It is now 4 years since the introduction of the new direct oral anticoagulants into clinical practice. Therefore, the Italian Association of Hospital Cardiologists (ANMCO) has deemed necessary to ...update the previous position paper on the prevention of thrombo-embolic complications in patients with non-valvular atrial fibrillation, which was published in 2013. All available scientific evidence has been reviewed, focusing on data derived from both clinical trials and observational registries. In addition, all issues relevant to the practical clinical management of oral anticoagulation with the new direct inhibitors have been considered. Specific clinical pathways for optimal use of oral anticoagulation with the new directly acting agents are also developed and proposed for clinical implementation. Special attention is finally paid to the development of clinical algorithms for medium and long-term follow-up of patients treated with new oral direct anticoagulants.
Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of ...underestimating the complexities involved in treating FEP in 'real-world' services.
The Psychosis early Intervention and Assessment of Needs and Outcome (PIANO) trial is part of a larger research program (Genetics, Endophenotypes and Treatment: Understanding early Psychosis - GET UP) which aims to compare, at 9 months, the effectiveness of a multi-component psychosocial intervention versus treatment as usual (TAU) in a large epidemiologically based cohort of patients with FEP and their family members recruited from all public community mental health centers (CMHCs) located in two entire regions of Italy (Veneto and Emilia Romagna), and in the cities of Florence, Milan and Bolzano. The GET UP PIANO trial has a pragmatic cluster randomized controlled design. The randomized units (clusters) are the CMHCs, and the units of observation are the centers' patients and their family members. Patients in the experimental group will receive TAU plus: 1) cognitive behavioral therapy sessions, 2) psycho-educational sessions for family members, and 3) case management. Patient enrollment will take place over a 1-year period. Several psychopathological, psychological, functioning, and service use variables will be assessed at baseline and follow-up. The primary outcomes are: 1) change from baseline to follow-up in positive and negative symptoms' severity and subjective appraisal; 2) relapse occurrences between baseline and follow-up, that is, episodes resulting in admission and/or any case-note records of re-emergence of positive psychotic symptoms. The expected number of recruited patients is about 400, and that of relatives about 300. Owing to the implementation of the intervention at the CMHC level, the blinding of patients, clinicians, and raters is not possible, but every effort will be made to preserve the independency of the raters. We expect that this study will generate evidence on the best treatments for FEP, and will identify barriers that may hinder its feasibility in 'real-world' clinical settings, patient/family conditions that may render this intervention ineffective or inappropriate, and clinical, psychological, environmental, and service organization predictors of treatment effectiveness, compliance, and service satisfaction.
We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping ...vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR) to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS) was 15 months (95% CI, 8–33). Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy) after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16–61). Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The effects of circadian blood pressure (BP) changes on the echocardiographic parameters of left ventricular (LV) hypertrophy were investigated in 235 consecutive subjects (137 unselected untreated ...patients with essential hypertension and 98 healthy normotensive subjects) who underwent 24-hour noninvasive ambulatory blood pressure monitoring (ABPM) and cross-sectional and M-mode echocardiography. In the hypertensive group, LV mass index correlated with nighttime (8:00 PM to 6:00 AM) systolic (r = 0.51) and diastolic (r = 0.35) blood pressure more closely than with daytime (6:00 AM to 8:00 PM) systolic (r = 0.38) and diastolic (r = 0.20) BP, or with casual systolic (r = 0.33) and diastolic (r = 0.27) BP. Hypertensive patients were divided into two groups by presence (group 1) and absence (group 2) of a reduction of both systolic and diastolic BP during the night by an average of more than 10% of the daytime pressure. Casual BP, ambulatory daytime systolic and diastolic BP, sex, body surface area, duration of hypertension, prevalence of diabetes, quantity of sleep during monitoring, funduscopic changes, and serum creatinine did not differ between the two groups. LV mass index, after adjustment for the age, the sex, the height, and the daytime BP differences between the two groups (analysis of covariance) was 82.4 g/m2 in the normotensive patient group, 83.5 g/m2 in hypertensive patients of group 1 and 98.3 g/m2 in hypertensive patients of group 2 (normotensive patients vs. group 1, p = NS; group 1 vs. group 2, p = 0.002).
