Very-high Risk Research Articles

Potentially Toxic Element Contamination in Soils Affected by the Antimony Mine Spill in Northwest China.

This study provides a comprehensive assessment of the potential ecological and health risks in the area of the antimony mine spill in Longnan, Northwest China, and identifies the sources of potentially toxic elements (PTEs) in the soil as a result of the spill. The geo-accumulation index and enrichment factor show that the study area is highly contaminated with arsenic (As), mercury (Hg) and antimony (Sb). The ecological risk index in the tailings spill area ranged from 320.43 to 5820.46 (mean: 1489.82), indicating a very-high potential ecological risk, with mean values of 104.86, 1118.87 and 248.84 for As, Hg and Sb, respectively. The multivariate statistical analysis suggested that Sb and Hg come from tailings leakage, while copper (Cu), nickel (Ni) and zinc (Zn) may be imported from natural sources, and As and lead (Pb) originate from agricultural activities. In addition As and Sb pose a high health risk. With the exception of the non-carcinogenic risk in adults, all other risks are significantly exceeded in other populations, with children being the highest-risk group. These findings provide important quantitative information for the assessment and management of PTE contamination in other tailings spill areas.

MP63-06 BACILLUS CALMETTE-GUERIN VS IMMEDIATE RADICAL CYSTECTOMY IN EAU DEFINED VERY HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER PATIENTS

You have accessJournal of UrologyCME1 Apr 2023MP63-06 BACILLUS CALMETTE-GUERIN VS IMMEDIATE RADICAL CYSTECTOMY IN EAU DEFINED VERY HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER PATIENTS Roberto Contieri, Patrick Hensley, Wei Shen Tan, Valentina Grajales, Kelly Bree, Charles C Guo, Graciela M Nogueras-Gonzalez, Neema Navai, Colin P Dinney, and Ashish M Kamat Roberto ContieriRoberto Contieri More articles by this author , Patrick HensleyPatrick Hensley More articles by this author , Wei Shen TanWei Shen Tan More articles by this author , Valentina GrajalesValentina Grajales More articles by this author , Kelly BreeKelly Bree More articles by this author , Charles C GuoCharles C Guo More articles by this author , Graciela M Nogueras-GonzalezGraciela M Nogueras-Gonzalez More articles by this author , Neema NavaiNeema Navai More articles by this author , Colin P DinneyColin P Dinney More articles by this author , and Ashish M KamatAshish M Kamat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003321.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: European Association of Urology (EAU) guidelines recommend offering immediate radical cystectomy (iRC) to all very high-risk (VHR) non-muscle invasive bladder cancer (NMIBC) patients and reserving BCG for only those who refuse or are unfit for RC. Herein, we assessed survival outcomes of VHR NMIBC patients treated with BCG versus iRC. METHODS: We performed an IRB approved retrospective study analyzing VHR NMIBC patients according to the EAU definition diagnosed between 2000 and 2020. Survival outcomes between the following patient cohorts were compared: 1) Immediate RC versus BCG and 2) Immediate RC versus delayed RC. Primary endpoint was overall-(OS) and cancer-specific survival (CSS). The cumulative incidence (CI) method was used to estimate the risk of cancer-specific mortality (CSM) after accounting for other causes of death as a competing risk event. Multivariate competing-risks regression analyses were used to predict CSM. RESULTS: A total of 235 VHR patients were identified (157 BCG versus 78 iRC). The median follow-up was 45.8 months. Patients treated with iRC were younger (68 yrs vs. 72 yrs; p<0.01), had a higher prevalence of lymphovascular invasion (LVI) (29.5% vs 4.5%; p<0.01) and variant histology (53.8% vs 16.6%; p<0.01) at diagnosis. The 5-yr OS and CSM were 80.2% and 5.3% in patients undergoing BCG and 88.1% and 4.9% in patients undergoing iRC. Survival outcomes did not significantly differ between the two groups (p=0.604 and p=0.955, respectively; Figure). Treatment strategy was not associated with CSM in the multivariate competing-risk regression model (Sub-standardized Hazard ratio (SHR): 1.54; 95% CI 0.24 – 9.68; p=0.65). Among the patients treated with BCG, 5-yr PF rate was 82.6%. A total of 39 (24.8%) patients underwent delayed RC following recurrence after BCG. Patients who underwent delayed RC did not exhibit worse oncological outcomes relative to those treated with iRC (SHR: 0.66, 95% CI: 0.17-2.61, p=0.56). CONCLUSIONS: Survival outcomes following initial treatment with intravesical BCG (with delayed RC if needed) for selected VHR NMIBC can be effective and oncologically safe. Source of Funding: This research was supported by the Wayne B. Duddlesten Professorship in Cancer Research, the Raymond and Maria Floyd Bladder Cancer Research Foundation Grant, NIH/NCI UTMD Anderson SPORE in Genitourinary Cancer (p50CA091846), the Cancer Center Support Grant (NCI Grant P30 CA016672) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e873 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Roberto Contieri More articles by this author Patrick Hensley More articles by this author Wei Shen Tan More articles by this author Valentina Grajales More articles by this author Kelly Bree More articles by this author Charles C Guo More articles by this author Graciela M Nogueras-Gonzalez More articles by this author Neema Navai More articles by this author Colin P Dinney More articles by this author Ashish M Kamat More articles by this author Expand All Advertisement PDF downloadLoading ...

