Background. SARS-CoV-2 infection is heterogeneous in clinical presentation and disease evolution. To investigate whether immune response to the virus can be influenced by genetic factors, we compared HLA and AB0 frequencies in organ transplant recipients and waitlisted patients according to presence or absence of SARS-CoV-2 infection. Methods.A retrospective analysis was performed on an Italian cohort composed by transplanted and waitlisted patients in a January 2002 to March 2020 time frame. Data from this cohort were merged with the Italian registry of COVID + subjects, evaluating infection status of transplanted and waitlisted patients. A total of 56 304 cases were studied with the aim of comparing HLA and AB0 frequencies according to the presence (n = 265, COVID + ) or absence (n = 56 039, COVID -) of SARS-CoV-2 infection. Results. The cumulative incidence rate of COVID-19 was 0.112% in the Italian population and 0.462% in waitlisted/ transplanted patients (OR = 4.2; 95% CI, 3.7-4.7; P < 0.0001). HLA-DRB1*08 was more frequent in COVID + (9.7% and 5.2%: OR = 1.9, 95% CI, 1.2-3.1; P = 0.003; P c = 0.036). In COVID + patients, HLA-DRB1*08 was correlated to mortality (6.9% in living versus 17.5% in deceased: OR = 2.9, 95% CI, 1.15-7.21; P = 0.023). Peptide binding prediction analyses showed that these DRB1*08 alleles were unable to bind any of the viral peptides with high affinity. Finally, blood group A was more frequent in COVID + (45.5%) than COVIDpatients (39.0%; OR = 1.3; 95% CI, 1.02-1.66; P = 0.03). Conclusions. Although preliminary, these results suggest that HLA antigens may influence SARS-CoV-2 infection and clinical evolution of COVID-19 and confirm that blood group A individuals are at greater risk of infection, providing clues on the spread of the disease and indications about infection prognosis and vaccination strategies.

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BackgroundThe cardio-protective effects of flavonoids are still controversial; many studies referred to the benefits of specific foods, such as soy, cocoa, tea. A population-based cohort of middle-aged adults, coming from a semi-rural area where the consumption of those foods is almost negligible, was studied.AimsThe primary objective was establishing if flavonoid intake was inversely associated with the cardiovascular (CV) risk evaluated after 12-year follow-up; the associations between flavonoid intake and CV incidence and mortality and all-cause mortality were also evaluated.MethodsIn 2001–2003, a cohort of 1,658 individuals completed a validated food-frequency questionnaire. Anthropometric, laboratory measurements, medical history and the vital status were collected at baseline and during 2014. The CV risk was estimated with the Framingham risk score.ResultsIndividuals with the lowest tertile of flavonoid intake showed a worse metabolic pattern and less healthy lifestyle habits. The 2014 CV risk score and the increase in the risk score from baseline were significantly higher with the lowest intake of total and all subclasses of flavonoids, but isoflavones, in a multiple regression model. During follow-up, 125 CV events and 220 deaths (84 of which due to CV causes) occurred. CV non-fatal events were less frequent in individuals with higher flavonoid intake (HR = 0.64; 95%CI 0.42–1.00 and HR = 0.46; 95%CI 0.28–0.75 for the second and third tertiles, respectively) in Cox-regression models, after multiple adjustments. All subclasses of flavonoids, but flavones and isoflavones, were inversely correlated with incident CV events, with HRs ranging from 0.42 (flavan-3-ols) to 0.56 (anthocyanidins). Being in the third tertile of flavan-3-ols (HR = 0.68; 95% CI 0.48–0.96), anthocyanidins (HR = 0.66; 95% CI 0.46–0.95) and flavanones (HR = 0.59; 95% CI 0.40–0.85) was inversely associated with all-cause mortality. Total and subclasses of flavonoids were not significantly associated with the risk of CV mortality.ConclusionsFlavonoid intake was inversely associated with CV risk, CV non-fatal events and all-cause mortality in a cohort with a low consumption of soy, tea and cocoa, which are typically viewed as the foods responsible for flavonoid-related benefits.

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We conducted the first-in-human study of 18 F-fluoroethyl triazole [Tyr 3 ] octreotate ( 18 F-FET-βAG-TOCA) in patients with neuroendocrine tumors (NETs) to evaluate biodistribution, dosimetry, and safety. Despite advances in clinical imaging, detection and quantification of NET activity remains a challenge, with no universally accepted imaging standard. Methods: Nine patients were enrolled. Eight patients had sporadic NETs, and 1 had multiple endocrine neoplasia type 1 syndrome. Patients received 137-163 MBq (mean ± SD, 155.7 ± 8 MBq) of 18 F-FET-βAG-TOCA. Safety data were obtained during and 24 h after radioligand administration. Patients underwent detailed wholebody PET/CT multibed scanning over 4 h with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated with OLINDA 1.1. Results: All patients tolerated 18 F-FET-βAG-TOCA with no adverse events. Over 60% parent radioligand was present in plasma at 60 min. High tumor (primary and metastases)-to-background contrast images were observed. Physiologic distribution was seen in the pituitary, salivary glands, thyroid, and spleen, with low background distribution in the liver, an organ in which metastases commonly occur. The organs receiving highest absorbed dose were the gallbladder, spleen, stomach, liver, kidneys, and bladder. The calculated effective dose over all subjects (mean ± SD) was 0.029 ± 0.004 mSv/MBq. Conclusion: The favorable safety, imaging, and dosimetric profile makes 18 F-FET-βAG-TOCA a promising candidate radioligand for staging and management of NETs. Clinical studies in an expanded cohort are ongoing to clinically qualify this agent.