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Background: The aim of this study was to analyze the risk factors for hemorrhagic complications in patients who underwent robotic-assisted partial nephrectomy. Methods: We retrospectively reviewed the records of 260 patients who underwent robotic-assisted partial nephrectomy. Hemorrhagic complications were defined as bleeding, hematoma, or arteriovenous fistula requiring hemostatic medication, blood transfusion, or therapeutic intervention. Hemorrhagic complications were graded according to the modified Clavien classification system, and the hemorrhagic complication group comprised only those complications with Clavien grade II or higher. Thereafter, we investigated the presence of any relevant association between perioperative factors and hemorrhagic complications. Results: Of 260 patients included in the study, 32 (12.3%) had hemorrhagic complications. The postoperative hemoglobin level was significantly lower in the hemorrhagic complication group than in the group without complications. The hemorrhagic complication group had significantly more essential blood loss and a significantly longer length of hospital stay. In the univariate analysis, type 2 diabetes mellitus, Radius-scores tumor size as maximal diameter exophytic/endophytic properties of the tumor nearness of the deepest portion of the tumor to the collecting system or renal sinus anterior (a)/posterior (p) descriptor location relative to the polar line., sum of the renal size plus renal sinus involvement in the PADUA score is a simple anatomical system that can be used to predict the risk of surgical and medical perioperative complications in patients undergoing open NSS, prolonged console time (>180 minutes), prolonged warm ischemic time (>25 minutes), and method of pedicle control were statistically significant risk factors. In the multivariate logistic regression analysis, warm ischemic time >25 minutes was the only significant risk factor for hemorrhagic complications (odds ratio, 3.51; 95% confidence interval, 1.28-9.59; p = 0.01). Conclusion: Patients who undergo robotic-assisted partial nephrectomy with a warm ischemic time >25 minutes are significantly more likely to have hemorrhagic complications and should hence receive careful perioperative follow-up. [ABSTRACT FROM AUTHOR]

Background: In patients undergoing radical prostatectomy (RP) for prostate cancer (PCa), preoperative prediction of extraprostatic extension (EPE) can facilitate patient selection for nerve-sparing procedures. Since both multiparametric magnetic resonance imaging (mpMRI) and prostate health index (PHI) have shown promise for the diagnosis and prognostication of PCa, we investigated whether a combination of mpMRI and PHI evaluations can improve the prediction of EPE after RP. Methods: Patients diagnosed with PCa and treated with RP were prospectively enrolled between February 2017 and July 2019. Preoperative blood samples were analyzed for PHI (defined as [p2PSA/fPSA] × vtPSA), and mpMRI examinations were performed and interpreted by a single experienced uroradiologist retrospectively. The area under the receiver operating characteristic curve (ROC) was used to determine the performance of mpMRI, PHI, and their combination in predicting EPE after RP. Results: A total of 163 patients were included for analysis. The pathological T stage was T3a or more in 59.5%. Overall staging accuracy of mpMRI for EPE was 72.4% (sensitivity and specificity: 73.2% and 71.2%, respectively). The area under the ROC of the combination of mpMRI and PHI in predicting EPE (0.785) was higher than those of mpMRI alone (0.717; p = 0.0007) and PHI alone (0.722; p = 0.0236). mpMRI showed false-negative non-EPE results in 26 patients (16%), and a PHI threshold of >40 could avoid undiagnosed EPE before RP in 21 of these 26 patients. Conclusion: The combination of PHI and mpMRI may better predict the EPE preoperatively, facilitating preoperative counseling and tailoring the need for nerve-sparing RP. [ABSTRACT FROM AUTHOR]

Multiple repression domains (RDs) seen in certain corepressors that mediate transcriptional repression have been shown to be nonredundant. One RD conserved in N-coR and SMRT represses transcription by interacting directly with class II HDAC4/5. Endogenous N-CoR and SMRT associate with HDAC4 in a complex that does not have HDAC1 or mSin3A. The first instance of one corepressor using definite domains to engage multiple HDAC complexes has been seen. Alternative HDAC complexes may mediate specific repression pathways in leukemic and normal cells.

