Veneto Region Of Italy Research Articles

P137 GEOGRAPHIC DIFFERENCES IN CANCER RISK LONG AFTER ACS. THE ABC 7–7A* STUDY ON HEART DISEASE

Abstract Background Increased risk of cancer and cancer death has been reported in patients with Acute Coronary Syndrome (ACS). We investigated the long–term geographic differences in those risks. Methods In this prospective study, we enrolled 586 ACS patients admitted to hospitals in three provinces in the Veneto region of Italy. The patients were classified as residing in urban or rural areas in each province. Results With 3 exceptions, all patients completed the 22–year follow–up or were followed until death. Urban (46%) and rural (54%) residents shared most of their baseline demographic and clinical characteristics. Pre–existing malignancy was noted in 16 patients, whereas 106 patients developed cancer during follow–up and 99 patients died due to the malignancy. The urban/rural incidence rate of new malignancy per 1000 person–years was (9/32 in the north, 19/21 in the middle, and 18/13 in the southern province) and the urban/rural incidence rate of neoplastic death per 1000 person–years was (10/23 in the north, 16/17 in the middle, and 17/11 in the southern province). Unadjusted Cox regression analysis revealed increasing hazards ratios (HRs) for malignancy onset from urban to rural areas (HR = 3.0; 95%CI=1.5–6.2; p = 0.02). Also, we found a strong positive interaction between urban/rural areas and provinces with risk increasing from the urban to rural areas from southern to northern provinces (HR 2.1; 95% CI 1.3–3.5; p = 0.002), even with a fully adjusted model. Geographic areas, additionally, showed a strong positive interaction for the risk of cancer death, with risk increasing from the urban to rural areas from southern to northern provinces (HR = 1.9; 95%CI=1.1–3.0; p = 0.01) with the unadjusted Cox regression analysis. The fully adjusted Cox regression and Fine–Gray competing risk regression models provided similar results. We did not observe an urban/rural difference or an interaction between the geographic areas in non–neoplastic death risk. Conclusion This analysis reveals the significant urban/rural difference in the long–term risk of cancer onset and cancer death among unselected ACS patients. These results highlight the importance of implementing a preventive policy based on area–specific knowledge.

Empowerment via delegation? The administrative capacity-building potential of Cohesion Policy urban development strategies

ABSTRACT The study examines the implementation of urban development strategies in Scotland, UK, and the Veneto Region of Italy and fills an important gap in the knowledge about the capacity-building potential of such strategies. Following a principal-agent approach, the investigation shows that narrow delegation models incentivize compliance, are less conducive to capacity-building and reinforce an administrative capacity paradox. By contributing an original framework for the study of delegation models, a fine-grained understanding of administrative capacity that acknowledges the importance of agency for the success of capacity-building initiatives and policy recommendations for the period 2021–27, the research will be of interest to scholars and practitioners alike.

A Retrospective Database Analysis to Estimate the Burden of Acute Otitis Media in Children Aged

This study aimed to assess trends in the incidence of acute otitis media (AOM), a common childhood condition, following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in the Veneto region of Italy in 2010. AOM episodes (overall, simple, and recurrent (≥3 or ≥4 episodes in 6 or 12 months, respectively, with ≥1 episode in the preceding 6 months)) in children <15 years of age were identified in Pedianet from 2010–2017. Interrupted time series analyses were conducted to assess changes in the annual incidence rates (IRs) in early (2010–2013) and late (2014–2017) PCV13 periods. In total, 72,570 children (402,868 person-years) were identified; 21,048 had 41,683 AOM episodes. Mean annual AOM IR was 103/1000 person-years (95% confidence interval: 102–104), decreasing from 126 to 79/1000 person-years. AOM IRs were highest in children 2–4 years of age, followed by <2 and 5–14 years of age. Overall and simple AOM IRs decreased among children 0–14 years of age, including 2–4 and 5–14 years of age, while recurrent AOM IRs decreased in children <2 years of age. Following PCV13 introduction, AOM IRs decreased substantially in children <15 years of age, with the greatest benefit observed in older children, driven by a reduction in simple AOM IRs. AOM disease burden remains substantial.

