Therapeutic Efficacy of Autologous Non-Mobilized Enriched Circulating Endothelial Progenitors in Patients With Critical Limb Ischemia　- The SCELTA Trial.

BACKGROUND: The therapeutic efficacy of bone marrow mononuclear cells (BM-MNC) autotransplantation in critical limb ischemia (CLI) has been reported. Variable proportions of circulating monocytes express low levels of CD34 (CD14+CD34lowcells) and behave in vitro as endothelial progenitor cells (EPCs). The aim of the present randomized clinical trial was to compare the safety and therapeutic effects of enriched circulating EPCs (ECEPCs) with BM-MNC administration.Methods and Results:ECEPCs (obtained from non-mobilized peripheral blood by immunomagnetic selection of CD14+and CD34+cells) or BM-MNC were injected into the gastrocnemius of the affected limb in 23 and 17 patients, respectively. After a mean of 25.2±18.6-month follow-up, both groups showed significant and progressive improvement in muscle perfusion (primary endpoint), rest pain, consumption of analgesics, pain-free walking distance, wound healing, quality of life, ankle-brachial index, toe-brachial index, and transcutaneous PO2. In ECEPC-treated patients, there was a positive correlation between injected CD14+CD34lowcell counts and the increase in muscle perfusion. The safety profile was comparable between the ECEPC and BM-MNC treatment arms. In both groups, the number of deaths and major amputations was lower compared with eligible untreated patients and historical reference patients. CONCLUSIONS: This study supports previous trials showing the efficacy of BM-MNC autotransplantation in CLI patients and demonstrates comparable therapeutic efficacy between BM-MNC and EPEPCs.

Extracorporeal Photopheresis for Second-Line Treatment of Chronic Graft-versus-Host Diseases: Results from a Health Technology Assessment in Italy.

OBJECTIVES: To develop a comparative, cost-effectiveness, and budget impact analysis of Therakos online extracorporeal photopheresis (ECP) compared with the main alternatives used for the treatment of steroid-refractory/resistant chronic graft-versus-host disease (cGvHD) in Italy. METHODS: The current therapeutic pathway was identified by searching medical databases and from the results of a survey of practice in Italian clinical reference centers. A systematic review was performed to evaluate the efficacy and safety of second-line alternatives. Budget impact and cost-effectiveness analyses were performed from the Italian National Health Service perspective over a 7-year time horizon through the adaption of a Markov model. The following health states were considered: complete and partial response, stable disease, and progression. A discount rate of 3% was applied to costs and outcomes. RESULTS: The most common alternatives used in Italy for the management of steroid-refractory/resistant cGvHD were ECP, mycophenolate, pentostatin, and imatinib. The literature review highlighted that complete and partial responses are higher with ECP than with the alternatives while serious adverse events are less common. The economic analysis showed that Therakos online ECP represents the dominating alternative, in that it delivers greater benefit at a lower cost. In fact, according to the alternatives considered, cost saving ranged from €3237.09 to €19,903.51 per patient with 0.04 to 0.21 quality-adjusted life-year gained. CONCLUSIONS: Therakos online ECP should be considered an effective, safe, and cost-effective alternative in steroid-refractory/resistant cGvHD. There is inequality in access, and a dedicated reimbursement tariff, however, should be introduced to overcome these barriers.

Simulation in neurology.

Simulation is a frontier for disseminating knowledge in almost all the fields of medicine and it is attracting growing interest because it offers a means of developing new teaching and training models, as well as of verifying what has been learned in a critical setting that simulates clinical practice. The role of simulation in neurology, until now limited by the obvious physical limitations of the dummies used to train students and learners, is now increasing since, today, it allows anamnestic data to be related to the instrumental evidence necessary for diagnosis and therapeutic decision-making, i.e., to the findings of neurophysiological investigations (EEG, carotid and vertebral echography and transcranial Doppler, for example) and neuroradiological investigations (CT, MRI imaging), as well as vital parameter monitoring (ECG, saturimetry, blood pressure, respiratory frequency, etc.). Simulation, by providing learners with opportunities to discuss, with experts, different profiles of biological parameters (both during the simulation itself and in the subsequent debriefing session), is becoming an increasingly important tool for training those involved in evaluation of critical neurological patients (stroke, Guillan Barrè syndrome, myasthenia, status epilepticus, headache, vertigo, confusional status, etc.) and complex cases. In this SIMMED (Italian Society for Simulation in Medicine) position paper, the applications (present and, possibly, future) of simulation in neurology are reported.

Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular risk.

NSAIDs are largely used for the treatment of a huge variety of clinical conditions in order to relieve symptoms related to inflammation.The use of NSAIDs is associated with a potential increased risk of gastrointestinal and cardiovascular complications.The cardiovascular risk related to NSAIDs administration is often underestimated and it is frequently believed to be less important than the gastrointestinal risk. Adverse effects of NSAIDs are specifically related to their underlying mechanisms of action.The most plausible mechanism underlying the cardiovascular risk of NSAIDs has been identified in the profound inhibition of COX-2-dependent PGI2 in the presence of incomplete and intermittent inhibition of platelet COX-1. Nevertheless, the cardiovascular risk related to the use of NSAIDs is not only due to the COX-2 selectivity. An important determinant of the clinical effects of NSAIDs depends on the pharmacokinetic features of the different drugs such as half-life, and type of formulations, which can influence the extent and duration of patient exposure to COXisozyme inhibition. The aim of this review is to analyse the mechanisms behind the cardiovascular risk of different NSAIDs.

[Artificial intelligence applied to the electrocardiogram.] / L'intelligenza artificiale applicata all'elettrocardiogramma.

Artificial intelligence is able to read and interpret Ecg traces quickly and precisely, increasing the diagnostic capacity and offering the possibility of anticipating preventive therapies. However, there is no evidence on the clinical utility and cost-effectiveness of certain practical applications. In fact, the literature shows the prognostic importance in favor of prevention, but clear evidence is not available that correcting strokes, embolisms, heart failure early improves quality and life span of patients.

Worldwide impact of COVID-19 on hospital admissions for non-ST-elevation acute coronary syndromes (NSTACS): a systematic review with meta-analysis of 553,038 cases.

BACKGROUND: How COVID-19 impacted non-ST-segment elevation acute coronary syndromes (NSTACS) is object of controversial reports. AIM: To systematically review studies reporting NSTACS hospitalizations during COVID-19 pandemic, and analyze whether differences in COVID-19 epidemiology, methodology of report, or public health-related factors could contribute to discrepant findings. METHODS: Comprehensive search (MedLine, Embase, Scopus, Web-of-Science, Cochrane Register), of studies reporting NSTACS hospitalizations during COVID-19 pandemic compared with a reference period, following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Data were independently extracted by multiple investigators and pooled using a random-effects model. Health-related metrics were from publicly available sources, and analyzed through multiple meta-regression modelling. RESULTS: We retrieved 102 articles (553 038 NSTACS cases, 40 countries). During peak COVID-19 pandemic, overall Incidence Rate-Ratio (IRR) of NSTACS hospitalizations over reference period decreased (0.70, 95% CI 0.66-0.75; p < 0.00001). Significant heterogeneity was detected among studies (I2= 98%; p < 0.00001). Importantly, wide variations were observed among, and within, countries. No significant differences were observed by study quality, whereas comparing different periods within 2020 resulted in greater decrease ((IRR: 0.61; CI: 0.53-0.71) than comparing 2020 vs previous years (IRR: 0.74; CI 0.69-0.79). Among many variables, major predictors of heterogeneity were: Sars-Cov-2 reproduction rate/country, number of hospitals queried, reference period length; country stringency index and socio-economical indicators did not significantly contribute. CONCLUSIONS: During COVID-19 pandemic NSTACS hospitalizations decreased significantly worldwide. However, substantial heterogeneity emerged among countries, and within the same country. Factors linked to public health management, but also to methodologies to collect results may have contributed to this heterogeneity. Trial registration: The protocol was registered in PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42022308159).

Exploring the definition and methodology of "best practice" in the health care literature: a scoping review protocol.

