Alessandro Verde

Azienda Ospedaliera Niguarda Ca' Granda, Milano, Lombardy, Italy

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Publications (34)78.8 Total impact

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    ABSTRACT: Background: Left ventricular assist device (LVAD) implantation improves survival and quality of life in patients with advanced heart failure (HF). Despite these advantages, LVADs are not free from risks. Among all adverse events (AE), pump thrombosis and bleeding, especially of the gastrointestinal (GI) tract, have been reported to occur with increasing frequency in some CF-LVADs. The INCOR LVAD system is a third-generation, continuous flow, axial pump with active magnetic levitation, avoiding the potential downsides of mechanical bearings. Methods: The aim of this retrospective study was to review the Italian clinical experience with the INCOR LVAD and to determine the prevalence of GI bleeding and pump thrombosis. All patients implanted between January 2006 and May 2012 were considered eligible. Results: The total population consisted of 42 patients. LVAD indication was BTT in 36 (86%) and DT in 6 (14%) patients; 31 patients (74%) were INTERMACS class 1 or 2. Mean support time was 525 ± 570 days. The 1-year and 2-year survival rates were 74% and 60%, respectively. The most frequent AE was driveline infection (0.33 events PPY) followed by stroke with consequence (0.17 events PPY), sepsis (0.07 events PPY), and right HF (0.05 events PPY). No episodes of pump thrombosis or GI bleeding were observed. Conclusions: In this cohort of high-risk, advanced HF patients, the INCOR LVAD provided effective support with improved survival. Moreover, the absence of GI bleeding and pump thrombosis demonstrates a favorable characteristic of this device. Further prospective studies are needed to confirm these data.
    No preview · Article · Nov 2015 · The International journal of artificial organs

  • No preview · Article · Apr 2015 · The Journal of Heart and Lung Transplantation

  • No preview · Conference Paper · Apr 2015
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    Full-text · Dataset · Mar 2015
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    ABSTRACT: There is a paucity of data about mid-term outcome of patients with advanced heart failure (HF) treated with left ventricular assist device (LVAD) in Europe, where donor shortage and their aging limit the availability and the probability of success of heart transplantation (HTx). The aim of this study is to compare Italian single-centre mid-term outcome in prospective patients treated with LVAD vs. HTx. We evaluated 213 consecutive patients with advanced HF who underwent continuous-flow LVAD implant or HTx from 1/2006 to 2/2012, with complete follow-up at 1 year (3/2013). We compared outcome in patients who received a LVAD (n = 49) with those who underwent HTx (n = 164) and in matched groups of 39 LVAD and 39 HTx patients. Patients that were treated with LVAD had a worse risk profile in comparison with HTx patients. Kaplan–Meier survival curves estimated a one-year survival of 75.5 % in LVAD vs. 82.3 % in HTx patients, a difference that was non-statistically significant [hazard ratio (HR) 1.46; 95 % confidence interval (CI) 0.74–2.86; p = 0.27 for LVAD vs. HTx]. After group matching 1-year survival was similar between LVAD (76.9 %) and HTx (79.5 %; HR 1.15; 95 % CI 0.44–2.98; p = 0.78). Concordant data was observed at 2-year follow-up. Patients treated with LVAD as bridge-to-transplant indication (n = 22) showed a non significant better outcome compared with HTx with a 95.5 and 90.9 % survival, at 1- and 2-year follow-up, respectively. Despite worse preoperative conditions, survival is not significantly lower after LVAD than after HTx at 2-year follow-up. Given the scarce number of donors for HTx, LVAD therapy represents a valid option, potentially affecting the current allocation strategy of heart donors also in Europe.