The resulting protein expression caused by folate stress in Escherichia coli was analyzed using trimethoprim treatment. Results of the experiment revealed that interruption of folate metabolism using glycine, methionine, inosine and thymine significantly modified the pattern of protein expression in E. coli. Furthermore, trimethoprim triggers changes in cellular metabolism consequently decreasing translational fidelity of several proteins.

Abstract: Single nucleotide polymorphisms (SNPs) within the regulatory elements of a gene can alter gene expression, making these SNPs of prime importance for candidate gene association studies. We aimed to determine whether such regulatory variants are associated with clinical outcomes in three cohorts of patients with prostate cancer. We used RegulomeDB to identify potential regulatory variants based on in silico predictions and reviewed genome‐wide experimental findings. Overall, 131 putative regulatory SNPs with the highest confidence score on predicted functionality were investigated in two independent localized prostate cancer cohorts totalling 458 patients who underwent radical prostatectomy. The statistically significant SNPs identified in these two cohorts were then tested in an additional cohort of 504 patients with advanced prostate cancer. We identified one regulatory SNPs, rs1646724, that are consistently associated with increased risk of recurrence in localized disease (P = .003) and mortality in patients with advanced prostate cancer (P = .032) after adjusting for known clinicopathological factors. Further investigation revealed that rs1646724 may affect expression of SLC35B4, which encodes a glycosyltransferase, and that down‐regulation of SLC35B4 by transfecting short hairpin RNA in DU145 human prostate cancer cell suppressed proliferation, migration and invasion. Furthermore, we found increased SLC35B4 expression correlated with more aggressive forms of prostate cancer and poor patient prognosis. Our study provides robust evidence that regulatory genetic variants can affect clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to analyze the risk factors for hemorrhagic complications in patients who underwent robotic-assisted partial nephrectomy., Methods: We retrospectively reviewed the records of 260 patients who underwent robotic-assisted partial nephrectomy. Hemorrhagic complications were defined as bleeding, hematoma, or arteriovenous fistula requiring hemostatic medication, blood transfusion, or therapeutic intervention. Hemorrhagic complications were graded according to the modified Clavien classification system, and the hemorrhagic complication group comprised only those complications with Clavien grade II or higher. Thereafter, we investigated the presence of any relevant association between perioperative factors and hemorrhagic complications., Results: Of 260 patients included in the study, 32 (12.3%) had hemorrhagic complications. The postoperative hemoglobin level was significantly lower in the hemorrhagic complication group than in the group without complications. The hemorrhagic complication group had significantly more essential blood loss and a significantly longer length of hospital stay. In the univariate analysis, type 2 diabetes mellitus, Radius-scores tumor size as maximal diameter exophytic/endophytic properties of the tumor nearness of the deepest portion of the tumor to the collecting system or renal sinus anterior (a)/posterior (p) descriptor location relative to the polar line., sum of the renal size plus renal sinus involvement in the PADUA score is a simple anatomical system that can be used to predict the risk of surgical and medical perioperative complications in patients undergoing open NSS, prolonged console time (>180 minutes), prolonged warm ischemic time (>25 minutes), and method of pedicle control were statistically significant risk factors. In the multivariate logistic regression analysis, warm ischemic time >25 minutes was the only significant risk factor for hemorrhagic complications (odds ratio, 3.51; 95% confidence interval, 1.28-9.59; p = 0.01)., Conclusion: Patients who undergo robotic-assisted partial nephrectomy with a warm ischemic time >25 minutes are significantly more likely to have hemorrhagic complications and should hence receive careful perioperative follow-up., Competing Interests: Conflicts of interest: Dr William J. Huang, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Background: There are models to predict pathological outcomes based on established clinical and prostate-specific antigen (PSA)-derived parameters; however, they are not satisfactory. p2PSA and its derived biomarkers have shown promise for the diagnosis and prognosis of prostate cancer (PCa). The aim of this study was to investigate whether p2PSA-derived biomarkers can assist in the prediction of aggressive pathological outcomes after radical prostatectomy (RP)., Methods: We prospectively enrolled patients who were diagnosed with PCa and treated with RP between February 2017 and December 2018. Preoperative blood samples were analyzed for tPSA, free PSA (fPSA), percentage of fPSA (%fPSA), [-2]proPSA (p2PSA), and percentage of p2PSA (%p2PSA). Prostate health index (PHI) was calculated as (p2PSA/fPSA) × √tPSA. Prostate volume was determined by transrectal ultrasound using the ellipsoid formula, and PHI density was calculated as PHI/prostate volume. The areas under the receiver operating characteristic curve were estimated for various PSA/p2PSA derivatives. Aggressive pathological outcomes measured after RP were defined as pathological T3 or a Gleason score (GS) >6 as determined in RP specimens., Results: One hundred and forty-four patients were included for analysis. Postoperative GS was >6 in 86.1% of the patients, and pT stage was T3a or more in 54.2%. Among all PSA- and p2PSA-derived biomarkers, PHI density was the best biomarker to predict aggressive pathological outcomes after RP. The odds ratio of having an aggressive pathological outcome of RP was 8.796 (p = 0.001). In multivariate analysis, adding %fPSA to base model did not improve the accuracy (area under curve), but adding PHI and PHI density to base model improved the accuracy by 2% and 16%, respectively, in predicting pT3 stage or GS ≥ 7. The risk of pT3 stage or GS ≥ 7 was 20.8% for PHI density <1.125, and 64.6% for PHI density >1.125 (sensitivity: 74.6% and specificity: 88.9%)., Conclusion: PHI density may further aid in predicting aggressive pathological outcomes after RP. This biomarker may be useful in preoperative counseling and may have potential in decision making when choosing between definitive treatment and active surveillance of newly diagnosed PCa.

