Humoral response to SARS-CoV-2 mRNA vaccine on in ABO blood type incompatible kidney transplant recipients treated with low-dose rituximab.

We aimed to evaluate the humoral response after the second and third doses of SARS-CoV-2 mRNA vaccine in ABO blood type incompatible kidney transplant (KT) recipients treated with rituximab. This retrospective study conducted between June 2021 and June 2022 included 131 KT recipients and 154 nontransplant controls who had received mRNA vaccines. We compared the seropositivity (anti-SARS-CoV-2 spike IgG antibody titer ≥ 0.8 U/mL) after the second and third vaccinations. Furthermore, we evaluated the impact of pretransplant vaccination for seropositivity. Of the 131 KT recipients, 50 had received the third dose of mRNA vaccine. The antibody titer was significantly increased after the third dose of mRNA vaccine. The seropositivity rate after the third dose of mRNA vaccine increased from 36 to 70%. We observed no significant difference in seropositivity after the third dose of mRNA vaccine in ABO incompatibility, rituximab use, mycophenolate mofetil use, and age at KT. Of the nine recipients who had received the second or third dose of the mRNA vaccine prior to the KT, eight of the recipients were seropositive both before and after the KT. Our results suggest that ABO incompatibility or rituximab use was not significantly associated with seropositivity.

Can Erectile Dysfunction Severity Predict Major Adverse Cardiovascular Events in Men Undergoing Dialysis? A Prospective Cohort Study.

PURPOSE: To evaluate the impact of severe erectile dysfunction (ED) on future major adverse cardiovascular events (MACE) in men on dialysis. MATERIALS AND METHODS: This prospective cohort study included 71 men on dialysis. ED was assessed using the Sexual Health Inventory for Men (SHIM). Men were divided into the mild/moderate ED (SHIM score ≥8) and severe ED (SHIM score ≤7) groups. The primary endpoint was MACE-free survival. MACE was a composite of myocardial infarction, cardiovascular death, and stroke. The secondary endpoints were cardiac event-free survival and overall survival (OS). Moreover, the predictive abilities of severe ED for 5-year MACE, 5-year cardiac events, and 5-year overall mortality were evaluated. RESULTS: The median age and follow-up period of the included men were 64 years and 58 months, respectively. The median SHIM score was 4.0; all had a degree of ED, and 64.7% had severe ED. In the background-adjusted multivariable analyses, severe ED was not significantly associated with shorter MACE-free survival (hazard ratio [HR], 1.890; 95% confidence interval [CI], 0.533-6.706; p=0.324), cardiac event-free survival (HR, 2.081; 95% CI, 0.687-6.304; p=0.195), and OS (HR, 0.817; 95% CI, 0.358-1.863; p=0.630). Severe ED did not significantly improve the predictive abilities for 5-year MACE, 5-year cardiac events, and 5-year overall mortality (p=0.110, p=0.101, and p=0.740, respectively). CONCLUSIONS: ED severity was not associated with shorter MACE-free survival, cardiac event-free survival, or OS, and ED severity could not improve the predictive abilities for these outcomes in men undergoing dialysis.

Impact of an optimized surveillance protocol based on the European Association of Urology substratification on surveillance costs in patients with primary high-risk non-muscle-invasive bladder cancer.

OBJECTIVES: The optimal frequency and duration of surveillance in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) remain unclear. The aim of the present study is to develop an optimal surveillance protocol based on the European Association of Urology (EAU) substratification in order to improve surveillance costs after transurethral resection of bladder tumor (TURBT) in patients with primary high-risk NMIBC. MATERIALS AND METHODS: We retrospectively evaluated 428 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. Patients were substratified into the highest-risk and high-risk without highest-risk groups based on the EAU guidelines. An optimized surveillance protocol that enhances cost-effectiveness was then developed using real incidences of recurrence after TURBT. A recurrence detection rate ([number of patients with recurrence / number of patients with surveillance] × 100) of ≥ 1% during a certain period indicated that routine surveillance was necessary in this period. The 10-year total surveillance cost was compared between the EAU guidelines-based protocol and the optimized surveillance protocol developed herein. RESULTS: Among the 428 patients with primary high-risk NMIBC, 97 (23%) were substratified into the highest-risk group. Patients in the highest-risk group had a significantly shorter recurrence-free survival than those in the high-risk without highest-risk group. The optimized surveillance protocol promoted a 40% reduction ($394,990) in the 10-year total surveillance cost compared to the EAU guidelines-based surveillance protocol. CONCLUSION: The optimized surveillance protocol based on the EAU substratification could potentially reduce over investigation during follow-up and improve surveillance costs after TURBT in patients with primary high-risk NMIBC.

