Clinical value of prostate health index as an indicator for recommending magnetic resonance imaging in patients with gray-zone prostate-specific antigen level.

PURPOSE: To evaluate the usefulness of prostate health index (PHI) as an indicator for recommending magnetic resonance imaging (MRI) in patients with prostate-specific antigen (PSA) gray zone level < 10 ng/mL. METHODS: 443 patients who underwent prostate biopsy (PB) after serum PHI test and MRI between April 2019 and December 2022 were enrolled. For patients with visible lesion on MRI with Prostate Imaging Reporting and Data System Score (PI-RADS) ≥ 3, MRI-targeted PB was performed in addition to systematic 12-core PB. RESULTS: The optimal cutoff value of PHI for predicting PI-RADS ≥ 3 lesions was 39.6, which was significantly associated with overall prostate cancer (OR 3.07, p = 0.018) and clinically significant prostate cancer (csPCa) (OR 4.15, p = 0.006) at MRI-targeted PB cores. When MRI was restricted to patients with PHI ≥ 39.6 alone, 28.7% of unnecessary MRI could be saved at the cost of missing 13.6% of csPCa. When omitting MRI for patients with PHI < 39.6 and PSAD < 0.12 ng/mL2, unnecessary MRI could be reduced by 20.1% with the risk of missing 6.2% of csPCa. With addition of systematic PB, 21.0% of patients with negative MRI-targeted PB were diagnosed as csPCa. CONCLUSIONS: For patients in PSA gray zone, PHI of 39.6 might be an indicator for MRI and further MRI-targeted PB in additional to PSAD of 0.12 ng/mL2, reducing 20.1% of unnecessary MRI with the minimal risk of missing 6.2% of csPCa. To maximize csPCa detection, combining both MRI-targeted and systematic PB should be also considered.

Prognosis after radical prostatectomy in men older than 75 years: long-term results from a single tertiary center.

Background: Despite longer lifespans, guidelines for prostate cancer treatment recommend surgery for those with over 10 years of life expectancy, potentially leaving older patients undertreated. This study examines the outcomes of radical prostatectomy (RP) in a large cohort of men older than 75 years. Materials and methods: We retrospectively analyzed 636 patients from a pool of 4,500 RP cases at a single tertiary institution from 2004 to 2022. Patients younger than 75 years or with incomplete records were excluded. Baseline clinical variables, including PSA and biopsy grade group (GG), as well as postoperative pathology and oncological outcomes, were assessed. Achievement of continence based on no pads and ≤1 pad at last follow-up were evaluated. Results: Mean age and PSA were 76.4 years and 15.3 ng/ml, respectively. At biopsy, GG1 and 2 were found in 18.1% and 31.5%, respectively, with 28.5% harboring GG4-5 tumors. After RP, 41.5% had GG upgrade compared to biopsy results, with 46.5% with ≥pT3 tumors. In a mean follow-up of 41.5 months, 82.3% were able to attain total continence of 0 pads, and 89.5% used ≤1 pads at the last follow-up. Overall and cancer-specific mortality was observed in 4.3% and 0.9%, respectively, and biochemical recurrence (BCR) occurred in 20.3% after a median of 154 months. At multivariate analysis, age was not a significant factor for BCR, whereas preoperative PSA, biopsy GG, margin positivity, and lymph node invasion were significant. Conclusion: RP is feasible in men older than 75 years with decent oncological outcome, with absolute age insignificant within this age group. Risk of undertreatment should be acknowledged, and definite treatment must be considered.

Primary photochemistry of the dark- and light-adapted states of the YtvA protein from Bacillus subtilis.