MP67-04 VALIDATION OF NOVEL PREOPERATIVE RISK CATEGORIES ON THE PREDICTION OF CLINICAL RECURRENCE IN PATIENTS CANDIDATE FOR RADICAL PROSTATECTOMY FOR CLINICALLY LOCALIZED PROSTATE CANCER. RESULTS OF A LARGE, MULTI-INSTITUTIONAL SERIES

You have accessJournal of UrologyCME1 Apr 2023MP67-04 VALIDATION OF NOVEL PREOPERATIVE RISK CATEGORIES ON THE PREDICTION OF CLINICAL RECURRENCE IN PATIENTS CANDIDATE FOR RADICAL PROSTATECTOMY FOR CLINICALLY LOCALIZED PROSTATE CANCER. RESULTS OF A LARGE, MULTI-INSTITUTIONAL SERIES Elio Mazzone, Giorgio Gandaglia, Francesco Barletta, Andrea Necchi, Daniele Raggi, Laura Marandino, Armando Stabile, Vito Cucchiara, Giuseppe Rosiello, Gabriele Sorce, Francesco Pellegrino, Simone Scuderi, Daniele Robesti, Mario De Angelis, Antony Pellegrino, Mattia Longoni, Pietro Scilipoti, Francesco Montorsi, and Alberto Briganti Elio MazzoneElio Mazzone More articles by this author , Giorgio GandagliaGiorgio Gandaglia More articles by this author , Francesco BarlettaFrancesco Barletta More articles by this author , Andrea NecchiAndrea Necchi More articles by this author , Daniele RaggiDaniele Raggi More articles by this author , Laura MarandinoLaura Marandino More articles by this author , Armando StabileArmando Stabile More articles by this author , Vito CucchiaraVito Cucchiara More articles by this author , Giuseppe RosielloGiuseppe Rosiello More articles by this author , Gabriele SorceGabriele Sorce More articles by this author , Francesco PellegrinoFrancesco Pellegrino More articles by this author , Simone ScuderiSimone Scuderi More articles by this author , Daniele RobestiDaniele Robesti More articles by this author , Mario De AngelisMario De Angelis More articles by this author , Antony PellegrinoAntony Pellegrino More articles by this author , Mattia LongoniMattia Longoni More articles by this author , Pietro ScilipotiPietro Scilipoti More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003330.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Most of the preoperative risk tools predicting prostate cancer (PCa) recurrence after radical prostatectomy (RP) considered biochemical recurrence (BCR) as the main endpoint when developed. However, not all patients with a BCR ultimately progress to clinical recurrence (CR). We aimed at internally validating a novel preoperative risk classification in predicting CR in patients treated with RP. METHODS: Overall, 2,901 patients treated with RP and who received pre-op mpMRI between 2014 -2022 at eight referral centers were identified. The study outcome was 5-yr CR defined as positive imaging after BCR. Kaplan-Meier and multivariable Cox regression models tested time and predictors of CR. Predictors consisted of PSA, biopsy grade group, MRI stage (organ-confined vs extracapsular extension vs. seminal vesicles invasion) and maximum diameter of lesion at MRI. These variables defined four risk groups based on the novel classification. The tool accuracy was compared to the EAU risk classification and CAPRA score in predicting 5-year CR using Harrel’s c-index. Decision curve analyses (DCA) compared the net-benefit associated with each of the risk tools. RESULTS: Overall, 937 (32%), 1006 (35%), 848 (30%) and 110 (3%) had low, intermediate, high and very-high risk disease according to the novel classification. Median follow-up was 43 months. At KM analyses, 5-year CR-free survival rates were 94, 90, 83 and 71% in, respectively, low, intermediate, high and very-high risk groups (p<0.01). The novel model tested for prediction CR in Cox regression analyses depicted good discrimination at internal validation (c-index 76%). After testing the accuracy of the EAU risk groups and the CAPRA score in our cohort, the novel model showed higher c index (78 vs. 69 vs. 73%). At DCA, our novel model showed a higher net-benefit compared to other models (Figure 1). CONCLUSIONS: We internally validated a novel preoperative risk tool to predict CR after RP. Our model exhibited higher accuracy as compared to available tools in the prediction of stronger oncologic endpoints at mid-term follow-up. This data reinforces the utility of this patient stratification for preoperative counselling and outcome predictions. Source of Funding: no © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e944 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elio Mazzone More articles by this author Giorgio Gandaglia More articles by this author Francesco Barletta More articles by this author Andrea Necchi More articles by this author Daniele Raggi More articles by this author Laura Marandino More articles by this author Armando Stabile More articles by this author Vito Cucchiara More articles by this author Giuseppe Rosiello More articles by this author Gabriele Sorce More articles by this author Francesco Pellegrino More articles by this author Simone Scuderi More articles by this author Daniele Robesti More articles by this author Mario De Angelis More articles by this author Antony Pellegrino More articles by this author Mattia Longoni More articles by this author Pietro Scilipoti More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement PDF downloadLoading ...

