Group B Streptococcus Rectovaginal Colonization and Resistance Patterns in HIV-Positive Compared to HIV-Negative Pregnant Patients.

OBJECTIVE: The objective of our study is to determine if human immunodeficiency virus (HIV)-positive pregnant patients have a higher rate of group B streptococcus (GBS) rectovaginal colonization compared with HIV-negative pregnant patients. STUDY DESIGN: Our study is a multi-site retrospective study performed at Ochsner Louisiana State University-Health Shreveport and Monroe campuses including patients who delivered between December 2011and June 2019. Rates of GBS rectovaginal colonization between HIV-positive pregnant patients were compared with a control group of HIV-negative patients. The control group was age and race matched in a 2:1 fashion. The primary outcome was to investigate rates of GBS rectovaginal colonization. Secondary outcomes included GBS culture antibiotic sensitivities, presence of GBS urinary tract infection, GBS positivity based on HIV viral load, and GBS positivity based on new vs established diagnosis of HIV. Continuous data were analyzed using an unpaired t-test, and categorical data were analyzed using a Chi-squared test. The probability level of <0.05 was set as statistically significant. RESULTS: A total of 225 patients were included in the final analysis, 75 HIV-positive and 150 HIV-negative controls. Demographic differences were noted. HIV-positive patients were more likely to deliver preterm and were more likely to deliver via cesarean section. Our primary outcome showed no significant differences in incidence of GBS colonization between HIV-positive patients and control group (n = 31, 41.3% vs n = 46, 30.6%, p = 0.136). Antibiotic resistance patterns showed no significant difference between the two groups. There were no significant differences in GBS positivity based on HIV viral load. CONCLUSION: Our study does not show a statistically significant difference in the incidence of GBS colonization between HIV-positive patients and HIV-negative controls. KEY POINTS: · HIV-positive pregnant patients do not have an increased risk of GBS rectovaginal colonization.. · HIV-positive pregnant patients have similar rates of GBS colonization regardless of viral load.. · GBS antibiotic sensitivities are similar in HIV-positive and HIV-negative pregnant patients..

Chronic hypertension in pregnancy: are outcomes the same in patients on antihypertensives?

OBJECTIVE: To investigate differences in maternal and fetal outcomes among pregnant patients with chronic hypertension requiring antihypertensives for adequate control versus those who do not require antihypertensives. STUDY DESIGN: Single-site retrospective cohort study including pregnant patients with chronic hypertension from 2015-2018. Two groups included those who required antihypertensives versus those who did not. Primary outcome is composite morbidity: pregnancy loss after 20 weeks, IUGR, maternal death, maternal stroke or TIA, pulmonary edema, renal failure, hypertensive emergency, HELLP syndrome, placental abruption or delivery before 34 weeks. Secondary outcomes included development of severe features, indication for preterm labor less than 37 weeks, incidence of severe range blood pressures, and neonatal outcomes. Student t, chi square, and Kruskal-Wallis tests where appropriate. Logistic regression used to account for potential confounders. RESULTS: Study cohort included 117 on antihypertensives and 114 not on antihypertensives. Use of antihypertensives was associated with the composite primary outcome (Odds ratio [OR], 3.88; 95% confidence interval [CI], 1.66-9.78). Use of antihypertensive medications was also associated with increased risk of prenatal diagnosis of IUGR, delivery prior to 34 weeks, development of severe features, severe blood pressure during pregnancy, earlier mean gestational age at delivery, lower mean birth weight, and higher risk of NICU admission. Logistic regression analysis showed that the association between medication requirement and our composite primary outcome persisted even after adjustment for age, BMI, and presence of gestational diabetes. CONCLUSION: Our findings show an association between the requirement of antihypertensive medication use a significantly higher risk of composite primary outcome, prenatal diagnosis of IUGR, delivery prior to 34 weeks, and the development of severe features.

Cell-type specific distribution and activation of type I IFN pathway molecules at the placental maternal-fetal interface in response to COVID-19 infection.

