Placental delayed villous maturation is associated with fetal congenital heart disease.

BACKGROUND: The placenta is crucial for the overall development and lifelong health of the fetus. Abnormal placental development and function occur in pregnancies with fetal congenital heart disease. However, studies that use standardized diagnostic criteria and incorporate control populations are lacking. This limits the generalizability of current research and the ability to determine the specific placental abnormalities associated with congenital heart disease. OBJECTIVE: This study applied consensus statement guidelines (known as the Amsterdam criteria) for placental pathology interpretation to compare the frequency and pattern of abnormalities in pregnancies with fetal congenital heart disease to demographically matched control pregnancies and evaluate for differences in placental abnormalities by cardiac physiology. STUDY DESIGN: A single-center retrospective cohort study was conducted from January 2013 to June 2019. Infants with a prenatal diagnosis of moderate-severe congenital heart disease who were born at ≥37 weeks of gestation were included. A control group born at ≥37 weeks of gestation but without fetal congenital heart disease or other major pregnancy complications was matched to the congenital heart disease group on maternal race and ethnicity and infant sex. Using the Amsterdam criteria, placental pathology findings were categorized as delayed villous maturation, maternal vascular malperfusion, fetal vascular malperfusion, and inflammatory lesions. The frequency of placental abnormalities was compared between groups, and logistic regression was performed to evaluate the association of clinical and sociodemographic factors with delayed villous maturation, maternal vascular malperfusion, and fetal vascular malperfusion. RESULTS: There were 194 pregnancies with fetal congenital heart disease and 105 controls included, of whom 83% in the congenital heart disease group and 82% in the control group were of non-Hispanic White race and ethnicity. Compared with controls, pregnancies with fetal congenital heart disease had higher rates of delayed villous maturation (6% vs 19%; P<.001) and maternal vascular malperfusion (19% vs 34%; P=.007) but not fetal vascular malperfusion (6% vs 10%; P=.23). Infants with congenital heart disease with 2-ventricle anatomy displayed the highest odds of delayed villous maturation compared with controls (odds ratio, 5.5; 95% confidence interval, 2.2-15.7; P<.01). Maternal vascular malperfusion was 2.2 times higher (P=.02) for infants with 2-ventricle anatomy and 2.9 times higher (P=.02) for infants with single-ventricle physiology with pulmonic obstruction. Within the congenital heart disease group, delayed villous maturation was associated with higher maternal body mass index, polyhydramnios, larger infant birth head circumference, and infant respiratory support in the delivery room, whereas maternal vascular malperfusion was associated with oligohydramnios. In multivariable models adjusting for cardiac diagnosis, associations of delayed villous maturation persisted for infant birth head circumference (odds ratio, 1.2; 95% confidence interval, 1.0-1.5; P=.02) and infant respiratory support in the delivery room (odds ratio, 3.0; 95% confidence interval, 1.3-6.5; P=.007). CONCLUSION: Pregnancies with fetal congenital heart disease displayed higher rates of delayed villous maturation and maternal vascular malperfusion than controls, suggesting that placental maldevelopment may relate to maternal factors. Future investigations are needed to determine the association of these abnormalities with postnatal infant outcomes.

Child Firearm Injury Circumstances and Associations With Violence Intervention Program Enrollment.

INTRODUCTION: Pediatric firearm injuries are the leading cause of death among American children. While assault is the most commonly cited cause, few studies have investigated circumstances surrounding such injuries. Violence intervention programs (VIPs) have been utilized to combat firearm violence, though a similar lack of knowledge exists regarding possible associations between firearm injury circumstances and youth VIP enrollment. METHODS: This cross-sectional study included children aged 6-17 y who presented to an urban level 1 pediatric trauma center with firearm injuries from 2014 to 2017. Victim demographics and enrollment in a VIP were obtained from medical records, as well as circumstances surrounding the injuries based on account of the victim, victim's family/friends, and/or police present at the hospital. Circumstances included location of the shooting, if the shooter was known to the victim, and if the shooting was confirmed by the victim or their contacts to have been accidental or an intentional assault. Medical record numbers were used to locate victims in our trauma registry in order to obtain their assigned international classification of disease codes. Wilcox-rank sum, Pearson's chi-squared and Fisher's exact tests were used to detect associations between demographics, VIP enrollment, and shooting circumstances. RESULTS: 156 victims of firearm injury were described, including primarily Black adolescent males. 72% of victims were shot outdoors by an unknown shooter, the motivation of which was unknown in 93% of cases. 36% of these shootings were "drive-by". The majority of victims received international classification of disease codes for assault, though shootings that were confirmed by the victim to have been intentional assaults were relatively uncommon (13.4%). Most children lived in the same zip code in which they were shot (71%), and three particular zip codes accounted for 40% of shootings. 26% of victims chose to enroll in the VIP, and those that were victims of confirmed assaults (odds ratio 3.5) as well as those admitted to the hospital (odds ratio 2.4) were significantly more likely to enroll. CONCLUSIONS: Based on victim account, children living in an urban setting are more frequently victims of unclearly motivated, outdoor neighborhood shootings rather than intentional assaults. More accurate understanding of the causes of pediatric firearm injuries should inform both recruitment into VIPs, as well as a balancing of VIPs with community-level interventions to address firearm violence.

