De-implementation of Routine Maternal Oxygen Supplementation for Intrauterine Fetal Resuscitation: A Retrospective Cohort Study.

OBJECTIVE: Current practice guidelines for laboring patients with category II intrapartum tracings recommend maternal oxygen supplementation despite emerging randomized data challenging its benefit and utility. We aim to validate that de-implementing maternal oxygen supplementation for fetal resuscitation did not increase the risk of neonatal acidemia in a real-world setting. DESIGN: This is a retrospective observational study conducted at a single tertiary care center from January 2019 to June 2021. All laboring deliveries during the study period was reviewed and eligible participants included singleton or twin pregnancies between 23-42 weeks gestational age with persistent category II tracings. Known major fetal anomalies, contraindications to labor, and maternal indication for O2 supplementation, including active COVID-19, were excluded. Cohorts were allocated based on time of delivery. Those occurring prior to our hospital policy change identified as historical controls and deliveries after April 1, 2020, as the post-de-implementation cohort. Primary outcome was fetal acidemia, defined as umbilical cord pH < 7.2. Secondary outcomes included severe acidemia (pH < 7.0), 5-minute Apgar score < 4 and neonatal intensive care admission. Regression analyses controlling for known variables associated with neonatal acidemia generated adjusted odds ratios with 95% confidence intervals. RESULTS: Among 9088 deliveries during the study period, 1162 tracings were flagged as persistent category II, including 681 (59%) in the post-intervention group. The two cohorts had comparable baseline and obstetric characteristics. No difference in neonatal acidemia was observed between the post-de-implementation group and historical controls (13.8% vs 15.4%, aOR 0.87, 95% CI 0.62-1.22). Severe acidemia, 5-minute Apgar < 4 and neonatal intensive care admission were not increased in the post-de-implementation group. CONCLUSIONS: De-implementation of routine maternal oxygen supplementation for fetal resuscitation did not increase likelihood for neonatal acidemia in a real-world setting, validating guidelines recommending against the intervention.

An Analysis of the Timing for Closure of a Diverting Loop Ileostomy.

A diverting loop ileostomy (DLI) is used to protect a distal gastrointestinal anastomosis at risk of leakage. While patients typically prefer early DLI closure, surgeons vary in opinion regarding optimal timing. This study evaluated whether the timing of DLI closure impacts outcomes.A retrospective review was performed on patients who underwent DLI creation within one health care system between 2012 and 2020. Patient characteristics and postoperative outcomes were compared across ileostomies closed in ≤2 months, 2-4 months, and >4 months. Outcomes examined included anastomotic leak, other complications, reintervention, and death within 30 days.A total of 500 DLIs were analyzed for the study, 455 of which were closed. The three closure groups were similar in patient characteristics and comorbidities. None of the outcome variables analyzed in this study demonstrated a statistically significant difference between groups, suggesting that in patients otherwise fit for surgery, DLI closure can be safely performed within 2 months of creation.

Masked pregnancy-associated hypertension as a predictor of adverse outcomes.

