111 research outputs found
A system to integrate unstructured and semistructured information resources: an application in an innovation design process
A system that integrates different tools, from multicriteria analysis and mathematical programming but also cognitive and social psychology, can be proposed to cope with complexities and uncertainties that generate criticality in the socio technical approach. The purpose of this paper is to examine the potentialities of this system, above all in terms of information fusion and use in various contexts, and to propose an application in relation to an industrial project, in order to support the conceptual phase of the design processr
Associations of Tissue Tumor Mutational Burden and Mutational Status With Clinical Outcomes With Pembrolizumab Plus Chemotherapy Versus Chemotherapy For Metastatic NSCLC
Biomarker; Pembrolizumab; Tissue tumor mutational burdenBiomarcador; Pembrolizumab; CÃ rrega mutacional del tumor tissularBiomarcador; Pembrolizumab; Carga mutacional del tumor tisularIntroduction
We evaluated tissue tumor mutational burden (tTMB) and mutations in STK11, KEAP1, and KRAS as biomarkers for outcomes with pembrolizumab plus platinum-based chemotherapy (pembrolizumab-combination) for NSCLC among patients in the phase 3 KEYNOTE-189 (ClinicalTrials.gov, NCT02578680; nonsquamous) and KEYNOTE-407 (ClinicalTrials.gov, NCT02775435; squamous) trials.
Methods
This retrospective exploratory analysis evaluated prevalence of high tTMB and STK11, KEAP1, and KRAS mutations in patients enrolled in KEYNOTE-189 and KEYNOTE-407 and the relationship between these potential biomarkers and clinical outcomes. tTMB and STK11, KEAP1, and KRAS mutation status was assessed using whole-exome sequencing in patients with available tumor and matched normal DNA. The clinical utility of tTMB was assessed using a prespecified cutpoint of 175 mutations/exome.
Results
Among patients with evaluable data from whole-exome sequencing for evaluation of tTMB (KEYNOTE-189, n = 293; KEYNOTE-407, n = 312) and matched normal DNA, no association was found between continuous tTMB score and overall survival (OS) or progression-free survival for pembrolizumab-combination (Wald test, one-sided p > 0.05) or placebo-combination (Wald test, two-sided p > 0.05) in patients with squamous or nonsquamous histology. Pembrolizumab-combination improved outcomes for patients with tTMB greater than or equal to 175 compared with tTMB less than 175 mutations/exome in KEYNOTE-189 (OS, hazard ratio = 0.64 [95% confidence interval (CI): 0.38‒1.07] and 0.64 [95% CI: 0.42‒0.97], respectively) and KEYNOTE-407 (OS, hazard ratio = 0.74 [95% CI: 0.50‒1.08 and 0.86 [95% CI: 0.57‒1.28], respectively) versus placebo-combination. Treatment outcomes were similar regardless of KEAP1, STK11, or KRAS mutation status.
Conclusions
These findings support pembrolizumab-combination as first-line treatment in patients with metastatic NSCLC and do not suggest the utility of tTMB, STK11, KEAP1, or KRAS mutation status as a biomarker for this regimen.All authors’ institutions received research funding from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, for the conduct of this study
A Multi-Criteria Methodology to Support Public Administration Decision Making Concerning Sustainable Energy Action Plans
For municipalities that have joined the Covenant of Mayors promoted by the European Commission, the Sustainable Energy Action Plan (SEAP) represents a strategic tool for achieving the greenhouse gas reductions required by 2020. So far as the energy retrofit actions in their residential building stock are concerned, which in the small-to-medium municipalities are responsible for more than 60% of CO2 emissions, the scenarios for intervening are normally decided on the basis of an economic (cost/performance) analysis. This type of analysis, however, does not take into account important aspects for small and medium-sized communities such as social aspects, environmental impacts, local economic development and employment. A more comprehensive and effective tool to support the choices of public administrators is the multi-criteria analysis. This study proposes a methodology that integrates multi-criteria analysis in order to support Public Administration/Local Authorities in programming Sustainable Energy Action Plans with a more targeted approach to sustainability. The methodology, based on the ELECTRE III method, was applied to a medium-size municipality in the Lombardy region of Italy. The results obtained with this approach are discussed in this pape
Performing oncological procedures during COVID-19 outbreak: a picture from an Italian cancer center
Aim:
Since SARS-CoV-2 infection rapidly spread around the world, Italy has quickly become one of the most affected countries. Healthcare systems introduced strict infection control measures to ensure optimal care, especially in frail groups such as cancer patients (pts). This study investigated the efficacy of SARS-CoV-2 pre-procedure screening and whether COVID-19 influenced timely diagnosis and therapy.
Methods:
Data of oncological procedures of pts with confirmed or suspected cancer diagnosis, treated at Oncology Department or coming from Emergency Department of San Luigi Gonzaga Hospital between June 2020 and March 2021 were retrospectively collected. A nasopharyngeal swab (NPS) was performed in outpatients 24/48 h before procedures. Inpatients were tested by NPS before and after hospitalization.
