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In the wake of recent COVID-19 pandemics scientists around the world rushed to deliver numerous CADD (Computer-Aided Drug Discovery) methods and tools that could be reliably used to discover novel drug candidates against the SARS-CoV-2 virus.

Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) results in electrical and structural remodeling of the atria, and the extent of remodeling has already been found to be associated with higher AF recurrence rate after catheter ablation (CA). Recently, a novel echocardiographic parameter derived from tissue Doppler imaging (TDI), called PA-TDI, has been introduced to assess the total atrial activation time, as a non-invasive surrogate of fibrosis and atrial cardiomyopathy. The aim of the study was to investigate the role of PA-TDI interval as predictor of AF ablation efficacy. Methods Consecutive patients with persistent or paroxysmal symptomatic AF referred to our Center to perform radiofrequency ablation or cryoablation procedures were prospectively enrolled. In these patients, a complete transthoracic echocardiographic examination was performed before and after the ablation procedure, including assessment of the PA-TDI interval. Results From October 2018 to May 2020, 221 consecutive patients (mean age 61 ± 9 years, 74% male, mean BMI 26.5 ± 3.6, mean Ejection Fraction 61 ± 6%) symptomatic for AF, undergoing the procedure ablation (first procedure or re-do) were enrolled. Out of the blanking period, 25% of patients experienced recurrence of arrhythmia during follow-up (mean 16 months). Compared to patients who did not relapse, patients with AF recurrence have a generally longer post-procedural PA-TDI interval (139.6 ± 22.1 msec vs 153.9 ± 33 msec, respectively). In the multivariable analysis only post-procedure PA-TDI and re-do interventions were found to be independent predictors of AF recurrence. A PA-TDI cut-off>144msec identifies patients at risk of post ablation AF recurrence with sensitivity 58.7% and specificity 73.5% (AUC 0.697). Conclusions The PA-TDI interval is an independent predictor of AF recurrence after catheter ablation. This echocardiographic parameter is easily obtainable, low-cost, reproducible, and accessible even in peripheral centers.

SARS-CoV-2 infection causes a multisystemic disease that affects numerous organs beyond the respiratory system. Thus, it is well known that COVID-19 is associated with a wide range of hematological disorders; however, it remains unclear how the SARS-CoV-2 virus is able to navigate from tissue to tissue. In this work, we performed a comprehensive analysis of the pleiotropic effects of a prototypical coronavirus in its natural host, the validated preclinical model of murine hepatitis virus (MHV). Throughout this study we compared our results with the real-world data from COVID-19 patients (including autopsies). Thus, the presence of viral RNA was only detected in less than 25% of the human serum samples, whereas all had multiple positive nasal swabs for SARS-CoV-2. Notably, we found viral RNA not only in lungs, but also in heart and kidney of deceased COVID-19 patients. Subsequently, we investigated the association between viral organotropism and clinical manifestations employing the MHV murine model. Results from RT-qPCR and viral infectivity showcased the presence of viral RNA and infectious particles in multiple organs including liver, lung, brain, heart, kidney, spleen and pancreas, and even the blood of infected mice. Surprisingly, when comparing plasma and red blood cells (RBCs)-enriched fraction, higher viral load levels were detected in RBCs, with decreased RBC count, and hematocrit and hemoglobin levels in infected mice. Next, we treated infected mice with hemin triggering more aggressive symptoms. Strikingly, when combining hemin treatment with chloroquine (a compound that known to interact with the heme group and induces a conformational change in its structure) the infection and its clinical manifestations were distinctly attenuated. Computational docking suggested that heme is able to bind to MHV Spike protein in a similar way to the one, experimentally observed for SARS-CoV-2. Overall, our results lead to a global perspective of COVID-19 beyond the canonical focus on the respiratory system, and strongly support the multi-organ extent of coronavirus infection through specific interactions with RBC hemoproteins.

Coastal dunes are extremely fragile and threatened ecotones, which play a key environmental role in terms of functional connection between terrestrial and marine ecosystems. To counteract the hydrogeological vulnerability in coastal risk areas, reliance can be made on soil bioengineering techniques, consisting of planting native species in combination with natural inert materials. These interventions involve the use of typical Mediterranean plant species, which are fundamental for increasing soil surface protection as well as for their ecologic function in coastal dune consolidation. Monitoring studies on plant growth parameters are useful to assess the suitability of the different species to be used in soil bioengineering works. Hence, this study aimed to (i) identify some Mediterranean herbaceous and shrubby plant species to be used in coastal interventions, (ii) evaluate different plant propagation methods and short-term growth parameters, and (iii) provide useful insights into field management strategies before and after transplanting.Juniperus phoenicea L., Juniperus macrocarpa Sm., Pistacia lentiscus L., Tamarix africana Poir. and Tamarix gallica L. were the selected shrubs species while Ammophila arenaria (L.) Link, Sporobolus pungens (Schreb.) Kunth., Agropyron junceum (L.) P. Beauv., Eryngium maritimum L., Calystegia soldanella (L.) R. Br., and Pancratium maritimum L. were the selected herbaceous species. As to shrubs, seeds and cuttings proved the best propagation methods with an efficiency of up to 90%. Agamic propagation methods, on the other hand, were the most efficient (80–90%) for the herbaceous species. After transplantation, all the species showed an adaptation period to the new climatic and edaphic conditions. In particular, Pistacia lentiscus L. was found withered with the presence of some radical shoots.

Background The echocardiographic evaluation of cardiac output relies on the product of the flow across the left ventricular outflow tract (LVOT), estimated through its velocity time integral (LVOT-VTI), and its cross-sectional area, estimated through the formula πr2. Considering the geometrical assumption behind such formula, LVOT-VTI has been proposed as a more reproducible surrogate of cardiac systolic function and showed prognostic value in the critical care setting. However, the role of such measure in patients with chronic heart failure (HF) remains unexplored. Objective To assess the clinical and prognostic significance of LVOT-VTI in a contemporary cohort of patients with chronic HF. Methods Outpatients with chronic HF with a LV ejection fraction Results Finally, 971 patients were enrolled (71±12 years, 72% men, 50% ischemic etiology, LVEF 35±9%). Most patients showed a NYHA class I-II (74%) and were treated with ACE-inhibitors/ARBs or ARNI (81%), beta-blockers (95%), and mineralocorticoid receptor antagonists (71%). Patients were distinguished in three subgroups according to LVOT-VTI tertiles 0.05). Over a median follow-up of 22 (9–34) months, 103 (11%) patients met the primary endpoint. LVOT-VTI significantly stratified the risk of death, observing 65 (20%), 21 (7%), and 17 (5%) events across the subgroups with values Conclusion LVOT-VTI is associated with disease severity and is a strong predictor of all-cause death in patients with chronic HF. Funding Acknowledgement Type of funding sources: None.

