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Gleason grade group (GG) is the most powerful prognostic variable in localized prostate cancer; however, interobserver variability remains a challenge. Artificial intelligence algorithms applied to histopathologic images standardize grading, but most have been tested only for agreement with pathologist GG, without assessment of performance with respect to oncologic outcomes. We compared deep learning-based and pathologist-based GGs for an association with metastatic outcome in three surgical cohorts comprising 777 unique patients. A digitized whole slide image of the representative hematoxylin and eosin-stained slide of the dominant tumor nodule was assigned a GG by an artificial intelligence-based grading algorithm and was compared with the GG assigned by a contemporary pathologist or the original pathologist-assigned GG for the entire prostatectomy. Harrell's C-indices based on Cox models for time to metastasis were compared. In a combined analysis of all cohorts, the C-index for the artificial intelligence-assigned GG was 0.77 (95% confidence interval [CI]: 0.73-0.81), compared with 0.77 (95% CI: 0.73-0.81) for the pathologist-assigned GG. By comparison, the original pathologist-assigned GG for the entire case had a C-index of 0.78 (95% CI: 0.73-0.82). PATIENT SUMMARY: Artificial intelligence-enabled prostate cancer grading on a single slide was comparable with pathologist grading for predicting metastatic outcome in men treated by radical prostatectomy, enabling equal access to expert grading in lower resource settings.
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AIM: To explore Australian and New Zealand nursing and midwifery educators' planetary health knowledge, views, confidence and teaching practices. DESIGN: A cross-sectional survey design. METHODS: An online survey was sent to Australian and New Zealand nursing and midwifery educators across the 45 Schools of Nursing and Midwifery between July and September 2023. The online survey consisted of 29 open- and closed-ended questions about nursing and midwifery educators' planetary health knowledge, views, confidence and teaching practices. RESULTS: There was a total of 127 responses to the first open-ended question. A total of 97 nursing and midwifery educators then completed the remaining questions. While educators had mostly positive views about integrating planetary health into their teaching, they lacked the knowledge and/or confidence to do so effectively. CONCLUSION: Australian and New Zealand nursing and midwifery educators acknowledge that planetary health should be included in nursing and midwifery curricula, but most reported a deficit in knowledge and/or confidence to integrate these complex concepts into their teaching. When considering planetary health, most educators focussed on climate change, which demonstrates their limited understanding of the concept of planetary health. IMPLICATIONS FOR THE PROFESSION: All nurses and midwives need to understand how the health of the planet and human civilization are interconnected and be prepared to address complex global health challenges now and in the future. Across the world, key healthcare organizations have called upon nursing and midwifery educators to prepare the healthcare workforce to practice in a more sustainable way, including supporting decarbonization of healthcare. However, our study has demonstrated that nursing and midwifery educators do not feel ready to respond due to a lack of required knowledge and/or confidence. REPORTING METHOD: We used the Consensus-Based Checklist for Reporting of Survey Studies (CROSS). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
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BACKGROUND: Climate Change is causing frequent and sever extreme weather events globally, impacting human health and well-being. Primary healthcare (PHC) nurses' are at the forefront of addressing these challenges and must be prepared. PURPOSE: This scoping revieww explored literature on the preparedness of the PHC nursing workforce for extreme weather events and identify gaps in knowledge and practice. METHODS: Using Arksey and O'Malley's framework, a comprehensive search was conducted across PubMed, Scopus, CINHAL, Web of Sciences, and ProQuest, on studies from 2014-2024, addressing PHC nurses' preparedness. DISCUSSION: Nine studies were identified and highlighted a need for preparedness training and facility-based preparedness plans. Key themes included prioritizing regional networks, clinical leadership, service delivery, health information, health workforce, medical products and technologies, and financing. CONCLUSION: Strengthening PHC nurses' resilience against extreme weather requires targeted professional development, mental health support, comprehensive planning, and collaborative efforts. Future strategies should enhance PHC nurses' capacity through training, support, and policy development.
