Oncogenic Signaling Pathways in The Cancer Genome Atlas.

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFß signaling, p53 and ß-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy.

Fate induction in CD8 CAR T cells through asymmetric cell division.

Early expansion and long-term persistence predict efficacy of chimeric antigen receptor T cells (CARTs)1-7, but mechanisms governing effector versus memory CART differentiation and whether asymmetric cell division induces differential fates in human CARTs remain unclear. Here we show that target-induced proximity labelling enables isolation of first-division proximal-daughter and distal-daughter CD8 CARTs that asymmetrically distribute their surface proteome and transcriptome, resulting in divergent fates. Target-engaged CARs remain on proximal daughters, which inherit a surface proteome resembling activated-undivided CARTs, whereas the endogenous T cell receptor and CD8 enrich on distal daughters, whose surface proteome resembles resting CARTs, correlating with glycolytic and oxidative metabolism, respectively. Despite memory-precursor phenotype and in vivo longevity, distal daughters demonstrate transient potent cytolytic activity similar to proximal daughters, uncovering an effector-like state in distal daughters destined to become memory CARTs. Both partitioning of pre-existing transcripts and changes in RNA velocity contribute to asymmetry of fate-determining factors, resulting in diametrically opposed transcriptional trajectories. Independent of naive, memory or effector surface immunophenotype, proximal-daughter CARTs use core sets of transcription factors known to support proliferation and effector function. Conversely, transcription factors enriched in distal daughters restrain differentiation and promote longevity, evidenced by diminished long-term in vivo persistence and function of distal-daughter CARTs after IKZF1 disruption. These studies establish asymmetric cell division as a framework for understanding mechanisms of CART differentiation and improving therapeutic outcomes.

Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine.

Precision medicine initiatives across the globe have led to a revolution of repositories linking large-scale genomic data with electronic health records, enabling genomic analyses across the entire phenome. Many of these initiatives focus solely on research insights, leading to limited direct benefit to patients. We describe the biobank at the Colorado Center for Personalized Medicine (CCPM Biobank) that was jointly developed by the University of Colorado Anschutz Medical Campus and UCHealth to serve as a unique, dual-purpose research and clinical resource accelerating personalized medicine. This living resource currently has more than 200,000 participants with ongoing recruitment. We highlight the clinical, laboratory, regulatory, and HIPAA-compliant informatics infrastructure along with our stakeholder engagement, consent, recontact, and participant engagement strategies. We characterize aspects of genetic and geographic diversity unique to the Rocky Mountain region, the primary catchment area for CCPM Biobank participants. We leverage linked health and demographic information of the CCPM Biobank participant population to demonstrate the utility of the CCPM Biobank to replicate complex trait associations in the first 33,674 genotyped individuals across multiple disease domains. Finally, we describe our current efforts toward return of clinical genetic test results, including high-impact pathogenic variants and pharmacogenetic information, and our broader goals as the CCPM Biobank continues to grow. Bringing clinical and research interests together fosters unique clinical and translational questions that can be addressed from the large EHR-linked CCPM Biobank resource within a HIPAA- and CLIA-certified environment.

Responsible, practical genomic data sharing that accelerates research.

Data sharing anchors reproducible science, but expectations and best practices are often nebulous. Communities of funders, researchers and publishers continue to grapple with what should be required or encouraged. To illuminate the rationales for sharing data, the technical challenges and the social and cultural challenges, we consider the stakeholders in the scientific enterprise. In biomedical research, participants are key among those stakeholders. Ethical sharing requires considering both the value of research efforts and the privacy costs for participants. We discuss current best practices for various types of genomic data, as well as opportunities to promote ethical data sharing that accelerates science by aligning incentives.

Examining linguistic shifts between preprints and publications.