PD39-04 MPMRI OF THE PROSTATE IN PATIENTS CARRYING A HIGH CLINICAL RISK OF PROSTATE CANCER DIAGNOSIS: IS THIS IMAGING TEST NECESSARY FOR DIAGNOSTIC PURPOSES IN THIS SUBSET OF PATIENTS?

PD39-04 MPMRI OF THE PROSTATE IN PATIENTS CARRYING A HIGH CLINICAL RISK OF PROSTATE CANCER DIAGNOSIS: IS THIS IMAGING TEST NECESSARY FOR DIAGNOSTIC PURPOSES IN THIS SUBSET OF PATIENTS?

MP61-12 WHICH MEN WITH CN1 PROSTATE CANCER AT PSMA PET/CT REPRESENT THE IDEAL CANDIDATE TO RADICAL PROSTATECTOMY? DEVELOPMENT OF A NOVEL RISK STRATIFICATION TOOL FOR INDIVIDUALIZED APPROACHES BASED ON A LARGE, MULTI-INSTITUTIONAL SERIES

MP61-12 WHICH MEN WITH CN1 PROSTATE CANCER AT PSMA PET/CT REPRESENT THE IDEAL CANDIDATE TO RADICAL PROSTATECTOMY? DEVELOPMENT OF A NOVEL RISK STRATIFICATION TOOL FOR INDIVIDUALIZED APPROACHES BASED ON A LARGE, MULTI-INSTITUTIONAL SERIES

Cardiovascular toxicity in breast cancer patients - contributors and role of cardioprotective drugs.