Acute kidney injury requiring kidney replacement therapy in childhood lupus nephritis: a cohort study of the Pediatric Nephrology Research Consortium and Childhood Arthritis and Rheumatology Research Alliance.

BACKGROUND: Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for development of chronic kidney disease. In adults with LN, AKI severity correlates with the incidence of kidney failure and patient survival. Data on AKI outcomes in children with LN, particularly those requiring kidney replacement therapy (KRT), are limited. METHODS: A multicenter, retrospective cohort study was performed in children diagnosed between 2010 and 2019 with LN and AKI stage 3 treated with dialysis (AKI stage 3D). Descriptive statistics were used to characterize demographics, clinical data, and kidney biopsy findings; treatment data for LN were not included. Logistic regression was used to examine the association of these variables with kidney failure. RESULTS: Fifty-nine patients (mean age 14.3 years, 84.7% female) were identified. The most common KRT indications were fluid overload (86.4%) and elevated blood urea nitrogen/creatinine (74.6%). Mean follow-up duration was 3.9 ± 2.9 years. AKI recovery without progression to kidney failure occurred in 37.3% of patients. AKI recovery with later progression to kidney failure occurred in 25.4% of patients, and there was no kidney recovery from AKI in 35.6% of patients. Older age, severe (> 50%) tubular atrophy and interstitial fibrosis, and National Institutes of Health (NIH) chronicity index score > 4 on kidney biopsy were associated with kidney failure. CONCLUSIONS: Children with LN and AKI stage 3D have a high long-term risk of kidney failure. Severe tubular atrophy and interstitial fibrosis at the time of AKI, but not AKI duration, are predictive of kidney disease progression. A higher resolution version of the Graphical abstract is available as Supplementary information.

An Amplitude-Integrated EEG Evaluation of Neonatal Opioid Withdrawal Syndrome.

OBJECTIVE: Infants with neonatal opioid withdrawal syndrome (NOWS) have disrupted neurobehavior that requires hospitalization and treatment. This article aimed to evaluate electroencephalography (EEG) abnormalities using amplitude-integrated EEG (aEEG) in NOWS. STUDY DESIGN: Eighteen term born infants with NOWS were recruited prospectively for an observational pilot study. aEEG monitoring was started within 24 hours of recruitment and twice weekly through discharge. aEEG data were analyzed for background and seizures. Severity of withdrawal was monitored using the modified Finnegan scoring (MFS) system. RESULTS: Fifteen neonates had complete datasets. Thirteen (87%) had continuous aEEG background in all recordings. None had sleep-wake cyclicity (SWC) at initial recording. Brief seizures were noted in 9 of 15 (60%) infants. Lack of SWC was associated with higher MFS scores. At discharge, 8 of 15 (53%) had absent or emerging SWC. CONCLUSION: aEEG abnormalities (absent SWC) are frequent and persist despite treatment at the time of discharge in the majority of patients with NOWS. Brief electrographic seizures are common. Neonates with persistent aEEG abnormalities at discharge warrant close follow-up. KEY POINTS: · EEG abnormalities are common and persist after clinical signs resolve in patients with NOWS.. · Short subclinical seizures may be seen.. · aEEG may identify neonates who need follow-up..

Parental Mental Health Care After Their Child's Pediatric Intensive Care Hospitalization.

