Diagnostic and Prognostic Role of CD93 in Cardiovascular Disease: A Systematic Review

Introduction. Cluster of Differentiation (CD) 93 (also known as complement protein 1 q subcomponent receptor C1qR1 or C1qRp) is a transmembrane glycoprotein that can also be present in a soluble (sCD93) form. Recent studies have investigated the role of this protein in cardiovascular disease (CVD). The present systematic review aims to assess the associations between CD93 and cardiovascular (CV) risk factors and disease at both the proteomic and genomic levels. Methods. We conducted systematic searches in the PubMed, EMBASE, and Web of Science databases to identify all human studies since inception to February 2023 that investigated the role of CD93 in CV risk factors, CVD, and CV-associated outcomes. The data collection and analysis have been independently conducted by two reviewers. The search terms included: cardiovascular, heart failure, acute stroke, myocardial infarction, stroke, peripheral artery disease, cardiovascular death, MACE, hypertension, metabolic syndrome, hyperuricemia, diabetes, cd93, c1qr, C1qR1, complement protein 1 q subcomponent receptor. Results. A total of 182 references were identified, and 15 studies investigating the associations between CD93 protein levels or CD93 genetic polymorphisms and the development or prevalence of CV risk factors (i.e., hypertension, dyslipidemia, and obesity) and CVD (i.e., heart failure, coronary artery disease, and ischemic stroke) were included. Although promising, the quality and dimension of the analyzed studies do not allow for a definitive answer to the question of whether CD93 may hold diagnostic and prognostic value in CVD

Traditional landscape and rural development: comparative study in three terraced areas in northern, central and southern Italy to evaluate the efficacy of GAEC standard 4.4 of cross compliance

The recent National Strategic Plan 2007-2013 has introduced landscape as a strategic objective of the rural sector. This represents a minor revolution in the way of visualizing the role of the landscape, together with that of agriculture and the rural territory as a whole, and demonstrates the importance of treating the landscape with a systematic point of view. As part of the Efficond project, three sample areas have been identified, each of about 800-1000 hectares, in zones with important historical - cultural landscapes that are included in the National Catalogue of Historical Rural Landscapes. For each sample area a methodology has been applied, defined Historical Cultural Evaluation Approach, developed as part of a project for the monitoring of the Tuscan landscape that we have simplified and adapted. This methodology is based on the consideration that the landscape is the result of the centuries-old interaction between man and the environment, and so to define an element of the landscape as characteristic it is necessary to evaluate the land use dynamics and landscape changes that took place in the past, identifying those that have persisted for a long time, are slowly evolving or stabilized. The study of the historical landscape, which in the proposed methodology refers to the 50’s, has been done through the interpretation and analysis of aerial photographs taken on the GAI flight in 1954, and has allowed the characteristic, traditional and historical elements of that landscape to be identified and an insight to be gained into the cultural identity of the area. Through the creation of specific indices of density and intensity of the terracing obtained by photo-interpretation, field surveys and GIS elaborations, it was possible to classify the sample areas for this specific and important landscape element, compare the results in two periods and evaluate their frequency in the territory. Multi-temporal comparative analysis is being used increasingly often, especially for the study of territories of value, and in our case has been accompanied both by mapping of the landscape dynamics, which identifies the areas subject to transformations in the considered period, and by tables and figures that allow the evolution of a unit of land use to be followed, observing how this has evolved over time. The evaluation of these evolutionary dynamics has then been integrated with a set of indices, in part borrowed from landscape ecology, and in part specifically developed for areas historically shaped by man, which demonstrate that the landscape has become less fragmented and that the layout of fields has been adapted to a different agricultural model that has profoundly changed the structure of the traditional landscape. The efficacy of the laws protecting the characteristic elements of the landscape is strictly linked to the maintenance of its diversity and typicality and conservation of the complexity of the landscape mosaic. Its evaluation necessitates a historical analysis of the evolutionary dynamics conducted at a purely local level

Sepsis Team Organizational Model to Decrease Mortality for Intra-Abdominal Infections: Is Antibiotic Stewardship Enough?

