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BackgroundERAS is an evidence-based multimodal perioperative protocol focused on stress reduction and promoting a return to function. The aim of this work is to perform a cost-consequence analysis for the implementation of ERAS in major lung resection by means of minimally invasive surgery (VATS) from the public health service perspective, evaluating resource consumption and clinical outcomes with respect to a control group of past patients, which did not adopt an ERAS protocol.MethodsOutcome differences (re-intervention rates, major and minor intraoperative and postoperative complications, readmissions, and mortality) as well as the costs of preoperative, operative, and postoperative care were estimated. The sample consisted of 64 consecutive patients enrolled in the ERAS programme between April 2021 and August 2022, compared to a control group (historical cohort) comprising 31 patients treated from April 2020 to December 2020, prior to the implementation of the ERAS programme. The study sample comprises patients who fulfil the established ERAS protocol inclusion criteria, including general criteria (acceptance of the protocol, proximity of residence, absence of contraindications to physiotherapy and early mobilisation), surgical criteria (anatomical lung resection up to lobectomy, absence of extensive resection, good possibility of conducting the operation in VATS) and anaesthesiologic criteria (ASA ≤2). Costs were quantified using the national health system perspective.ResultsThe average length-of-stay was at least one day shorter in the ERAS group [

This article considers different governance structures, policies, and strategies that focus on the sustainable development of mountain areas in the European Alpine region and investigates how different countries integrate sustainable development into their mountain policies. Even though mountain areas cover around one third of European land, only a few countries have established place-based policies for their sustainable development. We analyzed 4 cases (Austria, France, Italy, and Switzerland) to reveal extremely diverse systems in terms of policies and actions. Furthermore, we scrutinized the sustainable development governance frameworks in policies directed at mountain areas, comparing national legislation. We also performed 4 semistructured interviews with national experts in mountain governance. Our results show that interacting with different stakeholders is a precondition for place-based sustainable development processes. We conclude by providing evidence-based policy recommendations for the sustainable development of mountain areas.

Acute myocardial infarction still represents the major cause of mortality in high-income countries. Therefore, considerable efforts have been focused on the treatment of myocardial infarctions in the acute and long-term phase, with special attention being paid to reperfusion strategies and adjunctive antithrombotic therapies. In fact, despite the successful mechanical recanalization of the epicardial conduit, a substantial percentage of patients still experience poor myocardial reperfusion or acute/subacute in-stent thrombosis. Due the delayed onset of action of currently available oral antiplatelet therapies, glycoprotein (GP) IIb–IIIa inhibitors could be expected to improve clinical outcomes, especially when administrated in the early phase of the infarction, due to the larger platelet composition of fresh thrombi, the dynamic nature of early thrombi, and the larger amount of viable myocardium existing in the early, as compared to a delayed, phase. Considerable evidence has accumulated regarding the benefits from GP IIb–IIIa inhibitors on mortality, especially among high-risk patients and when administered as an upstream strategy. Therefore, based on currently available data, GP IIb–IIIa inhibitors can be considered when the drug can be administered within the first 3 h of symptom onset and among high-risk patients (e.g., those with advanced Killip class or an anterior myocardial infarction). Even though it is not universally accepted, in our opinion, this strategy should be implemented in a pre-hospital setting (in an ambulance) or as soon as possible when arriving at the hospital (at the Emergency Room or Coronary Care Unit, irrespective of whether they are in spoke or hub hospitals). A new, second-generation GP IIb–IIIa inhibitor (zalunfiban) appears to be highly suitable as a pre-hospital pharmacological facilitation strategy at the time of first medical contact due to its favourable features, including its simple subcutaneous administration, rapid onset of action (15 min), and limited time of action (with a half-life of ~1 h), which is likely to minimize the risk of bleeding. The ongoing CELEBRATE trial, including 2499 STEMI patients, may potentially provide compelling data to support the upstream treatment of STEMI patients undergoing mechanical reperfusion. In fact, although the current therapeutic target of increased rates of timely reperfusion has been achieved, the future goal in myocardial infarction treatment should be to achieve the most rapid reperfusion prior to primary percutaneous coronary intervention, thus further minimizing myocardial damage, or, in some cases, even preventing it completely, and improving survival.

Abstract Background Metastatic disease in tumors originating from the gastrointestinal tract can exhibit varying degrees of tumor burden at presentation. Some patients follow a less aggressive disease course, characterized by a limited number of metastatic sites, referred to as “oligo-metastatic disease” (OMD). The precise biological characteristics that define the oligometastatic behavior remain uncertain. In this study, we present a protocol designed to prospectively identify OMD, with the aim of proposing novel therapeutic approaches and monitoring strategies. Methods The PREDICTION study is a monocentric, prospective, observational investigation. Enrolled patients will receive standard treatment, while translational activities will involve analysis of the tumor microenvironment and genomic profiling using immunohistochemistry and next-generation sequencing, respectively. The first primary objective (descriptive) is to determine the prevalence of biological characteristics in OMD derived from gastrointestinal tract neoplasms, including high genetic concordance between primary tumors and metastases, a significant infiltration of T lymphocytes, and the absence of clonal evolution favoring specific driver genes (KRAS and PIK3CA). The second co-primary objective (analytic) is to identify a prognostic score for true OMD, with a primary focus on metastatic colorectal cancer. The score will comprise genetic concordance (> 80%), high T-lymphocyte infiltration, and the absence of clonal evolution favoring driver genes. It is hypothesized that patients with true OMD (score 3+) will have a lower rate of progression/recurrence within one year (20%) compared to those with false OMD (80%). The endpoint of the co-primary objective is the rate of recurrence/progression at one year. Considering a reasonable probability (60%) of the three factors occurring simultaneously in true OMD (score 3+), using a significance level of α = 0.05 and a test power of 90%, the study requires a minimum enrollment of 32 patients. Discussion Few studies have explored the precise genetic and biological features of OMD thus far. In clinical settings, the diagnosis of OMD is typically made retrospectively, as some patients who undergo intensive treatment for oligometastases develop polymetastatic diseases within a year, while others do not experience disease progression (true OMD). In the coming years, the identification of true OMD will allow us to employ more personalized and comprehensive strategies in cancer treatment. Trial registration ClinicalTrials.gov ID NCT05806151.

