Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study.

AIMS/HYPOTHESIS: This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19). METHODS: The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days. RESULTS: We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th-75th percentile) 28.4 (25.0-32.4) kg/m2. Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5-14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors. CONCLUSIONS/INTERPRETATION: In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04324736.

First report of bilateral pheochromocytoma in the clinical spectrum of HIF2A-related polycythemia-paraganglioma syndrome.

CONTEXT: Molecular genetic research has so far resulted in the identification of 10 well-characterized susceptibility genes for hereditary pheochromocytoma (PHEO) or paraganglioma (PGL). Recently, a new syndrome characterized by multiple PGLs and somatostatinomas associated with congenital polycythemia due to somatic mutations in HIF2A has been reported. OBJECTIVE: The aim of the study was to define the genetic defect in a new case of bilateral PHEO and multiple PGLs associated with congenital polycythemia. PATIENT: A female patient presented with neonatal polycythemia (treated by phlebotomies, 1 session approximately every 4 mo), mildly enlarged cerebral ventricles, and bilateral PHEO and multiple PGLs. There was no family history of any neuroendocrine tumor or polycythemia. Surgical removal of the tumors only temporarily normalized plasma erythropoietin (Epo) levels and discontinued phlebotomies. No germline mutations were initially detected in the SDHB, SDHC, SDHD, VHL, and PHD2 genes, known to be associated with polycythemia. The PHEOs presented with a typical noradrenergic biochemical phenotype. RESULTS: A heterozygous missense mutation (c.1589C>T) was identified in exon 12 of HIF2A, resulting in an alanine 530 substitution in the HIF-2α protein with valine (A530V). This somatic mutation was detected in the tissue from 1 PHEO and 1 PGL, with no HIF2A germline mutation found. This mutation led to stabilization of HIF-2α and hence a gain-of-function phenotype, as in previously published studies. CONCLUSION: This case represents the first association of a somatic HIF2A gain-of-function mutation with PHEO and congenital polycythemia, and it alerts physicians to perform proper genetic screening in patients presenting with multiple norepinephrine-producing PHEOs and polycythemia. This report also extends the previous findings of a new syndrome of only multiple PGLs, somatostatinomas, and polycythemia to multiple PHEOs.