High Rates of Placental Inflammation Among Samples Collected by the MOMI Consortium.

BACKGROUND: The Multi-Omics for Mothers and Infants (MOMI) consortium aims to improve birth outcomes. Preterm birth is a major obstetric complication globally causing significant infant and childhood morbidity and mortality. OBJECTIVES: We analyzed placental samples (basal plate, placenta/chorionic villi and/or the chorionic plate) collected by the 5 MOMI sites: The Alliance for Maternal and Newborn Health Improvement (AMANHI) Bangladesh, AMANHI Pakistan, AMANHI Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Bangladesh and GAPPS Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. STUDY DESIGN: The teams provided biopsies from 166 singleton preterm (<37 weeks) and 175 term (≥37 weeks) deliveries. They were formalin-fixed and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphological analyses. Other placental biopsies (n = 35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. RESULTS: The morphological analyses revealed a surprisingly high rate of inflammation involving the basal plate, placenta/chorionic villi and/or the chorionic plate. The rate in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs. the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes as differentially expressed (DE) between placentas from preterm vs. term births (123 upregulated, 144 downregulated). Mapping the DE genes onto single cell RNA-seq data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathological findings, GO (Gene Ontology) analyses highlighted leukocyte infiltration/activation and inflammatory responses in both the fetal and maternal compartments. CONCLUSION: The relationship between placental inflammation and preterm birth is appreciated in developed countries. Here, we show that this link also exists in developing geographies. Also, among the participating sites, we found geographic- and/or population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Academic accomplishments of Black neurosurgeons in the United States.

OBJECTIVE: Neurosurgery has remained relatively homogeneous in terms of racial and gender diversity, trailing behind national demographics. Less than 5% of practicing neurosurgeons in the United States identify as Black/African American (AA). Research and academic productivity are highly emphasized within the field and are crucial for career advancement at academic institutions. They also serve as important avenues for mentorship and recruitment of diverse trainees and medical students. This study aimed to summarize the academic accomplishments of AA neurosurgeons by assessing publication quantity, h-index, and federal grant funding. METHODS: One hundred thirteen neurosurgery residency training programs accredited by the Accreditation Council for Graduate Medical Education in 2022 were included in this study. The American Society of Black Neurosurgeons registry was reviewed to analyze the academic metrics of self-identified Black or AA academic neurosurgeons. Data on the academic rank, leadership position, publication quantity, h-index, and race of neurosurgical faculty in the US were obtained from publicly available information and program websites. RESULTS: Fifty-five AA and 1393 non-AA neurosurgeons were identified. Sixty percent of AA neurosurgeons were fewer than 10 years out from residency training, compared to 37.4% of non-AA neurosurgeons (p = 0.001). AA neurosurgeons had a median 32 (IQR 9, 85) publications compared to 52 (IQR 22, 122) for non-AA neurosurgeons (p = 0.019). AA neurosurgeons had a median h-index of 12 (IQR 5, 24) compared to 16 (IQR 9, 31) for non-AA colleagues (p = 0.02). Following stratification by academic rank, these trends did not persist. No statistically significant differences in the median amounts of awarded National Institutes of Health funding (p = 0.194) or level of professorship attained (p = 0.07) were observed between the two cohorts. CONCLUSIONS: Racial disparities between AA and non-AA neurosurgeons exist in publication quantity and h-index overall but not when these groups are stratified by academic rank. Given that AA neurosurgeons comprise more junior faculty, it is expected that their academic accomplishments will increase as more enter academic practice and current neurosurgeons advance into more senior positions.

Health-Related Quality of Life Outcomes in Meningioma Patients Based upon Tumor Location and Treatment Modality: A Systematic Review and Meta-Analysis.

Patients with meningiomas may have reduced health-related quality of life (HRQoL) due to postoperative neurological deficits, cognitive dysfunction, and psychosocial burden. Although advances in surgery and radiotherapy have improved progression-free survival rates, there is limited evidence regarding treatment outcomes on HRQoL. This review examines HRQoL outcomes based on tumor location and treatment modality. A systematic search in PubMed yielded 28 studies with 3167 patients. The mean age was 54.27 years and most patients were female (70.8%). Approximately 78% of meningiomas were located in the skull base (10.8% anterior, 23.3% middle, and 39.7% posterior fossae). Treatment modalities included craniotomy (73.6%), radiotherapy (11.4%), and endoscopic endonasal approach (EEA) (4.0%). The Karnofsky Performance Scale (KPS) was the most commonly utilized HRQoL instrument (27%). Preoperative KPS scores > 80 were associated with increased occurrence of postoperative neurological deficits. A significant difference was found between pre- and post-operative KPS scores for anterior/middle skull base meningiomas (SBMs) in comparison to posterior (SBMs) when treated with craniotomy. Post-craniotomy SF-36 scores were lower for posterior SBMs in comparison to those in the anterior and middle fossae. Risk factors for poor neurological outcomes include a high preoperative KPS score and patients with posterior SBMs may experience a greater burden in HRQoL.

