Molecular Crowding: The History and Development of a Scientific Paradigm.

It is now generally accepted that macromolecules do not act in isolation but "live" in a crowded environment, that is, an environment populated by numerous different molecules. The field of molecular crowding has its origins in the far 80s but became accepted only by the end of the 90s. In the present issue, we discuss various aspects that are influenced by crowding and need to consider its effects. This Review is meant as an introduction to the theme and an analysis of the evolution of the crowding concept through time from colloidal and polymer physics to a more biological perspective. We introduce themes that will be more thoroughly treated in other Reviews of the present issue. In our intentions, each Review may stand by itself, but the complete collection has the aspiration to provide different but complementary perspectives to propose a more holistic view of molecular crowding.

Defining Strategies of Modulation of Antiplatelet Therapy in Patients With Coronary Artery Disease: A Consensus Document from the Academic Research Consortium.

Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions.

TransCatheter aortic valve implantation and fractional flow reserve-guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and multivessel or advanced coronary disease: The transcatheter valve and vessels trial (TCW trial): Design and rationale.

BACKGROUND: Patients with severe aortic stenosis (AS) frequently present with concomitant obstructive coronary artery disease (CAD). In those, current guidelines recommend combined coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) as the preferred treatment option, although this surgical approach is associated with a high rate of clinical events. Combined transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) with or without FFR have evolved as a valid alternative for cardiac surgery in patients with AS and multivessel or advanced CAD. To date, no dedicated trial has prospectively evaluated the outcomes of a percutaneous versus surgical treatment for patients with both severe AS and CAD. AIMS: To investigate whether fractional-flow reserve (FFR)-guided PCI and TAVI is noninferior to combined CABG and SAVR for the treatment of severe AS and multivessel or advanced CAD. METHODS: The Transcatheter Valve and Vessels (TCW) trial (clinicaltrial.gov: NCT03424941) is a prospective, randomized, controlled, open label, international trial. Patients ≥ 70 years with severe AS and multivessel (≥ 2 vessels) or advanced CAD, deemed feasible by the heart team for both; a full percutaneous or surgical treatment, will be randomised in a 1:1 fashion to either FFR-guided PCI followed by TAVI (intervention arm) vs. CABG and SAVR (control arm). The primary endpoint is a patient-oriented composite of all-cause mortality, myocardial infarction, disabling stroke, unscheduled clinically-driven target vessel revascularization, valve reintervention, and life threatening or disabling bleeding at 1 year. The TCW trial is powered for noninferiority, and if met, superiority will be tested. Assuming a primary endpoint rate of 30% in the CABG-SAVR arm, with a significance level α of 5%, a noninferiority limit delta of 15% and a loss to follow-up of 2%, a total of 328 patients are needed to obtain a power of 90%. The primary endpoint analysis is performed on an intention-to-treat basis. SUMMARY: The TCW Trial is the first prospective randomized trial that will study if a less invasive percutaneous treatment for severe AS and concomitant advanced CAD (i.e., FFR-guided PCI-TAVI) is noninferior to the guidelines recommended approach (CABG-SAVR).

The unexpected social cost of inguinal hernioplasty procedures derived from the COVID-19 pandemic: Surgical trend analysis based on an Italian hospital series.

BACKGROUND: The majority of inguinal hernias are usually paucisymptomatic, so are restored electively. The main purpose of this study is to assess the trends in hernia repair surgery before and during the pandemic period, analyzing an Italian hospital series of 390 patients, in an attempt to quantify the negative impact regarding social costs derived from the Covid-19 outbreak. Moreover, we want to focus on the concept of apparently minor pathology as hernioplasty which could represent a life-threatening condition for patients. METHODS: The study population consisted of all patients operated for inguinal hernia in a General Surgery Unit from 2019 to 2021, divided into a pre-pandemic and a pandemic period. RESULTS: The Covid-19 pandemic increased urgent operations in a complicated setting. A statistically significant difference was found regarding the trend of hospitalization length as well as a strong positive correlation between the severity of hernia and the hospitalization length. CONCLUSIONS: During the pandemic, it has been registered a mishandling of inguinal hernias to the detriment of both the healthcare system and patients, due to multifactorial issues and, in particular, to the restrictions imposed by the regional government that erroneously declassed hernia pathology as a minor problem for public health. We do believe that patients, after diagnosis of inguinal hernia, should learn the Taxis maneuver for its feasibility and ease of execution, in order to reduce access to emergencies in many cases and likewise to better pain and discomfort perceived, even in the event of unexpected worldwide healthcare scenario.

Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials.

AIMS: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients. METHODS AND RESULTS: A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation. CONCLUSION: In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen. STUDY REGISTRATION: PROSPERO registration number CRD42021284004.

Perivascular adipose tissue as a source of therapeutic targets and clinical biomarkers.

Obesity is a modifiable cardiovascular risk factor, but adipose tissue (AT) depots in humans are anatomically, histologically, and functionally heterogeneous. For example, visceral AT is a pro-atherogenic secretory AT depot, while subcutaneous AT represents a more classical energy storage depot. Perivascular adipose tissue (PVAT) regulates vascular biology via paracrine cross-talk signals. In this position paper, the state-of-the-art knowledge of various AT depots is reviewed providing a consensus definition of PVAT around the coronary arteries, as the AT surrounding the artery up to a distance from its outer wall equal to the luminal diameter of the artery. Special focus is given to the interactions between PVAT and the vascular wall that render PVAT a potential therapeutic target in cardiovascular diseases. This Clinical Consensus Statement also discusses the role of PVAT as a clinically relevant source of diagnostic and prognostic biomarkers of vascular function, which may guide precision medicine in atherosclerosis, hypertension, heart failure, and other cardiovascular diseases. In this article, its role as a 'biosensor' of vascular inflammation is highlighted with description of recent imaging technologies that visualize PVAT in clinical practice, allowing non-invasive quantification of coronary inflammation and the related residual cardiovascular inflammatory risk, guiding deployment of therapeutic interventions. Finally, the current and future clinical applicability of artificial intelligence and machine learning technologies is reviewed that integrate PVAT information into prognostic models to provide clinically meaningful information in primary and secondary prevention.

Prognostic role of CRP-independent inflammatory patterns in patients undergoing primary percutaneous interventions.

BACKGROUND: Despite the key pathophysiological role of inflammation in the development of coronary artery disease (CAD), the evaluation of inflammatory status has not been clearly established in patients presenting with acute coronary syndrome (ACS). The aim of this study is to evaluate the prevalence of CRP-independent inflammatory patterns in patients referred for primary percutaneous coronary intervention (pPCI) and to determine their one-year relationship with adverse clinical outcomes. METHODS: We carried out a single-centre, observational study consecutively enrolling all patients presenting at a large-volume PCI hub with a diagnosis of ST-segment elevation myocardial infarction (STEMI) and treated with pPCI. Systemic immune-inflammatory index (SII) was calculated at admission and discharge. According to different SII trajectories patients were divided into four patterns: 'persistent-low', 'down-sloping', 'up-sloping' and 'persistent-high' patterns. The primary endpoint was a composite of all-cause of death and myocardial infarction (MI) at a one-year follow-up. RESULTS: Among the total 2353 subjects enrolled, 44% of them belonged to 'persistent-low', 31% to 'down-sloping', 4% to 'up-sloping' and 21% to 'persistent-high' pattern. The primary endpoint was observed in 8% of patients with a 'persistent-low', 12% with a 'down-sloping', 27% with an 'up-sloping' and 25% with a persistent-high pattern (p = 0.001). After multivariate analysis, 'up-sloping' (OR: 3.2 [1.59-3.93]; p = 0.001) and 'persistent-high' (OR: 4.1 [3.03-4.65]; p = 0.001) patterns emerged as independent predictors of one-year adverse events. CONCLUSIONS: 'Persistent-high' and 'up-sloping' CRP-independent inflammatory patterns in patients undergoing primary PCI are associated with an increased risk of adverse events at one-year follow-up. The prognostic value of these inflammatory patterns might be helpful to individualize potential therapeutic targets.

Oligo-metastatic neoPlasms from the gastro-intestinal tract: iDentIfiCaTIon of cliNical and molecular drivers: the PREDICTION study.

