Osteosarcoma has a poor prognosis due to chemo-resistance and/or metastases. Increasing evidence shows that long non-coding RNAs (lncRNAs) can play an important role in drug sensitivity and cancer metastasis. Using osteosarcoma cell lines, we identified a positive correlation between the expression of a lncRNA and ANRIL, and resistance to two of the three standard-of-care agents for treating osteosarcoma—cisplatin and doxorubicin. To confirm the potential role of ANRIL in chemosensitivity, we independently inhibited and over-expressed ANRIL in osteosarcoma cell lines followed by treatment with either cisplatin or doxorubicin. Knocking-down ANRIL in SAOS2 resulted in a significant increase in cellular sensitivity to both cisplatin and doxorubicin, while the over-expression of ANRIL in both HOS and U2OS cells led to an increased resistance to both agents. To investigate the clinical significance of ANRIL in osteosarcoma, we assessed ANRIL expression in relation to clinical phenotypes using the osteosarcoma data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset. Higher ANRIL expression was significantly associated with increased rates of metastases at diagnosis and death and was a significant predictor of reduced overall survival rate. Collectively, our results suggest that the lncRNA ANRIL can be a chemosensitivity and prognosis biomarker in osteosarcoma. Furthermore, reducing ANRIL expression may be a therapeutic strategy to overcome current standard-of-care treatment resistance.

Eltrombopag is approved for the treatment of chronic immune thrombocytopenia purpura (ITP) in pediatric patients 1 year and older who have demonstrated an insufficient response to corticosteroids and intravenous immunoglobulin. We present the case of a 2-year-old boy with chronic immune thrombocytopenia purpura who developed life-threatening adverse effects of acute liver failure, metabolic acidosis and encephalopathy with standard drug dosing. To our knowledge, this is the first case of eltrombopag-induced hepatic encephalopathy highlighting the critical need for prescribers to exercise caution when prescribing eltrombopag in the pediatric setting.

Coronavirus disease 2019 (COVID-19) infection causes a variety of extrapulmonary complications in pediatric patients. Multisystem inflammatory syndrome and hemophagocytic lymphohistiocytosis (HLH) are related to hypercytokinemia in COVID-19 patients. HLH is a disorder of exaggerated inflammation resulting in a cytokine storm and unrestricted hemophagocytosis. HLH can be primary (familial) or secondary (acquired). Secondary HLH (sHLH) can occur in patients with rheumatologic, oncologic, or infectious diseases. The link between COVID-19 and HLH has been reported in pediatric patients. Here we report a case of a pediatric patient who developed refractory sHLH secondary to COVID-19 infection and required a hematopoietic cell transplant for the cure.