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OBJECTIVE: SARS-CoV-2 disease (COVID-19) has become a pandemic disease, determining a public health emergency. The use of artificial intelligence in identifying easily available biomarkers capable of predicting the risk for severe disease may be helpful in guiding clinical decisions. The aim of the study was to investigate the ability of interleukin (IL)-6, troponin I, and D-dimer to identify patients with COVID-19 at risk for intensive care unit (ICU)-admission and death by using a machine-learning predictive model. PATIENTS AND METHODS: Data on demographic characteristics, underlying comorbidities, symptoms, physical and radiological findings, and laboratory tests have been retrospectively collected from electronic medical records of patients admitted to Policlinico A. Gemelli Foundation from March 1, 2020, to September 15, 2020, by using artificial intelligence techniques. RESULTS: From an initial cohort of 425 patients, 146 met the inclusion criteria and were enrolled in the study. The in-hospital mortality rate was 15%, and the ICU admission rate was 41%. Patients who died had higher troponin I (p-value<0.01) and IL -6 values (p-value=0.04), compared to those who survived. Patients admitted to ICU had higher lev- els of troponin I (p-value<0.01) and IL-6 (p-val- ue<0.01), compared to those not admitted to ICU. Threshold values to predict in-hospital mortality and ICU admission have been identified. IL-6 levels higher than 15.133 ng/L have been associated with a 22.91% risk of in-hospital mortality, and IL-6 levels higher than 25.65 ng/L have been as- sociated with a 56.16% risk of ICU admission. Troponin I levels higher than 12 ng/L have been associated with a 26.76% risk of in-hospital mortality and troponin I levels higher than 12 ng/L have been associated with a 52.11% risk of ICU admission. CONCLUSIONS: Levels of IL-6 and troponin I are associated with poor COVID-19 outcomes. Cut-off values capable of predicting in-hospi- tal mortality and ICU admi

Objective: Coronavirus disease 2019 (COVID-19) has evolved into a global pandemic, affecting a wide range of medical and surgical specialties. During COVID-19, we assisted in the reallocation of medical resources and services, as well as social distancing measures, and many patients with chronic diseases and comorbidities may have experienced difficulties in obtaining the correct medical care. The aim of the study was to investigate the impact of the COVID-19 pandemic on major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral arterial disease (PAD) and chronic limb-threatening ischemia (CLTI), compared to previous years. Patients and methods: We evaluated 1,335 hospital admissions of 877 patients with PAD admitted to Policlinico A. Gemelli Hospital between January 2017 and February 2020 and 368 hospital admissions of 272 patients with PAD admitted to the Policlinico A. Gemelli Hospital between March 2020 and March 2021. Data on demographic characteristics, comorbidities, symptoms, physical and radiological findings, laboratory tests, and routine visits before or after discharge were collected from electronic medical records. Results: Emergency room (ER) admissions among PAD patients during COVID-19 were higher than before the pandemic [190 (51.63%) vs. 579 (43.37%), p = 0.01]. A MACE was found in 78 (5.84%) pre-pandemic hospitalizations and 126 (34.24%) pandemic hospitalizations (p < 0.01). A MALE was identified in 942 (70.56%) pre-pandemic hospitalizations and 331 (89.95%) pandemic hospitalizations (p < 0.01). Amputation rates during the pandemic were higher than before the pandemic [80 (21.74%) vs. 191 (14.31%), p < 0.01]. The number of in-hospital deaths did not differ between the pandemic and pre-pandemic periods [11 (2.99%) vs. 51 (3.82%), p = 0.55]. Conclusions: In patients with PAD and CLTI, the number of MACE, MALE, and amputations was higher during the COVID-19 period compared to the thr

Dietary risk factors play a fundamental role in the prevention and progression of atherosclerosis and PAD (Peripheral Arterial Disease). The impact of nutrition, however, defined as the process of taking in food and using it for growth, metabolism and repair, remains undefined with regard to PAD. This article describes the interplay between nutrition and the development/progression of PAD. We reviewed 688 articles, including key articles, narrative and systematic reviews, meta-analyses and clinical studies. We analyzed the interaction between nutrition and PAD predictors, and subsequently created four descriptive tables to summarize the relationship between PAD, dietary risk factors and outcomes. We comprehensively reviewed the role of well-studied diets (Mediterranean, vegetarian/vegan, low-carbohydrate ketogenic and intermittent fasting diet) and prevalent eating behaviors (emotional and binge eating, night eating and sleeping disorders, anorexia, bulimia, skipping meals, home cooking and fast/ultra-processed food consumption) on the traditional risk factors of PAD. Moreover, we analyzed the interplay between PAD and nutritional status, nutrients, dietary patterns and eating habits. Dietary patterns and eating disorders affect the development and progression of PAD, as well as its disabling complications including major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nutrition and dietary risk factor modification are important targets to reduce the risk of PAD as well as the subsequent development of MACE and MALE.