Preprints allow researchers to make their findings available to the scientific community before they have undergone peer review. Studies on preprints within bioRxiv have been largely focused on article metadata and how often these preprints are downloaded, cited, published, and discussed online. A missing element that has yet to be examined is the language contained within the bioRxiv preprint repository. We sought to compare and contrast linguistic features within bioRxiv preprints to published biomedical text as a whole as this is an excellent opportunity to examine how peer review changes these documents. The most prevalent features that changed appear to be associated with typesetting and mentions of supporting information sections or additional files. In addition to text comparison, we created document embeddings derived from a preprint-trained word2vec model. We found that these embeddings are able to parse out different scientific approaches and concepts, link unannotated preprint-peer-reviewed article pairs, and identify journals that publish linguistically similar papers to a given preprint. We also used these embeddings to examine factors associated with the time elapsed between the posting of a first preprint and the appearance of a peer-reviewed publication. We found that preprints with more versions posted and more textual changes took longer to publish. Lastly, we constructed a web application (https://greenelab.github.io/preprint-similarity-search/) that allows users to identify which journals and articles that are most linguistically similar to a bioRxiv or medRxiv preprint as well as observe where the preprint would be positioned within a published article landscape.

Acute exercise alters brain glucose metabolism in aging and Alzheimer's disease.

There is evidence that aerobic exercise improves brain health. Benefits may be modulated by acute physiological responses to exercise, but this has not been well characterized in older or cognitively impaired adults. The randomized controlled trial 'AEROBIC' (NCT04299308) enrolled 60 older adults who were cognitively healthy (n = 30) or cognitively impaired (n = 30) to characterize the acute brain responses to moderate [45-55% heart rate reserve (HRR)] and higher (65-75% HRR) intensity acute exercise. Each participant received two fluorodeoxyglucose positron emission tomography (FDG-PET) scans, one at rest and one following acute exercise. Change in cerebral glucose metabolism from rest to exercise was the primary outcome. Blood biomarker responses were also characterized as secondary outcomes. Whole grey matter FDG-PET standardized uptake value ratio (SUVR) differed between exercise (1.045 ± 0.082) and rest (0.985 ± 0.077) across subjects [Diff = -0.060, t(58) = 13.8, P < 0.001] regardless of diagnosis. Exercise increased lactate area under the curve (AUC) [F(1,56) = 161.99, P < 0.001] more in the higher intensity group [mean difference (MD) = 97.0 ± 50.8] than the moderate intensity group (MD = 40.3 ± 27.5; t = -5.252, P < 0.001). Change in lactate AUC and FDG-PET SUVR correlated significantly (R2 = 0.179, P < 0.001). Acute exercise decreased whole grey matter cerebral glucose metabolism. This effect tracked with the systemic lactate response, suggesting that lactate may serve as a key brain fuel during exercise. Direct measurements of brain lactate metabolism in response to exercise are warranted. KEY POINTS: Acute exercise is associated with a drop in global brain glucose metabolism in both cognitively healthy older adults and those with Alzheimer's disease. Blood lactate levels increase following acute exercise. Change in brain metabolism tracks with blood lactate, suggesting it may be an important brain fuel. Acute exercise stimulates changes in brain-derived neurotrophic factor and other blood biomarkers.

A field guide to cultivating computational biology.

Evolving in sync with the computation revolution over the past 30 years, computational biology has emerged as a mature scientific field. While the field has made major contributions toward improving scientific knowledge and human health, individual computational biology practitioners at various institutions often languish in career development. As optimistic biologists passionate about the future of our field, we propose solutions for both eager and reluctant individual scientists, institutions, publishers, funding agencies, and educators to fully embrace computational biology. We believe that in order to pave the way for the next generation of discoveries, we need to improve recognition for computational biologists and better align pathways of career success with pathways of scientific progress. With 10 outlined steps, we call on all adjacent fields to move away from the traditional individual, single-discipline investigator research model and embrace multidisciplinary, data-driven, team science.

The effect of non-linear signal in classification problems using gene expression.