Association between Aortic Calcification Burden and the Severity of Erectile Dysfunction in Men Undergoing Dialysis: A Cross-Sectional Study.

PURPOSE: Accelerated atherosclerosis is a major complication in patients with end-stage renal disease and it plays an important role in the pathogenesis of erectile dysfunction (ED). However, the association between aortic calcification burden and the severity of ED remains unclear. The aim of the present study was to investigate this association in men undergoing dialysis. MATERIALS AND METHODS: This cross-sectional study included 71 men undergoing peritoneal dialysis and/or hemodialysis between July 2016 and May 2018 at Mutsu General Hospital. ED was assessed with the Sexual Health Inventory for Men (SHIM). Patients were divided into the mild/moderate (SHIM score ≥8) and severe ED groups (SHIM score ≤7). Aortic calcification index (ACI) was examined as a clinical indicator of abdominal aortic calcification. Multivariable logistic regression analysis was performed to identify the significant factors associated with severe ED. RESULTS: The median age of the study participants was 64 years; all had ED, with 64.8% having severe ED. In the multivariable analyses, a slight association was observed between ankle-brachial index and severe ED (odds ratio [OR], 0.058; p=0.072), whereas ACI was significantly associated with severe ED (OR, 1.022; p=0.022). CONCLUSIONS: Aortic calcification burden was independently associated with severe ED.

Humoral response after SARS-CoV-2 mRNA vaccination in patients with prostate cancer using steroids.

OBJECTIVES: The effect of concomitant steroid use on the antibody response to a SARS-CoV-2 vaccine in patients with prostate cancer (PC) remains unknown. We aimed to evaluate the rates of antispike immunoglobulin G (IgG) antibody response to the BNT162b2 mRNA vaccine in patients with PC using steroids. METHODS: This cross-sectional study conducted from June 21, 2021 to January 5, 2022 included 215 patients with PC who received the second dose of the BNT162b2 mRNA vaccine at least 7 days before the measurement of titers of IgG antibodies against the receptor-binding domain of SARS-CoV-2 spike (S) protein. We compared the rate of anti-SARS-CoV-2 S IgG ≥15 U/mL between patients with or without concomitant steroid use. RESULTS: Of 215, we identified 33 patients who had concomitant steroid use. Of these, 12 and 21 patients were metastatic castration-sensitive PC and castration-resistant PC (CRPC), respectively. Patients with concomitant steroid use had a significantly lower rate of antibody titer ≥15 U/mL than those without steroid use (82% vs. 95%, P = 0.021). Patients with CRPC with concomitant steroid use (n =21) also had a lower rate of antibody titer ≥15 U/mL (71%) than those without steroid use (93%, P = 0.051), although this was not statistically different. Increased number of systemic treatments administered after diagnosis of CRPC (3 lines or more) were significantly associated with antibody titers <15 U/mL (97% vs. 77%, P <0.001). CONCLUSION: The humoral response to the BNT162b2 mRNA vaccine was significantly lower in patients with concomitant steroid use. Anti-SARS-CoV-2 S antibody titers were affected by CRPC status, the accumulation of post-CRPC treatments, and steroid use.

Selective reaction monitoring approach using structure-defined synthetic glycopeptides for validating glycopeptide biomarkers pre-determined by bottom-up glycoproteomics.