BACKGROUND: Masked hypertension has been described in nonpregnant populations as elevated blood pressure in the home setting that is not reproduced on clinical assessment. Patients with masked hypertension have a greater risk of cardiovascular morbidity than patients who have blood pressures within normal range or those with white coat hypertension. OBJECTIVE: This study aimed to determine whether masked pregnancy-associated hypertension detected on Connected Maternity Online Monitoring, a remote home blood pressure monitoring system, is associated with higher rates of hypertensive disorders of pregnancy during delivery admission and maternal and neonatal morbidities. STUDY DESIGN: This was a retrospective cohort study of all patients on Connected Maternity Online Monitoring who delivered at 6 hospitals in a single healthcare system between October 2016 and December 2020. Patients were classified as having either normal blood pressure or masked pregnancy-associated hypertension. Masked pregnancy-associated hypertension was defined as remotely detected systolic blood pressure of ≥140 mm Hg or diastolic blood pressure of ≥90 mm Hg after 20 weeks of gestation on 2 occasions before diagnosis in a clinical setting. The chi-square test and Student t test were used for demographic and outcomes comparisons. Logistic regression was used to adjust outcomes by race, insurance, and body mass index. RESULTS: A total of 2430 deliveries were included in our analysis, including 165 deliveries that met the criteria for masked pregnancy-associated hypertension. Clinically established pregnancy-associated hypertension, defined at the time of delivery, was more common in the masked pregnancy-associated hypertension group than in the normotensive group (66% vs 10%; adjusted odds ratio, 17.2; 95% confidence interval, 11.91-24.81). Patients with masked pregnancy-associated hypertension had higher rates of preeclampsia with severe features on delivery admission than normotensive patients (28% vs 2%; adjusted odds ratio, 23.35; 95% confidence interval, 14.25-38.26). Preterm delivery (16% vs 7%; adjusted odds ratio, 2.47; 95% confidence interval, 1.55-3.94), cesarean delivery(38% vs 26%; adjusted odds ratio, 1.58; 95% confidence interval, 1.13-2.23), small for gestational age (11% vs 5%; adjusted odds ratio, 2.27; 95% confidence interval, 1.31-3.94), and neonatal intensive care unit admission (8% vs 4%; adjusted odds ratio, 2.20; 95% confidence interval, 1.18-4.09) were more common among patients with masked pregnancy-associated hypertension than among normotensive patients. CONCLUSION: With more outcomes research, remote blood pressure monitoring may prove to be an important tool in identifying pregnancies at risk of complications related to masked hypertension.

Pregnancy Outcomes in Patients After Completion of the mRNA Coronavirus Disease 2019 (COVID-19) Vaccination Series Compared With Unvaccinated Patients.

OBJECTIVE: To compare frequency of perinatal death between pregnant patients who completed the mRNA coronavirus disease 2019 (COVID-19) vaccination series and unvaccinated patients. METHODS: This retrospective cohort study included 15,865 pregnant patients who delivered 16,132 newborns after 20 weeks of gestation within a large regional health system between January 1, 2021, and December 31, 2021. Patients who received two doses of mRNA vaccine (Pfizer-BioNTech [BNT162b2] or Moderna [mRNA-1273]) were included in the vaccinated group and were compared with unvaccinated patients. Exclusions included partial vaccination, viral-vector vaccine, major congenital anomalies, and higher-order multiple gestation. Our primary outcome was perinatal death, including stillbirth and neonatal death, which was evaluated by logistic regression. Unadjusted odds ratios and adjusted odds ratios (aORs) were reported, controlling for age, body mass index (BMI), diabetes, hypertension, smoking, twin gestation, and insurance status. Propensity score matching was also performed. RESULTS: A total of 15,865 patients were included in the final analysis: 2,069 in the vaccination group and 13,796 in the control group. Only 13.0% of the cohort was included in the vaccination group; however, the vaccination rate increased over the course of the study period as the vaccine became more widely available and accepted. Vaccinated patients were older, with higher rates of people of non-Black racial non-Hispanic ethnic backgrounds, people with private insurance, and those with higher BMIs. Vaccination was associated with a lower incidence of perinatal death (0.5% vaccinated group vs 0.8% unvaccinated group, aOR 0.20 0.05-0.88). Vaccination against COVID-19 was also associated with lower rates of preterm delivery (aOR 0.63, 0.48-0.82), neonates with very low birth weight (aOR 0.35, 0.15-0.84), and neonatal intensive care unit (NICU) admission (aOR 0.66, 0.52-0.85). The association between vaccination and lower rates of perinatal death was no longer significant after propensity score matching. CONCLUSION: In a large retrospective cohort study, receipt of the primary mRNA COVID-19 vaccination series was associated with a lower rate of several adverse pregnancy outcomes, including perinatal death, preterm delivery, neonates with very low birth weight, and NICU admission. Although the decreased rates of perinatal death did not remain significant after propensity score matching, there was evidence of directional benefit for vaccinated patients.