Those building predictive models from transcriptomic data are faced with two conflicting perspectives. The first, based on the inherent high dimensionality of biological systems, supposes that complex non-linear models such as neural networks will better match complex biological systems. The second, imagining that complex systems will still be well predicted by simple dividing lines prefers linear models that are easier to interpret. We compare multi-layer neural networks and logistic regression across multiple prediction tasks on GTEx and Recount3 datasets and find evidence in favor of both possibilities. We verified the presence of non-linear signal when predicting tissue and metadata sex labels from expression data by removing the predictive linear signal with Limma, and showed the removal ablated the performance of linear methods but not non-linear ones. However, we also found that the presence of non-linear signal was not necessarily sufficient for neural networks to outperform logistic regression. Our results demonstrate that while multi-layer neural networks may be useful for making predictions from gene expression data, including a linear baseline model is critical because while biological systems are high-dimensional, effective dividing lines for predictive models may not be.

RNA sequences that direct selective ADAR editing from a SELEX library bearing 8-azanebularine.

Adenosine Deaminases Acting on RNA (ADARs) catalyze the deamination of adenosine to inosine in double-stranded RNA (dsRNA). ADARs' ability to recognize and edit dsRNA is dependent on local sequence context surrounding the edited adenosine and the length of the duplex. A deeper understanding of how editing efficiency is affected by mismatches, loops, and bulges around the editing site would aid in the development of therapeutic gRNAs for ADAR-mediated site-directed RNA editing (SDRE). Here, a SELEX (systematic evolution of ligands by exponential enrichment) approach was employed to identify dsRNA substrates that bind to the deaminase domain of human ADAR2 (hADAR2d) with high affinity. A library of single-stranded RNAs was hybridized with a fixed-sequence target strand containing the nucleoside analog 8-azanebularine that mimics the adenosine deamination transition state. The presence of this nucleoside analog in the library biased the screen to identify hit sequences compatible with adenosine deamination at the site of 8-azanebularine modification. SELEX also identified non-duplex structural elements that supported editing at the target site while inhibiting editing at bystander sites.

Menstrual education programs for girls and young women with intellectual and developmental disabilities: A systematic review.

BACKGROUND: Providing menstrual education and guidance for menstrual management for girls and young women with intellectual disabilities is recommended to ensure smooth pubertal transitions and to support menstrual self-agency. METHOD: The purpose of this systematic review is to explore menstrual education interventions for girls and young women with intellectual disabilities. RESULTS: Nine studies were included. Interventions were provided in small groups (n = 4) and individually (n = 5). Most studies used dolls (n = 7) and task analysis (n = 7) to teach pad-replacement skills. All reported significant improvements in participant skills and/or knowledge following the intervention. Only one study addressed self-agency and self-esteem as an outcome of the intervention. Menstrual education for girls and young women with intellectual disabilities is largely focused on pad-replacement skills. CONCLUSION: Further research is needed to understand the impact of menstrual health and hygiene education on variables apart from skill improvement such as self-agency and long-term health outcomes related to menstrual health.

wenda_gpu: fast domain adaptation for genomic data.

MOTIVATION: Domain adaptation allows for the development of predictive models even in cases with limited sample data. Weighted elastic net domain adaptation specifically leverages features of genomic data to maximize transferability but the method is too computationally demanding to apply to many genome-sized datasets. RESULTS: We developed wenda_gpu, which uses GPyTorch to train models on genomic data within hours on a single GPU-enabled machine. We show that wenda_gpu returns comparable results to the original wenda implementation, and that it can be used for improved prediction of cancer mutation status on small sample sizes than regular elastic net. AVAILABILITY AND IMPLEMENTATION: wenda_gpu is available on GitHub at https://github.com/greenelab/wenda_gpu/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Multiple and contrasting pressures determine intraspecific phytochemical variation in a tropical shrub.

