Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day-17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered

Book Review: Working towards Equity by Dustin Galer

Book Review of Working towards Equity: Disability Rights Activism and Employment in Late Twentieth-Century Canada. By Dustin Galer. University of Toronto Press, 2018. 309 pages. ISBN 97814875013

Gestational Vitamin D3 Supplementation and Sun Exposure Significantly Influence Cord Blood Vitamin D Status and 3-Epi-25-Hydroxyvitamin D3 Levels in Term Newborns

Background and aims. High prevalence of hypovitaminosis D is worldwide reported among pregnant women and newborns. We assessed cord blood 25-hydroxyvitamin D3 [25(OH)D3] and 3-epi-25-hydroxyvitamin D3 (C3-epimer) levels in relation to assumed maternal risk factors for hypovitaminosis D.Methods. We enrolled 246 term newborns during summer. 175/246 mothers were supplemented with a daily variable dosage (200-1,000 IU) of vitamin D3 during pregnancy. Cord blood 25(OH)D3 and C3-epimer concentrations were analyzed by high performance liquid chromatography tandem mass spectrometry. Results. Median cord blood 25(OH)D3 levels were 23.4 ng/mL (16.9-28.8). The prevalences of vitamin D sufficiency (≥30.0 ng/mL), insufficiency (20.0-29.9 ng/mL), and deficiency (<20.0 ng/mL) were 19.9%, 45.9%, and 34.2%, respectively. Non-Caucasian ethnicity, housewife life, weight excess, negligible sun exposure and absent gestational vitamin D supplementation were associated with both reduced cord blood 25(OH)D3 and C3-epimer levels. C3-epimer/25(OH)D3 ratio was 15.1% (13.6%-18.4%) and it was not related to any of the assumed risk factors for hypovitaminosis D. Conclusions. Cord blood vitamin D deficiency was common, particularly in newborns from mother not receiving vitamin D supplementation and with poor sun exposure. C3-epimer levels were high in cord blood, causing possible misclassification of vitamin D status if they were not distinguished from 25(OH)D3 concentration

Epidemiology, Clinical Features and Prognostic Factors of Pediatric SARS-CoV-2 Infection: Results From an Italian Multicenter Study

Background: Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear and optimal treatment is debated. The objective of our study was to investigate epidemiological, clinical and therapeutic characteristics of pediatric SARS-CoV-2 infection, focusing on risk factors for complicated and critical disease. Methods: The present multicenter Italian study was promoted by the Italian Society of Pediatric Infectious Diseases, involving both pediatric hospitals and general pediatricians/family doctors. All subjects under 18 years of age with documented SARS-CoV-2 infection and referred to the coordinating center were enrolled from March 2020. Results: As of 15 September 2020, 759 children were enrolled (median age 7.2 years, IQR 1.4; 12.4). Among the 688 symptomatic children, fever was the most common symptom (81.9%). Barely 47% of children were hospitalized for COVID-19. Age was inversely related to hospital admission (p < 0.01) and linearly to length of stay (p = 0.014). One hundred forty-nine children (19.6%) developed complications. Comorbidities were risk factors for complications (p < 0.001). Viral coinfections, underlying clinical conditions, age 5-9 years and lymphopenia were statistically related to ICU admission (p < 0.05). Conclusions: Complications of COVID-19 in children are related to comorbidities and increase with age. Viral co-infections are additional risk factors for disease progression and multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) for ICU admission

Dietary intake and major food sources of polyphenols in people with type 2 diabetes: The TOSCA.IT Study

