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This systematic review assesses currently available clinical information on which cannabinoids and what range of doses have been used to achieve positive effects in a diversity of medical context.The data were collected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol guidelines. Inclusion criteria were articles that assessed administration of any cannabinoid to any clinical population, reported in the ClinicalTrials.gov or PubMed databases, that involved a comparison with other treatment or placebo and a result measurement to assess the effectiveness or ineffectiveness of the cannabinoid. Exclusion criteria were review or letter; articles not in the English language; not full-text articles; not a clinical trial, case report, case series, open-label trial, or pilot study; administration in animals, in vitro, or in healthy participants; cannabinoids administered in combination with other cannabinoids (except for cannabidiol [CBD] or tetrahydrocannabinol [THC]) or as whole cannabis extracts; no stated concentration; inhalation or smoke as a route of administration; and no results described. The articles were assessed by the risk of bias.In total, 1668 articles were recovered, of which 55 studies met the inclusion criteria for 21 diseases. Positive effects were reported in clinical studies: 52% with THC (range, 0.01-0.5 mg/kg/d [0.62-31 mg/d]), 74% with CBD (range, 1-50 mg/kg/d [62-3100 mg/d]), 64% with THC-CBD (mean, 1:1.3 mg/kg/d [ratio, 1:1]), and 100% with tetrahydrocannabivarin (THCV) (0.2 mg/kg/d).THC, CBD, and THCV can regulate activity in several pathologies. New studies of cannabinoids are highly encouraged because each patient is unique and requires a unique cannabinoid medication.

Takotsubo syndrome (TTS) is an acute and usually reversible heart failure syndrome, frequently associated with emotional or physical stress. Its pathophysiology remains largely unclear, although several mechanisms related to catecholaminergic storm have been proposed. In this study we analyzed during the acute phase of TTS and at follow-up both hemorheological parameters and biomarkers of endothelial damage, whose time course has never been fully explored. In 50 TTS women, we analyzed several hemorheological parameters [whole blood viscosity (WBV) at 0.512 s

The present paper describes a sampling-event dataset on species belonging to two families of Diptera (Syrphidae and Asilidae) collected between 2012 and 2019 in two Italian beech forests located in the central Apennines. The reference dataset consists of an annotated checklist and has been published on Zenodo. Syrphidae and Asilidae are two widespread and key ecological groups, including predator, pollinator and saproxylic species. Despite their pivotal role in both natural and man-made ecosystems, these families are still poorly known in terms of local distribution and open-access sampling-event data are rare in Italy. This open-access dataset includes 2,295 specimens for a total of 21 Asilidae and 65 Syrphidae species. Information about the collection (e.g. place, date, methods applied, collector) and the identification (e.g. species name, author, taxon ID) of the species is provided. Given the current biodiversity crisis, the publication of checklists, sampling-event data and datasets on insect communities in open-access repositories is highly recommended, as it represents the opportunity to share biodiversity information amongst different stakeholders. Moreover, such data are also a valuable source of information for nature reserve managers responsible for monitoring the conservation status of protected and endangered species and habitats and for evaluating the effects of conservation actions over time.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), has provoked more than six million deaths worldwide and continues to pose a major threat to global health. Enormous efforts have been made by researchers around the world to elucidate COVID-19 pathophysiology, design efficacious therapy and develop new vaccines to control the pandemic. To this end, experimental models are essential. While animal models and conventional cell cultures have been widely utilized during these research endeavors, they often do not adequately reflect the human responses to SARS-CoV-2 infection. Therefore, models that emulate with high fidelity the SARS-CoV-2 infection in human organs are needed for discovering new antiviral drugs and vaccines against COVID-19. Three-dimensional (3D) cell cultures, such as lung organoids and bioengineered organs-on-chips, are emerging as crucial tools for research on respiratory diseases. The lung airway, small airway and alveolus organ chips have been successfully used for studies on lung response to infection by various pathogens, including corona and influenza A viruses. In this review, we provide an overview of these new tools and their use in studies on COVID-19 pathogenesis and drug testing. We also discuss the limitations of the existing models and indicate some improvements for their use in research against COVID-19 as well as future emerging epidemics.

In human medicine, the progression from early neoplasia development to either complete resolution of tumorigenesis and associated inflammation or chronicity and fatal outcomes remain difficult to predict. Resolution of inflammation is an active process that stimulates the termination of the inflammatory response and promotes return to homeostasis, while failure in resolution contributes to the development of a number of diseases. To understand how resolution pathways contribute to tumorigenesis, we defined and employed a cumulative score based on the expression level of genes involved in synthesis, signaling, and metabolism of the D-series resolvin (RvD). This score was used for comparative analyses of clinical, cellular, and molecular features of tumors, based on RNA-sequencing (RNA-seq) datasets collected within The Cancer Genome Atlas (TCGA) program. Our results indicate that higher RvD scores are associated with better clinical outcome of patients with head and neck squamous cell carcinoma (HNSC), and with molecular and cellular signatures indicative of enhanced anti-tumor immunity and better response to immune-checkpoint inhibitors (ICI), also in human papilloma virus (HPV) negative HNSC subtypes. Thus, higher activity of the RvD pathway identifies patients with improved resolution and a more efficient immune reaction against cancer.

Se presentan los resultados de seguridad y evolución clínica de 87 pacientes que recibieron plasma de convaleciente en la sala de Clínica Médica del Hospital Argerich en Buenos Aires. Tres pacientes tuvieron sobrecarga de volumen. Hubo 33 pases a Terapia Intensiva (37,9%) y 21 casos requirieron asistencia respiratoria mecánica (24,1%). Fallecieron 18 pacientes (20,7%). Tres de ellos por limitación del esfuerzo terapéutico y 15 en Terapia Intensiva. La mortalidad en Terapia Intensiva fue del 45,4%. Hubo solo 10 casos que recibieron plasma dentro de las 72 horas del comienzo de síntomas: de ellos, 1 caso de asistencia respiratoria y 1 fallecido; entre 72 horas y una semana recibieron plasma 25 casos con 26,9% de asistencia respiratoria y 20% de mortalidad, y de los 50 pacientes que recibieron mas allá de la primera semana, 25,4% requirieron de asistencia respiratoria y 24% fallecieron. Nuestra serie no pudo demostrar efecto beneficioso en la administración temprana de plasma y no fue diseñada para medir eficacia. El procedimiento fue bien tolerado en la gran mayoría de los pacientes.