OBJECTIVES: Post-traumatic stress disorder, depression, and anxiety have all been found in parents of PICU survivors. How these research findings translate to actual use of mental health services by parents remains unknown. DESIGN: Retrospective observational cohort study. SETTING: Insurance claims data from 2006 to 2013 obtained from the IBM MarketScan Commercial Database. PATIENTS: Parents of PICU survivors. INTERVENTIONS: We examined rates of: 1) mental health diagnoses, 2) outpatient mental health visits, and 3) prescriptions for antidepressants and anxiolytics among parents, 6 months before and 6 months after their child's PICU admission, using each parent as their own control. MEASUREMENTS AND MAIN RESULTS: Of the 95,070 parents identified, 9.5% received a new mental health diagnosis in the 6 months after their child's PICU hospitalization, which represented a 110% increase from pre-PICU rates. A smaller proportion of parents were given new prescriptions for antidepressants (3.4%) and anxiolytics (3.9%) in the 6 months after their child's PICU hospitalization. Mothers were twice as likely to receive a new mental health diagnosis and be taking a new medication than fathers in the post-PICU period. The parental diagnosis of acute stress disorder or post-traumatic stress disorder increased by 87% from the pre-PICU to the post-PICU period. CONCLUSIONS: After their child's PICU hospitalization, the proportion of parents with a new mental health diagnosis nearly doubled. Mothers were at nearly twice the risk of receiving a new mental health diagnosis and receiving a new mental health medication compared with fathers. The proportion of parents receiving mental healthcare is much lower than the proportion reporting mental health symptoms in long-term outcomes studies. Whether this indicates a gap in healthcare delivery for parents with mental health symptoms remains unknown.

Maturational patterns of left ventricular rotational mechanics in pre-term infants through 1 year of age.

BACKGROUND: Pre-mature birth impacts left ventricular development, predisposing this population to long-term cardiovascular risk. The aims of this study were to investigate maturational changes in rotational properties from the neonatal period through 1 year of age and to discern the impact of cardiopulmonary complications of pre-maturity on these measures. METHODS: Pre-term infants (<29 weeks at birth, n = 117) were prospectively enrolled and followed to 1-year corrected age. Left ventricular basal and apical rotation, twist, and torsion were measured by two-dimensional speckle-tracking echocardiography and analysed at 32 and 36 weeks post-menstrual age and 1-year corrected age. A mixed random effects model with repeated measures analysis was used to compare rotational mechanics over time. Torsion was compared in infants with and without complications of cardiopulmonary diseases of pre-maturity, specifically bronchopulmonary dysplasia, pulmonary hypertension, and patent ductus arteriosus. RESULTS: Torsion decreased from 32 weeks post-menstrual age to 1-year corrected age in all pre-term infants (p < 0.001). The decline from 32 to 36 weeks post-menstrual age was more pronounced in infants with cardiopulmonary complications, but was similar to healthy pre-term infants from 36 weeks post-menstrual age to 1-year corrected age. The decline was due to directional and magnitude changes in apical rotation over time (p < 0.05). CONCLUSION: This study tracks maturational patterns of rotational mechanics in pre-term infants and reveals torsion declines from the neonatal period through 1 year. Cardiopulmonary diseases of pre-maturity may negatively impact rotational mechanics during the neonatal period, but the myocardium recovers by 1-year corrected age.

Patient Expectation and Satisfaction with Different Prosthetic Treatment Modalities.

PURPOSE: To investigate the relationships between gender, age, patients' perceptions about the dentists' conduct, number of adjustments, treatment type, and expectation prior to prosthetic treatment and patient satisfaction with their treatments. MATERIALS AND METHODS: Data were integrated from four studies that measured patient expectations before treatment and satisfaction after treatment using a visual analog scale (VAS) from 0 to 10. These scores were given for each of four aspects of the therapeutic outcomes: chewing, esthetics, phonetics, and comfort. Patients' perceptions about the dentists' conduct was also assessed using a Likert-scale questionnaire. The total sample size, after combining the data from all four studies, was 223 subjects. Bivariate and multivariable analyses were performed. The covariates entertained were gender, age, treatment type, patients' perceptions about the dentists' conduct, number of adjustments, and expectation prior to denture fabrication. RESULTS: In the entire sample, 115 (51.57%) patients were females and 108 (48.43%) were males. They ranged in age from 28 to 81 years old; the mean age was 53.2 years (SD = 11.5). Combining four treatments together, there was no significant difference between patients' expectation and satisfaction scores for all four items. There were no significant differences between expectation and satisfaction for different genders. Multivariable analysis showed that patient expectation, satisfaction and the difference (satisfaction score-expectation score) scores for all four aspects were associated with treatment type (implant treatments were favored), and expectation prior to prosthetic treatment (the higher the expectation, the higher the satisfaction) was associated with satisfaction and difference scores. Satisfaction and difference scores for chewing were associated with number of adjustments and satisfaction, and satisfaction and difference scores for phonetics and comfort were associated with how well the dentist explained the intended treatment before performing it. CONCLUSIONS: Patient satisfaction was associated with treatment type (implant treatments were favored), expectations prior to prosthetic treatment (the higher the expectation, the higher the satisfaction), and how well the dentist explained the intended treatment before performing it.

