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Background and Purpose: Castration-resistant prostate cancer (CRPC) is a common male malignancy that requires new therapeutic strategies due to acquired resistance to its first-line treatment, docetaxel. The benefits of vitamin D on prostate cancer (PCa) progression have been previously reported. This study aimed to investigate the effects of vitamin D on chemoresistance in CRPC., Experimental Approach: Structure function relationships of potent vitamin D analogues were determined. The combination of the most potent analogue and docetaxel was explored in chemoresistant primary PCa spheroids and in a xenograft mouse model derived from a patient with a chemoresistant CRPC., Key Results: Here, we show that Xe4MeCF3 is more potent than the natural ligand to induce vitamin D receptor (VDR) transcriptional activities and that it has a larger therapeutic window. Moreover, we demonstrate that VDR agonists restore docetaxel sensitivity in PCa spheroids. Importantly, Xe4MeCF3 reduces tumour growth in a chemoresistant CRPC patient-derived xenograft. In addition, this treatment targets signalling pathways associated with cancer progression in the remaining cells., Conclusion and Implications: Taken together, these results unravel the potency of VDR agonists to overcome chemoresistance in CRPC and open new avenues for the clinical management of PCa., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objective: Custodiol is an intracellular, crystalloid cardioplegia solution that is a single-dose alternative to multi-dose cold blood cardioplegia; however, there is scarce data regarding its use in infants and children. The objective of this study was to compare its impact on myocardial function in infants., Methods: Single-center retrospective review including 132 patients <12 months old undergoing biventricular repair. There were 106 patients who received single-dose Custodiol and 27 patients who received multi-dose blood cardioplegia. Demographic and echocardiographic data were compared between the two groups., Results: Patients receiving Custodiol were slightly younger (100 ± 62 days) and lower weight (4.7 ± 1.3 kg) compared to 152 ± 86 days and 5.2 ± 1.3 kg for blood cardioplegia (p < 0.05). The Society of Thoracic Surgeons/European Association for Cardio-Thoracic Surgery Congenital Heart Surgery score was similar between both groups. Average cardiopulmonary bypass time was similar between both groups (Custodiol 93 ± 54 minutes vs. blood 81 ± 44 minutes, p = 0.46) as was aortic cross-clamp time (Custodiol 58 ± 33 minutes vs. cold blood 53 ± 33 minutes, p = 0.62). Pre-operative left ventricular ejection fraction was similar for blood 73 ± 8% versus Custodiol 70 ± 9%, p = 0.21. There was also no intergroup difference in left ventricular ejection fraction 24 hours post op (blood 64 ± 9% vs. Custodiol 65 ± 12%, p = 0.53) or at discharge (blood 66 ± 10% vs. Custodiol 66 ± 11%, p = 0.95). The pre-operative right ventricle function by fractional area change was also similar in blood cardioplegia (46 ± 13%) versus Custodiol (48 ± 9%, p = 0.38) and showed similar drops in parameters in the two groups 24 hours after surgery and at discharge., Conclusion: Single-dose Custodiol is as safe as blood cardioplegia for myocardial protection in congenital cardiac surgery for the cross-clamp times evaluated in this study. Evaluation at longer cross-clamp times would be helpful to determine if there is a greater benefit to single-dose Custodiol versus more repeated doses of blood cardioplegia for longer cross-clamp times.

Objectives: To assess if prostatic urethral lift (PUL) can be as effective on larger prostates. PUL is an endoscopic device that retracts prostatic tissue to relieve benign prostatic hypertrophy (BPH) obstruction. In 2013, PUL was approved for patients with a prostate size of <80 g and no median lobes. The approval was primarily based on the L.I.F.T. study, which only evaluated patients with prostates between 30 and 80 g in size., Materials and Methods: Seventy-four patients underwent PUL between April 2, 2014, and December 2, 2015, for BPH management. Fifty-one patients were in the <80 g prostate group (median: 46 g, range: 20-78 g) and 23 in the >80 g prostate group (median: 112 g, range: 81-254 g). Student t-tests and Fisher's exact tests were used to compare continuous and categorical variables. p-Value of <0.05 was considered statistically significant., Results: Median time between PUL and follow-up AUA symptom score (AUASS) was 144 days. A difference between the numbers of PUL implants used was seen. A significant improvement in AUASSs was seen in both groups following the procedure. There was no significant difference in age, AUASS before or after the procedure, or need for an additional outlet procedure between the two groups., Conclusion: Early experience finds that a sufficient number of men with larger prostates appear to benefit from PUL. Patients with >80 g prostate size were more likely to have a median lobe and may benefit from resection of the median lobe at time of the PUL. Long-term follow-up is needed to evaluate the durability of the PUL procedure.