Clusterin is a heavily glycosylated protein that is upregulated in various cancer and neurological diseases. The findings by the Hancock and Iliopoulos group that levels of the tryptic glycopeptide derived from plasma clusterin, 372Leu-Ala-Asn-Leu-Thr-Gln-Gly-Glu-Asp-Gln-Tyr-Tyr-Leu-Arg385 with a biantennary disialyl N-glycan (A2G2S2 or FA2G2S2) at Asn374 differed significantly prior to and after curative nephrectomy for clear cell renal cell carcinoma (RCC) patients motivated us to verify the feasibility of this glycopeptide as a novel biomarker of RCC. To determine the precise N-glycan structure attached to Asn374, whether A2G2S2 is composed of the Neu5Acα2,3Gal or/and the Neu5Acα2,6Gal moiety, we synthesized key glycopeptides having one of the two putative isomers. Selective reaction monitoring assay using synthetic glycopeptides as calibration standards allowed "top-down glycopeptidomics" for the absolute quantitation of targeted label-free glycopeptides in a range from 313.3 to 697.5 nM in the complex tryptic digests derived from serum samples of RCC patients and healthy controls. Our results provided evidence that the Asn374 residue of human clusterin is modified dominantly with the Neu5Acα2,6Gal structure and the levels of clusterin bearing an A2G2S2 with homo Neu5Acα2,6Gal terminals at Asn374 decrease significantly in RCC patients as compared with healthy controls. The present study elicits that a new strategy integrating the bottom-up glycoproteomics with top-down glycopeptidomics using structure-defined synthetic glycopeptides enables the confident identification and quantitation of the glycopeptide targets pre-determined by the existing methods for intact glycopeptide profiling.

Risk score-based substratification improves surveillance costs after transurethral resection of bladder tumor in patients with primary high-risk non-muscle-invasive bladder cancer.

High-risk non-muscle-invasive bladder cancer (NMIBC) has a heterogeneity and intensive surveillances after transurethral resection of bladder tumor (TURBT) are major factors of increased costs. Therefore, we aimed to develop optimized surveillance protocols based on the risk score-based substratifications to improve surveillance costs. We retrospectively evaluated 428 patients with primary high-risk NMIBC who underwent TURBT. Patients were substratified into intra-lower, intra-intermediate, and intra-higher groups or UUT-lower, UUT-intermediate, and UUT-higher groups by summing each of the independent risk factors of intravesical and UUT recurrences, respectively. The optimized surveillance protocols that enhance cost-effectiveness were then developed using real incidences of recurrence after TURBT. The 10-year total surveillance costs were compared between the European Association of Urology (EAU) guidelines-based and optimized surveillance protocols. The Kaplan-Meier curves of intravesical and UUT recurrence-free survivals were clearly separated among the substratified groups. The optimized surveillance protocols promoted a 43% reduction ($487,599) in the 10-year total surveillance cost compared to the EAU guidelines-based surveillance protocol. These results suggest that the optimized surveillance protocols based on risk score-based substratifications could potentially reduce over investigation and improve surveillance costs after TURBT in patients with primary high-risk NMIBC.

Relationships of low-grade systemic inflammation and nutritional status with erectile dysfunction severity in men on dialysis.

BACKGROUND: Low-grade systemic inflammation and malnutrition are frequently observed in patients on dialysis and contribute to the development of endothelial dysfunction; however, the role of these conditions in erectile dysfunction (ED) severity remains to be elucidated. OBJECTIVES: To investigate the relationships of low-grade systemic inflammation and nutritional status with ED severity in men on dialysis. MATERIALS AND METHODS: The present study included 71 men on dialysis. The sexual health inventory for men (SHIM) was used to assess ED. Men were classified as the mild/moderate (SHIM score ≥ 8) and severe ED (SHIM score ≤ 7) groups. C-reactive protein/albumin ratio (CAR) and Geriatric Nutritional Risk Index (GNRI) were used to evaluate low-grade systemic inflammation and nutritional status, respectively. We performed multivariate analysis to assess the relationships of CAR and GNRI with severe ED. RESULTS: The median age of the included men was 64 years old. All men had any degree of ED with 65% having severe ED. In the univariate analyses, a significant association was observed between elevated CAR (≥0.09) and severe ED (odds ratio [OR]: 4.038, p = 0.025), whereas no significant association was observed between lower GNRI (<92) and severe ED (OR: 2.357, p = 0.109). In the multivariate analysis, an association between elevated CAR and severe ED was still significant (OR: 5.985, p = 0.010). DISCUSSION AND CONCLUSION: Low-grade systemic inflammation was significantly associated with ED severity, whereas lower GNRI was not. These results may be helpful for further research to identify the optimal treatment for men suffering from severe ED.

Significance of pelvic lymph node dissection during radical prostatectomy in high-risk prostate cancer patients receiving neoadjuvant chemohormonal therapy.

