Molecular Refinement of Clinical Staging in Hepatocellular Carcinoma Patients Evaluated for Potentially Curative Therapies

Abstract: Aim: VEGF and AFP mRNA determinations in the blood are promising prognostic factors for patients with HCC. This study explores their potential prognostic synergy in a cohort of HCC patients evaluated for potentially curative therapies. Methods: One hundred twenty-four patients with a diagnosis of HCC were prospectively enrolled in the study. Inclusion criteria were: (a) histological diagnosis of HCC and assessment of tumour grade and (b) determination of AFP mRNA status and VEGF levels in the blood before therapy. Results: At baseline evaluation, 40% of the study group had AFP mRNA in the blood (AFP mRNA positive), and 35% had VEGF > 23 pg ml(-1) (VEGF positive). Surgery was performed in 58 patients (47%), 54 (43%) had tumour ablation, and 12 had chemoembolisation (10%). Median follow-up and survival of the study group were 19 and 26 months (range, 1 to 60), respectively. The association of AFP mRNA and VEGF proved to be prognostically more accurate than their single use in discriminating the risk of death (ROC curve analysis) and survival probability (Cox analysis). In particular, we identified 3 main molecular stages (p < 0,0001): both negative (3-year survival = 63%), one positive (3-year survival = 40%), both positive (3-year survival = 16%). Multivariate analysis identified BCLC staging, surgery, and molecular staging as the most significant survival variables. Conclusions: The preoperative determination of AFP mRNA status and VEGF may potentially refine the prognostic evaluation of HCC patients and improve the selection process for potentially curative therapies

Simultaneous Localization and Mapping in a Formula Student Autonomous Vehicle

Mapping an unknown environment exploiting sensors measurements and simultaneously localize a mobile robotic platform within it represents a crucial task for modern robotics. This problem is typically referred to as Simultaneous Localization And Mapping (SLAM) and solving it efficiently is still one of the most challenging task of mobile robotics. This work is focused on the SLAM problem in the autonomous racing context, where precision, reliability and performance need to be taken to an extreme level. A series of competitions, coordinated by the Society of Automotive Engineers (SAE), challenge every year teams from universities all over the world to compete with small, formula-style autonomous vehicles. A survey about the state-of-the-art SLAM solutions in a racing context, presented in this master thesis, leads to a final implementation which wants to be reliable and accurate in the result. Autonomous race car softwares also needs to respect important constraints in terms of computational performance. Different techniques and optimizations has been applied in order to reduce the computational time and to respect the real-time con- straint. The implemented solution has been firstly validated in a simulated environment, enabling in-depth evaluation of the final algorithm. Subsequently, the algorithm was deployed on the real autonomous vehicle, called Kerub-EVO, of the University of Pisa Formula SAE team for on-track test ses- sions

Time Synchronization Sensitivity in SV-based PMU Consistency Assessment

Modern power systems are rapidly transitioning towards a fully digital substation paradigm. Based on the IEC 61850, a common communication protocol between the different intelligent electronic devices (IEDs) promises a significant enhancement in terms of efficiency and interoperability. In this context, synchronization represents a crucial aspect as it allows us to rigorously compare measurements taken at the same time in different locations. In this paper, we consider a measurement chain for synchrophasor estimation based on digital inputs: an instrument transformer, a stand-alone merging unit (SAMU) and a phasor measurement unit (PMU). Both the SAMU and the PMU are equipped with independent synchronization sources. In case the SAMU loses its synchronization, the final measurement result would be considered invalid until a complete restoration of the SAMU synchronization status. In view of a longer continuity of operation, this paper proposes an alternative approach to evaluate the PMU Time Quality in real-time. This approach allows for continuing crucial monitoring and control operations, such as state estimation and fault detection, even in the presence of temporary loss of synchronization. A characterization, in both simulated and experimental conditions, proves the potential and reliability of the proposed approach. In the considered test case, the come-back within a sufficient time quality is correctly detected in less than 200 s, while waiting for the full restoration of the SAMU time reference would cost several minutes

Preoperative Sinonasal Computed Tomography Score in Chronic Rhinosinusitis with Nasal Polyps