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Mudança Climática , Humanos , Clima Extremo , Atenção Primária à Saúde , Enfermagem de Atenção Primária , Planejamento em Desastres , Adulto , Feminino , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: To achieve consensus on the knowledge and skills that undergraduate/pre-licensure nursing students require to steward healthcare towards a more sustainable future. DESIGN: A two-phase real-time Delphi study. METHODS: Phase 1 included the generation of Planetary Health, climate change and sustainability knowledge and skill statements based on a review of relevant literature. Phase 2 consisted of a real-time Delphi survey designed to seek consensus on the proposed statements from a panel of 42 international experts. RESULTS: Of the 49 survey statements, 44 (90%) achieved ≥75% consensus and 26 (53%) achieved ≥80% consensus. Three were removed and 32 were modified to improve clarity of language. CONCLUSION: The knowledge and skills statements that emerged through this Delphi study can serve as a guide for incorporating Planetary Health, climate change and sustainability into nursing education programs. IMPLICATIONS FOR THE PROFESSION: Incorporating Planetary Health and climate change education into nursing programs has the potential to produce more environmentally conscious and socially responsible nurses. IMPACT: The absence of consensus on the essential knowledge and skills expected of nursing students has hindered the advancement of curricula and impacted educators' confidence in teaching Planetary Health and climate change. This study has resulted in a meticulously crafted framework of knowledge and skill statements that will be beneficial to educators, the future nursing workforce, and, ultimately, the individuals and communities whom nurses serve. REPORTING METHOD: This paper adheres to the Conducting and REporting DElphi Studies (CREDES) reporting guideline. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
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STUDY OBJECTIVES: Continuous positive airway pressure (CPAP) is considered effective treatment for moderate-severe obstructive sleep apnea (OSA). Clinicians measure compliance to treatment by the number of hours CPAP is used per 24 hours. There have been very few studies examining the patients' lived experience of CPAP and the barriers to use. This study examined the patients' experience of OSA, CPAP use and treatment during COVID-19. METHODS: This CPAP patient experience qualitative study was part of a larger project. The overarching study was a three-armed nonblinded randomized controlled trial of patients on CPAP for treatment of OSA using standard care or one of two telemedicine interventions. Patients who had completed the RCT study were invited to be interviewed via telephone, about their OSA diagnosis, CPAP experiences, their experience of using telemedicine and the impact of SARS-CoV-2 (COVID-19). RESULTS: Fifteen patients (five from each arm of the trial) took part in a semi-structured interview. Thematic analysis identified three themes: day to day living, standard hospital care versus telemedicine management and living though COVID-19 with CPAP. CONCLUSIONS: All participants described significant symptoms caused by their OSA before diagnosis. While CPAP treatment was often described as challenging, patients discussed the improvement in their symptoms with treatment. There were differing opinions on virtual appointments, however the consensus was the use of telemedicine to support CPAP treatment was well received. COVID-19 appeared to have little effect on the patient experience.
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OBJECTIVES: Psychological distress can occur following diagnosis and treatment for prostate cancer, compromising psychosocial wellbeing. Improved recognition and management of distress by healthcare professionals can enhance clinical practice and promote evidence-based prostate cancer care. This paper explores the effectiveness and feasibility of the online Distress Screening for Prostate Cancer course, designed to improve healthcare professionals' understanding of screening for prostate cancer-related distress. It aims to evaluate whether this e-learning course increases learners' knowledge of distress screening for prostate cancer. METHODS: Healthcare professionals were invited to enroll in the online course and complete optional evaluation questions. The pretest posttest design identified changes in learners' knowledge about distress screening for people with prostate cancer, including prevalence, risk factors, assessment and management strategies for distress (nâ¯=â¯149). Learners also rated satisfaction in a cross-sectional survey (nâ¯=â¯116). Most respondents were nurses, including Prostate Cancer Specialist Nurses. RESULTS: Learners' knowledge of distress screening was higher after course completion. Improvement between pre- and posttest results was statistically significant for four of ten items, including risk of prostate cancer-related distress, and suicidality, and the purpose of distress screening. Learners reported high satisfaction with course content, structure, engagement, relevance, and approach. They particularly valued the narrative-based approach and interactivity. Small numbers encountered technological problems and some offered suggestions to improve learner feedback. CONCLUSIONS: The course improved healthcare professionals' knowledge of distress among people affected by prostate cancer. Learners found the e-learning format feasible and acceptable. IMPLICATIONS FOR NURSING PRACTICE: Deeper understanding of the psychological implications of diagnosis and treatment of prostate cancer can help healthcare professionals respond to and manage distress among men and their families, and provide supportive care to improve health-related quality of life. Access to an online course can offer effective, feasible education on distress screening.