BackgroundThis observational study considers the sex-specific incidence of the most incident cancers as recorded in the population-based Veneto Regional Cancer Registry over a period of more than 30 years (1987-2019).MethodsThe Veneto Regional Cancer Registry collected data for the time interval 1987–2019. Significant changes in incidence trends calculated on age-standardized incidence rates (Annual Percent Change—APC) were identified by join point regression analysis.ResultsOverall, the incidence trend for all cancers decreased in males and remained stable in females. In nine cancer sites, the incidence trends showed consistent differences by sex (oral cavity, esophagus, colon rectum and anus, liver, larynx, lung, cutaneous malignant melanoma, bladder, and thyroid gland). Other malignancies did not show significant sex-related differences (stomach, pancreas, biliary tract, kidney/urinary tract, central nervous system, multiple myeloma, non-Hodgkin lymphoma, and leukemia).ConclusionIn the period 1987–2019, this study revealed sex-related differences in cancer incidence trends. Over time, cancer incidence remained higher in males, with a decreasing epidemiological impact, plausibly resulting from prevention campaigns against environmental cancer risk factors, as tobacco and alcohol. Conversely, a significant decrease was not observed in the incidence trend in females. These findings contribute essential insights for profiling the epidemiological map of cancer in a large Italian population, allowing comparison with other European cancer epidemiology studies and providing updated data supporting sex-related primary and secondary cancer prevention strategies.

Vitamin D is rightly recognized as an essential key factor in the regulation of calcium and phosphate homeostasis, affecting primary adequate bone mineralization. In the last decades, a more complex and wider role of vitamin D has been postulated and demonstrated. Cardiovascular diseases have been found to be strongly related to vitamin D levels, especially to its deficiency. Pre-clinical studies have suggested a direct role of vitamin D in the regulation of several pathophysiological pathways, such as endothelial dysfunction and platelet aggregation; moreover, observational data have confirmed the relationship with different conditions, including coronary artery disease, heart failure, and hypertension. Despite the significant evidence available so far, most clinical trials have failed to prove any positive impact of vitamin D supplements on cardiovascular outcomes. This discrepancy indicates the need for further information and knowledge about vitamin D metabolism and its effect on the cardiovascular system, in order to identify those patients who would benefit from vitamin D supplementation.

Extensive evidence highlights the significant influence of dyadic, emotional teacher-student relationship (TSR) on students’ cognitive functioning, socio-emotional development, and overall well-being. However, it remains unclear whether the TSR construct and its manifestations can be generalized across cultures. This qualitative study investigated TSR among 60 primary school teachers in Belgium, China, and Italy (i.e., countries with varying positions on the collectivistic-individualistic continuum of culture). Through semi-structured interviews and metatheme analysis, the study examined the similarities and differences in TSR across these countries, revealing a nuanced and diverse picture in various cultural contexts. The findings align with the existing TSR model by including dimensions of closeness, conflict, and dependency, while also extending the model to identify additional dimensions such as authority, balance, distance, fairness, increasing student motivation, patience, and strictness. Regarding cultural perspective, teachers from these three countries exhibited similar conceptualizations of closeness, conflict, fairness, increasing student motivation, patience, and strictness, whereas the conceptualization of dependency, authority, balance, and distance may be influenced by (collectivistic versus individualistic) culture. Moreover, the manifestations of TSR varied across countries, highlighting the influence of cultural factors such as cultural norms, collectivistic versus individualistic values, and the perceived legitimacy of teacher authority. These findings shed light on the complexities of TSR across countries and emphasize the significance of culturally sensitive approaches in fostering positive TSR in education.

Key points FMECA is a proactive risk assessment tool that has proved useful in identifying potential failures in the process of prescribing and administering cancer treatments, which is a high-risk process. The analysis evidenced 22 failures modes, distributed over the various phases of the process. In order to reduce the likelihood of the cause, or to improve the chances of a failure mode being detected, this work identified a number of recommendations to be adopted in the administration of cancer treatment in an outpatient setting.

Abstract Background The RCC treatment landscape has evolved dramatically over the past decade. The purpose of this study is to present a real-world data estimation of RCC’s cost-of-illness for this tumour’s clinical pathway. Methods This investigation is a population-based cohort study using real-world data, which considers all RCC incident cases diagnosed in Local Unit 6 of the Province of Padua in 2016 and 2017 as registered by the Veneto Cancer Registry. Data on drug prescriptions, the use of medical devices, hospital admissions, and visits to outpatient clinics and emergency departments were collected by means of administrative databases. We evaluated the costs of all healthcare procedures performed in the 2 years of follow-up post-RCC diagnosis. The overall and annual average real-world costs per patient, both as a whole and by single item, were calculated and stratified by stage of disease at diagnosis. Results The analysis involved a population of 148 patients with a median age of 65.8 years, 66.22% of whom were male. Two years after diagnosis, the average total costs amounted to €21,429 per patient. There is a steady increment in costs with increasing stage at diagnosis, with a total amount of €41,494 spent 2 years after diagnosis for stage IV patients, which is 2.44 times higher than the expenditure for stage I patients (€17,037). In the first year, hospitalization appeared to be the most expensive item for both early and advanced disease. In the second year, however, outpatient procedures were the main cost driver in the earlier stages, whereas anticancer drugs accounted for the highest costs in the advanced stages. Conclusions This observational study provides real-world and valuable estimates of RCC’s cost-of-illness, which could enable policymakers to construct dynamic economic cost-effectiveness evaluation models based on real world costs’ evaluation.