We aimed to determine the survival and staging benefit of limited pelvic lymph node dissection (PLND) during radical prostatectomy (RP) in high-risk prostate cancer (PC) patients treated with neoadjuvant chemohormonal therapy. We retrospectively analyzed 516 patients with high-risk localized PC (< cT4N0M0) who received neoadjuvant androgen-deprivation therapy plus estramustine phosphate followed by RP between January 2010 and March 2020. Since we stopped limited PLND for such patients in October 2015, we compared the surgical outcomes and biochemical recurrence-free survival (BCR-FS) between the limited-PLND group (before October 2015, n = 283) and the non-PLND group (after November 2015, n = 233). The rate of node metastases in the limited-PLND group were 0.8% (2/283). Operation time was significantly longer (176 vs. 162 min) and the rate of surgical complications were much higher (all grades; 19 vs. 6%, grade ≥ 3; 3 vs. 0%) in the limited-PLND group. The inverse probability of treatment weighting-Cox analysis revealed limited PLND had no significant impact on BCR-FS (hazard ratio, 1.44; P = 0.469). Limited PLND during RP after neoadjuvant chemohormonal therapy showed quite low rate of positive nodes, higher rate of complications, and no significant impact on BCR-FS.

Renal metastasis of ovarian granulosa cell tumor.

Introduction: We would like to present a rare case of metastatic renal tumor. Case presentation: A 60-year-old woman presented to our department with a left renal tumor. She underwent a total hysterectomy and right adnexal resection for a stage IA ovarian granulosa cell tumor approximately 15 years ago, followed by left adnexal resection and postoperative chemotherapy with gemcitabine and paclitaxel 6 years ago. She received six courses of gemcitabine and carboplatin to treat a stage IC clear cell adenocarcinoma of the ovary.The patient was diagnosed with the left renal tumor and underwent a laparoscopic left nephrectomy. Immunostaining was positive for α-inhibin and SF-1 and showed FOXL2 402C→G (C134W) mutation. Finally, the patient was diagnosed with renal metastasis of a granulosa cell tumor. Conclusion: To our knowledge, this is a very rare case of renal metastasis of a granulosa cell tumor with the FOXL2 mutation in an adult.

Machine learning diagnosis by immunoglobulin N-glycan signatures for precision diagnosis of urological diseases.

Early diagnosis of urological diseases is often difficult due to the lack of specific biomarkers. More powerful and less invasive biomarkers that can be used simultaneously to identify urological diseases could improve patient outcomes. The aim of this study was to evaluate a urological disease-specific scoring system established with a machine learning (ML) approach using Ig N-glycan signatures. Immunoglobulin N-glycan signatures were analyzed by capillary electrophoresis from 1312 serum subjects with hormone-sensitive prostate cancer (n = 234), castration-resistant prostate cancer (n = 94), renal cell carcinoma (n = 100), upper urinary tract urothelial cancer (n = 105), bladder cancer (n = 176), germ cell tumors (n = 73), benign prostatic hyperplasia (n = 95), urosepsis (n = 145), and urinary tract infection (n = 21) as well as healthy volunteers (n = 269). Immunoglobulin N-glycan signature data were used in a supervised-ML model to establish a scoring system that gave the probability of the presence of a urological disease. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC). The supervised-ML urologic disease-specific scores clearly discriminated the urological diseases (AUC 0.78-1.00) and found a distinct N-glycan pattern that contributed to detect each disease. Limitations included the retrospective and limited pathological information regarding urological diseases. The supervised-ML urological disease-specific scoring system based on Ig N-glycan signatures showed excellent diagnostic ability for nine urological diseases using a one-time serum collection and could be a promising approach for the diagnosis of urological diseases.

TMEM2 expression is downregulated as bladder cancer invades the muscle layer.

