Spontaneous skull base cerebrospinal fluid leak during pregnancy: a case report and review of the literature.

BACKGROUND: Idiopathic intracranial hypertension can lead to dural defects and spontaneous leakage of cerebrospinal fluid (CSF) from the skull base. Skull base CSF leaks are rarely reported in pregnancy but pose unique challenges for obstetricians and anesthesiologists. CASE PRESENTATION: A 31-year-old G4P1021 at 14 weeks developed debilitating headaches and CSF rhinorrhea. Brain imaging revealed a bony defect of the sphenoid sinus with a meningoencephalocele and a partially empty sella, consistent with CSF leakage from a skull base defect. The patient was neurologically stable without signs of meningitis; thus, management was focused on symptomatic alleviation. A planned cesarean section was performed at 38 weeks under spinal anesthesia. The patient had spontaneous marked improvement of her symptoms postpartum. CONCLUSION: Pregnancy may exacerbate skull base CSF leaks, requiring careful management with a multidisciplinary team. Neuraxial anesthesia can safely be performed in pregnant individuals with spontaneous skull base CSF leakage, but further studies are needed to determine the safest mode of delivery in these patients.

Perinatal Outcomes in Obese Women with One Abnormal Value on 3-Hour Oral Glucose Tolerance Test.

OBJECTIVE: This study aimed to determine if one abnormal value of four on the diagnostic 3-hour oral glucose tolerance test (OGTT) is associated with adverse perinatal outcomes in obese women. STUDY DESIGN: This is a secondary analysis of a prospective study of nulliparous women in eight geographic regions. Women with body mass index <30 kg/m2 and pregestational diabetes mellitus (GDM) were excluded. Four groups were compared: (1) normal 50-g 1-hour glucose screen, (2) elevated 1-hour glucose screen with normal 100-g 3-hour diagnostic OGTT, (3) elevated 1-hour glucose screen and one of four abnormal values on 3-hour OGTT, and (4) GDM. Using multivariable logistic regression adjusting for covariates, the women in the groups with dysglycemia were compared with those in the normal screen group for maternal and neonatal outcomes. RESULTS: Among 1,713 obese women, 1,418 (82.8%) had a normal 1-hour glucose screen, 125 (7.3%) had a normal 3-hour diagnostic OGTT, 72 (4.2%) had one abnormal value on their diagnostic OGTT, and 98 (5.7%) were diagnosed with GDM. The one abnormal value group had increased risk of large for gestational age (LGA) neonates (adjusted odds ratio [aOR] = 2.24, 95% confidence interval [CI]: 1.31-3.82), cesarean delivery (aOR = 2.19, 95% CI: 1.34-3.58), and hypertensive disorders of pregnancy (aOR = 2.19, 95% CI: 1.32-3.63) compared with normal screens. The one abnormal value group also had an increased risk of preterm birth <37 weeks (aOR = 2.63, 95% CI: 1.43-4.84), neonatal respiratory support (aOR = 2.38, 95% CI: 1.23-4.60), and neonatal hyperbilirubinemia (aOR = 2.00, 95% CI: 1.08-3.71). There was no association between one abnormal value with shoulder dystocia and neonatal hypoglycemia. CONCLUSION: For obese women, one abnormal value on the 3-hour OGTT confers increased perinatal adverse outcomes. These women should be studied further to determine if nutrition counseling and closer fetal monitoring improve outcomes even in the absence of a diagnosis of GDM. KEY POINTS: · Study of obese women with one abnormal value on OGTT.. · Adverse maternal and neonatal outcomes were found, including more LGA neonates.. · Neonates were not at increased risk of hypoglycemia..

Mutation of neuron-specific chromatin remodeling subunit BAF53b: rescue of plasticity and memory by manipulating actin remodeling.

Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b is essential for the differentiation of neuronal precursor cells into neurons. We generated transgenic mice lacking subdomain 2 of Baf53b (BAF53bΔSB2). Long-term synaptic potentiation (LTP) and long-term memory, both of which are associated with phosphorylation of the actin severing protein cofilin, were assessed in these animals. A phosphorylation mimic of cofilin was stereotaxically delivered into the hippocampus of BAF53bΔSB2 mice in an effort to rescue LTP and memory. BAF53bΔSB2 mutant mice show impairments in phosphorylation of synaptic cofilin, LTP, and memory. Both the synaptic plasticity and memory deficits are rescued by overexpression of a phosphorylation mimetic of cofilin. Baseline physiology and behavior were not affected by the mutation or the experimental treatment. This study suggests a potential link between nBAF function, actin cytoskeletal remodeling at the dendritic spine, and memory formation. This work shows that a targeted manipulation of synaptic function can rescue adult plasticity and memory deficits caused by manipulations of nBAF, and thereby provides potential novel avenues for therapeutic development for multiple intellectual disability disorders.

Multisite Verification of a Targeted CFTR Polymerase Chain Reaction/Capillary Electrophoresis Assay That Evaluates Pathogenic Variants Across Diverse Ethnic and Ancestral Groups.

CONTEXT.­: Existing targeted cystic fibrosis screening assays miss important pathogenic CFTR variants in the ethnically diverse US population. OBJECTIVE.­: To evaluate the analytic performance of a multiplex polymerase chain reaction (PCR)/capillary electrophoresis (CE) CFTR assay panel that simultaneously interrogates primary pathogenic variants of different ethnic/ancestral groups. DESIGN.­: Performance characteristic assessment and variant coverage comparison of the panel with a focus on ethnicity-specific CFTR variants were performed. Sample DNA was primarily from whole blood or cell lines. Detection of CFTR carriers was compared across several commercially available CFTR kits and recommended variant sets based on panel content. RESULTS.­: The panel interrogated 65 pathogenic CFTR variants representing 92% coverage from a recent genomic sequencing survey of the US population, including 4 variants with top 5 frequency in African or Asian populations not reflected in other targeted panels. In simulation studies, the panel represented 95% of carriers across the global population, resulting in a 6.9% to 19.0% higher carrier detection rate compared with 10 targeted panels or variant sets. Precision and sensitivity/specificity were 100% concordant. Multisite sample-level genotyping accuracy was 99.2%. Across PCR and CE instruments, sample-level genotyping accuracy was 97.1%, with greater than 99% agreement for all variant-level metrics. CONCLUSIONS.­: The CFTR assay achieves 92% or higher coverage of CFTR variants in diverse populations and provides improved pan-ethnic coverage of minority subgroups of the US populace. The assay can be completed within 5 hours from DNA sample to genotype, and performance data exceed acceptance criteria for analytic metrics. This assay panel content may help address gaps in ancestry-specific CFTR genotypes while providing a streamlined procedure with rapidly generated results.

Diet quality, community food access, and glycemic control among nulliparous individuals with diabetes.

Better diet quality regardless of community food access was associated with a higher likelihood of glycemic control in early pregnancy among nulliparous individuals with pregestational diabetes. These findings highlight the need for interventions that address nutrition insecurity for pregnant individuals living with diabetes.

Risk factors and perinatal outcomes for persistent placenta previa in nulliparas.

BACKGROUND: Placenta previa diagnosed on midtrimester ultrasound often resolves by the third trimester. Multiparity and previous cesarean delivery have been associated with persistence of placenta previa at delivery. Risk factors for persistent placenta previa in nulliparas are not well characterized. OBJECTIVE: This study aimed to identify risk factors for persistent placenta previa in the nulliparous population, and evaluate differences in outcomes between persistent and resolved placenta previa. STUDY DESIGN: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b), a prospective cohort study that observed 10,037 nulliparous individuals throughout pregnancy. Nulliparas diagnosed with placenta previa on midtrimester ultrasound were included in this analysis. Baseline characteristics and delivery outcomes of nulliparas with persistent placenta previa were compared with those of nulliparas with resolved placenta previa. Multivariate logistic regression with stepwise model selection was used for adjusted analyses. RESULTS: A total of 171 nulliparas (1.7%) in the nuMoM2b study were diagnosed with placenta previa on midtrimester ultrasound, of whom 17% (n=29) had persistent placenta previa at delivery. When compared with those with resolved placenta previa, nulliparas with persistent placenta previa were more likely to be older (median, 32 years [interquartile range, 30-37] vs 29 years [interquartile range, 25-31]; P<.01), have a previous pregnancy of <20 weeks (48.3% vs 22.5%; P=.01), have a previous dilation and curettage/evacuation procedure (27.6% vs 10.6%; P=.03), or have a pregnancy that resulted from assisted reproductive technology (31% vs 4.9%; P=.01). After adjusting for potential confounders, maternal age (adjusted odds ratio, 1.11; 95% confidence interval, 1.02-1.21), in vitro fertilization (adjusted odds ratio, 9.00; 95% confidence interval, 1.97-41.14), and previous pregnancy of <20 weeks (adjusted odds ratio, 2.77; 95% confidence interval, 1.10-6.95) remained statistically significant risk factors for persistent placenta previa. Persistent placenta previa was also associated with higher likelihood of antepartum admission (10.3% vs 0%; P<.01), preterm delivery (34.5% vs 12%; P<.01), lower neonatal birthweight (median, 2847 g [interquartile range, 2655-3310] vs 3263 g [interquartile range, 2855-3560]), and cesarean delivery (100% vs 20.4%; P<.001), but there were no differences in overall pregnancy or neonatal outcomes. CONCLUSION: In nulliparous individuals diagnosed with placenta previa on midtrimester ultrasound, older maternal age, previous pregnancy of <20 weeks, and in vitro fertilization are associated with persistent placenta previa at delivery.

