A Case Report of Spontaneous Vaginal Delivery Under General Anesthesia in a Patient With a Large Cerebral Aneurysm.

Cerebral aneurysms are rarely encountered in pregnancy. Their antepartum and intrapartum management remain clinically challenging, primarily due to concern regarding potential rupture. We present a case of a patient in preterm labor at risk for imminent delivery with a 10mm cerebral aneurysm. She was recommended for cesarean section (CS), yet delivered via spontaneous vaginal delivery in the operating room after induction of general anesthesia for the intended CS. Her aneurysm and neurologic function remained intact postpartum. Cerebral aneurysms <5mm are unlikely to undergo significant growth during pregnancy. The presence of a cerebral aneurysm is not automatically a contraindication to the Valsalva maneuver. The recommendation for which patients with unruptured cerebral aneurysms should deliver by CS, operative vaginal delivery, or unassisted vaginal delivery (i.e., which patients should avoid Valsalva maneuver intrapartum), is complex and requires multidisciplinary discussion.

The genetic etiologies of bilateral renal agenesis.

OBJECTIVE: The goal of this study was to review and analyze the medical literature for cases of prenatal and/or postnatally diagnosed bilateral renal agenesis (BRA) and create a comprehensive summary of the genetic etiologies known to be associated with this condition. METHODS: A literature search was conducted as a scoping review employing Online Mendeliain Inheritance in Man, PubMed, and Cochrane to identify cases of BRA with known underlying genetic (chromosomal vs. single gene) etiologies and those described in syndromes without any known genetic etiology. The cases were further categorized as isolated versus non-isolated, describing additional findings reported prenatally, postnatally, and postmortem. Inheritance pattern was also documented when appropriate in addition to the reported timing of diagnosis and sex. RESULTS: We identified six cytogenetic abnormalities and 21 genes responsible for 20 single gene disorders associated with BRA. Five genes have been reported to associate with BRA without other renal anomalies; sixteen others associate with both BRA as well as unilateral renal agenesis. Six clinically recognized syndromes/associations were identified with an unknown underlying genetic etiology. Genetic etiologies of BRA are often phenotypically expressed as other urogenital anomalies as well as complex multi-system syndromes. CONCLUSION: Multiple genetic etiologies of BRA have been described, including cytogenetic abnormalities and monogenic syndromes. The current era of the utilization of exome and genome-wide sequencing is likely to significantly expand our understanding of the underlying genetic architecture of BRA.

Obesity Contributes to Transformation of Myometrial Stem-Cell Niche to Leiomyoma via Inducing Oxidative Stress, DNA Damage, Proliferation, and Extracellular Matrix Deposition.

Leiomyomas (fibroids) are monoclonal tumors in which myometrial stem cells (MSCs) turn tumorigenic after mutation, abnormal methylation, or aberrant signaling. Several factors contribute to metabolic dysfunction in obesity, including abnormal cellular proliferation, oxidative stress, and DNA damage. The present study aims to determine how adipocytes and adipocyte-secreted factors affect changes in MSCs in a manner that promotes the growth of uterine leiomyomas. Myometrial stem cells were isolated from the uteri of patients by fluorescence-activated cell sorting (FACS) using CD44/Stro1 antibodies. Enzyme-linked immunosorbent assay (ELISA), Western blot, and immunocytochemistry assays were performed on human adipocytes (SW872) co-cultured with MSCs and treated with leptin or adiponectin to examine the effects of proliferation, extracellular matrix (ECM) deposition, oxidative damage, and DNA damage. Co-culture with SW872 increased MSC proliferation compared to MSC culture alone, according to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results. The expressions of PCNA and COL1A increased significantly with SW872 co-culture. In addition, the expression of these markers was increased after leptin treatment and decreased after adiponectin treatment in MSCs. The Wnt/ß-catenin and TGF-ß/SMAD signaling pathways promote proliferation and ECM deposition in uterine leiomyomas. The expression of Wnt4, ß-catenin, TGFß3, and pSMAD2/3 of MSCs was increased when co-cultured with adipocytes. We found that the co-culture of MSCs with adipocytes resulted in increased NOX4 expression, reactive oxygen species production, and γ-H2AX expression. Leptin acts by binding to its receptor (LEP-R), leading to signal transduction, resulting in the transcription of genes involved in cellular proliferation, angiogenesis, and glycolysis. In MSCs, co-culture with adipocytes increased the expression of LEP-R, pSTAT3/STAT3, and pERK1/2/ERK/12. Based on the above results, we suggest that obesity may mediate MSC initiation of tumorigenesis, resulting in leiomyomas.