Background and objective: COVID-19 infection in pregnancy significantly increases risks of adverse pregnancy outcomes. However, little is known how the innate immunity at the placental maternal-fetal interface responds to COVID-19 infection. Type I IFN cytokines are recognized as a key component of the innate immune response against viral infection. In this study, we specifically evaluated expression of IFN antiviral signaling molecules in placentas from women infected with COVID-19 during pregnancy. Methods: Expression of IFN activation signaling pathway molecules, including cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), interferon regulatory factor 3 (IRF3), Toll-like receptor 7 (TLR7), mitochondrial antiviral-signaling protein (MAVS), and IFNß were determined in formalin-fixed paraffin embedded (FFPE) placental tissue sections (villous and fetal membrane) by immunostaining. A total of 20 placentas were examined, 12 from COVID-19 patients and 8 from non-COVID-19 controls. Patient demographics, clinical data, and placental pathology report were acquired via EPIC medical record review. Results: Except BMI and placental weight, there was no statistical difference between COVID and non-COVID groups in maternal age, gestational age at delivery, gravity/parity, delivery mode, and newborn gender and weight. In COVID-exposed group, the main pathological characteristics in the placental disc are maternal and fetal vascular malperfusion and chronic inflammation. Compared to non-COVID controls, expression of IFN activation pathway molecules were all upregulated with distinct cell-type specific distribution in COVID-exposed placentas: STING in villous and decidual stromal cells; IRF3 in cytotrophoblasts (CTs) and extra-villous trophoblasts (EVTs); and TLR7 and MAVS in syncytiotrophoblasts (STs), CTs, and EVTs. Upregulation of STING, MAVS and TLR7 was also seen in fetal endothelial cells. Conclusions: STING, IRF3, TLR7, and MAVS are key viral sensing molecules that regulate type I IFN production. Type I IFNs are potent antiviral cytokines to impair and eradicate viral replication in infected cells. The finding of cell-type specific distribution and activation of these innate antiviral molecules at the placental maternal-fetal interface provide plausible evidence that type I IFN pathway molecules may play critical roles against SARS-CoV-2 infection in the placenta. Our findings also suggest that placental maternal-fetal interface has a well-defined antiviral defense system to protect the developing fetus from SARS-CoV-2 infection.

Mutational analyses of novel rat models with targeted modifications in inflammatory bowel disease susceptibility genes.

Mutations and single base pair polymorphisms in various genes have been associated with increased susceptibility to inflammatory bowel disease (IBD). We have created a series of rat strains carrying targeted genetic alterations within three IBD susceptibility genes: Nod2, Atg16l1, and Il23r, using CRISPR/Cas9 genome editing technology. Knock-out alleles and alleles with known human susceptibility polymorphisms were generated on three different genetic backgrounds: Fischer, Lewis and Sprague Dawley. The availability of these rat models will contribute to our understanding of the basic biological roles of these three genes as well as provide new potential IBD animal models.

The Atg16l1 gene: characterization of wild type, knock-in, and knock-out phenotypes in rats.

ATG16L1 is a ubiquitous autophagy gene responsible, in part, for formation of the double-membrane bound autophagosome that delivers unwanted cellular debris and intracellular pathogens to the lysosome for degradation. A single, nonsynonymous adenine to guanine polymorphism resulting in a threonine to alanine amino acid substitution (T300A) directly preceded by a caspase cleavage site (DxxD) causes an increased susceptibility to Crohn's disease (CD) in humans. The mechanism behind this increased susceptibility is still being elucidated, however, the amino acid change caused by this point mutation results in increased ATG16L1 protein sensitivity to caspase 3-mediated cleavage. To generate novel rat strains carrying genetic alterations in the rat Atg16l1 gene, we first characterized the wild-type rat gene. We identified four alternative splice variants with tissue-specific expression. Using CRISPR-Cas9 genome editing technology, we developed a knock-in rat model for the human ATG16L1 T300A CD risk polymorphism, as well as a knock-out rat model to evaluate the role of Atg16l1 in autophagy as well as its potential effect on CD susceptibility. These are the first reported rat strains with alterations of the Atg16l1 gene. Consistent with studies of the effects of human ATG16L1 polymorphisms, models exhibit morphological abnormalities in both Paneth and goblet cells, but do not develop spontaneous intestinal permeability or inflammatory bowel disease. Analysis of the gut microbiota does not show inherent differences in bacterial composition between wild-type and genetically modified animals. These Atg16l1 strains are valuable new animal models for the study of both autophagy and CD susceptibility.