HDAC3 is a critical negative regulator of long-term memory formation.

Gene expression is dynamically regulated by chromatin modifications on histone tails, such as acetylation. In general, histone acetylation promotes transcription, whereas histone deacetylation negatively regulates transcription. The interplay between histone acetyltranserases and histone deacetylases (HDACs) is pivotal for the regulation of gene expression required for long-term memory processes. Currently, very little is known about the role of individual HDACs in learning and memory. We examined the role of HDAC3 in long-term memory using a combined genetic and pharmacologic approach. We used HDAC3-FLOX genetically modified mice in combination with adeno-associated virus-expressing Cre recombinase to generate focal homozygous deletions of Hdac3 in area CA1 of the dorsal hippocampus. To complement this approach, we also used a selective inhibitor of HDAC3, RGFP136 [N-(6-(2-amino-4-fluorophenylamino)-6-oxohexyl)-4-methylbenzamide]. Immunohistochemistry showed that focal deletion or intrahippocampal delivery of RGFP136 resulted in increased histone acetylation. Both the focal deletion of HDAC3 as well as HDAC3 inhibition via RGFP136 significantly enhanced long-term memory in a persistent manner. Next we examined expression of genes implicated in long-term memory from dorsal hippocampal punches using quantitative reverse transcription-PCR. Expression of nuclear receptor subfamily 4 group A, member 2 (Nr4a2) and c-fos was significantly increased in the hippocampus of HDAC3-FLOX mice compared with wild-type controls. Memory enhancements observed in HDAC3-FLOX mice were abolished by intrahippocampal delivery of Nr4a2 small interfering RNA, suggesting a mechanism by which HDAC3 negatively regulates memory formation. Together, these findings demonstrate a critical role for HDAC3 in the molecular mechanisms underlying long-term memory formation.

Twin gestation in a uterus didelphys with only one functional cervix: A case report.

INTRODUCTION: Twin gestation in a uterus didelphys with one fetus in each uterine cavity is rare and presents unique challenges in antepartum and intrapartum care. CASE PRESENTATION: A 35-year-old woman with a uterus didelphys became pregnant with twins, with one fetus in each uterus, after intrauterine insemination of a single visible cervix. Multiplanar ultrasonography showed the presence of one complete cervix and a second hypoplastic cervix; it was unclear whether she could deliver both twins vaginally. Her pregnancy was complicated by fetal growth restriction of twin B. At 38 weeks, the patient underwent scheduled cesarean section and delivered two viable twins. CONCLUSION: Determining the precise anatomy of Mullerian duct anomalies, including the cervix and vagina, is important for obstetrical management.

Inadvertent Perforation of a Gravid Uterus During Laparoscopy.