This study investigated the relationship between sinonasal inflammatory involvement according to the computed tomography (CT) staging system (Lund–Mackay score) with clinical, laboratory, histopathological and prognostic features of chronic rhinosinusitis with nasal polyps (CRSwNP). Seventy-eight patients with CRSwNP who had undergone surgery were enrolled. Total (p = 0.0062), ethmoid (p = 0.0496), sphenoid (p = 0.0335), ostiomeatal complex (OMC) (p = 0.0235) and frontal (p = 0.0164) CT scores were predictive of non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD) in the univariate analysis. Total (p = 0.0022), ethmoid (p = 0.0290), sphenoid (p = 0.0370), frontal (p = 0.0116), maxillary (p = 0.0357) and OMC (p = 0.0058) CT scores were predictve of asthma at the univariate analysis. No significant differences were found between patients with vs. without allergy in terms of total and partial CT scores. High blood eosinophil counts (>0.24 vs. ≤0.24 cells × 109/L) resulted in being associated with total (p = 0.0213), maxillary (p = 0.0227) and ethmoid (p = 0.0491) CT scores in the univariate analysis. Higher ethmoid (p = 0.0006) and total sinonasal (p = 0.0027) CT scores were found to predict histopathologically eosinophil CRSwNPs in the univariate analysis. CT scores did not result as predictive of NSAID-exacerbated respiratory disease, asthma, or blood eosinophil count at the multivariate analysis. Risk of relapse was related to the presence of NERD (p = 0.0207, HR [95% CI] 3.914 [1.232–12.435]), higher preoperative total (HR = 1.098 95%CI: 1.001–1.204, p = 0.0486) and frontal sinus CT scores (HR = 1.555 95%CI: 1.006–1.886, p = 0.0218), but these results were not confirmed by the multivariable analysis. Sinonasal CT scores showed significant differences in this heterogeneous inflammatory condition. Identifying CRSwNP characteristics is necessary to avoid generic treatments with poor outcomes

Trends in Gas Sensor Development for Hydrogen Safety

Gas sensors are applied for facilitating the safe use of hydrogen in, for example, fuel cell and hydrogen fuelled vehicles. New sensor developments, aimed at meeting the increasingly stringent performance requirements in emerging applications are presented based on in-house technical developments and a literature study. The strategy of combining different detection principles, i.e. sensors based on electrochemical cells, semiconductors or field effects in combination with thermal conductivity sensor or catalytic combustion elements, in one new measuring system is reported. This extends the dynamic measuring range of the sensor while improving sensor reliability to achieve higher safety integrity through diverse redundancy. The application of new nanoscaled materials, nano wires, carbon tubes and graphene as well as the improvements in electronic components of field-effect, resistive-type and optical systems are evaluated in view of key operating parameters such as sensor response time, low energy consumption and low working temperature.JRC.F.2-Cleaner energ

Effects and clinical implications of sacubitril/valsartan on left ventricular reverse remodeling in patients affected by chronic heart failure: A 24-month follow-up

Background: Compared to angiotensin inhibition, angiotensin-neprilysin “blockade” improves mortality and reduces hospitalizations in patients with heart failure (HF) with reduced ejection fraction (EF). Sacubitril/valsartan is known to influence left ventricular (LV) reverse remodeling with systolic function improvement, although underlying mechanisms remain partially unclear. Our objectives were to evaluate whether sacubitril/valsartan promotes LV remodeling and improves LV ejection fraction (LVEF) (above the 35% threshold by echocardiographic evaluation) and to identify predictors of reverse remodeling in a real-world setting. Methods: New York Heart Association (NYHA) class II–III patients with EF ≤ 35% were consecutively enrolled. All patients were on optimal medical therapy on the initiation of sacubitril/valsartan therapy. Full clinical and multi-parametric echocardiographic evaluation, electrocardiogram, and laboratory tests were performed at baseline and after 3, 6, 12, and 24 months. Results: In total, 69 patients were recruited from July 2016 to August 2018. Reverse remodeling was observed in 57.7% (30/52) of patients, occurring within 3, 6, 12, and 24 months in 2, 11, 13, and 4 patients, respectively. Twenty-four (46%) patients showed LVEF improvement above the threshold of 35% during follow-up, occurring in 1, 10, 9, and 4 patients within 3, 6, 12, and 24 months, respectively. Primitive dilated cardiomyopathy and female gender were identified as significant predictors of reverse remodeling. NYHA class was improved in both remodeling and non-remodeling patients. Conclusion: Sacubitril/valsartan promotes favorable cardiac remodeling and significantly improves LVEF in a significant proportion of HF patients within 24 months, both in NYHA class II and III patients with HF

Fecal lactoferrin and intestinal permeability are effective non-invasive markers in the diagnostic work-up of chronic diarrhea.

Non-invasive markers able to identify patients with chronic diarrhea at risk of organic disease are missing. Aim of the study was to assess the diagnostic ability of intestinal permeability (IP) test and fecal lactoferrin (FL) in distinguishing functional from organic disease in patients with chronic diarrhea. We retrospectively enrolled patients referring to the gastroenterology outpatient clinic for chronic diarrhea. Among the 103 patients included, 40 % had an organic disease, with IP and FL levels significantly higher compared to those with a functional disorder (p < 0.0001). Sensitivity, specificity, positive and negative likelihood ratios, area under ROC curves of FL were superior to those of IP in discriminating functional and organic disease (FL: 87.8 and 93.6 %, 13.61 and 0.13, 0.9375; IP: 61.0 and 90.3 %, 6.3 and 0.43, 0.7691). When combining the two tests, the diagnostic ability of FL did not improve. In subgroup analysis, IP confirmed its ability to detect small bowel alterations, while FL could identify both small bowel and colonic alterations. In conclusion, FL is valid to detect inflammation in the gastrointestinal tract, while IP can effectively identify small bowel damage in chronic diarrhea patients. Together these tests could recognize both the presence of intestinal damage and its site

Galectin-3 predicts long-term cardiovascular death in high-risk patients with coronary artery disease.