OBJECTIVE: This review will map and define the terminology used in health care literature for "best practice" as well as its underpinning framework/methodology. INTRODUCTION: Numerous international organizations and institutions have sought to develop models or frameworks to guide health care providers to integrate the best evidence into clinical practice. However, different concepts related to best practice have been used, both in the biomedical literature and by public institutions, leading to a lack of consistency in definitions of the term. This poses a potential difficulty for clinical professionals in applying evidence effectively to achieve desired patient outcomes. INCLUSION CRITERIA: This review will adopt the following inclusion criteria: i) the study must contain a definition of the term "best practice" or its related concepts; ii) the concept of best practice must refer to clinical activities and not have organizational features; and iii) any study design can be included. Studies will be excluded if they describe a definition of best practice that is not directly related to clinical practice (eg, business). METHODS: The review will follow the JBI methodology for scoping reviews. An initial search of MEDLINE identified keywords and MeSH terms. MEDLINE (PubMed), Embase, CINAHL (EBSCOhost), and Google Scholar will be searched from 2001 until the present, the year in which the first definition of best practice appeared in the literature. Four pairs of reviewers will independently select studies and perform data extraction and data synthesis. Data will be presented in figures or tables, accompanied by a narrative summary. Searches will be limited to articles in English, Italian, German, French, and Spanish. REVIEW REGISTRATION: Open Science Framework: https://osf.io/52vxe/.

The Italian Society of Cardiology and Working Group on Telecardiology and Informatics 2023 updated position paper on telemedicine and artificial intelligence in cardiovascular disease.

In 2015, the Italian Society of Cardiology and its Working Group on Telemedicine and Informatics issued a position paper on Telecardiology, resuming the most eminent evidence supporting the use of information and communication technology in principal areas of cardiovascular care, ranked by level of evidence. More than 5 years later and after the global shock inflicted by the SARS-CoV-2 pandemic, an update on the topic is warranted. Recent evidence and studies on principal areas of cardiovascular disease will be therefore reported and discussed, with particular focus on telemedicine for cardiovascular care in the COVID-19 context. Novel perspectives and opportunities disclosed by artificial intelligence and its applications in cardiovascular disease will also be discussed. Finally, modalities by which machine learning have realized remote patient monitoring and long-term care in recent years, mainly filtering critical clinical data requiring selective hospital admission, will be provided.

Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention.

INTRODUCTION: Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. METHODS AND ANALYSIS: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. ETHICS AND DISSEMINATION: This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's course and findings through regular meetings. TRIAL REGISTRATION NUMBER: NCT05339841.

Atherothrombotic burden and medium-term prognosis in patients with acute ischemic stroke: findings of the SIRIO study.

BACKGROUND: Short- and medium-term mortality after acute stroke is related to the severity of the index event and the patient's age. However, recent studies have reassessed the prognostic value of the systemic atherothrombotic burden in these patients, not only in the long term. This post hoc analysis of the findings of the SIRIO trial (Stroke in Italy and Related Impact on Outcome) examined the prognostic impact of systemic atherothrombosis. METHODS: SIRIO was a multicenter observational study enrolling patients during the acute phase of stroke of both ischemic and hemorrhagic origin. The present analysis, however, only covered patients with ischemic stroke. At baseline, the main personal and clinical details were recorded and patients were classified as having either polyvascular disease or single arterial disease on the basis of whether they had symptomatic atherothrombotic disease in other sites besides the cerebrovascular location. For all patients we calculated the Essen Stroke Risk Score (ESRS), dividing them into groups with scores of less than 3 or 3 and more. We recorded total mortality and nonfatal vascular events 12 months after enrolment. Multivariate logistic regression analysis was used to select predictors of medium-term mortality and nonfatal cardiovascular events. There were 2,561 patients with ischemic stroke, 823 of them classified as having polyvascular disease; 940 (out of 2,485) had an ESRS of less than 3 and 1,545 had a score of 3 or more. RESULTS: The combined endpoint 'death (all causes) and nonfatal cardiovascular events within 12 months of hospital discharge' was significantly dependent on the following factors: ESRS, Rankin scale and National Institutes of Health Stroke Scale scores, and polyvascular disease. Polyvascular disease status significantly affected mortality and nonfatal cardio- and cerebrovascular events after discharge (OR = 1.44, 95% CI = 1.10-1.88). Age was also confirmed as a significant predictor of the combined endpoint. CONCLUSIONS: Besides age and the clinical severity of the index event, symptomatic involvement of several vascular districts was also an important predictor of mortality and nonfatal cardiovascular events in the medium term in patients with ischemic stroke.