Introduction. Sepsis is an overwhelming reaction to infection with significant morbidity, requiring urgent interventions in order to improve outcomes. The 2016 Sepsis-3 guidelines modified the previous definitions of sepsis and septic shock, and proposed some specific diagnostic and therapeutic measures to define the use of fluid resuscitation and antibiotics. However, some open issues still exist. Methods. A literature research was performed on PubMed and Cochrane using the terms “sepsis” AND “intra-abdominal infections” AND (“antibiotic therapy” OR “antibiotic treatment”). The inclusion criteria were management of intra-abdominal infection (IAI) and effects of antibiotic stewardships programs (ASP) on the outcome of the patients. Discussion. Sepsis-3 definitions represent an added value in the understanding of sepsis mechanisms and in the management of the disease. However, some questions are still open, such as the need for an early identification of sepsis. Sepsis management in the context of IAI is particularly challenging and a prompt diagnosis is essential in order to perform a quick treatment (source control and antibiotic treatment). Antibiotic empirical therapy should be based on the kind of infection (community or hospital acquired), local resistances, and patient’s characteristic and comorbidities, and should be adjusted or de-escalated as soon as microbiological information is available. Antibiotic Stewardship Programs (ASP) have demonstrated to improve antimicrobial utilization with reduction of infections, emergence of multi-drug resistant bacteria, and costs. Surgeons should not be alone in the management of IAI but ideally inserted in a sepsis team together with anaesthesiologists, medical physicians, pharmacists, and infectious diseases specialists, meeting periodically to reassess the response to the treatment. Conclusion. The cornerstones of sepsis management are accurate diagnosis, early resuscitation, effective source control, and timely initiation of appropriate antimicrobial therapy. Current evidence shows that optimizing antibiotic use across surgical specialities is imperative to improve outcomes. Ideally every hospital and every emergency surgery department should aim to provide a sepsis team in order to manage IAI

Nonalcoholic fatty liver disease and increased risk of 1-year all-cause and cardiac hospital readmissions in elderly patients admitted for acute heart failure

Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for heart failure (HF). Although some progress has been made in improving survival among patients admitted for HF, the rates of hospital readmissions and the related costs continue to rise dramatically. We sought to examine whether NAFLD and its severity (diagnosed at hospital admission) was independently associated with a higher risk of 1-year all-cause and cardiac re-hospitalization in patients admitted for acute HF. We studied 212 elderly patients who were consecutively admitted with acute HF to the Hospital of Negrar (Verona) over a 1-year period. Diagnosis of NAFLD was based on ultrasonography, whereas the severity of advanced NAFLD fibrosis was based on the fibrosis (FIB)-4 score and other non-invasive fibrosis scores. Patients with acute myocardial infarction, severe valvular heart diseases, endstage renal disease, cancer, known liver diseases or decompensated cirrhosis were excluded. Cox regression was used to estimate hazard ratios (HR) for the associations between NAFLD and the outcome(s) of interest. The cumulative rate of 1-year all-cause re-hospitalizations was 46.7% (n = 99, mainly due to cardiac causes). Patients with NAFLD (n = 109; 51.4%) had remarkably higher 1-year all-cause and cardiac re-hospitalization rates compared with their counterparts without NAFLD. Both event rates were particularly increased in those with advanced NAFLD fibrosis. NAFLD was associated with a 5-fold increased risk of 1-year all-cause re-hospitalization (adjusted-hazard ratio 5.05, 95% confidence intervals 2.78-9.10, p<0.0001) after adjustment for established risk factors and potential confounders. Similar results were found for 1-year cardiac re-hospitalization (adjusted-hazard ratio 8.05, 95% confidence intervals 3.77-15.8, p<0.0001). In conclusion, NAFLD and its severity were strongly and independently associated with an increased risk of 1-year all-cause and cardiac re-hospitalization in elderly patients admitted with acute HF

Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: An observational cohort study

Background: Iron metabolism and immune response to SARS-CoV-2 have not been described yet in intensive care patients, although they are likely involved in Covid-19 pathogenesis. Methods: We performed an observational study during the peak of pandemic in our intensive care unit, dosing D-dimer, C-reactive protein, troponin T, lactate dehydrogenase, ferritin, serum iron, transferrin, transferrin saturation, transferrin soluble receptor, lymphocyte count and NK, CD3, CD4, CD8 and B subgroups of 31 patients during the first 2 weeks of their ICU stay. Correlation with mortality and severity at the time of admission was tested with the Spearman coefficient and Mann-Whitney test. Trends over time were tested with the Kruskal-Wallis analysis. Results: Lymphopenia is severe and constant, with a nadir on day 2 of ICU stay (median 0.555 109/L; interquartile range (IQR) 0.450 109/L); all lymphocytic subgroups are dramatically reduced in critically ill patients, while CD4/CD8 ratio remains normal. Neither ferritin nor lymphocyte count follows significant trends in ICU patients. Transferrin saturation is extremely reduced at ICU admission (median 9%; IQR 7%), then significantly increases at days 3 to 6 (median 33%, IQR 26.5%, p value 0.026). The same trend is observed with serum iron levels (median 25.5 μg/L, IQR 69 μg/L at admission; median 73 μg/L, IQR 56 μg/L on days 3 to 6) without reaching statistical significance. Hyperferritinemia is constant during intensive care stay: however, its dosage might be helpful in individuating patients developing haemophagocytic lymphohistiocytosis. D-dimer is elevated and progressively increases from admission (median 1319 μg/L; IQR 1285 μg/L) to days 3 to 6 (median 6820 μg/L; IQR 6619 μg/L), despite not reaching significant results. We describe trends of all the abovementioned parameters during ICU stay. Conclusions: The description of iron metabolism and lymphocyte count in Covid-19 patients admitted to the intensive care unit provided with this paper might allow a wider understanding of SARS-CoV-2 pathophysiology