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Pessoal de Saúde , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/psicologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/enfermagem , Pessoa de Meia-Idade , Adulto , Pessoal de Saúde/educação , Pessoal de Saúde/psicologia , Estudos Transversais , Estresse Psicológico , Angústia Psicológica , Programas de Rastreamento/métodos , Feminino , Educação a Distância/métodos , Conhecimentos, Atitudes e Prática em Saúde , Instrução por Computador/métodos , Inquéritos e Questionários , Enfermagem Oncológica/educação , Enfermagem Oncológica/métodosRESUMO
Ambulance staff wellbeing programs aim to support the bio-psycho-social and sometimes spiritual needs of paramedics. While evidence demonstrates strong connections between spirituality and/or religion to wellbeing outcomes, little is known about spiritual care in ambulance services or its impact. The aim of this study was to investigate paramedics' perspectives on the role and value of Australian ambulance chaplains. A cross-sectional online study of registered paramedics in Australia was conducted between November and December 2022. Analysis of the 150 responses identified that paramedics viewed the chaplain's role as one built on professional caring relationships that provided proactive and reactive care in paramedic workplaces. Chaplains were perceived to promote wellbeing by incorporating emotional, psychological, social and spiritual care, and assisting paramedics to access additional support. Perceived religiousness of chaplains and organisational factors were barriers to paramedics accessing chaplains, while pre-existing relationships and shared experiences positively influenced paramedics decision to seek chaplain support.
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Ambulâncias , Humanos , Estudos Transversais , Austrália , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Ambulâncias/estatística & dados numéricos , Clero/psicologia , Clero/estatística & dados numéricos , Inquéritos e Questionários , Espiritualidade , Papel Profissional , Assistência Religiosa , Serviços Médicos de Emergência/estatística & dados numéricos , Pessoal Técnico de Saúde/psicologia , Pessoal Técnico de Saúde/estatística & dados numéricosRESUMO
BACKGROUND: Nurses, the largest healthcare workforce, are well placed to provide leadership in initiatives that promote planetary health. Yet, few practical examples of nurse leadership in the health sector's response to climate change are evident in the scholarly literature. AIM: The aim of this discussion paper is to profile Australian nurses who are leading initiatives designed to champion planetary health and promote sustainable practice. METHODS: The paper presents a series of case studies derived from interviews conducted in October and November 2023. FINDINGS: The nurses' experiences and insights, along with the challenges they have encountered, are presented as evidence of Kouzes and Posner's five practices of exemplary leadership. CONCLUSION: The case studies demonstrate that appointment of more nurses with climate and sustainability expertise will accelerate the implementation of responsive strategies that target waste management, emissions reduction and climate resilience across healthcare organisations.
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Mudança Climática , Liderança , Austrália , Humanos , Papel do Profissional de Enfermagem , Adulto , Feminino , Masculino , Pessoa de Meia-IdadeRESUMO
Introduction: Obstructive sleep apnea (OSA) is a common sleep breathing disorder and is associated with increased cardiovascular risk and daytime sleepiness. Continuous positive airway pressure (CPAP) is a treatment for OSA, which splints the airway open. The introduction of telemedicine in CPAP devices offers clinical staff an alternative method of reviewing patients, monitoring treatment, and reducing clinical time. Materials and Methods: A randomized control trial was conducted with patients randomized to one of three arms: Arm 1 (standard care), Arm 2 (modem and a virtual appointment), and Arm 3 (modem, smart device application DreamMapper™, and a virtual appointment). Ninety participants requiring treatment with CPAP following a diagnosis of OSA were recruited and data collected at baseline, 14 days, and 180 days. Additional contacts or appointments were also recorded. Results: Ninety participants (n = 90) were recruited (68% males and 32% females) with an average age of 52.0 ± 13.13 years and apnea/hypopnea index (AHI) 43.5 ± 21.92 (events/h). There was a statistically significant difference between the three arms in the average clinical time taken for the first follow-up appointment (p = 0.001). There was a statistically significant difference between the three arms in the number of additional appointments or contacts required (p = 0.03). Discussion and Conclusion: Telemedicine reduced clinical time at first follow-up, and in patients who received standard care or a smart device application to monitor their own CPAP treatment, there were significantly less additional appointments required when compared with telemedicine support in the form of a modem alone.
