Purpose: Various predictive tools have been developed to predict insignificant prostate cancer (PCa) for active surveillance, however, these models cannot reflect all the refinements of current medicine. Thus, we aimed to develop a novel model to predict clinically insignificant PCa incorporating these factors. Materials and Methods: We developed a novel nomogram to predict the probability of insignificant PCa (total tumor volume less than 2.5 cm3, index tumor volume less than 1.3 cm3, organ confined disease and no Gleason pattern 4 or 5) using preoperative data of 790 Korean patients who underwent radical prostatectomy. To evaluate the predictive accuracy, the area under the receiver operating characteristic curve (AUC) was calculated. Next, the predicted probability versus the actual probability was compared. This examination was performed by calibration plotting using 1,000 bootstrap resamples. Results: Of the 790 patients, 668 (84.6%) had clinically significant PCa, and 122 (15.4%) had insignificant PCa. We developed a novel predictive model for clinically insignificant PCa using clinical stage less than T2a, biopsy Gleason sum less than 7, ratio of positive biopsy cores less than 10%, neutrophil-to-lymphocyte ratio, and multiparametric magnetic resonance imaging (mpMRI) visibility, which discriminated patients with clinically insignificant PCa from those with significant PCa with an AUC of 0.9135 (95% confidence interval, 0.9127–0.9143). The calibration plot showed a well-calibrated prediction that had little over- or underestimation. Conclusions We proposed a novel predictive model for insignificant PCa to more accurately select patients for active surveillance using the results from mpMRI and prebiopsy laboratory marker.

Purpose: Various predictive tools have been developed to predict insignificant prostate cancer (PCa) for active surveillance, however, these models cannot reflect all the refinements of current medicine. Thus, we aimed to develop a novel model to predict clinically insignificant PCa incorporating these factors. Materials and Methods: We developed a novel nomogram to predict the probability of insignificant PCa (total tumor volume less than 2.5 cm3, index tumor volume less than 1.3 cm3, organ confined disease and no Gleason pattern 4 or 5) using preoperative data of 790 Korean patients who underwent radical prostatectomy. To evaluate the predictive accuracy, the area under the receiver operating characteristic curve (AUC) was calculated. Next, the predicted probability versus the actual probability was compared. This examination was performed by calibration plotting using 1,000 bootstrap resamples. Results: Of the 790 patients, 668 (84.6%) had clinically significant PCa, and 122 (15.4%) had insignificant PCa. We developed a novel predictive model for clinically insignificant PCa using clinical stage less than T2a, biopsy Gleason sum less than 7, ratio of positive biopsy cores less than 10%, neutrophil-to-lymphocyte ratio, and multiparametric magnetic resonance imaging (mpMRI) visibility, which discriminated patients with clinically insignificant PCa from those with significant PCa with an AUC of 0.9135 (95% confidence interval, 0.9127–0.9143). The calibration plot showed a well-calibrated prediction that had little over- or underestimation. Conclusions We proposed a novel predictive model for insignificant PCa to more accurately select patients for active surveillance using the results from mpMRI and prebiopsy laboratory marker.

Background: and purpose Whether pharmacologically altered high-density lipoprotein cholesterol (HDL-C) affects the risk of cardiovascular events is unknown. Recently, we have reported the Prevention of Cardiovascular Events in Asian Patients with Ischaemic Stroke at High Risk of Cerebral Haemorrhage (PICASSO) trial that demonstrated the non-inferiority of cilostazol to aspirin and superiority of probucol to non-probucol for cardiovascular prevention in ischemic stroke patients (clinicaltrials.gov: NCT01013532). We aimed to determine whether on-treatment HDL-C changes by cilostazol and probucol influence the treatment effect of each study medication during the PICASSO study. Methods: Of the 1,534 randomized patients, 1,373 (89.5%) with baseline cholesterol parameters were analyzed. Efficacy endpoint was the composite of stroke, myocardial infarction, and cardiovascular death. Cox proportional hazards regression analysis examined an interaction between the treatment effect and changes in HDL-C levels from randomization to 1 month for each study arm. Results: One-month post-randomization mean HDL-C level was significantly higher in the cilostazol group than in the aspirin group (1.08 mmol/L vs. 1.00 mmol/L, P<0.001). The mean HDL-C level was significantly lower in the probucol group than in the non-probucol group (0.86 mmol/L vs. 1.22 mmol/L, P<0.001). These trends persisted throughout the study. In both study arms, no significant interaction was observed between HDL-C changes and the assigned treatment regarding the risk of the efficacy endpoint. Conclusions Despite significant HDL-C changes, the effects of cilostazol and probucol treatment on the risk of cardiovascular events were insignificant. Pharmacologically altered HDL-C levels may not be reliable prognostic markers for cardiovascular risk.