Introduction: This study aimed to test a computer-driven cardiovascular model for the evaluation of the visceral flow during intra-aortic balloon pump (IABP) assistance. Methods: The model includes a systemic and pulmonary circulation as well as a heart contraction model. The straight polyurethane tube aorta had a single visceral while four windkessel components mimicked resistance compliance of the brachiocephalic, renal and sub-mesenteric, pulmonary, and systemic circulation. Twelve flow probes were placed in the circuit to measure pressures and flows with the IABP on and off. Results: With the balloon off, the meantime to reach the steady state was 48 ± 16 s; with the balloon on, this figure was 178 ± 20 s. The stability of pressure and flow signals was obtained after 72 ± 11 min. The number of cycles of stability of the system was 93 [86–103]. Measurements were reliable either with samples of 10 or 20 beats. Bland Altman method demonstrated the reliability of measurements. Finally, all measurements were comparable to published in vivo data. Conclusion: The presented mock circulation was reliable and gave values with high accuracy both at baseline and during mechanical assistance. This system allows evaluation of the mesenteric flow during IABP, under different clinical/hemodynamic conditions. Nonetheless, its translational potential needs to be further evaluated

Abstarct Methods and Materials From July 2006 to December 2015, 295 patients suitable for breast-conserving therapy entered a single-arm phase II study and were treated with IOERT as radical treatment. Inclusion criteria were age >50, postmenopausal status, cT1N0M0 stage, grade G1-G2, positive estrogen receptor status; unicentric and unifocal disease, histologically proven invasive ductal carcinoma no previous breast irradiation, good performance status. Results With a median follow-up of 7.1 years (95% CI, 6.5;7.4) 6 women (2.0%) experienced a true local recurrence (reappearance of the tumour in the same quadrant). Five-year overall survival and local recurrence-free survival were 96% (95% CI, 92.9;97.8) and 94.9% (95% CI, 91.6;97.0) respectively. Conclusion Our trial suggests that, in highly selected early stage breast cancers, a single-dose IOERT can be safely delivered with excellent results and very low long-term recurrence rates.

Background Beat-to-beat stroke volume (SV) results from the interplay between left ventricular function and arterial load. Fluid challenge induces time-dependent responses in cardiac performance and peripheral vascular and capillary characteristics. Objective To assess whether analysis of the determinants of the haemodynamic response during fluid challenge can predict the final response at 10 and 30 min. Design Observational multicentric cohort study. Setting Three university ICUs. Patients 85 ICU patients with acute circulatory failure diagnosed within the first 48 h of admission. Intervention(s) The fluid challenge consisted of 500 ml of Ringer's solution infused over 10 min. A SV index increase at least 10% indicated fluid responsiveness. Main outcome measures The SV, pulse pressure variation (PPV), arterial elastance, the systolic-dicrotic pressure difference (SAP-Pdic) and cardiac cycle efficiency (CCE) were measured at baseline, 1, 2, 3, 4, 5, 10, 15 and 30 min after the start of the fluid challenge. All haemodynamic data were submitted to a univariable logistic regression model and a multivariable analysis was then performed using the significant variables given by univariable analysis. Results The multivariable model including baseline PPV, and the changes of arterial elastance at 1 min and of the CCE and SAP-Pdic at 5 min when compared with their baseline values, correctly classified 80.5% of responders and 90.7% of nonresponders at 10 min. For the response 30 min after starting the fluid challenge, the model, including the changes of PPV, CCE, SAP-Pdic at 5 min and of arterial elastance at 10 min compared with their baseline values, correctly identified 93.3% of responders and 91.4% of nonresponders. Conclusion In a selection of mixed ICU patients, a statistical model based on a multivariable analysis of the changes of PPV, CCE, arterial elastance and SAP-Pdic, with respect to baseline values, reliably predicts both the early and the late response to a standardised fluid challenge. Trial registration ACTRN12617000076370.

Background: In spite of the increased use of Trans-catheter Aortic Valve Implantation (TAVI) due to the better patient selection, well-trained operators and improved technology, the choice of the best anesthesia regimen remains an open question. In particular, it remains to be clarified whether deep sedation (DS) in spontaneous breathing or femoral local anesthesia (LA) is best. Objective: This study compared the hemodynamic variations determined by deep sedation (DS) with spontaneous breathing and local femoral anesthesia (LA) in 2 groups of patients submitted to TAVI with two different kinds of anesthesia, using a beat-by-beat pulse contour method (MostCare(®-UP)). Methods: 82 patients with severe aortic stenosis and similar baseline characteristics and indications underwent trans-femoral TAVI: 50 with LA and 32 with DS. All patients were submitted to minimally invasive hemodynamic monitoring. The following parameters were measured: pressure indexes: systolic, diastolic, mean (SysP, DiaP, MAP) and dicrotic (DicP) pressures; flow indexes: cardiac output (CO), stroke volume (SV); ventriculo-arterial coupling indexes (VAC): peripheral arterial elastance (Ea(P)), systemic vascular resistance (SVR); cardiovascular system performance: cardiac cycle efficiency (CCE), dP/dt(max_rad). Results: The TAVI procedure was successful in 89% of patients (VARC-2 criteria) with no difference between the 2 groups. Anesthesia induction determined a higher decrease of pressures in DS than in LA (P

The CHAARTED and LATITUDE trials demonstrated improved outcomes with docetaxel or abiraterone plus androgen deprivation therapy in metastatic hormone sensitive prostate cancer (mHSPC) using two different prognostic scores. The aim of our study was to assess the concordance between the two scores and if these retained their prognostic value exclusively in de novo mHSPC. De novo mHSPC patients referring to our institution were retrospectively stratified according to the CHAARTED and LATITUDE classifications: high volume/high risk (HV/HR), low-volume/low-risk (LV/LR), and HVorHR (HV/LR and LV/HR). The Kaplan-Meier method and Cox proportional-hazard models were used to estimate hazard ratios for overall survival. The study population included 106 patients. Concordance between the CHAARTED and LATITUDE classifications was observed in 86.8% of cases (65.1% HV/HR, 21.7% LV/LR), while 13.2% of patients fulfill the criteria of only one of the two classifications (HVorHR). When analyzed independently, the CHAARTED and LATITUDE classifications maintained their prognostic value (mOS 28.2 months in HV versus 60.9 months in LV, p = 0.006; 28.2 months in HR versus 40.6 months in LR, p = 0.017). The LR/LV population showed significantly longer mOS compared to the HR/HV group (72.6 months versus 26.3 months; p = 0.005), and to HVorHR patients (35.1 months; p = 0.003). No difference in OS was observed between HV/HR and HVorHR patients. ECOG PS ≥ 1 and patient age improved the prognostic value of the two classifications with multivariate analysis. Our study showed a lack of complete concordance between the CHAARTED and LATITUDE classifications. The analysis confirmed the role of these prognostic scores to stratify de novo mHSPC patients in clinical practice.

Vitreous cutters are surgical devices used during vitrectomy to remove the vitreous humor from the eye and replace it with tamponade fluids. The aim of the present work is to assess the performance of the EVA Phaco-vitrectomy System vitreous cutter (Dutch Ophthalmic Research Center (DORC) BV; Zuidland, The Netherlands) used with diff erent needle sizes and blade shapes. The analysis is based on laboratory measurements of fluid flow performed using the particle image velocimetry (PIV) technique.

