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Aim: This review represents a joint effort of the Italian Societies of Cardiology (SIC) and Diabetes (SID) to define the state of the art in a field of great clinical and scientific interest which is experiencing a moment of major cultural advancements, the cardiovascular risk management in type 2 diabetes mellitus. Data synthesis: Consists of six chapters that examine various aspects of pathophysiology, diagnosis and therapy which in recent months have seen numerous scientific innovations and several clinical studies that require extensive sharing. Conclusions: The continuous evolution of our knowledge in this field confirms the great cultural vitality of these two cultural spheres, which requires, under the leadership of the scientific Societies, an ever greater and effective collaboration.

Background: Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are frequent and progressive conditions that share traditional risk factors: obesity, type 2 diabetes and hypertension. Aims: To evaluate whether an independent relationship exists between liver steatosis and fibrosis and different CKD phenotypes. Methods: Cross sectional study based on data from the 2017–18 cycle of the National Health and Nutrition Examination Survey. Vibration controlled transient elastography (VCTE) was performed in a US representative sample allowing the simultaneous assessment of liver steatosis (CAP: controlled attenuation parameter) and fibrosis (LSM: liver stiffness measurement) and their relationships with CKD phenotypes (albuminuria and reduced estimated glomerular filtration rate, eGFR). Results: 4746 adult participants had a complete VCTE exam. Prevalence of liver steatosis and significant fibrosis was 33.7% (95%CI: 30.9–36.6%) and 8.9% (95%CI: 7.5–10.5%), respectively. Logistic regression analysis showed that liver fibrosis, but not steatosis, was associated with albuminuria (OR 2.19, 95%CI: 1.49–3.20) and albuminuria or reduced eGFR (OR 2.18, 95%CI: 1.59–3.00) also when adjusted for age, sex, ethnicity, BMI, diabetes, blood pressure categories, glycated haemoglobin, use of renin-angiotensin-aldosterone system blockers and CAP. Conclusions: In the general US population liver fibrosis assessed using VCTE is associated with CKD, and in particular with the albuminuric phenotype, regardless of traditional risk factors.

CONTEXT: Laparoscopic sleeve gastrectomy (LSG) is a recognized effective procedure of bariatric surgery but a poor response in weight loss may still represent a clinical problem. To date there are no validated predictors useful to better perform patient selection.OBJECTIVE: to establish the association of baseline anthropometric, metabolic and psychologic features with the percent total (%TWL) and excess (%EWL) weight loss 12 months after surgery.DESIGN: retrospective longitudinal analysis of a set of data about obese attending the outpatients service of a single obesity center from June 2016 to June 2019.PATIENTS: 106 obese patients underwent LSG with pre-surgery evaluation and follow-up at 12 months after surgery.MAIN OUTCOME: weight loss 12 months after LSG.RESULTS: patients who achieved a %TWL higher than the observed median (≥34%) were younger, with a lower fasting plasma glucose and HbA1c, with a lower prevalence of hypertension and with a lower score in the impulsiveness scale, compared to the patients with a %TWL <34%. Similar findings were found when was considered %EWL. Multivariable stepwise regression analysis showed that younger age, lower impulsiveness, higher than normal urinary free cortisol and lower HbA1c were associates with higher %TWL, explaining about 31.5% of the outcome.CONCLUSION: metabolic and psychologic features at baseline were independently associated with weight loss and explained a non-negligible effect on the response to LSG. These data suggest that careful metabolic and psychologic profiling could help in sharper indications and personalized pre- and post-surgical follow-up protocols in candidates for LSG.

Background: Sodium glucose transporter 2 inhibitors (SGLT2-i) reduce renal and cardiovascular events in patients with type 2 diabetes (T2D) and their use is recommended by the 2020 KDIGO guidelines in patients with T2D and chronic kidney disease (CKD). The aim of this study is to estimate the proportion of patients with T2D and CKD in the US that should be treated with these agents for renal and cardiovascular protection. Methods: We conducted a retrospective analysis of 2005–2018 National Health and Nutrition Examination Survey (NHANES) data. We focused on participants with a prior diagnosis of diabetes or that met diagnostic criteria for diabetes during the survey, with the exclusion of probable type 1 diabetic patients. Inclusion criteria for completed and ongoing renal and cardiovascular outcome trials in patients with CKD were applied. Results: We estimated that 35.3% of patients with T2D in the US (projected to 8.96 million) should be treated with SGLT2-i according to the 2020 KDIGO guidelines. Moreover, 2.9–10.1% (projected to 0.75–2.55 million) met the inclusion criteria for dedicated kidney outcome trials, which were focused on a population of individuals with proteinuria. Conclusions: About a third of patients with T2D in the US should be treated with an SGLT2-i. While compelling evidence of renal protection is present for patients with proteinuria, all patients with CKD obtain a cardiovascular benefit with this class of drugs.