PURPOSE: In this study, we attempted to characterize capsaicin's effects with regard to the apoptosis of murine bladder cancer cells (MBT-2) as well as the pharmacodynamics of nano-encapsulated capsaicin formulation for intravesical instillation. MATERIALS AND METHODS: We assessed the viability of the MBT-2 cells via MTT staining, agarose gel electrophoresis, and flow cytometric apoptosis analysis. Intravesical reagents were instilled into 3 groups of male white New Zealand rabbits. Instillation agents were nano-encapsulated capsaicin dissolved in saline, capsaicin dissolved in saline, and capsaicin dissolved in dimethyl sulfoxide (DMSO). We also determined the pharmacokinetics of urine, plasma, and bladder tissue after intravesical capsaicin instillation. RESULTS: Capsaicin treatment was determined to reduce cell viability in a time- and dose-dependent manner. The capsaicin concentrations in the urine of the rabbits decreased in each of the treatment groups, but we noted a more profound reduction of capsaicin concentration in the nano-encapsulated capsaicin group. Plasma concentrations were definitely lower as compared with the levels measured in the bladder tissue and urine. We noted distinctive differences in patterns of concentration change between the capsaicin with normal saline solution (NSS) or DMSO and the nano-encapsulated capsaicin groups. The concentration of nano-encapsulated capsaicin in the tissue appeared to increase directly with tissue depth. CONCLUSIONS Our results show that capsaicin can induce apoptosis in MBT-2 cells, as well as the excellent permeation properties of nano-encapsulated capsaicin. Treatment with intravesical capsaicin may be a promising alternative therapeutic modality for the treatment of bladder cancer.

BACKGROUND AND OBJECTIVES: Few studies were evaluated the effect of blindness on outcome in animal models, though a potential effect of blinding has been reported in clinical trials. We evaluated the effects of adipose tissue-derived stem cells (ADSCs) on cavernous nerve injury (CNI)-induced erectile dysfunction (ED) in the rat and examined how proper blinding of the outcome assessor affected treatment effect. METHODS AND RESULTS: We searched in Pubmed, EMBASE, Cochrane and Web of Science databases from inception to January 2019. We included CNI animal model, randomized controlled experiments, and ADSC intervention. Erectile function and structural changes were assessed by intracavernous pressure and mean arterial pressure (ICP/MAP) ratios, neuronal nitric oxide synthase (nNOS) levels, cavernous smooth muscle and collagen (CSM/collagen) ratios, and cyclic guanosine monophosphate (cGMP). RESULTS: Nineteen studies were included in the final meta-analysis. The ICP/MAP ratio of the ADSC treatment group increased compared to the control group (SMD=1.33, 95%CI: 1.11~1.56, I²=72%). The nNOS level (SMD=2.29, 95%CI: 1.74~2.84, I²=75%), CSM/collagen (SMD=2.57, 95%CI: 1.62~3.52; I²=85%), and cGMP (SMD=2.96, 95%CI: 1.82~4.10, I²=62%) were also increased in the ADSC treatment group. Preplanned subgroup analysis was conducted to explore the source of heterogeneity. Five studies with blinded outcome assessment were significantly less effective than the unblinded studies (SMD=1.33, 95%CI: 0.86~1.80; SMD=1.81, 95%CI: 1.17~2.46, respectively). CONCLUSIONS: ADSCs might be effective in improving erectile function and structural change in CNI-induced ED. However, non-blinded outcome assessors might cause detection bias and overestimate treatment efficacy. Therefore, the ADSC efficacy must be further evaluated with a rigorous study design to avoid bias.
Animals ; Arterial Pressure ; Bias (Epidemiology) ; Blindness ; Collagen ; Erectile Dysfunction ; Guanosine Monophosphate ; Male ; Models, Animal ; Muscle, Smooth ; Nitric Oxide Synthase Type I ; Population Characteristics ; Rats ; Stem Cells ; Treatment Outcome

BACKGROUND AND PURPOSE: This study evaluated the outcome following surgery for carotid artery stenosis in a single institution during a 10-year period and the relevance of aging to access to surgery. METHODS: Between January 2001 and December 2010, 649 carotid endarterectomies (CEAs) were performed in 596 patients for internal carotid artery occlusive disease at our institution; 596 patients received unilateral CEAs and 53 patients received bilateral CEAs. Data regarding patient characteristics, comorbidities, stroke, mortality, restenosis, and other surgical complications were obtained from a review of medical records. Since elderly and high-risk patients comprise a significant proportion of the patient group undergoing CEAs, differences in comorbidity and mortality were evaluated according to age when the patients were divided into three age groups: <70 years, 70-79 years, and > or =80 years. RESULTS: The mean age of the included patients was 67.5 years, and 88% were men. Symptomatic carotid stenosis was observed in 65.7% of patients. The rate of perioperative stroke and death (within 30 days of the procedure) was 1.84%. The overall mortality rate was higher among patients in the 70-79 years and >80 years age groups than among those in the <70 years age group, but there was no significant difference in stroke-related mortality among these three groups. CONCLUSIONS: CEA over a 10-year period has yielded acceptable outcomes in terms of stroke and mortality. Therefore, since CEA is a safe and effective strategy, it can be performed in elderly patients with acceptable life expectancy.
Aged* ; Aging ; Carotid Artery, Internal ; Carotid Stenosis ; Comorbidity ; Endarterectomy ; Endarterectomy, Carotid* ; Humans ; Life Expectancy ; Male ; Medical Records ; Mortality ; Retrospective Studies* ; Stroke

