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Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background and Aims: Interest in the role of atrial substrate in maintaining Atrial Fibrillation (AF) is growing. Fibrosis is the culprit in the electrical derangement of the myocytes. Many cardiovascular risk factors are known to be linked to atrial scarring; among them Uric Acid (UA) is emerging. The purpose of our study is to find whether UA is associated with Left Atrium (LA) with pathological substrate., Methods and Results: 81 patients who underwent radiofrequency transcatheter ablation for nonvalvular AF at the cardiological department of the Niguarda Hospital were enrolled in an observational, cross-sectional, single-center study. UA levels were analysed before the procedure. High density electroanatomic mapping of the LA was performed and patients were divided according to the presence or not of areas of pathological substrate (bipolar voltage <0.5 mV in sinus rhythm). 19 patients showed a LA with pathological substrate. These subjects showed a significant higher prevalence of persistent phenotype of AF (84.2 vs. 25.8%, p < 0.001). UA levels were significantly higher in the group of patients with LA with pathological substrate (6.8 ± 1.9 vs 5.3 ± 1.4 mg/dL, p < 0.001) as well as the prevalence of hyperuricemia (26.5 vs. 6.5%, p = 0.021). The association between uric acid LA with pathological substrate remains significant even after correction for confounding factors (age, left ventricular dysfunction, valvular disease, arrythmia phenotype and furosemide use) and also when the ratio UA/creatinine was evaluated., Conclusions: In a population of patients who underwent AF ablation, higher UA levels were significantly associated with pathological LA substrate at electro-anatomical mapping., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Direct anchoring of PM and ICD leads over cephalic vein body is officially discouraged by manufactures due to a supposed risk of conductor fracture or insulation failure, however careful tightening of anchoring knots can probably prevent lead damage. Direct anchoring (DA) technique is routinely used in our center for all leads inserted by cephalic vein while standard anchoring sleeves are used to secure subclavian leads only. Aim of the study is to assess short- and long-term safety of cephalic direct anchoring technique., Methods: All patients undergoing PM and ICD implantation in our center from November 2014 to March 2016 were consecutively enrolled. Primary endpoints were acute lead fracture, lead dislodgement and chronic lead failure. Secondary endpoint was a composite of short-term surgical complications (pocket hematoma, pneumothorax, and pericardial effusion) plus device infections. Subclavian leads secured with sleeve anchoring (SA) were used as control., Results: A total of 550 leads were implanted in 310 consecutive patients. DA involved 323 leads (59%) while SA was used for 227 (41%). Median follow-up was 50 months (IQR 24-62 months). 17 lead malfunctions (3.1%) were observed during follow-up. No difference was observed between groups (10 DA vs. 7 SP, P=ns). Survival analysis found no difference between groups. Secondary endpoints were not statistically different between groups (5 vs. 1, P=0.08)., Conclusions: Direct anchoring technique of PM and ICD leads is a safe technique and does not increase lead malfunction risk.