[Pain in Italy. Background examination. Operative proposals]. / Dolore in Italia. Analisi della situazione. Proposte operative.

The aim of this document is to protect public health through the diffusion on the national territory of appropriate pain treatment guidelines and the definition of a practical, diagnostic and therapeutic tool, which contributes to the diffusion of Law no. 38/2010, particularly through information and health professionals training. The lack of systematic pain evaluation and of an appropriate diagnostic-therapeutic approach are the main issues that make patients treatment remains very poor and inadequate. The 41% of patients with chronic pain states they have not received adequate pain control. The pain incidence in the Italian population is 21.7%, which corresponds to approximately 13 million inhabitants. Consequently, becomes significant identifying the tools and methods to help health professionals to recognize the pain nature, providing a global intervention, which includes the evaluation of patient and of the pathology's clinical characteristics, in order to guarantee an adequate therapeutic choice and a minimization of risks associated with therapy. International guidelines for pain management recommend pain evaluation according to its characteristics, in order to recognize the pain nature (nociceptive pain - inflammatory pain and structural mechanical pain -, neuropathic pain) and an adequate therapy, taking into account pain intensity (analgesics or their associations for management of non-inflammatory pain; for management of inflammatory pain, NSAIDs which may be associated with a central analgesic; drugs with action on ion channels and on neurotransmitters reuptake for management of neuropathic pain). The inadequate management of "pain's suffering patient" underlined the need for health professionals to dispose of a practical and effective tool, a "methods-guide". This tool wishes to become a valuable support for pain examination, from first diagnostic approach to appropriate prescription's dispensing. Authors hope to guide health professionals in the right direction to achieve the cultural change awaited from the application of Law no. 38/2010.

[Sodium balance and peritoneal ultrafiltration in refractory heart failure].

About 5% of patients with heart failure (HF) reach the end-stage of disease, becoming refractory to therapy. The clinical course of end-stage HF is characterized by repeated hospitalizations, severe symptoms, and poor quality of life. Peritoneal ultrafiltration (PUF), removing water and sodium (Na+), can benefit patients with end-stage HF. However, effects on fluid and electrolyte removal have not been fully characterized. In this pilot study in patients with chronic HF and moderate chronic renal failure, we evaluated the effects of water and sodium removal through PUF on ventricular remodeling, re-hospitalization, and quality of life. Patients with end-stage HF (NYHA class IV, ≥3 HF hospitalization/year despite optimal therapy), not eligible for heart transplantation underwent peritoneal catheter positioning and began a single-day exchange with icodextrin at night (n=6), or 1-2 daily exchanges with hypertonic solution (3.86%) for 2 hours with 1.5-2 L fill volume (n=3). At baseline, average ultrafiltration was 500±200 ml with icodextrin, and 700±100 ml with hypertonic solution. Peritoneal excretion of Na+ was greater with icodextrin (68±4 mEq/exchange) compared to hypertonic solution (45±19 mEq/exchange). After a median 12-month follow-up, rehospitalizations decreased, while NYHA class and quality of life (by Minnesota Living with HF questionnaire), improved. In end-stage HF patients, PUF reduced re-hospitalization and improved quality of life. It can be an additional treatment to control volume and sodium balance.

Worldwide differences of hospitalization for ST-segment elevation myocardial infarction during COVID-19: A systematic review and meta-analysis.

