Early childhood-onset rumination syndrome is clinically distinct from adolescent-onset rumination syndrome.

OBJECTIVES: Rumination syndrome (RS) beginning in early childhood or infancy is understudied and challenging to treat. Our objective is to compare the characteristics and outcomes of early-onset (EO) and adolescent-onset (AO) patients with RS. METHODS: We conducted an ambidirectional cohort study of children diagnosed with RS at our institution. Patients were included in two groups: EO (RS symptom onset ≤5 years and diagnosis ≤12 years) and AO (onset >12 years). Patient characteristics, severity, and outcomes were compared between the groups. RESULTS: We included 49 EO and 52 AO RS patients. The median ages of symptom onset and diagnosis in EO were 3.5 and 6 years, respectively; AO, 14.5 and 15 years. EO RS had a slight male predominance while AO was predominantly female (p = 0.016). EO patients were more likely to have developmental delay (24% vs. 8%, p = 0.029) and less likely to have depression (0% vs. 23%, p < 0.001) or anxiety (14% vs. 40%, p = 0.004). At baseline, EO RS was less severe than AO RS: EO RS had greater regurgitation frequency (p < 0.001) but lower vomiting frequency (p = 0.001), resulting in less meal skipping (p < 0.001), reliance on tube feeding or parenteral nutrition (p < 0.001), and weight loss (p = 0.035). EO RS symptoms improved over time: at follow-up, patients had lower regurgitation (p < 0.001) and vomiting frequency (p < 0.001) compared to baseline. CONCLUSION: EO RS is clinically distinct from AO RS, with differences in sex distribution, comorbid conditions, and severity of initial presentation. The pathogenesis and natural history of EO RS may be distinct from that of AO RS.

Multidisciplinary Tiered Care Is Effective for Children and Adolescents With Rumination Syndrome.

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.

Neuroblastoma RAS viral oncogene homolog mRNA is differentially spliced to give five distinct isoforms: implications for melanoma therapy.

Neuroblastoma RAS viral oncogene homolog is a commonly mutated oncogene in melanoma, and therapeutic targeting of neuroblastoma RAS viral oncogene homolog has proven difficult. We characterized the expression and phenotypic functions of five recently discovered splice isoforms of neuroblastoma RAS viral oncogene homolog in melanoma. Canonical neuroblastoma RAS viral oncogene homolog (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 tumours 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 signalling analysis indicated that the isoforms signalled differentially through the mitogen-activated protein kinase and PI3K pathways and A375 cells over-expressing isoform-2 or isoform-5 showed resistance to vemurafenib treatment in vitro. The neuroblastoma RAS viral oncogene homolog isoforms appear to play varying roles in melanoma phenotype and could potentially serve as biomarkers for therapeutic response and disease prognosis.