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IntroductionChronic treatment with phosphodiesterase type 5 inhibitors (PDE5) is effective in an animal model of diabetes‐induced erectile dysfunction (DMED). In addition, recent research indicates that glycemic control can restore DMED.AimsWe evaluated the effect of chronic administration of PDE5 combined with glycemic control on DMED.MethodsSprague‐Dawley rats (8 weeks old) were divided into five groups (n = 10 each): normal control (C), diabetes (DM), DM treated with insulin (DM‐I), DM treated with PDE5 (DM‐P), and DM treated with insulin and PDE5 (DM‐I + P). Rats in the diabetic groups received an injection of streptozotocin (45 mg/kg). After 10 weeks of induced diabetes, the DM‐I group was treated with a daily injection of neutral protamine Hagedorn, and the DM‐P group was treated with a daily dosage of 20 mg/kg PDE5 (DA‐8159) for 4 weeks. The DM‐I + P group was treated with both treatments simultaneously. After 14 weeks of induced diabetes, an evaluation of erectile function and histological and biochemical markers of corporal tissue was performed.Main Outcome MeasuresErectile function and histological and biochemical markers in corporal tissue.ResultsRats in the DM group showed markedly lower erectile parameters than those in the C group, whereas rats in the DM‐I and DM‐P groups showed intermediate erectile function between the DM and C groups. Rats in the DM‐I + P group showed restored erectile function, comparable with group C. A comparison of apoptotic index, expression of the endothelial marker, and phosphorylation of endothelial nitric oxide synthase and Akt displayed a similar pattern with the results from cavernosometry (DM < DM‐I = DM‐P < DM‐I + P = C, P < 0.05). The distribution of phosphorylated myosin phosphatase target subunit 1 was in the reverse order.ConclusionsChronic administration of PDE5 or glycemic control with insulin resulted in restoration of overt DMED. The combination of both treatments was superior to monotherapy with insulin or PDE5. Choi WS, Kwon OS, Cho SY, Paick J‐S, and Kim SW. Effect of chronic administration of PDE5 combined with glycemic control on erectile function in streptozotocin‐induced diabetic rats. J Sex Med 2015;12:600–610.  相似文献   
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Background: Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings. Materials and methods: In this study, we assessed the combined prognostic utility of IDC/C, and CAPRA-S for BCR in 3 PCa patient cohorts. Results: CAPRA-S+IDC/C improved the predictive accuracy of BCR in all 3 cohorts (P < .001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P < .001, Cohort 2; P < .001, Cohort 3; P = .003), intermediate (Cohort 1; P < .001, Cohort 2; P = .006, Cohort 3; P = .03) and high-risk (Cohort 1-3; P < .001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRA-S low-risk (Cohorts 1; P < .001 and Cohort 3; P = .003) patients. Conclusion: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery.  相似文献   
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BackgroundThe use of plaque incision and graft techniques (PIG) for the treatment of severe Peyronie's disease (PD), may lead to erectile dysfunction (ED); graft size is 1 of the contributing factors for post-PIG ED. Recently the iGrafter software APP was introduced using a mathematical algorithm to distribute the incisions along the penile length resulting in a smaller grafting area.AimCompare 2 PIG techniques, the Double-Y(DY) and iGrafter, in 3 main aspects: (i) Total grafting area; (ii) The variation in calculating the grafting to be used; (iii) time to perform the PIG.MethodsSix urologists with expertise in sexual medicine performed both techniques twice using four 3-D validated training models for PD with a standard 60° uniplanar dorsal curvature.OutcomesThe graft areas and operative partial and total time for each step of the operation were recorded for each procedure. Unpaired t-test and the coefficient of variation for graft area across surgeons was calculated comparing both techniques.ResultsFor all surgeons, the use of iGrafter resulted in 2 grafts, for the DY technique in 1 graft. Overall, TT for the iGrafter was significantly longer than for DY technique (49.4 ± 11 vs 40.7 ± 5.7 minute; P = .02), The iGrafter grafting area was significantly smaller (11.6 ± 1.2 vs 23.3 ± 5.4 cm2; P: .01), representing a 50.2% area reduction when compared to the DY. The variation of graft area, using the iGrafter also yielded a more consistent graft across all surgeons (CV = 10.56% vs 23.28%).Clinical SignificanceThe iGrafter, when compared to DY technique, reduced the graft area by 50%, which potentially means less erectile dysfunction.Strengths and LimitationsOur study eliminates anatomical variations found in a real clinical case making it possible to compare surgical techniques with the same penile anatomy. However, the 3D-printed model cannot replicate the living human tissue property preventing a simulation close to actual surgery.ConclusionThe use of the iGrafter software for PIG surgery has shown to be a promising technique for severe PD management resulting in smaller graft size (about 50% smaller when compared to the DY), although it might be more time-consuming.Tourchi A, Nascimento B, de Freita Miranda A, et al. Grafting Area Reduction in Peyronie's Disease Surgery: Comparative Assessment Between Double Y Vs iGrafter APP Using 3D-Printed Penile Models. J Sex Med 2022;19:669–675.  相似文献   
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Background

Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.