BACKGROUND: Discrepant data were reported about hospital admissions for ST-segment elevation myocardial infarction (STEMI) during COVID-19 pandemic. We reviewed studies reporting STEMI hospitalizations during COVID-19 pandemic, investigating whether differences in COVID-19 epidemiology or public health-related factors could explain discrepant findings in different countries. METHODS: Search through MedLine, Embase, Scopus, Web-of-Science, Cochrane Register of Controlled Trials, of studies comparing STEMI admissions during COVID-19 pandemic with a reference period, without language restrictions, as registered in PROSPERO International Prospective Register of Systematic Reviews. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed. Data independently extracted by multiple investigators were pooled using a random-effects model. Health-related metrics were from publicly-available sources. RESULTS: We included 79 articles (111,557 STEMI cases, from 57 countries). During peak COVID-19 pandemic, overall incidence rate-ratio (IRR) of STEMI hospitalizations over reference period decreased (0.80; 95% CI 0.76-0.84; p < 0.05). Although wide variations and significant heterogeneity were detected among studies (I2 = 89%; p < 0.0001), no significant differences were observed by report methodology (survey vs registry), or observation/reference period. However, large differences emerged at country level not explained by COVID-related epidemiological data, nor by public health strategies. Instead, IRRs for STEMI admissions were inversely related to hospital bed availability in each country (p < 0.05). CONCLUSIONS: During COVID-19 pandemic hospitalization for STEMI significantly decreased, although to a smaller extent than initially reported. Large variability emerged across countries, unrelated to COVID-related epidemiology or social containment measures. Disparities in healthcare organization likely contributed, indicating that proper organization of emergency medicine should be preserved during pandemics.

Ventilatory and ECMO treatment of H1N1-induced severe respiratory failure: results of an Italian referral ECMO center.

BACKGROUND: Since the first outbreak of a respiratory illness caused by H1N1 virus in Mexico, several reports have described the need of intensive care or extracorporeal membrane oxygenation (ECMO) assistance in young and often healthy patients. Here we describe our experience in H1N1-induced ARDS using both ventilation strategy and ECMO assistance. METHODS: Following Italian Ministry of Health instructions, an Emergency Service was established at the Careggi Teaching Hospital (Florence, Italy) for the novel pandemic influenza. From Sept 09 to Jan 10, all patients admitted to our Intensive Care Unit (ICU) of the Emergency Department with ARDS due to H1N1 infection were studied. All ECMO treatments were veno-venous. H1N1 infection was confirmed by PCR assayed on pharyngeal swab, subglottic aspiration and bronchoalveolar lavage. Lung pathology was evaluated daily by lung ultrasound (LUS) examination. RESULTS: A total of 12 patients were studied: 7 underwent ECMO treatment, and 5 responded to protective mechanical ventilation. Two patients had co-infection by Legionella Pneumophila. One woman was pregnant. In our series, PCR from bronchoalveolar lavage had a 100% sensitivity compared to 75% from pharyngeal swab samples. The routine use of LUS limited the number of chest X-ray examinations and decreased transportation to radiology for CT-scan, increasing patient safety and avoiding the transitory disconnection from ventilator. No major complications occurred during ECMO treatments. In three cases, bleeding from vascular access sites due to heparin infusion required blood transfusions. Overall mortality rate was 8.3%. CONCLUSIONS: In our experience, early ECMO assistance resulted safe and feasible, considering the life threatening condition, in H1N1-induced ARDS. Lung ultrasound is an effective mean for daily assessment of ARDS patients.

[Catheter ablation in hospitalized patients diagnosed with atrial fibrillation: real-world evidence from Italian health administrative databases.] / Ablazione transcatetere nei pazienti ricoverati con diagnosi di fibrillazione atriale: real-world evidence da database amministrativi sanitari italiani.