none200nononeVitale, M.; Masulli, M.; Rivellese, A.A.; Bonora, E.; Cappellini, F.; Nicolucci, A.; Squatrito, S.; Antenucci, D.; Barrea, A.; Bianchi, C.; Bianchini, F.; Fontana, L.; Fornengo, P.; Giorgino, F.; Gnasso, A.; Mannucci, E.; Mazzotti, A.; Nappo, R.; Palena, A.P.; Pata, P.; Perriello, G.; Potenziani, S.; Radin, R.; Ricci, L.; Romeo, F.; Santini, C.; Scarponi, M.; Serra, R.; Timi, A.; Turco, A.A.; Vedovato, M.; Zavaroni, D.; Grioni, S.; Riccardi, G.; Vaccaro, O; Rivellese, Angela Albarosa; Cocozza, Sara; Auciello, Stefania; Turco, Anna Amelia; Bonora, Enzo; Cigolini, Massimo; Pichiri, Isabella; Brangani, Corinna; Tomasetto, Elena; Perriello, Gabriele; Timi, Alessia; Squatrito, Sebastiano; Sinagra, Tiziana; Longhitano, Sara; Tropea, Vanessa; Ballardini, Giorgio; Babini, Anna Carla; Ripani, Raffaella; Gregori, Giovanna; Dolci, Maria; Bruselli, Laura; Salutini, Isabella; Mori, Mary; Baccetti, Fabio; Lapolla, Annunziata; Sartore, Giovanni; Burlina, Silvia; Chilelli, Nino Cristiano; Buzzetti, Raffaella; Venditti, Chiara; Potenziani, Stella; Carlone, Angela; Galluzzo†, Aldo; Giordano, Carla; Torregrossa, Vittoria; Corsi, Laura; Cuneo, Giacomo; Corsi, Simona; Tizio, Biagio; Clemente, Gennaro; Citro, Giuseppe; Natale, Maria; Salvatore, Vita; Di Cianni, Graziano; Lacaria, Emilia; Russo, Laura; Iannarelli, Rossella; de Gregorio, Antonella; Sciarretta, Filomena; D’Andrea, Settimio; Montani, Valeria; Cannarsa, Emanuela; Dolcetti, Katia; Cordera, Renzo; Bonabello, Laura Affinito; Mazzucchelli, Chiara; Giorda, Carlo Bruno; Romeo, Francesco; Bonetto, Caterina; Antenucci, Daniela; Baldassarre, Maria Pompea Antonia; Iovine, Ciro; Nappo, Rossella; Ciano, Ornella; Dall’Aglio, Elisabetta; Mancastroppa, Giovanni; Grimaldi, Franco; Tonutti, Laura; Boemi, Massimo; D’Angelo, Federica; Leotta, Sergio; Fontana, Lucia; Lauro, Davide; Rinaldi, Maria Elena; Cignarelli, Mauro; la Macchia, Olga; Fariello, Stefania; Tomasi, Franco; Zamboni, Chiara; Dozio, Nicoletta; Trevisan, Roberto; Scaranna, Cristiana; Del Prato, Stefano; Miccoli, Roberto; Bianchi, Cristina; Garofolo, Monia; Pugliese, Giuseppe; Salvi, Laura; Rangel, Graziela; Vitale, Martina; Anichini, Roberto; Tedeschi, Anna; Corsini, Elisa; Cucinotta, Domenico; Di Benedetto, Antonino; Giunta, Loretta; Ruffo, Maria Concetta; Bossi, Antonio Carlo; Carpinter, Rita; Dotta, Francesco; Ceccarelli, Elena; Bartolo, Paolo Di; Caselli, Chiara; Luberto, Alessandra; Santini, Costanza; Mazzotti, Arianna; Calbucci, Giovanni; Consoli, Agostino; Ginestra, Federica; Calabrese, Maria; Zogheri, Alessia; Ricci, Lucia; Giorgino, Francesco; Laviola, Luigi; Ippolito, Claudia; Tarantino, Lucia; Avogaro, Angelo; Vedovato, Monica; Gnasso, Agostino; Carallo, Claudio; Scicchitano, Caterina; Zavaroni, Donatella; Livraga, Stefania; Perin, Paolo Cavallo; Forrnengo, Paolo; Prinzis, Tania; de Cosmo, Salvatore; Palena, Antonio Pio; Bacci, Simonetta; Mannucci, Edoardo; Lamanna, Caterina; Pata, Pietro; Lettina, Gabriele; Aiello, Antimo; Barrea, Angelina; Lalli, Carlo; Scarponi, Maura; Franzetti, Ivano; Radin, Raffaella; Serra, Rosalia; Petrachi, Francesca; Asprino, Vincenzo; Capra, Claudio; Cigolini, Massimo; Forte, Elisa; Potenziani, Stella; Reggiani, Giulio Marchesini; Forlani, Gabriele; Montesi, Luca; Mazzella, Natalia; Piatti, Pier Marco; Monti, Lucilla; Stuccillo, Michela; Auletta, Pasquale; Petraroli, Ettore; Capobianco, Giuseppe; Romano, Geremia; Cutolo, Michele; de Simone, Giosetta; Caiazzo, Gennaro; Nunziata, Peppe; Sorrentino, Susy; Amelia, Umberto; Calatola, Pasqualino; Capuano, GelsominaVitale, M.; Masulli, M.; Rivellese, A. A.; Bonora, Enzo; Cappellini, F.; Nicolucci, A.; Squatrito, S.; Antenucci, D.; Barrea, A.; Bianchi, C.; Bianchini, FRANCESCA