Is COVID-19 enough? Which underestimated conditions characterise the adoption of complex information infrastructures in small and medium-sized enterprises

The COVID-19 pandemic crisis has forced firms to leverage information and digital technologies to resist its disruptive effects. The shift to digital, however, requires the availability of information infrastructure, such as enterprise resource planning (ERP), that can enable effective digitisation of processes and practices.This paper investigates the role of the pandemic crisis on boosting intentions to adopt ERP systems in SMEs by mitigating the barrier factors that hinder their adoption.To investigate the impact of the pandemic on ERP adoption decisions, we ran a quantitative study among 147 SMEs in the Veneto region in Italy and applied a fuzzy set qualitative comparative analysis model to study them. Our results show that the pandemic crisis has boosted this adoption, shaping the configuration of conditions that characterise ERP adoption.

The effect of social and personal norms on stated preferences for multiple soil functions: evidence from Australia and Italy

Although soil degradation has become a global phenomenon that might severely threaten the provision of a large range of ecosystem services, not much is known about the economic value of soil functions such as carbon sequestration and rainfall water infiltration. Knowing these values would be an important input into the recently developed concept of Soil Security. This paper aimed at closing this gap for a broad set of soil functions valued at the regional level in the Veneto region in Italy and New South Wales in Australia. The study not only elicits non‐market values by a choice experiment but also investigates the impact of personal norm activation and social norms on stated preferences, by a hybrid choice model with multiple latent variables. As the survey was conducted in two countries, our study offers evidence of the external validity of both social norm effects and personal norm activation. The results reveal that respondents positively value the conservation of the soil functions and that both personal norm activation and social norm clearly affect stated preferences.

368 Serial vs. single cardiovascular screening of adolescent athletes

Abstract The primary objective of preparticipation cardiovascular evaluation (PPCE) in young athletes is to detect asymptomatic individuals with cardiovascular disease (CVD) at risk of sudden cardiac death (SCD). The study population included a consecutive series of competitive athletes age 12–18 years who underwent PPCE, which according to Italian law is mandatory and based on yearly evaluations, at the Center for Sports Medicine of Treviso (Veneto region of Italy), from 2009 to 2019. The screening protocol included personal and family history questionnaire, physical examination, resting 12-lead ECG, and limited stress testing for evaluation of exertional ventricular arrhythmias. 2,3 This latter test was performed using a bicycle with constant-load increases (i.e. 2 W/kg in female participants and 3 W/kg in male participants) for 3 min for at least 85% or more of maximal heart rate was achieved, plus 3 min of postexercise monitoring. 3 Athletes with a positive medical history and abnormal physical examination, ECG, or stress test underwent further investigations. The diagnostic yield of the initial screening session was compared with that of repeat PPCEs. Athletes with a definitive diagnosis of CVD at risk of SCD were considered ineligible for competitive sports, although they received a tailored programme for leisure physical activity and were enrolled in a yearly follow-up programme. Outcome data of screened athletes, either eligible or ineligible to play competitive sports, were obtained from office visits, hospital records, or interrogation of the Registry of Juvenile SCD of the Veneto region. The study population included 15 127 consecutive athletes (64% male, 96% White) who underwent a total of 53 396 annual PPCEs (mean 3.7 per athlete) over the 11-year study period. The median age at first screening was 13 years [interquartile range (IQR): 12–14]. Sixty-three athletes (65% male) were diagnosed with a CVD at risk of SCD such as congenital heart disease (n = 17), ion channel disease (n = 11), inherited cardiomyopathy (n = 13), isolated nonischaemic left ventricular scar (NLVS) with ventricular arrhythmias (n = 18), or other (n = 4); 266 athletes had cardiac conditions not associated with SCD. Seventeen of the 63 athletes (27%) with atrisk CVD had a positive family history, symptoms, or abnormal physical examination, 38 (60%) had ECG abnormalities, and 32 (51%) developed arrhythmias on limited exercise testing. CVDs more frequently identified on repeat evaluation included inherited cardiomyopathies [7/11 (64%)], NLVS with ventricular arrhythmias [15/18 (83%)], and long QT syndrome [7/11 (64%)]. During a mean follow-up of 6.7 ± 3.5 years, 1 athlete with a negative PPCE experienced an episode of aborted SCD attributable to ventricular fibrillation that remained unexplained after a comprehensive diagnostic workup (event rate, 0.98/100 000 athletes per year). These results show that annual cardiovascular screening of adolescent athletes increased by three times the diagnostic yield of CVD at risk of SCD compared with a once-only (initial) evaluation. Inherited cardiomyopathies and isolated NLVS with ventricular arrhythmias were the CVDs more frequently identified on repeat evaluation.