The Post-transplant Lymphoproliferative Disorders-Metagenomic Shotgun Microbial Sequencing (PTLD-MSMS) Study Methods and Protocol.

Post-transplant lymphoproliferative disorders (PTLDs) remain a feared complication of transplantation, with significant morbidity and mortality. The oncogenic Epstein-Barr virus (EBV) is a key pathogenic driver in 50%-80% of cases. Numerous prognostic indices, comprising multiple clinical, epidemiological and tumor characteristics, including EBV tumor positivity, do not consistently associate with worse patient survival, suggesting a potential role for EBV genome variants in determining outcome. However, the precision medicine tools for determining if a viral genome variant is pathogenic are very limited compared with human genome variants. Further, targeted studies have not implicated a specific viral etiological agent in EBV-negative PTLD. Using novel cutting-edge technologies, we are extracting viral nucleic acids from formalin-fixed, paraffin-embedded archived, or frozen PTLD tissues or plasma, to test for all vertebrate viruses simultaneously in an unbiased fashion, using metagenomic shotgun sequencing (MSS). We are collecting such samples from multiple transplant centers to address the following specific aims and close the following knowledge gaps: (1) Validate our novel observation that PTLD tissue positivity by MSS for anellovirus (and confirmed by PCR) serves as a biomarker for higher transplant recipient mortality after the diagnosis of PTLD; (2) determine the role of other oncogenic viruses in EBV-negative PTLD by unbiased MSS of multiple viral groupings, confirmed by other techniques; and (3) develop the necessary computational, algorithmic and software analytic tools required to determine association of EBV genome variants with worse presentations or outcomes in PTLD. Study completion will contribute to better patient care and may provide avenues for novel therapies.

P2Y(6) agonist uridine 5'-diphosphate promotes host defense against bacterial infection via monocyte chemoattractant protein-1-mediated monocytes/macrophages recruitment.

Extracellular nucleotides are important messengers involved in series crucial physiological functions through the activation of P2 purinergic receptors. The detailed function and mechanism of the P2Y family in regulating immune response against invaded pathogens still remains unknown. In this study, the activation of purinoreceptor P2Y(6) by UDP was found to play a crucial role in promoting host defense against invaded bacteria through monocytes/macrophages recruitment. The expression level of P2Y(6) was much higher than other purinoreceptors in RAW264.7 cells, bone marrow macrophages, and peritoneal macrophages determined by real-time PCR. The supernatant of UDP (P2Y(6)-specific agonist)-treated RAW264.7 cells exhibited direct chemotaxis to monocytes/macrophages in vitro through Boyden Chambers assay. Meanwhile, the releasing of MCP-1 (MCP-1/CCL2) was enhanced obviously by UDP both in mRNA and protein level. Furthermore, the activation of P2Y(6) receptor by UDP also promotes ERK phosphorylation and AP-1 activation in a concentration- and time-dependent manner in RAW264.7 cells. This UDP-induced activation could be inhibited by P2Y(6) selectivity antagonist (MRS2578), MEK inhibitor (U0126), and MCP-1 blocking Ab, respectively. Moreover, i.p. injection with UDP resulted in a more efficacious clearance of invaded Escherichia coli and lower mortality in peritonitis mouse model. Together, our studies demonstrate that P2Y(6) receptor could be a novel mediator in upregulating innate immune response against the invaded pathogens through recruiting monocytes/macrophages.

Retinopathy of prematurity: risk stratification by gestational age.