OBJECTIVE: Few studies investigated the role of different predictors of advanced liver fibrosis in unselected populations. Here, we estimate the prevalence of steatosis and fibrosis in the general United States population by means of transient elastography and evaluate the impact of blood pressure (BP) and diabetes on disease severity.METHODS: This is a cross-sectional study of United States adults participating in the 2017-2018 cycle of the National Health and Nutrition Examination Survey. Participants underwent a transient elastography examination, and liver steatosis and fibrosis were estimated through the controlled attenuation parameter (CAP) score and liver stiffness measurement (LSM), respectively.RESULTS: Four thousand, three hundred and seventy-one participants had reliable transient elastography and BP readings. Steatosis (CAP ≥ 248 dB/m), advanced fibrosis (LSM ≥ 9.6 kPa) and cirrhosis (LSM ≥ 13 kPa) were present in 56.9, 5.5 and 2.9% of participants, respectively. After controlling for potential confounders, risk of steatosis increased proportionally going from participants with optimal (reference) to those with normal [odds ratio (OR) 1.24, 95% confidence interval (CI) 0.83-1.86], high normal (OR 1.41, 95% CI 1.01-1.97) and elevated BP (OR 1.64, 95% CI 1.21-2.21), whereas no significant association was found between BP status and liver fibrosis. Conversely, presence of diabetes increased the risk of both steatosis (OR 2.15, 95% CI 1.49-3.11) and advanced fibrosis (OR 2.25, 95% CI 1.36-3.72).CONCLUSION: Liver steatosis and fibrosis are highly prevalent in the multiethnic United States adult population, raising concerns for future incidence of cirrhosis and its complications. BP status was associated with a progressively higher risk of steatosis, whereas obesity and diabetes were consistently associated with both steatosis and fibrosis.

Ruxolitinib is an anti-inflammatory drug that inhibits the Janus kinase-signal transducer (JAK-STAT) pathway on the surface of immune cells. The potential targeting of this pathway using JAK inhibitors is a promising approach in patients affected by coronavirus disease 2019 (COVID-19). Ruxolitinib was provided as a compassionate use in patients consecutively admitted to our institution for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. Inclusion criteria were oxygen saturation less than or equal to 92%, signs of interstitial pneumonia, and no need of mechanical ventilation. Patients received 5 mg b.i.d. of ruxolitinib for 15 days, data were collected at baseline and on days 4, 7, and 15 during treatment. Two main targets were identified, C-reactive protein (CRP) and PaO2/FiO2 ratio. In the 31 patients who received ruxolitinib, symptoms improved (dyspnea scale) on day 7 in 25 of 31 patients (80.6%); CRP decreased progressively from baseline (79.1 ± 73.4 mg/dl) to day 15 (18.6 ± 33.2, p = 0.022). In parallel with CRP, PO2/FiO2 ratio increased progressively during the 3 steps from 183 ± 95 to 361 ± 144 mmHg (p < 0.001). In those patients with a reduction of polymerase chain reaction less than or equal to 80%, delta increase of the PO2/FiO2 ratio was significantly more pronounced (129 ± 118 vs. 45 ± 35 mmHg, p = 0.02). No adverse side effects were recorded during treatment. In patients hospitalized for COVID-19, compassionate-use of ruxolitinib determined a significant reduction of biomarkers of inflammation, which was associated with a more effective ventilation and reduced need for oxygen support. Data on ruxolitinib reinforces the hypothesis that targeting the hyperinflammation state, may be of prognostic benefit in patients with SARS-CoV-2 infection. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Some

Lucrezia Ferrario,1 Fabrizio Schettini,1 Angelo Avogaro,2 Chiara Bellia,3 Federico Bertuzzi,4 Graziella Bonetti,5 Antonio Ceriello,6 Marcello Ciaccio,3,7 Massimiliano Corsi Romanelli,8,9 Elena Dozio,9 Luca Falqui,10 Angela Girelli,11 Antonio Nicolucci,12 Gianluca Perseghin,13,14 Mario Plebani,15 Umberto Valentini,11 Martina Zaninotto,15 Silvana Castaldi,9,16 Emanuela Foglia1 1Centre for Health Economics, Social and Health Care Management, Università Carlo Cattaneo - LIUC, Castellanza, Italy; 2Department of Medicine, University-Hospital of Padova, Padova, Italy; 3Section of Clinical Biochemistry and Clinical Molecular Medicine, Department of Biopathology and Medical Biotechnologies, University of Palermo, Palermo, Italy; 4Diabetology Unit, Grande Ospedale Metropolitano Niguarda Hospital, Milan, Italy; 5Department of Medicine Services, Valcamonica Hospital, Esine, Italy; 6Department of Cardiovascular and Metabolic Diseases, Multimedica Research Institute, Milan, Italy; 7Department of Laboratory Medicine, University-Hospital of Palermo, Palermo, Italy; 8Service of Laboratory Medicine 1-Clinical Pathology, Policlinico San Donato, Milan, Italy; 9Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy; 10Department of Medicine, Diabetes and Endocrinology, Multimedica Research Institute, Milan, Italy; 11Diabetes Care Unit, Spedali Civili Hospital, Brescia, Italy; 12Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy; 13Department of Medicine and Surgery, Università degli Studi di Milano Bicocca, Milan, Italy; 14Department of Medicine and Rehabilitation, Unit of Metabolic Medicine, Policlinico di Monza, Monza, Italy; 15Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy; 16Fondazione Ca’ Granda Ospedale Maggiore Policlinico Research Institute of Milano, Milano, ItalyCorrespondence: Lucrezia FerrarioCentre for Health Economics, Social and Health Care