Intraspecific phytochemical variation across a landscape can cascade up trophic levels, potentially mediating the composition of entire insect communities. Surprisingly, we have little understanding of the processes that regulate and maintain phytochemical variation within species, likely because these processes are complex and operate simultaneously both temporally and spatially. To assess how phytochemistry varies within species, we tested the degree to which resource availability, contrasting soil type, and herbivory generate intraspecific chemical variation in growth and defense of the tropical shrub, Piper imperiale (Piperaceae). We quantified changes in both growth (e.g., nutritional protein, above- and below-ground biomass) and defense (e.g., imide chemicals) of individual plants using a well-replicated fully factorial shade-house experiment in Costa Rica. We found that plants grown in high light, nutrient- and richer old alluvial soil had increased biomass. High light was also important for increasing foliar protein. Thus, investment into growth was determined by resource availability and soil composition. Surprisingly, we found that chemical defenses decreased in response to herbivory. We also found that changes in plant protein were more plastic compared to plant defense, indicating that constitutive defenses may be relatively fixed, and thus an adaptation to chronic herbivory that is common in tropical forests. We demonstrate that intraspecific phytochemical variation of P. imperiale is shaped by resource availability from light and soil type. Because environmental heterogeneity occurs over small spatial scales (tens of meters), herbivores may be faced with a complex phytochemical landscape that may regulate how much damage any individual plant sustains.

Changes of creative ability and underlying brain network connectivity throughout the lifespan.

Creativity, or divergent thinking, is essential to and supported by cognitive functions necessary for everyday tasks. The current study investigates divergent thinking and its neural mechanisms from adolescence to late adulthood. To do this, 180 healthy participants completed a creativity task called the egg task including 86 adolescents (mean age (SD) = 13.62 (1.98)), 52 young adults (24.92 (3.60), and 42 older adults (62.84 (7.02)). Additionally, a subsample of 111 participants completed a resting-state fMRI scan. After investigating the impact of age on different divergent thinking metrics, we investigated the impact of age on the association between divergent thinking and resting-state functional connectivity within and between major resting-state brain networks associated with creative thinking: the DMN, ECN, and SN. Adolescents tended to be less creative than both young and older adults in divergent thinking scores related to expansion creativity, and not in persistent creativity, while young and older adults performed relatively similar. We found that adolescents' functional integrity of the executive control network (ECN) was positively associated with expansion creativity, which was significantly different from the negative association in both the young and older adults. These results suggest that creative performance and supporting brain networks change throughout the lifespan.

New Nostocyclophanes from Nostoc linckia.

Six new nostocyclophanes and four known compounds have been isolated from Nostoc linckia (Nostocaceae) cyanobacterial strain UTEX B1932. The new compounds, nostocyclophanes E-J (1-6), were characterized by NMR and MS techniques. The known compounds were nostocyclophanes B-D, previously isolated from this strain, and dedichloronostocyclophane D. Structural modifications on the new [7.7]paracyclophane analogs 1-5, isolated from the 80% methanol fraction, range from simple changes such as the lack of methylation or halogenation to more unusual modifications such as those seen in nostocyclophane H (4), in which the exocyclic alkyl chains are of different length; this is the first time this modification has been observed in this family of natural products. In addition, nostocyclophane J (6) is a linear analog in which C-20 is chlorinated in preparation for the presumed enzymatic Friedel-Craft cyclization needed to form the final ring structure, analogous to the biosynthesis of the related cylindrocyclophanes. Nostocyclophane D, dedichloronostocyclophane D, and nostocyclophanes E-J demonstrated moderate to weak growth inhibition against MDA-MB-231 breast cancer cells.

Pseudomonas aeruginosa lasR mutant fitness in microoxia is supported by an Anr-regulated oxygen-binding hemerythrin.