BACKGROUND: Catheter ablation (CA) is recommended for treating paroxysmal/persistent atrial fibrillation (AF) as an alternative to antiarrhythmic drugs after failure or intolerance, or as first-line in limited cases. This study has described patients affected by AF and treated or not with CA, from the perspective of the Italian National Healthcare System (INHS). METHODS: From the healthcare administrative data collected in the ReS (Ricerca e Salute) database, from 2016 to 2017, patients with main/secondary diagnosis of AF (index date) were split into two cohorts by presence/absence of CA procedure in the same hospital discharge form. The cohorts were characterized by gender, age, comorbidities. Consumptions (DDD) of antiarrhythmic, anticoagulant, antiplatelet and antihypertensive drugs, hospitalizations for AF, hemorrhagic stroke/intracranial hemorrhage, ischemic stroke/transient ischemic attack, extra cranial major bleeding and heart failure, outpatient specialist care and healthcare costs paid by the INHS were assessed. RESULTS: Out of >5 million inhabitants in 2016-2017, 33,940 patients were hospitalized with a diagnosis of AF, 990 (2.9%) were treated with CA in the same hospitalization (32,950 without CA). Patients with CA were mostly males (66.8%; 48.5% without CA). On average, they were aged (±SD) 65±12 (78±11 without CA) and affected by one comorbidity (≥3 in patients without CA). During the observational period, beta-blockers were the most prescribed to both cohorts, followed by antiarrhythmic drugs to patients with CA and by direct oral anticoagulants to those without. The 29.7% of subjects with CA were hospitalized due to relevant cardiovascular diagnoses during the previous year (7.4% without CA) and 93.4% in the first follow-up year (29.7% without CA). The 80-90% of cohorts resorted to the outpatient specialist care. Electrocardiograms and the cardiology visits were performed to the 62.5% and 31.1% of the cohort with CA (39.5% and 13% without CA) in the first follow-up year. On average, the INHS spent about € 4000 in the previous year and around € 10,000 in the first follow-up year per patient of both cohorts, while around € 3000 and € 4000 for a patient respectively with and without CA. At least half of the total costs were due to hospitalizations, followed by pharmaceuticals and outpatient specialist care. CONCLUSIONS: This study confirm a post-CA suboptimal monitoring.

Response of serum proteome in patients undergoing infrarenal aortic aneurysm repair.

BACKGROUND: Postoperative organ dysfunction in conventional surgery for abdominal aortic aneurysm (AAA) is associated with a complex inflammatory reaction, with activation of coagulation and fibrinolysis. A prospective,observational study was performed to define the complex plasma proteomic changes after AAA repair and to identify factor(s) that may affect myocardial function in uncomplicated procedures. METHODS: Ten patients undergoing infrarenal AAA repair were investigated. Eight subjects subjected to major abdominal surgery served as controls. Hemodynamic changes were continuously monitored by using the pressure recording analytical method technique. The time course of plasma proteins was investigated after induction of anesthesia and at different times after surgery (6 h, 12 h, 24 h, 36 h) by using two-dimensional difference gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and Western blot. The effects of plasma on the functional properties of isolated rat ventricular myocytes were also investigated. RESULTS: In AAA patients alone, 18 spots were found to change more than two-fold in expression level, spot identification revealing an increased thrombin generation 6 h after surgery. At the same time cardiac cycle efficiency significantly reduced versus baseline (-0.5 +/- 0.9 vs. 0.18 +/- 0.3 in AAA patients, P < 0.01; 0.4 +/- 0.1 vs. 0.2 +/- 0.3 in control surgery, not significant; P < 0.01 group x time interaction at ANOVA). Plasma obtained 6 h after AAA surgery dose-dependently inhibited contractile function of control rat myocytes (percent shortening fell by 51% with 10% of AAA plasma and was abolished with 20% of AAA plasma, P < 0.001 for both). The inhibitory response was abolished by thrombin antagonism. CONCLUSIONS: These findings show for the first time the possible role of thrombin generation within the complex activation of inflammatory response in causing hemodynamic instability in the early postoperative period after AAA surgery.

International open-label studies to assess the efficacy and safety of single-pill amlodipine/atorvastatin in attaining blood pressure and lipid targets recommended by country-specific guidelines: the JEWEL programme.