The Economic Impact Of Physical Activity In Different Chronic Diseases: A Regional Cost-saving Pilot Study In Italy

PURPOSE: High levels of sedentary behaviour (SB) and physical inactivity (PI) are associated with an increased risk of non-communicable diseases (NCDs) and are responsible for a substantial economic burden. Previous studies acknowledge the cost-effectiveness of physical activity (PA) intervention, but few is known in specific local settings. This study aims to provide cost-saving data of PA intervention in Veneto Region in Italy. METHODS: Pilot study investigating the cost-saving potential of PA in NCDs, in particular in sedentary population. Further percutaneous coronary intervention (PCI) in coronary artery disease, hospitalisations in chronic obstructive pulmonary disease (COPD), surgery in colorectal cancer and in femur fracture were considered in the evaluation. Disease-specific epidemiological, SB an PA data were obtained from national or regional registries, and relative risks reduction due to PA were derived from literature. Health-care costs were assessed using Veneto Region data from Diagnosis Related Groups reports. For each NCD, costs reduction due to PA intervention were calculated. All costs were expressed in Euros (€). RESULTS: Estimated cost-savings that would result from PA intervention could amount to: 10.320.249 € in the whole population and 3.199.277 € in the inactive population for further PCI; 5.671.016 € in the whole population and 2.035.895 € in the sedentary population for hospitalisations in COPD; 6.805.326 € in the whole population and 1.810.217 € for bowel resection in colorectal cancer; 3.020.567 € in the whole population and 803.471 € in the sedentary population for surgery intervention in femur fracture. Veneto Region Health System could save per year between 5.716.008 €, in a more conservative analysis considering just the sedentary population, and 18.936.992 € in a less conservative one. CONCLUSIONS: PA interventions seem to be cost-saving in Veneto Region if direct health-care costs are considered. It can be assumed that taking into account indirect costs would have an even greater effect. Veneto Region should seriously consider investing in PA implementation to improve the health of its citizens and to save public money.

Colorectal cancer incidence and mortality after negative fecal immunochemical tests by age 70: A prospective observational study.

Limited endoscopy capacity usually represents the main barrier to the extension of screening to subjects older than 70, given the high positivity rate in this age group. We assessed CRC incidence and mortality by number of previous negative fecal immunochemical tests (FIT) among subjects turning 70. We selected persons aged 70 years who had received their last screening invitation when they were 68 or 69 years old within the population-based screening program in the Veneto region of Italy. Subjects with a positive FIT were excluded. We calculated 10-year cumulative CRC incidence and mortality in cohorts of subjects having performed zero, one, two or three negative FITs over the last three screening rounds before turning 70. Out of 117 858 subjects included in the study (46.4% men), 33.7% had never participated in screening (zero negative FITs), 23.3% had had one-negative FIT, 20.1% two-negative FITs and 22.9% three negative FITs. The 10-year cumulative CRC incidence was 29.7 per 1000 subjects with zero FITs, and respectively, 14.5, 11.7 and 9.6 per 1000 subjects with one, two and three negative FITs. The corresponding figures for 10-year cumulative mortality were 9.3, 3.5, 2.2 and 2.1 per 1000 in the four study cohorts. Figures were roughly double for men than for women for all the study cohorts. In order to use more efficiently limited endoscopy resources, and to minimize the potential harms related to false positive results in the elderly, screening among people aged 70 to 74 might be restricted to those with zero previous negative FITs.