    Full-text · Article · Mar 2015 · Heart and Vessels
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    ABSTRACT: Mechanical unloading by left ventricular assist devices (LVADs) in advanced heart failure (HF), in addition to improving symptoms and end-organ perfusion, is supposed to stimulate cellular and molecular responses which can reverse maladaptive cardiac remodeling. As microRNAs (miRNAs) are key regulators in remodeling processes, a comparative miRNA profiling in transplanted hearts of HF patients with/without LVAD assistance could aid to comprehend underlying molecular mechanisms. Next generation sequencing (NGS) was used to analyze miRNA differential expression in left ventricles of HF patients who underwent heart transplantation directly () or following a period of LVAD support (). After data validation by quantitative real-time PCR, association with functional clinical parameters was investigated. Bioinformatics’ tools were then used for prediction of putative targets of modulated miRNAs and relative pathway enrichment. The analysis revealed 13 upregulated and 10 downregulated miRNAs in failing hearts subjected to LVAD assistance. In particular, the expression level of some of them (miR-338-3p, miR-142-5p and -3p, miR-216a-5p, miR-223-3p, miR-27a-5p, and miR-378g) showed correlation with off-pump cardiac index values. Predicted targets of these miRNAs were involved in focal adhesion/integrin pathway and in actin cytoskeleton regulation. The identified miRNAs might contribute to molecular regulation of reverse remodeling and heart recovery mechanisms.
    Full-text · Article · Feb 2015 · BioMed Research International
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    ABSTRACT: Background: Preoperative right ventricular (RV) dysfunction and postoperative RV failure negatively affect morbidity and mortality after left ventricular assist device (LVAD) implantation. Among the various echocardiographic parameters of RV systolic function, the 2D strain imaging has been recently proposed as an alternative approach to provide insights into the quantification of myocardial deformation. Aim of the present study is to observe whether right ventricular longitudinal strain (RVLS) may have clinical implications after LVAD implantation. Methods: Comprehensive transthoracic echocardiography for the evaluation of RV function was prospectively collected in 9 males patients (age 58±6 years) before LVAD implantation. Echocardiographic studies were performed using a Vivid E9 (GE Vingmed, Horten, Norway); the tricuspid annular plane systolic excursion (TAPSE), the pulsed tissue Doppler imaging on the tricuspidal lateral annulus (S'), and the RV fractional area change (RVFAC) were calculated in accordance with the current recommendations of American Society of Echocardiography. The images were analyzed off-line to calculate the free wall RVLS (the higher in absolute values, the better) using a commercially available semi-automated 2D strain software (EchoPac, GE). Right heart catheterization was also performed. During the post-operative period we recorded the need and the duration of intravenous inotrope support, inhaled nitric oxide, and blood transfusions. Correlation between variables was performed by Spearman's test. Results: About half of the patients showed pulmonary hypertension (mean pulmonary artery pressure ≥25 mmHg) during right heart catheterization. Several patients showed various degrees of RV dysfunction according the standard parameters: 62% of patients had TAPSE <15 mm, 56% had FAC <30%, and 62% had S'<0.10 m/sec. Nevertheless TAPSE, S', and FAC did not correlate with the variables recorded during post-operative period. A close negative correlation between free wall RVLS with the number of the days that lasted the inotropic support was found (P%=0.01, r%=-0.84). No significant correlations were found for RVLS with inhaled nitric oxide (p%=0.10, r%=-0.61, even though in trend) or number of blood transfusion (p%=0.69, r%=-0.16). Discussion: The determination of patients who are at greater risk for developing postoperative RV failure after LVAD remains a challenge. Recent studies underlines the limitations of classical echocardiographic indices; a new additional noninvasive tool, such as RVLS, could provide a better estimation of RV systolic performance.