Direct Oral Anticoagulants Versus Warfarin for Venous Thromboembolism Prophylaxis in Patients With Nephrotic Syndrome: A Retrospective Cohort Study.

BACKGROUND: Evidence supporting venous thromboembolism (VTE) prophylaxis with direct oral anticoagulants (DOACs) in patients with nephrotic syndrome (NS) is limited to case reports. OBJECTIVE: The purpose of this study was to compare bleeding and thromboembolic events in this population. METHODS: A retrospective cohort study was conducted in adults with NS initiated on a DOAC or warfarin for VTE prophylaxis between January 2013 and July 2021 within the Ochsner Health System. Patients with study drug exposure within the preceding 7 days, acute VTE within the preceding 6 months, or ≤7 days of study drug exposure were excluded. The primary outcome was the composite rate of major bleeding and clinically relevant nonmajor bleeding. Secondary outcomes included time to major bleeding and rate of new thromboembolic events. This study was approved by the Ochsner Health System Institutional Review Board. RESULTS: Twenty-five DOAC and 19 warfarin patients were included. The primary outcome occurred in 8% vs 26.3% (P = 0.21) of patients treated with a DOAC or warfarin, respectively, and was driven by major bleeding (4% vs 21%, P = 0.25). Other secondary outcomes were similar between cohorts. The study was limited by a small sample size. CONCLUSION AND RELEVANCE: Use of DOACs for VTE prophylaxis resulted in a nonstatistically significant, but clinically relevant lower rate of major bleeding compared to warfarin. This study provides comparative data showing safe and effective use of DOACs in patients with NS. Prospective, randomized studies are needed to confirm results.

Safety-Related Outcomes of Novel mRNA COVID-19 Vaccines in Pregnancy.

OBJECTIVE: The objective of this study was to describe the safety profile and demographic data for a cohort of pregnant individuals who received an mRNA coronavirus disease 2019 (COVID-19) vaccine. STUDY DESIGN: Prospective cohort study (with exposure matching) of individuals with active pregnancy who underwent immunization with a novel mRNA COVID-19 vaccine matched 1:2 with vaccinated age-matched female nonregnant controls was carried out. The primary outcome was defined as any vaccine-related complaints as defined in the original safety data. Secondary outcomes included specific complaints, COVID-19 screening test, and positive COVID-19 test. RESULTS: Eighty-three vaccinated pregnant persons were age-matched with 166 female controls, all of whom were vaccinated between December 2020 and January, 2021. There was no difference in race or ethnicity between the groups. The mean body mass index of pregnant patients was lower than that of controls (26.1 vs. 29.2, p = 0.002). The frequency of complaints following vaccine administration was not different between pregnant and nonpregnant patients (18.1 vs. 16.9%, p = 0.201). Pregnant individuals were more likely to report fever (4.8 vs. 0.6%, p = 0.044) and gastrointestinal symptoms (4.8 vs. 0%, p = 0.012). CONCLUSIONS: Side effect profiles of COVID-19 vaccine administration at our institution were relatively similar between pregnant and nonpregnant individuals and no serious complications occurred in either group. As COVID-19 infection in pregnancy can have significant morbidity, our data support the continued use of the vaccine for pregnant patients. KEY POINTS: · Pregnant and nonpregnant women had a similar frequency of complaints.. · No serious adverse outcomes were observed in either group.. · Pregnant women were more likely to report fever and gastrointestinal side effects which may reflect gestationally mediated physiological responses to immunization..

Genetic diversity of Trypanosoma cruzi parasites infecting dogs in southern Louisiana sheds light on parasite transmission cycles and serological diagnostic performance.

