Objectives: Rumination syndrome (RS) can be challenging to treat and data on treatment outcomes in children are limited. The objective of this study was to evaluate outcomes of children with RS treated with tailored outpatient and inpatient strategies. Methods: We performed a retrospective cohort study of children <18 years old with RS evaluated at our institution from 2018 to 2020. At our institution, we use a multidisciplinary, tiered approach to treatment based on presentation severity. Children with RS either undergo outpatient treatment program (OP) or participate in an intensive outpatient program (IOP) or an intensive inpatient program (IP). We reviewed baseline characteristics and assessed severity (including frequency of regurgitation/vomiting, route of nutrition, and weight loss) at baseline, at completion of treatment, and at a follow-up time point. Results: We included 171 children with RS (64% female, median age 13 years, interquartile range (IQR) 10-15), 123 of whom had post-treatment data after completing OP, IOP, or IP. At baseline, 66% of patients were vomiting daily and 40% were losing weight. After treatment, 72% of OP, 95% of IOP, and 96% of IP patients reported that symptoms were better or fully resolved compared to baseline. In all 3 treatment groups, patients were vomiting, losing weight, and skipping meals significantly less after treatment compared to baseline. At follow-up (median 5.3 months), 86% of IOP and 66% of IP patients had symptoms that remained better or resolved. Conclusions: RS can cause severe symptoms, impacting nutritional status and school participation. However, multidisciplinary care in a tiered approach leads to significant symptomatic improvement.
NRAS is a commonly mutated oncogene in melanoma and therapeutic targeting of NRAS has proven difficult. We characterized the expression and phenotypic functions of 5 recently discovered splice isoforms of NRAS in melanoma. Canonical NRAS (isoform-1) was expressed to the highest degree and its expression was significantly increased in melanoma metastases compared to primary lesions. Isoform-5 expression in metastases showed a significant, positive correlation with survival and tumors over-expressing isoform-5 had significantly decreased growth in a xenograft model. In contrast, over-expression of any isoform resulted in enhanced proliferation, and invasiveness was increased with over-expression of isoform-1 or isoform-2. Downstream signaling analysis indicated that the isoforms signaled differentially through the MAPK and PI3K pathways and A375 cells over-expressing isoform-2 or isoform-5 showed resistance to vemurafenib treatment in vitro. The NRAS isoforms appear to play varying roles in melanoma phenotype and could potentially serve as biomarkers for therapeutic response and disease prognosis.
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