BACKGROUND: Metastatic disease in tumors originating from the gastrointestinal tract can exhibit varying degrees of tumor burden at presentation. Some patients follow a less aggressive disease course, characterized by a limited number of metastatic sites, referred to as "oligo-metastatic disease" (OMD). The precise biological characteristics that define the oligometastatic behavior remain uncertain. In this study, we present a protocol designed to prospectively identify OMD, with the aim of proposing novel therapeutic approaches and monitoring strategies. METHODS: The PREDICTION study is a monocentric, prospective, observational investigation. Enrolled patients will receive standard treatment, while translational activities will involve analysis of the tumor microenvironment and genomic profiling using immunohistochemistry and next-generation sequencing, respectively. The first primary objective (descriptive) is to determine the prevalence of biological characteristics in OMD derived from gastrointestinal tract neoplasms, including high genetic concordance between primary tumors and metastases, a significant infiltration of T lymphocytes, and the absence of clonal evolution favoring specific driver genes (KRAS and PIK3CA). The second co-primary objective (analytic) is to identify a prognostic score for true OMD, with a primary focus on metastatic colorectal cancer. The score will comprise genetic concordance (> 80%), high T-lymphocyte infiltration, and the absence of clonal evolution favoring driver genes. It is hypothesized that patients with true OMD (score 3+) will have a lower rate of progression/recurrence within one year (20%) compared to those with false OMD (80%). The endpoint of the co-primary objective is the rate of recurrence/progression at one year. Considering a reasonable probability (60%) of the three factors occurring simultaneously in true OMD (score 3+), using a significance level of α = 0.05 and a test power of 90%, the study requires a minimum enrollment of 32 patients. DISCUSSION: Few studies have explored the precise genetic and biological features of OMD thus far. In clinical settings, the diagnosis of OMD is typically made retrospectively, as some patients who undergo intensive treatment for oligometastases develop polymetastatic diseases within a year, while others do not experience disease progression (true OMD). In the coming years, the identification of true OMD will allow us to employ more personalized and comprehensive strategies in cancer treatment. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05806151.

Prognostic significance of the SYNTAX score and SYNTAX score II in patients with myocardial infarction treated with percutaneous coronary intervention.

OBJECTIVES: We aimed to evaluate the prognostic significance of the SYNTAX score (SS) and SYNTAX score II (SS-II) in a contemporary real-world cohort of myocardial infarction (MI) patients treated with percutaneous coronary intervention (PCI). BACKGROUND: The role of SS and SS-II in the prognostic stratification of patients presenting with MI and undergoing PCI has been poorly investigated. METHODS: This study included MI patients treated with PCI from January 2015 to April 2020 at the University Hospital of Salerno. Patients were divided into tertiles according to the baseline SS and SS-II values. The primary outcome measure was all-cause mortality at long-term follow-up; secondary outcome measures were cardiovascular (CV) death and MI. RESULTS: Overall, 915 patients were included in this study. Mean SS and SS-II were 16.1 ± 10.0 and 31.6 ± 11.5, respectively. At propensity weighting adjusted Cox regression analysis, both SS (hazard ratio [HR]: 1.02; 95% confidence interval [CI]: 1.02-1.06; p = 0.017) and SS-II (HR: 1.08; 95% CI: 1.07-1.10; p < 0.001) were significantly associated with the risk of all-cause mortality at long-term follow-up; both SS (HR 1.04; CI 1.01-1.06; p < 0.001) and SS-II (HR 1.08; CI 1.06-1.10; p < 0.001) were significantly associated with the risk of CV death, but only SS-II showed a significant association with the risk of recurrent MI (HR 1.03; CI 1.01-1.05; p < 0.001). At 5 years, SS-II showed a significantly higher discriminative ability for all-cause mortality than SS (area under the curve: 0.82 vs. 0.64; p < 0.001). SS-II was able to reclassify the risk of long-term mortality beyond the SS (net reclassification index 0.88; 95% CI: 0.38-1.54; p = 0.033). CONCLUSIONS: In a real-world cohort of MI patients treated with PCI, SS-II was a stronger prognostic predictor of long-term mortality than SS.

Prevalence and clinical significance of electrocardiographic signs of atrial myopathy in rheumatoid arthritis: results from the EDRA study.

