OBJECTIVEHigh-quality data comparing endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) to shunt and ETV alone in North America are greatly lacking. To address this, the Hydrocephalus Clinical Research Network (HCRN) conducted a prospective study of ETV+CPC in infants. Here, these prospective data are presented and compared to prospectively collected data from a historical cohort of infants treated with shunt or ETV alone.METHODSFrom June 2014 to September 2015, infants (corrected age ≤ 24 months) requiring treatment for hydrocephalus with anatomy suitable for ETV+CPC were entered into a prospective study at 9 HCRN centers. The rate of procedural failure (i.e., the need for repeat hydrocephalus surgery, hydrocephalus-related death, or major postoperative neurological deficit) was determined. These data were compared with a cohort of similar infants who were treated with either a shunt (n = 969) or ETV alone (n = 74) by creating matched pairs on the basis of age and etiology. These data were obtained from the existing prospective HCRN Core Data Project. All patients were observed for at least 6 months.RESULTSA total of 118 infants underwent ETV+CPC (median corrected age 1.3 months; common etiologies including myelomeningocele [30.5%], intraventricular hemorrhage of prematurity [22.9%], and aqueductal stenosis [21.2%]). The 6-month success rate was 36%. The most common complications included seizures (5.1%) and CSF leak (3.4%). Important predictors of treatment success in the survival regression model included older age (p = 0.002), smaller preoperative ventricle size (p = 0.009), and greater degree of CPC (p = 0.02). The matching algorithm resulted in 112 matched pairs for ETV+CPC versus shunt alone and 34 matched pairs for ETV+CPC versus ETV alone. ETV+CPC was found to have significantly higher failure rate than shunt placement (p < 0.001). Although ETV+CPC had a similar failure rate compared with ETV alone (p = 0.73), the matched pairs included mostly infants with aqueductal stenosis and miscellaneous other etiologies but very few patients with intraventricular hemorrhage of prematurity.CONCLUSIONSWithin a large and broad cohort of North American infants, our data show that overall ETV+CPC appears to have a higher failure rate than shunt alone. Although the ETV+CPC results were similar to ETV alone, this comparison was limited by the small sample size and skewed etiological distribution. Within the ETV+CPC group, greater extent of CPC was associated with treatment success, thereby suggesting that there are subgroups who might benefit from the addition of CPC. Further work will focus on identifying these subgroups.

ObjectiveTo develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment.MethodsTo illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks.ResultsAs of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female.ConclusionsCollectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD.

OBJECTIVEEndoscopic third ventriculostomy combined with choroid plexus cauterization (ETV+CPC) has been adopted by many pediatric neurosurgeons as an alternative to placing shunts in infants with hydrocephalus. However, reported success rates have been highly variable, which may be secondary to patient selection, operative technique, and/or surgeon training. The objective of this prospective multicenter cohort study was to identify independent patient selection, operative technique, or surgical training predictors of ETV+CPC success in infants.METHODSThis was a prospective cohort study nested within the Hydrocephalus Clinical Research Network’s (HCRN) Core Data Project (registry). All infants under the age of 2 years who underwent a first ETV+CPC between June 2006 and March 2015 from 8 HCRN centers were included. Each patient had a minimum of 6 months of follow-up unless censored by an ETV+CPC failure. Patient and operative risk factors of failure were examined, as well as formal ETV+CPC training, which was defined as traveling to and working with the experienced surgeons at CURE Children’s Hospital of Uganda. ETV+CPC failure was defined as the need for repeat ETV, shunting, or death.RESULTSThe study contained 191 patients with a primary ETV+CPC conducted by 17 pediatric neurosurgeons within the HCRN. Infants under 6 months corrected age at the time of ETV+CPC represented 79% of the cohort. Myelomeningocele (26%), intraventricular hemorrhage associated with prematurity (24%), and aqueductal stenosis (17%) were the most common etiologies. A total of 115 (60%) of the ETV+CPCs were conducted by surgeons after formal training. Overall, ETV+CPC was successful in 48%, 46%, and 45% of infants at 6 months, 1 year, and 18 months, respectively. Young age (< 1 month) (adjusted hazard ratio [aHR] 1.9, 95% CI 1.0–3.6) and an etiology of post–intraventricular hemorrhage secondary to prematurity (aHR 2.0, 95% CI 1.1–3.6) were the only two independent predictors of ETV+CPC failure. Specific subgroups of ages within etiology categories were identified as having higher ETV+CPC success rates. Although training led to more frequent use of the flexible scope (p < 0.001) and higher rates of complete (> 90%) CPC (p < 0.001), training itself was not independently associated (aHR 1.1, 95% CI 0.7–1.8; p = 0.63) with ETV+CPC success.CONCLUSIONSThis is the largest prospective multicenter North American study to date examining ETV+CPC. Formal ETV+CPC training was not found to be associated with improved procedure outcomes. Specific subgroups of ages within specific hydrocephalus etiologies were identified that may preferentially benefit from ETV+CPC.