Pseudomonas aeruginosa strains with loss-of-function mutations in the transcription factor LasR are frequently encountered in the clinic and the environment. Among the characteristics common to LasR-defective (LasR-) strains is increased activity of the transcription factor Anr, relative to their LasR+ counterparts, in low-oxygen conditions. One of the Anr-regulated genes found to be highly induced in LasR- strains was PA14_42860 (PA1673), which we named mhr for microoxic hemerythrin. Purified P. aeruginosa Mhr protein contained the predicted di-iron center and bound molecular oxygen with an apparent Kd of ∼1 µM. Both Anr and Mhr were necessary for fitness in lasR+ and lasR mutant strains in colony biofilms grown in microoxic conditions, and the effects were more striking in the lasR mutant. Among genes in the Anr regulon, mhr was most closely coregulated with the Anr-controlled high-affinity cytochrome c oxidase genes. In the absence of high-affinity cytochrome c oxidases, deletion of mhr no longer caused a fitness disadvantage, suggesting that Mhr works in concert with microoxic respiration. We demonstrate that Anr and Mhr contribute to LasR- strain fitness even in biofilms grown in normoxic conditions. Furthermore, metabolomics data indicate that, in a lasR mutant, expression of Anr-regulated mhr leads to differences in metabolism in cells grown on lysogeny broth or artificial sputum medium. We propose that increased Anr activity leads to higher levels of the oxygen-binding protein Mhr, which confers an advantage to lasR mutants in microoxic conditions.

Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis.

Myasthenia gravis (MG) is a neuromuscular, autoimmune disease caused by autoantibodies that target postsynaptic proteins, primarily the acetylcholine receptor (AChR) and inhibit signaling at the neuromuscular junction. The majority of patients under 50 y with AChR autoantibody MG have thymic lymphofollicular hyperplasia. The MG thymus is a reservoir of plasma cells that secrete disease-causing AChR autoantibodies and although thymectomy improves clinical scores, many patients fail to achieve complete stable remission without additional immunosuppressive treatments. We speculate that thymus-associated B cells and plasma cells persist in the circulation after thymectomy and that their persistence could explain incomplete responses to resection. We studied patients enrolled in a randomized clinical trial and used complementary modalities of B cell repertoire sequencing to characterize the thymus B cell repertoire and identify B cell clones that resided in the thymus and circulation before and 12 mo after thymectomy. Thymus-associated B cell clones were detected in the circulation by both mRNA-based and genomic DNA-based sequencing. These antigen-experienced B cells persisted in the circulation after thymectomy. Many circulating thymus-associated B cell clones were inferred to have originated and initially matured in the thymus before emigration from the thymus to the circulation. The persistence of thymus-associated B cells correlated with less favorable changes in clinical symptom measures, steroid dose required to manage symptoms, and marginal changes in AChR autoantibody titer. This investigation indicates that the diminished clinical response to thymectomy is related to persistent circulating thymus-associated B cell clones.

The Cesarean Scar of Pregnancy: Ultrasound Findings and Expectant Management Outcomes.

