Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C

Peri-operative Chemotherapy in Patients with Oesophageal and Gastro-oesophageal Junction Cancer – Three Years of Experience

Peri-operative chemotherapy has been found to benefit patients with oesophageal and gastro-oesophageal junction adenocarcinoma. This study’s aim was to evaluate the efficacy and tolerance of this treatment. The study included patients with carcinoma of the lower oesophagus and gastro-oesophageal junction in whom the disease was evaluated as potentially operable. Chemotherapy (CHT) consisted of three preoperative and three postoperative cycles of intravenous epirubicin and cisplatin on day 1 plus a continuous infusion of fluorouracil for 21 days (ECF) or oral capecitabine for 14 days (ECCap). Postoperative radio-chemotherapy (CRT) with fluorouracil or capecitabine after CHT was indicated in patients with two and more positive lymph nodes. Sixty-three patients started the treatment. Median follow-up was 32 months. Preoperative CHT was completed by 62 patients, 52 had surgery, 46 had radical resection, 25 patients had pN0 and 21 patient pN plus findings. Postoperative CHT was started in 39 (62%) patients and completed in 32 (51%). Ten (16%) patients had postoperative CRT. Adverse events of grade 3 and 4 were: neutropenia 17%, vomiting 8%, fatigue 5%, diarrhoea 3%. Reasons for omitting surgery in 11 (17%) patients were: progression in 7 patients, medically unfit in 3 patients, other in 1 patient. In the reporting period there were recurrences in 39 of all patients, in 7 locoregional only, in 10 distant plus locoregional, and in 19 distant metastases. Median survival was 24.1 months and 3-year survival rate was 42%. Peri-operative chemotherapy ECF/ECCap was feasible and well tolerated. Radical resection was performed in most patients