Introduction Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor for at least 1 month is the mainstay of therapy after an acute coronary syndrome (ACS). Despite several randomized controlled trials (RCTs) having compared different DAPT regimens after an ACS, the choice of the optimal P2Y12 receptor inhibitor is still debated. Purpose We aimed to compare the efficacy and safety profiles of the new P2Y12 receptor inhibitors (prasugrel and ticagrelor) versus clopidogrel in patients with ACS through a meta-analysis of RCTs. Methods We performed an extensive literature search, from January 1970 to December 2021 using PubMed database. Studies were eligible if they were RCTs directly comparing different oral P2Y12 receptor inhibitors in patients with ACS. Data on study methods, patient characteristics, and outcomes of interest (all-cause and cardiovascular death, recurrent myocardial infarction, stroke, major and non-major bleeding) were extracted from the original publications. We performed a meta-analysis using a random-effects model with the Mantel–Haenszel method. The effect measures of each study included were calculated and reported as odds ratio (OR) with 95% confidence interval (CI), visually presented in forest plots. A two-sided p-value Results A total of 117 studies were available for the analysis; after full reading 11 studies were eligible to be analyzed. The 11 studies reported data on 50,722 patients: 25,424 [50.1%] taking a new oral P2Y12 receptor inhibitor and 25,298 [49.9%] taking clopidogrel. Patients receiving ticagrelor or prasugrel showed a lower risk of all-cause mortality (OR 0.88, 95% confidence interval [CI] 0.80–0.97, I2=8%), cardiovascular mortality (OR 0.88, 95% CI 0.81–0.95, I2=0%), and recurrent myocardial infarction (OR 0.86, 95% CI 0.76–0.97, I2=43%) compared to those receiving clopidogrel. The two groups did not differ significantly concerning the risk of stroke (OR 0.98, 95% CI 0.82–1.17, I2=0%), major bleeding (OR 1.05, 95% CI 0.97–1.15, I2=0%), or non-major bleeding (OR 1.36, 95% CI 0.85–2.20, I2=67%). By restricting the analysis to the studies comparing ticagrelor versus clopidogrel, the ticagrelor group showed a lower risk of all-cause mortality (OR 0.79, 95% CI 0.70–0.90, I2=0%), but a higher risk of non-major bleeding (OR 1.67, 95% CI 1.05–2.66, I2=30%). There was no significant difference between ticagrelor and clopidogrel in terms of cardiovascular death (OR 0.87, 95% CI 0.73–1.05, I2=0%), stroke (OR 1.06, 95% CI 0.85–1.13, I2=0%), or major bleeding (OR 1.02, 95% CI 0.93–1.12, I2=0%). Conclusions In patients with an ACS, a DAPT strategy with aspirin plus either prasugrel or ticagrelor is associated with a reduced risk of all-cause and cardiovascular mortality as well as of recurrent myocardial infarction compared to aspirin plus clopidogrel, without an increased risk of bleeding. Funding Acknowledgement Type of funding sources: None.

Background A reliable echocardiographic algorithm for the estimation of precapillary wedge pressure (PCWP) and pulmonary vascular resistances (PVR) has been recently validated by our group in a large cohort of patients undergoing right heart catheterization (RHC) (1). Those metrics may add relevant clinical and prognostic information in patients with heart failure (HF). Objective To assess the clinical/prognostic significance of echocardiographic derived PCWP and PVR in a large cohort of chronic HF patients on modern treatments. Methods Outpatients with chronic HF with either reduced (≤40%) or mildly reduced LVEF (41–49%) underwent a thorough clinical multiparametric assessment and were followed-up for a composite endpoint of cardiac death, appropriate ICD shock, or first HF hospitalization. Results Out of 1,483 patients prospectively enrolled (70±12 years, 73% males, 42% ischemic etiology, LVEF 35±8%), PCWP (16.4±5.8 mmHg) was elevated (>15 mmHg) in 53% of cases, while PVR (1.7±0.7) was elevated (>3 WU) in 6% of cases. Of the latter group, most (92%) had also elevated PCWP. Patients with increased PCWP were older, had a higher heart rate and lower cardiac output, showed a higher degree of left and right chamber remodeling, had a higher neurohormonal activation, worse renal function, worse functional capacity and ventilatory efficiency on effort (all p Conclusion The estimation of PCWP and PVR by echocardiography add relevant clinical and prognostic information and may help in the decision making in patients with HF. Funding Acknowledgement Type of funding sources: None.