The primary (100 fs to 10 ns) and secondary (10 ns to 100 µs) photodynamics in the type II light-oxygen-voltage (LOV) domain from the blue light YtvA photoreceptor extracted from Bacillus subtilis were explored with transient absorption spectroscopy. The photodynamics of full-length YtvA were characterized after femtosecond 400 nm excitation of both the dark-adapted D447 state and the light-adapted S390 state. The S390 state relaxes on a 43 min time scale at room temperature back into D447, which is weakly accelerated by the introduction of imidazole. This is ascribed to an obstructed cavity in YtvA that hinders access to the embedded FMN chromophore and is more open in type I LOV domains. The primary photochemistry of dark-adapted YtvA is qualitatively similar to that of the type I LOV domains, including AsLOV2 from Avena sativa, but exhibits an appreciably higher (60% greater) terminal triplet yield, estimated near the maximal ΦISC value of ≈78%; the other 22% decays via non-triplet-generating fluorescence. The subsequent secondary dynamics are inhomogeneous, with three triplet populations co-evolving: the faster-decaying (I)T* population (38% occupancy) with a 200 ns decay time is nonproductive in generating the S390 adduct state, a slower (II)T* population (57% occupancy) exhibits a high yield (Φadduct ≈ 100%) in generating S390 and a third (5%) (III)T*population persists (>100 µs) with unresolved photoactivity. The ultrafast photoswitching dynamics of the S390 state appreciably differ from those previously resolved for the type I AcLOV2 domain from Adiantum capillus-veneris [Kennis, J. T., et al. (2004) J. Am. Chem. Soc. 126, 4512], with a low-yield dissociation (Φdis ≈ 2.5%) reaction, which is due to an ultrafast recombination reaction, following photodissociation, and is absent in AcLOV2, which results in the increased photoswitching activity of the latter domain.

Sodium dodecyl sulfate adsorption onto positively charged surfaces: monolayer formation with opposing headgroup orientations.

The adsorption and structure of sodium dodecyl sulfate (SDS) layers onto positively charged films have been monitored in situ with vibrational sum-frequency-generation (SFG) spectroscopy and surface plasmon resonance (SPR) sensing. Substrates with different charge densities and polarities used in these studies include CaF2 at different pH values as well as allylamine and heptylamine films deposited onto CaF2 and Au substrates by radio frequency glow discharge deposition. The SDS films were adsorbed from aqueous solutions ranging in concentration from 0.067 to 20 mM. In general the SFG spectra exhibited well resolved CH and OH peaks. However, at SDS concentrations between 1 and 8 mM the SFG CH and OH intensities decreased close to background levels. Combined data sets from molecular conformation, orientation, and order sensitive SFG with mass sensitive SPR suggest that the observed changes in SFG intensities above 0.2 mM are related to structural arrangements in the SDS layer. A model is proposed where the SFG intensity minimum between 1 and 8 mM is associated with a monolayer containing two headgroup orientations, one pointing toward the substrate and one pointing toward the solution phase. The SFG peaks observed at concentrations below 0.2 mM are dominated by the presence of adsorbed contaminants such as fatty alcohols (e.g., dodecanol), which are more surface active than SDS. As SDS solution concentration is increased above 1 mM SDS molecules are incorporated in the surface layer, with dodecanol continuing to be present in the surface layer for solution concentrations up to at least the critical micelle concentration.

Cytoreductive nephrectomy in the age of immunotherapy-based combination treatment.

Renal cell carcinoma (RCC) displays a wide spectrum of oncological prognosis and clinical behavior, and is noted for its generally poor outcome in metastatic settings. However, the introduction of immunotherapy after the cytokine era has changed the landscape of treatment for metastatic RCC, outperforming previous targeted therapy and providing new hope for patients with advanced disease. Cytoreductive nephrectomy (CN) has been the center of controversy, with questionable survival benefit when compared to systemic therapy. Despite discouraging results from the two randomized clinical trials (CARMENA & SURTIME), interest into the role of CN is being rekindled, and contemporary real-world studies provide supporting evidence to suggest that CN may still have a role in well-selected patients treated or expecting treatment with immunotherapy, not only for symptomatic control but also for oncological benefit. In this review article, we attempt to review the modern insight into the role of CN for metastatic RCC in contemporary medicine, with a focus on treatment with immune checkpoint inhibitor combination-based immunotherapy.