Risk of malignancy long after acute coronary syndrome in selected urban and rural areas and comparison with smoking risk: the ABC-7* study on Heart Disease

BackgroundIncreased cancer risk has been reported in patients with acute coronary syndrome (ACS).ObjectivesTo investigate geographic differences in risk malignancy long after ACS.MethodsWe enrolled 586 ACS patients admitted to hospitals in three provinces in the Veneto region of Italy in this prospective study. Patient’s residency was classified into three urban and three nearby rural areas.ResultsAll (except for 3) patients completed the follow-up (22 years or death) and 54 % were living in rural areas. Sixteen patients had pre-existing malignancy, and 106 developed the disease during follow-up. Cancer prevalence was 17 % and 24 % (p = 0.05) and incidence of malignancy was 16 and 21/1000 person-years for urban and rural areas, respectively. In unadjusted logistic regression analysis, cancer risk increased from urban to rural areas (odds ratio [OR] 3.4;95 % confidence interval [CI] 1.7–7.1; p = 0.001), with little change from north to south provinces (OR 1.5;95 % CI 1.0-2.2; p = 0.06). Yet, we found a strong positive interaction between urban-rural areas and provinces (OR 2.1;95 % CI 1.2–3.5; p = 0.003). These results kept true in the fully adjusted model. Unadjusted Cox regression analysis revealed increasing hazards ratios (HRs) for malignancy onset from urban to rural areas (HR 3.0;95 % CI 1.5–6.2; p = 0.02), but not among provinces (HR 1.3;95 % CI 1.0–2.0; p = 0.14). Also, we found a strong positive interaction between geographic areas (HR 2.1;95 % CI 1.3–3.5; p = 0.002), even with a fully adjusted model.ConclusionsThe results in unselected real-world patients demonstrate a significant geographic difference in malignancy risk in ACS patients, with the highest risk in the north-rural area.

INSPIRE standards as a framework for artificial intelligence applications: a landslide example

Abstract. This study presents a landslide susceptibility map using an artificial intelligence (AI) approach based on standards set by the INSPIRE (Infrastructure for Spatial Information in the European Community) framework. INSPIRE is a European Union spatial data infrastructure (SDI) initiative to standardize spatial data across borders to ensure interoperability for management of cross-border infrastructure and environmental issues. However, despite the theoretical effectiveness of the SDI, few real-world applications make use of INSPIRE standards. In this study, we show how INSPIRE standards enhance the interoperability of geospatial data and enable deeper knowledge development for their interpretation and explainability in AI applications. We designed an ontology of landslides, embedded with INSPIRE vocabularies, and then aligned geology, stream network, and land cover datasets covering the Veneto region of Italy to the standards. INSPIRE was formally extended to include an extensive landslide type code list, a landslide size code list, and the concept of landslide susceptibility to describe map application inputs and outputs. Using the terms in the ontology, we defined conceptual scientific models of areas likely to generate different types of landslides as well as map polygons representing the land surface. Both landslide models and map polygons were encoded as semantic networks and, by qualitative probabilistic comparison between the two, a similarity score was assigned. The score was then used as a proxy for landslide susceptibility and displayed in a web map application. The use of INSPIRE-standardized vocabularies in ontologies that express scientific models promotes the adoption of the standards across the European Union and globally. Further, this application facilitates the explanation of the generated results. We conclude that public and private organizations, within and outside the European Union, can enhance the value of their data by making them INSPIRE-compliant for use in AI applications.