Background Amyloid transthyretin cardiomyopathy (ATTR-CM) has become treatable. Wild-type ATTR-CM is an age-related disorder. Establishing the exact prevalence of ATTR-CM in elderly subjects from the general population may be useful for healthcare providers and policy makers alike. Methods The Characterizing the burden of Amyloid Transthyretin CardiomyopatHy in the elderly (CATCH) study is a population screening on all subjects aged ≥65 years followed by general practitioners working in a part of Tuscany (Italy) where there is no cluster of variant ATTR. The study started on March 12, 2021 and is ongoing. The first step of the evaluation includes clinical history and physical examination, electrocardiogram, transthoracic echocardiogram, and blood sampling with measurement of N-terminal pro-B-type natriuretic peptide and high-sensitivity (hs) troponin T. The following elements are searched: 1) any clinical red flag of amyloidosis (history of carpal tunnel syndrome, lumbar spine stenosis, etc.), 2) interventricular septal thickness ≥12 mm or other echocardiographic red flags, 3) hs-troponin T higher than the upper reference limit (14 ng/L). Patients with any of these elements are referred to a second step including diphosphonate scintigraphy and the search for a monoclonal protein in the serum and urine. The standard diagnostic workup for CA is then followed until the diagnosis is confirmed or discarded. Results As of October 13, 2021, 514 subjects ≥65 years have been evaluated for possible participation. Among them, 135 (26%) could not be contacted, were reluctant to enter the study, died before being contacted, or were bedridden. Out of the other 379 subjects, 329 (87%) have already undergone the first step. Forty percent of individuals (n=132) have been referred to the second step. Thirteen subjects have declined (10%); 69 patients have undergone diphosphonate scintigraphy and the search for a monoclonal protein (while the other 50 are awaiting these exams). Two subjects showed an intense myocardial uptake of the diphosphonate tracer (Perugini score 2–3) and no monoclonal protein, and were then diagnosed with ATTR-CM. They were both women, aged 83 and 78 years, both mildly symptomatic for dyspnea (New York Heart Association II) and with unexplained hypertrophy. The search for TTR gene mutation was negative in the first case and is still ongoing in the second. Based on these preliminary data, the prevalence of ATTR-CM in the elderly population can be calculated as 2/266=0.8% (Figure 1). Conclusions The CATCH study is expected to enroll at least 1,000 subjects and will provide the first data on the epidemiology of ATTR-CM in elderly subjects. Based on an interim analysis, almost 1 in 100 individuals ≥65 years has ATTR-CM. Funding Acknowledgement Type of funding sources: None.

Background Reduced left ventricular ejection fraction (LVEF) has been used as a key criterion for the management of mitral regurgitation (MR) in patients with heart failure (HF), including the decision about mitral valve repair. However, LVEF, not taking into account mitral regurgitant volume, may be an imprecise predictor of outcome in HF patients with MR. Conversely, the estimation of the forward volume through the LV outflow tract (LVOT) may be a better metric in this setting. In this regard, LVOT velocity time integral (LVOT–VTI), not relying on geometrical assumptions, has been shown to be more reproducible than the calculated stroke volume (i.e., LVOT–VTI * LVOT cross sectional area). Objective To assess the prognostic significance of LVOT–VTI in a contemporary cohort of patients with chronic HF and significant MR. Methods Consecutive patients with chronic HF with reduced (≤40%) or mildly reduced (41–49%) LVEF and moderate–to–severe or severe MR, according to the latest European Society of Cardiology criteria, were selected and followed–up for the endpoint of cardiac death. Results 287 patients were enrolled in the study (74±11 years, 70% men, 46% ischemic etiology, HFrEF 89%, LVEF 30±9%, mean LVOT–VTI 20±5 cm). Most patients showed a NYHA class II (40%) or III (31%) and received beta–blockers (93%), ACE–inhibitors/ARBs or ARNI (77%), and mineralocorticoid receptor antagonists (76%). One hundred and ten patients (39%) had permanent atrial fibrillation and 82 (29%) a cardiac resynchronization therapy device. Over a median follow–up of 33 (16–47) months, 114 patients died, 71 of whom for cardiac cause, and 28 underwent mitral valve repair/replacement. The risk of cardiac death increased proportionally to the decrease of LVOT–VTI (Figure 1, panel A), with an optimal prognostic cut–off of 17 cm (Figure 1, panel B). Reduced LVOT–VTI was associated with higher NYHA class, NT–proBNP concentration, and worse right ventricle systolic function (all p Conclusion Left ventricular forward volume, noninvasively estimated through LVOT–VTI, but not LVEF, predicts the risk of cardiac death in patients with chronic HF and significant MR.

Background Neuromodulation by percutaneous stellate ganglion block (PSGB) with local anaesthetic has proved its antiarrhythmic effect suitable for an emergency setting. Purpose To assess the efficacy and safety of PSGB performed with an anterior anatomical approach in patients with refractory electrical storm refractory. Methods Patients with electrical storm at the Policlinico S.Matteo of Pavia were enrolled from November 2017 to January 2022. Left PSGB (PLSGB) was performed after failure of at least one intravenous antiarrhythmic drug. Its repetition or a continuous infusion of the local anaesthetic were considered in selected cases. Clinical data, characteristics of the block and complications were collected. The efficacy was evaluated by comparing the number of arrhythmias treated with ATP or DC–shocks by external or internal defibrillator 1 hour before the block with 1 hour after the block. Per–patient efficacy was assessed by comparing the number of ATP/shocks in the 12 hours before the first procedure with that in the 12 hours after the last one. Results 37 patients were enrolled: 76% male, mean age 65 years; 11 with dilated cardiomyopathy, 18 with chronic ischemic heart disease, 11 with STEMI, 3 with NSTEMI, 1 with ARVC and 1 with drug intoxication. A total of 62 PLSGBs were performed: 19 for VT, 26 for VF and 17 for both VT and VF episodes; 15 on intubated patients, 4 in extracorporeal circulation, 7 in cardiogenic/septic shock, 28 on patients on single antiplatelet therapy, 11 on dual antiplatelet therapy, 33 on anticoagulant therapy. PLSGBs were performed during intravenous infusion of antiarrhythmics (amiodarone in 30, lidocaine in 37 procedures). The local anaesthetic used was lidocaine in 27/62 PLSGB, bupivacaine in 6/62 and both in 29/62. The per–procedure analysis showed a significant reduction of the number of ATP/shocks in the hour after PLSGB compared with the hour before [0 (0–0) vs 5 (1–8) p Conclusions This is the case series with the highest number of PLSGB for antiarrhythmic purposes in literature and it confirms its efficacy and safety in refractory electrical storm. The exiguity of the equipment required makes the anatomical approach suitable to be easily performed by cardiologists.

