To investigate the adverse effects of clozapine on cardiovascular ion channels, we examined the inhibitory effect of clozapine on voltage-dependent K+(Kv) channels in rabbit coronary arterial smooth muscle cells. Clozapine-induced inhibition of Kv channels occurred in a concentration-dependent manner with an halfinhibitory concentration value of 7.84 ± 4.86 µM and a Hill coefficient of 0.47 ± 0.06.Clozapine did not shift the steady-state activation or inactivation curves, suggesting that it inhibited Kv channels regardless of gating properties. Application of train pulses (1 and 2 Hz) progressively augmented the clozapine-induced inhibition of Kv channels in the presence of the drug. Furthermore, the recovery time constant from inactivation was increased in the presence of clozapine, suggesting that clozapineinduced inhibition of Kv channels is use (state)-dependent. Pretreatment of a Kv1.5 subtype inhibitor decreased the Kv current amplitudes, but additional application of clozapine did not further inhibit the Kv current. Pretreatment with Kv2.1 or Kv7 subtype inhibitors partially blocked the inhibitory effect of clozapine. Based on these results, we conclude that clozapine inhibits arterial Kv channels in a concentrationand use (state)-dependent manner. Kv1.5 is the major subtype involved in clozapineinduced inhibition of Kv channels, and Kv2.1 and Kv7 subtypes are partially involved.

Purpose: We aimed to investigate the risk factors and patterns of locoregional recurrence (LRR) after radical nephrectomy (RN) in patients with locally advanced renal cell carcinoma (RCC). Materials and Methods: We retrospectively analyzed 245 patients who underwent RN for non-metastatic pT3-4 RCC from January 2006 to January 2016. We analyzed the risk factors associated with poor locoregional control using Cox regression. Anatomical mapping was performed on reference computed tomography scans showing intact kidneys. Results: The median follow-up duration was 56 months (range, 1 to 128 months). Tumor extension to renal vessels or the inferior vena cava (IVC) and Fuhrman’s nuclear grade IV were identified as independent risk factors of LRR. The 5-year actuarial LRR rates in groups with no risk factor, one risk factor, and two risk factors were 2.3%, 19.8%, and 30.8%, respectively (p < 0.001). The locations of LRR were distributed as follows: aortocaval area (n=2), paraaortic area (n=4), retrocaval area (n=5), and tumor bed (n=11). No LRR was observed above the celiac axis (CA) or under the inferior mesenteric artery (IMA). Conclusion Tumor extension to renal vessels or the IVC and Fuhrman’s nuclear grade IV were the independent risk factors associated with LRR after RN for pT3-4 RCC. The locations of LRR after RN for RCC were distributed in the tumor bed and regional lymphatic area from the bifurcation of the CA to that of the IMA.

Background: and Purpose We aimed to develop a model predicting early recanalization after intravenous tissue plasminogen activator (t-PA) treatment in large-vessel occlusion. Methods: Using data from two different multicenter prospective cohorts, we determined the factors associated with early recanalization immediately after t-PA in stroke patients with large-vessel occlusion, and developed and validated a prediction model for early recanalization. Clot volume was semiautomatically measured on thin-section computed tomography using software, and the degree of collaterals was determined using the Tan score. Follow-up angiographic studies were performed immediately after t-PA treatment to assess early recanalization. Results: Early recanalization, assessed 61.0±44.7 minutes after t-PA bolus, was achieved in 15.5% (15/97) in the derivation cohort and in 10.5% (8/76) in the validation cohort. Clot volume (odds ratio [OR], 0.979; 95% confidence interval [CI], 0.961 to 0.997; P=0.020) and good collaterals (OR, 6.129; 95% CI, 1.592 to 23.594; P=0.008) were significant factors associated with early recanalization. The area under the curve (AUC) of the model including clot volume was 0.819 (95% CI, 0.720 to 0.917) and 0.842 (95% CI, 0.746 to 0.938) in the derivation and validation cohorts, respectively. The AUC improved when good collaterals were added (derivation cohort: AUC, 0.876; 95% CI, 0.802 to 0.950; P=0.164; validation cohort: AUC, 0.949; 95% CI, 0.886 to 1.000; P=0.036). The integrated discrimination improvement also showed significantly improved prediction (0.097; 95% CI, 0.009 to 0.185; P=0.032). Conclusions The model using clot volume and collaterals predicted early recanalization after intravenous t-PA and had a high performance. This model may aid in determining the recanalization treatment strategy in stroke patients with large-vessel occlusion.