    No preview · Conference Paper · Jan 2015
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    ABSTRACT: Aim: Although the left ventricular (LV) unloading due to LVAD, in some patients (PTs) with severe mitral regurgitation (MR) and severe LV and left atrium dilation, a suboptimal results of LVAD implantation, characterized by persistent relevant MR, elevated left atrial and pulmonary pressure and low cardiac output was observed. The aim of this work is the use of the numerical simulator of the cardiovascular system (NM) to simulate PTs candidate to LVAD implantation with severe MR to assess if NM can predict in advance which PTs will be responder to LVAD therapy and which PTs need a mitral valvuloplasty (MV). Methods: Baseline and acute data after LVAD implantation of 5 PTs with severe MR were collected. PTs baseline were reproduced by the NM and then the effect of LVAD implantation was simulated with and without MV. Simulations results were compared to acute measured data. Results: Comparing measured and simulated data, it can be deduced that the NM can well reproduce PTs baseline and predict the haemodynamic effects of LVAD implantation in all 5 PTs. Moreover the model was able to identify the PTs in which the LVAD implantation did not improve haemodynamic significantly due to severe MR and persistent high LV volumes. Finally the NM can predict the effect of LVAD implantation and MV performed in one of the 5 PTs. Conclusions: NM could be useful to support clinicians in LVAD PTs selection and to optimize and personalize LVAD therapy.
    No preview · Conference Paper · Sep 2014
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    ABSTRACT: Aim: VAD management training is a relevant issue involving all medical professionals deputed to advanced heart failure treatment. The aim of this work is the development of a computational cardiovascular simulator (CCS) to support learning of VAD management, focusing on VAD and circulatory system interactions. Methods: The CCS is a component of a comprehensive platform aimed at VAD management training. The lumped parameter computational circulatory model includes heart, systemic and pulmonary circulations and baroreflex. The CCS includes sub-models of continuous flow VADs, for both atrio-aortic and apical connections and of iv drug infusion. The CCS is able to simulate patients’ specific conditions or to generate preset or random pathologies offering to the trainee the possibility to manage the VAD and the related therapeutic actions such as drug or liquid administration. Further, the CCS can be used locally or remotely to enhance its training possibilities merged into a Learning Management System. Results: The whole model was verified with clinical and experimental data. It was used for training of medical professionals on specific clinical cases and on predefined hemodynamic pathological conditions.
    No preview · Conference Paper · Sep 2014
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    ABSTRACT: Background Cardiomyocyte apoptosis increases in heart failure (HF) and is implicated in disease progression. The apoptotic cell is not inevitably committed to death and appropriate therapy like Left Ventricular Assist Device (LVAD) support could offer a rescue of cellular functions. Literature data regarding the modulation of the apoptotic process during LVAD support are still controversial. Methods To assess whether LVAD implantation modifies the apoptotic profile in the heart, cardiac tissue was collected from end-stage HF patients before LVAD implant (pre-LVAD, n = 22), at LVAD removal (post-LVAD, n = 6), and from stable HF patients on medical therapy without prior circulatory support (HTx, n = 7) at heart transplantation, as control. Caspase (Casp)-3, Bax, Bcl-2, and Hsp72 cardiac mRNA and protein expression was evaluated by real-time PCR and WB in the three groups of patients. Immunohistochemical analysis, TUNEL assay, and DNA laddering analysis were performed; cellular size and interstitial fibrosis content were also determined. Results All the apoptotic indices were increased in post-LVAD group compared to pre-LVAD, specially anti-apoptotic Hsp72 and pro-apoptotic Bax, (Hsp72: 3.27 ± 0.41 vs 0.76 ± 0.14, p < 0.001; Bax: 2.15 ± 0.38 vs 1.10 ± 0.29, p = 0.035; post-LVAD vs pre-LVAD, respectively). The significant increase in Hsp72 was confirmed by WB and immunohistochemical analysis. Conclusion LVAD appears to induce an activation of apoptotic mediators, mainly at the mitochondrial level, while the following activation of Casp-3 is reduced by the significant increase of Hsp72, whose enhancement could be an important factor in cardiac remodeling associated with LVAD support.