Funding Acknowledgements Type of funding sources: None. Background Infections and malfunction are major indications to transvenous lead extraction. Managing extracted patients represents a clinical and interventional challenge, since this population may be at higher risk for mechanical, vascular or infective complications. The use of leadless pacing systems has been described as a potentially useful technology that could tackle the obstacles that affect this peculiar population. The study aimed to investigate feasibility and long-term outcomes of M-TPS implant in a specific patient population, like post transvenous lead extraction patients, which represent a challenge for conventional cardiac pacing. Methods Between May 2014 and November 2021, 155 patients (120 males, 77.42%, mean age 78 ± 9 y) underwent M-TPS implantation in our Center, targeting a non-apical site of delivery when feasible. A subgroup of 48 patients (39 males, 81.25%) had undergone transvenous lead extraction. All patients fulfilled standard criteria for pacemaker implantation with specific indication to receive VVI pacing. The outcome evaluation included electrical performance (capture threshold, pacing impedance, R wave amplitude) before hospital discharge and then followed at 1, 6, and 12 months and then annually. Major complications were defined as life-threatening events, required surgical intervention or any event causing significant hemodynamic instability or resulting in death. High pacing threshold (HPT) was defined as 1.0 V/0.24 ms. Results In 48/155 cases (39 males, 81,25%) M-TPS was implanted after successful transvenous lead extraction. There were no statistically significant differences between groups for demographics characteristics, and PM implant indications. The implant procedure was successful in all cases and no device-related events were registered during follow-up. In particular, no device infection and/or malfunction were reported. Patients were followed-up for an average of 24 months (median 18 months). No differences were observed between groups in procedure duration, single device delivery (group 1 vs group 2: 63.21% vs 73.91%, p=0.20), fluoroscopy time (group 1 vs group 2: 11.79 ± 7.53 vs 10.49 ± 6.19 minutes, p=0.64), electrical performance at implant (group 1 vs group 2: pacing threshold 0.54 ± 0.35 V/0.24 ms vs 0.62 ± 0.32 V/0.24 ms, p=0.09; impedance 758.02 ± 227.89 Ohm vs 724.26 ± 178.14 Ohm, p=0.36; R wave amplitude 10.1 ± 4.73 mV vs 9.59 ± 5.30 mV, p=0.50) and at 18 month F-U (group 1 vs group 2: pacing threshold 0.50 ± 0.10 V/0.24 ms vs 0.85 ± 0.9 V/0.24 ms, p=0.45; impedance 559.58 ± 94.43 Ohm vs 543.34 ± 64.39 Ohm, p=0.69; R wave amplitude 12.00 ± 5.06 mV vs 13.42 ± 5.77 mV, p=0.55). Conclusions Leadless pacemaker implant is a feasible, safe and effective option for patients treated with transvenous lead extraction, with electrical performance and outcomes comparable to a cohort of naïve patients at long-term follow up.

Funding Acknowledgements Type of funding sources: None. Introduction Data on left atrial/left atrial appendage (LA/LAA) thrombus resolution after non–vitamin K antagonist (VKA) oral anticoagulant treatment (OAT) are scarce. Purpose The aim of this study was to explore retrospectively the resolution of LA/LAA spontaneous echo-contrast or thrombus in patients with nonvalvular atrial fibrillation (AF) or atrial flutter (AFL) after OAT in a real-world single center practice. Methods A single center retrospective analysis of patients with AF/AFL who underwent a transesophageal echocardiography (TEE) for an electrical cardioversion and/or atrial fibrillation ablation was performed. Patients showing LA/LAA echo-contrast or thrombus and with at least one TEE follow up to detect the resolution of LA/LAA echo-contrast/thrombus were included and analyzed. Results Among 277 TEE performed, 73 cases (26%) of LA/LAA echo-contrast or thrombus were detected in our hospital. Among them, a total of 53 patients showed LAA/LA echo-contrast (19%) and 20 (7%) patients showed a thrombus. Patients with echo-contrast or thrombus were usually male (78% vs 72%, p=0.05) with more comorbidities, as hypertension (90% vs 72%, p=0.03) and congestive heart failure (36% vs 17%, p=0.007) and with an overall higher CHA2DS2-Vasc score (3.5±1.5 vs 3±1, p=0.0001). All they were under chronic anticoagulation with a VKA (65%) or with a NOAC (35%), without differences between groups. (p=NS). At the TTE/TEE analysis, they showed a comparable ejection fraction (55±11 vs 55±22%, p=NS), a trend for an increased LA dilatation (27±8 vs 26±6 cm2, p=0.07) and a low LAA peak velocity (94% vs 19%, p=0.0001). The Echo-contrast Group maintained the same OAT strategy in 49 patients (93%), switching from VKA to NOAC in 3 cases (6%) and from NOAC to NOAC in 1 (1%). The Thrombus Group kept the same OAT strategy with a NOAC in 6 cases (30%) and changed the strategy in 14 patients (70%). Particularly, they titrated NOAC dose in 1 (5%) and the VKA dose in 4 (20%), switched from NOAC to VKA in 5 (25%), from VKA to NOAC in 3(15%) and from NOAC to NOAC in 1 (5%). Smoke resolution was observed in LA/LAA smoke group in 1/10 cases (10%) after a median time of 52 days (20-135) and LA/LAA thrombus resolution 8/15 (53%) after a median time of 45 days (25-180). Patients with the thrombus resolution had a lower CHA2DS2-Vasc score (3.5±2 vs 4±1, p=0.05), and showed a trend for a more frequent use of a NOAC (37.5 vs 28%, p=0.07) and a longer overall anticoagulation time (7.5 vs 4 months, p=0.08). At one-year follow-up, 1 ischemic stroke (1.9%) and 2 deaths (3.8%) were observed only in the Echo-contrast group. Conclusion(s) In OAT patients with an LA/LAA thrombus changing the OAT strategy is associated with thrombus resolution in more than 50% of cases, after an appropriate anticoagulation period and in lower CHAD2S2Vasc patients. Chronic OAT strategy confirmation, also with NOAC, is rarely effective, also in case of echo-contrast resolution.