Evaluation of the efficiency of transurethral enucleation with bipolar energy according to prostate volume for patients with benign prostate hyperplasia.

Background: This study evaluated the efficiency and safety of transurethral enucleation with bipolar energy (TUEB) using a spatula loop according to prostate volume. Methods: We retrospectively evaluated 398 patients who underwent TUEB for benign prostatic hyperplasia at a single tertiary hospital between August 2018 and December 2022. The patients were divided into three groups according to estimated prostate volume (ePV): ≤40 mL (n = 67), 40-80 mL (n = 200), and ≥80 mL (n = 131). To compare the efficiency of TUEB, perioperative parameters including TUEB and enucleation efficiencies, were calculated as enucleated tissue weight per operation time and enucleated tissue weight per enucleation time, respectively. Preoperative and postoperative functional outcomes such as the International Prostate Symptom Score (IPSS), quality-of-life (QoL) score, maximum flow rate (Qmax), and post-void residual urine volume (PVR), were also compared. Results: The IPSS total score, voiding sub-score, Qmax, and PVR improved after TUEB in all groups (all p < 0.05). The TUEB and enucleation efficiencies increased with increasing ePVs (all P < 0.001). When comparing the three prostate volume groups, there were no significant differences in functional outcomes within 12 months after TUEB (all-Bonferroni adjusted P > 0.017). A total of 57 patients experienced adverse events after TUEB, with no significant differences between the three groups (p = 0.507). Conclusion: As prostate volume increases, the perioperative efficiency of TUEB is enhanced. Meanwhile, small prostates did not show significant differences in the improvement of functional outcomes and complications in comparison with larger prostates.

The learning curve for transurethral enucleation with bipolar energy for benign prostate hyperplasia: a single-surgeon experience of 494 patients.

This study was performed to investigate the learning curve of transurethral enucleation with bipolar energy (TUEB) for benign prostatic hyperplasia. The study involved 494 consecutive patients who underwent TUEB for benign prostatic hyperplasia from August 2018 to March 2022 by one surgeon (SJJ, Seoul National University Bundang Hospital, Seongnam, Korea). The patients were followed up at 1 week, 1 month, 3 months, and 6 months postoperatively. To evaluate the learning curve of TUEB, perioperative parameters including the enucleation ratio (enucleated tissue weight/transitional zone volume), TUEB efficiency (enucleated tissue weight/operation time), and enucleation efficiency (enucleated tissue weight/enucleation time) were analyzed. Functional outcomes and postoperative complications were also assessed, including the International Prostate Symptom Score (IPSS), IPSS quality-of-life (QoL) score, and uroflowmetry outcomes. The patients' median age was 72 (interquartile range [IQR]: 66-78) years, and the estimated prostate volume and transitional zone volume were 63.0 (IQR: 46.0-90.6) ml and 37.1 (IQR: 24.0-60.0) ml, respectively. The enucleation ratio, TUEB efficiency, and enucleation efficiency were 0.60 (IQR: 0.46-0.54) g ml-1, 0.33 (IQR: 0.22-0.46) g min-1, and 0.50 (IQR: 0.35-0.72) g min-1, respectively, plateauing after 70 cases. The functional outcomes, including total IPSS, IPSS QoL score, and uroflowmetry outcomes, significantly improved at 6 months after TUEB (all P < 0.05), but without significant differences over the learning curve. Sixty-five (13.2%) patients developed complications after TUEB, 21.5% of whom experienced major complications (Clavien-Dindo grade ≥3). The rate of major complications declined as the number of TUEB cases increased (P = 0.013). Our results suggest that the efficiency of TUEB stabilized within 70 procedures.