Perfluorooctanoic acid induces transcriptomic alterations in second trimester human cytotrophoblasts.

Poly- and perfluroroalkylated substances (PFAS) are a major class of surfactants used in industry applications and consumer products. Despite efforts to reduce the usage of PFAS due to their environmental persistence, compounds such as perfluorooctanoic acid (PFOA) are widely detected in human blood and tissue. Although growing evidence supports that prenatal exposures to PFOA and other PFAS are linked to adverse pregnancy outcomes, the target organs and pathways remain unclear. Recent investigations in mouse and human cell lines suggest that PFAS may impact the placenta and impair trophoblast function. In this study, we investigated the effects of PFOA on cytotoxicity and the transcriptome in cultured second trimester human cytotrophoblasts (CTBs). We show that PFOA significantly reduces viability and induces cell death at 24 h, in a concentration-dependent manner. At subcytotoxic concentrations, PFOA impacted expression of hundreds of genes, including several molecules (CRH, IFIT1, and TNFSF10) linked with lipid metabolism and innate immune response pathways. Furthermore, in silico analyses suggested that regulatory factors such as peroxisome proliferator-activated receptor-mediated pathways may be especially important in response to PFOA. In summary, this study provides evidence that PFOA alters primary human CTB viability and gene pathways that could contribute to placental dysfunction and disease.

Proteomic analyses of primary human villous trophoblasts exposed to flame retardant BDE-47 using SWATH-MS.

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants and recognized developmental toxicants that are detectable in placental tissues. Higher levels of in utero PBDE exposure have been associated with an increased risk of adverse birth outcomes. During pregnancy, cytotrophoblasts (CTBs) from the placenta play critical roles in the formation of the maternal-fetal interface via uterine invasion and vascular remodeling. The differentiation of these cells towards an invasive phenotype is crucial for proper placental development. We previously have shown that BDE-47 can impact CTB viability and hinder the ability of these cells to migrate and invade. To expand on potential toxicological mechanisms, we utilized quantitative proteomic approaches to identify changes in the global proteome of mid-gestation primary human CTBs after exposure to BDE-47. Using sequential window acquisition of all theoretical fragment-ion spectra (SWATH), we identified 3024 proteins in our CTB model of differentiation/invasion. Over 200 proteins were impacted as a function of BDE-47 exposure (1 µM and 5 µM) across the treatment period (15, 24, and 39 h). The differentially expressed molecules displayed time- and concentration-dependent changes in expression and were enriched in pathways associated with aggregatory and adhesive processes. Network analysis identified CYFIP1, a molecule previously unexplored in a placental context, to be dysregulated at BDE-47 concentrations previously seen to impact CTB migration/invasion. Our SWATH-MS dataset thus demonstrates BDE-47 impacts the global proteome of differentiating CTBs and serves as a valuable resource for further understanding of the relationship between environmental chemical exposures and placental development and function. AVAILABILITY OF DATA AND MATERIAL: Raw chromatograms are deposited on the MassIVE proteomic database (https://massive.ucsd.edu) under accession number MSV000087870. Normalized relative abundances are also available as Table S1.

Enhanced recovery after surgery (ERAS) for craniotomies in the treatment of brain tumors: A systematic review.

INTRODUCTION: Postoperative complications after craniotomy for brain tumors include pain, nausea/vomiting, and infection. A standardized enhanced recovery after surgery (ERAS) protocol is not widely accepted for this common neurosurgical procedure. Few studies have explored its application. METHODS: A literature search of PubMed, Cochrane, and Google Scholar databases was performed between January 1992 and March 2023. Original studies that implemented an ERAS protocol for patients that underwent craniotomy for brain tumors were included. The following variables were evaluated: hospital length of stay (LOS), postoperative pain, postoperative nausea and vomiting (PONV) prophylaxis, non-opioid analgesia, and quality of life (QOL). RESULTS: Twelve studies with a total of 1309 patients met inclusion criteria, including ten randomized controlled trials, one nonrandomized controlled trial, and one quality control study. Most frequently assessed metrics included hospital LOS, PONV prophylaxis, and non-opioid analgesia. A significant reduction in postoperative LOS was observed in 7 studies with ERAS or ERAS components. ERAS was significantly associated with pain reduction on the visual analog scale and verbal numerical rating scale (n=8). Non-opioid analgesia in ERAS improved postoperative pain control (n=4) and decreased the duration of pain (n=1). Three of six studies found no difference in PONV in ERAS vs. control. No studies reported an increase in postoperative complications using ERAS vs. control. One study showed greater patient satisfaction at 30-day follow-up with improved QOL. CONCLUSION: Implementing ERAS protocol may enhance outcomes and quality of life in patients with moderate evidence for improved recovery in those undergoing craniotomy for brain tumors.