Background Sudden cardiac death is a major issue in industrialised countries and survival of patients after out–of–hospital cardiac arrest (OHCA) remains low. Acute myocardial infarction (AMI) is the principal cause of OHCA and myocardial revascularisation plays a positive role on survival. In this setting little is known about the role of complete (CR) versus culprit–only revascularisation (IR) on survival. Purpose The aim of this study was to assess whether CR could lead to a better one–year survival as compared to IR. Methods. Among patients prospectively enrolled in the Lombardia CARe OHCA registry from January 1 2015 to May 1 2021, who underwent a coronary angiography (CAG) at the Fondazione IRCCS Policlinico San Matteo were enrolled in this study. CAGs were retrospectively reviewed by two interventional cardiologists. Prehospital and survival data were retrieved from the registry. Results We enrolled 239 patients [mean age 63.7±12.4 years; male 79.9%; shockable presenting rhythm 84.1%; AMI at post ROSC ECG 67.9%; ejection fraction 37% (30–45), circulatory support with ECMO 10.9%]. Among the 119 (50%) patients with multi–vessel disease, 82 (69%) received IR whereas 37 (31%) received CR [8 during the first procedure, 29 in a second procedure with a median time after OHCA of 5 (2.5–10) days]. This latter group showed significantly higher one–year survival (54.9% vs 16.2%, p Conclusions Complete revascularisation is independently associated with a better one–year survival in patients resuscitated from an out–of–hospital cardiac arrest.

Introduction Cardiac arrests in sports can involve professional athletes, amateurs, but also spectators of sports competitions. Sports facilities are the only ones for which the current law provides for the presence of an automatic external defibrillator (AED) and trained personnel, unlike other public places (schools, work, street, station, general public buildings) where it is only recommended. Objective To compare patient characteristics, presentation rhythm, bystander cardiopulmonary resuscitation (CPR), AED use before emergency medical services (EMS) arrival, and return of spontaneous circulation (ROSC) longer than 30 seconds in the Utstein category of out–of–hospital cardiac arrests (OHCAs) in sports compared to events in other public places. Materials and Methods We considered all the OHCAs occurred from 01/01/2015 to 31/12/2020 in the provinces of Pavia, Lodi, Cremona, Mantua and Varese (2400000 inhabitants), excluding the OHCAs occurred at home, in long–term care facilities and witnessed by the EMS. Results During the study period, 22 OHCAs occurred in sports and 552 in other public places (school, work, street, station, public buildings). The age is similar in the two groups [sport 59 years (IQR 53.5–66.7) vs other 63 years (IQR 51–75), p = 0.2]. In sports, there is a trend in favor of shockable rhythms (13/22=59% vs 185/552=33%, p = 0.1). The percentage of CPR performed by bystanders in sports is significantly higher than in other public places (20/22=91% vs 299/552=54%, p = 0.003), as the bystander AED use (11/22=50% vs 64/552=12%, p Conclusions During sports competitions there is a greater ability to intervene in case of cardiac arrest, which determines a higher probability of obtaining ROSC, although in terms of age or presentation rhythm the patients are comparable to OHCA victims in other places public. These results suggest the need for an AED and trained personnel in other public places as well.

Background Atrial fibrillation (AF) results in electrical and structural remodeling of the atria, and the extent of remodeling has already been found to be associated with higher AF recurrence rate after catheter ablation (CA). Recently, a novel echocardiographic parameter derived from tissue Doppler imaging (TDI), called PA–TDI, has been introduced to assess the total atrial activation time, as a non–invasive surrogate of fibrosis and atrial cardiomyopathy. The aim of the study was to investigate the role of PA–TDI interval as predictor of AF ablation efficacy. Methods Consecutive patients with persistent or paroxysmal symptomatic AF referred to our Center to perform radiofrequency ablation or cryoablation procedures were prospectively enrolled. In these patients, a complete transthoracic echocardiographic examination was performed before and after the ablation procedure, including assessment of the PA–TDI interval. Results From October 2018 to May 2020, 221 consecutive patients (mean age 61 ± 9 years, 74% male, mean BMI 26.5 ± 3.6, mean Ejection Fraction 61 ± 6%) symptomatic for AF, undergoing the procedure ablation (first procedure or re–do) were enrolled. Out of the blanking period, 25% of patients experienced recurrence of arrhythmia during follow–up (mean 16 months). Compared to patients who did not relapse, patients with AF recurrence have a generally longer post–procedural PA–TDI interval (139.6 ± 22.1 msec vs 153.9 ± 33 msec, respectively). In the multivariable analysis only post–procedure PA–TDI and re–do interventions were found to be independent predictors of AF recurrence. A PA–TDI cut–off> 144msec identifies patients at risk of post ablation AF recurrence with sensitivity 58.7% and specificity 73.5% (AUC 0.697). Conclusions The PA–TDI interval is an independent predictor of AF recurrence after catheter ablation. This echocardiographic parameter is easily obtainable, low–cost, reproducible, and accessible even in peripheral centers.

Background Once the return of spontaneous circulation (ROSC) after an out–of–hospital cardiac arrest (OHCA) is achieved in patients with an ST–elevation myocardial infarction, the acquisition of a 12–lead electrocardiogram (ECG) is strongly recommended in order to determine candidates for urgent coronary angiography. However, little is known so far about the association of ECG features and survival to hospital discharge in OHCA patients. Methods We analysed all the post–ROSC ECGs collected from January 2015 to December 2018 in three European centres (Pavia, Lugano and Vienna). For every ECG, the main features were analysed and filed in the database together with the pre–hospital data collected for every patient according to the Utstein style. Results We collected 370 ECGs: 287 males (77.6%); median age 62 years old (IQR 53–70 years); 121 from Pavia (32.7%), 38 from Lugano (10.3%) and 211 from Vienna (57.0%). In Cox univariable regression, age older than 62 years [HR 1.7 (95% IC 1.1–2.4), p = 0.007], QRS wider than 120 msec [HR 1.87 (95% IC 1.3–2.7), p Conclusions Our study confirms the central role of ECG in STEMI patients resuscitated after an OHCA and proves that post–ROSC ECG features can be used for both the selection of patients who may benefit from urgent coronary angiography as well as for prognostic stratifications.