ANTONIA; Fontana, L.; Fornengo, P.; Giorgino, FRANCESCO LIBERO; Gnasso, A.; Mannucci, E.; Mazzotti, Alfredo; Nappo, R.; Palena, A. P.; Pata, P.; Perriello, G.; Potenziani, S.; Radin, R.; Ricci, Laura; Romeo, Francesco; Santini, C.; Scarponi, M.; Serra, Roberto; Timi, A.; Turco, A. A.; Vedovato, M.; Zavaroni, D.; Grioni, S.; Riccardi, Giovanna; Vaccaro, O; Rivellese, Angela Albarosa; Cocozza, Sara; Auciello, Stefania; Turco, Anna Amelia; Bonora, Enzo; Cigolini, Massimo; Pichiri, Isabella; Brangani, Corinna; Tomasetto, Elena; Perriello, Gabriele; Timi, Alessia; Squatrito, Sebastiano; Sinagra, Tiziana; Longhitano, Sara; Tropea, Vanessa; Ballardini, Giorgio; Babini, Anna Carla; Ripani, Raffaella; Gregori, Giovanna; Dolci, Maria; Bruselli, Laura; Salutini, Isabella; Mori, Mary; Baccetti, Fabio; Lapolla, Annunziata; Sartore, Giovanni; Burlina, Silvia; Chilelli, NINO CRISTIANO; Buzzetti, Raffaella; Venditti, Chiara; Potenziani, Stella; Carlone, Angela; Galluzzo†, Aldo; Giordano, Carla; Torregrossa, Vittoria; Corsi, Laura; Cuneo, Giacomo; Corsi, Simona; Tizio, Biagio; Clemente, Gennaro; Citro, Giuseppe; Natale, Maria; Salvatore, Vita; Di Cianni, Graziano; Lacaria, Emilia; Russo, Laura; Iannarelli, Rossella; de Gregorio, Antonella; Sciarretta, Filomena; D’Andrea, Settimio; Montani, Valeria; Cannarsa, Emanuela; Dolcetti, Katia; Cordera, Renzo; Bonabello, Laura Affinito; Mazzucchelli, Chiara; Giorda, Carlo Bruno; Romeo, Francesco; Bonetto, Caterina; Antenucci, Daniela; Baldassarre, Maria Pompea Antonia; Iovine, Ciro; Nappo, Rossella; Ciano, Ornella; Dall’Aglio, Elisabetta; Mancastroppa, Giovanni; Grimaldi, Franco; Tonutti, Laura; Boemi, Massimo; D’Angelo, Federica; Leotta, Sergio; Fontana, Lucia; Lauro, Davide; Rinaldi, Maria Elena; Cignarelli, Mauro; la Macchia, Olga; Fariello, Stefania; Tomasi, Franco; Zamboni, Chiara; Dozio, Nicoletta; Trevisan, Roberto; Scaranna, Cristiana; Del Prato, Stefano; Miccoli, Roberto; Bianchi, Cristina; Garofolo, Monia; Pugliese, Giuseppe; Salvi, Laura; Rangel, Graziela; Vitale, Martina; Anichini, Roberto; Tedeschi, Anna; Corsini, Elisa; Cucinotta, Domenico; Di Benedetto, Antonino; Giunta, Loretta; Ruffo, Maria Concetta; Bossi, Antonio Carlo; Carpinter, Rita; Dotta, Francesco; Ceccarelli, Elena; Bartolo, Paolo Di; Caselli, Chiara; Luberto, Alessandra; Santini, Costanza; Mazzotti, Arianna; Calbucci, Giovanni; Consoli, Agostino; Ginestra, Federica; Calabrese, Maria; Zogheri, Alessia; Ricci, Lucia; Giorgino, FRANCESCO LIBERO; Laviola, Luigi; Ippolito, Claudia; Tarantino, Lucia; Avogaro, Angelo; Vedovato, Monica; Gnasso, Agostino; Carallo, Claudio; Scicchitano, Caterina; Zavaroni, Donatella; Livraga, Stefania; Perin, Paolo Cavallo; Forrnengo, Paolo; Prinzis, Tania; de Cosmo, Salvatore; Palena, Antonio Pio; Bacci, Simonetta; Mannucci, Edoardo; Lamanna, Caterina; Pata, Pietro; Lettina, Gabriele; Aiello, Antimo; Barrea, Angelina; Lalli, Carlo; Scarponi, Maura; Franzetti, Ivano; Radin, Raffaella; Serra, Rosalia; Petrachi, Francesca; Asprino, Vincenzo; Capra, Claudio; Cigolini, Massimo; Forte, Elisa; Potenziani, Stella; Reggiani, Giulio Marchesini; Forlani, Gabriele; Montesi, Luca; Mazzella, Natalia; Piatti, Pier Marco; Monti, Lucilla; Stuccillo, Michela; Auletta, Pasquale; Petraroli, Ettore; Capobianco, Giuseppe; Romano, Geremia; Cutolo, Michele; de Simone, Giosetta; Caiazzo, Gennaro; Nunziata, Peppe; Sorrentino, Susy; Amelia, Umberto; Calatola, Pasqualino; Capuano, Gelsomin