BACKGROUND: Single-pill amlodipine/atorvastatin targets the two most common modifiable cardiovascular risk factors, hypertension and dyslipidaemia. We evaluated the clinical utility of this single pill to help patients across Europe and Canada achieve country-specific targets for blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C). DESIGN: Two 16-week, open-label studies conducted in 122 study centres across the United Kingdom and Canada (JEWEL 1) and 113 centres across 11 European countries (JEWEL 2). METHODS: Patients with uncontrolled BP and controlled/uncontrolled LDL-C qualifying for treatment according to local governing guidelines were administered single-pill amlodipine/atorvastatin with appropriate lifestyle modification. Eight dosages of amlodipine/atorvastatin (5/10-10/80 mg) were titrated to achieve country-specific BP and LDL-C targets. The primary outcome was the percentage of patients reaching country-specific BP and LDL-C targets in 16 weeks. RESULTS: Among 2245 patients enrolled in the studies (JEWEL 1, n = 1138; JEWEL 2, n = 1107), 62.9% in JEWEL 1 and 50.6% in JEWEL 2 achieved both country-specific BP and LDL-C goals. BP was reduced by 20.4/10.7 and 21.8/12.6 mmHg in JEWEL 1 and JEWEL 2, respectively, and reductions in LDL-C were 0.90 mmol/l (34.8 mg/dl) and 1.09 mmol/l (42.2 mg/dl), respectively. The most common adverse events were peripheral oedema (11.0%), joint swelling (2.9%) and headache (2.9%), of which, only oedema was linked to study treatment. CONCLUSION: Single-pill amlodipine/atorvastatin is an effective and well-tolerated treatment, which in a real-world setting helped more than half of the patients achieve both BP and LDL-C targets as recommended by local guidelines. Although fewer patients met their goals in JEWEL 2 than JEWEL 1, reductions in BP and LDL-C were slightly greater in JEWEL 2, suggesting that the observed differences are likely because of more stringent targets in Europe than in the UK/Canada.

Totally endoscopic subxiphoid pericardioscopy: early steps with a new surgical tool.

BACKGROUND: Pericardial pathology still has challenging diagnostic and treating issues. To reduce surgical trauma and pain for the patient, the authors developed a totally endoscopic echo-guided approach for both diagnostic and operative pericardioscopy. METHODS: Three steps moved from animal model (8 pigs) through concomitant open-chest interventions (7 patients) to closed-chest interventions for 10 patients with a diagnosis of severe pericardial effusion. RESULTS: A lesion of the right ventricle in one patient (10%) due to imperfect preoperative pericardial visualization needed sternotomy for repair. All the patients, except the aforementioned one, underwent surgery with local anesthesia or mild sedation. No method-related mortality was reported. CONCLUSION: The closed-chest nonintrapleural approach to the pericardium may represent an evolution, with a positive impact on the treatment of this pathology. Therapeutic maneuvers with rigid instruments in nonintubated patients are possible. Accurate patient selection and technical refinement should increase the safety and effectiveness of the method.

Atorvastatin decreases elevated soluble CD40L in subjects at high cardiovascular risk. Atorvastatin on inflammatory markers study: a substudy of ACTFAST.

The CD40/CD40 ligand plays a role in the inflammatory and prothrombotic processes in atherosclerosis. We analyzed whether short-term treatment with atorvastatin affects soluble CD40 ligand (sCD40L) plasma levels in subjects at high cardiovascular risk. sCD40L plasma concentrations were measured in 852 subjects from the Atorvastatin on Inflammatory Markers (AIM) Study, a 12-week prospective multicenter, open-label trial which enrolled statin-free subjects with coronary heart disease (CHD), CHD-equivalent (diabetes, peripheral vascular disease, or cerebrovascular disease), or a 10-year CHD risk >20%. Subjects were assigned to atorvastatin (10-80 mg/day) based on LDL-C at screening. Overall, sCD40L levels were not different in patients at high cardiovascular risk compared with healthy subjects. When sCD40L levels were divided in quartiles, patients in the highest quartile (N=213) had higher sCD40L concentrations than age- and gender-matched healthy subjects (N=29) (P<0.0001). Interestingly, all doses of atorvastatin significantly diminished sCD40L levels in subjects at the highest quartile. Furthermore, atorvastatin treatment decreased sCD40L more markedly in subjects with metabolic syndrome compared with those without metabolic syndrome. In conclusion, atorvastatin diminishes sCD40L plasma levels, more markedly so in subjects with metabolic syndrome. Our results indicate that short-term treatment with atorvastatin exhibits anti-inflammatory and antithrombotic effects in subjects at high cardiovascular risk.