Background: and Purpose We aimed to develop a model predicting early recanalization after intravenous tissue plasminogen activator (t-PA) treatment in large-vessel occlusion. Methods: Using data from two different multicenter prospective cohorts, we determined the factors associated with early recanalization immediately after t-PA in stroke patients with large-vessel occlusion, and developed and validated a prediction model for early recanalization. Clot volume was semiautomatically measured on thin-section computed tomography using software, and the degree of collaterals was determined using the Tan score. Follow-up angiographic studies were performed immediately after t-PA treatment to assess early recanalization. Results: Early recanalization, assessed 61.0±44.7 minutes after t-PA bolus, was achieved in 15.5% (15/97) in the derivation cohort and in 10.5% (8/76) in the validation cohort. Clot volume (odds ratio [OR], 0.979; 95% confidence interval [CI], 0.961 to 0.997; P=0.020) and good collaterals (OR, 6.129; 95% CI, 1.592 to 23.594; P=0.008) were significant factors associated with early recanalization. The area under the curve (AUC) of the model including clot volume was 0.819 (95% CI, 0.720 to 0.917) and 0.842 (95% CI, 0.746 to 0.938) in the derivation and validation cohorts, respectively. The AUC improved when good collaterals were added (derivation cohort: AUC, 0.876; 95% CI, 0.802 to 0.950; P=0.164; validation cohort: AUC, 0.949; 95% CI, 0.886 to 1.000; P=0.036). The integrated discrimination improvement also showed significantly improved prediction (0.097; 95% CI, 0.009 to 0.185; P=0.032). Conclusions The model using clot volume and collaterals predicted early recanalization after intravenous t-PA and had a high performance. This model may aid in determining the recanalization treatment strategy in stroke patients with large-vessel occlusion.

Background: The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. Methods: This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. Results: Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53%) and infection (44%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. Conclusions Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.

OBJECTIVE: To retrospectively determine whether the use of the Prostate Imaging Reporting and Data System (PI-RADS) version 2 (v2) helps predict long-term outcomes for prostate cancer (PCa) patients following radical prostatectomy (RP). MATERIALS AND METHODS: A total of 166 patients with localized PCa evaluated with multiparametric magnetic resonance imaging (mpMRI) at 3T before RP were enrolled. Three groups were created based on PI-RADS v2 score used to predict clinical outcomes: group A, ≥ 3; group B, ≥ 4; group C, 5. We calculated biochemical recurrence-free survival (RFS) and progression-free survival (PFS). Cox proportion hazards models were used to identify variables predictive of biochemical recurrence and disease progression. RESULTS: During a median follow-up of 9.1 years, biochemical recurrence occurred in 67 patients (40.4%) and disease progression occurred in 55 patients (33.1%). In all groups, 10-year RFS and 10-year PFS were significantly lower for PI-RADS scores ≥ 3, ≥ 4 and 5 than for score < 3, < 4 and < 5 (p <0.05), respectively. In multivariate analysis, PI-RADS score ≥ 3 and score 5 were significant independent risk marker for biochemical recurrence (hazard ratio [HR] = 5.58, p = 0.018; HR = 1.75, p = 0.033) and disease progression (HR = 3.99, p = 0.047; HR = 2.31, p = 0.040). Moderate inter-observer agreement was seen for PI-RADS scoring. CONCLUSION: PI-RADS v2 may be used to predict long-term outcomes following RP in PCa.
Disease Progression ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Information Systems ; Magnetic Resonance Imaging ; Male ; Multivariate Analysis ; Passive Cutaneous Anaphylaxis ; Prognosis ; Proportional Hazards Models ; Prostate ; Prostatectomy ; Prostatic Neoplasms ; Recurrence ; Retrospective Studies

PURPOSE: To compare biopsy performance of 2 approaches for multiparametric magnetic resonance imaging (MRI) guided biopsy and transrectal ultrasonography (TRUS)-guided biopsy with 2nd and 3rd repeat biopsy patients in prostate cancer detection. MATERIALS AND METHODS: This retrospective study reviewed 2,868 patients who was performed prostate biopsy between September 2013 to March 2017 at Samsung Medical Center, Seoul, Korea with TRUS-guided random biopsy and MRI fusion, MRI cognitive, and MRI-guided biopsy as 2nd and 3rd repeat biopsy and propensity matching was applied to reduce bias. Detection rate of each study was compared with 1:1 matching. RESULTS: Among 265 patients who performed TRUS 2nd biopsy, positivity rate for prostate cancer (PCa) was 18.49% (n=49/265) while 54.72% (n=145/265) for MRI-guided biopsy. In 3rd biopsy, positivity rate for PCa of TRUS biopsy was 17.74% (n=11/62) while 56.45% (n=35/62) for MRI guided biopsy. There was no significant difference in the detection rate for the patient with Gleason score 8 or more. CONCLUSIONS: MRI-guided biopsy was associated with a higher detection rate of prostate cancer with especially in patients with prior negative biopsy.
Bias (Epidemiology) ; Biopsy ; Cohort Studies ; Humans ; Korea ; Magnetic Resonance Imaging ; Neoplasm Grading ; Passive Cutaneous Anaphylaxis ; Propensity Score ; Prostate ; Prostatic Neoplasms ; Retrospective Studies ; Seoul ; Ultrasonography