PURPOSE: Specific immunoglobulin G4 (sIgG4) and immunoglobulin E (IgE)-blocking factors produced by subcutaneous immunotherapy (SCIT) play a critical role in the induction of allergen tolerance. However, comparative studies of available SCIT reagents on the induction of sIgG4 are limited. We compared increases in sIgG4 for three different house dust mite (HDM) SCIT reagents. MATERIALS AND METHODS: Seventy-two HDM sensitized allergic patients were enrolled and classified into four groups: 1) control (n=27), 2) SCIT with Hollister-Stier® (n=19), 3) Tyrosine S® (n=16), and 4) Novo-Helisen® (n=10). Levels of specific IgE (sIgE), sIgG4, and IgE blocking factor to Dermatophagoides farinae (D. farinae) were measured using ImmunoCAP (sIgE, sIgG4) and enzyme-linked immunosorbent assay (ELISA) (IgE-blocking factors). Levels were measured before and 13.9±6.6 months after the SCIT. The allergen specificity and the induction levels of sIgE and sIgG4 were confirmed by immunoblot analysis. RESULTS: After SCIT, sIgG4 levels to D. farinae increased significantly; however, the increases differed significantly among the SCIT groups (p<0.001). Specific IgG4 levels to D. farinae were highest in Hollister-Stier® (3.7±4.1 mg/L), followed by Novo-Helisen® (2.2±2.3 mg/L) and Tyrosine S® (0.7±0.5 mg/L). In addition, patients who were administered using Hollister-Stier® showed the most significant decrease in IgE/IgG4 ratio (p<0.001) and increase in blocking factor (p=0.009). Finally, according to IgE immunoblot results, the Hollister-Stier® group showed the most significant attenuation of IgE binding patterns among others. CONCLUSION: Currently available SCIT reagents induce different levels of specific IgG4, IgE/IgG4 ratio, and IgE-blocking factor.
Dermatophagoides farinae ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins* ; Immunotherapy* ; Indicators and Reagents ; Mites* ; Pyroglyphidae ; Sensitivity and Specificity ; Tyrosine

PURPOSE: Specific immunoglobulin G4 (sIgG4) and immunoglobulin E (IgE)-blocking factors produced by subcutaneous immunotherapy (SCIT) play a critical role in the induction of allergen tolerance. However, comparative studies of available SCIT reagents on the induction of sIgG4 are limited. We compared increases in sIgG4 for three different house dust mite (HDM) SCIT reagents. MATERIALS AND METHODS: Seventy-two HDM sensitized allergic patients were enrolled and classified into four groups: 1) control (n=27), 2) SCIT with Hollister-Stier® (n=19), 3) Tyrosine S® (n=16), and 4) Novo-Helisen® (n=10). Levels of specific IgE (sIgE), sIgG4, and IgE blocking factor to Dermatophagoides farinae (D. farinae) were measured using ImmunoCAP (sIgE, sIgG4) and enzyme-linked immunosorbent assay (ELISA) (IgE-blocking factors). Levels were measured before and 13.9±6.6 months after the SCIT. The allergen specificity and the induction levels of sIgE and sIgG4 were confirmed by immunoblot analysis. RESULTS: After SCIT, sIgG4 levels to D. farinae increased significantly; however, the increases differed significantly among the SCIT groups (p<0.001). Specific IgG4 levels to D. farinae were highest in Hollister-Stier® (3.7±4.1 mg/L), followed by Novo-Helisen® (2.2±2.3 mg/L) and Tyrosine S® (0.7±0.5 mg/L). In addition, patients who were administered using Hollister-Stier® showed the most significant decrease in IgE/IgG4 ratio (p<0.001) and increase in blocking factor (p=0.009). Finally, according to IgE immunoblot results, the Hollister-Stier® group showed the most significant attenuation of IgE binding patterns among others. CONCLUSION: Currently available SCIT reagents induce different levels of specific IgG4, IgE/IgG4 ratio, and IgE-blocking factor.
Dermatophagoides farinae ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins* ; Immunotherapy* ; Indicators and Reagents ; Mites* ; Pyroglyphidae ; Sensitivity and Specificity ; Tyrosine