Amniotic fluid-derived stem cell potential for therapeutic and surgical use: A review of the literature.

OBJECTIVE: Spina bifida is a debilitating neutral tube defect affecting many infants. The impact and severity of spina bifida depends on whether the patient exhibits a closed defect, spina bifida occulta, or an open defect, spina bifida aperta. Patients with spina bifida have physical and mental disabilities which merit further research into less invasive, more successful treatments. In addition to serving as protection for the growing fetus and facilitating nutrient exchange, amniotic fluid (AF) is a rich source of a mixed population of stem cells. As such, in vitro culture of AF-derived stem cells has shown promise among therapeutic and surgical applications. We present a critical evaluation of the current preclinical efforts, amniotic fluid-derived stem cell (AFSC) culture process, and the subsequent therapeutic application, with a focus on improvements for spina bifida outcomes in the pediatric patient population. METHOD: An evidence - based literature review to investigate the current literature surrounding AFSC culture and use, with an emphasis on the benefits for spina bifida treatment. RESULTS: 47 literature sources from PubMed and three studies from ClinicalTrials.gov. CONCLUSION: This review synthesizes the current literature, which shows promising data on AFSC pluripotency, as well as successful in utero coverage from AFSC - supported environments in a multitude of animal models.

Sucrase-isomaltase Gene Variants in Patients With Abnormal Sucrase Activity and Functional Gastrointestinal Disorders.

OBJECTIVES: The aim of the study was to determine prevalence and characterize sucrase-isomaltase (SI) gene variants of congenital sucrase-isomaltase deficiency in non-Hispanic white pediatric and young adult patients with functional gastrointestinal disorders (FGIDs), and abnormal sucrase activity on histologically normal duodenal biopsy. METHODS: Clinical symptoms and disaccharidase activities data were collected for an abnormal (low) sucrase (≤25.8 U, n = 125) activity group, and 2 normal sucrase activity groups with moderate (≥25.8-≤55 U, n = 250) and high (>55 U, n = 250) sucrase activities. SI gene variants were detected by next-generation sequencing of DNA from formalin-fixed paraffin-embedded tissues of these patients. FGIDs symptoms based on Rome IV criteria and subsequent clinical management of abnormal sucrase activity cases with pathogenic SI gene variants were analyzed. RESULTS: Thirteen SI gene variants were found to be significantly higher in abnormal sucrase cases with FGIDs symptoms (36/125, 29%; 71% did not have a pathogenic variant) compared to moderate normal (16/250, 6.4%, P < 0.001) or high normal (5/250, 2.0%, P < 0.001) sucrase groups. Clinical management data were available in 26 of abnormal sucrase cases, and only 10 (38%) were correctly diagnosed and managed by the clinicians. Concomitant lactase deficiency (24%; 23/97) and pan-disaccharidase deficiency (25%; 13/51) were found in the abnormal sucrase group. CONCLUSIONS: Heterozygous and compound heterozygous mutations in the SI gene were more prevalent in cases with abnormal sucrase activity presenting with FGIDs, and normal histopathology. This suggests heterozygous pathogenic variants of congenital sucrase-isomaltase deficiency may present as FGIDs. Concomitant lactase or pan-disaccharidase deficiencies were common in abnormal sucrase cases with SI gene variants.

Fibroblast growth factor receptor 1 gene mutation as a potential risk factor for spontaneous intracranial hemorrhage in pediatric low-grade glioma patients.

Background: Fibroblast growth factor receptor 1 (FGFR1) mutations have been associated with poorer prognoses in pediatric central nervous system tumor patients. A recent study highlighted a link between FGFR1 mutations and spontaneous intracranial hemorrhage (ICH), demonstrating that all patients with an FGFR1 alteration experienced hemorrhage at some point during their course of treatment. Methods: The current study examined 50 out of 67 pediatric patients with low-grade gliomas (LGGs) who had genomic testing between 2011 and 2022 at our institution to determine whether a correlation exists between FGFR1 mutations and spontaneous ICH. Results: We found that of the 50 patients with genomic data, 7 (14%) experienced ICH, and an additional spontaneous hemorrhage was recorded; however, no genomic testing was performed for this case. Five of the seven patients (71.4%) had an FGFR1 modification. In our patient population, 6 expressed a detectable FGFR1 mutation (66.7% [4/6] had N546K alteration, 16.7% [1/6] FGFR1 exons duplication, and 16.7% [1/6] had a variant of unknown significance [VUS]). The patient with the FGFR1 VUS had no reported spontaneous hemorrhage. Statistical analysis found a significant association between FGFR1 and spontaneous intracranial hemorrhage (P-value = < .0001). In the patient population, all cases of PTPN11 alterations (n = 3) co-occurred with FGFR1 mutations. Conclusions: Our case series highlights this link between the FGFR1 mutation and spontaneous intracranial hemorrhage in pediatric LGGs.

A multi-institutional pediatric dataset of clinical radiology MRIs by the Children's Brain Tumor Network.

Pediatric brain and spinal cancers remain the leading cause of cancer-related death in children. Advancements in clinical decision-support in pediatric neuro-oncology utilizing the wealth of radiology imaging data collected through standard care, however, has significantly lagged other domains. Such data is ripe for use with predictive analytics such as artificial intelligence (AI) methods, which require large datasets. To address this unmet need, we provide a multi-institutional, large-scale pediatric dataset of 23,101 multi-parametric MRI exams acquired through routine care for 1,526 brain tumor patients, as part of the Children's Brain Tumor Network. This includes longitudinal MRIs across various cancer diagnoses, with associated patient-level clinical information, digital pathology slides, as well as tissue genotype and omics data. To facilitate downstream analysis, treatment-naïve images for 370 subjects were processed and released through the NCI Childhood Cancer Data Initiative via the Cancer Data Service. Through ongoing efforts to continuously build these imaging repositories, our aim is to accelerate discovery and translational AI models with real-world data, to ultimately empower precision medicine for children.

The Gut Microbiome Alterations in Pediatric Patients with Functional Abdominal Pain Disorders.

In this prospective longitudinal study, we enrolled 54 healthy pediatric controls and 28 functional abdominal pain disorders (FAPDs) pediatric patients (mean age was 11 ± 2.58 years old). Fecal samples and symptom questionnaires were obtained from all participants over the course of the year. Clinical data assessment showed that FAPDs patients were more symptomatic than the control group. Microbiome analysis revealed that Phylum Bacteroidetes was higher in FAPDs compared to the control group (p < 0.05), while phylum Firmicutes was lower in FAPDs (p < 0.05). In addition, Verrucomicrobiota was higher in the control group than the FAPDs (p < 0.05). At the genus level the relative abundance of 72 bacterial taxa showed statistically significant differences between the two groups and at the school term levels. In the control group, Shannon diversity, Observed_species, and Simpson were higher than the FAPDs (p < 0.05), and beta diversity showed differences between the two groups (PERMANOVA = 2.38; p = 0.002) as well. Using linear discriminant analysis effect size (LEfSe), Enterobacteriaceae family and Megaspherae showed increased abundances in vacation term (LDA score > 2.0, LEfSe, p < 0.05). In the FAPDs group, the severity of symptoms (T-scores) correlated with 11 different taxa bacterial relative abundances using Pearson's correlation and linear regression analyses. Our data showed that gut microbiome is altered in FAPDs compared to the control. Differences in other metrics such as alpha- and beta diversity were also reported between the two groups. Correlation of the severity of the disease (T-scores) correlated with gut microbiome. Finally, our findings support the use of Faecalibacterium/Bacteroides ratio as a potential diagnostic biomarker for FAPDs.