Association of Multiple Sclerosis with PM 2.5 levels. Further evidence from the highly polluted area of Padua Province, Italy

BackgroundFifty years of epidemiological survey and intra-regional differences in prevalence suggest that environmental factors may be associated with increased multiple sclerosis (MS) risk in Northern Italy. Based on the findings of a previous study carried out in the highly polluted Padan Plain, we further explored the relationship between PM2.5 levels and MS prevalence by comparing bordering areas characterized by quite different environmental conditions, namely the Municipality of Padua and the special protected zone (SPZ) of the Euganean Hills Regional Park, located 15 km from the City. MethodsThree territories were identified; 1) the SPZ, extending over an area of 15.096 hectares and having a total population of 23,980 inhabitants, 2) the urban area of Padua, with a total population of 210,440 inhabitants and repeatedly recognized by the European Invironmental Agency as one of the most polluted Cities of Europe, 3) the Intermediate Zone (IZ), i.e., the area in between the previous two, including part of the urban territories of eight villages adjacent to the SPZ. Demographic and socio-economical data were obtained from official government sources (www.istat.it and www.regione.veneto.it). All Italian MS patients residing in these three areas on December 31, 2018, were registered. PM2.5 concentrations (annual average 1998–2018, μg/m3) were measured by satellite. The correlation between PM2.5 concentrations and MS prevalence was analysed. ResultsMS prevalence was significantly higher in Padua City (265/100.000) compared to both the SPZ of the Euganean Hills Park (160/100,000; p < 0.0001) and the IZ (194.4/100,000). Prevalence strongly associated with the annual average concentration of PM2.5 (r = 0.89 p < 0.00001). ConclusionIn the Province of Padua, one of the most polluted areas of Europe, MS prevalence is strongly associated with PM2.5 exposure. Our findings suggest that air pollutants may be one of the possible environmental risk factors for MS in the Veneto Region of Italy.

Promoting health and preventing non-communicable diseases: evaluation of the adherence of the Italian population to the Mediterranean Diet by using the PREDIMED questionnaire.

A health promotion program was conducted in the Veneto Region in Italy. Participants were screened for non-communicable diseases and were referred to the nutrition clinic. The aim of this study was to assess the adherence to the Mediterranean diet in the Italian population by using the "PREvención con DIeta MEDiterránea" questionnaire. The data showed that 63% of the participants were overweight, 57% presented hypercholesterolemia, 36% were hypertensive and 43% had high blood glucose levels. The results highlighted a low consumption of protective foods against non-communicable diseases such as fruit, vegetables, fresh fish, legumes and oily dried fruit. Overall, only 6% of the subjects who visited the nutritional clinic had the maximum adherence to the Mediterranean diet, 73% had an average adherence, followed by 21% with low adherence. Multivariable analysis between risk factors and socio-demographic characteristics and the adherence to Mediterranean diet revealed that male gender relates directly (p =0.002, AOR = 2.95) to a low adherence. There are three criteria in the questionnaire for a point in favour of Mediterranean diet which we believe to be inadequate, as they are not in accordance with the Italian guidelines for healthy eating. The "PREvención con DIeta MEDiterránea" questionnaire, if associated with a food frequency questionnaire or a food intake record, could become a useful tool for nutritional counseling in our Country.

Neurosurgery in times of a pandemic: a survey of neurosurgical services during the COVID-19 outbreak in the Veneto region in Italy