OBJECTIVE: The nomenclature has evolved from low implantation to cesarean scar pregnancy (CSP) and criteria are recommended for identification and management. Management guidelines include pregnancy termination due to life-threatening complications. This article applies ultrasound (US) parameters recommended by the Society for Maternal Fetal Medicine (SMFM) in women who were expectantly managed. STUDY DESIGN: Pregnancies were identified between March 1, 2013 and December 31, 2020. Inclusion criteria were women with CSP or low implantation identified on US. Studies were reviewed for niche, smallest myometrial thickness (SMT), and location of basalis blinded to clinical data. Clinical outcomes, pregnancy outcome, need for intervention, hysterectomy, transfusion, pathologic findings, and morbidities were obtained by chart review. RESULTS: Of 101 pregnancies with low implantation, 43 met the SMFM criteria at < 10 weeks and 28 at 10 to 14 weeks. At < 10 weeks, SMFM criteria identified 45out of 76 women; of these 13 required hysterectomy; there were 6 who required hysterectomy but did not meet the SMFM criteria. At 10 to < 14 weeks, SMFM criteria identified 28 out of 42 women; of these 15 required hysterectomy. US parameters yielded significant differences in women requiring hysterectomy, at < 10 weeks and 10 to < 14 weeks' gestational age epochs, but the sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of these US parameters have limitations in identifying invasion to determine management. Of the 101 pregnancies, 46 (46%) failed < 20 weeks, 16 (35%) required medical/surgical management including 6 hysterectomies, and 30 (65%) required no intervention. There were 55 pregnancies (55%) that progressed beyond 20 weeks. Of these, 16 required hysterectomy (29%) while 39 (71%) did not. In the overall cohort of 101, 22 (21.8%) required hysterectomy and an additional16 (15.8%) required some type of intervention, while 66.7% required no intervention. CONCLUSION: SMFM US criteria for CSP have limitations for discerning clinical management due to lack of discriminatory threshold. KEY POINTS: · The SMFM US criteria for CSP at <10 or <14 weeks have limitations for clinical management.. · The sensitivity and specificity of the ultrasound findings limit the utility for management. · The SMT of <1 mm is more discriminating than <3 mm for hysterectomy..

Is Response to a Pre-implant Diagnostic Peripheral Nerve Block Associated With Efficacy After Peripheral Nerve Stimulation Implantation? A Ten-Year Enterprise-Wide Analysis.

OBJECTIVES: This study aimed to assess whether patient response to targeted diagnostic peripheral nerve block before peripheral nerve stimulator (PNS) device implantation is associated with efficacy after PNS implantation. MATERIALS AND METHODS: The electronic medical records from the Mayo Clinic Enterprise (three quarternary care medical centers and additional satellite medical centers) were reviewed to identify patients who underwent PNS implantation between January 2014 and January 2023. A primary outcome of interest was to assess whether administration of a preimplant diagnostic peripheral nerve block predicted pain relief at three months and six months after temporary and permanent PNS implantation. Another primary outcome was to investigate whether there was an association between the pain relief from a preimplant diagnostic peripheral nerve block and pain relief after three and six months after temporary or permanent PNS therapy. Linear regression analysis was conducted for outcomes of interest. RESULTS: Of 193 eligible patients who underwent PNS therapy, a total of 173 patients were included in the final analysis and were stratified into either the temporary PNS cohort (n = 112) or the permanent PNS cohort (n = 61). Overall, 77.5% of all patients (134/173) underwent a preimplant diagnostic peripheral nerve block and reported a mean percentage relief of 70.1 ± 27.0 from the diagnostic block. Of patients in the temporary PNS cohort, there was no difference in postimplant percentage pain relief between patients who received a diagnostic block (n = 93) and control patients (n = 19) at three months (35.4 ± 36.0 vs 49.8 ± 36.1, respectively; ß -14.45, 95% CI -32.98 to 4.07, p = 0.125) or at six months (23.3 ± 30.8 vs 45.7 ± 40.0, respectively; ß -22.39, 95% CI -46.86 to 2.08, p = 0.072). Of patients in the permanent PNS cohort, there was no difference in postimplant percentage pain relief between patients who received a diagnostic block (n = 41) and control patients (n = 20) at three months (42.4 ± 34.3 vs 43.2 ± 42.4, respectively; ß -0.79, 95% CI -23.56 to 21.99, p = 0.945) or at six months (44.3 ± 35.0 vs 38.8 ± 40.9, respectively; ß 5.42, 95% CI -20.04 to 30.88, p = 0.669). Pain relief from preimplant diagnostic blocks was associated with postimplant pain relief from temporary PNS at three months (ß 0.33, 95% CI 0.04-0.61, p = 0.025). However, pain relief from preimplant diagnostic blocks did not predict postimplant pain relief from temporary PNS at six months, or permanent PNS at three months and six months. CONCLUSIONS: Administration of a diagnostic block is not associated with superior pain relief at three or six months after PNS implantation to that of an approach without diagnostic block. Pain relief from a diagnostic block may potentially predict short-term pain relief after temporary PNS therapy, although future prospective studies are warranted to evaluate the prognostic utility of diagnostic blocks.