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Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono , Telemedicina , Humanos , Masculino , Pressão Positiva Contínua nas Vias Aéreas/métodos , Pressão Positiva Contínua nas Vias Aéreas/instrumentação , Feminino , Apneia Obstrutiva do Sono/terapia , Pessoa de Meia-Idade , Adulto , Agendamento de Consultas , Idoso , Fatores de Tempo , Cooperação do Paciente/estatística & dados numéricosRESUMO
OBJECTIVES: The objectives of this review were to appraise the available literature regarding nursing students' knowledge of and attitudes towards pain management; and secondly, to examine the instruments currently used to measure students' knowledge of and attitudes towards pain management. DESIGN: This review was conducted using Whittemore and Knafl's five-stage framework for integrative reviews. DATA SOURCES: A comprehensive search to retrieve relevant studies published in English between 1978 and 2022 was conducted using the databases: CINAHL, MEDLINE, Embase and Scopus databases. An updated search of the same databases was performed to identify studies published in 2023-2024. REVIEW METHODS: The initial search located 558 articles. One more relevant article was identified from an updated search test. Total of 244 duplicated records were removed. The remaining 315 studies were eligible for screening. After screening and checking for eligibility, 29 included articles were critically appraised using the Joanna Briggs Institute critical appraisal tools. RESULTS: Synthesis of the findings of the 29 included studies indicated that, internationally, nursing students have limited knowledge and often hold negative attitudes towards pain. Various instruments have been used to measure students' knowledge and attitudes towards pain. Most studies used true/false or multiple-choice questions and Likert-type scales. The validity and reliability of most of the tools were reported to be acceptable. The most commonly used instrument was the Knowledge and Attitudes Survey Regarding Pain. CONCLUSION: The findings from this review suggest the need for refinement of pain education programs to improve nursing students' knowledge of and attitudes towards pain management. Future research should focus on understanding the personal and environmental factors that impact students' level of knowledge and attitudes so as to inform curriculum development and ultimately the quality of the care graduates provide.
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Conhecimentos, Atitudes e Prática em Saúde , Manejo da Dor , Estudantes de Enfermagem , Humanos , Estudantes de Enfermagem/psicologia , Manejo da Dor/métodos , Manejo da Dor/psicologia , Bacharelado em Enfermagem/métodosRESUMO
BACKGROUND: The increase in intensive care unit (ICU) capacity compelled by the COVID-19 pandemic required the rapid deployment of non-critical-care registered nurses to the ICU setting. The upskill training needed to prepare these registered nurses for deployment was rapidly assembled due to the limited timeframe associated with the escalating pandemic. Scoping the literature to identify the content, structure, and effectiveness of the upskill education provided is necessary to identify lessons learnt during the COVID-19 pandemic response so that they may guide workforce preparation for future surge planning. AIM: The aim of this scoping review was to map the literature to identify the available information regarding upskill training and preparedness of non-critical-care registered nurses deployed to the ICU during the COVID-19 pandemic. METHODS: This scoping review was conducted in accordance with JBI methodology. A protocol outlined the review questions and used the participants, concept, and context framework to define the inclusion and exclusion criteria. A search of healthcare databases MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), Cochrane, and Scopus was supplemented with a grey literature search via Google. RESULTS: Screening and review found 32 manuscripts that met the inclusion criterion for examination. Analysis revealed variation in duration of programs, theoretical versus practical content, face-to-face or online mode of delivery, and duration of preparation time at the bedside in the ICU setting. Data on contributors to preparedness for deployment were sparse but included training, support, peer education, buddy time, and clarity around responsibilities and communication. DISCUSSION: Evaluation of upskill education was mostly limited to post-training surveys. Few studies explored the preparedness of deployed registered nurses as an outcome of their upskill training or described measures of effectiveness of ICU deployment. CONCLUSION: There is limited evidence describing preparedness of non-critical-care registered nurses on deployment to the ICU. Further research is needed to identify what elements of upskill education led to preparedness and effective deployment to the ICU setting.
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COVID-19 , Unidades de Terapia Intensiva , Humanos , COVID-19/enfermagem , SARS-CoV-2 , Pandemias , Recursos Humanos de Enfermagem Hospitalar/educaçãoRESUMO
Fibroblast activation protein (FAP) is a serine protease upregulated at sites of tissue remodeling and cancer that represents a promising therapeutic and molecular imaging target. In prostate cancer, studies of FAP expression using tissue microarrays are conflicting, such that its clinical potential is unclear. Furthermore, little is known regarding FAP expression in benign prostatic tissues. Here we demonstrated, using a novel iterative multiplex IHC assay in standard tissue sections, that FAP was nearly absent in normal regions, but was increased consistently in regions of proliferative inflammatory atrophy (PIA). In carcinoma, FAP was expressed in all cases, but was highly heterogeneous. High FAP levels were associated with increased pathological stage and cribriform morphology. We verified that FAP levels in cancer correlated with CD163+ M2 macrophage density. In this first report to quantify FAP protein in benign prostate and primary tumors, using standard large tissue sections, we clarify that FAP is present in all primary prostatic carcinomas, supporting its potential clinical relevance. The finding of high levels of FAP within PIA supports the injury/regeneration model for its pathogenesis and suggests that it harbors a protumorigenic stroma. Yet, high levels of FAP in benign regions could lead to false positive FAP-based molecular imaging results in clinically localized prostate cancer.