Total Intracorporeal Versus Open Bladder Cuffing in Robotic Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

OBJECTIVE: To evaluate a single institution experience of total intracorporeal bladder cuffing and distal ureterectomy (DUBC) in robotic radical nephrouretectomy (RNU) for upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: One hundred sixty-eight patients treated for UTUC with robotic RNU at our institution from May 2009 to October 2019 were retrospectively analyzed. Ninety-two patients underwent total intracorporeal DUBC after robotic dock repositioning, whereas 76 patients underwent open methods via Gibson incision. Perioperative outcomes including operation time, estimated blood loss (EBL), transfusion rates, use of painkillers, Visual analogue scale (VAS) pain scores, and complication rates were compared, as well as pathological and oncological outcomes. Uni- and multi-variate Cox regression models were performed for survival analysis. RESULTS: There were no significant differences in baseline patient characteristics between the 2 groups. Patients who underwent intracorporeal bladder cuffing had less EBL (169.8 ± 150.4 vs 214.6 ± 157.0, P = .091) and decreased pain at 1 week (VAS score 1.18 ± 1.1 vs 2.2 ± 1.1, P = .017). Pathological outcomes were not significantly different, and oncological outcomes including local and intravesical recurrence, cancer-specific and overall mortality were comparable to patients who received extracorporeal bladder cuffing. Intracorporeal bladder cuffing was not associated with increased risk of progression on univariate analysis (HR 0.600, 95% CI, 0.314-1.147; P = .122). CONCLUSION: Based on our experience, intracorporeal DUBC can be a safe and oncologically non-inferior alternative method to RNU, with benefits of decreased EBL and postoperative pain. Future prospective trials are necessary to further validate our results.

Polygenic risk score for tumor aggressiveness and early-onset prostate cancer in Asians.

We attempted to assess the performance of an ethnic-specific polygenic risk score (PRS) designed from a Korean population to predict aggressive prostate cancer (PCa) and early-onset (age < 60). A PRS score comprised of 22 SNPs was computed in 3695 patients gathered from one of 4 tertiary centers in Korea. Males with biopsy or radical prostatectomy-proven PCa were included for analysis, collecting additional clinical parameters such as age, BMI, PSA, Gleason Group (GG), and staging. Patients were divided into 4 groups of PRS quartiles. Intergroup differences were assessed, as well as risk ratio and predictive performance based on GG using logistic regression analysis and AUC. No significant intergroup differences were observed for BMI, PSA, and rate of ≥ T3a tumors on pathology. Rate of GG ≥ 2, GG ≥ 3, and GG ≥ 4 showed a significant pattern of increase by PRS quartile (p < 0.001, < 0.001, and 0.039, respectively). With the lowest PRS quartile as reference, higher PRS groups showed sequentially escalating risk for GG ≥ 2 and GG ≥ 3 pathology, with a 4.6-fold rise in GG ≥ 2 (p < 0.001) and 2.0-fold rise in GG ≥ 3 (p < 0.001) for the highest PRS quartiles. Combining PRS with PSA improved prediction of early onset csPCa (AUC 0.759) compared to PRS (AUC 0.627) and PSA alone (AUC 0.736). To conclude, an ethnic-specific PRS was found to predict susceptibility of aggressive PCa in addition to improving detection of csPCa when combined with PSA in early onset populations. PRS may have a role as a risk-stratification model in actual practice. Large scale, multi-ethnic trials are required to validate our results.

Germline DNA-Repair Genes and HOXB13 Mutations in Korean Men with Metastatic Prostate Cancer: Data from a Large Korean Cohort.