The purpose of this study was to analyze the effect of the coronavirus disease 2019 (COVID-19) outbreak and of the subsequent lockdown on the neurosurgical services of the Veneto region in Italy compared to the previous 4 years. A survey was conducted in all 6 neurosurgical departments in the Veneto region to collect data about surgical, inpatient care and endovascular procedures during the month of March for each year from 2016 to 2020. Safety measures to avoid infection from SARS-CoV-2 and any COVID-19 cases reported among neurosurgical patients or staff members were considered. The mean number of neurosurgical admissions for the month of March over the 2016-2019 period was 663, whereas in March 2020 admissions decreased by 42%. Emergency admissions decreased by 23%. The average number of neurosurgical procedures was 697, and declined by 30% (range -10% to -51% in individual centers). Emergency procedures decreased in the same period by 23%. Subarachnoid hemorrhage and spontaneous intracerebral hemorrhage both decreased in Veneto-by 25% and 22%, respectively. Coiling for unruptured aneurysm, coiling for ruptured aneurysm, and surgery for ruptured aneurysm or arteriovenous malformation diminished by 49%, 27%, and 78%, respectively. Endovascular procedures for acute ischemic stroke (AIS) increased by 33% in 2020 (28 procedures in total). There was a slight decrease (8%) in brain tumor surgeries. Neurosurgical admissions decreased by 25% and 35% for head trauma and spinal trauma, respectively, while surgical procedures for head trauma diminished by 19% and procedures for spinal trauma declined by 26%. Admissions and surgical treatments for degenerative spine were halved. Eleven healthcare workers and 8 patients were infected in the acute phase of the pandemic. This multicenter study describes the effects of a COVID-19 outbreak on neurosurgical activities in a vast region in Italy. Remodulation of neurosurgical activities has resulted in a significant reduction of elective and emergency surgeries compared to previous years. Most likely this is a combined result of cancellation of elective and postponable surgeries, increase of conservative management, increase in social restrictions, and in patients' fear of accessing hospitals. Curiously, only endovascular procedures for AIS have increased, possibly due to reduced physical activity or increased thrombosis in SARS-CoV-2. The confounding effect of thrombectomy increase over time cannot be excluded. No conclusion can be drawn on AIS incidence. Active monitoring with nasopharyngeal swabs, wearing face masks, and using separate pathways for infected patients reduce the risk of infection.

Morphological and genetic characterization of 13 Italian local chicken breeds

Morphological and genetic characterization of 13 Italian local chicken breeds

Early Phase Management of the SARS-CoV-2 Pandemic in the Geographic Area of the Veneto Region, in One of the World's Oldest Populations.

The first cases of Coronavirus disease-2019 (COVID-19) were reported on 21 February in the small town of Vo’ near Padua in the Veneto region of Italy. This event led to 19,286 infected people in the region by 30 June 2020 (39.30 cases/10,000 inhabitants). Meanwhile, Rovigo Local Health Unit n. 5 (ULSS 5), bordering areas with high epidemic rates and having one of the world’s oldest populations, registered the lowest infection rates in the region (19.03 cases/10,000 inhabitants). The aim of this study was to describe timing and event management by ULSS 5 in preventing the propagation of infection within the timeframe spanning from 21 February to 30 June. Our analysis considered age, genetic clusters, sex, orography, the population density, pollution, and economic activities linked to the pandemic, according to the literature. The ULSS 5 Health Director General’s quick decision-making in the realm of public health, territorial assistance, and retirement homes were key to taking the right actions at the right time. Indeed, the number of isolated cases in the Veneto region was the highest among all the Italian regions at the beginning of the epidemic. Moreover, the implementation of molecular diagnostic tools, which were initially absent, enabled health care experts to make quick diagnoses. Quick decision-making, timely actions, and encouraging results were achieved thanks to a solid chain of command, despite a somewhat unclear legislative environment. In conclusion, we believe that the containment of the epidemic depends on the time factor, coupled with a strong sense of awareness and discretion in the Health Director General’s decision-making. Moreover, real-time communication with operating units and institutions goes hand in hand with the common goal of protecting public health.

Using Wearable Devices to Monitor Physical Activity in Patients Undergoing Aortic Valve Replacement: Protocol for a Prospective Observational Study.