Background Amyloid transthyretin cardiomyopathy (ATTR–CM) has become treatable. Wild–type ATTR–CM is an age–related disorder. Establishing the exact prevalence of ATTR–CM in elderly subjects from the general population may be useful for healthcare providers and policy makers. Methods The Characterizing the burden of Amyloid Transthyretin CardiomyopatHy in the elderly (CATCH) study is a population screening on all subjects aged ≥65 years followed by general practitioners in a part of Tuscany (Italy) where there is no cluster of variant ATTR. The study started on March 12, 2021 and is ongoing. Patients with 1) any clinical red flag of amyloidosis, 2) interventricular septal thickness ≥12 mm or other echocardiographic red flags, and/or 3) hs–troponin T > 14 ng/L are referred to diphosphonate scintigraphy and search for a monoclonal protein. Results As of October 13, 2021, 514 subjects ≥65 years have been evaluated for possible participation. Among them, 135 (26%) could not be contacted, were reluctant to enter the study, died before being contacted, or were bedridden. Out of the other 379 subjects, 329 (87%) have already undergone the first step. Forty percent of individuals (n = 132) have been referred to the second step. Thirteen subjects have declined (10%); 69 patients have undergone diphosphonate scintigraphy and the search for a monoclonal protein (while the other 50 are awaiting these exams). Two subjects showed an intense myocardial uptake of the diphosphonate tracer (Perugini score 2–3) and no monoclonal protein, and were then diagnosed with ATTR–CM. They were both women, aged 83 and 78 years, both mildly symptomatic for dyspnea (New York Heart Association II) and with unexplained hypertrophy. The search for TTR gene mutation was negative in the first case and is still ongoing in the second. Based on these preliminary data, the prevalence of ATTR–CM in the elderly population can be calculated as 2/266=0.8%. Conclusions The CATCH study is expected to enroll at least 1,000 subjects and will provide the first data on the epidemiology of ATTR–CM in elderly subjects. Based on an interim analysis, almost 1 in 100 individuals ≥65 years has ATTR–CM.

Introduction According to the European Society of Cardiology guidelines secondary prevention ICD implantation is a class I indication only for those patients with an estimated survival > 1 year with a good functional status. However, it is not specified how to assess the functional status and its evaluation could be quite difficult in the case of out–of–hospital cardiac arrest (OHCA) survivors with major neurological outcomes. Cerebral Performance Category (CPC) is the most widespread scale to define the neurological and functional outcome of OHCA survivors, but it is not known if it can be used to guide ICD implantation. Objective To evaluate whether the presence of a bad neurological outcome (CPC > 2) at discharged could be used as a prognostic index in order to evaluate the implantation of an ICD in OHCA survivors. Materials and Methods. We considered all the patients who had a cardiac arrest from 01/10/2014 to 30/09/2019 presenting a CPC> 2 at discharge. The territory included was that of the Province of Pavia (550000 inhabitants) from 2014 to 2018 and of the Provinces of Pavia, Lodi, Cremona and Mantua (1550000 inhabitants) from 2019. We assessed the survival and the neurological status variation at 1–year. Results In the study period, CPR was attempted in 2998 confirmed OHCAs. 227 patients (7.6%) were discharged alive and in 218 of these, CPC was available. 51 patients (23.4%) had a CPC>2 at discharge (22 CPC = 3, 24 CPC = 4 and 5 CPC = A). 1–year follow–up was available in 200 patients: among 158 alive, 12 (7.6%) had CPC>2 (7 CPC = 3 and 5 CPC = 4). 1–year survival of patients with CPC>2 at discharge was significantly lower those discharged with CPC≤2 (39.6% vs 91.6% p 2 survived at 1 year: a good cerebral performance was recovered in 6 patients (31.6%), while CPC>2 persisted in 11 (58%) and the CPC value was unknown in 2 of them. Conclusions Our results highlight that 1–year survival is quite low in patients with CPC>2 at discharge and that an improvement in cerebral performance occurs only in a minority of them. This evidence suggests the need for clinical re–evaluation after the event in order to carefully evaluate whether to implant an ICD in this kind of patients.

This study comprises a critical review of modeling of pesticides in surface waters. The aim was to update the status of the use of models to simulate the fate of pesticides from diffuse sources. ISI papers were selected on Scopus and the information concerning the study areas, type of pesticides (herbicides, fungicides and insecticides), the model, and the methodology adopted (i.e., calibration and/or validation, spatial and temporal scales) were analyzed. The studies were carried out in Europe (55.5%), North America (22.3%), Asia (13.9%) and South America (8.3%). The Soil and Water Assessment Tool proved to be the most used model (45.95%). Herbicides were the most modeled pesticides (71.4%), followed by insecticides (18.2%) and fungicides (10.4%). The main herbicides modeled were atrazine, metolachlor, isoproturon, glyphosate, and acetochlor. Insecticides such as chlorpyrifos and metaldehyde. Chlorothalonil, and fungicides (i.e., tebuconazole) were the most widely investigated. Based on published studies, it was found that modeling approaches for assessing the fate of pesticides are constantly evolving and the model algorithms work well with diverse watershed conditions, management strategies, and pesticide properties. Several papers reported concentrations of pesticides exceeding ecotoxicological thresholds revealing that water contamination with pesticides used in agriculture and urban areas is a priority issue of current global concern.

The preparation of gold nanoparticles with multimodal properties such as near-infrared absorption, high surface-enhanced Raman scattering, cell internalization and low cytotoxicity is a challenging task. In this study, we developed a sustainable protocol to develop gold nanoparticles, using trisodium citrate as reducing, stabilizing, and shape-modulating agent at ambient conditions (25 °C). Reduction of gold salt at room temperature at a peculiar ratio R(Ccitrate/CHAuCl4) and concentration of reactants resulted in the formation of non-spherical, homogenous mixture of gold nanoparticles with polyhedral shapes. The protocol is extremely simple and does not even require stirring or mechanical shaking. The as-synthesized gold nanoparticles, even though multi-shaped, displayed a single monomodal peak in dynamic light scattering with polydispersity index of 0.098, representative of a fairly good monodisperse system. We investigated the optical properties of the nanoparticles both experimentally and by two-dimensional Finite-Difference-Time-Domain modeling. Due to the presence of shapes such as nanorods, nanotriangles, and prismatic, these nanoparticles exhibited a high surface-enhanced Raman scattering activity and a wide absorption range extending up to the near-infrared region, which makes them useful candidate for photothermal therapy too. We characterized the nanoparticles by electron microscopy, UV–vis–NIR spectroscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. We have also developed an enhanced numerical diffusion limited aggregation model to simulate the growth of the particles, including the particle interfacial energy as a parameter of the system. Numerical results matched with the experimental data, and the model revealed being effective in reproducing size, shape, and morphological characteristics of non-spherical nanoparticles obtained under real experimental conditions. Finally, in vitro studies and nanoparticles cellular uptake were performed on a model cell line of mouse brain endothelium (bEnd.3) to assess biocompatibility. The main advantage of the proposed method lies in its simplicity with no other requirement like refluxing at elevated temperature, mechanical stirring, electromagnetic radiations, ultrasound, toxic chemicals, or seed mediation.