OBJECTIVE: To identify gestational age (GA) specific risk factors for severe ROP (sROP). STUDY DESIGN: Single-center cohort stratified by GA into <24 weeks, 24-26 weeks and ≥27 weeks. RESULTS: 132/1106 (11.9%) developed sROP. Time to full feeds was the only risk factor [HR 1.003 (1.001-1.006), p = 0.04] for infants<24 weeks GA. For infants 24-26 weeks GA, a higher GA was protective [HR 0.66 (0.51-0.85), p < 0.01], whereas steroids for bronchopulmonary dysplasia (BPD) [HR 2.21 (1.28-3.26), p < 0.01], patent ductus arteriosus (PDA) ligation [HR 1.99 (1.25-3.11), p < 0.01] and use of nitric oxide [HR 1.96 (1.11-3.30), p = 0.01] increased the hazard of sROP. Increasing birthweight was protective [HR 0.70 (0.54-0.89), p < 0.01] in infants ≥27 weeks GA. Cumulative hazard of sROP reached 1.0 by fifteen weeks for <24 weeks GA, 0.4 by twenty weeks for 24-26 weeks GA, and 0.05 by twenty weeks after birth for ≥27 weeks GA. CONCLUSIONS: Risk factors, cumulative hazard, and time to sROP vary by GA.

COVID-19 Pandemic Effects on the Epidemiology and Mortality of Pediatric Firearm Injuries; A Single Center Study.

BACKGROUND: The COVID-19 pandemic has been associated with increased firearm injuries amongst adults, though the pandemic's effect on children is less clearly understood. METHODS: This cross-sectional study was performed at a Level 1 Pediatric Trauma Center and included youths 0-19 years. The trauma registry was retrospectively queried for firearm injuries occurring pre-COVID-19 pandemic (March 2015-February 2020). Baseline data was compared to prospectively collected data occurring during the COVID-19 pandemic (March 2020-March 2022). Fischer's exact, Pearson's Chi-square and/or correlation analysis was used to compare pre and post-COVID-19 firearm injury rates and intent, victim demographics and disposition. Temporal relationships between firearm injury rates and local COVID-19 death rates were also described. RESULTS: 413 pre-COVID-19 firearm injuries were compared to 259 pandemic firearm injuries. Victims were mostly Black males with a mean age of 13.4 years. Compared to the 5 years pre-pandemic, monthly firearm injury rates increased 51.5% (6.8 vs 10.3 shootings/month), including a significant increase (p = 0.04) in firearm assaults/homicides and a relative decrease in unintentional shootings. Deaths increased 29%, and there were significantly fewer ED discharges and more admissions to OR and/or PICU (p = 0.005). There was a significant increase in Black victims (p = 0.01) and those having Medicaid or self-pay (p<0.001). Firearm injury spikes were noted during or within the 3 months following surges in local COVID-19 death rates. CONCLUSIONS: The COVID-19 pandemic was associated with an increase in the frequency and mortality of pediatric firearm injuries, particularly assaults amongst Black children following surges in COVID death rates. Increased violence-intervention services are needed, particularly amongst marginalized communities. LEVEL OF EVIDENCE: This is a prognostic study, evaluating the effects of the COVID-19 pandemic on pediatric firearm injuries, including victim demographics, injury intent and mortality. This study is retrospective and observational, making it Oxford Level III evidence.

Cognitive deficits and altered functional brain network organization in pediatric brain tumor patients.

Survivors of pediatric brain tumors experience significant cognitive deficits from their diagnosis and treatment. The exact mechanisms of cognitive injury are poorly understood, and validated predictors of long-term cognitive outcome are lacking. Resting state functional magnetic resonance imaging allows for the study of the spontaneous fluctuations in bulk neural activity, providing insight into brain organization and function. Here, we evaluated cognitive performance and functional network architecture in pediatric brain tumor patients. Forty-nine patients (7-18 years old) with a primary brain tumor diagnosis underwent resting state imaging during regularly scheduled clinical visits. All patients were tested with a battery of cognitive assessments. Extant data from 139 typically developing children were used as controls. We found that obtaining high-quality imaging data during routine clinical scanning was feasible. Functional network organization was significantly altered in patients, with the largest disruptions observed in patients who received propofol sedation. Awake patients demonstrated significant decreases in association network segregation compared to controls. Interestingly, there was no difference in the segregation of sensorimotor networks. With a median follow-up of 3.1 years, patients demonstrated cognitive deficits in multiple domains of executive function. Finally, there was a weak correlation between decreased default mode network segregation and poor picture vocabulary score. Future work with longer follow-up, longitudinal analyses, and a larger cohort will provide further insight into this potential predictor.