PURPOSE: We compared biopsy results and surgical outcomes of magnetic resonance imaging (MRI)-guided biopsy with transrectal ultrasonography (TRUS)-guided biopsy to demonstrate efficacy of MRI-guided biopsy on previous biopsy negative patients. MATERIALS AND METHODS: We retrospectively reviewed data of 120 patients who were categorized into MRI-guided biopsy groups (n=20) and TRUS-guided biopsy groups (n=100). All patients were diagnosed with prostate cancer (PCa) and had undergone radical prostatectomy (RP) after MRI-guided or TRUS-guided repeat biopsy between January 2010 and March 2016. Detection rate of significant cancer and Gleason score upgrading and downgrading were examined, in addition to biopsy results and subsequent RP outcomes. RESULTS: Median values for prostate-specific antigen level of the TRUS-guided biopsy group and the MRI-guided biopsy group were 6.67 and 5.86 ng/mL (p=0.303), respectively. Median prostate volume of each group (34.1 mL vs. 23.5 mL, p=0.007), number of positive cores (2.0 vs. 3.0, p=0.001) and maximum cancer/core rate (30.0% vs. 60.0%, p<0.001) were statistically different. Positive core rates of each group were 21.9% and 87.1%, respectively. Pathologic T stage was the only variable that showed difference in surgical outcomes (p=0.002). Most of PCa was confirmed as clinically significant PCa after RP in MRI-guided biopsy group (95%). CONCLUSIONS: MRI-guided biopsy showed higher positive core rate and detection rate of clinically significant PCa than TRUS-guided biopsy in repeat biopsy setting. Prospective multicenter large-scale study and accumulation of data is expected to further define superiority of the MRI-guided biopsy.
Biopsy* ; Humans ; Magnetic Resonance Imaging ; Neoplasm Grading ; Passive Cutaneous Anaphylaxis ; Prospective Studies ; Prostate ; Prostate-Specific Antigen ; Prostatectomy ; Prostatic Neoplasms ; Retrospective Studies ; Ultrasonography

PURPOSE: To determine the negative predictive value (NPV) of multiparametric magnetic resonance imaging (mp-MRI) for clinically significant cancer (CSC) based on the Prostate Imaging-Reporting and Data System (PI-RADS) version 2 in very low-risk or low-risk prostate cancer patients. MATERIALS AND METHODS: We retrospectively analyzed 380 patients with low risk of prostate cancer who underwent mp-MRI before radical prostatectomy (RP) from 2011 to 2013. Of the 380 patients, 142 patients were in the very low risk group. CSC at RP was defined as follows: any T3−4, G3+4 with tumor volume>15%, G4+3 or higher. In the very low risk and low risk groups, we analyzed the rate of CSC according to PI-RADS score and calculated the NPV of mp-MRI for detection of CSC. RESULTS: In the low risk group, 20.8% (n=79) of patients had PI-RADS version 2 score 1–2 and 17.4% (n=66) of patients had PI-RADS version 2 score 3. In the very low risk group, 26.8% (n=38) of patients had PI-RADS version 2 score 1–2 and 17.6% (n=25) of patients had PI-RADS version 2 score 3 in the very low risk group. Rates of CSC were 33.7% (n=128) and 16.9% (n=24) in the low risk and very low risk groups, respectively. The NPV of MRI was 93.7% in the very low risk group and 78.6% in the low risk group. CONCLUSIONS: The NPV of PI-RADS for CSC is high in the very low risk group, but not in the low risk group. Further multicenter studies are needed to investigate the utility of PI-RADS version 2 for NPV.
Humans ; Information Systems* ; Magnetic Resonance Imaging* ; Prostate* ; Prostatectomy* ; Prostatic Neoplasms* ; Retrospective Studies

BACKGROUND/AIMS: Although laparoscopic fundoplication is a well-established therapy for gastroesophageal reflux disease (GERD) in Western countries, the mainstay of GERD treatment in Korea is long-term proton pump inhibitor (PPI) use. The aim of the present study was to evaluate nationwide data regarding antireflux surgery in Korea. METHODS: Data from 2011 to 2014 were collected from the Korean Antireflux Surgery Study Group and then analyzed. RESULTS: A total of 87 patients underwent laparoscopic fundoplication for the treatment of GERD. Preoperatively, typical symptoms were present in 81 patients (93%) and atypical symptoms were present in 51 patients (59%). Twenty-seven patients (31%) had poor PPI responses. The average surgical time and postoperative hospital stay were 116.3±42.3 minutes and 4.3±3.1 days, respectively. At 3 months after surgery, typical symptoms were completely controlled in 86.3% of patients and partially controlled in 11.7%, whereas atypical symptoms were completely controlled in 63.3% of patients and partially controlled in 23.3%. CONCLUSIONS: This study showed that although atypical symptoms and PPI nonresponders are common, the complete control rates of typical and atypical symptoms were 86.3% and 63.3%, respectively. Laparoscopic fundoplication is an efficacious method of controlling the symptoms of GERD and has an acceptable rate of postoperative morbidity and adverse symptoms.
Fundoplication ; Gastroesophageal Reflux ; Humans ; Korea* ; Length of Stay ; Methods ; Operative Time ; Proton Pump Inhibitors ; Proton Pumps