Breast cancer (BC) patients treated with anthracyclines and/or anti-HER2-targeted therapies (AHT) are highly associated with cardiovascular toxicity (CVT). Our objective was to evaluate the risk of CVT secondary to cancer treatment and the role of cardioprotective-drugs (CPD) in BC patients. We collected a retrospective cohort of females with BC treated with chemotherapy and/or AHT from 2017 to 2019. CVT was defined as LVEF<50% or decline ≥10% during follow-up. As CPD, we considered renin-angiotensin-aldosterone-system inhibitors and beta-blockers. A subgroup analysis of the AHT patients was also performed. A total of 203 women were enrolled. The majority had high or very-high CVT risk score and normal cardiac function at presentation. As for CPD, 35.5% were medicated pre-chemotherapy. All patients were submitted to chemotherapy; AHT were applied to 41.7%. During a 16 months follow-up, 8.5% developed CVT. There was a significant decrease of GLS and LVEF at 12-months (decrease of 1.1% and 2.2%, p<0.001). AHT and combined therapy were significantly associated with CVT. In the AHT sub-group analysis (n=85), 15.7% developed CVT. Patients previously medicated with CPD had a significative lower incidence of CVT (2.9% vs 25.0%, p=0.006). Patients already on CPD presented a higher LVEF at 6-months follow-up (62.5% vs 59.2%, p=0.017). Patients submitted to AHT and anthracycline therapy had higher risk of developing CVT. In the AHT sub-group, pre-treatment with CPD was significantly associated with a lower prevalence of CVT. These results highlight the importance of cardio-oncology evaluation and strengthen the value of primary prevention.

History of peripheral artery disease and cardiovascular risk of real-world patients with acute coronary syndrome: Role of inflammation and comorbidities

BackgroundPatients with acute coronary syndromes (ACS) remain at risk of cardiovascular disease (CVD) recurrences. Peripheral artery disease (PAD) may identify a very high risk (VHR) group who may derive greater benefit from intensified secondary prevention. MethodsAmong ACS-patients enrolled in the prospective multi-center Special Program University Medicine (SPUM), we assessed the impact of PAD on major cardiovascular events (MACE: composite of myocardial infarction, stroke and all-cause death) and major bleeding. Multivariate analysis tested the relation of each significant variable with MACE, as well as biomarkers of inflammation and novel markers of atherogenesis. ResultsOut of 4787 ACS patients, 6.0% (n = 285) had PAD. PAD-patients were older (p < 0.001), with established CVD and signs of increased persistent inflammation (hs-CRP; 23.6 ± 46.5 vs 10.4 ± 27.2 mg/l, p < 0.001 and sFlt-1; 1399.5 ± 1501.3 vs 1047.2 ± 1378.6 ng/l, p = 0.018). In-hospital-death (3.2% vs 1.4%, p = 0.022) and -MACE (5.6% vs 3.0%, p = 0.017) were higher in PAD-patients. MACE at 1 year (18.6% vs 7.9%,p < 0.001) remained increased even after adjustment for confounders (Adj. HR 1.53, 95% CI: 1.14–2.08, p = 0.005). Major bleeding did not differ between groups (Adj. HR 1.18; 95% CI 0.71–1.97, p = 0.512). Although PAD predicted MACE, PAD-patients were prescribed less frequently for secondary prevention at discharge. ConclusionsIn this real-world ACS patient cohort, concomitant PAD is a marker of VHR and is associated with increased and persistent inflammation, higher risk for MACE without an increased risk of major bleeding. Therefore, a history of PAD may be useful to identify those ACS patients at VHR who require more aggressive secondary prevention.

Integrated Flood Hazard Vulnerability Modeling of Neluwa (Sri Lanka) Using Analytical Hierarchy Process and Geospatial Techniques

This research aimed to apply the geospatial techniques and Analytical Hierarchy Process (AHP) approach to find vulnerable areas in terms of flooding in the Neluwa area, Sri Lanka. The study incorporated nine relevant criteria for the vulnerability classification under three sub-criteria; the built environment, physical environment, and socio-economic environment. Under the built environment, road networks and buildings were chosen as sub-criteria. The Normalized Difference Vegetation Index (NDVI), slope, elevation, water bodies, and stream density were taken as physical criteria. Land use and population density were considered as socio-economic criteria. All the criteria are set correctly in raster data, and their contents were well adduced. The study consisted of the use of different levels of criteria and combinations of different processes. The analytical results reveal that 14.24% and 30.24% of the total area are at a very-high risk and high risk for flooding, respectively. Only 5.17% of the land was classified as a risk-free area. Eastern, central, and western divisions of the study area are highly vulnerable to floods due to their low slopes. Based on the produced maps, the spatial extents and levels of risk were systematically identified. Data obtained through qualitative judgments related to the field were validated based on the approach used. The potential of this approach is effective in assessing the spatial vulnerability of these flood-affected areas. Using such criteria and a model-based approach will be constructive in identifying different flood scenarios and in providing a remunerative guideline for potential anticipatory measures and better land-based planning in the area.