While lung ultrasonography (LUS) proved to be a useful diagnostic and prognostic tool in acute phase of COVID 19 pneumonia, its role in detecting long-term pulmonary sequelae has yet to be explored. In our prospective observational study we assessed the potential of LUS in detecting the presence of computed tomography (CT) fibrotic-like changes after 6 months from COVID-19 pneumonia. Patients who were discharged with a diagnosis of severe COVID-19 pneumonia were enrolled. After 6 months from hospital discharge they underwent LUS, chest CT scan and pulmonary function tests. A logistic regression analysis was performed to assess the association between presence of symptoms, LUS score and diffusing capacity for carbon monoxide (DLCO) at 6-month after hospital discharge and CT scan fibrotic-like changes. A second logistic model was performed to assess the value of some predefined baseline factors (age, sex, worst PaO2/FiO2, ventilator support, worst CRP value, worst D-dimer value and worst LUS score during hospitalization) to predict fibrotic-like changes on 6-month CT scan. Seventy-four patients were enrolled in the study. Twenty-four (32%) showed lung abnormalities suitable for fibrotic-like changes. At multivariate logistic regression analysis LUS score after 6 months from acute disease was significantly associated with fibrotic-like pattern on CT scan. The second logistic model showed that D-dimer value was the only baseline predictive variable of fibrotic-like changes at multivariate analysis. LUS performed after 6 months from severe COVID-19 pneumonia may be a promising tool for detection and follow-up of pulmonary fibrotic sequelae., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Coronavirus disease 2019 (COVID-19) represents a major health problem in terms of deaths and long-term sequelae. We conducted a retrospective cohort study at Montichiari Hospital (Brescia, Italy) to better understand the determinants of outcome in two different COVID-19 outbreaks. A total of 634 unvaccinated patients admitted from local emergency room to the Internal Medicine ward with a confirmed diagnosis of SARS-CoV-2 infection and a moderate-to-severe COVID-19 were included in the study. A group of 260 consecutive patients during SARS-CoV-2 first wave (from February to May 2020) and 374 consecutive patients during SARS-CoV-2 2nd/3rd wave (from October 2020 to May 2021) were considered. Demographic data were not significantly different between waves, except a lower prevalence of female sex during first wave. Mortality was significantly higher during the 1 st wave than in the following periods (24.2% vs. 11%; p < 0.001). Time from symptoms onset to hospital admission was longer during first wave (8 ± 6 vs. 6 ± 4 days; p < 0.001), while in-hospital staying was significantly shorter (10 ± 14 vs. 15 ± 11 days; p < 0.001). Other significant differences were a larger use of corticosteroids and low-molecular weight heparin as well less antibiotic prescription during the second wave. Respiratory, bio-humoral and X-ray scores were significantly poorer at the time of admission in first-wave patients. After a multivariate regression analysis, C-reactive protein and procalcitonin values, % fraction of inspired oxygen on admission to the Internal Medicine ward and length of hospital stay and duration of symptoms were the strongest predictors of outcome. Concomitant anti-hypertensive treatment (including ACE-inhibitors and angiotensin-receptor blockers) did not affect the outcome. In conclusion, our data suggest that earlier diagnosis, timely hospital admission and rational use of the therapeutic options reduced the systemic inflammatory response and were associated to a better outcome during the 2nd/3rd wave., (© 2022. The Author(s).)

Introduction: Cardiac rehabilitation (CR) is an effective tool for secondary prevention after acute coronary syndrome (ACS)., Aim: Aim of our study was to find the significant determinants of exercise capacity (evaluated with the six-minute walking test-6-MWT) and functional improvement in patients undergoing CR after an ACS., Methods: The study group included 298 patients (mean age 61.6 ± 10.2 years; males 80.2%) who, after ACS, were enrolled in CR program at Niguarda Hospital in Milan from 2015 to 2018. For all patients, we collected anamnestic, clinical and instrumental cardiological data. All patients performed a 6-MWT at the beginning (6-MWT-1) and at the end (6-MWT-2) of CR program. Δ meters were used to represent functional improvement., Results: Multiple linear regression models were carried out for 6-MWT-1, 6-MWT-2, Δ meters and % Δ meters. Standardized regression coefficients showed that age (β = - 0.237; p < 0.001), BMI (β = - 0.116; p = 0.006) and heart rate (β = - 0.082; p = 0.040) were determinants of exercise capacity (6MWT-1 and 2), whereas age (β = -.231; p = 0.004), sex (β = - 0.187; p = 0.008) and BMI (β = - 0.164; p = 0.022) were determinants of functional improvement (Δ meters)., Conclusions: Our data showed that functional improvement after CR in ACS patients is mainly related to non-cardiological variables. Instead it is related to intrinsic factors, both modifiable (BMI) and non-modifiable (age, sex)., (© 2021. The Author(s).)

Uric acid (UA) is the final product of the catabolism of endogenous and exogenous purine nucleotides. While its association with articular gout and kidney disease has been known for a long time, new data have demonstrated that UA is also related to cardiovascular (CV) diseases. UA has been identified as a significant determinant of many different outcomes, such as all-cause and CV mortality, and also of CV events (mainly Acute Coronary Syndromes (ACS) and even strokes). Furthermore, UA has been related to the development of Heart Failure, and to a higher mortality in decompensated patients, as well as to the onset of atrial fibrillation. After a brief introduction on the general role of UA in CV disorders, this review will be focused on UA's relationship with CV outcomes, as well as on the specific features of patients with ACS and Chronic Coronary Syndrome. Finally, two issues which remain open will be discussed: the first is about the identification of a CV UA cut-off value, while the second concerns the possibility that the pharmacological reduction of UA is able to lower the incidence of CV events.