Surgical Outcomes of Awake Craniotomy for Treatment of Arteriovenous Malformations in Eloquent Cortex: A Systematic Review.

OBJECTIVE: Arteriovenous malformations (AVMs) located in eloquent brain regions are historically associated with a poor prognosis. Awake craniotomy (AC) with the adjunct of brain mapping has the potential of identifying non-eloquent gyri to maximize resection, thereby theoretically decreasing the risk of neurologic deficits. With limited evidence regarding the efficacy of AC in treatment of eloquent AVMs, this review aims to investigate its surgical outcomes. METHODS: A systematic search in the PubMed database was performed to identify all relevant studies up to February 2022. RESULTS: A total of 13 studies were extracted for quantitative analysis, yielding a total of 46 patients. The mean age was 34.1 years, and most patients were female (54.8%). Seizures were the most frequently reported presenting symptom (41%, 19 of 46 cases). Spetzler-Martin Grade III was the most prevalent (45.9%, 17 cases) with a mean nidus size of 32.6 mm. Seventy-four percent of AVMs were located on the left side, with the frontal lobe being the most common location (30%, 14 of 46 cases). The most common eloquent regions were language (47.8%, 22 of 46 cases), motor (17.4%, 8 of 46 cases), and language + motor cortices (13.1%, 6 of 46 cases). Complete resection of AVM was achieved in 41 patients (89%). Intraoperative complications occurred in 14 of 46 cases (30.4%) with transient postoperative neurologic deficits in 14 patients (30.4%). CONCLUSIONS: AC may enable precise microsurgical excision of eloquent AVMs with preservation of critical brain functions. Risk factors for poor outcomes include eloquent AVMs located in the language + motor regions and the occurrence of intraoperative complications such as seizures/hemorrhage.

Neurosurgical management of patients with neurocutaneous melanosis: a systematic review.

OBJECTIVE: Neurocutaneous melanocytosis (NCM), also referred to as neurocutaneous melanosis, is a rare neurocutaneous disorder characterized by excess melanocytic proliferation in the skin, leptomeninges, and cranial parenchyma. NCM most often presents in pediatric patients within the first 2 years of life and is associated with high mortality due to proliferation of melanocytes in the brain. Prognosis is poor, as patients typically die within 3 years of symptom onset. Due to the rarity of NCM, there are no specific guidelines for management. The aims of this systematic review were to investigate approaches toward diagnosis and examine modern neurosurgical management of NCM. METHODS: A systematic review was performed using the PubMed database between April and December 2021 to identify relevant articles using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search criteria were created and checked independently among the authors. Inclusion criteria specified unique studies and case reports of NCM patients in which relevant neurosurgical management was considered and/or applied. Exclusion criteria included studies that did not report associated neurological diagnoses and neuroimaging findings, clinical reports without novel observations, and those unavailable in the English language. All articles that met the study inclusion criteria were included and analyzed. RESULTS: A total of 26 extracted articles met inclusion criteria and were used for quantitative analysis, yielding a cumulative of 74 patients with NCM. These included 21 case reports, 1 case series, 2 retrospective cohort studies, 1 prospective cohort study, and 1 review. The mean patient age was 16.66 years (range 0.25-67 years), and most were male (76%). Seizures were the most frequently reported symptom (55%, 41/74 cases). Neurological diagnoses associated with NCM included epilepsy (45%, 33/74 cases), hydrocephalus (24%, 18/74 cases), Dandy-Walker malformation (24%, 18/74 cases), and primary CNS melanocytic tumors (23%, 17/74 cases). The most common surgical technique was CSF shunting (43%, 24/56 operations), with tethered cord release (4%, 2/56 operations) being the least frequently performed. CONCLUSIONS: Current management of NCM includes CSF shunting to reduce intracranial pressure, surgery, chemotherapy, radiotherapy, immunotherapy, and palliative care. Neurosurgical intervention can aid in the diagnosis of NCM through tissue biopsy and resection of lesions with surgical decompression. Further evidence is required to establish the clinical outcomes of this rare entity and to describe the diverse spectrum of intracranial and intraspinal abnormalities present.