Purpose Local recurrence after treatment of ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) is more common than after mastectomy, but it is unclear if patterns of invasive recurrence vary by initial surgical therapy. Among patients with invasive recurrence after treatment for DCIS, we compared patterns of first recurrence between those originally treated with BCS vs. mastectomy. Methods From 2000 to 2016, women with an invasive recurrence occurring ≥ 6 months after initial treatment for DCIS were retrospectively identified. Clinicopathologic features and adjuvant treatment of the initial DCIS, as well as characteristics of first invasive recurrences, were compared between patients who had undergone BCS vs. mastectomy. Results 452 patients with an invasive recurrence after surgery for DCIS were identified: 367 patients (81%) had initially undergone BCS and 85 patients (19%) mastectomy. Patients originally treated with mastectomy were younger and were more likely to have had high grade, necrosis, and multifocal or multicentric DCIS (p p p = 0.12). Conclusions Among women who experienced a first invasive recurrence after treatment for DCIS, those who had originally undergone mastectomy more commonly presented with advanced disease compared to those treated with BCS, likely related to the absence of the breast and the higher risk profile of their initial DCIS.

Neoadjuvant chemotherapy (NAC) is used to convert patients with inoperable locally advanced breast cancer (LABC) to operability, but has not traditionally been used to avoid mastectomy or axillary dissection in this subset. The purpose of this study was to determine the rates of pathologic complete response (pCR) in LABC patients, and identify factors predictive of pCR to determine if responding patients might be suitable for limited surgery. From 2006 to 2016, 1522 patients received NAC followed by surgery; 321 had advanced disease in the breast (cT4) and/or in the nodes (cN2/N3). pCR rates were assessed by T and N stage, and receptor subtype. Of 321 LABC patients, 223 were cT4, 77 were cN2, and 82 were cN3. Forty-three percent were hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative (HR+/HER2−), 23% were triple negative, and 34% were HER2+. The overall pCR rate was 25% and differed by receptor subtype (HR+/HER2− 7%, triple negative 23%, HER2+ 48%; p

Objectives:To provide an appraisal of the evolving paradigms in the pathophysiology of sepsis and propose the evolution of a new phenotype of critically ill patients, its potential underlying mechanism, and its implications for the future of sepsis management and research.Design:Literature search us

The Cammarota stream is located in Northern Puglia (Southern Italy) and is characterized by the presence of intact and destroyed check dams. Here in-fields measurements of the Leaf Area Index (LAI) were conducted to detect the variability of riparian vegetation along fifty-three riverbed transects. The observed values ranged from 0.26 to 5.71. The lower ones were found in those reaches where destroyed or strongly damaged check dams are located, and, consequently, riverbed erosive processes are present. The higher LAI values were found in those reaches with the presence of intact or slightly damaged check dams, characterized by a higher geomorphological stability. LAI measurement were also conducted in a nearby stream, named Vallone della Madonna, with intact check dams and sound riparian vegetation. Here the observed values of LAI ranged between 4.08 and 5.93, which are similar to those found in the Cammarota reaches with good geomorphological conditions. LAI values from both streams were also retrieved from Landsat 8 and Pleiades 1A satellite images using three different equations to derive LAI values from the Normalized Difference Vegetation Index (NDVI) and its corrected form. A statistical analysis was performed for every formula used.

In this work, we propose an IoT edge-based energy management system devoted to minimizing the energy cost for the daily-use of in-home appliances. The proposed approach employs a load scheduling based on a load shifting technique, and it is designed to operate in an edge-computing environment naturally. The scheduling considers all together time-variable profiles for energy cost, energy production, and energy consumption for each shiftable appliance. Deadlines for load termination can also be expressed. In order to address these goals, the scheduling problem is formulated as a Markov decision process and then processed through a reinforcement learning technique. The approach is validated by the development of an agent-based real-world test case deployed in an edge context.

Breast tumors in pregnancy are often times diagnosed at advanced stages secondary to difficulty distinguishing between pathologic from normal physiologic changes. Often benign, phyllodes tumors are rare fibroepithelial stromal tumors of the breast, most commonly diagnosed in the 4th and 5th decades of life. However, these tumors may be characterized by malignancy with metastases in 10% of cases. In this paper, we report a novel case of a young woman presenting at 8 weeks gestation with a large borderline phyllodes tumor. An exceedingly rare condition, with only nine previously reported cases, phyllodes tumors in pregnancy frequently display more aggressive characteristics with larger median tumor size, more malignant potential, and more rapid growth rate. Here, we describe our experience safely and effectively treating this rare condition in a young gravid women with mastectomy and immediate breast reconstruction in the second trimester.

Wire localization is currently the most widely used localization strategy for excision of nonpalpable breast lesions. Its disadvantages include patient discomfort, wire-related complications such as wire displacement/fracture, and operating room delays related to difficulties during wire placement. We have implemented the technique of intraoperative ultrasound-guided excision using hydrogel-encapsulated (HydroMARK) biopsy clips for lesion localization. We hypothesize that this method is as effective as wire localization for breast conserving therapy. This is a retrospective review of 220 consecutive patients who underwent segmental mastectomy or excisional biopsy using wire localization or hydrogel-encapsulated clip localization from January 2014 to July 2015. Data were collected and analyzed. Statistical analyses for differences between groups were performed using t tests and Mann-Whitney rank-sum analyses. A total of 107 excisions were performed using hydrogel-encapsulated clip localization, and 113 excisions were performed using the traditional wire localization technique; 68 % of our patients underwent excision for malignant pathology. Wire placement took a mean of 46 minutes (range 20–180 min), compared with 5 minutes for ultrasound localization (p