OBJECTIVES: We sought to determine whether the increased risk of atrial fibrillation and stroke in rheumatoid arthritis (RA) can be accounted for by an increased prevalence of electrocardiographic markers of atrial myopathy. METHODS: We retrospectively evaluated clinical and electrocardiographic data of 218 RA patients prospectively enrolled in the Endothelial Dysfunction Evaluation for Coronary Heart Disease Risk Estimation in Rheumatoid Arthritis study (EDRA study ClinicalTrials.gov: NCT02341066) and 109 controls matched by age and gender. The prevalence of interatrial blocks (IAB, partial - pIAB or advanced - aIAB), abnormal P-wave terminal force in lead V1 (aPtfV1) and atrial myopathy (electrocardiographically defined as the presence of 1) aIAB, or 2) pIAB plus abnormal aPtfV1) was assessed in each group. RA patients were followed-up for 5 years for incident atrial fibrillation and cardiovascular events. RESULTS: Barring the prevalence of hyperlipidaemia and obesity, the demographic characteristics and cardiovascular risk profile of RA patients and controls were comparable. All subjects enrolled in the study were free from previous cardiovascular disease and atrial fibrillation. Compared to controls, RA patients had longer P-wave duration (118±12 vs. 112±10 ms, p<0.001) and higher prevalence of pIAB (43% vs. 21%, p<0.001) and abnormal PtfV1 (27% vs. 10%, p<0.001). Accordingly, atrial myopathy was significantly more prevalent (15% vs 4%, p=0.003) in RA patients. In multiple regression, male gender (OR [95% CI] = 3.09 [1.48-6.47], p=0.003) and RA (OR [95% CI] = 4.83 [1.58-14.73], p=0.006) were independently associated with atrial myopathy. Atrial myopathy was not significantly associated with incident atrial fibrillation or cardiovascular events in RA patients after 5 years of follow-up. CONCLUSIONS: Electrocardiographic markers of atrial myopathy are independently associated with RA. Further studies with larger sample size and longer follow-up are needed to determine whether the increased prevalence of atrial myopathy contributes to the increased risk of atrial fibrillation and stroke in this group.

Lipoprotein associated- phospholipase A2 in STEMI vs. NSTE-ACS patients: a marker of cardiovascular atherosclerotic risk rather than thrombosis.

The precise role of Lipoprotein associated phospholipase A2 (Lp-PlA2) in the pathogenesis of acute coronary syndromes (ACS) and in the prediction of future cardiovascular events is still debated. So far, few data exist on the variations of Lp-PlA2 activity in ACS and especially in NSTE-ACS vs. STEMI patients, where thrombotic and atherosclerotic mechanisms could play a differential role. The aim of the present study was, then, to compare Lp-PlA2 activity according to the type of ACS presentation. METHODS: A consecutive cohort of patients undergoing coronary angiography for acute coronary syndrome (ACS) were included and divided according to presentation for non ST-segment elevation-ACS or ST-segment elevation Myocardial Infarction (STEMI). Lp-PLA2 activity was assessed in blood samples drawn at admission using the Diazyme Lp-PlA2 Activity Assay. RESULTS: We included in our study 117 patients, of whom 31 (26.5%) presented with STEMI. STEMI patients were significantly younger (p = 0.05), displayed a lower rate of hypertension (p = 0.002), previous MI (p = 0.001) and PCI (p = 0.01) and used less frequently statins (p = 0.01) and clopidogrel (p = 0.02). White blood cells and admission glycemia were increased in STEMI (p = 0.001, respectively). The prevalence and severity of CAD was not different according to ACS types, but for a higher prevalence of thrombus (p < 0.001) and lower TIMI flow (p = 0.002) in STEMI. The levels of Lp-PlA2 were significantly lower in STEMI as compared to NSTE-ACS patients, (132 ± 41.1 vs. 154.6 ± 40.9 nmol/min/mL, p = 0.01). In fact, the rate of patients with Lp-PlA2 above the median (148 nmol/min/mL) was significantly lower in STEMI patients as compared to NSTE-ACS (32.3% vs. 57%, p = 0.02, adjusted OR[95% CI] = 0.20[0.06-0.68], p = 0.010). Moreover, a direct linear relationship was observed between Lp-PlA2 and LDL-C (r = 0.47, p < 0.001), but not with inflammatory biomarkers. CONCLUSION: The present study shows that among ACS patients, the levels of Lp-PlA2 are inversely associated with STEMI presentation and thrombotic coronary occlusion, being instead increased in NSTE-ACS patients, therefore potentially representing a marker of more aggressive chronic cardiovascular disease with an increased risk of recurrent cardiovascular events.

Management of acute coronary syndromes in older adults.