BACKGROUND: Laparoscopic surgery is safe in pregnancy, but is not without risk. Inadvertent uterine perforation of the gravid uterus is a rare complication. CASES: Three pregnant women had inadvertent uterine perforation during laparoscopic surgery. All patients were counseled regarding the risks of an "incidental fetoscopy" and elected to continue the pregnancy. Two delivered after preterm premature rupture of membranes at 32 and 36 weeks' gestation, and one twin pregnancy delivered at 30 weeks due to preeclampsia. CONCLUSION: Surgical planning of the gravid patient undergoing laparoscopic surgery should include demarcation of the most superior aspect of the uterine fundus, either via physical examination or, if not conclusive, via preoperative or intraoperative ultrasound.

Assessing the Approach to HIV Case Management.

Case management is a standard practice for assisting people living with HIV in the United States. While HIV case management has resulted in positive outcomes for clients and their families, clients still face challenges. As part of an evaluation of Utah's Ryan White Part B Program, the Utah Department of Health and researchers from the University of Utah assessed the use of a tiered approach for case management in eight other states to determine the feasibility and potential effectiveness of this approach. Through review of publicly available materials and interviews with health department employees, we examined each state's 1) definitions of tiers, 2) acuity scales, 3) services provided within the tiers, 4) qualifications of case managers, and 5) how evaluations were conducted. This article summarizes how these various features might be combined to create a model that states could use for tiered case management. We developed a three-tiered model using a numeric summary for nine items to assess acuity, with levels defined as maintenance outreach support services, brief-contact management, and medical/non-medical management. Since none of the states reviewed had an existing formal evaluation tool, we propose areas to be covered in an annual formal evaluation.

Parturient With Barnes Syndrome (Thoracolaryngopelvic Dysplasia) Undergoing Cesarean Delivery of a Neonate With Barnes Syndrome: A Case Report.

This case describes a parturient with Barnes syndrome, a rare disorder characterized by subglottic stenosis, thoracic dystrophy, and small pelvic inlet, who underwent cesarean delivery of a neonate diagnosed with Barnes syndrome. Live simulation training was performed by multidisciplinary team to prepare for the spinal anesthetic, personnel flow between 2 operating rooms, and management of various airway scenarios for the newborn. After delivery, the neonate underwent laryngoscopy-bronchoscopy with successful intubation in the operating room because of labored breathing. Airway evaluation revealed subglottic stenosis, tracheomalacia/bronchomalacia. Collaboration among perinatologists, obstetric/pediatric anesthesiologists, pediatric head and neck surgeons, and neonatologists was integral to perioperative management of both the mother and child.

Computed tomography blush and splenic injury: does it always require angioembolization?

The implication of splenic contrast blush on computed tomography (CT) in blunt trauma patients and whether it is an indication for angioembolization (AE) remains controversial. Our objective was to determine whether CT blush and its subsequent treatment have any impact on outcomes in blunt trauma patients with low-grade splenic injuries. A retrospective review identified adult patients with splenic injury (American Association for the Surgery of Trauma grades 1 to 3) from blunt abdominal trauma who were evaluated with a CT scan over a 3.5-year period at a Level I trauma center. Patient groups analyzed included: observation patients with no CT blush (n = 110), observation patients with CT blush (n = 18), and AE patients with CT blush (n = 22). Patients with CT blush who were observed did not demonstrate significantly worse outcomes compared with the patients with no CT blush. Additionally, patients with CT blush who underwent AE did not show any significant improvement in outcomes compared with patients who were observed with CT blush. Our study suggests that CT blush does not predict worse outcomes for blunt trauma patients with low-grade splenic injury who underwent observation. Furthermore, AE does not seem to provide any advantage to this subset of patients.

The neuron-specific chromatin regulatory subunit BAF53b is necessary for synaptic plasticity and memory.

Recent exome sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several human intellectual disabilities and cognitive disorders. However, it is currently unknown how mutations in BAF complexes result in impaired cognitive function. Postmitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Mice harboring selective genetic manipulations of BAF53b have severe defects in long-term memory and long-lasting forms of hippocampal synaptic plasticity. We rescued memory impairments in BAF53b mutant mice by reintroducing BAF53b in the adult hippocampus, which suggests a role for BAF53b beyond neuronal development. The defects in BAF53b mutant mice appeared to derive from alterations in gene expression that produce abnormal postsynaptic components, such as spine structure and function, and ultimately lead to deficits in synaptic plasticity. Our results provide new insight into the role of dominant mutations in subunits of BAF complexes in human intellectual and cognitive disorders.