Results:
Two hundred and twenty-one pts were included in this analysis. Median age was 73 years, males were 58%. Eastern Cooperative Oncology Group (ECOG) Performance Status was 0 or 1 in 88% of pts. The most frequent cancer type was lung cancer (57%). Stages IV were 77%. Two hundred and forty-three scheduled procedures were performed with diagnostic (n: 142; 58%), therapeutic (n: 55; 23%), and palliative (n: 46; 19%) intent. One hundred and four and 139 procedures were performed in out- and in-pts, respectively. Of the 234 NPS performed, 10 (4%) were positive. Two pts were infected during hospitalization, 8 in community. Most of them were asymptomatic, while only 2 had mild symptoms. Eight procedures (3%) were postponed, 1 cancelled, while 2 were performed in positive pts. Median time to resolution of the infection was 17 days (11–36). Median delay in the procedures was 25 days (14–55). Five pts started systemic treatment, after a median time of 37.5 days (13–57).
Conclusions:
SARS-CoV-2 infection led to the postponement of a small, but not negligible percentage of oncological procedures. However, the low infection rate observed suggests that structured screening for COVID-19 is critical for the best management of scheduled procedures during pandemic
Adjuvant chemotherapy for resected triple negative breast cancer patients: A network meta-analysis
The current standard of care for resected early-stage triple negative breast cancer (TNBC) patients who did not receive systemic preoperative therapy is adjuvant anthracycline- and taxane-based chemotherapy (CT). A network meta-analysis (NMA) of randomized controlled trials (phase III) enrolling patients with resected stage I-III TNBC comparing adjuvant regimens was performed. Overall survival (OS) and disease-free survival (DFS) data were extracted. A total of 27 phase III clinical trials were selected including 15,242 TNBC patients. This NMA showed an OS benefit from the incorporation of capecitabine into classic anthracycline/taxane-based combinations compared to anthracyclines with or without taxanes alone
Non-anthocyanin polyphenols in healthy and Flavescence dorée infected Barbera and Nebbiolo leaves
The first serious outbreak of Flavescence dorée (FD) in Piedmont (North-West Italy) dates back to 1998 in the Tortona area (Alessandria province). FD is a serious quarantine-worthy disease transmitted by the leafhopper Scaphoideus titanus Ball. Different Vitis vinifera L. biotypes react differently to the phytoplasma, in particular as to the accumulation of polyphenols in leaves. In this experimentation, we observed and described concentration and accumulation of the main classes of polyphenols in entire leaves and in leaf blades and veins of two varieties, Nebbiolo and Barbera, displaying different levels of susceptibility to FD. Their well-known different reactions could be related, at least partially, to leaf polyphenols, both as to concentrations and profiles. Nebbiolo displayed some specific traits: i) the higher percentage of incidence over totals of individual molecules known to be powerful antioxidants (caftaric acid over coutaric acid; quercetin glycosides over other flavonols); ii) the higher concentration of flavanols in veins with respect to Barbera and their wider profile (astilbin and a taxifolin-glycoside, this last accumulating exclusively in Nebbiolo)
The impact of COVID-19 on myocardial infarctions, strokes and out-of-hospital cardiopulmonary arrests: an observational retrospective study on time-sensitive disorders in the Friuli Venezia Giulia region (Italy)
The COVID-19 global pandemic has changed considerably the way time-sensitive disorders are treated. Home isolation, people's fear of contracting the virus and hospital reorganisation have led to a significant decrease in contacts between citizens and the healthcare system, with an expected decrease in calls to the Emergency Medical Services (EMS) of the Friuli-Venezia Giulia (FVG) region. However, mortality in clinical emergencies like acute ST-elevation myocardial infarction (STEMI), stroke and out-of-hospital cardiopulmonary arrest (OHCA) remained high. An observational retrospective cross-sectional study was carried out in FVG, taking into account the period between March 1, 2020, and May 31, 2020, the first wave of the COVID-19 pandemic, and comparing it with the same period in 2019. The flow of calls to the EMS was analysed and COVID-19 impact on time-sensitive disorders (STEMIs, ischemic strokes and OHCPAs) was measured in terms of hospitalisation, treatment and mortality. Despite a -8.01% decrease (p value ˂0.001) in emergency response, a 10.89% increase in calls to the EMS was observed. A lower number of advanced cardiopulmonary resuscitations (CPR) (75.8 vs 45.2%, p=0.000021 in April) and ROSC (39.1 vs 11.6%, p=0.0001 in April) was remarked, and survival rate dropped from 8.5 to 5%. There were less strokes (-27.5%, p value=0.002) despite a more severe onset of symptoms at hospitalisation with NHISS˃10 in 38.47% of cases. Acute myocardial infarctions decreased as well (-20%, p value=0.05), but statistical significances were not determined in the variables considered and in mortality. Despite a lower number of emergency responses, the number of calls to the EMS was considerably higher. The number of cardiac arrests treated with advanced CPR (ALS) was lower, but mortality was higher. The number of strokes decreased as well, but at the time of hospitalisation the clinical picture of the patient was more severe, thus affecting the outcome when the patient was discharged. Finally, STEMI patients decreased; however, no critical issues were observed in the variables taken into account, neither in terms of response times nor in terms of treatment times
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