Introduction The cardiovascular toxicity related to abiraterone and enzalutamide has been previously studied by our group. In this analysis, we aim to update our previous findings related to abiraterone and enzalutamide, including the new available evidence, both in castration-resistant and hormone-sensitive prostate cancer. Patients and Methods Prospective studies were identified by searching the MEDLINE/PubMed, Cochrane Library, and ASCO Meeting abstracts. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods. Results We included 7 articles in this meta-analysis, covering a total of 8660 patients who were used to evaluate cardiovascular toxicity. The use of new hormonal agents was associated with an increased risk of all-grade (RR, 1.36; 95% CI, 1.13-1.64; P = .001) and high-grade (RR, 1.84; 95% CI, 1.21-2.80; P = .004) cardiac toxicity. The use of new hormonal agents was also associated with an increased risk of all-grade (RR, 1.98; 95% CI, 1.62-2.43; P = .001) and high-grade (RR, 2.26; 95% CI, 1.84-2.77; P = .004) hypertension compared with the controls. Abiraterone was found to significantly increase the risk of both cardiac toxicity and hypertension, whereas enzalutamide significantly increases only the risk of hypertension. No differences were found based on the dose of prednisone used with abiraterone. The major limitation of this study is that data are available only as aggregate, and no single-patient information could be analyzed. Conclusions Abiraterone and enzalutamide significantly increase the incidence and RR of cardiovascular toxicity in patients affected by metastatic prostate cancer. Follow-up for the onset of treatment-related cardiovascular events should therefore be considered in these patients.

Objective: To evaluate preoperative total testosterone (TT) as a predictor of positive surgical margins (PSM) in prostate cancer (PCA). Patients and methods: During the period from November 2014 to July 2017, preoperative TT was measured in 476 PCA patients undergoing only radical prostatectomy (RP) and including all risk classes. Surgical margins were stated negative, focal positive (single and less than 1 mL), and multifocal positive (more than 1). The risk of TT and clinical factors associated with the risk of PSM (focal or multifocal versus negative) was evaluated by the multinomial logistic regression model. Results: Overall, PSM were detected in 149 cases (31.3%), which included 99 patients with focal cancer invasion (20.8%) and 50 subjects with multifocal cancer invasion (10.5%). In univariate analysis, PSM associated with higher median levels of TT and prostate-specific antigen than controls. Multifocal PSM associated with higher rates of high-risk PCA (42%) than focal (22.2%) or control cases (18.3%). In multivariate analysis, TT was the only independent factor positively associated with the risk of focal PSM when compared to controls (OR 1.002; p = 0.035). TT (OR 1.003; p = 0.002) and high-risk PCA (OR 1.002; p = 0.047) were independent factors, which positively associated with the risk of multifocal PSM when compared to controls. Risk models were computed. Conclusions: In a large and contemporary cohort of patients elected to primary RP, TT was an ­independent positive factor associated with the risk of focal and multifocal PSM. TT associated with aggressive PCA biology.

Background During a fluid challenge, the changes in cardiac performance and peripheral circulatory tone are closely related to the position of the ventricle on the Frank-Starling curve. Some patients have a good haemodynamic response to a fluid challenge, others hardly any response. The early haemodynamic effects of a fluid challenge could predict the final response before the entire fluid volume has been administered. Objective To assess whether a multivariate logistic regression model, including pulse pressure variation (PPV), cardiac cycle efficiency (CCE), arterial elastance and the difference between the dicrotic pressure and both systolic and mean arterial pressure (SAP - Pdic and MAP - Pdic) can predict cardiac responsiveness early during a fluid challenge in comparison with the standard procedure described elsewhere. Design Observational study. Setting Elective surgical patients undergoing laparotomy, enrolled in two Italian University Hospitals. Patients Fifty adult surgical patients, ventilated with a lung protective strategy, were enrolled and data from 46 were analysed. Interventions A fluid challenge consisting of 500 ml of crystalloid infused over 10 min. Main outcome measures and analysis The changes in CCE, arterial elastance, SAP - Pdic and MAP - Pdic were compared using analysis of variance. A multivariate logistic regression analysis utilising baseline values and the first minute measuring a variation statistically significant for the considered variables. Results At baseline, PPV correctly identified 70% of patients (89% of non-responders; 42% of responders). The model, including baseline PPV, ΔCCE and ΔSAP - Pdic, correctly identified the efficiency of fluid challenge in 87% of patients (84.2% of responders; 92.5 of non-responders) after 5 min from fluid challenge infusion. Conclusion In this pilot study conducted in a population of surgical patients mechanically ventilated with a VT less than 8 ml kg, a dynamic model of fluid challenge assessment, including PPV, ΔCCE and ΔSAP - Pdic, enhances the prediction of fluid challenge response after 5 min of a 10-min administration. Trial registration ACTRN12616001479493.

AimImmune checkpoint inhibitors of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) have recently entered in the therapeutic armamentarium of several types of cancer. Besides the surviva...

First-generation drug eluting stents (DES) reduced the incidence of restenosis and need for repeated target lesion revascularization but, in autoptic studies, frequently resulted in incomplete endothelial coverage, which is an important predictor of late adverse events and increased mortality after stent implantation. More recently, not only uncovered, but also malapposed or protruding struts have been considered vulnerable structures, as they are deemed to perturb blood flow, whereas only struts well embedded into the vessel wall are considered stable. We compared the number of uncovered and of other vulnerable (protruding or malapposed) struts among three different second-generation drug-eluting stents (DES) (Cre8, Biomatrix, Xience), using optical coherence tomography (OCT) 6 months after implantation. Moreover, we analyzed the relationship between the percentage of vulnerable struts and the clinical characteristics of patients. 60 patients with stable angina or non-ST-Elevation acute coronary syndrome and indication to percutaneous angioplasty were randomly assigned to receive one of the three DES. After 6 months, OCT images were obtained. After 6 months, OCT images were obtained (1289 cross sections; 10,728 struts). None of the three DES showed non-coated struts or areas of stent thrombosis. Significant differences in the average number of protruding struts (Cre8: 33.9 ± 12.6; Biomatrix: 26.2 ± 18.1; Xience: 13.2 ± 8.5; p

Objective. The SYNTAX trial was designed to evaluate whether multivessel disease patients could benefit from percutaneous or surgical revascularization using a paclitaxel eluting stents, but after the introduction of second generation stents, this score needs to be reevaluated. The aim of our study was to analyze the association between SYNTAX score and the prognosis of mul­tivessel patients submitted to percutaneous coronary intervention (PCI) and second generation everolimus eluting stents (EES) implantation.Materials and Methods. Data on 289 patients with multivessel coronary artery disease submitted to PCI with EES were stored in a dedicated database and retrospectively analyzed. During a mean follow-up period of 14.4±6.4 months, major adverse cardiac and cerebrovascular events (MACCE) including death from any cause, myocardial infarction, target lesion revascularization (TLR) and stroke, were systematically assessed. Results. The incidence of MACCE at follow-up was 13.1%; death from any cause occurred in 19 patients (6.6%) and myocardial infarction in 9 patients (3.1%). TLR was detected in 2.7% of patients and stroke was observed in 2 patients. The SYNTAX score did not prove to be an independent predictor of overall death at multivariable analysis.Conclusion. At mid-term follow-up, the incidence of MACCE in multivessel disease patients submit­ted to PCI and EES implantation was low; no significant association was found between SYNTAX score severity and MACCE at follow-up, suggesting that it should be modified after the introduction of EES.