Older patients are underrepresented in prospective studies and randomized clinical trials of acute coronary syndromes (ACS). Over the last decade, a few specific trials have been conducted in this population, allowing more evidence-based management. Older adults are a heterogeneous, complex, and high-risk group whose management requires a multidimensional clinical approach beyond coronary anatomic variables. This review focuses on available data informing evidence-based interventional and pharmacological approaches for older adults with ACS, including guideline-directed management. Overall, an invasive approach appears to demonstrate a better benefit-risk ratio compared to a conservative one across the ACS spectrum, even considering patients' clinical complexity and multiple comorbidities. Conversely, more powerful strategies of antithrombotic therapy for secondary prevention have been associated with increased bleeding events and no benefit in terms of mortality reduction. An interdisciplinary evaluation with geriatric assessment should always be considered to achieve a holistic approach and optimize any treatment on the basis of the underlying biological vulnerability.

Impact of chronic obstructive pulmonary disease on short-term outcome in patients with ST-elevation myocardial infarction during COVID-19 pandemic: insights from the international multicenter ISACS-STEMI registry.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study. METHODS: In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents. RESULTS: A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658-1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620-1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups. CONCLUSION: This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity. TRIAL REGISTRATION NUMBER: NCT04412655 (2nd June 2020).

Short-term dual antiplatelet therapy in diabetic patients admitted for acute coronary syndrome treated with a new-generation drug-eluting stent.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) admitted with acute coronary syndrome (ACS) and treated with a drug-eluting stent (DES) remains unclear. This is a prespecified sub-study from the Randomised Evaluation of short-term DUal antiplatelet therapy in patients with acute Coronary syndromE treated with a new generation DES (REDUCE) trial that was designed to determine the efficacy and safety of short-term versus standard 12 months DAPT in diabetic patients with ACS undergoing percutaneous coronary intervention (PCI) using the COMBO stent. METHODS: In this study we included ACS diabetic patients enroled in the REDUCE trial treated with the COMBO stent and randomly assigned to either 3 or 12 months of DAPT. The primary study endpoint was the composite of all-cause mortality, myocardial infarction (MI), stent thrombosis (ST), stroke, target vessel revascularisation (TVR), and bleeding complications at 12 and 24 months follow-up. RESULTS: A total of 307 diabetic patients were included, of which 162 (52.8%) in the 3 months DAPT group and 145 (47.2%) in the 12 months DAPT group. Patient characteristics, PCI success, and number of stents used were similar in the 3 and 12 months DAPT groups. Occurrence of the primary study endpoint at 12 and 24 months follow-up was comparable between the two groups (3.1 vs. 3.5%, p = 0.865, and 15.8 vs. 14.9%, p = 0.824, respectively). Moreover, the prevalence of the specific clinical outcome parameters (all-cause mortality), MI, ST, stroke, TVR, and bleeding was similar in both study groups. CONCLUSIONS: This sub-analysis shows similar clinical outcomes following 3 months DAPT as compared to 12 months DAPT in diabetic patients undergoing PCI for ACS using the COMBO stent. These results suggest that, even in this particular subset of patients, short duration of DAPT might be considered safe. Future larger studies are warranted to provide more precise estimations in terms of safety and efficacy of short term DAPT in these high-risk patients.

Relationship between vitamin D and cholesterol levels in STEMI patients undergoing primary percutaneous coronary intervention.

BACKGROUND AND AIMS: Special interest has been raised on vitamin D association with the metabolic profile, potentially interfering with lipid parameters and lipid-lowering therapies. The aim of the present study was to assess the impact of vitamin D on the cholesterol levels among patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. METHODS AND RESULTS: A consecutive cohort of 450 patients admitted for STEMI treated with pPCI were retrospectively identified and divided according to tertiles values of 25(OH). The levels of 25(OH)D were assessed at admission by chemiluminescence immunoassay kit LIAISON®Vitamin D assay (Diasorin Inc). Lower vitamin D was associated to a higher use of diuretics (p = 0.03), lower prevalence of lesions on bifurcations (p = 0.001) and smaller diameter of the target coronary vessel (p = 0.03), but higher coronary calcifications (p = 0.007). Total and LDL cholesterol levels were significantly increased in patients with lower vitamin D (p = 0.05 and p = 0.005), inversely relating with total cholesterol (r = -0.09, p = 0.06) and LDL-C (r = -013, p = 0.007), and directly with HDL-C (r = 0.16, p = 0.001). Results were not affected by statin therapy, with a significant relationship being confirmed for atherogenic lipids, but not for HDL-C in statin treated patients. In fact, at multivariate analysis, vitamin D in lower tertiles emerged as an independent predictor of LDL-C elevated or above the target (adjusted OR [95%CI] = 2.6 [1.51-4.44], p = 0.001). CONCLUSION: The present study shows that among patients with STEMI undergoing primary revascularization, lower levels of vitamin D are independently associated with a more atherogenic lipid profile. Similar results were observed in statin treated or naïve patients.

