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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

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.

Introduction: Studies have shown that a hemodynamic-guided therapy improves the post operative outcomes of high-risk patients.This study, evaluated if a short period through minimally invasive hemodynamic monitoring, pressure recording analytical method (PRAM), on admission to a post-cardiac surgery step-down unit (SDU), may identify patients at higher risk of 6-month adverse events after cardiac surgery. Methods: From December 2016-May 2017,173 patients were admitted in SDU within 24-48 hours of major cardiac surgery procedure, and submitted to clinical, laboratoristic and echocardiographic evaluation and a 1-hour PRAM recording to obtain a "biohumoral snapshot" of individual patient’s.156 173 patients (17 patients were lost at follow-up) were phone interviewed six months after surgery,to evaluate, as a composite end-point, the adverse events during follow-up. A multivariable logistic regression analysis was used to identify a model clinical-biohumoral (CBM) and clinical-biohumoral hemodynamics (CBHM). Results: No data from past clinical history and no conventional risk score (EuroScore II, STS score)independently predicted the risk of 6-month major events in our study. The risk of adverse events at six-month follow-up was directly related, in the CBM, to sustained post-operative cardiac arrhythmias, higher values of NT-proBNP and of arterial pH; inversely related to values of hs-C-reactive protein (hs-CRP) and, in the CBHM, to low values of cardiac cycle efficiency (CCE) and dP/dtmax. Conclusion: Our study although limited by its observational nature and by the limited number of patients enrolled, showed that a short period of minimally invasive hemodynamic monitoring increased the accuracy to identify patients at major risk of mid-term events after cardiac surgery.

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.

Backgrounds Central arterial pressure can be derived from analysis of the peripheral artery waveform. The aim of this study was to compare central arterial pressures measured from an intra-aortic catheter with peripheral radial arterial pressures and with central arterial pressures estimated from the peripheral pressure wave using a pressure recording analytical method (PRAM). Methods We studied 21 patients undergoing digital subtraction cerebral angiography under local or general anesthesia and equipped with a radial arterial catheter. A second catheter was placed in the ascending aorta for central pressure wave acquisition. Central (AO) and peripheral (RA) arterial waveforms were recorded simultaneously by PRAM for 90–180 s. During an off-line analysis, AO pressures were reconstructed (AOrec) from the RA trace using a mathematical model obtained by multi-linear regression analysis. The AOrec values obtained by PRAM were compared with the true central pressure value obtained from the catheter placed in the ascending aorta. Results Systolic, diastolic and mean pressures ranged from 79 to 180 mmHg, 47 to 102 mmHg, and 58 to 128 mmHg, respectively, for AO, and 83 to 174 mmHg, 47 to 107 mmHg, and 60 to 129 mmHg, respectively, for RA. The correlation coefficients between AO and RA were 0.86 (p

The number of aortic stenosis patients in Western countries is increasing, along with better life conditions and expectancies. Presently, the volume of percutaneous transcatheter aortic valve implantations (TAVIs) is incessantly increasing, and has already overcome the surgical replacement procedure volume. According to the literature, TAVI is a feasible procedure even among low surgical risk patients, and American guidelines have extended the indications for TAVI, including shifting patient evaluations from high/low STS scores to old/young patients, a “paradigm shift” of aortic stenosis evaluation. As a result, low-risk young (

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.