Ventricular-arterial (V-A) decoupling decreases myocardial efficiency and is exacerbated by tachycardia that increases static arterial elastance (Ea). We thus investigated the effects of heart rate (HR) reduction on Ea in septic shock patients using the beta-blocker esmolol. We hypothesized that esmolol improves Ea by positively affecting the tone of arterial vessels and their responsiveness to HR-related changes in stroke volume (SV). After at least 24 h of hemodynamic optimization, 45 septic shock patients, with an HR aeyen95 bpm and requiring norepinephrine to maintain mean arterial pressure (MAP) aeyen65 mmHg, received a titrated esmolol infusion to maintain HR between 80 and 94 bpm. Ea was calculated as MAP/SV. All measurements, including data from right heart catheterization, echocardiography, arterial waveform analysis, and norepinephrine requirements, were obtained at baseline and at 4 h after commencing esmolol. Esmolol reduced HR in all patients and this was associated with a decrease in Ea (2.19 +/- A 0.77 vs. 1.72 +/- A 0.52 mmHg l(-1)), arterial dP/dt (max) (1.08 +/- A 0.32 vs. 0.89 +/- A 0.29 mmHg ms(-1)), and a parallel increase in SV (48 +/- A 14 vs. 59 +/- A 18 ml), all p < 0.05. Cardiac output and ejection fraction remained unchanged, whereas norepinephrine requirements were reduced (0.7 +/- A 0.7 to 0.58 +/- A 0.5 A mu g kg(-1) min(-1), p < 0.05). HR reduction with esmolol effectively improved Ea while allowing adequate systemic perfusion in patients with severe septic shock who remained tachycardic despite standard volume resuscitation. As Ea is a major determinant of V-A coupling, its reduction may contribute to improving cardiovascular efficiency in septic shock.

This paper - aiming at encouraging a fruitful debate - intends to highlight the discontinuous evolution of the accounting solutions explored by notable bodies (Efrag-Oic, Iasb, Fasb, Kasb, etc.) with reference to transactions involving businesses under common control. The work finally recompose them in two basic categories (discussing their pros/cons as well), here analyzed: acquisition-type accounting, which emphasizes fair value (emergence of exchange or current amounts) vs. merger-type accounting, linked to historical costs (continuity values approach). The first cluster includes the pure-acquisition and the fresh-start method, whereas the second the predecessor basis and the pooling of interests techniques. The concrete identification of the proper methodology, in this regard, essentially requires the profound understanding of the underlying economics, architecture and key elements of a specific transaction shedding light on the most relevant and reliable information useful to stakeholders.

Resolution Pharmacology identifies drugs developed on the biology of the resolution phase of inflammation, the complex molecular and cellular network of events that ensure the tight temporal and spatial control on the inflammatory response. As such, new anti-inflammatory and pro-resolving drugs could derive from pro-resolving mediators and receptors. To implement faithful screening programs, however, it is important to rely on predictive signaling pathway relevant for the ultimate bio-action of interest. Herein we performed an analysis with four prototypical melanocortin receptor (MC1,3,4,5) agonists. The choice fell on the natural agonist αMSH, the small molecule BMS-470539, and the synthetic derivatives [D-Trp8]-γMSH and [Nle4,D-Phe7]-αMSH. We used human macrophages and quantified the effect of the four agonists on inhibition of cytokine release and promotion of efferocytosis. All agonists (1–10 μM) significantly inhibited cytokine release by LPS-stimulated cells whereas [D-Trp8]-γMSH was the most effective in inducing efferocytosis (∼60% increase). To study the signaling profile, we monitored cAMP accumulation and ERK1/2 phosphorylation, and constructed biased plots that revealed a marked biased profile of [D-Trp8]-γMSH toward phospho-ERK1/2. Correlation matrix analysis of all data pointed at phospho-ERK1/2 at any receptor as the most prominent pathway to attain pro-phagocytic actions, and MC1 receptor as the most relevant to drive anti-cytokine effects. In conclusion, the present study highlights the need to associate single-target signaling data with relevant functional outcomes. In this manner, we would increase our chances to optimize drug discovery programs during the early target validation and hit-to-lead phases.

BACKGROUND Residual aortic regurgitation (AR) complicates a not negligible number of transcatheter aortic valve replacement (TAVR) procedures, and its entity is not always clear at intraprocedural angiographic and echocardiographic control. We applied a minimally invasive hemodynamic monitoring system (Pressure Recording Analytical Method, PRAM) in the setting of TAVR, with the aim of identifying parameters that may help in detection and quantification of residual AR. METHODS We performed hemodynamic monitoring with PRAM in 43 patients undergoing trans-femoral TAVR. Investigated parameters were systolic (Psys, mm Hg), diastolic (Pdia, mm Hg), mean (MAP, mm Hg) and dicrotic pressure (Pdic, mm Hg), cardiac output (CO, L/min), stroke volume (SV, mL), cardiac cycle efficiency (CCE, Units), dP/dtmax_rad (mm Hg/ms), MAP-Pdic (mm Hg). RESULTS Procedural success was achieved in 86% of the patients; vascular complications occurred in 3 (6.9%), death in 2 (4.7%). Twenty (46.5%) patients had at least mild residual AR. CO, SV, CCE and dP/dtmax_rad changed significantly (p

Objective Visceral ischemia can be a potentially life-threatening complication of intra-aortic balloon pump (IABP) support. A shorter IABP catheter might lead to a reduction of visceral complications. In this animal study, we evaluate the effects of a 35-mL short catheter in comparison with a 40-mL standard-sized catheter. Methods Eighteen healthy swine underwent 120-minute ligation of the left anterior descending coronary artery followed by 6 hours of reperfusion being supported by either a short IABP catheter (short group) (n = 6) or a long IABP catheter (long group) (n = 6) or with no assistance (controls) (n = 6). Hemodynamics, visceral and coronary flows, as well as biochemical markers were evaluated throughout the different phases of the protocol. Results Mesenteric flows increased significantly at reperfusion (P < 0.001 both) remaining constant afterward (all, P > 0.05) in the short group, while remaining significantly lower in the long group at the start of reperfusion, remaining constantly lower than the short group and controls (P < 0.001 vs short, P < 0.003 vs controls). In both long and short groups, catheters improved renal flows at reperfusion (P < 0.001 both) without any further variation (P < 0.05). In the short group, the flows were higher during the whole of reperfusion (all, P < 0.05). Intra-aortic balloon pump support improved hemodynamic indices and coronary blood flows during reperfusion to a similar extent in both the small and the long group (P > 0.05). Conclusions The short IABP catheter proved to be as effective as the standard-sized catheter in supporting hemodynamics and coronary circulation. Furthermore, it even improves visceral flows in comparison with conventional IABP catheters.