Cell surface hyaluronidase transmembrane protein 2 (TMEM2), which also serves as a reportedly functions in malignancy of several solid tumors. However, TMEM2 involvement in bladder cancer (BCa) is unknown. Therefore, we investigate potential changes in expression of TMEM2 during BCa invasion and over the course of the epithelial mesenchymal transition (EMT). Immunohistochemical analysis of 127 clinical specimens revealed that TMEM2 expression changed with pathological stage (pT) and infiltration pattern (INF) and was highest in pTa-pT1 of INFa tumors and significantly lower at stages from pTa-pT1 to pT2 or 3 in INFb or INFc. E-cadherin expression was highest in INFa and lowest in INFc, a pattern comparable to TMEM2 expression. TMEM2 protein expression analysis of BCa cell lines showed that muscle-invasive T24 and YTS-1 cells with low TMEM2 expression exhibited EMT phenotypes in vitro, in contrast to high TMEM2-expressing non-muscle invasive RT4 cells. EMT-induced non-muscle invasive RT4 cells also showed significantly decreased plasma membrane expression of TMEM2. Our data suggested TMEM2 expression is higher in non-invasive cancers, whereas invasive cancer cells are less likely to express TMEM2 during muscle-invasion and "partial EMT".

Single immediate instillation of chemotherapy is associated with decreased recurrence and progression in patients with high-risk non-muscle-invasive bladder cancer who receive adjuvant induction bacillus Calmette-Guérin therapy.

OBJECTIVES: To investigate whether a single intravesical instillation of chemotherapy is associated with improved oncological outcomes in patients with high-risk non-muscle-invasive bladder cancer who receive adjuvant induction bacillus Calmette-Guérin therapy. METHODS: This multi-institutional retrospective study included 205 patients with high-risk non-muscle-invasive bladder cancer who received adjuvant induction bacillus Calmette-Guérin therapy. Patients were divided into two groups: those who received the combined therapy of a single instillation of chemotherapy plus subsequent adjuvant induction bacillus Calmette-Guérin therapy (combined therapy group), and those who received adjuvant induction bacillus Calmette-Guérin therapy alone (bacillus Calmette-Guérin monotherapy group). Multivariable analyses using the inverse probability of treatment weighting method and Fine-Gray competing risk regression models were performed to evaluate the impact of a single instillation of chemotherapy on intravesical recurrence-free survival and muscle-invasive bladder cancer-free survival. RESULTS: Among the 205 patients, 130 (63%) and 75 (37%) were classified as the combined therapy and bacillus Calmette-Guérin monotherapy groups, respectively. Multivariable analyses using the inverse probability of treatment weighting method showed that a single instillation of chemotherapy was significantly associated with longer intravesical recurrence-free survival (hazard ratio 0.279; P < 0.001) and muscle-invasive bladder cancer-free survival (hazard ratio 0.078; P < 0.001). Fine-Gray competing risk regression model revealed that a single instillation of chemotherapy was associated with a significantly lower probability of intravesical recurrence and muscle-invasive bladder cancer progression, with an adjusted subdistribution hazard ratio of 0.477 (P = 0.008) and 0.261 (P = 0.043), respectively. CONCLUSION: A single intravesical instillation of chemotherapy may be a potential treatment option in patients with high-risk non-muscle-invasive bladder cancer who receive adjuvant induction bacillus Calmette-Guérin therapy.

Seroprevalence of SARS-CoV-2 spike IgG antibodies after the second BNT162b2 mRNA vaccine in Japanese kidney transplant recipients.

We aimed to evaluate the seroprevalence and investigated factors associated with seropositivity after the second SARS-CoV-2 mRNA vaccination in kidney transplant (KT) recipients. This retrospective study conducted between June and November 2021 included 106 KT recipients and 127 healthy controls who received the second dose of the BNT162b2 mRNA vaccine at least 7 days before the measurement of antibody titers. The antibody titer against the receptor-binding domain of SARS-CoV-2 spike (S) protein was determined. We compared seroprevalence rates (immunoglobulin G [IgG] level of ≥ 0.8 or ≥ 15 U/mL) between the healthy controls and KT recipients and identified factors associated with impaired humoral response. The seroprevalence rate of the healthy controls and KT recipients was 98% and 22%, respectively. Univariate logistic regression analysis revealed that age > 53 years, rituximab use, mycophenolate mofetil use, and KT vintage < 7 years were negatively associated with the rate of anti-SARS-CoV-2 S IgG ≥ 15 U/mL in KT recipients. ABO blood type incompatible KT was not significantly associated with seroprevalence. Humoral response after the second BNT162b2 mRNA vaccine was greatly hindered by immunosuppression therapy in KT recipients. Older age, rituximab use, mycophenolate mofetil use, and KT vintage may play key roles in seroconversion.