    No preview · Article · Sep 2014 · Cardiovascular Pathology
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    ABSTRACT: Background Caspase (Casp)-1 has been indicated as a molecular target capable of preventing the progression of cardiovascular diseases, including heart failure (HF), due to its central role in promoting inflammation and cardiomyocyte loss. Aim of this study was to assess whether Left Ventricular Assist Device (LVAD) implantation modifies the inflammatory and apoptotic profile in the heart through the modulation of Casp-1 expression level. Methods Cardiac tissue was collected from end-stage HF patients before LVAD implant (pre-LVAD group, n = 22), at LVAD removal (post-LVAD, n = 6), and from stable HF patients on medical therapy without prior circulatory support (HTx, n = 7) at heart transplantation, as control. The cardiac expression of Casp-1, of its inhibitors caspase recruitment domain (CARD) only protein (COP) and CARD family, member 18 (ICEBERG) , was evaluated by real-time PCR in the three groups of patients. Results Casp-1 was increased in the pre-LVAD group compared to HTx (p = 0.006), while on the contrary the ICEBERG level was significantly decreased in pre-LVAD with respect to HTx patients (p < 0.001); no difference in COP expression level was found. Conclusions This study describes a specific pattern of the Casp-1 system associated with inflammation and apoptosis markers in patients who require LVAD insertion. The inflammation could be the key process regulating, in a negative loop, Casp-1 signaling and its down-stream effects, apoptosis included.
    No preview · Article · Aug 2014 · Cardiovascular Pathology
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    ABSTRACT: . The mechanical circulatory support (MCS) is an effective treatment in critically ill patients with end-stage heart failure (ESHF) that, however, may cause a severe multiorgan failure syndrome (MOFS) in these subjects. The impact of altered inflammatory response, associated to MOFS, on clinical evolution of MCS postimplantation patients has not been yet clarified. Methods . Circulating cytokines, adhesion molecules, and a marker of monocyte activation (neopterin) were determined in 53 MCS-treated patients, at preimplant and until 2 weeks. MOFS was evaluated by total sequential organ failure assessment score (tSOFA). Results . During MCS treatment, 32 patients experienced moderate MOFS (tSOFA
    Full-text · Article · Jul 2014 · Mediators of Inflammation

  • No preview · Conference Paper · Apr 2014
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    ABSTRACT: The immune response is crucial in the development of multi-organ failure (MOF) and complications in end-stage heart failure patients supported by left ventricular assist device (LVAD). However, at pre-implant, the association between inflammatory state and post-LVAD outcome is not yet clarified. Aim of the study was to assess the relationship among pre-implant levels of immune-related cytokines, postoperative inflammatory response and 3-month outcome in LVAD-patients. In 41 patients undergoing LVAD implantation, plasma levels of interleukin (IL)-6, IL-8, crucial for monocyte modulation, and urine neopterin/creatinine ratio (Neo/Cr), marker of monocyte activation, were assessed preoperatively, at 3 days, 1 and 4 weeks post-LVAD. MOF was evaluated by total sequential organ failure assessment (tSOFA) score. Intensive care unit (ICU)-death and/or post-LVAD tSOFA ≥11 was considered as main adverse outcome. Length of ICU-stay, 1 week-tSOFA score, hospitalisation and 3-month survival were considered additional end-points. During ICU-stay, 8 patients died of MOF, while 8 of the survivors experienced severe MOF with postoperative tSOFA score ≥11. Pre-implant level of IL-6 ≥ 8.3 pg/mL was identified as significant marker of discrimination between patients with or without adverse outcome (OR 6.642, 95% CI 1.201-36.509, p = 0.030). Patients were divided according to pre-implant IL-6 cutoff of 8.3 pg/ml in A [3.5 (1.2-6.1) pg/mL] and B [24.6 (16.4-38.0) pg/mL] groups. Among pre-implant variables, only white blood cells count was independently associated with pre-implant IL-6 levels higher than 8.3 pg/ml (OR 1.491, 95% CI 1.004-2.217, p = 0.048). The ICU-stay and hospitalisation resulted longer in B-group (p = 0.001 and p = 0.030, respectively). Postoperatively, 1 week-tSOFA score, IL-8 and Neo/Cr levels were higher in B-group. LVAD-candidates with elevated pre-implant levels of IL-6 are associated, after intervention, to higher release of monocyte activation related-markers, a clue for the development of MOF, longer clinical course and poor outcome.