SARS-CoV-2 infection determines a disease that predominantly affects lungs. However the cytokines storms, determined by the huge immune response to the infection, could affect also other organs and apparatus such as heart and vessels. Beyond the acute inflammation itself also hypercoagulative status has been linked to SARSCoV-2 infection and this surely relates to the increase seen in prevalence of pulmonary embolism and myocardial infarction. A number of cardiac abnormalities and pathologies have been observed, with special attention to cardiac arrhythmias and myocardial involvement. Furthermore, indirect damages determined by the reduction in acute and chronic cardiovascular care, results in a strong mortality and morbidity outcomes in cardiological patients. In this review we will summarise current knowledge on both direct and indirect cardiovascular damages determined by the SARS-CoV-2 pandemia., (© 2021. The Author(s).)

Background: Previously published studies evaluating a recombinant Der f 2-based immunotherapy have demonstrated efficacy in the treatment of dogs experimentally and naturally sensitized to house dust mites (HDM). Der f 2 sensitization is thought to play a minor role in European atopic dogs sensitized to HDM., Objective: The study evaluated the short-term efficacy of a recombinant Der f 2 product in the treatment of naturally sensitized atopic dogs in Switzerland and Hungary., Animals: Fifteen atopic dogs with positive test reactions to Dermatophagoides farinae (Df)., Material and Methods: Recombinant Der f 2 allergens were injected subcutaneously at increasing doses once weekly for 6 weeks. Canine Atopic Dermatitis Extent and Severity Index (CADESI-04), pruritus Visual Analog Scale (pVAS) and medication scores were assessed at days 0 and 42. Efficacy was recorded as excellent, good, fair or poor, depending on the number of scores decreasing by more than 50%., Results: Mean CADESI, pVAS and medication scores at inclusion were 35, 6 and 15 (SD = 30, 2, 7), respectively. At Day 42 the scores decreased to 8, 3 and 5, respectively (Wilcoxon matched pairs signed rank tests P = 0.0002, 0.002 and 0.001). Four dogs were classified as excellent responders with a reduction of >50% in all three scores. Nine dogs were classified as good (five) or fair (four) responders and scores deteriorated in two dogs., Conclusion: These data suggest that recombinant Der f2 allergens may be as effective and show benefit faster than traditional allergen immunotherapy in European dogs sensitized to Df., (© 2018 ESVD and ACVD.)

Dyspnea is a common presenting complaint in the emergency department (ED) and a leading cause of hospitalization in intensive care unit (ICU) and medical wards. Ultrasound (US) has traditionally been considered inadequate to explore the aerated lung. However, in the past 15 years LUS gained broader application, at least in part thanks to the interpretation of the artefacts generated by the interaction of US and lung structures/content. The total reflection of US beam occurring at the pleural level determines the artefactual image of the aerated lung: an homogenous 'foggy-like' picture under the pleural line. As the air content of the lungs decreases due to interstitial imbibition, deposition of collagen or presence of blood, vertical artefacts -arising from the pleural line and moving synchronously with the respiration- called B-lines appear. Multiple and bilateral B-lines identify the alveolar-interstitial syndrome (AIS). The most common cause of AIS is the wet lung: the more the congestion burden, the more the extent of the B-lines, which become confluent until the so-called white lung in case of pulmonary edema. Many studies showed a higher accuracy of LUS in diagnosing acute decompensated heart failure (ADHF) as compared to chest X-ray As recently shown, the integration of LUS to clinical assessment allow to differentiate cardiogenic dyspnea with sensitivity and specificity greater than 95 %. Moreover, LUS can easily detect pleural effusion -frequently present in ADHF-appearing as an anechoic area in the recumbent area of the thorax, delimited inferiorly by the diaphragmatic dome and superiorly by the aerated lung.