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OBJECTIVE: To identify, critically appraise and synthesise evidence of the use and effectiveness of the arts for enhancing pre-registration/prelicensure healthcare students' empathy skills. DESIGN: A systematic review of mixed methods literature. DATA SOURCES: A search of six electronic databases was conducted. REVIEW METHODS: Articles describing English language, peer-reviewed, primary research studies reporting empathy as an outcome of an arts-based intervention with pre-registration/prelicensure healthcare students (years 1-7) and published between 2000 and 2024 were eligible for inclusion. The JBI Manual for Evidence Synthesis guided the review and a convergent segregated methodology was used to synthesise the results. Methodological rigour of included studies was examined using the Mixed Methods Appraisal Tool. RESULTS: Twenty studies from 12 countries described the use of the arts to develop empathy, with visual arts being the most common approach (n = 8). Other modalities included film, drama, digital stories, literature, creative writing, music, poetry, photography and dance. Studies included nursing, medicine and dental, pharmacy and/or health sciences students. Ten studies used quantitative methods, three qualitative, and seven used mixed methods designs. Of the studies that presented pre-post outcome measures, nine reported significant gains in empathy scores at post-test and two reported non-significant gains in empathy. In eight studies, empathy scores demonstrated a significant intervention effect with effect sizes ranging from moderate (d = 0.52) to large (d = 1.19). Findings from qualitative studies revealed that arts pedagogies support students to better understand the perspectives of people with a lived experience of suffering but that these approaches are sometimes perceived negatively by students. CONCLUSIONS: Arts interventions generally have a positive effect on healthcare students' empathy levels and enable a nuanced conceptual understanding of empathy. Arts modalities used as a stimulus for active learning and supported with facilitated group-based discussion and/or reflection, tend to be most effective.
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Empatia , Humanos , Arte , Estudantes de Ciências da Saúde/psicologiaRESUMO
Background: The epidemiological patterns of COVID-19 varied across Australia and differed from most other countries. Few studies describe the impact that the pandemic had on nursing student wellbeing, education and career.Aim: This study aimed to investigate how the COVID-19 pandemic impacted on nursing students' well-being, clinical placement and learning.Design: Cross-sectional survey.Setting: Sydney, Australia.Participants: Second- and third-year nursing students.Methods: Second- and third-year nursing degree students were asked to participate in an ethically approved study during March to May 2021. The de-identified on-line survey consisted of 63 closed end question and one open ended question. On completion, the dataset was exported from Redcap and imported into SPSS for analysis. Open ended text data were analysed by two researchers.Results: Of the 105 participating nursing students, a third (n = 26/83, 31%) thought about changing their degree to a non-nursing degree. The acknowledged risk of caring for a COVID-19 patient incrementally increased stress (ß-coefficient = 0.6, p value = 0.009, 95% CI 0.2-0.9). Conversely students who intended to complete their degree were less likely to report stress. Students who had prior nursing experience were three times more likely to report an increased generalised anxiety level (OR 3.8, p-value = 0.02, 95% CI 1.2-12.2), yet they were less likely to experience personal accomplishment burnout compared to other students. Nursing students who contemplated a change of degree to a non-nursing degree were 15.7 times more likely to experience emotional exhaustion and were 3.5 times more likely to be report a risk of depersonalisation (p = 0.03, 95% CI, 1.3-11.5).Conclusion: The COVID-19 pandemic compromised nursing student well-being, and theoretical and practical learning. Findings have implications for healthcare and academic staff who teach nursing students. Implementation of student-centred evidence-based strategies to manage stress, burnout and anxiety, and to sustain a healthy student cohort is essential to retain the future nursing workforce.