Climate Change Risks on Mediterranean River Ecosystems and Adaptation Measures (Spain)

The Mediterranean is one of the most vulnerable regions to climate change impacts. Climate change scenarios predict that water temperature will increase up to 2.2–2.9ºC by the end of the century in Mediterranean rivers. This will cause an impact on water quality (oxygen dissolved reduction), reduce the available habitat of cold-water fish species and affect macroinvertebrates. Risk assessment methodology develops indicators that integrate hazard, exposure and vulnerability. Risk maps are key tools to prioritize the areas in which adaptation measures should be implemented in order to improve the adaptive capacity of ecosystems. The risk of habitat loss and ecosystem damage is very high in Mediterranean rivers. For RCP8.5, the 80% of the waterbodies that currently have brown trout presence are in High Risk (HR) or Very High Risk (VHR) of disappearing in the long term future (2070–2100) and the 35% in the short term (2010–2040). It will affect the middle sections first and the headwaters of the rivers later. The 92% of the waterbodies are in HR-VHR of macroinvertebrate family’s affection (2070–2100) and dissolved oxygen may be reduced by 0.5–0.75 mgO2/l (2070–2100). The restoration of the riverside vegetation is the main adaptation measure. This reduces significantly the stream temperature. Other measures are the groundwater protection and cold-water discharge from the reservoirs.

Transcriptomic Heterogeneity in High-risk Prostate Cancer and Implications for Extraprostatic Disease at Presentation on Prostate-specific Membrane Antigen Positron Emission Tomography

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has greater specificity and sensitivity for detection of extraprostatic prostate cancer (PCa) at presentation than conventional imaging. Although the long-term clinical significance of acting on these findings is unknown, it has been shown that the risk of upstaging is prognostic for long-term outcomes in men with high-risk (HR) or very high-risk (VHR) PCa. We evaluated the association between the risk of upstaging on PSMA PET and the Decipher genomic classifier score, a known prognostic biomarker in localized PCa that is being evaluated for its predictive ability to direct systemic therapy intensification. In a cohort of 4625 patients with HR or VHR PCa, the risk of upstaging on PSMA PET was significantly correlated with the Decipher score (p < 0.001). These results should be seen as hypothesis-generating and warrant further studies on the causal pathways linking PSMA findings, Decipher scores, extraprostatic disease, and long-term clinical outcomes. Patient summaryWe found significant correlation between the risk of having prostate cancer outside the prostate gland on a sensitive scan (based on prostate-specific membrane antigen [PSMA]) at initial staging and the Decipher genetic score. The results warrant further studies on the causal pathways between PSMA scan findings, Decipher scores, disease outside the prostate, and long-term outcomes.

Nonmetastatic Rhabdomyosarcoma in Children and Adolescents: Overall Results of the European Pediatric Soft Tissue Sarcoma Study Group RMS2005 Study.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The RMS2005 study included two phase III randomized trials for high-risk (HR) and observational trials for low (LR), standard (SR), and very high-risk (VHR) patients who have been partially reported. Herein, we present a comprehensive report of results achieved for the complete unselected nonmetastatic cohort and analyze the evolution of treatment in comparison with previous European protocols. After a median follow-up of 73.1 months, the 5-year event-free survival (EFS) and overall survival (OS) of the 1,733 patients enrolled were 70.7% (95% CI, 68.5 to 72.8) and 80.4% (95% CI, 78.4 to 82.3), respectively. The results by subgroup: LR (80 patients) EFS 93.7% (95% CI, 85.5 to 97.3), OS 96.7% (95% CI, 87.2 to 99.2); SR (652 patients) EFS 77.4% (95% CI, 73.9 to 80.5), OS 90.6% (95% CI, 87.9 to 92.7); HR (851 patients) EFS 67.3% (95% CI, 64.0 to 70.4), OS 76.7% (95% CI, 73.6 to 79.4); and VHR (150 patients) EFS 48.8% (95% CI, 40.4 to 56.7), OS 49.7% (95% CI, 40.8 to 57.9). The RMS2005 study demonstrated that 80% of children with localized rhabdomyosarcoma could be long-term survivors. The study has established the standard of care across the European pediatric Soft tissue sarcoma Study Group countries with the confirmation of a 22-week vincristine/actinomycin D regimen for LR patients, the reduction of the cumulative ifosfamide dose in the SR group, and for HR disease, the omission of doxorubicin and the addition of maintenance chemotherapy.

