Background: and Purpose This study aimed to investigate the applicability of deep learning (DL) model using diffusion-weighted imaging (DWI) data to predict the severity of aphasia at an early stage in acute stroke patients. Methods: We retrospectively analyzed consecutive patients with aphasia caused by acute ischemic stroke in the left middle cerebral artery territory, who visited Asan Medical Center between 2011 and 2013. To implement the DL model to predict the severity of post-stroke aphasia, we designed a deep feed-forward network and utilized the lesion occupying ratio from DWI data and established clinical variables to estimate the aphasia quotient (AQ) score (range, 0 to 100) of the Korean version of the Western Aphasia Battery. To evaluate the performance of the DL model, we analyzed Cohen’s weighted kappa with linear weights for the categorized AQ score (0–25, very severe; 26–50, severe; 51–75, moderate; ≥76, mild) and Pearson’s correlation coefficient for continuous values. Results: We identified 225 post-stroke aphasia patients, of whom 176 were included and analyzed. For the categorized AQ score, Cohen’s weighted kappa coefficient was 0.59 (95% confidence interval [CI], 0.42 to 0.76; P<0.001). For continuous AQ score, the correlation coefficient between true AQ scores and model-estimated values was 0.72 (95% CI, 0.55 to 0.83; P<0.001). Conclusions DL approaches using DWI data may be feasible and useful for estimating the severity of aphasia in the early stage of stroke.

The present study evaluated the anti-cancer activity of histone deacetylase (HDAC)-inhibiting CKD-581 in multiple myeloma (MM) and its pharmacological mechanisms. CKD-581 potently inhibited a broad spectrum of HDAC isozymes. It concentration-dependently inhibited proliferation of hematologic cancer cells including MM (MM.1S and RPMI8226) and T cell lymphoma (HH and MJ). It increased the expression of the dishevelled binding antagonist of β-catenin 3 (DACT3) in T cell lymphoma and MM cells, and decreased the expression of c-Myc and β-catenin in MM cells. Additionally, it enhanced phosphorylated p53, p21, cleaved caspase-3 and the subG1 population, and reversely, downregulated cyclin D1, CDK4 and the anti-apoptotic BCL-2 family. Finally, administration of CKD-581 exerted a significant anti-cancer activity in MM.1S-implanted xenografts. Overall, CKD-581 shows anticancer activity via inhibition of the Wnt/β-catenin signaling pathway in hematologic malignancies. This finding is evidence of the therapeutic potential and rationale of CKD-581 for treatment of MM.

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: The aim of the present study was to evaluate the efficacy and safety of the electromagnetic-type low-intensity extracorporeal shock wave therapy (Li-ESWT) in patients with erectile dysfunction (ED).MATERIALS AND METHODS: The randomized, sham-controlled, double-blind prospective study was performed at two referral hospitals. Participants were randomized in a 1:1 ratio to receive sham or Li-ESWT for 6 weeks. ED was evaluated at screening and at 4 and 7 weeks after treatment. Participants were asked to complete the international index of erectile function-erectile function (IIEF-EF) domain questionnaire, erection hardness scale (EHS), and sexual encounter profile questionnaire (SEPQ 2 and 3). The development of complications was investigated.RESULTS: Eighty-one of 96 patients completed the study. The median change in the IIEF-EF score in the Li-ESWT and sham groups was 5.1 and −2.2 (p<0.001), respectively, at the 7-week follow-up; 47.4% (18/38) patients had EHS <3, of which 77.8% (14/18) showed significant improvement in virtue of Li-ESWT treatment (p=0.001). A significant improvement was observed in the percentage of “Yes” responses to SEPQ 2 and 3 in the Li-ESWT group vs. sham group from baseline to 7-week follow-up (91.3% vs. 69.4%; p=0.008 and 50.0% vs. 14.3%; p=0.002, respectively). No patients reported pain or other adverse events during treatment or follow-up.CONCLUSIONS: Thus, Li-ESWT could have a role in improving erectile function. Furthermore, it is safe. We believe that Li-ESWT is an attractive new treatment modality for patients with ED.

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