BackgroundIn last few decades, several tools have been developed to measure physical function objectively; however, their use has not been well established in clinical practice.ObjectiveThis study aims to describe the preoperative physical function and to assess and compare 6-month postoperative changes in the physical function of patients undergoing treatment for aortic stenosis with either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). The study also aims to evaluate the feasibility of wearable devices in assessing physical function in such patients.MethodsThis is a prospective observational study. The enrollment will be conducted 1 month before patients’ SAVR/TAVR. Patients will be provided with the wearable device at baseline (activity tracker device, Garmin vívoactive 3). They will be trained in the use of the device, and they will be requested to wear it on the wrist of their preferred hand until 12 months after SAVR/TAVR. After baseline assessment, they will undergo 4 follow-up assessments at 1, 3, 6, and 12 months after SAVR/TAVR. At baseline and each follow-up, they will undergo a set of standard and validated tests to assess physical function, health-related quality of life, and sleep quality.ResultsThe ethics committee of Vicenza in Veneto Region in Italy approved the study (Protocol No. 943; January 4, 2019). As of October 2020, the enrollment of participants is ongoing.ConclusionsThe use of the wearable devices for real-time monitoring of physical activity of patients undergoing aortic valve replacement is a promising opportunity for improving the clinical management and consequently, the health outcomes of such patients.Trial RegistrationClinicaltrials.gov NCT03843320; https://tinyurl.com/yyareu5yInternational Registered Report Identifier (IRRID)DERR1-10.2196/20072

PFAS Environmental Pollution and Antioxidant Responses: An Overview of the Impact on Human Field.

Due to their unique properties, perfluorinated substances (PFAS) are widely used in multiple industrial and commercial applications, but they are toxic for animals, humans included. This review presents some available data on the PFAS environmental distribution in the world, and in particular in Europe and in the Veneto region of Italy, where it has become a serious problem for human health. The consumption of contaminated food and drinking water is considered one of the major source of exposure for humans. Worldwide epidemiological studies report the negative effects that PFAS have on human health, due to environmental pollution, including infertility, steroid hormone perturbation, thyroid, liver and kidney disorders, and metabolic disfunctions. In vitro and in vivo researches correlated PFAS exposure to oxidative stress effects (in mammals as well as in other vertebrates of human interest), produced by a PFAS-induced increase of reactive oxygen species formation. The cellular antioxidant defense system is activated by PFAS, but it is only partially able to avoid the oxidative damage to biomolecules.

How the COVID-19 lockdown affected the parents of offspring who needed palliative care in the Veneto region of Italy.

None. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Abstract S01-03: A prediction of prostate cancer deaths spiking by SARS-CoV-2 infection

Abstract COVID-19 is a global issue, with over 6.25 million cases in 213 countries and territories on June 1, 2020. Although this virus infects all groups, data indicate that the risk for severe disease and death is much higher in older men, which coincides with the same group of patients at risk for prostate cancer. A recent Italian study investigated the prevalence and severity of COVID-19 in men with prostate cancer. This study indicated that of a total of 4,532 men with COVID-19, from the Veneto region of Italy, 9.5% (n=430) had cancer and out of those around 30% (n=118) had prostate cancer. Data also indicated that male cancer patients had a 1.8-fold increased risk of COVID-19 infection and developed a more severe disease. Interestingly, they observed that the prostate cancer patients (n=4) treated with androgen-deprivation therapy (ADT) were less likely to develop COVID-19, and in those who were infected, the disease was less severe. In this current study, we focused on determining the genetic basis of the higher COVID-19 prevalence and severity in male patients and particularly for prostate cancer patients. Researchers found two genes that are essential for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). ACE2 is a SARS-CoV-2 receptor, whereas the serine protease, TMPRSS2, primes the virus for cell entry through cleavage of the viral spike protein (S). The expression of TMPRSS2 is significantly high in normal prostate tissue and is regulated in large part by an androgen response element in the promoter region. Therefore, we decided to investigate the status of these two genes in various tumors from The Cancer Genome Atlas (TCGA) database using the cBioportal platform. We analyzed over 46,000 tumor samples from 176 studies and found that aggressive metastatic prostate cancer, including neuroendocrine prostate cancer (NEPC), has significantly higher amplification (copy number alteration) of the ACE2 and TMPRSS2 genes compared to other cancers. Next, we focused on drugs that could simultaneously target ACE2 or TMPRSS2 and oncogenic pathways and would be beneficial for prostate cancer patients infected with SARS-CoV-2. Although several inhibitors are validated in literature for both ACE2 and TMPRSS2, very limited studies were performed to see the effect on cancer cells. Therefore, we analyzed a cytotoxic effect database of over 130,000 drugs on NCI-60 cell lines with COMPARE algorithm and found two relevant compounds, NSC-148958 (FT-701) and NSC-280594 (triciribine phosphate), which target ACE2 and TMPRSS2, respectively. Computational data are currently validating different prostate cancer cell-lines and their response to these drugs. In summary, our findings provide the premise that men who are at risk for or diagnosed with prostate cancer may be more susceptible to severe infection and death in response to SARS-CoV-2 due to the high expression of ACE2 and TMPRSS2, and triciribine phosphate and FT-701 could be a therapeutic intervention to target co-occurrence of COVID-19 and prostate cancer. Citation Format: Alakesh Bera, Eric Russ, Digonto Chatterjee, John Karaian, Madhan Subramanian, Sreejato Chatterjee, Surya Radhakrishnan, Michael Eklund, Harvey Pollard, Meera Srivastava. A prediction of prostate cancer deaths spiking by SARS-CoV-2 infection [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S01-03.