Background. Although the clinical effects of stent malapposition remain controversial, several analyses of stent registries consistently have found that malapposed struts were frequently identified in patients who experienced stent thrombosis. In this study, which is a subanalysis of the previously published CREBX-OCT study, we compared optical coherence tomography (OCT) analysis at the index percutaneous coronary intervention (PCI) and at six-month follow-up in 37 patients randomly assigned to receive, by a single operator, three different second-generation drug-eluting stents (Cre8, Biomatrix, and Xience) aiming to clarify if the malapposition observed at six-month follow-up was persistent or late-acquired. Moreover, we investigated if there were some differences in the behavior of the three different kinds of stents in relation to the struts malapposition. Material and Methods. We analyzed 614 and 599 cross sections and 5514 and 5377 struts at the index PCI and at six-month follow-up, respectively. The qualitative analysis of the plaque composition among the three groups did not show significant differences. Results. The lumen area did not significantly change from the index procedure to the six-month follow-up in the three groups; on the contrary, the number of malapposed struts increased significantly in the Cre8 and Biomatrix groups but not in the Xience group: 0.58 ± 1.51 and 3.29 ± 5.33 ( p < 0.023 ) in the Cre8 group, 0.55 ± 1.81 and 1.73 ± 2.28 ( p < 0.024 ) in the Biomatrix group, and 0.55 ± 1.5 and 0.25 ± 0.87 ( p < 0.166 ) in the Xience group, respectively. Conclusions. Therefore, the malapposition observed at six-month follow-up in our study population could be mainly considered as acquired and attributable to biomechanical reasons due to the structural differences among the three stents. This trial is registered with Clinical Trials.gov Identifier: NCT02850497.

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.

Aim: We evaluated the influence of intra-aortic balloon size and volume on mesenteric and renal flows. Methods: Thirty healthy swine underwent 120-minute ligation of the left anterior descending coronary artery followed by 6 hours of reperfusion. Then, they were randomly assigned to the following five groups of animals, with six animals in each group: no intra-aortic balloon pump (IABP), a short 35-mL IABP, a short 40-mL IABP, a long 35-mL IABP and a long 40-mL IABP. Superior mesenteric artery (SMA) and renal flows were measured at baseline (t0), at 2-hour ischemia (t1) and every hour thereafter until 6 hours of reperfusion (from tR1 to tR6). Results: SMA flows increased significantly at tR1 only in the two short IABP groups (p0.05). Renal flows appeared to be influenced by balloon length, but not by volume. Indeed, flows in the renal arteries rose during IABP treatment; the increase was significantly higher in the short balloon groups and throughout the whole reperfusion (all, pConclusions: Changes in visceral perfusion during IABP assistance were significantly related to balloon length, but not to its volume. This could be relevant for the evolution of balloon engineering design in order to reduce the incidence of mesenteric ischemia following IABP. Further research is necessary to confirm these findings.

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.

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.

Background Despite important results achieved for metastatic renal cell carcinoma, some patients could benefit from local treatments or an initial active surveillance (AS) period for recurrent disease. We aim to analyze: changes in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk class, the number of metastases and the disease burden from the start of AS to the beginning of systemic therapy; and if these changes influenced patient outcomes. Patients and Methods Patients who started AS at our institution from January 2007 to April 2016 were included. The Kaplan-Meier method was used to estimate total overall survival (tOS) and progression-free survival. Changes in IMDC class, number of metastatic sites, and tumor burden (TB) were evaluated and related to patient survival. Among the patients who started active treatment, progression-free survival and post surveillance OS (psOS) were evaluated. Results 52 patients were included in the analysis. Median time on AS and tOS were 18.3 and 80.1 months respectively. Baseline factors were not related to the time on AS apart from the IMDC classification (HR = 2.15; 95% CI: 1.19–3.87; P = 0.011). The increase in the number of metastatic sites during AS was correlated with poor tOS (HR = 2.86; 95% CI: 1.29–6.34; P = 0.010). The increase of the TB was a negative prognosis factor for tOS (HR = 1.16; 95% CI: 1.02–1.31; P = 0.024) and psOS (HR = 1.21; 95% CI: 1.07–1.40; P = 0.004). Both IMDC class and change in the TB at the start of therapy were related to psOS. The retrospective nature and the lack of an external review of the imaging are its main limitations. Conclusions During AS, patients rarely experience a deterioration of their IMDC prognostic class, and the change in the TB, more than the increase in the number of metastatic sites, may help physicians to make decisions about the early termination of AS and the start of systemic therapy.

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.

The proresolution lipid mediator lipoxin (LX)A