Dissociative identity precipitated by emergence from general anesthesia: A case report and analytical framework.

Background: Dissociative identity disorder (DID) is a complex and controversial psychiatric condition in which one person maintains at least two separate and distinct personalities. Patients with DID often report a history of childhood abuse and may have other comorbid psychiatric conditions. Psychosocial stressors may be triggers for DID inception or recurrence. While anesthetic agents, in particular ketamine, may induce a temporary dissociative state, it has not yet been reported that anesthesia can precipitate a dissociative identity. Case report: We report a case of a woman with a history of childhood sexual abuse and past suicide attempt who experienced an episode of dissociative identity on emergence from anesthesia. The episode resolved within 90 minutes and the patient was discharged home safely on hospital day two. Conclusion: This case adds to the literature of potentially precipitating factors of DID and we provide a unifying mechanistic hypothesis linking anesthesia to functional brain connectivity.

PEGylated Polymeric Nanoparticles Loaded with 2-Methoxyestradiol for the Treatment of Uterine Leiomyoma in a Patient-Derived Xenograft Mouse Model.

Leiomyomas, the most common benign neoplasms of the female reproductive tract, currently have limited medical treatment options. Drugs targeting estrogen/progesterone signaling are used, but side effects and limited efficacy in many cases are major limitation of their clinical use. Previous studies from our laboratory and others demonstrated that 2-methoxyestradiol (2-ME) is promising treatment for uterine fibroids. However, its poor bioavailability and rapid degradation hinder its development for clinical use. The objective of this study is to evaluate the in vivo effect of biodegradable and biocompatible 2-ME-loaded polymeric nanoparticles in a patient-derived leiomyoma xenograft mouse model. PEGylated poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles loaded with 2-ME were prepared by nanoprecipitation. Female 6-week age immunodeficient NOG (NOD/Shi-scid/IL-2Rγnull) mice were used. Estrogen-progesterone pellets were implanted subcutaneously. Five days later, patient-derived human fibroid tumors were xenografted bilaterally subcutaneously. Engrafted mice were treated with 2-ME-loaded or blank (control) PEGylated nanoparticles. Nanoparticles were injected intraperitoneally and after 28 days of treatment, tumor volume was measured by caliper following hair removal, and tumors were removed and weighed. Up to 99.1% encapsulation efficiency was achieved, and the in vitro release profile showed minimal burst release, thus confirming the high encapsulation efficiency. In vivo administration of the 2-ME-loaded nanoparticles led to 51% growth inhibition of xenografted tumors compared to controls (P < 0.01). Thus, 2-ME-loaded nanoparticles may represent a novel approach for the treatment of uterine fibroids.

Uterine Transcriptome: Understanding Physiology and Disease Processes.

In recent years, transcriptomics has enabled us to gain a deeper understanding of fundamental reproductive physiology, including the menstrual cycle, through a more precise molecular analysis. The endometrial mRNA transcript levels fluctuate during the normal menstrual cycle, indicating changes in the relative recruitment and abundance of inflammatory cells, as well as changes in the receptivity and remodeling of the endometrium. In addition to providing a more comprehensive understanding of the molecular underpinnings of pathological gynecological conditions such as endometriosis, leiomyomas, and adenomyosis through RNA sequencing, this has allowed researchers to create transcriptome profiles during both normal menstrual cycles and pathological gynecological conditions. Such insights could potentially lead to more targeted and personalized therapies for benign gynecological conditions. Here, we provide an overview of recent advances in transcriptome analysis of normal and pathological endometrium.

