeclampsia and placental abruption. METHODS. We analyzed the placenta for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through molecular and immunohistochemical assays and by and electron microscopy and measured the maternal antibody response in the blood to this infection. RESULTS. SARS-CoV-2 localized predominantly to syncytiotrophoblast cells at the materno-fetal interface of the placenta. Histological examination of the placenta revealed a dense macrophage infiltrate, but no evidence for the vasculopathy typically associated with preeclampsia. CONCLUSION. This case demonstrates SARS-CoV-2 invasion of the placenta, highlighting the potential for severe morbidity among pregnant women with COVID-19. FUNDING. Beatrice Kleinberg Neuwirth Fund and Fast Grant Emergent Ventures funding from the Mercatus Center at George Mason University. The funding bodies did not have roles in the design of the study or data collection, analysis, and interpretation and played no role in writing the manuscript.

FUNDING. Beatrice Kleinberg Neuwirth Fund and Fast Grant Emergent Ventures funding from the Mercatus Center at George Mason University. The funding bodies did not have roles in the design of the study or data collection, analysis, and interpretation and played no role in writing the manuscript.