Dietary intake and major food sources of polyphenols in people with type 2 diabetes: The TOSCA.IT Study

Purpose: Proper evaluation of polyphenols intake at the population level is a necessary step in order to establish possible associations with health outcomes. Available data are limited, and so far no study has been performed in people with diabetes. The aim of this work was to document the intake of polyphenols and their major food sources in a cohort of people with type 2 diabetes and in socio-demographic subgroups. Methods: We studied 2573 men and women aged 50â\u80\u9375 years. Among others, anthropometry was measured by standard protocol and dietary habits were investigated by food frequency questionnaire (EPIC). The intake of polyphenols was evaluated using US Department of Agriculture and Phenol-Explorer databases. Results: The mean total polyphenol intake was 683.3 ± 5.8 mg/day. Non-alcoholic beverages represented the main food source of dietary polyphenols and provided 35.5% of total polyphenol intake, followed by fruits (23.0%), alcoholic beverages (14.0%), vegetables (12.4%), cereal products and tubers (4.6%), legumes (3.7%) and oils (2.1%); chocolate, cakes and nuts are negligible sources of polyphenols in this cohort. The two most important polyphenol classes contributing to the total intake were flavonoids (47.5%) and phenolic acids (47.4%). Polyphenol intake increased with age and education level and decreased with BMI; furthermore, in the northern regions of Italy, the polyphenol intake was slightly, but significantly higher than in the central or southern regions. Conclusions: The study documents for the first time the intake of polyphenols and their main food sources in people with diabetes using validated and complete databases of the polyphenol content of food. Compared with published data, collected in people without diabetes, these results suggest a lower intake and a different pattern of intake in people with diabetes

Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial

Background The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. Methods TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50\ue2\u80\u9375 years with type 2 diabetes inadequately controlled with metformin monotherapy (2\ue2\u80\u933 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15\ue2\u80\u9345 mg) or a sulfonylurea (5\ue2\u80\u9315 mg glibenclamide, 2\ue2\u80\u936 mg glimepiride, or 30\ue2\u80\u93120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. Findings Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57\uc2\ub73 months. The primary outcome occurred in 105 patients (1\uc2\ub75 per 100 person-years) who were given pioglitazone and 108 (1\uc2\ub75 per 100 person-years) who were given sulfonylureas (hazard ratio 0\uc2\ub796, 95% CI 0\uc2\ub774\ue2\u80\u931\uc2\ub726, p=0\uc2\ub779). Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group (148 [10%] vs 508 [34%], p&lt;0\uc2\ub70001). Moderate weight gain (less than 2 kg, on average) occurred in both groups. Rates of heart failure, bladder cancer, and fractures were not significantly different between treatment groups. Interpretation In this long-term, pragmatic trial, incidence of cardiovascular events was similar with sulfonylureas (mostly glimepiride and gliclazide) and pioglitazone as add-on treatments to metformin. Both of these widely available and affordable treatments are suitable options with respect to efficacy and adverse events, although pioglitazone was associated with fewer hypoglycaemia events. Funding Italian Medicines Agency, Diabete Ricerca, and Italian Diabetes Society

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field