Relationship Among Surgical Fibroid Removal, Blood Pressure, and Biomarkers of Renin-Angiotensin-Aldosterone System Activation.

Fibroids are common benign neoplasms in women and have recently been associated with cardiometabolic risk factors including hypertension. The objective of this study is to determine whether fibroid removal is associated with lower blood pressure (BP). We performed a single-center IRB-approved retrospective chart review of patients undergoing hysterectomy/myomectomy for fibroids and other benign gynecological surgical procedures from January 2016 to December 2019, and a prospective cohort study of patients undergoing hysterectomy/myomectomy for fibroids from August 2021 to April 2022. We measured demographic factors, preoperative/postoperative BP on day of surgery and at postoperative visit. In our prospective cohort, to evaluate for alterations in the renin-angiotensin-aldosterone system (RAAS) induced by fibroid removal, we measured serum angiotensin-II (Ang-II) and angiotensin converting enzyme (ACE) levels pre- and post-operatively. In our retrospective study (n = 294; mean age 41.9 ± 10.6, 43.5% Black, 50% with fibroids), we found that compared to patients without fibroids, patients with fibroids had significantly elevated systolic BP (SBP) (pre-op: p = 0.0005; post-op: p = 0.02), although this did not hold after adjusting for covariates. Fibroid removal was associated with a marginally albeit not statistically significant decrease in SBP (p = 0.062). In our prospective study (n = 11), there was a significant decrease in SBP following fibroid removal, but no change in diastolic BP (p = 0.019, p = 0.18, respectively). Serum levels of Ang-II and ACE were not significantly altered following surgical fibroid removal (p = 0.72, p = 0.81, respectively). Altogether, these findings suggest that fibroids are not independently associated with BP or RAAS activation, but do suggest that fibroid removal may be associated with a small drop in SBP.

Modeling of vertical transmission and pathogenesis of cytomegalovirus in pregnancy: Opportunities and challenges.

In addition to facilitating nutrient, oxygen, and waste transfer between developing fetus and mother, the placenta provides important immune barrier function against infection. Elucidation of the complexity of placental barrier function at the maternal-fetal interface has been greatly aided through experimental model organism systems. In this review, we focus on models of vertical transmission of cytomegalovirus (CMV), a ubiquitous double-stranded DNA viruses whose vertical transmission during pregnancy can lead to devastating neurological and obstetric sequelae. We review the current evidence related to guinea pig and murine models of congenital CMV infection, discuss the possible translatability of a non-human primate model, and conclude with recently developed technology using human placental organoids.

Severe ovarian hyperstimulation syndrome requiring recurrent large-volume paracenteses until 21 weeks' gestation: a case report.

Objective: To report a case of severe ovarian hyperstimulation syndrome (OHSS) persisting into the late second trimester of a singleton pregnancy. Design: Case report. Setting: Academic tertiary care center. Patients: A 29-year-old woman with severe OHSS after fresh embryo transfer after controlled ovarian hyperstimulation requiring intervention until 21 weeks' gestation in a singleton pregnancy. Interventions: Thorough evaluation of an unusual case of severe OHSS and medical/procedural management of its sequelae in the setting of ongoing pregnancy. Main Outcome Measuress: The clinical development of severe OHSS during pregnancy and its effect on pregnancy outcomes. Results: Severe OHSS persisted until 21 weeks' gestation with reaccumulating ascitic fluid, which impacted pregnancy outcomes. Conclusions: Clinicians should be aware of the risk of severe OHSS and its possible effect on pregnancy outcomes beyond the first trimester.

Congenital Infection Influence on Early Brain Development Through the Gut-Brain Axis.

The mechanisms by which various pathogens cause congenital infections have been studied extensively, aiding in the understanding of the detrimental effects these infections can have on fetal/neonatal neurological development. Recent studies have focused on the gut-brain axis as pivotal in neurodevelopment, with congenital infections causing substantial disruptions. There remains controversy surrounding the purported sterility of the placenta as well as concerns regarding the effects of exposure to antibiotics used during pregnancy on neonatal microbiome development and how early exposure to microbes or antibiotics can shape the gut-brain axis. Long-term neurodevelopmental consequences, such as autism spectrum disorder, attention deficit hyperactivity disorder, and cerebral palsy, may be attributable, in part, to early life infection and changes in the immature gut microbiome. The goal of this review is thus to critically evaluate the current evidence related to early life infection affecting neurodevelopment through the gut-brain axis.