Background & aims: Alcohol use disorder (AUD) represents the most common cause of liver disease. The gut microbiota plays a critical role in the progression of alcohol-related liver damage. Aim of this study was to characterize the gut microbial composition and function in AUD patients with alcohol-associated liver disease (AALD). Methods: This study included 36 AUD patients (14 with cirrhosis) who were active drinkers and an equal number of matched controls. Stool microbial composition, serum levels of lipopolysaccharide, cytokines/chemokines and gut microbiota functional profile were assessed. Results: AUD patients had a decreased microbial alpha diversity as compared to controls (0.092 vs 0.130, P =.047) and a specific gut microbial signature. The reduction of Akkermansia and the increase in Bacteroides were able to identify AUD patients with an accuracy of 93.4%. Serum levels of lipopolysaccharide (4.91 vs 2.43, P =.009) and pro-inflammatory mediators (tumour necrosis factor alpha 60.85 vs 15.08, P =.001; interleukin [IL] 1beta 4.43 vs 1.72, P =.0001; monocyte chemoattractant protein 1 225.22 vs 16.43, P =.006; IL6 1.87 vs 1.23, P =.008) were significantly increased in AUD patients compared to controls and in cirrhotic patients compared to non-cirrhotic ones (IL6 3.74 vs 1.39, P =.019; IL8 57.60 vs 6.53, P =.004). The AUD-associated gut microbiota showed an increased expression of gamma-aminobutyric acid (GABA) metabolic pathways and energy metabolism. Conclusions: AUD patients present a specific gut microbial fingerprint, associated with increased endotoxaemia, systemic inflammatory status and functional alterations that may be involved in the progression of the AALD and in the pathogenesis of AUD.

Following publication of the original article [1], the authors noticed an error in “Methods/Study population” section. The date “June 1, 2018” which is in the “Study population” section should have been given as “June 1, 2013”. This has been corrected with this erratum.

Background and aims: The increasing prevalence of diabetes mellitus is causing a massive growth of peripheral artery disease incidences, a disabling complication of diabetic atherosclerosis, which leads often to the amputation of the affected limb. Critical limb ischemia is the terminal disease stage, which requires a prompt intervention to relieve pain and save limbs. However, patients undergoing revascularization often suffer from cardiovascular, cerebrovascular and major adverse limb events with poor outcomes. Furthermore, the same procedure performed in apparently similar patients has various outcomes and lack of an outcome predictive support causes a high lower limb arterial revascularization rate with disastrous effects for patients. We collected the main risk factors of major adverse limb events in a more readable and immediate format of the topic, to propose an overview of parameters to manage effectively peripheral artery disease patients and to propose basics of a new predictive tool to prevent from disabling vascular complications of the disease. Methods: Most recent and updated literature about the prevalence of major adverse limb events in peripheral artery disease was reviewed to identify possible main predictors. Results: In this article, we summarized major risk factors of limb revascularization failure and disabling vascular complications collecting those parameters principally responsible for major adverse limb events, which provides physio-pathological explanation of their role in peripheral artery disease. Conclusion: We evaluated and listed a panel of possible predictors of MALE (Major Adverse Limb Event) in order to contribute to the development of a predictive score, based on a summary of the main risk factors reported in scientific articles, which could improve the management of peripheral artery disease by preventing vascular accidents.