Lipoprotein(a) levels and risk of adverse events after myocardial infarction in patients with and without diabetes.

INTRODUCTION: The aim of this study was to evaluate the association of lipoprotein(a) [Lp(a)] levels with long-term outcome in patients with recent history of myocardial infarction (MI), and to investigate if diabetes may influence this association. METHODS: Consecutive MI patients who underwent urgent/emergent coronary angiography from February 2013 to June 2019 were prospectively collected. The primary outcome was the composite of MI recurrence and all-cause death. The propensity score weighting technique was used to account for covariates potentially influencing the relationship between Lp(a) levels and the study outcomes. RESULTS: The study population consisted of 1018 post-MI patients (median age 63 years). Diabetes was reported in 280 patients (27.5%), who showed lower Lp(a) levels than patients without diabetes (p = 0.026). At a median follow-up of 1121 days, the primary outcome was reported in 182 patients (17.9%). At univariable Cox regression analysis, Lp(a) was associated with the risk of the primary outcome in the overall population and in non-diabetic patients, but not in diabetics. The adjusted Cox regression analysis confirmed the independent association between Lp(a) values and the primary outcome in non-diabetic patients, but not in diabetics.Lp(a) levels > 70 mg/dL were independently associated with the risk of the primary outcome in non-diabetic patients (adjusted HR: 2.839; 95% CI, 1.382-5.832), but not in diabetics. CONCLUSIONS: In this real-world post-MI population, increasing Lp(a) levels were significantly associated with the risk of recurrent MI and all-cause death, and very high Lp(a) serum concentration independently predicted long-term outcome in non-diabetic patients, but not in diabetics.

Renal cell carcinoma: the population, real world, and cost-of-illness.

BACKGROUND: The RCC treatment landscape has evolved dramatically over the past decade. The purpose of this study is to present a real-world data estimation of RCC's cost-of-illness for this tumour's clinical pathway. METHODS: This investigation is a population-based cohort study using real-world data, which considers all RCC incident cases diagnosed in Local Unit 6 of the Province of Padua in 2016 and 2017 as registered by the Veneto Cancer Registry. Data on drug prescriptions, the use of medical devices, hospital admissions, and visits to outpatient clinics and emergency departments were collected by means of administrative databases. We evaluated the costs of all healthcare procedures performed in the 2 years of follow-up post-RCC diagnosis. The overall and annual average real-world costs per patient, both as a whole and by single item, were calculated and stratified by stage of disease at diagnosis. RESULTS: The analysis involved a population of 148 patients with a median age of 65.8 years, 66.22% of whom were male. Two years after diagnosis, the average total costs amounted to €21,429 per patient. There is a steady increment in costs with increasing stage at diagnosis, with a total amount of €41,494 spent 2 years after diagnosis for stage IV patients, which is 2.44 times higher than the expenditure for stage I patients (€17,037). In the first year, hospitalization appeared to be the most expensive item for both early and advanced disease. In the second year, however, outpatient procedures were the main cost driver in the earlier stages, whereas anticancer drugs accounted for the highest costs in the advanced stages. CONCLUSIONS: This observational study provides real-world and valuable estimates of RCC's cost-of-illness, which could enable policymakers to construct dynamic economic cost-effectiveness evaluation models based on real world costs' evaluation.

Incident reporting reduction during the COVID-19 pandemic in a tertiary Italian hospital: A retrospective analysis.

