Background: CycloZ, a combination of cyclo-His-Pro and zinc, has anti-diabetic activity. However, its exact mode of action remains to be elucidated. Methods: KK-Ay mice, a type 2 diabetes mellitus (T2DM) model, were administered CycloZ either as a preventive intervention, or as a therapy. Glycemic control was evaluated using the oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels. Liver and visceral adipose tissues (VATs) were used for histological evaluation, gene expression analysis, and protein expression analysis. Results: CycloZ administration improved glycemic control in KK-Ay mice in both prophylactic and therapeutic studies. Lysine acetylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, liver kinase B1, and nuclear factor-κB p65 was decreased in the liver and VATs in CycloZ-treated mice. In addition, CycloZ treatment improved mitochondrial function, lipid oxidation, and inflammation in the liver and VATs of mice. CycloZ treatment also increased the level of β-nicotinamide adenine dinucleotide (NAD+), which affected the activity of deacetylases, such as sirtuin 1 (Sirt1). Conclusion Our findings suggest that the beneficial effects of CycloZ on diabetes and obesity occur through increased NAD+ synthesis, which modulates Sirt1 deacetylase activity in the liver and VATs. Given that the mode of action of an NAD+ booster or Sirt1 deacetylase activator is different from that of traditional T2DM drugs, CycloZ would be considered a novel therapeutic option for the treatment of T2DM.

Purpose: To evaluate the clinical usefulness of the Seoul National University Prostate Cancer Risk Calculator (SNU-PCRC) to reduce unnecessary prostate biopsy and to increase the detection rate of high-risk cancer. Materials and Methods: We retrospectively analyzed 546 patients who underwent prostate biopsy between 2014 and 2016. The subjects were divided into 2 groups based on the type of risk calculator used: conventional and SNU-PCRC group. In the SNU-PCRC group, prostate biopsy was recommended when the probability of SNU-PCRC was more than 30%. Results: The SNU-PCRC group had significantly smaller prostate volume (p=0.010) and significantly more digital rectal examination and transrectal ultrasonography (TRUS) abnormalities (p=0.011 and p=0.010, respectively). Overall detection (71.9% vs. 32.1%) and high-risk cancer detection rates (40.6% vs. 19.3%) were significantly higher in the gray zone (prostate-specific antigen=4-10 ng/mL) (p<0.001 and p=0.006). The group with prostate cancer risk ≥30% on the SNU-PCRC compared to <30% group, overall detection rate of 72.3% versus 30.2% and high-risk detection rate of 60.6% versus 18.3% were significantly different (p<0.001 and p<0.001). Applying the SNU-PCRC to the conventional group could avoid unnecessary prostate biopsy in 50.6%. Conclusions SNU-PCRC is clinically useful to reduce unnecessary prostate biopsy and increase overall detection rate and high-risk cancer detection rate.

Purpose: To evaluate the clinical usefulness of the Seoul National University Prostate Cancer Risk Calculator (SNU-PCRC) to reduce unnecessary prostate biopsy and to increase the detection rate of high-risk cancer. Materials and Methods: We retrospectively analyzed 546 patients who underwent prostate biopsy between 2014 and 2016. The subjects were divided into 2 groups based on the type of risk calculator used: conventional and SNU-PCRC group. In the SNU-PCRC group, prostate biopsy was recommended when the probability of SNU-PCRC was more than 30%. Results: The SNU-PCRC group had significantly smaller prostate volume (p=0.010) and significantly more digital rectal examination and transrectal ultrasonography (TRUS) abnormalities (p=0.011 and p=0.010, respectively). Overall detection (71.9% vs. 32.1%) and high-risk cancer detection rates (40.6% vs. 19.3%) were significantly higher in the gray zone (prostate-specific antigen=4-10 ng/mL) (p<0.001 and p=0.006). The group with prostate cancer risk ≥30% on the SNU-PCRC compared to <30% group, overall detection rate of 72.3% versus 30.2% and high-risk detection rate of 60.6% versus 18.3% were significantly different (p<0.001 and p<0.001). Applying the SNU-PCRC to the conventional group could avoid unnecessary prostate biopsy in 50.6%. Conclusions SNU-PCRC is clinically useful to reduce unnecessary prostate biopsy and increase overall detection rate and high-risk cancer detection rate.