Diversity within US dermatology residency programs and opportunities to care for underserved populations: A 2020 survey study.

Dermatology is the second-least diverse medical specialty. In this survey study, we identified the current proportion of underrepresented in medicine (UIM) residents and faculty in dermatology residency programs, perceptions on the importance of program diversity, and various opportunities for dermatology residents to care for underserved populations. We found that programs that provided greater resident exposure to the care of underserved populations and those that strongly considered residency applicants' desire to work with underserved populations had greater percentages of UIM residents. These findings illustrate the importance of expanding diversity among residency programs as this may be key to improving health disparities among underserved populations. Additionally, we identified various barriers that programs have to incorporating service-oriented curricula, including faculty time and cost.

Longitudinal Evaluation of Donor-Derived Cellfree DNA in Pediatric Kidney Transplantation.

BACKGROUND AND OBJECTIVES: Donor-derived cellfree DNA (cfDNA) is a less-invasive marker of allograft injury compared with kidney biopsy. However, donor-derived cfDNA has not yet been extensively tested in children, where the test may have different characteristics. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We assayed donor-derived cfDNA (AlloSure; CareDx) from 290 stored plasma samples from a prospective biobank at our center, collected from 57 children monthly in the first year postkidney transplant between January 2013 and December 2019. We assessed the kinetic changes in donor-derived cfDNA levels within the first year post-transplant. We analyzed donor-derived cfDNA levels for associations with biopsy-proven acute rejection using area under the receiver operating characteristic curve to longitudinal plasma and urine BK viral loads using linear mixed models. We analyzed the prognostic effect of an elevated donor-derived cfDNA level on the eGFR 30 days after the assay via Kolmogorov-Smirnov two-sample tests or on measured GFR or interstitial fibrosis at 12 months post-transplant. RESULTS: The donor-derived cfDNA levels in children remained persistently elevated for at least 4 months post-transplant, more so if there is greater disparity in size between the donor and the recipient, before reaching a steady low level. A donor-derived cfDNA level of >1% discriminated between biopsy-proven acute rejection with a receiver operating characteristic area under the curve of 0.82 (95% confidence interval, 0.71 to 0.93). During BK viruria or viremia, patients had a significantly higher median donor-derived cfDNA than before or after and a significant rise within the same patient. A donor-derived cfDNA of >0.5% predicted a wider spread in the eGFR over the next 30 days but not the 12-month outcomes. CONCLUSIONS: In children, donor-derived cfDNA is a valuable, less invasive biomarker for assessment of allograft rejection and injury. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_10_27_CJN03840322.mp3.

Etiology- and region-specific characteristics of transependymal cerebrospinal fluid flow.

OBJECTIVE: Transependymal flow (TEF) of CSF, often delineated as T2-weighted hyperintensity adjacent to the lateral ventricles on MRI, is a known imaging finding, usually in the setting of CSF flow disturbances. Specific radiological features of TEF and their relationships with clinical markers of hydrocephalus and underlying disease pathology are not known. Here, the authors describe the radiological features and clinical associations of TEF with implications for CSF circulation in the setting of intracranial pathology. METHODS: After obtaining IRB review and approval, the authors reviewed the radiological records of all patients who underwent intracranial imaging with CT or MRI at St. Louis Children's Hospital, St. Louis, Missouri, between 2008 and 2019 to identify individuals with TEF. Then, under direct review of imaging, TEF pattern, degree, and location and underlying pathology and other radiological and clinical features pertaining to CSF circulation and CSF disturbances were noted. RESULTS: TEF of CSF was identified in 219 patients and was most prevalent in the setting of neoplasms (72%). In 69% of the overall cohort, TEF was seen adjacent to the anterior aspect of the frontal horns and the posterior aspect of the occipital horns of the lateral ventricles, and nearly half of these patients also had TEF dorsal to the third ventricle near the splenium of the corpus callosum. This pattern was independently associated with posterior fossa medulloblastoma when compared with pilocytic astrocytoma (OR 4.75, 95% CI 1.43-18.53, p = 0.0157). Patients with congenital or neonatal-onset hydrocephalus accounted for 13% of patients and were more likely to have TEF circumferentially around the ventricles without the fronto-occipital distribution. Patients who ultimately required permanent CSF diversion surgery were more likely to have the circumferential TEF pattern, a smaller degree of TEF, and a lack of papilledema at the time of CSF diversion surgery. CONCLUSIONS: CSF transmigration across the ependyma is usually restricted to specific periventricular regions and is etiology specific. Certain radiological TEF characteristics are associated with tumor pathology and may reflect impaired or preserved ependymal fluid handling and global CSF circulation. These findings have implications for TEF as a disease-specific marker and in understanding CSF handling within the brain.