BACKGROUND: Incident reporting (IR) is one of the most used systems to gain knowledge of adverse events (AEs) and to identify sources of risk. During COVID-19 pandemic, several organizational changes have been implemented to respond adequately and effectively to the emergency; this required the suspension of most deferrable activities. OBJECTIVE: The aim of this study is to investigate whether IR attitude of health workers has been reduced during the pandemic event. METHOD: A retrospective analysis was conducted at the Azienda Ospedale - Università di Padova (Italy), considering IR of years 2019 and 2020. To standardize the effects of the decrease in admissions, we considered the number of incidents per 1000 admissions. RESULTS: Data shows that during the first (March-May 2020) and second waves (October-December 2020) of the COVID-19 pandemic there was a statistically significant reduction in the rate of IR for every 1000 admissions (P = 0.001-Wilcoxon test), especially for AEs and in COVID-19 units. CONCLUSION: This study shows a reduction in IR especially during the first and second pandemic waves of COVID-19 in year 2020. Education and training interventions could be fundamental to raise awareness of the importance of IR in health workers, as this could provide opportunities to understand what is impacting on safety in a particular healthcare context and enable continuous improvement.

Thin-cap fibroatheroma predicts clinical events in diabetic patients with normal fractional flow reserve: the COMBINE OCT-FFR trial.

AIMS: The aim of this study was to understand the impact of optical coherence tomography (OCT)-detected thin-cap fibroatheroma (TCFA) on clinical outcomes of diabetes mellitus (DM) patients with fractional flow reserve (FFR)-negative lesions. METHODS AND RESULTS: COMBINE OCT-FFR study was a prospective, double-blind, international, natural history study. After FFR assessment, and revascularization of FFR-positive lesions, patients with ≥1 FFR-negative lesions (target lesions) were classified in two groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint compared FFR-negative TCFA-positive patients with FFR-negative TCFA-negative patients for a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or unstable angina requiring hospitalization at 18 months. Among 550 patients enrolled, 390 (81%) patients had ≥1 FFR-negative lesions. Among FFR-negative patients, 98 (25%) were TCFA positive and 292 (75%) were TCFA negative. The incidence of the primary endpoint was 13.3% and 3.1% in TCFA-positive vs. TCFA-negative groups, respectively (hazard ratio 4.65; 95% confidence interval, 1.99-10.89; P < 0.001). The Cox regression multivariable analysis identified TCFA as the strongest predictor of major adverse clinical events (MACE) (hazard ratio 5.12; 95% confidence interval 2.12-12.34; P < 0.001). CONCLUSIONS: Among DM patients with ≥1 FFR-negative lesions, TCFA-positive patients represented 25% of this population and were associated with a five-fold higher rate of MACE despite the absence of ischaemia. This discrepancy between the impact of vulnerable plaque and ischaemia on future adverse events may represent a paradigm shift for coronary artery disease risk stratification in DM patients.

Association of lower vitamin D levels with inflammation and leucocytes parameters in patients with and without diabetes mellitus undergoing coronary angiography.

BACKGROUND: Diabetes mellitus has been associated with a chronic low-grade inflammation and a higher risk of cardiovascular and infectious disease, that could be prevented by the effects of vitamin D. We aimed at evaluating the impact of vitamin D levels on the biomarkers of acute-phase response, inflammation and glucose metabolism in a large cohort of diabetic patients with cardiovascular disease. MATERIALS AND METHODS: Consecutive patients undergoing coronary angiography were included. Diabetes mellitus was defined as previous diagnosis, specific treatment administration (oral drug or insulin), fasting glycaemia >6.99 mmol/L or HbA1c >48 mmol/L. Glucose parameters, white blood cells, Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), C-reactive protein (CRP) and vitamin D were measured at admission. Vitamin D levels were measured by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc). RESULTS: We included 1472 diabetic patients and 2499 non-diabetic patients that were divided according to vitamin D tertiles. Among diabetic patients, lower levels of vitamin D were associated with female gender (P = .02), obesity (P = .004), active smoking and acute presentation (P < .001) and with a more atherogenic metabolic profile. The levels of white blood cells, leucocytes subfamilies, and inflammatory parameters significantly correlated with vitamin D levels in both patients with and without diabetes (diabetic: P = .012 for WBC, P = .004 for NLR and P < .001 for MLR and C-reactive protein, non-diabetic: P < .001 for WBC; NLR, MLR and C-reactive protein, respectively). Among diabetic patients, results were confirmed at multivariate analysis with no significant interaction according to glycaemic control. CONCLUSION: The present study demonstrates that, among patients with cardiovascular disease, vitamin D deficiency is associated with metabolic dysregulation and with an elevation of cellular and humoural inflammatory parameters, especially among diabetics, although not being dependent from glycaemic control.