    Full-text · Article · Mar 2014 · PLoS ONE
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    ABSTRACT: Background: Heart failure (HF) is affecting millions of people every year and it is characterized by impaired ventricular performance, exercise intolerance and shortened life expectancy. Despite significant advancements in drug therapy, mortality of the disease remains excessively high, as heart transplant remains the gold standard treatment for end-stage HF when no contraindications subsist. Traditionally, implanted Ventricular Assist Devices (VADs) have been employed in order to provide circulatory support to patients who cannot survive the waiting time to transplantation, reducing the workload imposed on the heart. In many cases that process could recover its contractility performance. Objectives: The SensorART platform focuses on the management and remote treatment of patients suffering from HF. It provides an interoperable, extendable and VAD-independent solution, which incorporates various hardware and software components in a holistic approach, in order to improve the quality of the patients' treatment and the workflow of the specialists. This paper focuses on the description and analysis of Specialist's Decision Support System (SDSS), an innovative component of the SensorART platform. Methods: The SDSS is a Web-based tool that assists specialists on designing the therapy plan for their patients before and after VAD implantation, analyzing patients' data, extracting new knowledge, and making informative decisions. Results: SDSS offers support to medical and VAD experts through the different phases of VAD therapy, incorporating several tools covering all related fields; Statistics, Association Rules, Monitoring, Treatment, Weaning, Speed and Suction Detection. Conclusions: SDSS and its modules have been tested in a number of patients and the results are encouraging.
    Full-text · Article · Feb 2014 · Methods of Information in Medicine
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    ABSTRACT: Introduction. Advanced heart failure (HF) is a multifactorial syndrome that shows an increasing prevalence in Western Countries. Recent evidences suggest that HF is associated with local and systemic metabolic derangements and the development of a progressive catabolic state (1). These changes influence survival of advanced HF patients and are linked to immune activation, systemic inflammation and insulin resistance (2). Increased levels of several adipokines have been described in advanced HF (2-4). In particular, elevated circulating levels of adiponectin are associated to poor survival (5). The aim of the study was to investigate the effect of LVAD support on circulating adiponectin in HF patients in order to evaluate adiponectin as a possible prognostic biomarker to be used in clinical setting. Materials and methods. Twenty-six end-stage HF patients (NYHA class III and IV; LVEF % < 25) undergoing LVAD implantation at Niguarda Hospital, Milan, were studied. Blood samples were obtained from patients at admission (baseline), and at 4 h, 1, 3, 7, 14, and 30 days after LVAD implant. Total adiponectin was measured by a dedicated ELISA (Linco Research, purchased by Pantec srl Torino). Standard statistical analysis was carried out using the SPSS 16.0 for Mac. The study protocol was approved by the Local Ethics Committee. All subjects gave written informed consent to participate in the study. Results. Of the 26 patients, 6 died due to multi-organ failure syndrome (MOFS) 7 days after implant (non survivors, NS), whereas 20 were alive at 1 month (survivors, S). At pre-implant, clinical and hemodynamic parameters as well as adiponectin levels did not differ between S and NS. Fig. 1 reports adiponectin time course in S and NS patients. In S patients, adiponectin levels remained significantly lower respect to baseline until 7 days after LVAD implant, while no time-course modulation was observed in NS. In particular, S patients showed a higher significant decrease of adiponectin compared to NS after 4h from LVAD implantation (Fig. 2). Conclusions. Our results showed how LVAD support of the failing myocardium is able to decrease adiponectin plasma levels, mainly in S patients. Adiponectin is an insulin-sensitizing and cardio-protective protein (6) that in HF accumulated in blood because of a functional adiponectin resistance. We could speculate that the reduction of adiponectin in S was related to a lesser adiponectin resistance, compared to NS patients. This is in tune with a recent study suggesting that LVAD implantation was associated with a resolution of myocardial adiponectin resistance (2). These findings support the adiponectin paradox in HF, that probably reflects the development of functional adiponectin resistance (7). In conclusion, early monitoring of circulating levels of adiponectin may be a reliable tool for outcome prediction in LVAD recipients.