BACKGROUND: Chagas disease is a neglected zoonosis of growing concern in the southern US, caused by the parasite Trypanosoma cruzi. We genotyped parasites in a large cohort of PCR positive dogs to shed light on parasite transmission cycles and assess potential relationships between parasite diversity and serological test performance. METHODOLOGY/PRINCIPAL FINDINGS: We used a metabarcoding approach based on deep sequencing of T. cruzi mini-exon marker to assess parasite diversity. Phylogenetic analysis of 178 sequences from 40 dogs confirmed the presence of T. cruzi discrete typing unit (DTU) TcI and TcIV, as well as TcII, TcV and TcVI for the first time in US dogs. Infections with multiple DTUs occurred in 38% of the dogs. These data indicate a greater genetic diversity of T. cruzi than previously detected in the US. Comparison of T. cruzi sequence diversity indicated that highly similar T. cruzi strains from these DTUs circulate in hosts and vectors in Louisiana, indicating that they are involved in a shared T. cruzi parasite transmission cycle. However, TcIV and TcV were sampled more frequently in vectors, while TcII and TcVI were sampled more frequently in dogs. CONCLUSIONS/SIGNIFICANCE: These observations point to ecological host-fitting being a dominant mechanism involved in the diversification of T. cruzi-host associations. Dogs with negative, discordant or confirmed positive T. cruzi serology harbored TcI parasites with different mini-exon sequences, which strongly supports the hypothesis that parasite genetic diversity is a key factor affecting serological test performance. Thus, the identification of conserved parasite antigens should be a high priority for the improvement of current serological tests.

In the heart of the city: Trypanosoma cruzi infection prevalence in rodents across New Orleans.

BACKGROUND: Trypanosoma cruzi - the causative agent of Chagas disease - is known to circulate in commensal pests, but its occurrence in urban environments is not well understood. We addressed this deficit by determining the distribution and prevalence of T. cruzi infection in urban populations of commensal and wild rodents across New Orleans (Louisiana, USA). We assessed whether T. cruzi prevalence varies according to host species identity and species co-occurrences, and whether T. cruzi prevalence varies across mosaics of abandonment that shape urban rodent demography and assemblage structure in the city. METHODS: Leveraging city-wide population and assemblage surveys, we tested 1428 rodents comprising 5 species (cotton rats, house mice, Norway rats, rice rats and roof rats) captured at 98 trapping sites in 11 study areas across New Orleans including nine residential neighborhoods and a natural area in Orleans Parish and a neighborhood in St. Bernard Parish. We also assayed Norway rats at one site in Baton Rouge (Louisiana, USA). We used chi-square tests to determine whether infection prevalence differed among host species, among study areas, and among trapping sites according to the number of host species present. We used generalized linear mixed models to identify predictors of T. cruzi infection for all rodents and each host species, respectively. RESULTS: We detected T. cruzi in all host species in all study areas in New Orleans, but not in Baton Rouge. Though overall infection prevalence was 11%, it varied by study area and trapping site. There was no difference in prevalence by species, but roof rats exhibited the broadest geographical distribution of infection across the city. Infected rodents were trapped in densely populated neighborhoods like the French Quarter. Infection prevalence seasonally varied with abandonment, increasing with greater abandonment during the summer and declining with greater abandonment during the winter. CONCLUSIONS: Our findings illustrate that T. cruzi can be widespread in urban landscapes, suggesting that transmission and disease risk is greater than is currently recognized. Our findings also suggest that there is disproportionate risk of transmission in historically underserved communities, which could reinforce long-standing socioecological disparities in New Orleans and elsewhere.

High prevalence of Trypanosoma cruzi infection in shelter dogs from southern Louisiana, USA.