PURPOSE: Germline mutations in DNA damage repair (DDR) genes such as BRCA2 have been associated with prostate cancer (PC) risk but has not been thoroughly evaluated for metastatic prostate cancer (mPC) in Asian men. This study attempts to evaluate frequency of DDR mutations in the largest cohort of Koreans. MATERIALS AND METHODS: We recruited 340 patients with mPC unselected for family history of cancer and compared to 495 controls. Whole genome sequencing was applied to assess germline pathogenic/likely pathogenic variants (PV/LPVs) in 26 DDR genes and HOXB13, including 7 genes (ATM, BRCA1/2, CHEK2, BRIP1, PALB2, and NBN) associated with hereditary PC. Comparisons to published Caucasian and Japanese cohorts were performed. RESULTS: Total of 28 PV/LPVs were identified in 30 (8.8%) patients; mutations were found in 13 genes, including BRCA2 (15 men [4.41%]), ATM (2 men [0.59%]), NBN (2 men [0.59%], and BRIP1 (2 men [0.59%]). Only one patient had HOXB13 mutation (0.29%). A lower rate of overall germline variant frequency was observed in Korean mPC compared to Caucasians (8.8% vs. 11.8%), but individual variants notably differed from Caucasian and geographically similar Japanese cohorts. PV/LPVs in DDR genes tended to increase gradually with higher Gleason scores (GS 7, 7.1%; GS 8, 7.5%; GS 9-10, 9.9%). CONCLUSIONS: BRCA2 was the most frequently mutated gene common to different cohorts supporting its importance, but differences in variant distribution in Korean mPC underscore the need for ethnic-specific genetic models. Future ethnic-specific analyses are warranted to verify our findings.

TNM-Based Head-to-Head Comparison of Urachal Carcinoma and Urothelial Bladder Cancer: Stage-Matched Analysis of a Large Multicenter National Cohort.

PURPOSE: Outcome analysis of urachal cancer (UraC) is limited due to the scarcity of cases and different staging methods compared to urothelial bladder cancer (UroBC). We attempted to assess survival outcomes of UraC and compare to UroBC after stage-matched analyses. MATERIALS AND METHODS: Total 203 UraC patients from a multicenter database and 373 UroBC patients in single institution from 2000 to 2018 were enrolled (median follow-up, 32 months). Sheldon stage conversion to corresponding TNM staging for UraC was conducted for head-to-head comparison to UroBC. Perioperative clinical variables and pathological results were recorded. Stage-matched analyses for survival by stage were conducted. RESULTS: UraC patients were younger (mean age, 54 vs. 67 years; p < 0.001), with 163 patients (80.3%) receiving partial cystectomy and 23 patients (11.3%) radical cystectomy. UraC was more likely to harbor ≥ pT3a tumors (78.8% vs. 41.8%). While 5-year recurrence-free survival, cancer-specific survival (CSS) and overall survival were comparable between two groups (63.4%, 67%, and 62.1% in UraC and 61.5%, 75.9%, and 67.8% in UroBC, respectively), generally favorable prognosis for UraC in lower stages (pT1-2) but unfavorable outcomes in higher stages (pT4) compared to UroBC was observed, although only 5-year CSS in ≥ pT4 showed statistical significance (p=0.028). Body mass index (hazard ratio [HR], 0.929), diabetes mellitus (HR, 1.921), pathologic T category (HR, 3.846), and lymphovascular invasion (HR, 1.993) were predictors of CSS for all patients. CONCLUSION: Despite differing histology, UraC has comparable prognosis to UroBC with relatively favorable outcome in low stages but worse prognosis in higher stages. The presented system may be useful for future grading and risk stratification of UraC.

Possibilities and limitations of using low biomass samples for urologic disease and microbiome research.

With the dogma of sterile urine no longer held as truth, numerous studies have implicated distinct changes in microbial diversity and composition to diseased subgroups in both benign and malignant urological diseases, ranging from overactive bladder to bladder and prostate cancer. Further facilitated by novel and effective techniques of urine culture and sequencing, analysis of the genitourinary microbiome holds high potential to identify biomarkers for disease and prognosis. However, the low biomass of samples included in microbiome studies of the urinary tract challenge researchers to draw definitive conclusions, confounded by technical and procedural considerations that must be addressed. Lack of samples and adequate true negative controls can lead to overestimation of microbial influence with clinical relevance. As such, results from currently available studies and assessment of their limitations required a thorough understanding. The purpose of this narrative review was to summarize notable microbiome studies in the field of urology with a focus on significant findings and limitations of study design. Methodological considerations in future research are also discussed.

Temporal changes of PIRADS scoring by radiologists and correlation to radical prostatectomy pathological outcomes.