A Unique High-Output Cardiac Hypertrophy Phenotype Arising From Low Systemic Vascular Resistance in Cantu Syndrome.

Background Cardiomegaly caused by left ventricular hypertrophy is a risk factor for development of congestive heart failure, classically associated with decreased systolic and/or diastolic ventricular function. Less attention has been given to the phenotype of left ventricular hypertrophy with enhanced ventricular function and increased cardiac output, which is potentially associated with high-output heart failure. Lack of recognition may pose diagnostic ambiguity and management complexities. Methods and Results We sought to systematically characterize high-output cardiac hypertrophy in subjects with Cantu syndrome (CS), caused by gain-of-function variants in ABCC9, which encodes cardiovascular KATP (ATP-sensitive potassium) channel subunits. We studied the cardiovascular phenotype longitudinally in 31 subjects with CS with confirmed ABCC9 variants (median [interquartile range] age 8 years [3-32 years], body mass index 19.9 [16.5-22.9], 16 male subjects). Subjects with CS presented with significant left ventricular hypertrophy (left ventricular mass index 86.7 [57.7-103.0] g/m2 in CS, n=30; 26.6 [24.1-32.8] g/m2 in controls, n=17; P<0.0001) and low blood pressure (systolic 94.5 [90-103] mm Hg in CS, n=17; 109 [98-115] mm Hg in controls, n=17; P=0.0301; diastolic 60 [56-66] mm Hg in CS, n=17; 69 [65-72] mm Hg in control, n=17; P=0.0063). Most (21/31) subjects with CS exhibited eccentric hypertrophy with normal left ventricular wall thickness. Congestive heart failure symptoms were evident in 4 of the 5 subjects with CS aged >40 years on long-term follow-up. Conclusions The data define the natural history of high-output cardiac hypertrophy resulting from decreased systemic vascular resistance in subjects with CS, a defining population for long-term consequences of high-output hypertrophy caused by low systemic vascular resistance, and the potential for progression to high-output heart failure.

Impact of Continuous Renal Replacement Therapy on Bivalirudin Dosing in Pediatric Extracorporeal Membrane Oxygenation.

There is an increasing interest in the use of bivalirudin for pediatric extracorporeal membrane oxygenation (ECMO) anticoagulation. However, dosing is not well described in those requiring continuous renal replacement therapy (CRRT). We aimed to determine whether CRRT affects bivalirudin dosing in pediatric ECMO patients. Children ≤18 years of age placed on ECMO and anticoagulated with bivalirudin for ≥24 hours from January 2019 to May 2020 were included. Bivalirudin doses were collected for 144 hours from initiation of bivalirudin or CRRT. Analysis was performed to determine whether CRRT, age, or weight affected bivalirudin dosing. Thirty-one children were included, and 11 (35%) required concomitant CRRT. There was no difference in age (median 9.1 versus 3.2 months, p = 0.15) or days on ECMO (median 11 versus 9, p = 0.7) between those who did or did not receive CRRT. The mean bivalirudin dosing was similar in patients who did or did not require CRRT (median and IQR: 0.13 mg/kg/hour [0.08-0.26] versus 0.15 mg/kg/hour [0.11-0.22], respectively, p = 0.13). Younger age ( p < 0.001) and lower weight ( p < 0.001) were associated with higher bivalirudin dosing. In our study, bivalirudin dosing did not differ if the patient required CRRT while on ECMO.

Impact of risk-based sexually transmitted infection screening in the emergency department.