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Esgotamento Profissional , COVID-19 , Bacharelado em Enfermagem , Estudantes de Enfermagem , Humanos , Estudos Transversais , Estudantes de Enfermagem/psicologia , Pandemias , COVID-19/epidemiologiaRESUMO
BACKGROUND: The impacts of climate change on planetary health are multifaceted and threaten public health gains made since World War II. Healthcare is the fifth largest global emitter of greenhouse gas emissions, demanding significant efforts to transition to an environmentally sustainable future. Addressing these issues will require collective societal action. In this regard, universities have a dual responsibility - (1) to tackle complex social, economic, and environmental challenges by championing sustainability initiatives designed to positively impact planetary health; and (2) to ensure that graduates are equipped with the knowledge, attitudes and skills needed to steward planetary health towards a more sustainable future. The future nursing and midwifery workforce must be educated to mitigate the health sector's impact on the environment, advocate for action on climate change, prepare for ongoing health impacts of unpredictable climate and environmental changes, and help communities and healthcare systems become more climate resilient. WHAT THIS PAPER CONTRIBUTES: To help increase nursing and midwifery educators' and students' capacity to support planetary-health related interventions, the overarching purpose of this paper is to provide a series of exemplars that illustrate sustainability initiatives used in four university-based clinical skills laboratories. These initiatives each demonstrate a commitment to the United Nation's Sustainable Development Goals and can be used to help embed the importance of planetary health in student learning.
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Laboratórios Clínicos , Tocologia , Humanos , Gravidez , Feminino , Atitude , Mudança Climática , EstudantesRESUMO
Cyclic high-dose testosterone administration, known as bipolar androgen therapy (BAT), is a treatment strategy for patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we report the results of a multicenter, single arm Phase 2 study (NCT03554317) enrolling 45 patients with heavily pretreated mCRPC who received BAT (testosterone cypionate, 400 mg intramuscularly every 28 days) with the addition of nivolumab (480 mg intravenously every 28 days) following three cycles of BAT monotherapy. The primary endpoint of a confirmed PSA50 response rate was met and estimated at 40% (N = 18/45, 95% CI: 25.7-55.7%, P = 0.02 one-sided against the 25% null hypothesis). Sixteen of the PSA50 responses were achieved before the addition of nivolumab. Secondary endpoints included objective response rate (ORR), median PSA progression-free survival, radiographic progression-free survival (rPFS), overall survival (OS), and safety/tolerability. The ORR was 24% (N = 10/42). Three of the objective responses occurred following the addition of nivolumab. After a median follow-up of 17.9 months, the median rPFS was 5.6 (95% CI: 5.4-6.8) months, and median OS was 24.4 (95% CI: 17.6-31.1) months. BAT/nivolumab was well tolerated, resulting in only five (11%) drug related, grade-3 adverse events. In a predefined exploratory analysis, clinical response rates correlated with increased baseline levels of intratumoral PD-1 + T cells. In paired metastatic tumor biopsies, BAT induced pro-inflammatory gene expression changes that were restricted to patients achieving a clinical response. These data suggest that BAT may augment antitumor immune responses that are further potentiated by immune checkpoint blockade.
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Nivolumabe , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Nivolumabe/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/patologia , Androgênios , Antígeno Prostático Específico , Intervalo Livre de Progressão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: Telomeres are terminal chromosomal elements that are essential for the maintenance of genomic integrity. The measurement of telomere content provides useful diagnostic and prognostic information, and fluorescent methods have been developed for this purpose. However, fluorescent-based tissue assays are cumbersome for investigators to undertake, both in research and clinical settings. METHODS: A robust chromogenic in situ hybridization (CISH) approach was developed to visualize and quantify telomere content at single cell resolution in human prostate tissues, both frozen and formalin-fixed, paraffin-embedded (FFPE). RESULTS: This new assay (telomere chromogenic in situ hybridization ["Telo-CISH"]) produces permanently stained slides that are viewable with a standard light microscope, thus avoiding the need for specialized equipment and storage. The assay is compatible with standard immunohistochemistry, thereby allowing simultaneous assessment of histomorphology, identification of specific cell types, and assessment of telomere status. In addition, Telo-CISH eliminates the problem of autofluorescent interference that frequently occurs with fluorescent-based methods. Using this new assay, we demonstrate successful application of Telo-CISH to help identify precancerous lesions in the prostate by the presence of markedly short telomeres specifically in the luminal epithelial cells. CONCLUSIONS: In summary, with fewer restrictions on the types of tissues that can be tested, and increased histologic information provided, the advantages presented by this novel chromogenic assay should extend the applicability of tissue-based telomere length assessment in research and clinical settings.