Purpose: To assess temporal improvement of prostate image reporting and data system (PIRADS) 3-5 lesion correlation to histopathologic findings from radical prostatectomy (RP) in prostate cancer (PCa). Materials and methods: A total of 1481 patients who underwent RP for biopsy-proven PCa between 2015 and 2019 were divided into 14 groups of 100 sequential readings for the evaluation of histopathological correlation with PIRADS readings. Temporal trends of PIRADS distribution and predictive performance for RP pathology were evaluated to assess underlying changes in prostate magnetic resonance imaging (MRI) interpretation by radiologists. Results: PIRADS 4-5 lesions were significantly correlated with the increasing rates of Gleason Group (GG) upgrade (p = 0.044) and decreasing rate of GG downgrade (p = 0.016) over time. PIRADS ≥3 lesions read after median 2 years of experience were shown to independently predict intermediate-high-risk (GG ≥ 3) PCa (odds ratio 2.93, 95% confidence interval 1.00-8.54; P= 0.049) in RP pathology. Preoperative GG ≥ 3 biopsy lesions with PIRADS 4-5 lesions were significantly more susceptible to GG upgrade (P= 0.035) and GG ≥ 4 RP pathology (p = 0.003) in experienced reads, in contrast to insignificant findings in early readings (p = 0.588 and 0.248, respectively). Conclusion: Preoperative MRI reports matched with RP pathology suggest an improved prediction of adverse pathology in PIRADS 3-5 lesions over time, suggesting a temporal change in PIRADS interpretation and predictive accuracy. Institutions with low volume experience should use caution in solely relying on MRI for predicting tumor characteristics. Future prospective trials and larger scale assessments are required to further validate our results.

Prediction of clinically significant prostate cancer using polygenic risk models in Asians.

PURPOSE: To develop and evaluate the performance of a polygenic risk score (PRS) constructed in a Korean male population to predict clinically significant prostate cancer (csPCa). MATERIALS AND METHODS: Total 2,702 PCa samples and 7,485 controls were used to discover csPCa susceptible single nucleotide polymorphisms (SNPs). Males with biopsy-proven or post-radical prostatectomy Gleason score 7 or higher were included for analysis. After genotype imputation for quality control, logistic regression models were applied to test association and calculate effect size. Extracted candidate SNPs were further tested to compare predictive performance according to number of SNPs included in the PRS. The best-fit model was validated in an independent cohort of 311 cases and 822 controls. RESULTS: Of the 83 candidate SNPs with significant PCa association reported in previous literature, rs72725879 located in PRNCR1 showed the highest significance for PCa risk (odds ratio, 0.597; 95% confidence interval [CI], 0.555-0.641; p=4.3×10-45). Thirty-two SNPs within 26 distinct loci were further selected for PRS construction. Best performance was found with the top 29 SNPs, with AUC found to be 0.700 (95% CI, 0.667-0.734). Males with very-high PRS (above the 95th percentile) had a 4.92-fold increased risk for csPCa. CONCLUSIONS: Ethnic-specific PRS was developed and validated in Korean males to predict csPCa susceptibility using the largest csPCa sample size in Asia. PRS can be a potential biomarker to predict individual risk. Future multi-ethnic trials are required to further validate our results.

The Prostate Health Index and multi-parametric MRI improve diagnostic accuracy of detecting prostate cancer in Asian populations.