1604P Aggregated analysis of treatment and survival outcome of all metastatic renal cell carcinoma patients treated from 2014 to 2018 in the Veneto region, Italy

Monitoring the use of high cost drugs at a population level is becoming increasingly relevant for regional Healthcare systems in order to appropriately program the allocation of resources and conduct budget impact analyses whenever a novel drug is approved. We planned a retrospective analysis of all prescriptions of high cost drugs to mRCC pts in the Veneto Region of Italy, years 2014-2018. Aggregated data of type of drug, line of treatment, treatment duration-TD, OS and costs were extracted from Veneto Healthcare database covering 4.9 million people. Average monthly cost of therapy was calculated dividing the cost of all drug resupplies dispensed to each patient by TD in mo of the same treatment. Managed entry agreements and clinical trials were not considered. We identified 1135 pts who started at least one line of systemic treatment for mRCC, and a total of 1665 treatments: 58% in first line, 26% second, 12% third, 4% fourth or further line. First-line pazopanib and sunitinib had a median DT of 10.5 and 9.7 mo (32.3% censored, p=0.51), and median OS of 28.6 and 26.2 mo (54.6% censored, p=0.61), respectively. Average monthly cost was estimated to be 3,583 and 2,679 euros for sunitinib and pazopanib, respectively (p<0.0001) (Table). Nivolumab and cabozantinib had a longer DT both in second line (compared to axitinib, everolimus and sorafenib (p<0.0001)) and third line (compared to everolimus or sorafenib, (p<0.0001)), although medians were not reached with all drugs (Table). Cost of second or third line treatment per patient was significantly higher for Nivolumab compared to all other drugs, p<0.0001 (Table). Our pupulation-based analysis confirms that first line pazopanib and sunitinib have comparable DT and OS, although cost of sunitinib without managed entry agreements is higher. Nivolumab and cabozantinib have superior DT both in second and third line setting, with nivolumab being the most expensive drug.Table 1604PDT, OS and average monthly cost of drugs per patient (NR=not reached)LineNDT (mo)pOS (mo)Pcost (euros)pFIRSTPazopanibSunitinib34461510.5 (8.7-12.9)9.7 (8.4-12.0)0.512.9.0 (21.7-35.3)26.8 (21.4-33.4)0.6126793583<0.0001SECONDAxitinibCabozantinibEverolimusNivolumabSorafenib11734123118285.9 (3.9-7.2)NR4.5 (3.1-5.0)8.7 (5.2-13.7)2.8 (1.6-3.7)<0.000113.8 (10.8-24.6)NR12.2 (9.0-15.6)NR12.5 (5.4-19.4)<0.00013.0442860335755593261<0.0001THIRDCabozantinibEverolimusNivolumabSorafenib30585261NR3.8 (2.9-4.5)4.8 (2.8-10.0)3.0 (2.2-5.6)<0.0001NR8.3 (6.9-14.3)NR8.9 (5.7-12.2)<0.00012939360253482920<0.0001 Open table in a new tab