Signed Distance Correlation (SiDCo): an online implementation of distance correlation and partial distance correlation for data-driven network analysis.

MOTIVATION: There is a need for easily accessible implementations that measure the strength of both linear and non-linear relationships between metabolites in biological systems as an approach for data-driven network development. While multiple tools implement linear Pearson and Spearman methods, there are no such tools that assess distance correlation. RESULTS: We present here SIgned Distance COrrelation (SiDCo). SiDCo is a GUI platform for calculation of distance correlation in omics data, measuring linear and non-linear dependencies between variables, as well as correlation between vectors of different lengths, e.g. different sample sizes. By combining the sign of the overall trend from Pearson's correlation with distance correlation values, we further provide a novel "signed distance correlation" of particular use in metabolomic and lipidomic analyses. Distance correlations can be selected as one-to-one or one-to-all correlations, showing relationships between each feature and all other features one at a time or in combination. Additionally, we implement "partial distance correlation," calculated using the Gaussian Graphical model approach adapted to distance covariance. Our platform provides an easy-to-use software implementation that can be applied to the investigation of any dataset. AVAILABILITY AND IMPLEMENTATION: The SiDCo software application is freely available at https://complimet.ca/sidco. Supplementary help pages are provided at https://complimet.ca/sidco. Supplementary Material shows an example of an application of SiDCo in metabolomics.

Randomized clinical trial of abluminus DES+ sirolimus-eluting stent versus everolimus-eluting DES for percutaneous coronary intervention in patients with diabetes mellitus: An optical coherence tomography study.

BACKGROUND: Diabetic patients are at higher risk of recurrent adverse events following percutaneous coronary intervention (PCI) than the nondiabetics. Despite the introduction of new generation drug-eluting stents, their efficacy in the diabetics is still limited. AIMS: To evaluate the efficacy of the Abluminus DES+ biodegradable polymer sirolimus-eluting stent in reducing neointimal hyperplasia in diabetic patients, compared to a durable polymer everolimus-eluting stent (DP-EES). METHODS: A total of 131 patients with diabetes and coronary artery disease were enrolled in six Italian centers and randomized in a 2:1 fashion to PCI with Abluminus DES+ or DP-EES: 85 were assigned to Abluminus DES+ and 46 to DP-EES. The primary endpoint was optimal coherence tomography (OCT)-derived neointimal volume at 9-12 months. Secondary endpoints included OCT-derived neointimal area, neointimal volume obstruction and adverse clinical events. RESULTS: The primary endpoint, neointimal volume, did not differ between Abluminus DES+ and DP-EES (29.11 ± 18.90 mm3 vs. 25.48 ± 17.04 mm3 , p = 0.40) at 9-12-month follow-up. This finding remained consistent after weighing for the sum of stents lengths (1.14 ± 0.68 mm3 vs. 0.99 ± 0.74 mm3 for Abluminus DES+ and DP-EES, respectively, p = 0.38). Similarly, other OCT-derived and clinical secondary endpoints did not significantly differ between the two groups. Rate of target lesion failure was high in both groups (21.2% for Abluminus DES+ and 19.6% for DP-EES). CONCLUSIONS: This preliminary study failed to demonstrate the superiority of the Abluminus DES+ over the DP-EES in diabetic patients in terms of neointimal proliferation.

Clinical SYNTAX score predicts outcomes of patients undergoing coronary artery bypass grafting.

BACKGROUND: The SYNTAX score (SS) is a determinant of outcome in patients undergoing percutaneous coronary intervention. In addition, it has been recently shown that the clinical SYNTAX score (cSS), obtained by adding clinical variables to the SS, improves the predictive power of the resulting risk model. We assessed the hypothesis that the use of the cSS may predict outcomes of patients undergoing coronary artery bypass grafting (CABG). METHODS: We measured the SYNTAX score in 874 patients undergoing isolated first time on-pump CABG. The clinical SYNTAX score was calculated at the time of the study using age, creatinine clearance and ejection fraction, the modified ACEF score, and analyses performed for major adverse cardiac and cerebrovascular events (MACCE) and all-cause mortality at 3-year follow-up. RESULTS: The mean age of the study population was 70.9 ± 8.1 years, and the median cSS 14.2 (range 2.1-286.5). The ROC curve analysis showed that a cSS >14.5 (81.4% sensitivity and 67.8% specificity) was a reliable tool in discrimination of patients for the occurrence of MACCE (AUC 0.78) and all-cause mortality (AUC 0.74). Kaplan-Meier survival analysis confirmed that patients belonging to higher cSS quartiles have poorer 3-year survival (P = .0001) and MACCE-free survival (P = .0001), with respect to those with lower cSS. CONCLUSIONS: This observational study has shown that the clinical SYNTAX score, incorporating the lesion-based SS and clinical-based ACEF score, predicted mid-term adverse outcomes of patients undergoing CABG and may play an important role in the risk stratification of this population. Further studies are needed to confirm these findings.