Aims To compare the effects of two thrombus aspiration devices, the manual catheter Export® and the more complex and expensive mechanical Angiojet®, on several indices of reperfusion in acute ST-elevation myocardial infarction (STEMI). Methods and results Clinical, hemodynamic and procedural characteristics of 185 STEMI patients, randomized to treatment with Export (n=95) or Angiojet (n=90) during primary percutaneous coronary intervention (PPCI) were analyzed. The primary endpoint was ST-segment elevation reduction 90min after culprit vessel re-opening. Secondary endpoints included variations in some angiographic parameters (TIMI Flow, TIMI Frame Count and Myocardial Blush Grade) and Infarct Size and Severity at myocardial scintigraphy. A significant reduction in ST-elevation was observed in both groups after PPCI without significant differences between the two groups. No significant difference between Angiojet vs. Export was observed in ST-segment resolution >50% and ≥70%, in TIMI Flow, TIMI Frame Count and Myocardial Blush Grade before vs. after PPCI and in Infarct Size and Severity. Conclusions PPCI with thrombus aspiration was effective in both groups of patients, without differences in myocardial reperfusion and necrosis indices. These results could support the routine use of manual devices during PPCI, reserving the more expensive Angiojet in case of manual device failure and persistent or massive intracoronary thrombosis, with favorable implications in terms of cost containment.

Patients' response to dual antiplatelet therapy (DAPT) is subject to variations and its monitoring allows to individualize this therapy. In this study, we evaluated if a strategy of tailored DAPT after platelet function testing could reduce high on-treatment platelet reactivity (HPR) and improve outcome of patients treated with stent implantation. In 257 patients undergoing percutaneous angioplasty, platelet function was measured by light transmittance aggregometry (LTA) using 10 µM/L adenosine-diphosphate (ADP) and 1 mM arachidonic acid (AA) as agonists. Patients with HPR by ADP (≥70%) were switched to double-dose clopidogrel, ticlopidine, prasugrel or ticagrelor; in patients with HPR by AA (≥20%) acetylsalicylic acid dose was increased if not contraindicated. Platelet function analysis was repeated 48 hours after therapy variation. At 20-month follow-up major adverse cardiovascular events (MACE) and bleedings were assessed. HPR was detected in 97/257 (37.7%) patients: 69/257 (26.8%) had HPR by ADP and 71/257 (27.6%) had HPR by AA. In patients with HPR by ADP or by AA, tailored DAPT determined a significant reduction in residual platelet reactivity. No significant difference in MACE or bleeding occurrence was documented in HPR patients treated with tailored DAPT vs. those without HPR. HPR patients treated with tailored DAPT had significant lower follow-up MACE and deaths vs. 139 HPR patients not switched, even after propensity score analysis. These results suggest that a DAPT tailored on platelet testing can improve antiplatelet response in HPR patients, possibly reducing their thrombotic events to a level similar to non-HPR patients, without increasing the risk of bleeding.

The involvement of microRNA (miR) in cystic fibrosis (CF) pathobiology is rapidly emerging. We previously documented that miR-181b controls the expression of the ALX/FPR2 receptor, which is recognized by the endogenous proresolution ligand, lipoxin (LX)A4. Here, we examined whether the miR-181b-ALX/FPR2 circuit was altered in CF. We examined human airways epithelial cells, normal (16HBE14o-), carrying the ΔF508 mutation (CFBE41o-) or corrected for this mutation (CFBE41o-/CEP-CFTR wt 6.2 kb), as well as monocyte-derived macrophages (MΦs) from CF patients. CFBE41o- cells exhibited higher miR-181b and reduced ALX/FPR2 levels compared to 16HBE14o- and CFBE41o-/CEP-CFTR wt 6.2 kb cells. An anti-mir-181b significantly enhanced ALX/FPR2 expression (+ 60%) as well as LXA4-induced increase in transepithelial electric resistance (+ 25%) in CFBE41o- cells. MΦs from CF patients also displayed increased miR-181b (+ 100%) and lower ALX/FPR2 levels (− 20%) compared to healthy cells. An anti-mir-181b enhanced ALX/FPR2 expression (+ 40%) and normalized receptor-dependent LXA4-induced phagocytosis of fluorescent-labeled zymosan particles as well as of Pseudomonas aeruginosa by CF-MΦs. These results provide the first evidence that miR-181b is overexpressed in CF cells, impairing some mechanisms of the ALX/FPR2-dependent pathway of inflammation resolution. Thus, targeting miR-181b may represent a strategy to enhance anti-inflammatory and anti-microbial defense mechanisms in CF.

Background and purpose Although several studies reported that drug-eluting stents (DES) are able to reduce restenosis incidence without increasing mortality, concerns still exist about their safety in ST-segment elevation myocardial infarction (STEMI) patients mainly for a possible higher rate of in-stent thrombosis. Recent evidence suggests a better safety profile of second-generation DES, but data on their outcome in STEMI are still poor. In this study we evaluated the impact on mortality and target lesion revascularization (TLR) of DES or bare metal stent (BMS) implantation in STEMI patients submitted to primary angioplasty. Methods and subjects We analyzed mortality and TLR in 1150 STEMI patients during a mean 43-month follow-up after DES (44.6%) or BMS (55.4%) implantation. A propensity score method was used to minimize bias. During follow-up, 223 deaths occurred. Essential results Unadjusted for potential confounders, DES implantation was associated with a significant reduction in all-cause mortality [hazard ratio (HR) 0.40; 95%CI 0.30–0.54] and TLR (HR 0.55; 95%CI 0.36–0.86); this latter was confirmed after propensity score analysis (HR 0.39; 95%CI 0.21–0.67). Second- (n = 179) vs. first- (n = 337) generation DES showed a further reduction in TLR (HR 0.17; 95%CI 0.05–0.57). Adjusted analyses showed a significant reduction in the combined end-point of all-cause mortality or TLR after both first- and second-generation DES vs. BMS implantation with a trend to a lower risk for second- vs. first-generation DES. Principal conclusions DES implantation in STEMI patients showed a significant reduction in TLR and in the combined endpoint of TLR or mortality. Second-generation DES showed a more protective effect on the combined endpoint, suggesting that they would be preferred in this setting.