Controversy remains whether the leukocyte genomic response to trauma or sepsis is dependent upon the initiating stimulus. Previous work illustrated poor correlations between historical models of murine trauma and sepsis (i.e., trauma-hemorrhage and lipopolysaccharide injection, respectively). The aim of this study is to examine the early genomic response in improved murine models of sepsis [cecal ligation and puncture (CLP)] and trauma [polytrauma (PT)] with and without pneumonia (PT+Pp). Groups of naïve, CLP, PT, and PT+Pp mice were killed at 2 h, 1 or 3 days. Total leukocytes were isolated for genome-wide expression analysis, and genes that were found to differ from control (false discovery rate adjusted P < 0.001) were assessed for fold-change differences. Spearman correlations were also performed. For all time points combined (CLP, PT, PT+Pp), there were 10,426 total genes that were found to significantly differ from naïve controls. At 2 h, the transcriptomic changes between CLP and PT showed a positive correlation ( r s) of 0.446 ( P < 0.0001) but were less positive thereafter. Correlations were significantly improved when we limited the analysis to common genes whose expression differed by a 1.5 fold-change. Both pathway and upstream analyses revealed the activation of genes known to be associated with pathogen-associated and damage-associated molecular pattern signaling, and early activation patterns of expression were very similar between polytrauma and sepsis at the earliest time points. This study demonstrates that the early leukocyte genomic response to sepsis and trauma are very similar in mice.

The aim of this study was to review two cases of ruptured hepatoblastoma treated with primary surgical resection. Hepatoblastoma is the most common primary liver malignancy of childhood, although it remains infrequent. A rare, but serious condition is when the tumor presents with spontaneous rupture. This is a well-known phenomenon; however, it is rarely reported in the literature, and the long-term outcomes of various management strategies are currently unclear. We present two cases of patients in whom primary surgical resection was performed and discuss outcomes, and also present a current literature review. Children with ruptured hepatoblastoma treated with emergency primary surgical resection, followed by adjuvant chemotherapy, may have favorable outcomes. Keywords : hepatoblastoma, rupture, surgical resection

The main aim of the present study is to contribute to the field of environmental research by providing new data on bottom ash samples derived from an oil power plant located in Southern Italy. To achieve this purpose, the mineralogical and chemical properties of representative bottom ash samples were investigated through the integrated employment of different analytical techniques, i.e., X-ray powder diffraction, scanning electron microscopy, X-ray fluorescence and atomic absorption spectrometry. The obtained experimental results show that quartz, alunogen, rhomboclase and potassium hydrogen silicate are the major crystalline phases of all the analyzed samples. Furthermore, the revealed main ash constituents are SiO2 and SO3, with low contents of Fe2O3 and Al2O3, and little amounts of CaO, Na2O, K2O, MgO, P2O5 and TiO2. Among the trace elements, very high amounts of heavy metals, i.e., V, Cr, Ni, La, Pb and Mo, were detected. The comparison of the obtained heavy metal abundance data with those reported in the literature highlights significant differences. Leaching test evidenced V, Ni and Cr values that make these ashes a potential contamination source for groundwater quality and for soil, nearby the ash disposal landfills area. All the obtained findings show that these materials are highly harmful for the human health, with a greater extent for the heavy metal concentrations.

The elderly are particularly susceptible to trauma, and their outcomes are frequently dismal. Such patients often have complicated clinical courses and ultimately die of infection and sepsis. Recent research has revealed that although elderly subjects have increased baseline inflammation as compared with their younger counterparts, the elderly do not respond to severe infection or injury with an exaggerated inflammatory response. Initial retrospective analysis of clinical data from the Glue Grant trauma database demonstrated that despite a similar frequency, elderly trauma patients have worse outcomes to pneumonia than younger subjects do. Subsequent analysis with a murine trauma model also demonstrated that elderly mice had increased mortality after posttrauma Pseudomonas pneumonia. Blood, bone marrow, and bronchoalveolar lavage sample analyses from juvenile and 20–24-mo-old mice showed that increased mortality to trauma combined with secondary infection in the aged are not due to an exaggerated inflammatory response. Rather, they are due to a failure of bone marrow progenitors, blood neutrophils, and bronchoalveolar lavage cells to initiate and complete an emergency myelopoietic response, engendering myeloid cells that fail to clear secondary infection. In addition, elderly people appeared unable to resolve their inflammatory response to severe injury effectively.

Current evidence suggests that neonatal immunity is functionally distinct from adults. Although TLR signaling through the adaptor protein, MyD88, has been shown to be critical for survival to sepsis in adults, little is known about the role of MyD88 or TRIF in neonatal sepsis. We demonstrate that TRIF−/− but not MyD88−/− neonates are highly susceptible to Escherichia coli peritonitis and bacteremia. This was associated with decreased innate immune recruitment and function. Importantly, we found that the reverse was true in adults that MyD88−/− but not TRIF−/− or wild-type adults are susceptible to E. coli peritonitis and bacteremia. In addition, we demonstrate that TRIF but not MyD88 signaling is critical for the TLR4 protective adjuvant effect we have previously demonstrated. These data suggest a differential requirement for the survival of neonates versus adults to Gram-negative infection, and that modulation of TRIF in neonates can be used to augment survival to neonatal sepsis.

Notes on the diatomaceous earth used in this study. (DOCX 18Â kb)

In assessing the impact of climate change on infrastructure, it is essential to consider the interactions between the atmosphere, vegetation and the near-surface soil. This paper presents an overview of these processes, focusing on recent advances from the literature and those made by members of COST Action TU1202 – Impacts of climate change on engineered slopes for infrastructure. Climate- and vegetation-driven processes (suction generation, erosion, desiccation cracking, freeze–thaw effects) are expected to change in incidence and severity, which will affect the stability of new and existing infrastructure slopes. This paper identifies the climate- and vegetation-driven processes that are of greatest concern, the suite of known unknowns that require further research, and lists key aspect that should be considered for the design of engineered transport infrastructure slopes in the context of climate change. ISSN:1470-9236 ISSN:0481-2085

Supporting figures to the Numerical Simulation Methods of the main text. (DOCX 608Â kb)