Quantification of urinary exosomal PSA for the diagnosis of prostate cancer: a study protocol with emphasis on application of clinical laboratory-based techniques.

BACKGROUND: Prostate cancer is the most common cancer in men and represents a major problem of public health. The current method of diagnosing/screening for prostate cancer is invasive and costly. There have been renewed and innovative studies on searching urinary biomarker for prostate cancer diagnosis, especially with the technologies of urinary exosomes. However, the technologies of urine exosomes usually need expensive machines such as ultracentrifuge and they are difficult to standardization, which hinder their application in clinical laboratory. OBJECTIVE: In this study, our objective is to detect urinary exosomes from prostate cancer for the development of a test to aid in the diagnosis of prostate cancer. METHODS: The exosomes from a prostate cancer cell line LNCaP was used to set up the techniques. For the analysis of urine samples of patients, the methods include the collection of first-void urine by using Colli-Pee device, the isolation of urine exosome by optimized precipitation method and the detection of exosomal PSA by Elecsys® total PSA. We have modified and optimized the isolation of urinary exosomes with precipitation method. RESULTS: By using the exosomes from the prostate cancer cell line, we have found that the urinary exosomal PSA can be quantified by automatic technique of Elecsys® total PSA. It will be a 2-year study. We shall start to include the patients and controls in the summer of 2024. We expect the results to be published in the last quarter of 2026. CONCLUSIONS: This is the first study to detect the urinary exosomal PSA by the technique of Elecsys® total PSA for the diagnosis of prostate cancer. This study emphasizes on the techniques suitable for the implementation in clinical laboratory, which will facilitate application of urinary exosomes to simplify and improve the diagnosis/screening of prostate cancer.

Immunogenicity of radiotherapy on bone metastases from prostate adenocarcinoma: What is the future for the combination with radiotherapy/immunotherapy?

Bone metastatic prostate cancers (PCa) are resistant to usual immunotherapies such as checkpoint inhibitors. The main hypothesis related to this immunoresistance is the lack of antigens to stimulate anti-tumor immunity. External radiation is a potential inducer antigens presentation and thus to immunotherapy proprieties. The aim of this review is to describe the tumor microenvironment specificities, especially in bone metastasis and the immune modifications after radiation therapy on a metastatic castration-resistant PCa population. PCa microenvironment is immunosuppressive because of many tumor factors. The complex interplay between PCa cells and bone microenvironment leads to a 'vicious circle' promoting bone metastasis. Furthermore, the immune and bone systems, are connected through an osteoclastogenic cytokine: the Receptor Activator Nuclear Factor Kappa B ligand. Adapted doses of ionizing radiation play a dual role on the tumor. Indeed, radiotherapy leads to immunogenicity by inducing damage associated with molecular patterns. However, it also induces an immunosuppressive effect by increasing the number of immunosuppressive cells. Interestingly, the abscopal effect could be used to optimize immunotherapy potential, especially on bone metastasis. Radiotherapy and immunotherapy combination is a promising strategy, however further studies are necessary to determine the more efficient types of radiation and to control the abscopal effect.

Comment on "Meta-analysis reveals declines in terrestrial but increases in freshwater insect abundances".

Van Klink et al (Reports, 24 April 2020, p. 417) argue for a more nuanced view of insect decline, and of human responsibility for this decline, than previously suggested. However, shortcomings in data selection and methodology raise questions about their conclusions on trends and drivers. We call for more rigorous methodology to be applied in meta-analyses of ecological data.

Reasons for transferral to emergency departments of terminally ill patients - a French descriptive and retrospective study.

BACKGROUND: Patients under palliative care and in hospital-at-home services are frequently transferred to emergency departments. We set out to identify the reasons for these presentations to determine the proportion that might be avoidable. METHODS: We conducted a retrospective study by assessment of patient files. We studied admissions to four emergency departments in an area of France (Puy-de-Dôme) between September 2011 and August 2013. Reasons for transfer and diagnostic conclusion by emergency doctors were noted. We collected date of admission, time spent, investigations and treatments performed and patients' outcomes after the medical conclusions. We also determined whether patients called the hospital-at-home service before going to the emergency department. From these data we discerned potentially avoidable and unavoidable consultations. RESULTS: We identified 52 transfers of patients from home to emergency departments. The most frequent reasons were: generalized weakness (11 cases), social isolation (8 cases) and end of life (7 cases). For 58 % of presentations, the investigations and treatments performed did not require presentation to an emergency department; 34 % of patients returned home after the visit, 41 % remained for simple observation and 20 % remained to receive special care. Two patients died in the emergency department. In 86 % of cases, presentations occurred when primary care was less readily available, and patients called home care services in only 42 % of cases before going to emergency departments. CONCLUSIONS: Half of the transfers to emergency departments were potentially avoidable for terminally ill patients in home care. To reduce this proportion we need to promote access to primary care, educate patients in hospital-at-home service and train care-givers and doctors in palliative medicine.