Reduction of High Cholesterol Levels by a Preferably Fixed-Combination Strategy as the First Step in the Treatment of Hypertensive Patients with Hypercholesterolemia and High/Very High Cardiovascular Risk: A Consensus Document by the Italian Society of Hypertension

The primary and secondary prevention strategies of atherosclerotic cardiovascular disease (ASCVD) largely rely on the management of arterial hypertension and hypercholesterolemia, two major risk factors possibly linked in pathophysiological terms by the renin-angiotensin system activation and that often coexist in the same patient synergistically increasing cardiovascular risk. The classic pharmacologic armamentarium to reduce hypercholesterolemia has been based in the last two decades on statins, ezetimibe, and bile acid sequestrants. More recently numerous novel, additive resources targeting different pathways in LDL cholesterol metabolism have emerged. They include drugs targeting the proprotein convertase subtilisin/kexin type 9 (PCSK9) (inhibitory antibodies; small-interfering RNAs), the angiopoietin-like protein 3 (inhibitory antibodies), and the ATP-citrate lyase (the inhibitory oral prodrug, bempedoic acid), with PCSK9 inhibitors and bempedoic acid already approved for clinical use. With the potential of at least halving LDL cholesterol levels faster and more effectively with the addition of ezetimibe than with high-intensity statin alone, and even more with the addition of the novel available drugs, this document endorsed by the Italian Society of Hypertension proposes a novel paradigm for the treatment of the hypertensive patient with hypercholesterolemia at high and very high ASCVD risk. Our proposal is based on the use as a first-line of a preferably fixed combination of lipid-lowering drugs, under the motto “Our goal: achieve control. No setback: combine and check”

From intensive care to step-down units: Managing patients throughput in response to COVID-19

Quality problem or issue: The on-going COVID-19 pandemic may cause the collapse of healthcare systems because of unprecedented hospitalization rates. Initial assessment: A total of 8.2 individuals per 1000 inhabitants have been diagnosed with COVID-19 in our province. The hospital predisposed 110 beds for COVID-19 patients: On the day of the local peak, 90% of them were occupied and intensive care unit (ICU) faced unprecedented admission rates, fearing system collapse. Choice of solution: Instead of increasing the number of ICU beds, the creation of a step-down unit (SDU) close to the ICU was preferred: The aim was to safely improve the transfer of patients and to relieve ICU from the risk of overload. Implementation: A nine-bed SDU was created next to the ICU, led by intensivists and ICU nurses, with adequate personal protective equipment, monitoring systems and ventilators for respiratory support when needed. A second six-bed SDU was also created. Evaluation: Patients were clinically comparable to those of most reports from Western Countries now available in the literature. ICU never needed supernumerary beds, no patient died in the SDU, and there was no waiting time for ICU admission of critical patients. SDU has been affordable from human resources, safety and economic points of view. Lessons learned: COVID-19 is like an enduring mass casualty incident. Solutions tailored on local epidemiology and available resources should be implemented to preserve the efficiency and adaptability of our institutions and provide the adequate sanitary response

Correction: Surgeons’ perspectives on artificial intelligence to support clinical decision-making in trauma and emergency contexts: results from an international survey

Correction: Surgeons' perspectives on artificial intelligence to support clinical decision-making in trauma and emergency contexts: results from an international surve

Atypical cardiac defects in patients with RASopathies: Updated data on CARNET study

Background: RASopathies are a set of relatively common autosomal dominant clinically and genetically heterogeneous disorders. Cardiac outcomes in terms of mortality and morbidity for common heart defects (such as pulmonary valve stenosis and hypertrophic cardiomyopathy) have been reported. Nevertheless, also Atypical Cardiac Defects (ACDs) are described. The aim of the present study was to report both prevalence and cardiac outcome of ACDs in patients with RASopathies. Methods: A retrospective, multicentric observational study (CArdiac Rasopathy NETwork—CARNET study) was carried out. Clinical, surgical, and genetic data of the patients who were followed until December 2019 were collected. Results: Forty‐five patients out of 440 followed in CARNET centers had ACDs. Noonan Syndrome (NS), NS Multiple Lentigines (NSML) and CardioFacioCutaneous Syndrome (CFCS) were present in 36, 5 and 4 patients, respectively. Median age at last follow‐up was 20.1 years (range 6.9–47 years). Different ACDs were reported, including mitral and aortic valve dysfunction, ascending and descending aortic arch anomalies, coronary arteries dilation, enlargement of left atrial appendage and isolated pulmonary branches diseases. Five patients (11%) underwent cardiac surgery and one of them underwent a second intervention for mitral valve replacement and severe pericardial effusion. No patients died in our cohort until December 2019. Conclusions: Patients with RASopathies present a distinct CHD spectrum. Present data suggest that also ACDs must be carefully investigated for their possible impact on the clinical outcome. A careful longitudinal follow up until the individuals reach an adult age is recommended