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Background: Immune checkpoint inhibitors (ICI) improve overall survival (OS) in patients with locally advanced, unresectable, or metastatic urothelial carcinoma (aUC), but response rates can be modest. We compared outcomes between patients with and without prior intravesical Bacillus Calmette-Guerin (BCG), who received ICI for aUC, hypothesizing that prior intravesical BCG would be associated with worse outcomes. Patients and Methods: We performed a retrospective cohort study across 25 institutions in US and Europe. We compared observed response rate (ORR) using logistic regression; progression-free survival (PFS) and OS using Kaplan-Meier and Cox proportional hazards. Analyses were stratified by treatment line (first line/salvage) and included multivariable models adjusting for known prognostic factors. Results: A total of 1026 patients with aUC were identified; 614, 617, and 638 were included in ORR, OS, PFS analyses, respectively. Overall, 150 pts had history of prior intravesical BCG treatment. ORR to ICI was similar between those with and without prior intravesical BCG exposure in both first line and salvage settings (adjusted odds radios 0.55 [P= .08] and 1.65 [P= .12]). OS (adjusted hazard ratios 1.05 [P= .79] and 1.13 [P= .49]) and PFS (adjusted hazard ratios 1.12 [P= .55] and 0.87 [P= .39]) were similar between those with and without intravesical BCG exposure in first line and salvage settings. Conclusion: Prior intravesical BCG was not associated with differences in response and survival in patients with aUC treated with ICI. Limitations include retrospective nature, lack of randomization, presence of selection and confounding biases. This study provides important preliminary data that prior intravesical BCG exposure may not impact ICI efficacy in aUC. © 2021

Plasma androgen receptor (AR) gain identifies metastatic castration-resistant prostate cancer (mCRPC) patients with worse outcome on abiraterone/enzalutamide, but its relevance in the context of taxane chemotherapy is unknown. We aimed to evaluate whether docetaxel is active regardless of plasma AR and to perform an exploratory analysis to compare docetaxel with abiraterone/enzalutamide. This multi-institutional study was a pooled analysis of AR status, determined by droplet digital polymerase chain reaction, on pretreatment plasma samples. We evaluated associations between plasma AR and overall/progression-free survival (OS/PFS) and prostate-specific antigen (PSA) response rate in 163 docetaxel-treated patients. OS was significantly shorter in case of AR gain (hazard ratio [HR] = 1.61, 95% confidence interval [CI] = 1.08-2.39, p = 0.018), but not PFS (HR = 1.04, 95% CI 0.74-1.46, p = 0.8) or PSA response (odds ratio = 1.14, 95% CI = 0.65-1.99, p = 0.7). We investigated the interaction between plasma AR and treatment type after incorporating updated data from our prior study of 73 chemotherapy-naive, abiraterone/enzalutamide-treated patients, with data from 115 first-line docetaxel patients. In an exploratory analysis of mCRPC patients receiving first-line therapies, a significant interaction was observed between plasma AR and docetaxel versus abiraterone/enzalutamide for OS (HR = 0.16, 95% CI = 0.06-0.46, p < 0.001) and PFS (HR = 0.31, 95% CI = 0.12-0.80, p = 0.02). Specifically, we reported a significant difference for OS favoring abiraterone/enzalutamide for AR-normal patients (HR = 1.93, 95% CI = 1.19-3.12, p = 0.008) and a suggestion favoring docetaxel for AR-gained patients (HR = 0.53, 95% CI = 0.24-1.16, p = 0.11). These data suggest that AR-normal patients should receive abiraterone/enzalutamide and AR-gained could benefit from docetaxel. This treatment selection merits prospective evaluation in a randomized trial. Patient summary: We investigated whether plasma androgen receptor (AR) predicted outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel, and we performed an exploratory analysis in patients treated with docetaxel or AR-directed drugs as first-line mCRPC therapy. We showed that plasma AR normal favored hormonal treatment, whilst plasma AR-gained patients may have had a longer response to docetaxel, suggesting that plasma AR status could be a useful treatment selection biomarker., V. Conteduca was funded by a European Society of Medical Oncology Translational Clinical Research Fellowship. A. Jayaram is supported by a grant from the Medical Research Council (MR/P002072/1). G. Attard is supported by a Cancer Research UK Advanced Clinician Scientist Grant (A22744). This work was funded in part by Prostate Cancer UK (PG12-49), the Instituto de Salud Carlos III (ISCII) PI16/01565 grant E. Gonzalez-Billalabeitia was funded by a grant from the Instituto de Salud Carlos III (ISCIII) PI15/01499. N. Romero-Laorden was funded by a grant from the Instituto de Salud Carlos III (CM14-00200). E. Castro is supported by a Prostate Cancer Foundation Young Investigator Award (2017). E. Castro and D. Olmos are supported by grants from the Ministerio de Economia, Industria y Competitividad (JCI-2014-19129 to E.C., RYC-2015-18625 to D.O.). B. Mellado and M. Marin-Aguilera work were supported by the Instituto de Salud Carlos III-Subdireccion General de Evaluacion y Fomento de la Investigacion (PI12/01226 and PI15/676) and co-funded by the European Regional Development Fund. Funding from CERCA Programme/Generalitat de Catalunya is gratefully acknowledged. During the conduct of the study, E. Castro was supported by a grant from the Ministerio de Educacion, Cultura y Deportes (CAS17/00182). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all data and had the final responsibility for the decision to submit for publication.