Data on the hemodynamic and cardiovascular effects of hypothermia in patients with cardiac arrest are scarce. The aim of this study was to evaluate the hemodynamic changes induced by hypothermia by means of Most Care(®) (pressure recording analytical method, PRAM methodology), a beat-to-beat hemodynamic monitoring method.We enrolled 20 patients with cardiac arrest (CA) consecutively admitted to our intensive cardiac care unit and treated with mild hypothermia (TH).While non-survivors showed no changes in haemodynamic variables throughout the study period, survivors exhibited a significant increase in systemic vascular resistance indexed during hypothermia and a trend towards lower values of heart rate and higher levels of mean arterial pressure.According to our data, PRAM methodology proved to be a feasible and clinically useful tool in CA patients treated with TH since it provides continuous beat-to-beat haemodynamic monitoring that is based on assessment of several haemodynamic variables. Moreover, we observed that survivors showed a different haemodynamic behaviour during hypothermia in respect to patients who died. However, further studies, performed in larger cohorts, are needed to better elucidate the haemodynamic effects of hypothermia in CA patients by means of PRAM methodology.

Background and Objective: Prostate cancer is an endocrine-dependent tumor which is still under-investigated for physiopathology factors related to its natural history. The association of pretreatment total testosterone (TT) serum levels with prostate cancer is still a controversial topic. The objective of this study was to investigate potential associations and functional relationships of preoperative TT serum level and pathology-detected Gleason score (pGS). Materials and Methods: Pretreatment and pathological variables of 220 patients operated with radical prostatectomy were retrospectively reviewed. Age, prostate-specific antigen (PSA), percentage of positive biopsy cores (P+), biopsy Gleason score (bGS), pGS, TT and free testosterone were the continuous variables, while clinical stage (cT: cT1c, cT2/3), biopsy Gleason pattern (bGP: ≤3+3, 3+4, >3+4), pathology Gleason pattern (pGP: ≤3+3, 3+4, >3+4), pathology stage (pT: pT2, pT3a, pT3b), pathology nodal staging (pN: pN0, pN1, pNx) and surgical margin invasion by cancer (R-, R+) were the categorical variables. Statistical methods were computed for assessing associations of TT and pGS; moreover, simple and multiple linear regression analysis (SLRA and MLRA) were used for assessing functional relationships of TT and pGS. Results: High-grade tumors (pGS ≥8.0) were associated with bGS >6.0 (p < 0.0001), pGP ≥3+4 (p < 0.0001), P+ >0.31% (p = 0.006), cT2/3 (p = 0.01), TT >15.5 nmol/l (p = 0.0004) and, to a lesser extent, PSA >6.27 μg/l (p = 0.06). The odds ratio (OR) ranked as follows: 2.01 (PSA >6.27 μg/l), 2.88 (cT2/3), 3.23 (P+ >0.31%), 5.53 (TT >15.5 nmol/l) and 12.09 (pGP ≥3+4 and pGS ≥8.0). On SLRA, pGS variation was significantly predicted by bGS (p < 0.0001), P+ (p < 0.0001), PSA (p = 0.0005) and TT (p = 0.02); on MLRA, pGS variation was still significantly predicted by bGS (p < 0.0001), P+ (p = 0.04), PSA (p = 0.03) and TT (p = 0.002). When bGS, P+, PSA and TT were dichotomized to their median value, only bGS (p < 0.0001) and TT (p = 0.001) showed independence in predicting pGS variation. The best model for predicting pGS variations was by dichotomizing TT above its median (>15.5 nmol/l) because the predictive coefficient increased to 0.32, which means that patients with TT >15.5 have a significantly higher estimated risk for high-grade pGS than patients with TT ≤15.5 nmol/l (OR = 1.31). Conclusion: In a patient population undergoing radical prostatectomy, increased pretreatment serum measurements of TT are associated with and functionally related to high-grade pGS; moreover, baseline TT together with bGS and PSA are important factors for predicting pGS and assessing high-grade tumors. Baseline TT serum levels might have prognostic potential for assessing treatment response for continuous as well as intermittent androgen deprivation therapy.

Previous studies analyzing the impact of hypertension (HTN) on myocardial infarction (MI) outcome reached conflicting results and scarce data are available in patients treated with percutaneous coronary intervention (PCI). In this study the prognostic impact of HTN history in ST-elevation MI (STEMI) and Non-STEMI (NSTEMI) patients treated with PCI was analyzed. We compared characteristics of 1,031 STEMI and 437 NSTEMI patients, in relation to the presence of HTN. Median follow-up duration was 40.2 months. HTN was significantly higher in NSTEMI vs. STEMI patients (p

Several studies have evaluated the prognostic impact of atrial fibrillation (AF) in ST-elevation myocardial infarction (STEMI) patients, but scarce data are available on the role of AF in non-ST-elevation acute coronary syndromes (NSTE-ACS). The aim of this study was to investigate long-term outcome of NSTE-ACS patients experiencing an episode of AF during in-hospital course. Of 1,147 NSTE-ACS patients, 54.4% for non-STEMI (NSTEMI) and 45.6% for unstable angina, 65 (5.7%) had an episode of AF. Long-term survival was compared with that of 1,082 NSTE-ACS patients who did not develop AF. Patients who developed AF, with respect to those who did not, were older and more frequently with NSTEMI at admission (69.2 vs. 53.5%, p = 0.013), diabetes, dyslipidemia and history of heart failure. Moreover, patients who developed AF had a significantly higher New York Heart Association class and lower values of glomerular filtration rate. During a median follow-up of 40.7 months, we observed a significantly higher mortality in NSTE-ACS patients who developed AF versus those who did not (42.2 vs. 19.8%, p0.001). AF occurrence in NSTE-ACS was a significant predictor of mortality at Cox regression (adjusted HR: 1.85; p = 0.03). After propensity score analysis, only patients with AF duration6 h showed a significantly higher mortality at Cox regression (p = 0.021). Our results suggest that NSTE-ACS patients who develop AF are characterized by a higher clinical complexity. The occurrence of AF, when longer than 6 h, represents an important negative prognostic factor for long-term survival.