Achievement of the ESC recommendations for secondary prevention of cardiovascular risk factors in high-risk patients with type 2 diabetes: A real-world national cohort analysis

AimTo assess compliance with European Society of Cardiology (ESC) secondary prevention recommendations in a nationwide contemporary population with diabetes mellitus (DM) and coronary artery disease. MethodWe conducted a retrospective observational study using linked health data in patients across Wales with DM undergoing percutaneous coronary intervention (2012–2017). The follow-up was for one year. We analysed the clinical characteristics, medications, target levels for HbA1c, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and blood pressure against the ESC prevention guidelines. ResultsOverall, 3478 patients with diabetes had available data at 1-year post-PCI. Only 43% had HbA1c levels <53 mmol/L, but 81% had blood pressure < 140/80 (current ESC targets).Prescribing frequency of the newer hypoglycaemic agents (glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors) was suboptimal, with a higher rate in patients with HbA1c ≥53 mmol/mol.Only 51% & 27% of the patients had LDL-C levels <1.8 &1.4 mmol/L (2016 & 2019 guidelines recommendations respectively), and 55% & 34% had non-HDL-C levels <2.6 & 2.2 mmol/L (2016 & 2019 guidelines respectively). Of the uncontrolled LDL-C patients, 42% (2016 target) and 35% (2019 target) were prescribed high-intensity statins. Females were more likely to have LDL-C targets above the recommended level. ConclusionAchievement of ESC treatment goals in this very-high risk cohort for DM and hyperlipidaemia was far from optimal, with a low prescription rate of the guidelines-recommended therapy. Target goals for hypertension were met more frequently. An up-to-date analysis reflecting the current practice against the most recent guidelines is warranted.

Validation of the novel risk-class for non-muscle invasive bladder cancer: Comparison of oncological outcomes between very-high risk and high risk patients

Validation of the novel risk-class for non-muscle invasive bladder cancer: Comparison of oncological outcomes between very-high risk and high risk patients

Real-World Use of Alirocumab: Experience from a Large Healthcare Provider.

With the emerging use of anti-PCSK9 monoclonal antibodies for lowering low-density lipoprotein cholesterol (LDL-C) levels, real-world evidence (RWE) is needed to evaluate drug effectiveness. This study aimed to characterize new users of alirocumab and evaluate its effectiveness in achieving LDL-C target levels. Included were patients initiating treatment with alirocumab from 1 August 2016 to 1 May 2020, with blood lipids evaluations during baseline (180 days prior to therapy initiation) and after 120 (±60) days of follow-up. Patients with treatment intensification during the follow-up period were excluded. LDL-C change from baseline and reaching LDL-C target levels, according to 2019 ESC/EAS guidelines, were evaluated. Among 623 included patients, 50.2% were men, the mean age was 65 years (±9 y), 62% were classified as very-high risk, and 76% had statin intolerance. During the follow-up, 65% (n = 407) were treated only with alirocumab. In 90% the initiation dose was 75 mg, and 21% were up-titrated. Alirocumab was associated with a 31.7% reduction in LDL-C, with 20.5% of patients reaching target levels. In this RWE study, alirocumab was used primarily as a single agent for eligible patients. Suboptimal use and adherence to therapy may have led to a lower LDL-C reduction compared to previous RCTs and most reported real-world studies.

Combining Phenylalanine and Leucine Levels Predicts 30-Day Mortality in Critically Ill Patients Better than Traditional Risk Factors with Multicenter Validation.