The pathology of the aorta is a challenge for medicine. Diagnostic and therapeutics move a huge volume of variables. This has let this pathology to be addressed by a big number of specialists. The surgical management of these pathologies implies an extraordinary effort on the part of many professionals, given the technical and technological complexity employed. Throughout these years, these efforts are paying off in the form of improved results, thanks to a systematic and protocolized approach within a group of experts (Aortic Committees or "Aortic team") in which they have to involve cardiologists, cardiac surgeons, vascular surgeons, anesthesiologists and radiologists, mainly. In this document, agreed between the Aorta working groups of the Spanish societies of Anesthesiology and Thoracic-Cardiovascular Surgery, it is sought to disseminate the most agreed working modes among the centers of greatest activity in the country by both specialties, as far as surgical treatment is concerned in descending chronical aortic pathology. We are aware of the constant evolution of therapeutics, which can undoubtedly make some of the opinions expressed here questionable and that will undoubtedly be modified in future editions. This document aims to be a working tool for the different professionals involved in the treatment of aorticpathology. (C) 2020 Sociedad Espanola de Anestesiologia, Reanimacion y Terapeutica del Dolor. Published by Elsevier Espana, S.L.U. All rights reserved.

Objectives: To compare clinical outcomes between patients with locally advanced (unresectable) or metastatic urothelial carcinoma (aUC) in the upper and lower urinary tract receiving immune checkpoint inhibitors (ICIs). Patients and Methods: We performed a retrospective cohort study collecting clinicopathological, treatment, and outcome data for patients with aUC receiving ICIs from 2013 to 2020 across 24 institutions. We compared the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) between patients with upper and lower tract UC (UTUC, LTUC). Uni- and multivariable logistic and Cox regression were used to assess the effect of UTUC on ORR, OS, and PFS. Subgroup analyses were performed stratified based on histology (pure, mixed) and line of treatment (first line, subsequent line). Results: Out of a total of 746 eligible patients, 707, 717, and 738 were included in the ORR, OS, and PFS analyses, respectively. Our results did not contradict the hypothesis that patients with UTUC and LTUC had similar ORRs (24% vs 28%; adjusted odds ratio [aOR] 0.73, 95% confidence interval [CI] 0.43–1.24), OS (median 9.8 vs 9.6 months; adjusted hazard ratio [aHR] 0.93, 95% CI 0.73–1.19), and PFS (median 4.3 vs 4.1 months; aHR 1.01, 95% CI 0.81–1.27). Patients with mixed-histology UTUC had a significantly lower ORR and shorter PFS vs mixed-histology LTUC (aOR 0.20, 95% CI 0.05–0.91 and aHR 1.66, 95% CI 1.06–2.59), respectively). Conclusion: Overall, patients with UTUC and LTUC receiving ICIs have comparable treatment response and outcomes. Subgroup analyses based on histology showed that those with mixed-histology UTUC had a lower ORR and shorter PFS compared to mixed-histology LTUC. Further studies and evaluation of molecular biomarkers can help refine patient selection for immunotherapy. © 2021 The Authors BJU International © 2021 BJU International Published by John Wiley & Sons Ltd