Objective: Few studies are available on the hemodynamic changes acutely determined by Primary Percutaneous Coronary Intervention (PCI) in ST-Elevation Myocardial Infarction (STEMI) patients, probably for the difficult evaluation of hemodynamic variables in this acute setting. Therefore, the paper is to evaluate the variations of several hemodynamic parameters determined by PCI using PRAM (Pressure Recording Analytical Method), minimally invasive hemodynamic monitoring. Methods: We analyzed in 20 STEMI patients submitted to PCI several hemodynamic variables, assessed with PRAM from radial/ femoral artery, 3-minute before PCI and at endprocedure. Variables measures were: systolic, diastolic, dicrotic and mean arterial pressures; heart rate (HR); stroke volume (SV); systemic vascular resistance (SVR); dP/dtmax; cardiac cycle efficiency (CCE). Results: In our patients HR, SVR and dP/dtmax decreased significantly (85 ± 6.3 to 77 ± 4.5, p = 0.002; 1738 ± 241 to 1450 ± 253, p = 0.022; 1.22 ± 0.11 to 1.11 ± 0.12, p = 0.007, respectively) while CCE and SV increased significantly (?0.25 ± 0.23 to ?0.01 ± 0.12, p

Aim: To investigate the potential of preoperative serum total testosterone (TT) in contributing to the definition of separate prostatectomy Gleason score (pGS) groups of the prostate cancer (PCa) population. Materials and Methods: The data of 220 patients operated on for PCa were retrospectively reviewed. No patient had previously received 5α-reductase inhibitor, luteinizing hormone-releasing analogs or testosterone replacement treatment. The patient population was grouped according to the pGS as 6 = 3+3, 7 = 3+4, 7 = 4+3 and 8-10. Eight variables were simultaneously investigated in each group: prostate-specific antigen (PSA), TT, free testosterone, age, percentage of positive prostate biopsy cores (P+), biopsy Gleason score (bGS), overall cancer volume estimated as percentage of prostate volume (V+) and prostate weight (Wi). Univariate analysis of variance (ANOVA), multivariate analysis of variance (MANOVA) and multivariate discriminant analysis (MDA) were the statistical methods used for evaluating the data. Results: There were 89 patients in pGS 6 = 3+3, 84 in pGS 7 = 3+4, 24 in pGS 7 = 4+3 and 23 in pGS 8-10. ANOVA showed that bGS (p < 0.0001), P+ (p < 0.0001), V+ (p < 0.0001), PSA (p = 0.0001), Wi (p = 0.0002) and TT (p = 0.01) were significantly different in the four pGS groups. MANOVA tests showed that only bGS (p < 0.0001), V+ (p = 0.0003), TT (p = 0.001) and, to a lesser extent, PSA (p = 0.06) were the significant variables that individually and independently contributed a significant amount to separation of the four pGS groups of the PCa population. MDA showed that the independent variables ranked as bGS (p < 0.0001), TT (p = 0.001), V+ (p = 0.001) and PSA (p = 0.06). Conclusions: Serum TT is a significant preoperative variable that independently contributes to separating the PCa population into pGS score groups. Pretreatment baseline serum TT levels should be measured and their inclusion in neural networks predicting PCa natural history be considered in the patient population diagnosed with PCa.

The proresolution lipid mediator lipoxin (LX)A

Lipoxin (LX)A

Aim: A preceding exploratory analysis has shown that follicle-stimulating hormone (FSH) was significantly correlated to and predicted by prostate-specific antigen (PSA) in a prostate cancer population. The aim of the study was to evaluate FSH physiopathology along the pituitary-testicular-prostate (PTP) axis at the time of initial diagnosis of prostate cancer in an operated population clustered according to the FSH/PSA ratio. Patients and Methods: The study included 93 patients who underwent standard radical prostatectomy. Age, percentages of positive cores at transrectal ultrasound scan biopsy (TRUSB) (P+), biopsy Gleason score (bGS), pathology Gleason score (pGS), luteinizing hormone (LH), FSH, prolactin hormone (PRL), total testosterone (TT), free testosterone (FT), estradiol (ESR) and PSA were the continuous variables. Category variables were pT and biopsy/pathology Gleason pattern I/II (b/pGPI/II). The population was clustered according to the FSH/PSA ratio which was computed from empirical data and then ranked for clustering the population as groups A (range 0.13 ≤ FSH/PSA ≤ 0.20), B (range 0.20 < FSH/PSA ≤ 0.50), C (range 0.50 < FSH/PSA ≤ 0.75), D (range 0.75 < FSH/PSA ≤ 1.00), E (range 1.00 < FSH/PSA ≤ 1.25), F (range 1.25 < FSH/PSA ≤ 2.00), G (range 2.00 < FSH/PSA ≤ 2.25), H (range 2.25 < FSH/PSA ≤ 6.40) and I (range 6.40 < FSH/ PSA ≤ 19.40). The model was assessed by simple linear regression analysis and differences between the groups were investigated by analysis of variance (ANOVA) for continuous variables and by contingency tables for category variables. Results: FSH was significantly correlated to and predicted by PSA in groups A (p = 0.04), B (p < 0.0001), C (p < 0.0001), D (p < 0.0001), E (p < 0.0001), F (p < 0.0001), G (p < 0.0001), H (p = 0.0001) and I (p = 0.001). Also, clusters (A–I) differed significantly for mean values of FSH (p < 0.0001), LH (p < 0.0001), TT (p = 0.04), PSA (p < 0.0001), bGS (p = 0.005), pGS (p = 0.01) and PSA/FT ratio (p < 0.0001); moreover, the nine groups showed significant different frequency distributions of pGPI (p = 0.02), pGPII (p = 0.0002) and bGPI (p = 0.04). Conclusion: The ranking FSH/PSA ratio significantly clustered, along the PTP axis, an operated population diagnosed with prostate cancer. Also, the ranking FSH/PSA ratio selected prostate cancer clusters expressing different levels of hormonal disorder along the PTP axis and prognostic potential with different risks of progression. As a theory, in the current advancing world, the ranking FSH/PSA model might be considered as an interesting and effective tool for prostate cancer study as well as individualized, risk-adapted approaches of the disease. However, confirmatory studies are needed.

A pivotal role in treating decompensated heart failure (HF) is played by inotropes and calcium sensitizers such as levosimendan. In this study, the authors evaluated whether levosimendan could determine further clinical and hemodynamic benefits in 31 HF patients (New York Heart Association [NYHA] class III or IV), after successful treatment with diuretics (n=15) or ultrafiltration (n=16). Systolic, diastolic, dicrotic, and mean arterial pressures; systemic vascular resistance (SVR); some classic hemodynamic variables (cardiac output [CO], stroke volume [SV], dP ⁄dtmax); and indices of cardiovascular system performance (cardiac cycle efficiency [CCE], cardiac power output) have been assessed by the pressure recording analytical method (PRAM), a minimally invasive monitoring system, before levosimendan infusion, at the end of treatment (EoT), and 36 hours after EoT (post-36). A significant increase in CCE, CO, SV, and dP ⁄dtmax and a significant decrease in diastolic and dicrotic arterial pressures and in SVR have been observed at EoT and at post-36. After the addition of levosimendan, a further reduction in signs and symptoms of HF and NYHA class was observed. Five patients showed an opposite trend of several hemodynamic parameters without any significant clinical improvement (nonresponders). In conclusion, most HF patients treated with diuretics or ultrafiltration receive additional clinical and hemodynamic benefits from levosimendan. The characterization of nonresponders could help in optimizing its use. Congest Heart Fail. 2012;18:47‐53. � 2011 Wiley Periodicals, Inc. Standard therapy for patients with decompensated heart failure (HF) and overhydration is aimed at achieving euvolemia and consists primarily of intravenous diuretics and vasodilators. Patients unresponsive to diuretic therapy or with renal dysfunction can be treated with ultrafiltration and those with hypotension can also be treated with inotropic agents. However, classic inotropic drugs are associated with increased myocardial oxygen consumption, major risk of arrhythmias, and reduced short- and long-term survival. Therefore, attention has been focused on calcium-sensitizing agents, 1,2 a novel class of inotropic drugs, among which levosimendan is the most studied. This group of drugs is able to enhance cardiac performance without increasing intracellular calcium and cyclic adenosine monophosphate levels and, consequently, without the deleterious effects associated with classic inotropic drugs. However, the effective role of levosimendan in the treatment of decompensated congestive HF is yet to be clarified because it is an inotropic agent indicated only when systolic arterial pressure is 90 mm Hg. Therefore, this study was performed to evaluate whether patients with decompensated HF successfully treated with standard therapy, including continuous diuretic infusion or ultrafiltration, receive further clinical and hemodynamic benefits from the addition of levosimendan. Hemodynamic parameters were assessed in the present study with the pressure recording analytical method (PRAM), a minimally invasive monitoring system. 3,4