Abstract Background The monoclonal antibody durvalumab, an immune‐checkpoint inhibitor (ICI) antiprogrammed death ligand 1 (PD‐L1), is available for unresectable stage III NSCLC patients as consolidation therapy following induction chemoradiotherapy, with very promising overall survival (OS) and progression‐free survial (PFS) results in registration trials. The purpose of this study was to provide policymakers with an estimate of the cost‐effectiveness of durvalumab in the treatment of non‐small cell lung cancer (NSCLC). Methods The study developed a Markov model covering a 5‐year period to compare costs and outcomes of treating PD‐L1 positive patients with or without durvalumab. We conducted a series of sensitivity analyses (Tornado analysis and Monte Carlo simulation) by varying some parameters to assess the robustness of our model and identify the parameters with the greatest impact on cost‐effectiveness. Results Prior to the release of durvalumab, the management of NSCLC over a 5‐year period cost €33 317 per patient, with an average life expectancy of 2.01 years. After the introduction of the drug, this increased to €37 317 per patient, with an average life expectancy of 2.13 years. Treatment with durvalumab led to an incremental cost‐effectiveness ratio (ICER) of €35 526 per year. OS is the variable that contributes the most to the variability of the ICER. Conclusions The study observed that durvalumab is a cost‐effective treatment option for patients with unresectable stage III NSCLC.

Abstract Background Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study. Methods In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents. Results A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658–1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620–1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups. Conclusion This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity. Trial registration number: NCT 04412655 (2nd June 2020).

Previous studies associated high-level exposure to ultraviolet radiation with a greater risk of cutaneous malignant melanoma (CMM). This study focuses on the changing incidence of CMM over time (from 1990 to 2017) in the Veneto region of Northeast Italy, and its Alpine area (the province of Belluno). The clinicopathological profile of CMM by residence is also considered. A joinpoint regression analysis was performed to identify significant changes in the yearly incidence of CMM by sex and age. For each trend, the average annual percent change (AAPC) was also calculated. In the 2017 CMM cohort, the study includes a descriptive analysis of the disease’s categorical clinicopathological variables. In the population investigated, the incidence of CMM has increased significantly over the last 30 years. The AAPC in the incidence of CMM was significantly higher among Alpine residents aged 0–49 than for the rest of the region’s population (males: 6.9 versus 2.4; females 7.7 versus 2.7, respectively). Among the Alpine residents, the AAPC was 3.35 times greater for females aged 0–49 than for people aged 50+. The clinicopathological profile of CMM was significantly associated with the place of residence. Over three decades, the Veneto population has observed a significant increase in the incidence of CMM, and its AAPC. Both trends have been markedly more pronounced among Alpine residents, particularly younger females. While epidemiology and clinicopathological profiles support the role of UV radiation in CMM, the young age of this CMM-affected female population points to other possible host-related etiological factors. These findings also confirm the importance of primary and secondary prevention strategies.

Abstract Background Assessment of the case‐fatality rate (CFR) of major bleeding on dual antiplatelet therapy (DAPT) may improve balancing risks and benefits of different durations of DAPT following percutaneous coronary intervention (PCI). Objectives To determine the CFR of major bleeding in patients on DAPT after PCI and to compare rates among different durations of DAPT. Methods Medline, Embase, and CENTRAL were searched from inception to August 2021 for randomized trials that reported fatal bleeding among patients who were randomized to ≥1 month of DAPT following PCI. Summary estimates for CFRs of major bleeding were calculated using the random‐effects inverse‐variance method. Statistical heterogeneity was evaluated using the I2 statistic. Results Of 2777 citations obtained by the search, 15 (48%) of 31 potentially eligible studies were excluded because fatal bleeding was not reported, leaving 16 studies that were included in the analysis. Overall, there were 823 major bleeding events including 91 fatal events in 48,884 patients who were assigned to receive DAPT during study follow‐up. The CFR of major bleeding was 10.8% (95% confidence interval [CI], 7.1–16.2; I2 = 50%) in the entire study population, and 13.8% (95% CI, 6.5–27.1; I2 = 28%), 11.2% (95% CI, 6.7–18.0; I2 = 0%), and 5.8% (95% CI, 3.0–11.1; I2 = 0%) in those on short‐term (≤6 months; n = 16,553), standard‐term (12 months; n = 19,453), and long‐term DAPT (>12 months; n = 10,238), respectively. Conclusion Fatal bleeding is not reported in many studies evaluating DAPT after PCI. The CFR of major bleeding on DAPT is substantial and may be higher in the first 12 months of DAPT than during long‐term DAPT.