ADAM10 facilitates rapid neural stem cell cycling and proper positioning within the subventricular zone niche via JAMC/RAP1Gap signaling.

The mechanisms that regulate neural stem cell (NSC) lineage progression and maintain NSCs within different domains of the adult neural stem cell niche, the subventricular zone are not well defined. Quiescent NSCs are arranged at the apical ventricular wall, while mitotically activated NSCs are found in the basal, vascular region of the subventricular zone. Here, we found that ADAM10 (a disintegrin and metalloproteinase 10) is essential in NSC association with the ventricular wall, and via this adhesion to the apical domain, ADAM10 regulates the switch from quiescent and undifferentiated NSC to an actively proliferative and differentiating cell state. Processing of JAMC (junctional adhesion molecule C) by ADAM10 increases Rap1GAP activity. This molecular machinery promotes NSC transit from the apical to the basal compartment and subsequent lineage progression. Understanding the molecular mechanisms responsible for regulating the proper positioning of NSCs within the subventricular zone niche and lineage progression of NSCs could provide new targets for drug development to enhance the regenerative properties of neural tissue.

Eclampsia with RCVS: Postpartum seizure provoked by methergine.

BACKGROUND: Eclampsia is a pregnancy complicationcharacterized bygeneralized tonic-clonicconvulsions.Not all seizures in pregnancy are eclamptic, and othercauses include epilepsy, infection,stroke,tumor, and ruptured aneurysm. CASE: A 19-year-old G1P0 presentedinlabor at term. She had a generalized tonic-clonicseizure one hour aftervaginaldelivery for which she received methergine for uterine atony. Seizure activity resolved with lorazepam and magnesium sulfate for presumed eclampsia.Brain imaging revealedvasoconstriction of theleftposterior cerebral artery and blood in the subarachnoid space,andshewas diagnosed with eclampsia with reversible cerebral vasoconstrictive syndrome (RCVS). CONCLUSION: RCVS isapregnancy-related cause of seizure that should remain on the differential for any patient presenting with a seizure in the peripartum period, especially with use of vasoconstrictive agents. Management is controversial but involves calcium channel blockers and magnesium sulfate, as well as avoidance of vasoconstrictive agents.

Which patients on a gynecologic oncology service will require perioperative transfusion? A single-center retrospective cohort study.

The purpose of this study was to determine which patient- or surgery-related factors are predictive of need for perioperative transfusion to avoid obtaining unnecessary pre-operative type and screens (T&S). We conducted an observational retrospective cohort study of 1200 women ≥ 18 years old undergoing gynecologic surgery for benign, possibly benign, or malignant indications on a gynecologic oncology service at a university medical center from 2009-2016. A logistic regression model was used to examine patient-related and surgery-related variables predictive of outcome of transfusion. Independent variables included patient demographics, comorbidities, and surgical indication surgical route, and surgical type. Dependent variable was transfusion outcome (T&S only, conversion to type and cross (T&C), or transfusion). Eight hundred ninety-nine (74.9%) women underwent pre-operative T&S, of which 118 (9.8%) were converted to T&C, and 80 (6.7%) received a transfusion of blood or blood products. Cancer indication, major surgery, and preoperative hematocrit less than 36% were significantly associated with need for transfusion (P = 0.002, P < 0.0001, P < 0.0001, respectively). Patients with a benign indication undergoing minor procedures and with normal preoperative hematocrit are least likely to require transfusion.

Vascular biology of uterine fibroids: connecting fibroids and vascular disorders.