BACKGROUND: While immune checkpoint inhibitors (ICIs) are approved in the first-line (1L) setting for cisplatin-unfit patients with programmed death-ligand 1 (PD-L1)-high tumors or for platinum (cisplatin/carboplatin)-unfit patients, response rates remain modest and outcomes vary with no clinically useful biomarkers (except for PD-L1). OBJECTIVE: We aimed to develop a prognostic model for overall survival (OS) in patients receiving 1L ICIs for advanced urothelial cancer (aUC) in a multicenter cohort study. DESIGN, SETTING, AND PARTICIPANTS: Patients treated with 1L ICIs for aUC across 24 institutions and five countries (in the USA and Europe) outside clinical trials were included in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used a stepwise, hypothesis-driven approach using clinician-selected covariates to develop a new risk score for patients receiving ICIs in the 1L setting. Demographics, clinicopathologic data, treatment patterns, and OS were collected uniformly. Univariate Cox regression was performed on 18 covariates hypothesized to be associated with OS based on published data. Variables were retained for multivariate analysis (MVA) if they correlated with OS (p < 0.2) and were included in the final model if p < 0.05 on MVA. Retained covariates were assigned points based on the beta coefficient to create a risk score. Stratified median OS and C-statistic were calculated. RESULTS AND LIMITATIONS: Among 984 patients, 357 with a mean age of 71 yr were included in the analysis, 27% were female, 68% had pure UC, and 13% had upper tract UC. Eastern Cooperative Oncology Group performance status ≥2, albumin 5, and liver metastases were significant prognostic factors on MVA and were included in the risk score. C index for new 1L risk score was 0.68 (95% confidence interval 0.65-0.71). Limitations include retrospective nature and lack of external validation. CONCLUSIONS: We developed a new 1L ICI risk score for OS based on data from patients with aUC treated with ICIs in the USA and Europe outside of clinical trials. The score components highlight readily available factors related to tumor biology and treatment response. External validation is being pursued. PATIENT SUMMARY: With multiple new treatments under development and approved for advanced urothelial carcinoma, it can be difficult to identify the best treatment sequence for each patient. The risk score may help inform treatment discussions and estimate outcomes in patients treated with first-line immune checkpoint inhibitors, while it can also impact clinical trial design and endpoints. TAKE HOME MESSAGE: A new risk score was developed for advanced urothelial carcinoma treated with first-line immune checkpoint inhibitors. The score assigned Eastern Cooperative Oncology Group performance status ≥2, albumin 5, and liver metastases each one point, with a higher score being associated with worse overall survival. Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.

A review of potential conflicts of interest for all the authors in relation to this study revealed further items that Rafael Morales-Barrera and Enrique Grande wish to disclose. The conflicts of interest statement with full disclosures is therefore as follows. Financial disclosures: Jose Luis Perez-Gracia certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Jose Luis Perez-Gracia has received grants or funding from Roche, had consultancies with Roche, and received honoraria from Roche. Yohann Loriot has received grants from Sanofi and fees for consulting or advisory roles from Astellas, AstraZeneca, Janssen, MSD, Roche, and Sanofi. Jonathan E. Rosenberg has received grants or funding from Bristol-Myers Squibb and Roche and has had consultancies with Agensys, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, EMD-Serono, Merck, Roche, and Seattle Genetics. Thomas Powles has received grants or funding from AstraZeneca and Roche and received honoraria from AstraZeneca, Bristol-Myers Squibb, Merck, and Roche. Andrea Necchi has received grants or funding from Amgen, AstraZeneca, and Merck & Co. Inc., had consultancies with Astellas/Seattle Genetics, AstraZeneca, Bayer, Merck & Co. Inc., Pfizer, and Roche, and received honoraria from Merck & Co. Inc., Pierre Fabre, and PeerVoice Roche. Syed A. Hussain has attended advisory board meetings with AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, Merck, Pierre Fabre, and Roche and received educational grants and institutional funding from Cancer Research UK, Boehringer Ingelheim, Janssen, and Eli Lilly. Morales-Barrera has no financial disclosures. Margitta M. Retz is employed by and affiliated with Technical University Munich, Germany Klnikum rechts der Isar, Department of Urology. Günter Niegisch has received grants or funding from 4SC AG, had consultancies with Bristol-Myers Squibb, IMS Health AG, medac GmbH, and Roche Pharma AG and received honoraria from Pfizer Pharma GmbH, Pierre Fabre Pharma GmbH, and Roche Pharma AG. Ignacio Durán has received grants or funding from Roche-Genentech, had consultancies with Bristol-Myers Squibb, Merck Sharp & Dohme Corp, and Roche-Genentech, and received honoraria from Merck Sharp & Dohme Corp, Pierre Fabre, and Roche. Christine Théodore has no financial disclosures. Betty Nelson, Xiaodong Shen, and Christina L. Derleth are employed by Genentech and own Roche stock. Jingjing Wang is a consultant of Genentech. Michiel S.van der Heijden has received grants or funding from Astellas and had consultancies with Astellas, AstraZeneca, Bristol-Myers Squibb, and Roche-Genentech. Rafael Morales-Barrera has received speaker honoraria or travel support from Bayer, Roche, Astellas, Janssen-Cilag, MSD, and Sanofi-Aventis. Enrique Grande has received honoraria for advisory boards, meetings, and/or lectures from Pfizer, BMS, IPSEN, Roche, Eisai, Eusa Pharma, MSD, Sanofi-Genzyme, Adacap, Novartis, Pierre Fabre, Lexicon, and Celgene, and has received unrestricted research grants from Pfizer, AstraZeneca, MTEM/Threshold, Roche, IPSEN, and Lexicon.