Methods

Using The Cancer Genome Atlas (n?=?436) and Cancer Genomics of the Kidney (n?=?89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments.

Results

Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age.

Conclusion

We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment.  相似文献   
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IntroductionWe examined national and regional trends in hospital‐based penile prosthetic surgery and identified patient‐specific factors predicting receipt of inflatable vs. semi‐rigid penile prostheses.AimsTo improve our understanding of the surgical treatment for erectile dysfunction (ED).MethodsWe utilized the Nationwide Inpatient Sample (NIS) from 1998 to 2010 in the United States and the California Office of Statewide Health Planning and Development (OSHPD) database from 1995 to 2010. Total number of penile implants performed and proportions of inflatable vs. semi‐rigid prosthesis were examined. Multivariate analysis (MVA) was performed to identify factors associated with selection of inflatable vs. semi‐rigid prostheses.Main Outcome MeasuresPrimary outcome measure is the total number of hospital‐based penile prosthetic surgeries performed in the United States over a 12‐year period (1998–2010). Secondary outcome measures include proportion of inflatable and semi‐rigid prosthesis implantations and factors influencing receipt of different prostheses.ResultsWe identified 53,967 penile prosthetic surgeries in the NIS; annual number implanted decreased from 4,703 to 2,338. Inflatable prostheses incurred higher costs but had a similar length of stay (LOS). In MVA, Caucasian race, Peyronie's disease, and private insurance were independently associated with receipt of an inflatable prosthesis. We identified 7,054 penile prostheses in OSHPD; annual number implanted decreased from 760 to 318. The proportion of inflatable prostheses increased significantly from 78.4% to 88.4% between 2001 and 2010. Inflatable prostheses incurred higher costs but had similar median LOS. In MVA, Caucasians and men without spinal cord injury were more likely to receive inflatable prosthesis.ConclusionHospital‐based penile prosthetic surgery has decreased substantially both nationwide and in California. In the United States, Caucasian race, Peyronie's disease, and private insurance were independently associated with receipt of an inflatable penile prosthesis. California population data correlated with national trends and can be utilized to further study surgical management of ED. Mirheydar HS, Palazzi KL, Parsons JK, Chang D, and Hsieh T‐C. Hospital‐based trends in penile prosthetic surgery. J Sex Med 2015;12:1092–1098.  相似文献   
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Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Objective

To assess the accuracy of available tools to predict LNI and to develop a novel model for men diagnosed via MRI-targeted biopsies.

Design, setting, and participants

A total of 497 patients diagnosed via MRI-targeted biopsies and treated with RP and extended pelvic lymph node dissection (ePLND) at five institutions were retrospectively identified.

Outcome measurements and statistical analyses

Three available models predicting LNI were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses. A nomogram predicting LNI was developed and internally validated.

Results and limitations

Overall, 62 patients (12.5%) had LNI. The median number of nodes removed was 15. The AUC for the Briganti 2012, Briganti 2017, and MSKCC nomograms was 82%, 82%, and 81%, respectively, and their calibration characteristics were suboptimal. A model including PSA, clinical stage and maximum diameter of the index lesion on multiparametric MRI (mpMRI), grade group on targeted biopsy, and the presence of clinically significant PCa on concomitant systematic biopsy had an AUC of 86% and represented the basis for a coefficient-based nomogram. This tool exhibited a higher AUC and higher net benefit compared to available models developed using standard biopsies. Using a cutoff of 7%, 244 ePLNDs (57%) would be spared and a lower number of LNIs would be missed compared to available nomograms (1.6% vs 4.6% vs 4.5% vs 4.2% for the new nomogram vs Briganti 2012 vs Briganti 2017 vs MSKCC).

Conclusions

Available models predicting LNI are characterized by suboptimal accuracy and clinical net benefit for patients diagnosed via MRI-targeted biopsies. A novel nomogram including mpMRI and MRI-targeted biopsy data should be used to identify candidates for ePLND in this setting.

Patient summary

We developed the first nomogram to predict lymph node invasion (LNI) in prostate cancer patients diagnosed via magnetic resonance imaging-targeted biopsy undergoing radical prostatectomy. Adoption of this model to identify candidates for extended pelvic lymph node dissection could avoid up to 60% of these procedures at the cost of missing only 1.6% patients with LNI.  相似文献   
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