Aims and background Hyperthermia, the heating of tumors to 41.5–43 °C, could be today considered the fourth pillar of the treatment of cancer. Employed for 20 years in Europe, the USA and Asia, hyperthermia, used in addition to radiotherapy, chemotherapy and surgery, increases both local control and overall survival, restores the chance of the surgery for inoperable tumors and allows a new low-dosage treatment of relapsed cancers previously treated with high radiotherapy dosage without increasing toxicity. Methods Hyperthermia can be either superficial, produced by a microwave generator, or regional, produced by a radiofrequency applicator with multiple antennas, which emanate a deep focalized or interstitial heating. Results The results are confirmed by phase III randomized trials, with level 1 evidence. A review of the international literature on hyperthermia, the experience of the University Hospital of Verona Radiotherapy Department (Italy) and a summary of the Symposium regarding the Evolution of Clinical Hyperthermia plus Radiotherapy during the Twentieth Congress of the French Society of Radiation Oncology (SFRO) are presented. Conclusions Hyperthermia is an important treatment modality in cancer treatment and its results are strongly supported by criteria of evidence-based medicine. Fifteen years of experience of the Radiation Oncology Department in Verona confirms the positive results obtained with international prospective trials, with level 1 evidence. Hyperthermia appears to be the fourth pillar beside surgery, radiotherapy and chemotherapy. Free full text available at www.tumorionline.it

Background Percutaneous coronary intervention (PCI) is considered to be the optimal type of revascularization in patients with ST-segment elevation myocardial infarction (STEMI). However, the long-term effectiveness of this procedure can be reduced by restenosis. This investigation was aimed at a prospective evaluation, in a group of STEMI patients of "the real world" (not involved in randomised trials), of the angiographic restenosis rate at a 6-month follow-up, and at identifying the relationship between restenosis and the patients' characteristics. Materials and methods Our study population consisted of 123 patients with STEMI submitted to primary PCI to then undergo stress echocardiography 3 months after PCI and an angiographic evaluation at a 6-month follow-up. Results a) In real life the restenosis rate is quite high (42.3%); b) no correlation was found between patients' clinical characteristics and restenosis; c) restenosis rate was higher in patients with bare metal stents than in those with drug-eluting stents (55.8% vs. 11.1%; p p =0.015) and when more than one stent was implanted. Moreover, a consistent number of patients showed restenosis though asymptomatic. Conclusions Our data suggest that primary PCI is associated with a high incidence of angiographic restenosis. No correlation was found between patients' clinical characteristics and restenosis. The length and the number of implanted stents seem to be associated with a more probable restenosis at six-month angiographic evaluation. Drug-eluting stent implantation seems to be associated with a lower incidence of restenosis even in STEMI patients.

Background At the Istituto di Clinica Medica Generale e Cardiologia (Florence, Italy), the widespread use of percutaneous coronary intervention (PCI) has markedly changed the hospital course of patients with acute myocardial infarction (AMI). These patients are typically transferred to the coronary care unit (CCU) only after primary PCI, whereas during the thrombolytic era, patients were first admitted to CCU before reperfusion. Objectives and methods The incidence, timing and setting of complications from symptom onset to hospital discharge in 689 consecutive AMI patients undergoing PCI were evaluated. Results Ventricular fibrillation occurred in 11% of patients, and most episodes (94.7%) occurred before or during PCI. Of all patients, 6.3% developed complete atrioventricular block (CAVB), and in 86.3% of these cases, the CAVB occurred before or during PCI; in 94.5%, a CAVB resolution occurred in the catheterization laboratory (CL). Thirty-one patients (4.5%) had impending shock on admission to the CL. Cardiogenic shock developed in 29 patients (4.2%), mostly in the prehospital phase or in the CL. Only four patients (less than 1%) developed cardiogenic shock later during their hospital course. Similarly, circulatory and ventilatory support, as well as temporary pacing and cardiac defibrillation, were used mostly in the prehospital phase or in the CL. During the CCU stay, 45 patients (6.5%) had hemorrhagic or vascular complications, and the incidence of post-PCI ischemia and early reocclusion of the culprit vessel were low (2.1% and 0.6%, respectively). Thus, cardiac complications usually associated with AMI were observed mainly before hospital admission or in the CL during the reopening of the target vessel. These complications were rarely observed after a successful PCI. Conclusions For AMI patients, the CL is not only the site of PCI, it is also where most life-threatening cardiac complications are observed and treated.

Background: The pressure recording analytical method (PRAM) is a method for real-time beat-to-beat quantification of peripheral blood flow based on the analysis of arterial waveform morphology. Since PRAM can be implemented in any conditions of flow, whether physiological or artificial, we assessed its accuracy in patients undergoing cardiac surgery during extracorporeal circulation (ECC), using the roller-pump device as the reference gold standard.Methods: We prospectively studied 32 patients undergoing elective coronary surgery. Flow values obtained by PRAM from the radial artery were compared with simultaneous values by thermodilution in physiological conditions of flow and with the roller-pump device readings during ECC.Results: Before and after ECC, the overall estimates of flow measured by PRAM closely agreed with thermodilution (mean difference 0.07±0.40 L/min). During ECC, PRAM estimates of flow also closely correlated with simultaneous pump readings (mean difference 0.11±0.33 L/min). At time of weaning from ECC, two patterns of hemodynamic adaptation were documented by PRAM following resumption of cardiac contraction: in most patients ( n = 26; 80%), cardiac output (CO) was stable (reduction ≤ 10% compared to the steady ECC phase); six patients (20%) showed a fall in CO exceeding 10% and up to 38%.Conclusions: PRAM provided accurate, continuous quantification of peripheral blood flow during each phase of cardiac surgery, including ECC, and allowed early recognition of patients with low CO during weaning from the pump.