[Management strategies and choice of antithrombotic treatment in patients admitted with acute coronary syndrome--executive summary for clinical practice. Consensus Document of the Regional Chapters of the Italian National Association of Hospital Cardiologists (ANMCO) and of the Italian Society of Emergency Medicine (SIMEU)]. / Strategie Assistenziali e Scelta della Terapia Antitrombotica nei Pazienti Ricoverati con Diagnosi di Sindrome Coronarica Acuta--Sintesi Operativa per la Pratica Clinica. Documento congiunto delle Sezioni Regionali del Lazio dell'Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) e della Società Italiana di Medicina di Emergenza-Urgenza (SIMEU).

This document has been developed by the Lazio regional chapters of two scientific associations, the Italian National Association of Hospital Cardiologists (ANMCO) and the Italian Society of Emergency Medicine (SIMEU), whose members are actively involved in the everyday management of Acute Coronary Syndromes (ACS). The document is aimed at providing a specific, practical, evidence-based guideline for the effective management of antithrombotic treatment (antiplatelet and anticoagulant) in the complex and ever changing scenario of ACS. The document employs a synthetic approach which considers two main issues: the actual operative context of treatment delivery and the general management strategy.

Improving Antibiotic Prescribing for Dentistry in France Using an Ontology.

Antibiotic overprescribing in dentistry is a major concern that contributes to the emergence of antimicrobial resistance. It is due in part to the misuse of antibiotics by dentists but also by other practitioners who see patients in emergency for dental care. We used the Protégé software to create an ontology regarding the most common dental diseases and the most used antibiotics to treat them. It is an easy shareable knowledge base that could be used directly as decision support tool to improve the use of antibiotics in dental care.

[GISE (Italian Society of Interventional Cardiology) Position paper: Short-term hospitalization for percutaneous coronary intervention; a helpful tool to manage post-COVID-19 backlogs]. / Position paper GISE (Società Italiana di Cardiologia Interventistica): Ricovero breve per la PCI in elezione, uno strumento per la "ripartenza".

Minimization of hospital lengths of stay has always been a key goal for healthcare systems. More so during the current COVID-19 pandemic. In fact, we have faced a reduction in no-COVID-19 admissions with the generation of huge backlogs. Low-risk patients undergoing elective percutaneous coronary intervention (PCI) can be candidate for short-term hospitalization, with consequent reduction of waiting lists. Several single-center and multicenter observational studies, multiple randomized trials and some meta-analyses have addressed this topic.In this position paper, we present a proposal for short hospitalization for elective PCI procedures in selected patients who present complications only exceptionally and exclusively immediately after the procedure, if the inclusion and exclusion criteria are met. Each Center can choose between admission in day surgery or one day surgery, extending hospital length of stay only for patients who present complications or who are candidate for urgent surgery. Short-term hospitalization considerably reduces costs even if, with the current model, it generally results in a parallel reduction in reimbursement. Hence, we present an actual model, already tested successfully in an Italian hospital, that warrants sustainability. This approach can then be tailored to single Centers.

Texture analysis in 177Lu SPECT phantom images: Statistical assessment of uniformity requirements using texture features.

The purpose of this study was to apply texture analysis (TA) to evaluate the uniformity of SPECT images reconstructed with the 3D Ordered Subsets Expectation Maximization (3D-OSEM) algorithm. For this purpose, a cylindrical homogeneous phantom filled with 177Lu was used and a total of 24 spherical volumes of interest (VOIs) were considered inside the phantom. The location of the VOIs was chosen in order to define two different configurations, i.e. gravity and radial configuration. The former configuration was used to investigate the uniformity of distribution of 177Lu inside the phantom, while the latter configuration was used to investigate the lack of uniformity from center towards edge of the images. For each VOI, the trend of different texture features considered as a function of 3D-OSEM updates was investigated in order to evaluate the influence of reconstruction parameters. TA was performed using CGITA software. The equality of the average texture feature trends in both spatial configurations was assumed as the null hypothesis and was tested by functional analysis of variance (fANOVA). With regard to the gravity configuration, no texture feature rejected the null hypothesis when the number of subsets increased. For the radial configuration, the statistical analysis revealed that, depending on the 3D-OSEM parameters used, a few texture features were capable of detecting the non-uniformity of 177Lu distribution inside the phantom moving from the center of the image towards its edge. Finally, cross-correlation coefficients were calculated to better identify the features that could play an important role in assessing quality assurance procedures performed on SPECT systems.