BackgroundInvasiveness is considered one of the cornerstones of every field of surgery, and video-assisted thoracoscopic (VATS) approaches are now routinely used worldwide to perform pulmonary resections. Recently, robotic-assisted thoracic surgery (RATS) has become the preferred technique in many centers; it is routinely performed using three or four ports with at least one service incision, contrasting with the real concept of invasiveness, especially when compared to uniportal VATS (U-VATS). Hereby, we present our early experience with uniportal RATS (U-RATS) pulmonary resections for early-stage lung cancer. Technical details of surgical steps are accurately described and commented on.ResultsTwenty-four consecutive patients with lung cancer underwent U-RATS anatomical pulmonary resections at our institute. All procedures were completed with the uniportal approach. The mean operative time was 210 min (range 120–350); in the last 10 cases, the operative time was significantly reduced (180 min) compared to the first 10 cases (232 min) (p

Background and aims: The dynamics and implications of intracoronary thrombus constituency in patients with ST-segment elevation myocardial infarction (STEMI) are not fully understood. We evaluated the expression of CD34, CD61and factor VIII surface markers in thrombi of patients with STEMI and its association with clinical and angiographic characteristics and major adverse cardiovascular events (MACE). Methods: Patients presenting with STEMI undergoing aspiration thrombectomy during primary percutaneous coronary intervention (pPCI) were included. Morphological, histopathological and immunohistochemical aspects of thrombi were assessed by two pathologists blinded to clinical variables and outcomes. Results: The mean age of the 245 patients included was 58 ± 12 years old, and 70 % were men. Regarding the thrombi microscopic patterns, 61 % were classified as recent, 20 % as lytic and 19 % as organized. There were higher levels of the CD61 index in patients with a history of heart failure. Smokers presented lower CD61 positive cells and CD61 index, but this association did not remain significant after multivariable analysis. There was an inverse correlation between CD61 positive cells and CD61 index with the time from onset of pain to the first medical contact, but no other significant association amongst clinical characteristics and antigenic expression. There was higher expression of the CD61 antigen in patients with in-hospital MACE, but statistical significance was borderline (p = 0.06). Conclusions: In this cohort of patients with STEMI, immunohistochemistry of coronary thrombus showed a significantly higher platelet content in patients with previous heart failure and a trend in those with in-hospital MACE. Thrombus' platelet content was inversely related to ischemic time.

Abstract Background A high prevalence of cardiovascular risk factors including age, male sex, hypertension, diabetes, and tobacco use, has been reported in patients with Coronavirus disease 2019 (COVID-19) who experienced adverse outcome. The aim of this study was to investigate the relationship between cardiovascular risk factors and in-hospital mortality in patients with COVID-19. Methods MEDLINE, Cochrane, Web of Sciences, and SCOPUS were searched for retrospective or prospective observational studies reporting data on cardiovascular risk factors and in-hospital mortality in patients with COVID-19. Univariable and multivariable age-adjusted analyses were conducted to evaluate the association between cardiovascular risk factors and the occurrence of in-hospital death. Results The analysis included 45 studies enrolling 18,300 patients. The pooled estimate of in-hospital mortality was 12% (95% CI 9–15%). The univariable meta-regression analysis showed a significant association between age (coefficient: 1.06; 95% CI 1.04–1.09; p

Abstract Background It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes–ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19. Methods The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality. Results A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73–0.85, p

Tetralogy of Fallot (TOF) is a heterogeneous congenital heart disease that is occasionally diagnosed during adulthood. However, although they are often asymptomatic, adult patients with uncorrected TOF often have a poor prognosis. Poor outcomes indicate the importance of the identification and management of these patients, especially in the context of intercurrent disease or noncardiac surgery. We describe a case of clinically silent TOF in a 51-year-old woman. TOF was unmasked during a major noncardiac surgery for a polytrauma and successfully treated with the cooperation of a multidisciplinary team. (Level of Difficulty: Advanced.)

IntroductionPromoting standardization and quality assurance (QA) in oncology on the strength of real-world data is essential to ensure better patient outcomes. Wide excision after primary tumor biopsy is a fundamental step in the therapeutic pathway for cutaneous malignant melanoma (CMM). The aim of this population-based cohort study is to assess adherence to wide local excision in a cohort of patients diagnosed with CMM and the impact of this recommended procedure on overall and disease-specific survival.Materials and MethodsThis retrospective cohort study concerns CMM patients diagnosed in the Veneto region (north-east Italy) in 2017, included in the high-resolution Veneto Cancer Registry, and followed up through linkage with the regional mortality registry up until February 29th, 2020. Using population-level real-world data, linking patient-level cancer registry data with administrative records of clinical procedures may shed light on the real-world treatment of CMM patients in accordance with current guidelines. After excluding TNM stage IV patients, a Cox regression analysis was performed to test whether the completion of a wide local excision was associated with a difference in melanoma-specific and overall survival, after adjusting for other covariates.ResultsNo wide excision after the initial biopsy was performed in 9.7% of cases in our cohort of 1,305 patients. After adjusting for other clinical prognostic characteristics, Cox regression revealed that failure to perform a wide local excision raised the hazard ratio of death in terms of overall survival (HR = 4.80, 95% CI: 2.05–11.22, p < 0.001) and melanoma-specific survival (HR = 2.84, 95% CI: 1.04–7.76, p = 0.042).ConclusionBy combining clinical and administrative data, this study on real-world clinical practice showed that almost one in ten CMM patients did not undergo wide local excision surgery. Monitoring how diagnostic-therapeutic protocols are actually implemented in the real world may contribute significantly to promoting quality improvements in the management of oncological patients.

Despite the fact that elderly patients represent a prevalent and challenging population in the current practice, few data exist on the impact of platelet parameters on cardiovascular risk in these patients. Therefore, the aim of the present study was to evaluate the impact of age on the immature platelet count (IPC) and their relationship with CAD. We included a total of 2236 consecutive patients undergoing coronary angiography in a single center. Elderly patients (age ≥ 75 years) were 756 (33.7%). IPC was measured at admission. Elderly patients were more often females (p < .001), with lower BMI and prevalence of smokers (p < .001), and a more complex cardiovascular risk profile and coronary disease (p = .02). Platelet count decreased with aging (p = .05), whereas no difference in the mean IPC was found between patients < or ≥75 years. In fact, advanced age did not emerge as an independent predictor of IPC above III tertile (≥8.6*10^6/ml), (adjusted OR[95%CI] = 0.97[0.78–1.21], p = .79). When considering elderly patients according to tertiles values of IPC (

Several preclinical studies suggested a potential benefit from combined treatment with inhibitors of epidermal growth factor receptor (EGFR) and angiogenesis, both effective in patients with advanced non-small-cell lung cancer (NSCLC). In pretreated patients with advanced EGFR wild type NSCLC, bevacizumab plus erlotinib improved progression-free survival as second-line therapy in the BeTa study and as maintenance therapy in the ATLAS trial, although the benefit was modest and did not translate into an advantage in overall survival. Disappointing results were reported with oral VEGF inhibitors plus erlotinib in pretreated patients with EGFR wild type NSCLC. On the contrary, erlotinib plus bevacizumab or ramucirumab showed a clinically relevant improvement of progression-free survival in naïve patients with EGFR mutations, leading to the approval of these two regimens as first-line treatment of NSCLC patients with EGFR mutant tumors. Several clinical studies are evaluating the feasibility and activity of osimertinib plus bevacizumab or ramucirumab. However, limits that could affect its use in clinical practice are the need of an intravenous infusion for angiogenesis inhibitors, the increased incidence of treatment associated adverse events, the exclusion of patients with tumors located in central position or at risk of hemorrhage. The identification of predictive biomarkers is an important goal of research to optimize the combined use of these agents.

Background: The identification of preventive strategies, such as statin therapy, is crucial for the management of contrast-induced nephropathy (CIN). Several studies showed the association between KIF6 polymorphism (replacement of Trp719 with Arg) and an increased cardiovascular risk, while others showed a correlation between ‘pleiotropic’ effects of statins and a reduction in cardiovascular events in the population with the risk allele due to the documented modulation of response to statin by KIF6 polymorphism. Aim of this study is to assess the impact of KIF6 polymorphism on the development of CIN. Methods: We analysed 1253 consecutive patients undergoing coronary angiography/PCI. Serum creatinine was collected at baseline, 24 and 48 hours after contrast exposure. We identified the different allelic patterns and assessed the incidence of CIN (absolute increase of 0.5mg/dL or relative >25% in creatinine at 24 and 48h). Results: KIF6 Arg mutation was found in 669 patients (heterozygotes n = 525, homozygotes n = 144). The total prevalence of CIN was 12.5% and we did not find any association between KIF6 polymorphism and CIN development (11.3%, 13.7%, 13.2% p = 0.30). At subgroups analysis among statin ‘naïve’ patients we found a higher prevalence of CIN in homozygous patients as compared to wild-type (20.7% vs 11.3%, p = 0.05), while opposite results were observed among patients with statin therapy (8.6% vs 13.2%, p = 0.28). Conclusion: KIF6 homozygous Arg was associated with a significant increase in the risk of CIN only among statin naive patients. Future studies are needed to evaluate the beneficial effects of statin especially in this subset of patients.

Historic quarters have been a significant component in creating the identity of historical cities in Iran. In the contemporary era, many of these historic landscapes have faced the collapse of their traditional and social foundations and been subjected to the degradation of their cultural, social and physical values. Given the dominant role of religion in the orientation of the political system in Iran, this article examines how religious differences have created significant spatial transformations in historic urban landscapes for religious minorities. Selecting the historic Armenian quarter in Isfahan (Julfa) as the case study, a new model for the preservation of historic landscapes in ghettos on a national scale has been proposed after having carried out the relevant research. Given the capacities in the constitution of the Islamic Republic of Iran, the findings of this research show that the model of federalism, if integrated into public policy, can promote the social freedom and rights of religious minorities in Iran by increasing the participation of local community and consequently, result in the sustainability of historic urban landscapes in the planning process.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been arisen on the use of renin-angiotensin system inhibitors (RASI) due to the potentially increased expression of Angiotensin-converting-enzyme (ACE)2 and patient's susceptibility to SARS-CoV2 infection. Diabetes mellitus have been recognized favoring the coronavirus infection with consequent increase mortality in COVID-19. No data have been so far reported in diabetic patients suffering from ST-elevation myocardial infarction (STEMI), a very high-risk population deserving of RASI treatment. Methods: The ISACS-STEMI COVID-19 registry retrospectively assessed STEMI patients treated with primary percutaneous coronary intervention (PPCI) in March/June 2019 and 2020 in 109 European high-volume primary PCI centers. This subanalysis assessed the prognostic impact of chronic RASI therapy at admission on mortality and SARS-CoV2 infection among diabetic patients. Results: Our population is represented by 3812 diabetic STEMI patients undergoing mechanical reperfusion, 2038 in 2019 and 1774 in 2020. Among 3761 patients with available data on chronic RASI therapy, between those ones with and without treatment there were several differences in baseline characteristics, (similar in both periods) but no difference in the prevalence of SARS-CoV2 infection (1.6% vs 1.3%, respectively, p = 0.786). Considering in-hospital medication, RASI therapy was overall associated with a significantly lower in-hospital mortality (3.3% vs 15.8%, p

Aunque la capacidad que tiene la reperfusión mecánica de lograr la recanalización epicárdica en casi todas las arterias ocluidas de forma aguda está acreditada, la reperfusión miocárdica óptima sigue siendo un asunto muy controvertido y solo se alcanza en el 50-70% de los pacientes con infarto de miocardio con elevación del segmento ST (IAMCEST)1. Ya se ha demostrado que son varios los factores que influyen en la reperfusión miocárdica incluido el grado de flujo TIMI (Thrombolysis in Myocardial Infarction), el tiempo de isquemia, la edad avanzada, la diabetes, la carga trombótica y el tamaño del vaso1-3. Por eso durante las últimas décadas, se han llevado a cabo diferentes estudios sobre tratamientos adyuvantes y dispositivos para mejorar la reperfusión tales como las terapias antitrombóticas4-5 y la trombectomía6. El uso de stents coronarios, sobre todo stents farmacoactivos, es el tratamiento estándar7 habiéndose puesto especial atención durante la última década a las técnicas de implante de stent8 y a cómo influyen estas en los resultados de la intervención. En un artículo publicado recientemente en REC: Interventional Cardiology, Vega et al.9 realizaron un ensayo aleatorizado para analizar el impacto que tiene la velocidad de desinflado del balón que despliega el stent en la perfusión miocárdica y...

Although mechanical reperfusion has been shown to achieve epicardial recanalization in almost all acutely occluded arteries, the optimal myocardial reperfusion still remains a major issue, and it is only achieved in barely 50% to 70% of the patients with ST- segment elevation myocardial infraction (STEMI).1 Several factors have been demonstrated to have an impact on myocardial reperfusion including preoperative Thrombolysis in Myocardial Infarction (TIMI) flow, ischemia time, ageing, diabetes, thrombus burden, and vessel size.1-3 Therefore, over the last few decades, several studies have been conducted on adjunctive therapies and devices to improve reperfusion such as antithrombotic therapies,4-5 and thrombectomy.6 The use of coronary stents, in particular drug-eluting stents, currently represents the standard of care,7 and considerable attention has been paid over the last decade on stenting techniques,8 and their impact on procedural results and outcomes. In a paper recently published in REC: Interventional Cardiology, Vega et al.9 conducted a randomized trial to address the impact of the delivery system speed deflation on myocardial perfusion and the outcomes of patients with STEMI treated with direct stenting. In fact, fast balloon deflation has been suggested to cause abrupt changes in coronary flow that may trigger the detachment of thrombotic material, and plaque fragments, disrupted by...

Background: Concerns have been raised on a potential interaction between renin-angiotensin system inhibitors (RASI) and the susceptibility to coronavirus disease 2019 (COVID-19). No data have been so far reported on the prognostic impact of RASI in patients suffering from ST-elevation myocardial infarction (STEMI) during COVID-19 pandemic, which was the aim of the present study. Methods: STEMI patients treated with primary percutaneous coronary intervention (PPCI) and enrolled in the ISACS-STEMI COVID-19 registry were included in the present sub-analysis and divided according to RASI therapy at admission. Results: Our population is represented by 6095 patients, of whom 3654 admitted in 2019 and 2441 in 2020. No difference in the prevalence of SARSCoV2 infection was observed according to RASI therapy at admission (2.5% vs 2.1%, p = 0.5), which was associated with a significantly lower mortality (adjusted OR [95% CI]=0.68 [0.51–0.90], P = 0.006), confirmed in the analysis restricted to 2020 (adjusted OR [95% CI]=0.5[0.33–0.74], P = 0.001). Among the 5388 patients in whom data on in-hospital medication were available, in-hospital RASI therapy was associated with a significantly lower mortality (2.1% vs 16.7%, OR [95% CI]=0.11 [0.084–0.14], p

Residual high on-treatment platelet reactivity (HTPR) despite dual antiplatelet therapy (DAPT) has emerged as a predictor of major ischemic events in patients undergoing percutaneous coronary interventions (PCIs), especially after an acute cardiovascular event. However, its determinants are still poorly defined. Therefore, the aim of the present study was to evaluate the role of the percentage of reticulated platelets on HTPR in patients on DAPT with ASA (100–160 mg) and prasugrel (10 mg). Platelet reactivity and the reticulated platelets fraction (immature platelets fraction [IPF]) were assessed at 30–90 days after an acute coronary syndrome. Aggregation was assessed by multiple-electrode aggregometry. HTPR was defined as ADP test > 417 AU × min. Our population is represented by 180 ACS patients undergoing stent implantation, divided according to median values of IPF (

Abstract City brand is a valuable asset that improves the competitive advantage of the city in the globalisation era. Relying on uniqueness and utilising various methods, cities endeavour to promote their reputation and sustainability level by attracting the capital and human resources. In the intense competition between the global cities, recognition of the factors that enhance the city’s reputation will improve urban planning and management framework. This study explores how the city could obtain the reputation that it deserves through a more in-depth study of the city branding phenomenon. For this purpose, some of the city branding practices criticised using the empirical analysis method. The finding highlights that although city branding with its complex nature is an effective tool for promoting the city’s reputation, residents and their priorities have an insufficient concentration in many city branding practices.

Heritage planning is the preservation, conservation, rehabilitation, restoration and management of heritage resources. This paper aims to propose an approach for specifying the values and importance of historic sites. In this study, the Historic Ur­ban Landscape approach is taken as the research framework. This approach mo­ves beyond the preservation of the physical environment and focuses on the entire human environment with all its tangible and intangible qualities. It seeks to increa­se the sustainability of planning and design interventions by taking into account the existing built environment, intangible heritage, cultural diversity, socio-economic and environmental factors along with local community values. This study indicates that a values-centered planning approach has emerged as a way of formalizing strategies for dealing with preservation challenges. The importance of values-centered preserva­tion is the framework it offers for dealing holistically with historic sites and addressing both the contemporary and historic values of a place, a task which includes a report comprising written material and graphic material. The contents of the report should be arranged to suit the site and the limitations on the task, but it will generally be in two sections: first, the assessment of cultural significance and second, the statement of cultural significance. Therefore, determining the significance of historic places is to be considered as the basis for planning and implementing management strategies and sustainable development. Furthermore, heritage planning needs a progression that goes from identification, to evaluation, to management and together form a basis for preservation policies.

Musica e luce hanno avuto da sempre un reciproco connubio implicito o esplicito. L’una e l’altra di richiamano sovente e, alcune volte, diventano talmente vicine fino a confondersi l’una nell’altra. In un recente volume di Gianni Bietti, significativamente titolato “La musica della luce” esplora il periodo più fertile del connubio implicito: quello dell’Illuminismo, o meglio quello che incrocia lo spirito dell’illuminismo, ovvero la luce della ragione che doveva guidare l’agire pratico degli uomini.

Conflicting results have been reported so far in pooled analyses and studies evaluating the optimum duration of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients. However, randomized clinical trials dedicated to this specific setting of higher thrombotic risk patients have only recently been completed, pointing at the noninferiority of a shorter strategy as compared to the traditional 12-month DAPT, furthermore allowing to reduce the risk of major bleeding complications. Therefore, a reconsideration of current clinical practice and guidelines should be certainly be advocated in light of the most recent updates, especially among ACS patients treated with percutaneous coronary intervention (PCI) and modern drug-eluting stents (DES). Our aim was to provide a comprehensive review of the available evidence on the optimal DAPT duration in ACS patients.

Vaccination against SARS-CoV-2 will likely be the most promising way to combat the pandemic. Even if mass vaccination is urgent, it should still always be supported by appropriate patient safety management. The aim of this study, based on failure mode, effects and criticality analysis (FMECA), was to identify possible failures and highlight measures that can be adopted to prevent their occurrence. A team of resident doctors in public health from the University of Padua and specialists in risk analysis in public health examined the mass vaccination process. A diagram was drafted to illustrate the various phases of mass vaccination, analyze the process, and identify all failure modes. Criticalities were ascertained by rating the severity, frequency and likelihood of failure detection on a scale of 1 to 10. We identified a total of 71 possible faults distributed over the various phases of the process, and 34 of them were classified as carrying a high risk. For the potentially high-risk failure modes, we identified 63 recommended actions to contain the cause of their occurrence or improve their detection. For the purpose of detecting potential failures, FMECA can be successfully applied to mass vaccination, which should be considered a high-risk process.

Background Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to characterize average daily ischemic rates (ADIRs) and average daily bleeding rates (ADBRs) over 1 year in patients aged >74 years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly ACS 2 trial, comparing low‐dose prasugrel (5 mg daily) with clopidogrel (75 mg daily). Methods and Results ADIRs and ADBRs were calculated as the total number of events, including recurrent events, divided by the number of patient‐days of follow‐up and assessed within different clinical phases: acute (0–3 days), subacute (4–30 days), and late (31–365 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of ADIRs and ADBRs and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, ADIRs were 2.6 times (95% CI, 2.4–2.9) higher than ADBRs. ADIRs were significantly higher in the clopidogrel arm than in the low‐dose prasugrel arm in the subacute phase (Padj

Climate change has dramatically affected the rainfall patterns and water systems in Central Italy. The vulnerability of this area to climate change and natural hazards necessitates that appropriate adaptation policies be put in place to protect heritage sites. This study aims to develop a cultural and natural heritage conservation framework for Central Italy that enhances the capacity of climate change adaptation for heritage resources. For this purpose, a comparison was made between the UNESCO (United National Educational, Scientific and Cultural Organization) Convention of 1972 and the European Landscape Convention of the Council of Europe to achieve a coherent vision for the protection of heritage resources in Europe. After describing the impacts of climate change on heritage resources in Central Italy, we analyze and suggest improvements to the conservation framework for wisely protecting heritage resources in a changing climate. The findings reveal that conservation sectors require assessments of the value of heritage resources at the territorial scale to effectively define conservation priorities, assess the vulnerabilities, and more precisely direct funding. In this respect, the integration of the European Landscape Convention with territorial planning may boost the unity of a conservation framework in terms of climate change while providing new opportunities for conservation authorities to develop adaptation policies.

Ethics applied to environment and landscape is a topic that has a wide range of approaches. The shared acknowledgement of environment as a value, is not enough to guarantee clear indications about how to inhabit it. Just a few words, to which the human experience assigned a key role in evaluating the correctness of our acts, guide us : solidarity, justice, quality of life, responsibility.

Focus of the paper are the models and practices of regional spatial planning activated in Italy in the most recent years, in order to evidence the innovation occurred and the challenges that regional planning institutions are facing. Compared to a theoretical and legislative framework that tends to separate the different types of regional planning (spatial, landscape, development planning), the experimental framework is characterized by pluralistic approaches in which a balance between a normative and a strategic nature of the territorial plan is searched, in order to introduce perspectives of economic and social development. In a continuous process of institutional reflexivity and learning, the regional institutions have now achieved that the notion of 'region' has become more about social interaction than geographical location. For that, interesting experiences of intraregional and interregional cooperation are developing, as called Interregional table of PadanoAlpine-Maritime Macro Area in Northern Italy, a place-based approach generating supra-local shared visions that are of a certain interest.

A partir de los años 40 del siglo XVI, el Ducado de Milán afrontó el problema de la financiación estatal a largo plazo sustituyendo progresivamente el mecanismo de los préstamos forzosos por la emisión directa de títulos de deuda pública, libremente suscritos, garantizados por un determinado ingreso fiscal destinado al pago de los intereses. Si el gobierno del ducado se vio empujado hacia esta dirección por el enorme desajuste de sus cuentas, el notable crecimiento de esta nueva forma de financiación, se concretó gracias a la buena acogida que tuvo por parte de una vasta pluralidad de sujetos, poseedores de fondos, que encontraron esta inversión acorde con sus propias exigencias. La generalización de la deuda pública y su exponencial incremento no parecen haberse traducido en un estéril drenaje de riqueza privada hacia objetivos bélicos y ni siquiera haber tenido efectos distorsionadores sobre la evolución de la economía real. Con la utilización de documentación proveniente del Archivio di Stato di Milano, del Archivo General de Simancas, de la Biblioteca Nazionale Braidense y del Archivio Storico della Camera di Commercio di Milano, para el caso lombardo se puede demostrar que esta forma de endeudamiento público a largo plazo, actuando en una situación de expansión monetaria, no desplazó las inversiones productivas, haciendo disminuir su flujo o encareciéndolas. Por el contrario, produjo un efecto prociclico tanto durante la fase expansiva entre la segunda mitad del siglo XVI y 1620 como en la reorganización económica que tuvo lugar después.

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OBJETIVO: Analisar o comportamento histológico do ELB, produzido conforme protocolo desenvolvido pelo autor principal, em seres humanos no decorrer de 49 meses através da aferição da proporção enxerto/osso neoformado em relação ao total de área mineralizada. MÉTODOS: Série de casos com 12 pacientes, oito femininos (66%) e quatro masculinos (34%), totalizando 13 biópsias, nos quais utilizou-se ELB e que posteriormente houve necessidade de reintervenção cirúrgica, no período de 2000 a 2011. As lâminas produzidas, coradas com hematoxilina-eosina (HE), foram analisadas por patologista e digitalizadas para a avaliação proposta. RESULTADOS: A média etária foi de 57 anos e o tempo médio de seguimento de 49 meses (6-115). A proporção média de ELB foi de 42% (13-85) e de osso neoformado de 58% (15-87) em relação ao total de área mineralizada. CONCLUSÕES: O presente estudo demonstra que o ELB utilizado apresenta característica osteocondutora e biocompatibilidade. O ELB apresentado é opção terapêutica a ser utilizada em cirurgias ortopédicas que necessitem preenchimento de deficiências ósseas.OBJECTIVE: To analyze the histological behavior of bovine lyophilized grafts (BLG) produced according to a protocol developed by the first author, in humans over a 49-month period by measuring the graft/bone neoformation ratio in relation to the total mineralized area. METHODS: This was a case series involving 12 patients: eight females (66%) and four males (34%), totaling 13 biopsies. BLG was used, and surgical reintervention was subsequently required during the period 2000 to 2011. The slides produced were stained with hematoxylin-eosin (HE), were analyzed by a pathologist and were digitized for the proposed evaluation. RESULTS: The mean age was 57 years and the mean follow-up was 49 months (range: 6-115). The average proportion of BLG was 42% range: 13-85) and neoformed bone, 58% (range: 15-87) in relation to the total area mineralized. CONCLUSIONS: This study demonstrated that the BLG used presented osteoconductive characteristics and biocompatibility. BLG is a therapeutic option that can be used in orthopedic surgery in which bone defects need to be filled.

Um banco de tumores com organização sistematizada das informações permite a elaboração de pesquisas em câncer com conclusões sólidas e científicas. Assim, há a necessidade de um protocolo específico, cuja principal vantagem seria a de agregar informações qualificadas sobre o doador às amostras tumorais utilizadas para a pesquisa. O objetivo deste trabalho foi desenvolver um protocolo de procedimentos simples, confiável e reproduzível, para adquirir e armazenar amostras de tumores do sistema músculo-esquelético. O planejamento deste protocolo tem como base os dados da literatura relacionada a bancos de tecidos neoplásicos, no período de 1969 a 2005. Descreve a captação, armazenamento das amostras e o histórico do doador. O banco de tumores com um protocolo eficiente permite armazenar amostras de tecido normal e neoplásico, além de registrar dados referentes a pacientes com lesões neoplásicas. Além disso, possibilita o fornecimento, aos pesquisadores em câncer, de amostras de tecido em condições ideais para a pesquisa.A Tumor Bank with systematic organization of data allows for the carrying out of cancer research with sound and scientific conclusions. The need thus arises for a specific protocol whose main advantage would be that of adding qualified donor information to tumor samples used in research. The purpose of this study was to develop a simple, reliable, and replicable procedures protocol to acquire and store samples of musculoskeletal tumors. The basis for the planning of this protocol comprises the information gathered in the literature relating to tumor tissue banks from 1969 to 2005. The paper describes the capture, storage, and donor background. The tumor bank with an efficient protocol allows to store both healthy and neoplastic tissue, and to record information relating to patients with neoplastic lesions. Furthermore, it enables supplying tissue samples in ideal research conditions.

Background. Despite guideline recommendations, chest radiography (CR) for the diagnosis of community-acquired pneumonia (CAP) in children is commonly used also in mild and/or uncomplicated cases. The aim of this study is to assess the reliability of lung ultrasonography (LUS) as an alternative test in these cases and suggest a new diagnostic algorithm.Methods. We reviewed the medical records of all patients admitted to the pediatric ward from February 1, 2013 to December 31, 2014 with respiratory signs and symptoms. We selected only cases with mild/uncomplicated clinical course and in which CR and LUS were performed within 24 h of each other. The LUS was not part of the required exams recorded in medical records but performed independently. The discharge diagnosis, made only on the basis of history and physical examination, laboratory and instrumental tests, including CR (without LUS), was used as a reference test to compare CR and LUS findings.Results. Of 52 selected medical records CAP diagnosis was confirmed in 29 (55.7%). CR was positive in 25 cases, whereas LUS detected pneumonia in 28 cases. Four patients with negative CR were positive in ultrasound findings. Instead, one patient with negative LUS was positive in radiographic findings. The LUS sensitivity was 96.5% (95% CI [82.2%–99.9%]), specificity of 95.6% (95% CI [78.0%–99.9%]), positive likelihood ratio of 22.2 (95% CI [3.2–151.2]), and negative likelihood ratio of 0.04 (95% CI [0.01–0.25]) for diagnosing pneumonia.Conclusion. LUS can be considered as a valid alternative diagnostic tool of CAP in children and its use must be promoted as a first approach in accordance with our new diagnostic algorithm.