Delayed Infection of Porous Polyethylene Implants After Oncologic Maxillectomy and Reconstruction: 2 Case Reports and Review of Literature.

Medpor porous polyethylene implants are commonly used for facial skeletal reconstruction due to reported biocompatibility, fibrovascularization, and durability. While uncommon, late implant infections are an important consideration. We report delayed infections in 2 patients after unilateral total oncologic maxillectomy and reconstruction using Medpor implants for an ossifying fibroma and squamous cell carcinoma, respectively. In the first patient, annual interval computed tomography (CT) scans showed no recurrence of tumor or inflammatory changes. The second was lost to follow-up after adjuvant chemoradiation 1 year after resection. Patients both presented with swelling, drainage, and erythema around the implant at a mean of 4.5 years following maxillectomy. Both failed several attempts at conservative treatment. Cultures of implants removed at a mean of 2.5 months after infection grew α-hemolytic Streptococcus in the first and multiple organisms in the second, showing that the potential for delayed infection should be considered years after reconstruction.

Prolonged Fetal Heart Rate Decelerations in Labor: Can We Reduce Unplanned Primary Cesarean Sections in This Group?

INTRODUCTION: Non-reassuring fetal tracing is the second leading cause of primary cesarean delivery in the United States. Prolonged fetal heart rate decelerations are non-reassuring fetal heart rate characteristics, which do not uniformly predict poor fetal outcome but can prompt obstetricians to proceed with cesarean delivery. The objective of this manuscript is to identify a strategy to reduce the primary cesarean section rate in patients with prolonged fetal heart rate decelerations in labor. METHODS: This is a retrospective cohort study over a 5-year period at an academic medical center, including patients undergoing primary cesarean section following labor induction, augmentation, or spontaneous labor who were noted to have prolonged fetal heart rate deceleration(s) in the 1 h prior to the time of delivery. Two groups were compared: "crash" cesarean sections versus "emergent" cesarean sections. The primary outcome was if fetal heart tones were rechecked in the operating room prior to cesarean section incision. Secondary outcomes included maternal-fetal monitoring versus Doppler fetal heart tones in the operating room, return to baseline noted in the operating room, fetal outcomes, fetal monitoring characteristics, and anesthesia type between crash versus emergent groups. RESULTS: Of 1969 term singleton cesarean sections, 119 patients met our inclusion criteria (emergent group n = 80) (crash group n = 39), which accounted for 13.9% of all primary cesarean sections during the study period. The emergent group had a significantly higher rate of reassessment of fetal heart tones in the operating room n = 61 (76.2%) versus the crash group n = 15 (38.4%) (p ≤ 0.0001). There were no statistically significant differences regarding fetal outcomes between the two groups. The crash group had a higher rate of category 1 fetal heart rate tracing prior to the prolonged deceleration, a longer median prolonged deceleration, and a deeper median nadir of the prolonged deceleration; these differences were statistically significant. The prolonged-to-delivery interval was significantly shorter in the crash group (median = 15 min) than tin he emergent group (median = 33 min) (p ≤ 0.0001). The crash group also had a higher rate of general anesthesia (n = 11, 28.2%) than the emergent group (n = 6, 7.5%) (p = 0.002). The crash group was specifically investigated. Of the 15 patients with fetal heart tones rechecked in the crash group, 7 had returned to baseline in the operating room, but underwent cesarean section without fetal monitoring. CONCLUSION: Our results indicate that the practice of placing patients on fetal monitor upon arrival to the operating room prior to performing crash cesarean delivery could reduce the rate of primary cesarean deliveries performed for prolonged decelerations in labor. When fetal heart tones have returned to baseline upon arrival in the operating room, the decision to proceed with cesarean delivery can be reconsidered. However, many clinical factors must be taken into consideration, and the decision to proceed is ultimately at the discretion of the obstetrics provider.

Clinical Utility of Weekly Laboratory Testing in the Outpatient Management of Preeclampsia and Gestational Hypertension.