In critically ill patients, risk scores are used; however, they do not provide information for nutritional intervention. This study combined the levels of phenylalanine and leucine amino acids (PLA) to improve 30-day mortality prediction in intensive care unit (ICU) patients and to see whether PLA could help interpret the nutritional phases of critical illness. We recruited 676 patients with APACHE II scores ≥ 15 or intubated due to respiratory failure in ICUs, including 537 and 139 patients in the initiation and validation (multicenter) cohorts, respectively. In the initiation cohort, phenylalanine ≥ 88.5 μM (indicating metabolic disturbance) and leucine < 68.9 μM (indicating malnutrition) were associated with higher mortality rate. Based on different levels of phenylalanine and leucine, we developed PLA scores. In different models of multivariable analyses, PLA scores predicted 30-day mortality independent of traditional risk scores (p < 0.001). PLA scores were then classified into low, intermediate, high, and very-high risk categories with observed mortality rates of 9.0%, 23.8%, 45.6%, and 81.8%, respectively. These findings were validated in the multicenter cohort. PLA scores predicted 30-day mortality better than APACHE II and NUTRIC scores and provide a basis for future studies to determine whether PLA-guided nutritional intervention improves the outcomes of patients in ICUs.

Effect of Flu Vaccination on Severity and Outcome of Heart Failure Decompensations

To investigate the relationship of seasonal flu vaccination with the severity of decompensation and long-term outcomes of patients with heart failure (HF). We analyzed 6147 consecutively enrolled patients with decompensated HF who presented to 33 Spanish emergency departments (EDs) during January and February of 2018 and 2019, grouped according to seasonal flu vaccination status. The severity of HF decompensation was assessed by the Multiple Estimation of Risk Based on the Emergency Department Spanish Score in Patients With Acute Heart Failure (MEESSI-AHF) + MEESSI scale, need of hospitalization and in-hospital all-cause mortality. The long-term outcomes analyzed were 90-day postdischarge adverse events and 90-day all-cause death. Associations between vaccination, HF decompensation severity and long-term outcomes were explored by unadjusted and adjusted logistic and Cox regressions by using 14 covariables that could act as potential confounders. Overall median (IQR) age was 84 (IQR = 77-89) years, and 56% were women. Vaccinated patients (n = 1139; 19%) were older, had more comorbidities and had worse baseline status, as assessed by New York Heart Association class and Barthel index, than did unvaccinated patients (n = 5008; 81%). Infection triggering decompensation was more common in vaccinated patients (50% vs 41%; P < 0.001). In vaccinated and unvaccinated patients, high or very-high risk decompensation was seen in 21.9% and 21.1%; hospitalization occurred in 72.5% and 73.7%; in-hospital mortality was 7.4% and 7.0%; 90-day postdischarge adverse events were 57.4% and 53.2%; and the 90-day mortality rate was 15.8% and 16.6%, respectively, with no significant differences between cohorts. After adjusting, vaccinated decompensated patients with HF had decreased odds for hospitalization (OR = 0.823, 95%CI = 0.709-0.955). In patients with HF, seasonal flu vaccination is associated with less severe decompensations.

Wildfire Risk Zone Mapping in Contrasting Climatic Conditions: An Approach Employing AHP and F-AHP Models

Wildfires are one of the gravest and most momentous hazards affecting rich forest biomes worldwide; India is one of the hotspots due to its diverse forest types and human-induced reasons. This research aims to identify wildfire risk zones in two contrasting climate zones, the Wayanad Wildlife Sanctuary in the Western Ghats and the Kedarnath Wildlife Sanctuary in the Himalayas, using geospatial tools, analytical hierarchy process (AHP), and fuzzy-AHP models to assess the impacts of various conditioning factors and compare the efficacy of the two models. Both of the wildlife sanctuaries were severely battered by fires in the past, with more than 100 fire incidences considered for this modeling. This analysis found that both natural and anthropogenic factors are responsible for the fire occurrences in both of the two sanctuaries. The validation of the risk maps, utilizing the receiver operating characteristic (ROC) method, proved that both models have outstanding prediction accuracy for the training and validation datasets, with the F-AHP model having a slight edge over the other model. The results of other statistical validation matrices such as sensitivity, accuracy, and Kappa index also confirmed that F-AHP is better than the AHP model. According to the F-AHP model, about 22.49% of Kedarnath and 17.12% of Wayanad fall within the very-high risk zones. The created models will serve as a tool for implementing effective policies intended to reduce the impact of fires, even in other protected areas with similar forest types, terrain, and climatic conditions.