Residual SYNTAX score following coronary artery bypass grafting.

Objectives: To quantify residual coronary artery disease measured using the SYNTAX score (SS) and its relation to outcomes after coronary artery bypass grafting (CABG). Methods: We conducted a retrospective analysis on a consecutive series of 1608 patients [mean age 68 years, standard deviation (SD): 7, F:M, 242:1366] undergoing first-time isolated CABG from 2004 to 2015. The baseline SS was retrospectively determined from preoperative angiograms, and the residual SS (rSS) was measured during assessment of the actual operative report for each patient after CABG. Patients were then stratified according to tercile cut points of low (rSS low 0-11, N = 537), intermediate (rSS mid >11-18.5, N = 539) and high residual SS (rSS high >18.5, N = 532). The Cox regression model was used to investigate the impact of rSS on major adverse cardiac and cerebrovascular events (MACCE) at 1 year. Results: The mean preoperative SS was 26.6 (SD: 9.4) (range 10.1-53), and the residual SS after CABG was 15.3 (SD: 8.4) (range 0-34) ( P < 0.001 versus preoperative). At 1 year, cumulative incidence of MACCE in the low rSS was 1.5% ( N = 8/537), 4.5% ( N = 24/539) in the intermediate and 8.8% ( N = 47/532) in the high rSS group. Kaplan-Meier analysis showed a statistically significant difference of MACCE-free survival between the three groups (log-rank test, P < 0.001). The estimated MACCE-free survival rate at 1 year was 98.1% [standard error (SE): 1.6] for the rSS low , 95.5% (SE: 1.9) for the rSS mid , and 90.5% (SE: 1.3) for the rSS high group, respectively. After multivariable adjustment, the rSS high group was independently associated with a higher incidence of MACCE at 1 year (hazard ratio 1.92, 95% confidence interval 1.21-3.23) compared to the rSS low group. Conclusions: These unanticipated findings suggest that a residual SS may be a useful tool for risk stratification of patients undergoing isolated first-time CABG. Our study may set the stage for further investigations addressing this important clinical question.

Early invasive versus early conservative strategy in non-ST-elevation acute coronary syndrome: An outcome research study.

BACKGROUND: An early invasive strategy (EIS) has been shown to yield a better clinical outcome than an early conservative strategy (ECS) in patients with non-ST-elevation acute coronary syndromes (NSTEACSs), particularly in those at higher risk according to the GRACE risk score. However, findings of the clinical trials have not been confirmed in registries. OBJECTIVE: To investigate the outcome of patients with NSTEACS treated according to an EIS or a ECS in a real-world all-comers outcome research study. METHODS: The primary hypothesis of the study was the non-inferiority of an ECS in comparison with an EIS as to a combined primary end-point of death, non-fatal myocardial infarction and hospital readmission for acute coronary syndromes at one year. Participating centres were divided into two groups: those with a pre-specified routine EIS and those with a pre-specified routine ECS. Two statistical analyses were performed: a) an 'intention to treat' analysis: all patients were considered to be treated according to the pre-specified routine strategy of that centre; b) a 'per protocol' analysis: patients were analysed according to the actual treatment applied. Cox model including propensity score correction was applied for all analyses. RESULTS: The intention to treat analysis showed an equivalence between EIS and ECS (11.4% vs. 11.1%) with regard to the primary end-point incidence at one year. In the three subgroups of patients according to the GRACE risk score (⩽ 108, 109-140, > 140), EIS and ECS confirmed their equivalence (5.3% vs. 3.9%, 8.4% vs. 7.6%, and 20.3% vs. 20.9%, respectively). When the per protocol analysis was applied, a reduction of the primary end-point at one year with EIS vs. ECS was demonstrated (6.2% vs. 15.3%, p=0.021); analysis of the subgroups according to the GRACE risk score numerically confirmed these data (3.1% vs. 6.5%, 5.1% vs. 10.0%, and 10.8% vs. 24.5%, respectively). CONCLUSIONS: In a real-life registry of all-comers NSTEACS patients, ECS was non-inferior to EIS; however, when EIS was applied according to clinical judgement, a reduction of clinical events at one year was demonstrated.