Background: Few prospective studies have focused on the performance of the Prostate Health Index (PHI) in Asian populations. Therefore, we aimed to evaluate the performance of the PHI in predicting prostate cancer (PCa) compared with standard prostate-specific antigen (PSA) tests., Methods: We prospectively enrolled patients with suspected PCa with a total PSA (tPSA) level 4 to 10 ng/mL or tPSA <4 ng/mL and a suspicious digital rectal examination between February 2017 and September 2018. All of the patients underwent a 12-core transrectal ultrasound-guided prostate biopsy. Prebiopsy blood samples were analyzed for tPSA, free PSA (fPSA), percentage of fPSA (%fPSA), [-2]proPSA (p2PSA), and percentage of p2PSA (%p2PSA). The PHI was calculated as (p2PSA/fPSA) × √tPSA. The areas under the receiver operating characteristic curve (AUCs) were estimated for the PSA derivatives in addition to their specificities at a prespecified sensitivity of 90%., Results: Of the 307 enrolled patients, 95 (30.9%) had PCa on biopsy. Excluding fPSA, all of the PSA derivatives were significantly different between the positive and negative biopsy groups. Of the various derivatives, the PHI (AUC: 0.783) showed the best performance in predicting the results of the initial biopsy compared with tPSA (AUC: 0.611). At a sensitivity of 90%, the PHI had the best specificity of 46.7% compared with 23.2% for tPSA. Using a PHI cutoff value of 35.15 for biopsy, 108 (35.2%) patients could have avoided undergoing a biopsy. To detect Gleason score ≥ 7 disease at 90% sensitivity, the threshold for PHI was 36.96 with a specificity of 52.1%., Conclusion: PHI was the best biomarker among the PSA derivatives in predicting PCa at biopsy in men with tPSA < 10 ng/mL. The risk of a Gleason score ≥ 7 increased with increasing PHI.