Effect of active anticancer therapy on serologic response to SARS-CoV-2 BNT162b2 vaccine in patients with urothelial and renal cell carcinoma.

OBJECTIVES: To evaluate the serologic response to the BNT162b2 messenger ribonucleic acid vaccine in patients with urothelial carcinoma and renal cell carcinoma. METHODS: Between June 2021 and November 2021, we retrospectively evaluated blood samples from 60 healthy controls (control group), 57 patients with urothelial carcinoma, and 28 patients with renal cell carcinoma who had received two doses of the BNT162b2 vaccine at Hirosaki University Hospital. We determined the immunoglobulin G antibody titers against the severe acute respiratory syndrome coronavirus 2 spike receptor-binding domain. Seropositivity was defined as ≥15 U/mL. We investigate factors associated with antibody titers and seropositivity in the patients with urothelial carcinoma and renal cell carcinoma. RESULTS: Antibody titers in the control, urothelial carcinoma, and renal cell carcinoma groups were 813, 431, and 500 U/mL, respectively. Seropositivity was 100%, 90%, and 96% in the control, urothelial carcinoma, and renal cell carcinoma groups, respectively. Of the 85 patients, 37 of 57 (65%) and 21 of 28 (75%) were actively undergoing anticancer treatment for urothelial carcinoma and renal cell carcinoma, respectively. Anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers and seropositivity was not significantly different between the patients with urothelial carcinoma and renal cell carcinoma. Anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers were not significantly associated with active anticancer therapy or steroid treatment for immune-related adverse events. Univariable logistic regression analysis revealed that older age and metastatic disease were significantly and negatively associated with seropositivity. CONCLUSIONS: Patients with urothelial carcinoma or renal cell carcinoma exhibited an adequate antibody response to the BNT162b2 vaccine. Active anticancer therapy was not significantly associated with seropositivity following vaccination with severe acute respiratory syndrome coronavirus 2 BNT162b2 in patients with urothelial carcinoma and renal cell carcinoma.

Associations of impaired grip strength and gait function with the severity of erectile dysfunction in men undergoing dialysis: a cross-sectional study.

OBJECTIVE: To investigate the associations of impaired muscle strength and gait function with the severity of erectile dysfunction (ED) in men undergoing dialysis. METHODS: This cross-sectional study included 63 men undergoing dialysis. ED was assessed with the Sexual Health Inventory for Men (SHIM). Patients were divided into the mild/moderate (SHIM score ≥8) and severe ED groups (SHIM score ≤7). Correlations between variables were analyzed using Spearman's rank correlation coefficient. Multivariable logistic regression analyses were performed to evaluate the impact of impaired grip strength and gait function on the severity of ED. RESULTS: The median age of the study participants was 62 years; all had ED, with 67% having severe ED. Spearman's rank correlation test demonstrated significant negative and positive correlations between gait function and SHIM score (ρ = -0.257, p = 0.042) and between grip strength and SHIM score (ρ = 0.305, p = 0.015), respectively. In the multivariable analyses, impaired grip strength was significantly associated with severe ED (odds ratio [OR]: 4.965, p = 0.017), whereas gait function was not (OR: 3.147, p = 0.064). CONCLUSION: Impaired muscle strength was significantly associated with severe ED, whereas impaired gait function had a marginal effect on this erectile condition.

Simultaneous analysis of serum α2,3-linked sialylation and core-type fucosylation of prostate-specific antigen for the detection of high-grade prostate cancer.