Workforce survey of PAs' genetic-genomic knowledge, attitudes, and application in practice.

OBJECTIVE: This study surveyed practicing physician associates/assistants (PAs) about their genetics-genomics knowledge, attitudes, and application in practice. METHODS: A 25-question electronic survey was emailed to each constituent organization of the American Academy of Physician Associates (AAPA) with a description of the study and a request to forward to their members. Additionally, a posting was displayed in the bulletin board section of the online AAPA Huddle. RESULTS: Of the 420 PAs who completed the survey, few are knowledgeable (25%) about or confident (13%) in applying a genomic approach to patient care, although most (61%) think genetics-genomics is important to delivering high-quality care. Remarkably, 97% of PAs surveyed are interested in genetics-genomics continuing medical education. CONCLUSIONS: PAs lack knowledge and confidence in integrating genetics-genomics into patient care; however, they have a positive attitude toward genetics-genomics and want to improve their knowledge and confidence through education.

Fetal heart rate tracings associated with eclamptic seizures.

BACKGROUND: Although there is a well-known association between fetal bradycardia and maternal eclampsia, the characteristics of fetal heart rate tracings after an eclamptic seizure have not previously been thoroughly described. Fetal heart rate changes are thought to be related to maternal lactic acidemia caused by vasospasm and uterine hyperactivity leading to placental hypoperfusion and fetal hypoxia. The decision to intervene in the case of an abnormal fetal heart rate tracing after an eclamptic seizure is often difficult; however, maternal resuscitation should be the primary focus. OBJECTIVE: This study aimed to quantify and characterize fetal heart rate changes associated with a maternal eclamptic seizure. Moreover, we sought to document subsequent obstetrical management following these seizures complicated by fetal heart rate decelerations. STUDY DESIGN: This was a retrospective study of fetal heart rate tracings associated with eclampsia during a 13-year period at a single institution. Eclampsia was diagnosed following the 2013 Executive Summary of the American College of Obstetricians and Gynecologists criteria. Tracings were independently reviewed and classified by 3 physicians using the National Institute of Child Health and Human Development Criteria. Hospital records were reviewed to ascertain obstetrical management after the eclamptic seizure. RESULTS: A total of 107 women were diagnosed with eclampsia from January 2009 to December 2021. Of these women, 31 experienced 34 intrapartum seizures during which time electronic fetal heart rate monitoring was ongoing. During the 34 seizures, fetal heart rate decelerations were documented in 79% of cases. The mean duration of bradycardia was 5.80±2.98 minutes with a range of 2 to 15 minutes. Fetal heart decelerations occurred, on average, 2.7±1.6 minutes after the onset of the eclamptic seizure. In half of the fetuses with fetal heart rate changes, fetal tachycardia followed, and in 48% of cases, there was minimal variability noted. As a result of the fetal heart rate tracings and clinical findings, 4 women underwent an emergent cesarean delivery, including 2 that were diagnosed with placental abruption. In this cohort, there were 4 cases of abruption. The mean duration from the seizure to delivery was 299±353 minutes. The mean neonatal cord pH was 7.20±0.11 with a mean base excess of -8.6±4.4 mmol/L. There was no perinatal death. CONCLUSION: After an eclamptic seizure, 79% of fetuses demonstrated prolonged decelerations, and half of the fetuses developed fetal tachycardia after recovery from the episode of bradycardia. Despite these periods of fetal heart rate decelerations associated with eclampsia, prioritization of maternal support and stabilization resulted in a favorable perinatal outcome without immediate operative intervention in more than two-thirds of cases.