Improving Infant Hydrocephalus Outcomes in Uganda: A Longitudinal Prospective Study Protocol for Predicting Developmental Outcomes and Identifying Patients at Risk for Early Treatment Failure after ETV/CPC

Infant hydrocephalus poses a severe global health burden; 80% of cases occur in the developing world where patients have limited access to neurosurgical care. Surgical treatment combining endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC), first practiced at CURE Children’s Hospital of Uganda (CCHU), is as effective as standard ventriculoperitoneal shunt (VPS) placement while requiring fewer resources and less post-operative care. Although treatment focuses on controlling ventricle size, this has little association with treatment failure or long-term outcome. This study aims to monitor the progression of hydrocephalus and treatment response, and investigate the association between cerebral physiology, brain growth, and neurodevelopmental outcomes following surgery. We will enroll 300 infants admitted to CCHU for treatment. All patients will receive pre/post-operative measurements of cerebral tissue oxygenation (SO2), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO2) using frequency-domain near-infrared combined with diffuse correlation spectroscopies (FDNIRS-DCS). Infants will also receive brain imaging, to monitor tissue/ventricle volume, and neurodevelopmental assessments until two years of age. This study will provide a foundation for implementing cerebral physiological monitoring to establish evidence-based guidelines for hydrocephalus treatment. This paper outlines the protocol, clinical workflow, data management, and analysis plan of this international, multi-center trial.

Efficacy and Safety of Selumetinib in Pediatric Patients With Neurofibromatosis Type 1: A Systematic Review and Meta-analysis

Background and Objectives:Although the recent approval of selumetinib is expected to transform the management of children with Neurofibromatosis type 1 (NF1), particularly those with symptomatic and inoperable PN, no systematic review has summarized their efficacy and safety based on the latest studies. This study was conducted to systematically evaluate the efficacy and safety of selumetinib in children with NF1Methods:Original articles reporting the efficacy and safety of selumetinib in patients with NF1 were identified in PubMed and EMBASE up to January 28, 2021. The pooled objective response rates (ORRs) and disease control rates (DCRs) were calculated using the DerSimonian–Laird method based on random-effects modeling. The pooled proportion of adverse events (AEs) was also calculated. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system.Results:Five studies involving 126 patients were included in our analysis. The studies had a very low to moderate quality of the evidence. The pooled ORR was 73.8% (95% CI: 57.3–85.5%), and the DCR was 92.5% (95% CI: 66.5–98.7%). The two most common AEs were diarrhea, which had a pooled rate of 63.8% (95% CI, 52.9–73.4%) and an increase in creatine kinase levels, which had a pooled rate of 63.3% (95% CI, 35.6–84.3%).Discussion:Our results indicate that selumetinib is an effective and safe treatment for pediatric patients with symptomatic, inoperable plexiform neurofibromas. Further larger-scale randomized controlled studies are needed to confirm the long-term outcome of patients treated with this drug.

Coronary Artery Stenting Affects Wall Shear Stress Topological Skeleton

Despite the important advancements in the stent technology for the treatment of diseased coronary arteries, major complications still affect the post-operative long-term outcome. The stent-induced flow disturbances, and especially the altered wall shear stress (WSS) profile at the strut level, play an important role in the pathophysiological mechanisms leading to stent thrombosis (ST) and in-stent restenosis (ISR). In this context, the analysis of the WSS topological skeleton is gaining more and more interest by extending the current understanding of the association between local hemodynamics and vascular diseases. The present study aims to analyze the impact that a deployed coronary stent has on the WSS topological skeleton. Computational fluid dynamics simulations were performed in three stented human coronary artery geometries reconstructed from clinical images. The selected cases presented stents with different designs (i.e., two contemporary drug eluting stents and one bioresorbable scaffold) and included regions with stent malapposition or overlapping. A recently proposed Eulerian-based approach was applied to analyze the WSS topological skeleton features. The results highlighted that the presence of single or multiple stents within a coronary artery markedly impacts the WSS topological skeleton. In particular, repetitive patterns of WSS divergence were observed at the luminal surface, highlighting a WSS contraction action proximal to the struts and a WSS expansion action distal to the struts. This WSS action pattern was independent from the stent design. In conclusions, these findings could contribute to a deeper understanding of the hemodynamic-driven processes underlying ST and ISR.

Outcome of esophageal atresia: inborn versus outborn patients

Summary Esophageal atresia (EA) is a rare congenital disease which is usually not of the detected prenatally. Due to the lack of prenatal diagnosis, some newborns with EA are born outside of specialized centers. Nevertheless, centralized care of EA has been proposed, even if a clear volume–outcome association in EA management remains unconfirmed. Furthermore, whether outcomes differ between outborn and inborn patients with EA has not been systematically investigated. Therefore, this single-center, retrospective study aimed to investigate EA management and outcomes with a special focus on inborn versus outborn patients. The following data were extracted from the medical records of infants with EA from 2009 to 2019: EA type, associated anomalies, complications, and long-term outcome. Patients were allocated into inborn and outborn groups. Altogether, 57 patients were included. Five patients were excluded (referral before surgery, loss of data, death before surgery [n = 1], and incorrect diagnosis [diverticulum, n = 1]). Among all patients, the overall survival rate was 96%, with no mortalities among outborn patients. The overall hospitalization period was shorter for outborn patients. The median follow-up durations were 3.8 years and 3.2 years for inborn and outborn patients, respectively. Overall, 15% of patients underwent delayed primary anastomosis (long-gap atresia [n = 4] and other reasons [n = 4]). Early complications included three anastomotic leakages and one post-operative fistula; 28% of patients developed strictures, which required dilatation, and 38% of patients showed relevant gastroesophageal reflux, which required fundoplication, without any differences between the groups. The two groups had comparable low mortality and expected high morbidity with no significant differences in outcome. The outborn group showed nonsignificant trends toward lower morbidity and shorter hospitalization periods, which might be explained by the overall better clinical status.