BACKGROUND: Chagas disease is a zoonotic disease caused by the protozoan parasite Trypanosoma cruzi. The role of dogs as sentinels has been proposed in multiple regions, as they are a domestic reservoir for T. cruzi. Our objective was to determine the prevalence of T. cruzi infection in shelter dogs from southern Louisiana, and assess its magnitude and distribution. RESULTS: A total of 540 dogs were enrolled, from 20 animal shelters, and tested for T. cruzi infection by serological tests (rapid test, ELISA and western blot) and PCR. We documented a high prevalence of T. cruzi infection with at least 6.9% (95% CI: 5.0-9.3%) seropositive and 15.7% (95% CI: 12.9-19.1%) PCR-positive dogs. Serological tests showed limited agreement, and concordance between serology and PCR was higher when considering reactivity to single serological tests. Trypanosoma cruzi infection was distributed evenly among shelters. Infection was significantly correlated with age (R2 = 0.99), indicating an incidence of new cases of 2.27 ± 0.25% per year. CONCLUSION: Trypanosoma cruzi infection is a significant and widespread veterinary problem in shelter dogs in the region, although it is mostly unnoticed by health professionals. This highlights the need for greater awareness of T. cruzi infection among the veterinary community and dog owners.

Resveratrol targeting of AKT and p53 in glioblastoma and glioblastoma stem-like cells to suppress growth and infiltration.

OBJECTIVE Glioblastoma multiforme (GBM) is an aggressive brain cancer with median survival of less than 2 years with current treatment. Glioblastomas exhibit extensive intratumoral and interpatient heterogeneity, suggesting that successful therapies should produce broad anticancer activities. Therefore, the natural nontoxic pleiotropic agent, resveratrol, was studied for antitumorigenic effects against GBM. METHODS Resveratrol's effects on cell proliferation, sphere-forming ability, and invasion were tested using multiple patient-derived GBM stem-like cell (GSC) lines and established U87 glioma cells, and changes in oncogenic AKT and tumor suppressive p53 were analyzed. Resveratrol was also tested in vivo against U87 glioma flank xenografts in mice by using multiple delivery methods, including direct tumor injection. Finally, resveratrol was delivered directly to brain tissue to determine toxicity and achievable drug concentrations in the brain parenchyma. RESULTS Resveratrol significantly inhibited proliferation in U87 glioma and multiple patient-derived GSC lines, demonstrating similar inhibitory concentrations across these phenotypically heterogeneous lines. Resveratrol also inhibited the sphere-forming ability suggesting anti-stem cell effects. Additionally, resveratrol blocked U87 glioma and GSC invasion in an in vitro Matrigel Transwell assay at doses similar to those mediating antiproliferative effects. In U87 glioma cells and GSCs, resveratrol reduced AKT phosphorylation and induced p53 expression and activation that led to transcription of downstream p53 target genes. Resveratrol administration via oral gavage or ad libitum in the water supply significantly suppressed GBM xenograft growth; intratumoral or peritumoral resveratrol injection further suppressed growth and approximated tumor regression. Intracranial resveratrol injection resulted in 100-fold higher local drug concentration compared with intravenous delivery, and with no apparent toxicity. CONCLUSIONS Resveratrol potently inhibited GBM and GSC growth and infiltration, acting partially via AKT deactivation and p53 induction, and suppressed glioblastoma growth in vivo. The ability of resveratrol to modulate AKT and p53, as well as reportedly many other antitumorigenic pathways, is attractive for therapy against a genetically heterogeneous tumor such as GBM. Although resveratrol exhibits low bioavailability when administered orally or intravenously, novel delivery methods such as direct injection (i.e., convection-enhanced delivery) could potentially be used to achieve and maintain therapeutic doses in the brain. Resveratrol's nontoxic nature and broad anti-GBM effects make it a compelling candidate to supplement current GBM therapies.

Clinton Woolsey: functional brain mapping pioneer.

Dr. Clinton Woolsey was a leading 20th-century neuroscientist for almost 4 decades. His most significant achievements were the novel use and refinement of evoked potential techniques to functionally map mammalian brains, the discovery of secondary cortical areas, and a wide repertoire of comparative neurofunctional studies across many species. The authors discuss his life and work through a historical context with contemporaries, highlight the primitive state of brain mapping before Woolsey, and review his involvement in advancing its rapid development through work at both Johns Hopkins University and University of Wisconsin in Madison. Dr. Woolsey's lasting impact on basic and clinical neuroscience, neurosurgery, and neurology and his important roles as a scientific mentor and leader are also described.