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Background: Many metastatic prostate cancer prognostics have been suggested, but few are validated. Nodal metastasis burden and baseline biochemical characteristics are overlooked in the currently accepted stratifications for metastatic hormone-sensitive prostate cancer (mHSPC). Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) is likely to increase the incidence of pelvic nodal and mHSPC undetected by conventional scans. However, there is no consensus on managing regional nodal metastasis (N1M0) and no separate guidelines for non-regional nodal (M1a) and low-volume bone (M1b) spread but collectively as a part of low-volume CHAARTED disease. Objectives: To assess the different prognostic factors for stage IV disease classified as CHAARTED low-volume on a real-world series of patients and to examine treatment preference for each of the disease subcategories. Methods and design: This retrospective cross-sectional study included patients diagnosed with HSPC at stage IV, with low-volume disease according to the CHAARTED criteria. Data were collected from the database of Portsmouth and St. Mary NHS Hospitals between February 2017 and August 2023. Patient characteristics were analysed, and prognostic factors were evaluated using Cox regression analysis. 5-year progression-free survival (PFS) was the primary outcome measure. Results: Data on 126 patients were analysed. Seven patients (6%) had N1M0, 28 (22%) M1a, and 91 (72%) M1b. 5-year PFS was 80.9% for M1a and 54.9% for M1b metastases, p = 0.3. High prostate-specific antigen (PSA) value (⩾25) was identified as an independent prognostic factor for PFS with HR = 2.80 (95% CI: 1.19–6.56), p = 0.0179. Variable treatment preference for each subclass reflects the uncertainty regarding the best regimen and the importance of consolidation prostate radiotherapy (cRT) in clinical practice. Conclusion: Early results of our data analysis underscore the significance of baseline PSA as an independent prognostic factor alongside anatomical tumour extent of spread in stage IV low-volume metastasis prostate cancer. There is no agreement on treatment for each subcategory, necessitating further real-world studies and clinical trials. Further follow-up would assess the prognostic benefit of cRT. [ABSTRACT FROM AUTHOR]

Aims: Increased Ankyrin Repeat Domain 1 (ANKRD1) levels linked to gain of function mutations have been associated to total anomalous pulmonary venous return and adult cardiomyopathy occurrence in humans. The link between increased ANKRD1 level and cardiac structural and functional disease is not understood. To get insight into this problem, we have generated a gain of function ANKRD1 mouse model by overexpressing ANKRD1 in the myocardium., Methods and Results: Ankrd1 is expressed non-homogeneously in the embryonic myocardium, with a dynamic nucleo-sarcomeric localization in developing cardiomyocytes. ANKRD1 transgenic mice present sinus venosus defect, which originates during development by impaired remodelling of early embryonic heart. Adult transgenic hearts develop diastolic dysfunction with preserved ejection fraction, which progressively evolves into heart failure, as shown histologically and haemodynamically. Transgenic cardiomyocyte structure, sarcomeric assembly, and stability are progressively impaired from embryonic to adult life. Postnatal transgenic myofibrils also present characteristic functional alterations: impaired compliance at neonatal stage and impaired lusitropism in adult hearts. Altogether, our combined analyses suggest that impaired embryonic remodelling and adult heart dysfunction in ANKRD1 transgenic mice present a common ground of initial cardiomyocyte defects, which are exacerbated postnatally. Molecular analysis showed transient activation of GATA4-Nkx2.5 transcription in early transgenic embryos and subsequent dynamic transcriptional modulation within titin gene., Conclusions: ANKRD1 is a fine mediator of cardiomyocyte response to haemodynamic load in the developing and adult heart. Increased ANKRD1 levels are sufficient to initiate an altered cellular phenotype, which is progressively exacerbated into a pathological organ response by the high ventricular workload during postnatal life. Our study defines for the first time a unifying picture for ANKRD1 role in heart development and disease and provides the first mechanistic link between ANKRD1 overexpression and cardiac disease onset., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)