OBJECTIVES: Sexually transmitted infections (STIs), including chlamydia, gonorrhea, and human immunodeficiency virus (HIV) pose a significant health burden in adolescents. Many adolescents receiving care in the emergency department (ED) are in need of testing, regardless of their chief complaint. Our objective was to determine whether an electronic, risk-based STI screening program in our ED was associated with an increase in STI testing among at-risk adolescents. METHODS: We conducted a retrospective cohort analysis of patient outcomes in our pediatric ED after integrating an Audio-enhanced Computer-Assisted Self-Interview (ACASI) as standard of care. It obtained a focused sexual history and generated STI testing recommendations. Patient answers and testing recommendations were integrated in real-time into the electronic health record. Patients who tested positive received treatment according to our standard-of-care practices. All patients 15-21 years of age were asked to complete this on an opt-out basis, regardless of the reason for their ED visit. Exclusions included those unable to independently use a tablet, severe illness, sexual assault, or non-English speaking. Our primary outcome was to describe STI-testing recommendations and test results among ACASI participants. We also compared STI testing between ACASI participants and those who were eligible but did not use it. RESULTS: In the first 13 months, 28.9% (1788/6194) of eligible adolescents completed the ACASI and 44.2% (321/790) accepted recommended STI testing. The mean age of participants was 16.6 ± 1.3 years, with 65.4% (1169) being female. Gonorrhea/chlamydia testing was significantly higher among participants vs. non-participants (20.1% [359/1788] vs 4.8% [212/4406]; p < 0.0001). The proportion of positive STI tests was similar between the two groups: 24.8% (89/359) vs. 24.5% (52/212; p = 0.94) were positive for chlamydia and/or gonorrhea, while 0.6% (2/354) participants vs. 0% non-participants (p > 0.99) were positive for HIV. Among participants whose chief complaints were unlikely to be related to STIs but accepted recommended testing, 20.9% (37/177) were positive for gonorrhea or chlamydia. CONCLUSIONS: Our program facilitated STI testing in the ED and identified many adolescents with STIs, even when their ED complaint was for unrelated reasons. More rigorous implementation is needed to determine the impact of deployment of ACASI to all eligible adolescents and addressing barriers to accepting STI testing recommendations.

Representation of female neurosurgeons as abstract authors at neurological surgery conferences.

OBJECTIVE: Female neurosurgeon representation has increased, but women still represent only 8.4% of neurosurgeons in the US. Women are significantly underrepresented as authors in neurosurgical and spine journals, a key indicator of professional success in academic medicine. In this study, the authors aimed to assess the gender diversity of first and last authors of accepted abstracts at neurosurgical conferences in 2015 and 2019. METHODS: Annual meeting abstracts for 2015 and 2019 of the American Association of Neurological Surgeons (AANS), Congress of Neurological Surgeons (CNS), and pediatrics, spine, stereotactic and functional surgery, and cerebrovascular AANS/CNS subspecialty sections were obtained and analyzed for gender. Partial data were obtained for tumor and pain sections. Composite gender data were obtained from the societies. Percentage differences were calculated using comparison of proportions testing. RESULTS: Overall, female neurosurgeons accounted for only 8.3% of first and 5.8% of last authors, and 7.2% of authors overall. The pediatrics section had the highest proportion of female neurosurgeons as first (13.7%) and last (12.4%) abstract authors, while the spine section had the lowest proportions of female neurosurgeon first (4.6%) and last (2.0%) authors. Qualitatively, a higher proportion of women were first authors, while a higher proportion of men were last authors. Overall, there was no significant change in female neurosurgeon authorship between 2015 and 2019. With regard to society demographics, female neurosurgeons accounted for only 6.3% of AANS membership. The pediatrics section had the highest proportion of female neurosurgeons at 18.1% and the stereotactic and functional surgery section had the lowest of the subspecialty sections (7.6%). While female neurosurgeons represented 12.6% of spine section membership, they represented only 4.7% of first authors (-7.9% difference; p < 0.0001) and 2.4% of last authors (-10.2% difference; p < 0.0001). For the 2019 cerebrovascular section, female neurosurgeons were underrepresented as presenting authors (5.8%) compared with their membership representation (14.8%, -9.0% difference; p = 0.0018). CONCLUSIONS: Despite an increase in the number of female neurosurgeons, there has not been a corresponding increase in the proportion of female neurosurgeons as abstract authors at annual neurosurgery conferences, and female neurosurgeons remain underrepresented as authors compared with their male colleagues.