The role of hypoxia and inflammation in the regulation of iron metabolism and erythropoiesis in COVID-19: The IRONCOVID study.

Coronavirus Disease (COVID-19) can be considered as a human pathological model of inflammation combined with hypoxia. In this setting, both erythropoiesis and iron metabolism appear to be profoundly affected by inflammatory and hypoxic stimuli, which act in the opposite direction on hepcidin regulation. The impact of low blood oxygen levels on erythropoiesis and iron metabolism in the context of human hypoxic disease (e.g., pneumonia) has not been fully elucidated. This multicentric observational study was aimed at investigating the prevalence of anemia, the alterations of iron homeostasis, and the relationship between inflammation, hypoxia, and erythropoietic parameters in a cohort of 481 COVID-19 patients admitted both to medical wards and intensive care units (ICU). Data were collected on admission and after 7 days of hospitalization. On admission, nearly half of the patients were anemic, displaying mild-to-moderate anemia. We found that hepcidin levels were increased during the whole period of observation. The patients with a higher burden of disease (i.e., those who needed intensive care treatment or had a more severe degree of hypoxia) showed lower hepcidin levels, despite having a more marked inflammatory pattern. Erythropoietin (EPO) levels were also lower in the ICU group on admission. After 7 days, EPO levels rose in the ICU group while they remained stable in the non-ICU group, reflecting that the initial hypoxic stimulus was stronger in the first group. These findings strengthen the hypothesis that, at least in the early phases, hypoxia-driven stimuli prevail over inflammation in the regulation of hepcidin and, finally, of erythropoiesis.

Prospective evaluation of metabolic syndrome and its features in a single-center series of hematopoietic stem cell transplantation recipients.

Available studies on metabolic syndrome (MS) after hematopoietic stem cell transplantation (HSCT) are retrospective with heterogeneous inclusion criteria, and little is known about the early post-transplant phase. In our prospective study, clinical and laboratory data were collected in 100 HSCT recipients, 48 allogeneic and 52 autologous, at baseline, at + 30, + 100 and + 360 days. At baseline, MS was observed in 24 patients, significantly associated with insulin resistance and leptin on multivariate analysis. At + 30, the diagnosis of MS was confirmed in 43 patients, significantly related to insulin resistance and allogeneic transplants. If the whole series was considered, patients with MS had significantly higher mortality from any cause. The baseline presence of any MS feature was a predictor of + 30 MS. Isolated occurrences of MS features were related to hyperleptinemia and hyperinsulinemia, except in the case of low HDL cholesterol, linked to adiponectin and resistin. Our data confirm that patients undergoing HSCT have a high prevalence of MS, with hyperleptinemia playing a major role. The early peak of new MS cases is primarily attributable to insulin resistance, notably but not exclusively immunosuppression-induced; the subsequent long-term increase in MS cases may be an effect of persistent adipokine imbalance.

Anemia management and transfusion strategy in internal medicine units: Less is more.

Blood transfusion is one of the most overused procedures, especially in elderly patients. Despite the current transfusion guidelines recommending a restrictive transfusion strategy in stable patients, the clinical practice varies according to physicians' experience and implementation of patient blood management. This study aimed to evaluate the anemia management and transfusion strategy in anemic elderly hospitalized and the impact of an educational program. We enrolled ≥ 65-year-old patients who presented or developed anemia during admission to a tertiary hospital's internal medicine and geriatric units. Patients with onco-hematological disorders, hemoglobinopathies and active bleeding were excluded. In the first phase, anemia management was monitored. In the second phase, the six participating units were divided into two groups and two arms: Educational (Edu) and non-educational (NE). During this phase, physicians in the Edu arm underwent an educational program for the appropriate use of transfusion and anemia management. In the third phase, anemia management was monitored. Comorbidities, demographic and hematological characteristics were similar in all phases and arms. The percentages of transfused patients during phase 1 were 27.7% in NE and 18.5% in the Edu arm. During phase 3, it decreased to 21.4% in the NE and 13.6% in the Edu arm. Hemoglobin levels at discharge and after 30 days were higher in the Edu group despite reduced use of blood transfusion. In conclusion, a more restrictive strategy was comparable or superior to the more liberal one in terms of clinical outcomes, with the advantage of saving red blood cell units and reducing related side effects.

Subclinical cerebrovascular disease in NAFLD without overt risk factors for atherosclerosis.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease is recognized not only as part of the metabolic syndrome but also as an independent predictor of cardiovascular disease. METHODS: In this study, NMR spectroscopy method, together with perfusion techniques, was used to detect subclinical brain vascular damage in subjects with NAFLD without overt atherosclerosis risk factors (i.e. hypertension, diabetes, hypercholesterolemia, obesity). RESULTS: The results suggest that subjects with histologically proven NAFLD have a reduced cerebral perfusion (CBFr) confined to limited brain areas, i.e., left semioval center and posterior cingulate cortex. No statistically significant differences in CBFr values were found, dividing the NAFLD cohort into subgroups, considering NAS score, presence/absence of NASH/fibrosis, and degree of steatosis. CONCLUSIONS: Our data suggest that NAFLD per se may be involved in cerebral atherosclerotic disease. It will be interesting to draw longitudinal studies to determine whether these changes could evolve in more serious cerebral injury.