Prediction of early and delayed postoperative deaths after coronary artery bypass surgery alone in Italy. Multivariate predictions based on Cox and logistic models and a chart based on the accelerated failure time model.

BACKGROUND: The aim of the multicenter OP-RISK (OPerative RISK) study was to investigate the early (28 days) and delayed (365 days) death rates following coronary artery bypass grafting (CABG) among patients representing a nationwide distribution [Centers in Northern (2), Central (1) and Southern (1) Italy] and further to define the multivariate risk factors for the early and delayed mortality after CABG. METHODS: Data were collected from 1126 patients undergoing CABG alone. Data were analyzed using Cox and logistic regression models, to accurately assess the major factors influencing survival over time after CABG. Having defined the significant factors, we constructed a chart of the absolute early risk of mortality using the accelerated failure time model. RESULTS: Using the Cox proportional hazards model and logistic regression we have demonstrated that age, preoperative ejection fraction and heart rate, and the duration of aortic cross-clamping are multivariate risk factors in the short and long term. The role of one arterial conduit was also assessed. CONCLUSIONS: The OP-RISK study produced relevant information for risk assessment and control in CABG and the results may form the basis for the objective quality assurance and accreditation of cardiac surgical institutions in Italy. Incidentally, Cox model appeared more adequate than logistic model for the assessment of the major factors influencing survival over time after CABG. The risk factors so assessed were used to construct a chart for practical predictive purposes.

Potential additive effects of ticagrelor, ivabradine, and carvedilol on sinus node.

A 51-year-old male patient presented to the emergency room with an anterior ST-elevation myocardial infarction. After a loading dose of both ticagrelor and aspirin, the patient underwent primary-PCI on the left anterior descending coronary artery with stent implantation. After successful revascularization, medical therapy included beta-blockers, statins, and angiotensin II receptor antagonists. Two days later, ivabradine was also administered in order to reduce heart rate at target, but the patient developed a severe symptomatic bradycardia and sinus arrest, even requiring administration of both atropine and adrenaline. Ivabradine and ticagrelor have been then suspended and this latter changed with prasugrel. Any other similar event was not reported during the following days. This clinical case raised concerns about the safety of the combination of beta-blockers and ivabradine in patients treated with ticagrelor, particularly during the acute phase of an acute coronary syndrome. These two latter drugs, in particular, might interact with the same receptor. In fact, ivabradine directly modulates the If-channel which is also modulated by the cyclic adenosine monophosphate levels. These latter have been shown to increase after ticagrelor assumption via inhibition of adenosine uptake by erythrocytes. Further studies are warrant to better clarify the safety of this association.

Complexity of coronary artery disease affects outcome of patients undergoing coronary artery bypass grafting with impaired left ventricular function.

OBJECTIVE: To determine whether the SYNTAX score can predict the outcomes of patients with left ventricular dysfunction undergoing coronary artery bypass grafting. METHODS: We studied a consecutive series of 191 patients (mean age, 67 ± 10 years) with a left ventricular ejection fraction of 40% or less who were undergoing isolated coronary artery bypass grafting. All patients were stratified according to their SYNTAX score, indicating coronary artery disease complexity: low, 0 to 22; intermediate, 23 to 32; and high, 33 or more. The primary outcome was all-cause mortality. Secondary outcomes included the late occurrence of major adverse cardiac and cerebrovascular events, left ventricular function, and New York Heart Association functional class. RESULTS: The mean SYNTAX score was 32 ± 13, and the mean preoperative left ventricular ejection fraction was 35% ± 6%. At a median follow-up of 43 months, the primary outcome had occurred in 46 of 191 patients (24%). Kaplan-Meier analysis showed a survival of 81% ± 15% for low, 77% ± 7% for intermediate, and 53% ± 7% for high coronary artery disease complexity (χ(2), 29.4; P = .001). The rate of major adverse cardiac and cerebrovascular events was significantly greater in patients with a SYNTAX score of 33 or more (P = .002). Greater degrees of left ventricular ejection fraction improvement were found in patients with a SYNTAX score of 32 or less (+15% ± 10% vs +4% ± 11%; P = .17) and translated into a better New York Heart Association functional class among patients with a lower SYNTAX score (P = .01). Receiver operating characteristic curve analysis showed the SYNTAX score (area under the curve, 0.70; 95% confidence interval, 0.63-0.77) to have the best predictive power for late mortality with respect to the preoperative left ventricular ejection fraction (area under the curve, 0.59; difference, P = .04) and incomplete revascularization (area under the curve, 0.55; difference, P = .02). CONCLUSIONS: The results of the present study have shown a direct relationship between coronary artery disease complexity and late outcomes of patients with left ventricular dysfunction who are undergoing coronary artery bypass grafting. Additional studies are needed to confirm these findings.