Micro-Abstract Peritoneal carcinomatosis (PC) is observed in approximately 10% of patients with colorectal cancer at the time of primary cancer resection. Most of these patients receive ...5-fluorouracil (5-FU)- or oxaliplatin-containing chemotherapy regimens as first-, second-, or third-line treatment. In the present study, sensitivity and resistance to drugs used to treat PC were better defined by a conventional chemosensitivity test than by biomarker expression.
We examined the prognostic significance of concentric remodeling of the left ventricle in patients with essential hypertension and normal left ventricular mass on echocardiography.
An ...echocardiographic pattern of concentric remodeling of the left ventricle has been associated with clinical features of increased cardiovascular risk, but the independent prognostic value of this finding in hypertensive patients with normal left ventricular mass has not been established.
Six hundred ninety-four patients with essential hypertension and normal left ventricular mass (<125 g/m2) on echocardiography were prospectively followed up for ≤7.7 years (mean 2.71). Baseline echocardiography and 24-h noninvasive ambulatory blood pressure monitoring were performed in all patients at the time of initial diagnostic evaluation. Concentric remodeling was defined by the thickness of the septum or posterior wall divided by the left ventricular radius at end-diastole ≥0.45.
Prevalence of concentric remodeling was 39.2%. During follow-up there were 29 cardiovascular morbid events. Cardiovascular morbidity, expressed as the combined number of fatal and nonfatal events per 100 patient-years, was 1.53 in the overall study group, 1.12 in the subgroup with normal left ventricular geometry and 2.39 in that with concentric remodeling. After assessment of the independent association with several covariates (age, gender, diabetes, left ventricular mass index, mean clinic blood pressure and mean 24-h ambulatory blood pressure) in Cox proportional hazard models, the risk of cardiovascular morbid events was higher in the group with concentric remodeling than in that with normal geometry (relative risk 2.56, 95% confidence interval 1.20 to 5.45, p < 0.01).
Concentric remodeling of the left ventricle, defined by the thickness of the septum or posterior wall divided by the left ventricular radius at end-diastole ≥0.45, is an important and independent predictor of increased cardiovascular risk in hypertensive patients with normal left ventricular mass on echocardiography.
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Background: Vaccination with dendritic cells (DC) is still a valid experimental option for metastatic melanoma (MM). However, only a few patients experience long-lasting objective ...responses and the majority of clinical responders afterwards relapse and die. Which mechanisms are actually responsible for this “secondary resistance” to whole tumor antigens-loaded DC vaccines is largely unknown. It has been hypothesized that suppressive immune cell subpopulations, regulatory T cells in particular, may progressively accumulate in tumor tissues thus hampering therapy-induced antitumor immune responses along time. To elucidate this issue we evaluated changes induced by immunologically effective DC vaccination in the composition of tumor-associated T cell subpopulations. Methods: 12 patients with MM previously enrolled in a phase I/II DC vaccine trial and for which tumor tissue taken before and after at least 4 induction vaccine doses were available, were included in the study. Intratumoral lymphocytes were evaluated by CD3, CD4, CD8, FoxP3 and GrB
immunostainings, and quantified by a computer-assisted method. A nonparametric two-tailed Wilcoxon signed-rank test was utilized for evaluating differences in the distribution of the number of cell positive for each marker on the total cell counts in pre- and post-vaccine biopsies. Results: Our data showed a considerable and statistically significant decrease of intratumoral FoxP3
+
regulatory T cells in melanoma tissues after DC vaccination. In addition, the concurrent increase of intratumoral activated cytotoxic T lymphocytes, as shown by CD8 and Granzyme B stainings, indicated that this decrease has likely a functional relevance. Conclusions: Our findings that vaccination with DC loaded with autologous tumor lysate strongly reduces the intratumoral content of regulatory T cells add strength to the rationale for the development of potentially more effective combination schedules where whole tumor antigen-loaded DC vaccine prime and partially activate tumor-specific low-affinity T cells in a first tumor antigen-focusing step, followed by boosting with non-maximal doses of anti-CTLA-4 antibodies.
The article ascertains the efficacy of Fenoldopam infusion in cardiac patients with acute kidney injury (AKI). The research conducted included 667 participants in a multicenter, randomized, ...double-blind, placebo-controlled, parallel group study in Italy. The findings indicated that Fenoldopam intervention did not reduce the need for renal replacement therapy or 30-day mortality risk in patients with AKI compared with the placebo-controlled group and an increased rate of hypotension was observed.
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