Fibroids are benign tumors caused by the proliferation of myometrial smooth muscle cells in the uterus that can lead to symptoms such as abdominal pain, constipation, urinary retention, and infertility. While traditionally thought of as a disease process intrinsic to the uterus, accumulating evidence suggests that fibroid growth may be linked with the systemic vasculature system, although cell-intrinsic factors are certainly of principal importance in their inception. Fibroids are associated with essential hypertension and preeclampsia, as well as atherosclerosis, for reasons that are becoming increasingly elucidated. Factors such as the renin-angiotensin-aldosterone system, estrogen, and endothelial dysfunction all likely play a role in fibroid pathogenesis. In this review, we lay out a framework for reconceptualizing fibroids as a systemic vascular disorder, and discuss how pharmaceutical agents and other interventions targeting the vasculature may aid in the novel treatment of fibroids.

Role of inflammation in benign gynecologic disorders: from pathogenesis to novel therapies†.

Emerging evidence supports the notion that inflammation fosters the development of common benign gynecologic disorders, including uterine leiomyoma, endometriosis, and adenomyosis. Numerous cytokines, chemokines, and growth and transcription factors have indisputable roles in the establishment and maintenance of benign gynecologic disorders by initiating complex cascades that promote proliferation, angiogenesis, and lesion progression. The interaction between inflammation and benign gynecologic disorders is orchestrated by a plethora of factors, including sex steroids, genetics, epigenetics, extracellular matrix, stem cells, cardiometabolic risk factors, diet, vitamin D, and the immune system. The role of inflammation in these disorders is not limited to local pathobiology but also extends to involve clinical sequelae that range from those confined to the reproductive tract, such as infertility and gynecologic malignancies, to systemic complications such as cardiovascular disease. Enhanced understanding of the intricate mechanisms of this association will introduce us to unvisited pathophysiological perspectives and guide future diagnostic and therapeutic implications aimed at reducing the burden of these disorders. Utilization of inflammatory markers, microRNA, and molecular imaging as diagnostic adjuncts may be valuable, noninvasive techniques for prompt detection of benign gynecologic disorders. Further, use of novel as well as previously established therapeutics, such as immunomodulators, hormonal treatments, cardiometabolic medications, and cyclooxygenase-2 and NF-κB inhibitors, can target inflammatory pathways involved in their pathogenesis. In this comprehensive review, we aim to dissect the existing literature on the role of inflammation in benign gynecologic disorders, including the proposed underlying mechanisms and complex interactions, its contribution to clinical sequelae, and the clinical implications this role entails.

Assisted reproductive technologies (ART) and placental abnormalities.

Objectives Assisted reproductive technologies (ART) may be associated with placental abnormalities including placenta previa, umbilical cord abnormalities, and placental abruption. Our study evaluates the relationship between ART and placental abnormalities compared with spontaneously conceived controls. Methods An IRB-approved cohort study was conducted including women who delivered between January 2013 and December 2018. We excluded delivery prior to 23 weeks and known fetal anomalies. Patients were matched with controls (2:1) for parity, age, and mode of delivery. Controls were women who had spontaneously conceived and delivered immediately preceding and following the index delivery. The primary outcome was placental abnormalities found on both antenatal ultrasound and pathology in ART gestations compared with spontaneously conceived gestations. Results There were 120 ART pregnancies and 240 matched control pregnancies identified. The groups were similar for parity, BMI, comorbidities, number of multiples, mode of delivery, and female newborns. The ART group had a higher maternal age (37.1±5 y vs. 30.0±5 y; p<0.001), greater preterm birth (29 vs. 6%; p<0.001), and lower BW (2,928±803 g vs. 3,273±586 g; p<0.001). The ART group had a higher incidence of placenta previa on ultrasound (4.0 vs. 0.4%, p=0.01), adherent placentas at delivery (3 vs. 0% p=0.014), placental abruption (2 vs. 0%; p=0.04), as well as an increased rate of velamentous cord insertion (12 vs. 3%, p<0.001) and marginal cord insertion (28 vs. 15%, p=0.002). ART demonstrated a two-fold likelihood of abnormal placental pathology. Conclusions ART is associated with increased rate of placental abnormalities, including abnormal umbilical cord insertion and increased rates of adherent placentation. This information may be beneficial in planning and surveillance in patients with ART pregnancies.