Agricultural exposures and risk of childhood neuroblastoma: a systematic review and meta-analysis.

While neuroblastoma accounts for an estimated 8% of childhood cancers, it causes about 15% of childhood cancer deaths in the United States. The role of agricultural exposures in the development of neuroblastoma is unclear. We conducted a systematic review and meta-analysis of studies examining the relationship between agricultural exposures and neuroblastoma. MEDLINE, EMBASE, Scopus, and Google Scholar were searched in February 2022, identifying 742 publications. Seventeen articles met the inclusion criteria; all were published between 1985 and 2020 and included 14 case-control, one cross-sectional, and two cohort studies. Random and fixed effects models were used to calculate summary odds ratios (sORs) and 95% confidence intervals (CIs). An increased odds of developing neuroblastoma with parental exposure to any pesticides (sOR = 1.25, 95% CI: 1.03-1.48; 4 studies), insecticides (sOR = 1.55, 95% CI: 1.19-1.91; 3 studies), and residential exposure to crops/vegetables (sOR = 1.04, 95% CI: 1.01-1.06; 2 studies) was seen. Heterogeneity was low in all analyses, and no publication bias was evident. No significant associations were found with agricultural occupations, herbicides, and agricultural dusts. The studies were limited by exposure measurements and small sample sizes. Further studies are needed to explore mechanisms in the development of neuroblastoma in children with parental agricultural exposures, especially pesticides, and to improve methods of measuring agricultural-related exposures.

Hemophagocytic lymphohistocytosis in trisomy 21: successful treatment with interferon inhibition.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation primarily driven by the cytokine interferon gamma. It can be either a genetic or acquired disorder associated with infection, malignancy, and rheumatologic disorders. Trisomy 21 can express a wide range of phenotypes which include immune dysregulation and shares inherent pathophysiology with a group of disorders termed interferonopathies. Knowledge of this overlap in seemingly unrelated conditions could provide a basis for future research, and most importantly, alternative therapeutic interventions in acute life threatening clinical scenarios. Herein, we describe two patients with trisomy 21 presenting with HLH that was refractory to conventional treatment. Both patients were successfully managed with novel interventions targeting the interferon pathway. CASE PRESENTATION: We describe a 17-month-old male and 15-month-old female with trisomy 21 presenting with a myriad of signs and symptoms including fever, rash, cytopenias, and hyperferritinemia, both ultimately diagnosed with HLH. Each had relapsing, refractory HLH over time requiring several admissions to the hospital receiving conventional high dose corticosteroids and interleukin-1 inhibition therapy. Successful steroid-free remission was achieved after targeting interferon inhibition with emapalumab induction followed by long-term maintenance on baricitinib. CONCLUSION: To our knowledge, these are the first reported cases of relapsed, refractory HLH in patients with trisomy 21 successfully treated with emapalumab and transitioned to a steroid-sparing regimen with oral baricitinib for maintenance therapy. Trisomy 21 autoimmunity and HLH are both thought to be driven by interferon gamma. Targeting therapy toward interferon signaling in both HLH and autoimmunity in trisomy 21 may have potential therapeutic benefits. Further investigation is needed to determine if trisomy 21 may predispose to the development of HLH given this common pathway.

Effect of physical activity on fatigue in childhood cancer survivors: a systematic review.

PURPOSE: Many children, adolescents, and young adult survivors of childhood cancer experience fatigue following cancer treatment. Physical activity has been shown to be effective in improving cancer-related fatigue in adult survivors, but there is a lack of evidence on its effect in childhood cancer survivors. In addition, there are no guidelines for treatment of fatigue in childhood cancer survivors. The purpose of this study was to examine the existing literature on the effect of physical activity on fatigue in children, adolescents, and young adult survivors of childhood cancer. METHODS: We conducted a systematic review to examine the effect of physical activity on fatigue in children, adolescents, and young adult survivors of childhood cancer. RESULTS: Nine studies were included. Most of the studies included reported an increase in physical activity and a decline in fatigue in the target patient population. Interpretation of these findings is limited due to small sample sizes, inadequate length of follow-up, and variability among reviewed studies. Quantitative analysis was not conducted due to significant variability in both the type of physical activity implemented and in the measurement of fatigue. CONCLUSIONS: Further research, with a larger sample size and consistency in both physical activity interventions and measurement of fatigue, is needed to add greater precision and confidence in the effect of physical activity on fatigue in childhood cancer survivors. Results of this research will help guide future recommendations on physical activity for the treatment of cancer-related fatigue in children, adolescents, and young adult survivors of childhood cancer.