BACKGROUND: Altered prostate-specific antigen (PSA) glycosylation patterns can be useful biomarkers in detecting high-grade prostate cancer (HGPC). The microfluidic immunoassay system can analyse α2,3-linked sialylated PSA (α2,3-Sia-PSA) and α1,6-linked fucosylated PSA (α1,6-Fuc-PSA) using different lectins, Mackkia amurensis agglutinin and Pholiota squarrosa lectin, respectively. Here, we investigated the diagnostic value of simultaneous analysis of α2,3-Sia-PSA and α1,6-Fuc-PSA for the detection of HGPC. METHODS: Men with serum PSA levels of 4-20 ng/mL who underwent prostate biopsy were included. The model to predict HGPC (Gleason grade ≥2) was constructed by multivariate logistic regression analysis, in combination with α2,3-Sia-PSA and α1,6-Fuc-PSA (SF index). RESULTS: In the development cohort (n = 150), the SF index showed good discrimination for HGPC (area under the receiver-operating curve (AUC) 0.842; 95% confidence interval (CI) 0.782-0.903), compared to the single PSA test (AUC 0.632, 95% CI 0.543-0.721), α2,3-Sia-PSA (AUC 0.711, 95% CI 0.629-0.793) and α1,6-Fuc-PSA (AUC 0.738, 95% CI 0.657-0.819). Decision-curve analysis showed the superior benefit of the SF index. In the validation cohort (n = 57), the SF index showed good discrimination for HGPC (AUC 0.769, 95% CI 0.643-0.895). CONCLUSIONS: The SF index could differentiate HGPC, providing useful information for decision making for prostate biopsy in men with abnormal PSA levels.

Utility of total cell-free DNA levels for surgical damage evaluation in patients with urological surgeries.

The evaluation of surgical damage is challenging because of the lack of specific biomarkers. Total cell-free DNA (cfDNA) levels have been reported to increase with external trauma and may be a biomarker for tissue damage. To investigate the utility of perioperative total cfDNA levels in evaluating surgical damage in urological surgeries. This multicenter, prospective, observational study included 196 patients scheduled for urological surgeries between September 2020 and July 2021. The primary outcome was the change in total cfDNA levels before and after urological surgery. The secondary outcome was the effect of surgical type on total cfDNA ratio before and after urological surgery. The postoperative median total cfDNA level of the 196 patients was significantly increased 2.5-fold compared to the preoperative level (185.2 ng/mL vs. 406.7 ng/mL, P < 0.001). The median total cfDNA before/after ratio was greater than four-fold for kidney transplantation, open cystectomy, and open adrenalectomy. The ratio was less than two-fold for laparoscopic adrenalectomy and robot-assisted radical prostatectomy. Major surgery showed a significant postoperative increase in total cfDNA levels, while minor surgery did not. Total cfDNA levels increased 2.5-fold after urological surgery and it can be used as an acute-phase biomarker for surgical damage.

Characteristics of α2,3-sialyl N-glycosylated PSA as a biomarker for clinically significant prostate cancer in men with elevated PSA level.

BACKGROUND: The presence of glycosylated isoforms of prostate-specific antigen (PSA) in prostate cancer (PC) cells is a potential marker of their aggressiveness. We characterized the origin of α2,3-sialylated prostate-specific antigen (S23PSA) by tissue-based sialylation-related gene expression and studied the performance of S23PSA density (S23PSAD) alone and in combination with multiparametric magnetic resonance imaging (MRI) for the detection of clinically significant prostate cancer in men with elevated PSA. METHODS: Tissue-based quantification of S23PSA and sialyltransferase and sialidase gene expression was evaluated in 71 radical prostatectomy specimens. The diagnostic performance of S23PSAD was studied in 1099 men retrospectively enrolled in a multicenter systematic biopsy (SBx) cohort. We correlated the S23PSAD with Prostate Imaging Reporting and Data System (PI-RADS) scores in 98 men prospectively enrolled in a single-center MRI-targeted biopsy (MRI-TBx) cohort. The primary outcome was the PC-diagnostic performance of the S23PSAD, the secondary outcome was the avoidable biopsy rate of S23PSAD combined with DRE and total PSA (tPSA), and with or without PI-RADS. RESULTS: S23PSA was significantly higher in Gleason pattern 4 and 5 compared with benign prostate tissue. In the retrospective cohort, the performance of S23PSAD for detecting PC was superior to tPSA or PSA density (PSAD) (AUC: 0.7758 vs. 0.6360 and 0.7509, respectively). In the prospective cohort, S23PSAD was superior to tPSA, PSAD, and PI-RADS (AUC: 0.7725 vs. 0.5901, 0.7439 and 0.7305, respectively), and S23PSAD + PI-RADS + DRE + tPSA was superior to DRE + tPSA+PI-RADS with avoidance rate of MRI-TBx (13% vs. 1%) at 30% risk threshold. CONCLUSIONS: The diagnostic performance of S23PSAD was superior to conventional strategies but comparable to mpMRI.