Management of Patients with Advanced Prostate Cancer. Part I : Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022

Background: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective: To present consensus voting results for select questions from APCCC 2022. Design, setting, and participants: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. Results and limitations: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.publishedVersionPeer reviewe

Management of patients with advanced prostate cancer. Part I: Intermediate-/high-risk and locally advanced disease, biochemical relapse, and side effects of hormonal treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022

© 2023 The Authors. Published by Elsevier on behalf of European Association of Urology. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1016/j.eururo.2022.11.002Background: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective: To present consensus voting results for select questions from APCCC 2022. Design, setting, and participants: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. Results and limitations: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.We gratefully acknowledge the following organisations for providing financial support for the APCCC 2022: The City of Lugano and Movember Foundation. Ros Eeles is supported by a National Institute of Health Research grant to the Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden NHS Foundation Trust. We also acknowledge sponsorship from several for-profit organisations for APCCC 2022, including Advanced Accelerator Applications, Amgen, Astellas, AstraZeneca, Bayer Health Care, Debiopharm, MSD, Janssen Oncology, Myovant Sciences, Orion Pharma, Pfizer Oncology, Roche, Telix Innovations SA, Ferring Pharmaceuticals, Lantheus, and Tolmar. These for-profit organisations supported the conference financially but had no input on the scientific content or the final publication.Accepted versio

Il Salento: spazio di dialogo e accoglienza

EnThe events that have characterized the end of 20th century and the begining of 21th century seem to bring the occidental civilization and the whole Earth to an age of important sociopolitical, economical and ambiental changes, with catastrophic consequences for the whole umanity. The resulted emegency state brings the poor population to the mass migration to occidental countries. All of these don't develop global strategies to solve the problem, but they prefer to adopt only provvisional solutions; only the magisterium of the Pope Bergoglio seems to focalize on the problem, and it identifies as the only possible solution the propension to the needs of poor and closer people and the world, with the eyes of sharing and mercy. This work wants to show how the land of Salento, according to its millenary history of welcome and integration, replies to the problems of migration, that see it in the front line since 1991, in the best way ever. Also, basing on the datas collected by the local Healt Institution, it's recognized that, according to the elements collected at nazional and European level, the fear of an healt emergency for the natives people, because of migrants coming, is totally unfounded.ItGli eventi che hanno caratterizzato la fine del XX e l'inizio del XXI secolo, sembrano aver consegnato la civiltà occidentale e l'intero globo terrestre ad un'era di cambiamenti socio-politici, economici e ambientali a carattere epocale, il cui esito si annuncia catastrofico per l'intera umanità. Lo stato emergenziale scaturito induce le popolazioni povere alla migrazione di massa verso i paesi occidentali. Questi stentano a sviluppare strategie globali perseguendo soluzioni provvisorie; solo il magistero di Papa Bergoglio sembra centrare il problema, indicando come unica soluzione possibile quella di guardare al prossimo ed ai bisogni del mondo con gli occhi della condivisione e della misericordia. Il presente lavoro intende mostrare come il Salento, in accordo con la sua storia millenaria di accoglienza e integrazione, abbia risposto nel migliore dei modi alle problematiche riguardanti il flussi migratori che lo vedono in prima linea a partire dal 1991. Inoltre, sulla base dei dati raccolti da parte degli Istituti Sanitari territoriali, si dimostra che, in accordo con quanto rilevato a livello nazionale ed europeo, il timore di un'emergenza sanitaria per le popolazioni residenti, a causa dell'arrivo dei migranti, è del tutto infondato

Systèmes d'analyses météorologiques dans le Nord-Est de l'Espagne : Validation de SAFRAN et SPAN

International audienceWe present an application and validation of the SAFRAN meteorological analysis system for north-east Spain. SAFRAN is also compared to the SPAN analysis system and the meteorological model HIRLAM-HNR, both operational at AEMET. This application of SAFRAN is intended for hydrological studies. This is the first study that shows an application of SAFRAN outside of France and that compares it with SPAN. This is also the first article validating SPAN's rainfall values. Using one year of observational data, the results show that both SAFRAN and SPAN have a similar performance, which is also similar to SAFRAN's performance in France. Thus, SAFRAN and SPAN are both good tools to force land surface models at high resolution in the area of SAFRAN works under the assumption of the existence of climatically homogeneous zones. Two different sets of zones were tested, one based on the AEMET meteorological warning zones and another one based on hydrological catchments. Better results were obtained when using meteorological warning zones. However, the difference is small. In north-east Spain, SAFRAN has the same limitations that were previously shown in France: the spatial structure of the fields is not realistic enough and wind speed is underestimated. As expected, both SAFRAN and SPAN work better in flat areas than over areas of steep relief. This can be a problem in hydrological studies, especially for the Ebro river basin, where most of the runoff is generated in the Pyrenees

bag3 gene expression is regulated by heat shock factor 1.

BAG3 protein, a member of the BAG co-chaperones family, sustains cell survival, through its interaction with the heat shock protein (HSP) 70, in a variety of normal and neoplastic cell types. bag3 gene expression is induced by stressful stimuli. Here we report for the first time that two of the three putative heat shock-responsive elements (HSEs) in bag3 promoter interact with the heat shock factor (HSF) 1 in vitro and in vivo. Furthermore, downmodulation of HSF1 protein levels by specific small interfering (si) RNAs results in reducing BAG3 protein levels, indicating that the transcription factor plays a major role in bag3 gene expression. Because of the anti-apoptotic role of BAG3 protein, these results disclose a previously unrecognized pathway, through which HSF1 maintains cell survival