Objective To investigate the utility of obtaining weekly laboratory testing in patients managed as an outpatient for gestational hypertension and preeclampsia without severe features. Study Design A multisite retrospective cohort study was performed evaluating preterm women diagnosed with gestational hypertension/preeclampsia managed in an outpatient setting between gestational ages of 23 0/7 and 36 6/7 . Patients were divided into two groups: weekly laboratory evaluation (laboratories group) and a no laboratories group. The primary study outcome was composite maternal morbidity including more than one of the following: development of severe features, HELLP syndrome, eclampsia, placental abruption, maternal intensive care unit admission, or maternal death. Results A total of 204 patients were included in this study, laboratories group ( n = 120) and no laboratories group ( n = 84). The laboratories group was older (28.8 vs. 26.6 years, p = 0.02), had a higher rate of chronic hypertension (44 [36.7%] vs. 17 [20.2%], p = 0.01), and more often experienced the primary composite outcome (53 [44.2%] vs. 24 [28.5%], p = 0.02). No patients in our cohort were delivered for abnormal laboratory values. Conclusion This study found that weekly laboratory testing may have minimal clinical utility in the outpatient management protocol in monitoring patients with mild gestational hypertension or preeclampsia. Delivery was guided by other clinical factors.

A novel conditional ZsGreen-expressing transgenic reporter rat strain for validating Cre recombinase expression.

The Cre/loxP recombination system has revolutionized the ability to genetically manipulate animal genomes in order to conditionally control gene expression. With recent advances in genome editing, barriers to manipulating the rat genome have been overcome and it is now possible to generate new rat strains (Cre drivers) in which Cre recombinase expression is carefully controlled temporally and/or spatially. However, the ability to evaluate and characterize these Cre driver strains is limited by the availability of reliable reporter rat strains. Here, we describe the generation and characterization of a new transgenic rat strain in which conditional expression of the ZsGreen fluorescent protein gene requires the presence of exogenous Cre recombinase. Breeding Cre-expressing rat strains to this stable ZsGreen reporter strain provides an ideal method for validating new rat Cre driver lines and will greatly accelerate the characterization pipeline.

Effects of Clove Oil as a Euthanasia Agent on Blood Collection Efficiency and Serum Cortisol Levels in Danio rerio.

Zebrafish are an important laboratory animal model for biomedical research and are increasingly being used for behavioral neuroscience. Tricaine methanesulfonate (MS222) is the standard agent used for euthanasia of zebrafish. However, recent studies of zebrafish behavior suggest that MS222 may be aversive, and clove oil might be a possible alternative. In this study, we compared the effects of MS222 or clove oil as a euthanasia agent in zebrafish on the volume of blood collected and on serum levels of cortisol. Greater amounts of serum could be collected and lower serum levels of cortisol were present in fish euthanized with clove oil compared with equipotent dose of MS222. Euthanasia with clove oil did not blunt the expected elevation of serum cortisol levels elicited by an acute premortem stress. According to our findings, clove oil is a fast-acting agent that minimizes the cortisol response to euthanasia in zebrafish and allows the collection of large volumes of blood postmortem. These results represent a significant refinement in euthanasia methods for zebrafish.

Differential susceptibility to colorectal cancer due to naturally occurring gut microbiota.

Recent studies investigating the human microbiome have identified particular bacterial species that correlate with the presence of colorectal cancer. To evaluate the role of qualitatively different but naturally occurring gut microbiota and the relationship with colorectal cancer development, genetically identical embryos from the Polyposis in Rat Colon (Pirc) rat model of colorectal cancer were transferred into recipients of three different genetic backgrounds (F344/NHsd, LEW/SsNHsd, and Crl:SD). Tumor development in the pups was tracked longitudinally via colonoscopy, and end-stage tumor burden was determined. To confirm vertical transmission and identify associations between the gut microbiota and disease phenotype, the fecal microbiota was characterized in recipient dams 24 hours pre-partum, and in Pirc rat offspring prior to and during disease progression. Our data show that the gut microbiota varies between rat strains, with LEW/SsNHsd having a greater relative abundance of the bacteria Prevotella copri. The mature gut microbiota of pups resembled the profile of their dams, indicating that the dam is the primary determinant of the developing microbiota. Both male and female F344-Pirc rats harboring the Lewis microbiota had decreased tumor burden relative to genetically identical rats harboring F344 or SD microbiota. Significant negative correlations were detected between tumor burden and the relative abundance of specific taxa from samples taken at weaning and shortly thereafter, prior to observable adenoma development. Notably, this naturally occurring variation in the gut microbiota is associated with a significant difference in severity of colorectal cancer, and the abundance of certain taxa is associated with decreased tumor burden.