El Municipio de Arauca ha tenido un proceso de desarrollo desacelerado en el sector agropecuario y agroindustrial, el cual ha estado enmarcado dentro de los conflictos armados que tienen lugar en el país, la debilidad estatal presente, la desarticulación y deficiencia que existe en la malla vial, desarrollo institucional, debilidad gremial y empresarial y los altos índices de corrupción del sector público. El Presente artículo pretende mostrar la valoración de la infraestructura tecnológica, las organizaciones y el apoyo institucional. Para cumplir este objetivo se utilizó la metodología AHP o el Proceso Analítico Jerárquico, utilizando fuentes de información secundaria como: documentos de política, documentos de entidades públicas y privadas, estudios y estadísticas de organismos de Naciones Unidas y documentos académicos. El análisis de la información recabada ha llevado a determinar que tienen potencial de desarrollo agroindustrial la cadena productiva del cacao y carne-lácteos, por el contrario no existen condiciones objetivas que permitan consolidar la cadena productiva del plátano y forestal como eje de desarrollo local. The Municipality of Arauca has had a decelerated development process in the agricultural and agroindustrial sector, which has been framed within the armed conflicts that take place in the country, the present state weakness, the disarticulation and deficiency that exists in the road mesh , Institutional development, corporate and trade weakness, and high corruption rates in the public sector. The present article intends to show the valuation of the technological infrastructure, the organizations and the institutional support. To achieve this objective, the AHP or Hierarchical Analytic Process was used, using secondary information sources such as: policy documents, documents of public and private entities, studies and statistics of United Nations agencies and academic documents. The analysis of the information collected has led to the determination that the production chain of cocoa and meat-dairy products have the potential of agro-industrial development, but there are no objective conditions to consolidate the banana and forestry.

In Puerto Rico, the first records of the transmission of Chikungunya (CHIKV) and Zika (ZIKV) viruses were confirmed in May 2014 and December 2015, respectively. Transmission of CHIKV peaked in September 2014, whereas that of ZIKV peaked in August 2016. The emergence of these mosquito‐transmitted arboviruses in the context of a lack of human population immunity allowed observations of whether the outbreaks were associated with Aedes aegypti (Diptera: Culicidae) densities and weather. Mosquito density was monitored weekly in four communities using sentinel autocidal gravid ovitraps (AGO traps) during 2016 in order to provide data to be compared with the findings of a previous study carried out during the 2014 CHIKV epidemic. Findings in two communities protected against Ae. aegypti using mass AGO trapping (three traps per house in most houses) were compared with those in two nearby communities without vector control. Mosquito pools were collected to detect viral RNA of ZIKV, CHIKV and dengue virus. In areas without vector control, mosquito densities and rates of ZIKV detection in 2016 were significantly higher, similarly to those observed for CHIKV in 2014. The density of Ae. aegypti in treated sites was less than two females/trap/week, which is similar to the putative adult female threshold for CHIKV transmission. No significant differences in mosquito density or infection rates with ZIKV and CHIKV at the same sites between years were observed. Although 2016 was significantly wetter, mosquito densities were similar.