Background: Carotid atherosclerosis represents one of the complications of diabetes mellitus. In particular, plaque instability contributes to disease progression and stroke incidence. High mobility group box-1 (HMGB1) is a nuclear protein involved in promotion and progression of atherosclerosis and cardiovascular diseases. The aim of this study was to analyze the relationship between HMGB1 serum levels, main inflammatory cytokines, the presence of internal carotid stenosis and unstable plaque in a diabetic population. Research design and methods: We studied 873 diabetic patients, including 347 patients with internal carotid artery stenosis (ICAS) who underwent carotid endarterectomy and 526 diabetic patients without internal carotid artery stenosis (WICAS). At baseline, HMGB1 and the main inflammatory cytokines serum levels were evaluated. For ICAS patients, the histological features of carotid plaque were also collected to differentiate them in patients with stable or unstable atherosclerotic lesions. Results: We found that HMGB1 serum levels, osteoprotegerin, high-sensitivity C-reactive protein, tumor necrosis factor-alpha and interleukin-6, were significantly higher in diabetic ICAS patients compared to diabetic WICAS patients. Among ICAS patients, individuals with unstable plaque had higher levels of these cytokines, compared to patients with stable plaque. A multivariable stepwise logistic regression analysis showed that HMGB1 and osteoprotegerin remained independently associated with unstable plaque in ICAS patients. Conclusions: The present study demonstrated that HMGB1 is an independent risk factor for carotid plaque vulnerability in an Italian population with diabetes mellitus, representing a promising biomarker of carotid plaque instability and a possible molecular target to treat unstable carotid plaques and to prevent stroke.

Background: Cardiovascular complications represent the major cause of morbidity and mortality of type 2 diabetes mellitus (T2DM) patients. In particular, peripheral artery disease (PAD) represents a frequent T2DM vascular complication and a risk factor for the development of major adverse cardiovascular events (MACE). Among adipokines, omentin-1 serum levels are reduced in T2DM patients with PAD and are inversely related to disease severity. Objective: To study the relationship between omentin-1 levels, at baseline, with outcomes after endovascular procedures in T2DM patients with PAD and chronic limb-threatening ischemia (CLTI). Research design and methods: We enrolled for our prospective non-randomized study, 207 T2DM patients with PAD and CLTI, requiring revascularization. Omentin-1 serum levels were collected before revascularization and patients incidence outcomes were evaluated at 1, 3, 6 and 12 months. Results: Omentin-1 was reduced in patients with more severe disease (27.24 ± 4.83 vs 30.82 ± 5.48 ng/mL, p < 0.001). Overall, 84 MACE and 96 major adverse limb events (MALE) occurred during the 12-month follow-up. We observed that omentin-1 levels were lower in patients with MACE (26.02 ± 4.05 vs 31.33 ± 5.29 ng/mL, p < 0.001) and MALE (26.67 ± 4.21 vs 31.34 ± 5.54 ng/mL, p < 0.001). The association between omentin-1, MACE and MALE remained significant after adjusting for major risk factors in a multivariate analysis. Receiver operating characteristics (ROC) curve using omentin-1 levels predicted incidence events (area under the curve = 0.80). Conclusions: We demonstrated that reduced omentin-1 levels, at baseline, are related with worse vascular outcomes in T2DM patients with PAD and CLTI undergoing an endovascular procedure.

The 2019 novel coronavirus [2019-nCoV], which started to spread from December 2019 onwards, caused a global pandemic. Besides being responsible for the severe acute respiratory syndrome 2 [SARS-CoV-2], the virus can affect other organs causing various symptoms. A close relationship between SARS-CoV-2 and the cardiovascular system has been shown, demonstrating an epidemiological linkage between SARS-CoV-2 and cardiac injury. There are emerging data regarding possible direct myocardial damage by 2019-nCoV. In this review, the most important available evidences will be discussed to clarify the precise mechanisms of cardiovascular injury in SARS-CoV-2 patients, even if further researches are needed.

Background: Peripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients. Objective: To evaluate the relationship between baseline serum levels of sortilin, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI). Research design and methods: We performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin levels were measured before the endovascular intervention and incident outcomes were assessed during a 12 month follow-up. Results: Sortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using sortilin levels the prediction of MACE incidence improved (area under the curve [AUC] = 0.94) and MALE (AUC = 0.72). Conclusions: This study demonstrates that sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.

Diabetes mellitus (DM) is an endemic disease, with growing health and social costs. The complications of diabetes can affect potentially all parts of the human body, from the heart to the kidneys, peripheral and central nervous system, and the vascular bed. Although many mechanisms have been studied, not all players responsible for these complications have been defined yet. High Mobility Group Box-1 (HMGB1) is a non-histone nuclear protein that has been implicated in many pathological processes, from sepsis to ischemia. The purpose of this review is to take stock of all the most recent data available on the role of HMGB1 in the complications of DM.

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