PURPOSE: The aim of this study was to evaluate the effectiveness of the Prostate Health Index (PHI) and prostate multi-parametric magnetic resonance imaging (mpMRI) in predicting prostate cancer (PCa) and clinically significant prostate cancer (csPCa) during initial prostate biopsy. MATERIALS AND METHODS: In total, 343 patients underwent initial prostate biopsy and were screened by use of PHI and prostate-specific antigen (PSA) levels between April 2019 and July 2021. A subgroup of 232 patients also underwent prostate mpMRI. Logistic regression analysis was performed to evaluate the accuracies of PSA, PHI, and mpMRI as predictors of PCa or csPCa. These predictive accuracies were quantified by using the area under the receiver operating characteristic curve. The different predictive models were compared using the DeLong test. RESULTS: Logistic regression showed that age, PSA, PHI, and prostate volume were significant predictors of both PCa and csPCa. In the mpMRI subgroup, age, PSA level, PHI, prostate volume, and mpMRI were predictors of both PCa and csPCa. The PHI (area under the curve [AUC]=0.693) was superior to the PSA level (AUC=0.615) as a predictor of PCa (p=0.038). Combining PHI and mpMRI showed the most accurate prediction of both PCa and csPCa (AUC=0.833, 0.881, respectively). CONCLUSIONS: The most accurate prediction of both PCa and csPCa can be performed by combining PHI and mpMRI. In the absence of mpMRI, PHI is superior to PSA alone as a predictor of PCa, and adding PHI to PSA can increase the detection rate of both PCa and csPCa.

Clinical benefits of retrograde bladder filling method prior to catheter removal after TURP for BPH: A prospective randomized trial.

PURPOSE: To evaluate possible benefits and clinical feasibility of retrograde bladder filling method prior to intra-vesical catheter removal after transurethral prostatectomy (TURP) for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Male patients undergoing TURP for BPH from January 2019 to October 2019 were randomized in a 1:1 ratio into either retrograde filling (RF) or spontaneous voiding (SV) methods at a single institution to determine safety and efficacy of RF (NCT04309032), with surgeons blinded to allocation. Perioperative outcomes including postoperative complications were compared between two groups. Clinician/patients' satisfaction level which was evaluated with postoperative questionnaires were also compared. RESULTS: A total of 56 patients were randomized into two groups and 56 were included in final analysis (28 men in RF group, 26 in SV group). No significant differences in baseline characteristics including age, prostate volume, or perioperative uroflowmetry were observed. However, RF significantly facilitated time to void (67.0±63.2 vs. 144.0±78.7 min; p<0.001) and time to discharge (168.4±57.2 vs. 218.9±106.9 min; p=0.046). Immediate postoperative complications were comparable in both methods with no significant difference. Overall patient and medical staff satisfaction showed tolerable and similar response by either procedure. CONCLUSIONS: RF method for intra-vesical catheter removal is a safe and satisfactory method that can facilitate early voiding detection and shorten the time to discharge. Further trials are required to further validate our results.

A smart, practical, deep learning-based clinical decision support tool for patients in the prostate-specific antigen gray zone: model development and validation.

OBJECTIVE: Despite efforts to improve screening and early detection of prostate cancer (PC), no available biomarker has shown acceptable performance in patients with prostate-specific antigen (PSA) gray zones. We aimed to develop a deep learning-based prediction model with minimized parameters and missing value handling algorithms for PC and clinically significant PC (CSPC). MATERIALS AND METHODS: We retrospectively analyzed data from 18 824 prostate biopsies collected between March 2003 and December 2020 from 2 databases, resulting in 12 739 cases in the PSA gray zone of 2.0-10.0 ng/mL. Dense neural network (DNN) and extreme gradient boosting (XGBoost) models for PC and CSPC were developed with 5-fold cross-validation. The area under the curve of the receiver operating characteristic (AUROC) was compared with that of serum PSA, PSA density, free PSA (fPSA) portion, and prostate health index (PHI). RESULTS: The AUROC values in the DNN model with the imputation of missing values were 0.739 and 0.708 (PC) and 0.769 and 0.742 (CSPC) in internal and external validation, whereas those of the non-imputed dataset were 0.740 and 0.771 (PC) and 0.807 and 0.771 (CSPC), respectively. The performance of the DNN model was like that of the XGBoost model, but better than all tested clinical biomarkers for both PC and CSPC. The developed DNN model outperformed PHI, serum PSA, and percent-fPSA with or without missing value imputation. DISCUSSION: DNN models for missing value imputation can be used to predict PC and CSPC. Further validation in real-life scenarios are need to recommend for actual implementation, but the results from our study support the increasing role of deep learning analytics in the clinical setting. CONCLUSIONS: A deep learning model for PC and CSPC in PSA gray zones using minimal, routinely used clinical parameter variables and data imputation of missing values was successfully developed and validated.