Indicators of waste management efficiency related to different territorial conditions.

The amount of waste produced and the control of separate collection are crucial issues for the planning of a territorial Integrated Waste Management System, enabling the allocation of each sorted waste fraction to the proper treatment and recycling processes. The present study focuses on assessing indicators of different waste management systems in areas characterized by different territorial conditions. The investigated case study concerns the municipalities of Emilia Romagna (northern Italy), which present a rather uniform socioeconomic situation, but a variety of geographic, urban and waste management characteristics. A survey of waste generation and collection rates was carried out, and correlated with the different territorial conditions, classifying the municipalities according to altitude and population density. The best environmental performances, in terms of high separate collection rate, were found on average in rural areas in the plain, while the lowest waste generation was associated with rural hill towns.

Ambulatory monitoring predicts development of drug-treated hypertension in subjects with high normal blood pressure.

BACKGROUND: High normal blood pressure (HNBP), i.e. blood pressure (BP) > or = 130/85 mmHg and <140/90 mmHg, is an important predictor of progression to established hypertension. DESIGN: The purpose of this retrospective study was the evaluation of the predictive value of ambulatory blood pressure monitoring (ABPM) for the development of drug-treated hypertension in subjects with HNBP and other risk factors. METHODS: We studied 127 subjects (69 M, 58 F, age 50 +/- 14 years): 59 subjects had normal BP (NBP: < 130/85 mmHg), 68 subjects had systolic and/or diastolic HNBP. All the subjects underwent ABPM. There were 21/68 (30.9%) subjects in the HNBP group vs. 1/59 (1.7%) in the NBP group with an elevated (>135/85 mmHg) daytime ambulatory blood pressure (ABP) (p < 0.01). RESULTS: After an average follow-up of 103 +/- 28 months, 27 subjects (39.7%) in the HNBP group and 4 subjects (6.8%) in the NBP group developed drug-treated hypertension (p < 0.01). An elevated daytime ABP correctly predicted development of drug-treated hypertension in 17/21 subjects (81%) of the HNBP group and in the only subject of the NBP group. Development of drug-treated hypertension was associated with higher office and ambulatory BP (p < 0.01) and pulse pressures (p < 0.05), longer follow-up (p < 0.05) and higher prevalence of hypercholesterolaemia and smoking (p < 0.01). CONCLUSIONS: We conclude that ABPM correctly predicts development of drug-treated hypertension in most subjects who were identified early as having a daytime mean ABP >135/85 mmHg. ABPM appears to be a useful clinical tool in the early diagnosis of hypertension in subjects with metabolic risk factors and smoking.

Permanent pacing lead insertion through the cephalic vein using an hydrophilic guidewire.

The cephalic vein (CV) should be preferred to the subclavian vein for the insertion of permanent pacing leads because of better results. Unfortunately, the direct lead introduction using the standard CV cutdown is often unsuccessful. This study evaluated the efficacy and safety of a steerable hydrophilic guidewire (HGW) for lead insertion through the CV. An HGW was successfully introduced through the cephalic vein and into the subclavian vein. Over a 6-month period, 115 consecutive patients underwent pacemaker implantation. In nine (7.8%) patients, the cephalic vein did not allow lead or guidewire introduction. The direct introduction of the leads through the CV was successful in 55 (51.9%) of 106 patients. In 14 (12.2%) additional patients, a lead was inserted through the CV using a standard guidewire. The use of an HGW and of a split introducer allowed successful insertion of at least one lead in 35 (30.4%) additional patients. Overall, the HGW was successful in 35 (94.6%) of 37 of patients in which the technique was attempted. The CV approach was successful in 104 (90.4%) of 115 patients. In conclusion, the use of an HGW allows the insertion of a pacing lead through the CV in the great majority of patients in whom direct introduction and the use of a standard guidewire had failed. The technique significantly improves the success rate of the CV approach and may help to improve the acute and long-term results of permanent cardiac pacing.