Objectives: The COVID-19 pandemic resulted in adaptations to pediatric resuscitation systems of care. The objective of this study was to determine the temporal association between the pandemic and pediatric in-hospital cardiac arrest (IHCA) process of care metrics, cardiopulmonary resuscitation (cardiopulmonary resuscitation) quality, and patient outcomes. Design: Multicenter retrospective analysis of a dataset comprising observations of IHCA outcomes pre pandemic (March 1, 2019 to February 29, 2020) versus pandemic (March 1, 2020 to February 28, 2021). Setting: Data source was the ICU-RESUScitation Project (“ICU-RESUS;” NCT028374497), a prospective, multicenter, cluster randomized interventional trial. Patients: Children (≤ 18 yr) who received cardiopulmonary resuscitation while admitted to the ICU and were enrolled in ICU-RESUS. Interventions: None. Measurements and Main Results: Among 429 IHCAs meeting inclusion criteria, occurrence during the pandemic period was associated with higher frequency of hypotension as the immediate cause of arrest. Cardiac arrest physiology, cardiopulmonary resuscitation quality metrics, and postarrest physiologic and quality of care metrics were similar between the two periods. Survival with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1–3 or unchanged from baseline) occurred in 102 of 195 subjects (52%) during the pandemic compared with 140 of 234 (60%) pre pandemic ( p = 0.12). Among survivors, occurrence of IHCA during the pandemic period was associated with a greater increase in Functional Status Scale (FSS) (i.e., worsening) from baseline (1 [0–3] vs 0 [0–2]; p = 0.01). After adjustment for confounders, IHCA survival during the pandemic period was associated with a greater increase in FSS from baseline (+1.19 [95% CI, 0.35–2.04] FSS points; p = 0.006) and higher odds of a new FSS-defined morbidity (adjusted odds ratio, 1.88 [95% CI, 1.03–3.46]; p = 0.04). Conclusions: Using the ICU-RESUS dataset, we found that relative to the year prior, pediatric IHCA during the first year of the COVID-19 pandemic was associated with greater worsening of functional status and higher odds of new functional morbidity among survivors.

ObjectiveTo identify candidate biomarkers associated with neuromyelitis optica spectrum disorder (NMOSD) using high-throughput technologies that broadly assay the concentrations of serum analytes and frequencies of immune cell subsets.MethodsSera, peripheral blood mononuclear cells (PBMCs), and matched clinical data from participants with NMOSD and healthy controls (HCs) were obtained from the Collaborative International Research in Clinical and Longitudinal Experience Study NMOSD biorepository. Flow cytometry panels were used to measure the frequencies of 39 T-cell, B-cell, regulatory T-cell, monocyte, natural killer (NK) cell, and dendritic cell subsets in unstimulated PBMCs. In parallel, multiplex proteomics assays were used to measure 46 serum cytokines and chemokines in 2 independent NMOSD and HC cohorts. Multivariable regression models were used to assess molecular and cellular profiles in NMOSD compared with HC.ResultsNMOSD samples had a lower frequency of CD16+CD56+ NK cells. Both serum cohorts and multivariable logistic regression revealed increased levels of B-cell activating factor associated with NMOSD. Interleukin 6, CCL22, and CCL3 were also elevated in 1 NMOSD cohort of the 2 analyzed. Multivariable linear regression of serum analyte levels revealed a correlation between CX3CL1 (fractalkine) levels and the number of days since most recent disease relapse.ConclusionsIntegrative analyses of cytokines, chemokines, and immune cells in participants with NMOSD and HCs provide congruence with previously identified biomarkers of NMOSD and highlight CD16+CD56+ NK cells and CX3CL1 as potential novel biomarker candidates.