Modulating LOV domain photodynamics with a residue alteration outside the chromophore binding site.

Phototropins, a class of light-activated protein kinases, are essential for several blue light responses in plants and algae, including phototropism. These proteins contain two internal light, oxygen, and voltage sensitive (LOV) domains, which bind flavin chromophores and undergo a reversible photochemical formation of a cysteinyl-flavin adduct as part of the light sensing process. While the photodynamic properties of such photosensory domains are dictated by interactions between the chromophore and surrounding protein, more distant residues can play a significant role as well. Here we explore the role of the Phe434 residue in the photosensory response of the second LOV domain of Avena sativa phototropin 1 (AsLOV2), a model photochemical system for these LOV domains. Phe434 is more than 6 Å from the FMN chromophore in AsLOV2; nevertheless, an F434Y point mutation is likely to change several structural features of the chromophore binding site, as we demonstrate using molecular dynamics simulations. Transient absorption signals spanning 15 decades in time were compared for wild-type AsLOV2 and the F434Y mutant, showing that the latter has significantly altered photodynamics, including (i) a faster intersystem crossing leading to triplet formation on a nanosecond time scale, (ii) biphasic formation of adduct-state kinetics on the microsecond time scale, and (iii) greatly accelerated ground-state recovery kinetics on a second time scale. We present mechanistic models that link these spectroscopic differences to changes in the configuration of the critical cysteine residue and in the chromophore's accessibility to solvent and oxygen according to MD trajectories and purging experiments. Taken together, these results demonstrate the importance of residues outside the chromophore-binding pocket in modulating LOV domain photodynamics.

Deconstructing the excited-state dynamics of ß-carotene in solution.

The femtosecond to nanosecond dynamics of the all-trans ß-carotene carotenoid dissolved in 3-methylpentane is characterized and dissected with excitation-wavelength and temperature-dependent ultrafast dispersed transient absorption signals. The kinetics measured after red-edge (490 nm) and blue-edge (400 nm) excitation were contrasted under fluid solvent (298 K) and rigid glass (77 K) conditions. In all four measured data sets, the S* population kinetics was resolved prompting the development of a modified multicompartment model. The temperature-dependent and excitation wavelength-dependent S* quantum yield is ascribed to a competition of population surmounting a weak (55 cm(-1)) energy barrier on the S(2) state to favor S(1) generation and rapid internal conversion that favors S* generation. When cooled from room temperature to 77 K, the S* decay time scale shifted significantly from 30 to 400 ps, which is ascribed to small-scale structural relaxation with a 115 cm(-1) energy barrier. For the first time under low-energy excitation conditions, the triplet state is observed and confirmed to not originate from S* or S(1), but from S(2). The interconnectivity of the S* and S(1) populations is discussed, and no observed population flow is resolved between S* and S(1). Comparison of samples obtained from different laboratories with different purity levels demonstrates that sample contamination is not the primary origin of the S* state.

Polygenic risk score for genetic evaluation of prostate cancer risk in Asian populations: A narrative review.

Decreasing costs of genetic testing and interest in disease inheritance has changed the landscape of cancer prediction in prostate cancer (PCa), and guidelines now include genetic testing for high-risk groups. Familial and hereditary PCa comprises approximately 20% and 5% of all PCa, respectively. Multifaceted disorders like PCa are caused by a combinatory effect of rare genes of high penetrance and smaller genetic variants of relatively lower effect size. Polygenic risk score (PRS) is a novel tool utilizing PCa-associated single nucleotide polymorphisms (SNPs) identified from genome-wide association study (GWAS) to generate an additive estimate of an individual's lifetime genetic risk for cancer. However, most PRS are developed based on GWAS collected from mainly European populations and do not address ethnic differences in PCa genetics. This review highlights the attempts to generate a PRS tailored to Asian males including data from Korea, China, and Japan, and discuss the clinical implications for prediction of early onset and aggressive PCa.