Efficacy, safety, adherence and persistence of PCSK9 inhibitors in clinical practice: A single country, multicenter, observational study (AT-TARGET-IT)

Background and aimsProprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9i) are recommended in patients at high and very-high cardiovascular (CV) risk, with documented atherosclerotic CV disease (ASCVD), and for very-high risk patients with familial hypercholesterolaemia not achieving LDL-cholesterol (LDL-C) goal while receiving maximally tolerated dose of lipid-lowering therapy (LLT). However, single country real-life data, reporting the use of PCSK9i in clinical practice, are limited. Therefore, we designed AT-TARGET-IT, an Italian, multicenter, observational registry on the use of PCSK9i in clinical practice. MethodsAll data were recorded at the time of the first prescription and at the latest observation preceding inclusion in the study. Results798 patients were enrolled. The median reduction in LDL-C levels was 64.9%. After stratification for CV risk, 63.8% achieved LDL-C target; of them, 83.3% took LLTs at PCSK9i initiation and 16.7% did not. 760 patients (95.2%) showed high adherence to therapy, 13 (1.6%) partial adherence, and 25 (3.1%) poor adherence. At 6 months, 99.7% of patients enrolled in the study remained on therapy; there were 519 and 423 patients in the study with a follow-up of at least 12 and 18 months, respectively. Persistence in these groups was 98.1% and 97.5%, respectively. Overall, 3.5% of patients discontinued therapy. No differences in efficacy, adherence, and persistence were found between alirocumab and evolocumab. ConclusionsPCSK9i are safe and effective in clinical practice, leading to very high adherence and persistence to therapy, and achievement of recommended LDL-C target in most patients, especially when used as combination therapy.

Assessment of the urban waterlogging resilience and identification of its driving factors: A case study of Wuhan City, China

With rapid urbanization and extreme rainstorm events associated with climate change, urban waterlogging has become one of the most frequent and severe disasters globally. In this study, a multi-dimensional and multi-process index system based on the Pressure-State-Response (PSR) framework was developed to measure the level of urban waterlogging resilience (UWR). The spatial distribution of UWR on a block scale was explored based on the entropy weight method with the natural breakpoint method (EWM-NBM) in the central district of Wuhan City, China. In addition, the effects of the runoff control facilities and early warning measures on UWR were also quantified. Further, the Geodetector was used to investigate the main driving factors of UWR and their interactions. Results showed that the constructed index system for UWR based on the PSR framework performed reasonably, and the EWM-NBM was validated to be effective in the integrated assessment. In terms of the validation results, 82.72 % of the recorded waterlogging points belonged to high and very-high risk levels. The spatial heterogeneity of UWR was significant in the study area where the higher-level UWR mainly appears in the areas near the undeveloped suburban and water bodies (lakes and rivers), and the lower-level UWR was concentrated in central urban areas with more impervious surfaces. There was a clear increasing trend in UWR after the implementation of runoff control facilities and early warning measures, but its spatial distribution remained almost invariant. Among all the indexes, the impervious surface percentage had the strongest (69.58 %) explanatory ability for the UWR, and mean annual precipitation (15.51 %), GDP (14.03 %), and population density (11.98 %) also demanded attention. Most driving factors of UWR showed nonlinear interactions. This research could provide a benchmark for urban planning to enhance UWR to mitigate the waterlogging within the main urban area.

Missing the mark -- new methods needed to detect and address high-risk pesticide residues in the global food supply

The primary metric used by regulators to track whether pesticide residues in food pose worrisome risks is the percent of samples tested in a given year that contain residues above applicable tolerances in the US and Maximum Residue Limits (MRLs) in most other countries. The Dietary Risk Index (DRI) system is used to determine the degree to which current policies governing allowed pesticide residue levels in food are keeping high-risk residues out of the global food supply. Residue data generated by the US Pesticide Data Program (PDP) and UK-Food Standards Agency (FSA) are utilized. Over the last 10 years 2449 samples of food have contained violative residues over applicable tolerances or MRLs. Of these, about 60% posed low or very-low dietary risks relative to acceptable dietary intake levels set by regulators. Conversely, only about 4% of high- and very-high risk samples tested by the US-PDP contained residues above the applicable tolerance. Accordingly, current US and UK policies are failing to flag most high-risk samples and are triggering more intense scrutiny and/or adverse regulatory actions in the case of many samples posing low or very-low risks. Recommendations are offered to enhance the ability to track and incrementally reduce pesticide dietary risks.