    Full-text · Conference Paper · Oct 2013
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    ABSTRACT: The aim of this study was to evaluate the transcriptomic profiling of C-type natriuretic peptide (CNP) and of its specific receptor, NPR-B in human leukocytes of heart failure (HF) patients as a function of clinical severity, assessing the possible changes with respect to healthy subjects (C). mRNA expression was evaluated by Real-time PCR and total RNA was extracted from leukocytes of C (n=8) and of HF patients (NYHA I-II n=7; NYHA III-IV n=13) with PAXgene Blood RNA Kit. Significantly higher levels of CNP mRNA expression were found in HF patients as a function of clinical severity (C=0.23±0.058, NYHA I-II=0.47±0.18, NYHA III-IV=2.58±0.71, p=0.005C vs NYHA III-IV, p=0.017 NYHA I-II vs NYHA III-IV) and NPR-B transcript levels resulted down-regulated in HF patients with higher NYHA class (C=2.2±0.61, NYHA I-II=2.76±0.46, NYHA III-IV=0.29±0.13, p=0.001C vs NYHA III-IV, p<0.0001 NYHA I-II vs NYHA III-IV). A significant negative correlation between CNP and NPR-B mRNA expression (r=0.5, p=0.03) was also observed. These results suggest a co-regulation of NPR-B and CNP expression supporting the relevance of this receptor in human disease characterized by a marked inflammatory/immune component and suggesting the possibility of manipulating inflammation via pharmacological agents selective for this receptor.
    No preview · Article · Jul 2013 · Peptides
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    Full-text · Article · Jul 2013 · International journal of cardiology
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    ABSTRACT: In this study the transcriptomic profiling of adenosine receptors (ARs) in human leukocytes of heart failure (HF) patients as a function of clinical severity, assessing the possible changes with respect to healthy subjects (C), was evaluated. Total RNA was extracted from leukocytes of C (n = 8) and of HF patients (NYHA I-II n = 9; NYHA III-IV n = 14) with a PAXgene Blood RNA Kit. An increase as a function of clinical severity was observed in each AR (A1R: C = 0.02 ± 0.009, NYHA I-II = 0.21 ± 0.09, NYHA III-IV = 3.6 ± 1.3, P = 0.03 C versus NYHA III-IV, P = 0.02 NYHA I-II versus NYHA III-IV; A2aR: C = 0.2 ± 0.05, NYHA I-II = 0.19 ± 0.04, NYHA III-IV = 1.32 ± 0.33, P = 0.005 C versus NYHA III-IV, P = 0.003 NYHA I-II versus NYHA III-IV; A2bR: C = 1.78 ± 0.36, NYHA I-II = 1.35 ± 0.29, NYHA III-IV = 4.07 ± 1.21, P = 0.03: NYHA I-II versus NYHA III-IV; A3R: C = 0.76 ± 0.21, NYHA I-II = 0.94 ± 0.19, NYHA III-IV = 3.14 ± 0.77, P = 0.01 C versus NYHA III-IV and NYHA I-II versus NYHA III-IV, resp.). The mRNA expression of the ectonucleoside triphosphate diphosphohydrolase (CD39) and the ecto-5'-nucleotidase (CD73) were also evaluated. They resulted up-regulated. These findings show that components of adenosine metabolism and signalling are altered to promote adenosine production and signalling in HF patients. Thus, HF may benefit from adenosine-based drug therapy after confirmation by clinical trials.
    Full-text · Article · Jul 2013
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    ABSTRACT: This work presents the Treatment Tool, which is a component of the Specialist's Decision Support Framework (SDSS) of the SensorART platform. The SensorART platform focuses on the management of heart failure (HF) patients, which are treated with implantable, left ventricular assist devices (LVADs). SDSS supports the specialists on various decisions regarding patients with LVADs including decisions on the best treatment strategy, suggestion of the most appropriate candidates for LVAD weaning, configuration of the pump speed settings, while also provides data analysis tools for new knowledge extraction. The Treatment Tool is a web-based component and its functionality includes the calculation of several acknowledged risk scores along with the adverse events appearance prediction for treatment assessment.
    No preview · Article · Jul 2013 · Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference