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Abstract Instrumental activities of daily living (IADL) are significant health indicators closely related to executive functions and able to detect mild cognitive impairment. A decline in IADL usually precedes ADL limitation, including taking medications, and may therefore predict a cognitive decline. We aimed to investigate the association of patients’ IADL score with other clinical factors, with a particular focus on the presence of a caregiver, and the impact on adherence to androgen receptor pathway inhibitors (ARPIs) and survival outcomes within the Meet-URO 5—ADHERE study. It was a large prospective multicentre observational cohort study monitoring adherence to ARPIs in 234 metastatic castrate-resistant PC (mCRPC) patients aged ≥ 70. We observed an association between impaired IADL and lower geriatric G8 scores (p

BackgroundImmune-checkpoint inhibitors (ICIs) have significantly improved metastatic renal cell carcinoma (mRCC) prognosis, although their efficacy in patients with bone metastases (BMs) remains poorly understood. We investigated the prognostic role of natremia in pretreated RCC patients with BMs receiving immunotherapy.Materials and methodsThis retrospective multicenter study included RCC patients with BMs receiving nivolumab as second-line therapy or beyond. Inclusion criteria involved baseline sodium levels (pre-ICI) and sodium levels after 4 weeks of nivolumab initiation (post-ICI). The population was divided into two groups based on the median value, and response rates, progression-free survival (PFS), and overall survival (OS) were assessed.ResultsAmong 120 eligible patients, those with pre-treatment sodium levels ≥140 mEq/L showed longer OS (18.7 vs. 12.0 months, p=0.04). Pre-treatment sodium levels ≥140 mEq/L were associated with better OS compared to levels

This study addresses the imperative need for adaptation strategies to climate impacts in coastal areas, particularly vulnerable to climate change effects. Under the Interreg project “AdriaClim,” our research aims to provide a comprehensive account of predicted climate impacts and corresponding adaptation measures for three key sectors for the coastal economy of the Puglia region (Southern Italy): coastal erosion, aquaculture, and tourism. Analyzing regional climate projections, predicted climatic anomalies for Apulia have been delineated. Together with a comprehensive description of the investigated sectors, the expected sectoral climate impacts have been identified. The respective adaptation measures for each sector have been evaluated in terms of coherence with the studied context and effectiveness, among those proposed in the literature. In aquaculture, climate change may influence ecosystem structure, functionality, production cycles, infrastructure, and organism physiology. Integrated multitrophic aquaculture (IMTA) emerges as a solution to enhance the resilience of Apulian aquatic production systems to climate change. For coastal tourism, the vulnerability to various climate impacts is emphasized. These impacts can directly influence tourist flows or indirectly alter the attractiveness of the Apulian Adriatic coast. Given the sector's strong ties to anthropic, natural, and cultural elements, a comprehensive adaptive approach proves most effective. Concerning coastal erosion, results underscore the prevalence of numerous stretches of eroding low coastline, with future projections indicating scenarios of widespread retreat along the southern Adriatic coast. Consequently, protective, and coastal management measures become imperative. The analyses and the obtained results serves as a valuable knowledge framework essential for formulating a climate change adaptation plan for the Apulian Adriatic coast, aligning with the regional authorities' orientations.

BackgroundImmunotherapies exhibit peculiar cancer response patterns in contrast to chemotherapy and targeted therapy. Some patients experience disease response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be continued after radiological progression if clinical benefit is observed. As a result, estimating progression-free survival (PFS) based on the first disease progression may not accurately reflect the actual benefit of immunotherapy.MethodsThe Meet-URO 15 study was a multicenter retrospective analysis of 571 pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. Time to strategy failure (TSF) was defined as the interval from the start of immunotherapy to definitive disease progression or death. This post-hoc analysis compared TSF to PFS and assess the response and survival outcomes between patients treatated beyond progression (TBP) and non-TBP. Moreover, we evaluated the prognostic accuracy of the Meet-URO score versus the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score based on TSF and PFS.ResultsOverall, 571 mRCC patients were included in the analysis. Median TSF was 8.6 months (95% CI: 7.0 – 10.1), while mPFS was 7.0 months (95% CI: 5.7 – 8.5). TBP patients (N = 93) had significantly longer TSF (16.3 vs 5.5 months; p < 0.001) and overall survival (OS) (34.8 vs 17.9 months; p < 0.001) but similar PFS compared to non-TBP patients. In TBP patients, a median delay of 9.6 months (range: 6.7-16.3) from the first to the definitive disease progression was observed, whereas non-TBP patients had overlapped median TSF and PFS (5.5 months). Moreover, TBP patients had a trend toward a higher overall response rate (33.3% vs 24.3%; p = 0.075) and disease control rate (61.3% vs 55.5%; p = 0.31). Finally, in the whole population the Meet-URO score outperformed the IMDC score in predicting both TSF (c-index: 0.63 vs 0.59) and PFS (0.62 vs 0.59).ConclusionWe found a 2-month difference between mTSF and mPFS in mRCC patients receiving nivolumab. However, TBP patients had better outcomes, including significantly longer TSF and OS than non-TBP patients. The Meet-URO score is a reliable predictor of TSF and PFS.

Application of an electric stimulus to a material with a metal-insulator transition can trigger a large resistance change. Resistive switching from an insulating into a metallic phase, which typically occurs by the formation of a conducting filament parallel to the current flow, is a highly active research topic. Using the magneto-optical Kerr imaging, we found that the opposite type of resistive switching, from a metal into an insulator, occurs in a reciprocal characteristic spatial pattern: the formation of an insulating barrier perpendicular to the driving current. This barrier formation leads to an unusual N-type negative differential resistance in the current-voltage characteristics. We further demonstrate that electrically inducing a transverse barrier enables a unique approach to voltage-controlled magnetism. By triggering the metal-to-insulator resistive switching in a magnetic material, local on/off control of ferromagnetism is achieved using a global voltage bias applied to the whole device.

Abstract Several modeling tools commonly used for supporting flood risk assessment and management are highly effective in representing physical phenomena, but provide a rather limited understanding of the multiple implications that flood risk and flood risk reduction measures have on highly complex systems such as urban areas. In fact, most of the available modeling tools do not fully account for this complexity—and related uncertainty—which heavily affects the interconnections between urban systems evolution and flood risk, ultimately resulting in an ineffective flood risk management. The present research proposes an innovative methodological framework to support decision‐makers involved in an urban regeneration process at a planning/strategic level, accounting for the multi‐dimensional implications of flood risk and of different flood risk management strategies. The adopted approach is based on the use of System Thinking principles and participatory System Dynamics modeling techniques, and pursues an integration between scientific and stakeholder knowledge. Reference is made to one of the case studies of the CUSSH and CAMELLIA projects, namely Thamesmead (London), a formerly inhospitable marshland currently undergoing a process of urban regeneration, and perceived as being increasingly vulnerable to flooding. It represents an interesting opportunity for building a replicable modeling approach to integrate urban development dynamics with flood risk, ultimately supporting policy and decision‐makers in identifying mitigation/prevention measures and understanding how they could help achieve multi‐dimensional benefits (e.g., environmental, social and economic).

Background: Up to 30% of patients with metastatic castration-resistant prostate cancer (mCRPC) develop visceral metastases, which are associated with a poor prognosis. Objectives: Efficacy of enzalutamide in mCRPC patients with measurable metastases, including visceral and/or extra-regional lymph nodes. Methods: In this phase II multicenter study, patients with mCRPC and measurable metastases received enzalutamide as the first line. Primary endpoint: 3-month (mo) disease control rate (DCR) defined as the proportion of patients with complete (CR) or partial response (PR) or stable disease (SD) as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoint: safety. Exploratory endpoint: the association between ARv7 splicing variants in basal circulating tumor cell (CTC)-enriched blood samples and treatment response/resistance using the AdnaTest ProstateCancerSelect kit and the AdnaTest ProstateCancer Panel AR-V7. Results: From March 2017 to January 2021, 68 patients were enrolled. One patient never started treatment. Median age: 72 years. A total of 52 patients (78%) received enzalutamide as a first line for mCRPC. The median follow-up was 32 months. At the 3-month assessment, 24 patients presented an SD, 1 patient achieved a CR, and 23 patients had a PR (3-mo-DCR of 72%). Discontinuations due to adverse events (AEs), disease-related death, or disease progression occurred in 9%, 6%, and 48% of patients. All patients reported at least one grade (G) 1–2 AE: the most common were fatigue (49%) and hypertension (33%). Six G3 AEs were reported: two hypertension, one seizure, one fatigue, one diarrhea, and one headache. Basal detection of ARv7 was significantly associated with poor treatment response (p = 0.034) and a nonsignificant association (p = 0.15) was observed between ARv7 detection and response assessments. At month 3, ARv7 was detected in 57%, 25%, and 15% of patients undergoing progressive disease, SD, and PR, respectively. Conclusion: The study met its primary endpoint, showing the efficacy of enzalutamide in men with mCRPC and measurable metastatic lesions in visceral and/or lymph node sites. Trial registration: ClinicalTrials.gov Identifier: NCT03103724. First Posted: 6 April 2017. First patient enrollment: 19 April 2017.

Summary: The neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammatory index (SII) have been reported as prognosticators in non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and melanoma. This analysis of the INVIDIa-2 study on influenza vaccination in patients with cancer treated with immune checkpoint inhibitors (ICIs) assessed NLR and SII on overall survival (OS) by literature-reported (LR), receiver operating characteristic curve (ROC)-derived (ROC) cutoffs or as continuous variable (CV). NLR and SII with ROC cutoffs of

Abstract Background There is little data on the relationship between novel cardiovascular risk factors and silent coronary artery disease (CAD) in diabetic patients. We investigated whether Lipoprotein(a), homocysteine and apolipoprotein(a) polymorphism are associated with angiographically assessed asymptomatic coronary artery disease (CAD) in diabetic patients. Methods 1,971 type 2 diabetic patients without clinical signs of cardiovascular diseases and with a negative history of CAD were consecutively evaluated. Among them, 179 patients showed electrocardiographic abnormalities suggestive of ischemia or previous asymptomatic myocardial infarction. These 179 patients were subjected to a non-invasive test for CAD (ECG stress testing and/or scintigraphy). Among patients with a highly positive stress testing (n = 19) or a positive scintigraphy (n = 74), 75 showed an angiographically documented CAD (CAD group). Seventy-five patients without CAD (NO CAD group) were matched by age, sex and duration of diabetes to CAD patients. In NO CAD patients an exercise ECG test, a 48-hour ambulatory ECG and a stress echocardiogram were negative for CAD. Results Lipoprotein(a) levels (22.0 ± 18.9 versus 16.0 ± 19.4 mg/dl; p < 0.05), homocysteine levels (13.6 ± 6.6 versus 11.4 ± 4.9 mmol/l; p < 0.05) and the percentage of subjects with at least one small apolipoprotein(a) isoform (70.7% versus 29.3%; p < 0.0001) were higher in CAD than NO CAD group. Logistic regression analysis showed that apolipoprotein(a) polymorphism (OR:8.65; 95%CI:3.05–24.55), microalbuminuria (OR:6.16; 95%CI:2.21–17.18), smoking (OR:2.53; 95%CI:1.05–6.08), HDL (OR:3.16; 95%CI:1.28–7.81), homocysteine (OR:2.25; 95%CI:1.14–4.43) and Lipoprotein(a) (OR:2.62; 95%CI:1.01–6.79) were independent predictors of asymptomatic CAD. Conclusions The present investigation shows an independent association of Lipoprotein(a), homocysteine and apo(a) polymorphism with silent CAD. Other studies are needed to establish whether these parameters are suitable for CAD screening in diabetic patients.

IntroductionMultiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS with an autoimmune pathogenesis. Over the years, numerous disease-modifying therapies (DMTs) have proven effective in disease control; to date, there is a need to identify a personalized treatment effective in ensuring disease-free status or no evidence of disease activity (NEDA).Objectiveidentify clinical, demographic and treatment approach characteristics that affect the maintenance of NEDA-3 and the occurrence of clinical relapses during a 6-years follow-up.Materials and methoda retrospective study was conducted on a cohort of MS patients followed up with six-year period. All participants were treated with first- or second-line MS drugs.Clinical relapse, NEDA-3 at 6 years and sustained EDSS were assessed as disease activity outcomes. Patients with follow-up of less than 6 years and insufficient clinical and radiological data were excluded from the study.ResultsTwo-hundred-eighty naive patients (mean age was 49.8 years, SD ± 11.35 years, 23–76, F/M 182/98), with MS were followed up for 6 years.The mean age at diagnosis was 34.3 years (SD ±11.5, 14–62 years), the mean EDSS score at the onset was 1.9 (±1.3), 76.8% of patients had an EDSS below or equal to 2.5 at diagnosis.In the cohort 37 (13.2%) directly received second-line treatment, 243 (86.8%) received first-line drugs.The analysis showed that second-line treatment from beginning had a protective effect for the achievement of NEDA-3 (p = 0.029), on the prevention of clinical relapse (p = 0.018) and on number of relapses (p = 0.010); this finding was confirmed by logistic regression analysis (p = 0.04) and Kaplan–Meier analysis (p = 0.034).ConclusionThe results of this study demonstrate the efficacy of targeted and early intervention so as to act in the right time window, ensuring a favorable outcome in both clinical and radiological terms; this could be decisive in reducing clinical relapse, disease progression and related disability. Therefore, prescribing highly effective drug in the early stages of the disease represents a leading strategy with the most favorable cost–benefit ratio.

Introduction: Androgen receptor pathway inhibitors (ARPIs) have been increasingly offered to older patients with prostate cancer (PC). However, prognostic factors relevant to their outcome with ARPIs are still little investigated. Methods and Materials: The Meet-URO network ADHERE was a prospective multicentre observational cohort study evaluating and monitoring adherence to ARPIs metastatic castrate-resistant PC (mCRPC) patients aged ≥70. Cox regression univariable and multivariable analyses for radiographic progression-free (rPFS) and overall survival (OS) were performed. Unsupervised median values and literature-based thresholds where available were used as cut-offs for quantitative variables. Results: Overall, 234 patients were enrolled with a median age of 78 years (73–82); 86 were treated with abiraterone (ABI) and 148 with enzalutamide (ENZ). With a median follow-up of 15.4 months (mo.), the median rPFS was 26.0 mo. (95% CI, 22.8–29.3) and OS 48.8 mo. (95% CI, 36.8–60.8). At the MVA, independent prognostic factors for both worse rPFS and OS were Geriatric G8 assessment ≤ 14 (p < 0.001 and p = 0.004) and PSA decline ≥50% (p < 0.001 for both); time to castration resistance ≥ 31 mo. and setting of treatment (i.e., post-ABI/ENZ) for rPFS only (p < 0.001 and p = 0.01, respectively); age ≥78 years for OS only (p = 0.008). Conclusions: Baseline G8 screening is recommended for mCRPC patients aged ≥70 to optimise ARPIs in vulnerable individuals, including early introduction of palliative care.

Abstract Background Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era. Methods We investigated the Meet-URO-15 study dataset of 571 pretreated mRCC patients receiving nivolumab as second or further lines about the prognostic role of the previous nephrectomy (received in either the localized or metastatic setting) in the overall population and according to the Meet-URO score groups. Results Patients who underwent nephrectomy showed a significantly reduced risk of death (HR 0.44, 95% CI 0.32–0.60, p

Summary: Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration. Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020. The trial's primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020, the results of which were reported previously. Secondary endpoints (data cut-off Jan 31, 2022) included the outcomes of patients to immunotherapy based on vaccine administration, for which the final results are reported herein. A propensity score matching by age, sex, performance status, primary tumour site, comorbidities, and smoking habits was planned for the present analysis. Only patients with available data for these variables were included. The outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease-control rate (DCR). Findings: The original study population consisted of 1188 evaluable patients. After a propensity score matching, 1004 patients were considered (502 vaccinated and 502 unvaccinated), and 986 of them were evaluable for overall survival (OS). At the median follow-up of 20 months, the influenza vaccination demonstrated a favourable impact on the outcome receiving ICI in terms of median OS [27.0 months (CI 19.5–34.6) in vaccinated vs. 20.9 months (16.6–25.2) in unvaccinated, p = 0.003], median progression-free survival [12.5 months (CI 10.4–14.6) vs. 9.6 months (CI 7.9–11.4), p = 0.049], and disease-control rate (74.7% vs. 66.5%, p = 0.005). The multivariable analyses confirmed the favourable impact of influenza vaccination in terms of OS (HR 0.75, 95% C.I. 0.62–0.92; p = 0.005) and DCR (OR 1.47, 95% C.I. 1.11–1.96; p = 0.007). Interpretation: The INVIDIa-2 study results suggest a favourable immunological impact of influenza vaccination on the outcome of cancer patients receiving ICI immunotherapy, further encouraging the vaccine recommendation in this population and supporting translational investigations about the possible synergy between antiviral and antitumour immunity. Funding: The Federation of Italian Cooperative Oncology Groups (FICOG), Roche S.p.A., and Seqirus.

Abstract Background It is well established that cancer patients infected with SARS‐CoV‐2 are at particularly elevated risk of adverse outcomes, but the comparison of SARS‐CoV‐2 infection risk between cancer patients and cancer‐free individuals has been poorly investigated on a population‐basis. Methods A population‐based study was thus conducted in Friuli Venezia Giulia region, northeastern Italy, to estimate prevalence and determinants of SARS‐CoV‐2 infection among cancer patients, as compared to cancer‐free individuals, and to evaluate adverse outcomes of SARS‐CoV‐2 infection. The study included 263,042 individuals tested for SARS‐CoV‐2 in February–December 2020 with cancer history retrieved through the regional cancer registry. Odds ratios (ORs) of SARS‐CoV‐2 positivity, with corresponding 95% confidence intervals (CIs), were calculated using multivariable logistic regression models, adjusted for sex and age. Hazard ratios (HRs) adjusted for sex and age for intensive care unit (ICU) admission and all‐cause death were estimated using Cox models. Results Among 26,394 cancer patients tested for SARS‐CoV‐2, the prevalence of infection was 11.7% versus 16.2% among 236,648 cancer‐free individuals, with a corresponding OR = 0.59 (95% CI: 0.57–0.62). The prevalence was much higher (29% in both groups) during the second pandemic wave (October–December 2020). Among cancer patients, age ≥80 years and cancer diagnosis ≥13 months before SARS‐CoV‐2 testing were the major risk factors of infection. Among 3098 infected cancer patients, the fatality rate was 17.4% versus 15.8% among 23,296 negative ones (HR = 1.63, 95% CI: 1.49–1.78), and versus 5.0% among 38,268 infected cancer‐free individuals (HR = 1.23, 95% CI: 1.12–1.36). No significant differences emerged when considering ICU admission risk. Conclusion Albeit cancer patients reported reduced SARS‐CoV‐2 infection risk, those infected showed higher mortality than uninfected ones and infected cancer‐free population. Study findings claim for continuing to protect cancer patients from SARS‐CoV‐2, without reducing the level of oncologic care.

Resistive switching usually occurs by the formation of conducting filaments in the direction of current flow. Here the authors study an intriguing type of volatile metal-to-insulator resistive switching in (La,Sr)MnO3, which occurs by the formation of an insulating barrier perpendicular to the current.

BackgroundTreatment choice for metastatic renal cell carcinoma (mRCC) patients is still based on baseline clinical and laboratory factors.MethodsBy a pre-specified analysis of the Meet-URO 15 multicentric retrospective study enrolling 571 pretreated mRCC patients receiving nivolumab, baseline and early dynamic variations (Δ) of neutrophil, lymphocyte, and platelet absolute cell counts (ACC) and their inflammatory ratios (IR) were evaluated alongside their association with the best disease response and overall (OS) and progression-free survival (PFS). Multivariable analyses on OS and PFS between baseline and Δ ACC and IR values were investigated with receiving operating curves-based cut-offs.ResultsThe analysis included 422 mRCC patients. Neutrophil-to-lymphocyte ratio (NLR) increased over time due to consistent neutrophil increase (p < 0.001). Higher baseline platelets (p = 0.044) and lower lymphocytes (p = 0.018), increasing neutrophil Δ (p for time-group interaction

Abstract Tsantsas, commonly referred to as “shrunken heads”, are unique and valuable antiquities that were produced by the Shuar, Achuar, Awajún/Aguaruna, Wampís/Huambisa, and Candoshi-Shampra (SAAWC) peoples until the mid twentieth century. Originally used with ceremonial purpose during important social group functions, tsantsas became monetarily valuable as keepsakes and curios during the nineteenth century as a result of Western/European cultural encroachment. Unmet demand resulted in the production of convincing forgeries that created confusion about the authenticity of existing collections. Ceremonial tsantsas are both human remains and valuable cultural items. Their production and purpose were negatively influenced by colonialism and the outside curio market; as such many institutions may choose to repatriate them to their places of origin. Herein, we report on the authentication and repatriation of a ceremonial tsantsa recently rediscovered in a university’s natural history collection. The personal memoirs of the original collector describe that it originated in the Ecuadorean Amazon. In consultation with the government of Ecuador, it was determined that authentication was required prior to repatriation. The tsantsa was compared to a list of thirty-three distinct characteristics shared by ceremonial tsantsas. These criteria were taken from those provided by Ecuador’s National Cultural Heritage Institute and those found in prior studies from the academic literature; they include notable skin and hair features, structure and facial anatomy, and evidence of traditional fabrication and modification. We were able to affirm 30 of the 33 authenticating indicators. As part of our protocol the tsantsa was scanned with a CT-imaging system. The resulting 3D images were invaluable in discerning subtle and difficult-to-visualize characteristics regarding the skin and patterns of modification, although there are limitations related to the small size of filamentous structures. The results of the authentication were accepted by the Ecuadorean government, and the tsantsa was repatriated in June 2019. An additional benefit of CT-imaging is that data files can be generated in order to create rapid prototypes via 3D printing. In fact, as our work demonstrates, artifacts of value can be repatriated while simultaneously preserved as a volumetric replica for the purposes of a collection.

Some correlated materials display an insulator-to-metal transition as the temperature is increased. In most cases, this transition can also be induced electrically, resulting in volatile resistive switching due to the formation of a conducting filament. While this phenomenon has attracted much attention due to potential applications, many fundamental questions remain unaddressed. One of them is its characteristic lengths: What sets the size of these filaments, and how does this impact resistive switching properties? Here, we use a combination of wide-field and scattering-type scanning near-field optical microscopies to characterize filament formation in NdNiO_{3} and SmNiO_{3} thin films. We find a clear trend: Smaller filaments increase the current density, yielding sharper switching and a larger resistive drop. With the aid of numerical simulations, we discuss the parameters controlling the filament width and, hence, the switching properties.

Guaranteeing the sustainability of irrigation under the increasing pressures related to resource scarcity and climate change is a major global challenge, specifically in water-scarce areas. The present work proposes a methodological approach and a technological solution to improve operation and management of a critical on-demand pressurized irrigation system. The potential of using an innovative off-grid valve, the green valve, for the real-time monitoring and adaptive control is proven through numerical simulations. Particular emphasis is given to the energy balance feasibility of the system during a typical irrigation season. Reference is made to a real network located in southern Italy.

The present work provides an insight into the emergency preparedness and coping capacity of Italian water utilities, based on the results of two ongoing research projects. Specific attention is given to the role that Water Safety Plans (WSPs) may have in this framework. The results of an online survey completed with a wide sample of Italian water utilities have been integrated with the evidence from targeted in-depth interviews, with the aim of: (i) characterizing the state of implementation of WSPs in Italy; (ii) identifying the main challenges, barriers and opportunities; (iii) describing the key issues related to the interactions among different institutions. A critical summary of the main evidence was structured in the form of a SWOT analysis.

There is a growing interest worldwide on the potential of nature-based solutions (NBSs) as measures for dealing with water-related risks while producing multiple co-benefits that can contribute to several societal challenges and many of the sustainable development goals. However, several barriers still hamper their wider implementation, such as mainly the lack of stakeholders’ engagement and the limited integration of stakeholders’ knowledge throughout the phases of NBS design and implementation. This is a crucial aspect to guarantee that the multidimensional implications of NBSs are adequately understood and considered by decision-makers. Innovative methods and tools for improving NBS design and supporting decision-makers in overcoming the main barriers to implementation, ultimately enhancing their effectiveness, are therefore needed. The present work proposes a combined approach based on the integration of fuzzy cognitive maps, hydraulic modeling, and participatory Bayesian belief networks aiming to facilitate the stakeholders’ engagement and the knowledge integration process in NBS design and assessment. The approach was developed and implemented within the NAIAD project in the Lower Danube demo site, specifically oriented to support the process of the Potelu Wetland restoration. First, fuzzy cognitive maps are adopted as a problem structuring method for eliciting stakeholders’ risk perception and problem understanding, and for constructing a causal model describing the system as a whole, with specific attention to the expected role of the NBS in reducing flood risk and addressing the key local challenges. Second, hydraulic modeling is used to analyze the effect of extreme floods starting from the retrospective analysis of a specific event and to model the potential benefits of risk reduction measures. Last, a Bayesian belief network is used to support the model integration process and a scenario analysis with a user-friendly tool. The whole process can be replicated in other areas and is particularly suitable to support an active engagement of stakeholders (both institutional and not) in the process of NBS design and assessment.

Background Until now, no robust data supported the efficacy, safety and recommendation for influenza vaccination in patients with cancer receiving immune checkpoint inhibitors (ICIs).Methods The prospective multicenter observational INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors (INVIDIa-2) study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving ICIs, enrolled in 82 Italian centers from October 2019 to January 2020. The primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020. Secondary endpoints regarded ILI severity and vaccine safety.Results The study enrolled 1279 patients; 1188 patients were evaluable for the primary endpoint analysis. Of them, 48.9% (581) received influenza vaccination. The overall ILI incidence was 8.2% (98 patients). Vaccinated patients were significantly more frequently elderly (p

Background: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need. Methods: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. The complete blood count before the first cycle of therapy was assessed by calculating neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI). Clinical factors included pre-treatment International Metastatic RCC Database Consortium (IMDC) score, line of therapy, and metastatic sites. Results: From October 2015 to November 2019, 571 mRCC patients received nivolumab as second- and further-line treatment in 69% and 31% of cases. In univariable and multivariable analyses all inflammatory indices, IMDC score, and bone metastases significantly correlated with overall survival (OS). The multivariable model with NLR, IMDC score, and bone metastases had the highest c-index (0.697) and was chosen for the developing of the score (Schneeweiss scoring system). After internal validation (bootstrap re-sampling), the final index (Meet-URO score) composed by NLR, IMDC score, and bone metastases had a c-index of 0.691. It identified five categories with distinctive OSs: group 1 (median OS – mOS = not reached), group 2 (mOS = 43.9 months), group 3 (mOS = 22.4 months), group 4 (mOS = 10.3 months), and group 5 (mOS = 3.2 months). Moreover, the Meet-URO score allowed for a fine risk-stratification across all three IMDC groups. Conclusion: The Meet-URO score allowed for the accurate stratification of pretreated mRCC patients receiving nivolumab and is easily applicable for clinical practice at no additional cost. Future steps include its external validation, the assessment of its predictivity, and its application to first-line combinations.