Objective Galectin-3 (Gal-3) can affect atherogenesis by multiple mechanisms, but it remains scarcely known whether plasma Gal-3 levels predict cardiovascular events in patients with coronary artery disease. Therefore, we investigated if Gal-3 predicts cardiovascular death in patients with coronary artery disease of the Genetic and ENvironmental factors In Coronary Artery disease study. Approach and Results In a prospective cohort study, we measured the plasma levels of Gal-3 in 1013 randomly selected patients who underwent coronary angiography and long-term follow-up to assess incident cardiovascular events. The primary end points were (1) cardiovascular death and (2) a composite of cardiovascular death, acute coronary syndrome, and stroke. Secondary end points entailed (1) acute myocardial infarction, (2) stroke, and (3) a composite fatal ischemic event including fatal myocardial infarction and stroke. The effect of Gal-3 on prognosis was assessed using Kaplan-Meier analysis and multivariate Cox's regression. During long-term follow-up (median, 7.2 years), 115 cardiovascular deaths occurred (15.2%), more commonly in the high Gal-3 tertile (25.2%) than in the intermediate and the low tertiles (13.6% versus 7.5%, respectively; P<0.001). The adverse prognostic effect of high Gal-3 was confirmed in subgroup analysis of the patients with angiographically documented coronary artery disease and also of those with a normal left ventricular ejection fraction. At multivariate analysis, Gal-3 was a predictor of cardiovascular mortality (hazard ratio, 1.79; 95% confidence interval, 1.10-2.93; P=0.020) along with age, left ventricular ejection fraction, and coronary atherosclerotic burden. Conclusions In high cardiovascular risk patients referred for coronary angiography Gal-3 is a strong independent predictor of cardiovascular death

The impact of cognitive aids on resuscitation performance in in-hospital cardiac arrest scenarios: a systematic review and meta-analysis

Different cognitive aids have been recently developed to support the management of cardiac arrest, however, their effectiveness remains barely investigated. We aimed to assess whether clinicians using any cognitive aids compared to no or alternative cognitive aids for in-hospital cardiac arrest (IHCA) scenarios achieve improved resuscitation performance. PubMed, EMBASE, the Cochrane Library, CINAHL and ClinicalTrials.gov were systematically searched to identify studies comparing the management of adult/paediatric IHCA simulated scenarios by health professionals using different or no cognitive aids. Our primary outcomes were adherence to guideline recommendations (overall team performance) and time to critical resuscitation actions. Random-effects model meta-analyses were performed. Of the 4.830 screened studies, 16 (14 adult, 2 paediatric) met inclusion criteria. Meta-analyses of eight eligible adult studies indicated that the use of electronic/paper-based cognitive aids, in comparison with no aid, was significantly associated with better overall resuscitation performance [standard mean difference (SMD) 1.16; 95% confidence interval (CI) 0.64; 1.69; I2 = 79%]. Meta-analyses of the two paediatric studies, showed non-significant improvement of critical actions for resuscitation (adherence to guideline recommended sequence of actions, time to defibrillation, rate of errors in defibrillation, time to start chest compressions), except for significant shorter time to amiodarone administration (SMD - 0.78; 95% CI - 1.39; - 0.18; I2 = 0). To conclude, the use of cognitive aids appears to have benefits in improving the management of simulated adult IHCA scenarios, with potential positive impact on clinical practice. Further paediatric studies are necessary to better assess the impact of cognitive aids on the management of IHCA scenarios

Prognostic Significance of CD105- and CD31-Assessed Microvessel Density in Paired Biopsies and Surgical Samples of Laryngeal Carcinoma

Small pretreatment laryngeal biopsies may not fully represent a tumor&rsquo;s biological profile. This study on laryngeal squamous cell carcinoma (LSCC) aimed to investigate the prognostic role of CD105- and CD31-assessed microvessel density (MVD) in paired biopsies and surgical specimens and the association and discrepancy between CD105- and CD31-assessed MVD in biopsies and surgical specimens. CD105- and CD31-assessed MVD was analyzed in paired biopsies and surgical specimens of 45 consecutive cases of LSCC. In the LSCC biopsies and surgical specimens, median CD105-assessed MVD was significantly higher in N+ than in N0 cases (p = 0.0008, and p = 0.0002, respectively). Disease-free survival (DFS) was associated with CD105- and CD31-assessed MVD in both biopsies and surgical specimens (p &lt; 0.0001 for all specimens). Multivariable Cox&rsquo;s regression showed that pathological grade (p &lt; 0.0001) and CD105-assessed MVD in LSCC biopsies (p = 0.0209) predicted DFS. Lin&rsquo;s concordance coefficient showed that CD31 overestimated MVD compared with CD105 in LSCC biopsies and surgical specimens. CD105-assessed MVD should be further investigated in larger LSCC series as a potential prognostic marker for identifying: patients at higher risk of recurrence who might warrant more aggressive therapy; and cN0 patients requiring elective neck dissection for a significant risk of regional metastasis