PURPOSE: Abnormalities in hemostasis and coagulation have been suggested in chronic renal failure (CRF). In this study, we compared processes of thrombus formation between rats with CRF and those with normal kidney function. MATERIALS AND METHODS: CRF was induced by 5/6 ablation/infarction of the kidneys in Sprague-Dawley rats, and surviving rats after 4 weeks were used. Ferric chloride (FeCl3)-induced thrombosis in the carotid artery was induced to assess thrombus formation. Whole blood clot formation was evaluated using rotational thromboelastometry (ROTEM). Platelet aggregation was assessed with impedance platelet aggregometry. RESULTS: FeCl3-induced thrombus formation was initiated faster in the CRF group than in the control group (13.2±1.1 sec vs. 17.8±1.0 sec, p=0.027). On histological examination, the maximal diameters of thrombi were larger in the CRF group than in the control group (394.2±201.1 µm vs. 114.0±145.1 µm, p=0.039). In extrinsic pathway ROTEM, the CRF group showed faster clot initiation (clotting time, 59.0±7.3 sec vs. 72.8±5.0 sec, p=0.032) and increased clot growth kinetics (α angle, 84.8±0.2° vs. 82.0±0.6°, p=0.008), compared to the control group. Maximal platelet aggregation rate was higher in the CRF group than in the control group (58.2±0.2% vs. 44.6±1.2%, p=0.006). CONCLUSION: Our study demonstrated that thrombogenicity is increased in rats with CRF. An activated extrinsic coagulation pathway may play an important role in increasing thrombogenicity in CRF.
Animals ; Blood Platelets ; Carotid Arteries ; Electric Impedance ; Hemostasis ; Kidney ; Kidney Failure, Chronic* ; Kinetics ; Models, Animal* ; Platelet Aggregation ; Rats* ; Rats, Sprague-Dawley ; Thrombelastography ; Thrombosis

BACKGROUND: Woman kidney donors face obstetric complication risks after kidney donation, such as gestational hypertension and preeclampsia. Studies on childbirth-related complications among Asian women donors are scarce. METHODS: This retrospective cohort study included woman donors aged 45 years or younger at the time of kidney donation in a single tertiary hospital between 1985 and 2014. Pregnancy associated complications were investigated using medical records and telephone questionnaires for 426 pregnancies among 225 donors. Matched non-donor controls were selected by propensity score and the maternal and fetal outcomes were compared with those of donors. Primary outcomes were differences in maternal complications, and secondary outcomes were fetal outcomes in pregnancies of the donor and control groups. RESULTS: A total of 56 cases had post-donation pregnancies. The post-donation pregnancies group was younger at the time of donation and older at the time of delivery than the pre-donation pregnancies group, and there were no differences in primary outcomes between the groups except the proportion receiving cesarean section. Comparison of the complication risk between post-donation pregnancies and non-donor matched controls showed no significant differences in gestational hypertension, preeclampsia, or composite outcomes after propensity score matching including age at delivery, era at pregnancy, systolic blood pressure, body weight, and estimated glomerular filtration ratio (odds ratio, 0.63; 95% confidence interval, 0.19–2.14; P = 0.724). CONCLUSION: This study revealed that maternal and fetal outcomes between woman kidney donors and non-donor matched controls were comparable. Studies with general population pregnancy controls are warranted to compare pregnancy outcomes for donors.
Asian Continental Ancestry Group ; Blood Pressure ; Body Weight ; Cesarean Section ; Cohort Studies ; Female ; Filtration ; Humans ; Hypertension, Pregnancy-Induced ; Kidney* ; Medical Records ; Pre-Eclampsia ; Pregnancy Outcome ; Pregnancy* ; Propensity Score ; Retrospective Studies ; Telephone ; Tertiary Care Centers ; Tissue Donors*

PURPOSE: To evaluate the clinicopathologic and oncological outcomes of advanced metastatic testicular cancer in Korean men who underwent retroperitoneal lymph node dissection (RPLND) following chemotherapy. MATERIALS AND METHODS: Data of 26 patients with testicular cancer who underwent RPLND after chemotherapy at 2 hospitals in Korea between September 2004 and June 2016 were retrospectively analyzed. Clinical and histopathological variables such as stage of the testicular cancer, age of the patients during surgery, size of the retroperitoneal lymph nodes (RPLNs), histopathological results, duration and complications related to the surgery, cancer recurrence, and mortality were analyzed. RESULTS: During testicular surgery, the T stage was pT1, pT2, and pT3 in 50% (n=13), 26.9% (n=7), and 15.3% (n=4) of the patients, respectively. Mixed germ cell tumor was the most common finding, seen in 73.1% (n=19) of patients. The indications for RPLND were residual lymph nodes after chemotherapy, 84.6% (n=22); and disease progression and remission, 7.7% (n=2). Pathological analysis revealed viable tumors in 19.2% of patients (n=5), necrotic/fibrotic tissue in 42.3% (n=11), and teratoma in 34.6% (n=9). Intraoperative and postoperative complications occurred in 23.1% (n=6) and 19.2% of patients (n=5). The median duration of follow-up was 27.5 months (interquartile range, 1.3–108.2 months); 11.5% (n=3) patients had recurrence, and 3.8% (n=1) died of progressive metastatic testicular cancer. CONCLUSIONS: Viable germ cell tumors were present in 19.2% of patients with testicular cancer who underwent RPLND after chemotherapy. This is the first study of its kind in the Korean population.
Disease Progression ; Drug Therapy ; Follow-Up Studies ; Humans ; Korea ; Lymph Node Excision* ; Lymph Nodes* ; Male ; Mortality ; Neoplasms, Germ Cell and Embryonal ; Postoperative Complications ; Recurrence ; Retrospective Studies ; Teratoma ; Testicular Neoplasms*

PURPOSE: Although asymptomatic coronary artery occlusive disease is common in stroke patients, the long-term advantages of undergoing evaluation for coronary arterial disease using multi-detector coronary computed tomography (MDCT) have not been well established in stroke patients. We compared long-term cardio-cerebrovascular outcomes between patients who underwent MDCT and those who did not. MATERIALS AND METHODS: This was a retrospective study in a prospective cohort of consecutive ischemic stroke patients. Of the 3117 patients who were registered between July 2006 and December 2012, MDCT was performed in 1842 patients [MDCT (+) group] and not in 1275 patients [MDCT (−) group]. Occurrences of death, cardiovascular events, and recurrent stroke were compared between the groups using Cox proportional hazards models and propensity score analyses. RESULTS: During the mean follow-up of 38.0±24.8 months, 486 (15.6%) patients died, recurrent stroke occurred in 297 (9.5%), and cardiovascular events occurred in 60 patients (1.9%). Mean annual risks of death (9.34% vs. 2.47%), cardiovascular events (1.2% vs. 0.29%), and recurrent stroke (4.7% vs. 2.56%) were higher in the MDCT (−) group than in the MDCT (+) group. The Cox proportional hazards model and the five propensity score-adjusted models consistently demonstrated that the MDCT (−) group was at a high risk of cardiovascular events (hazard ratios 3.200, 95% confidence interval 1.172–8.735 in 1:1 propensity matching analysis) as well as death. The MDCT (−) group seemed to also have a higher risk of recurrent stroke. CONCLUSION: Acute stroke patients who underwent MDCT experienced fewer deaths, cardiovascular events, and recurrent strokes during follow-up.
Asymptomatic Diseases ; Coronary Artery Disease/*diagnostic imaging/mortality ; Female ; Follow-Up Studies ; Humans ; Male ; Multidetector Computed Tomography/*utilization ; Propensity Score ; Proportional Hazards Models ; Prospective Studies ; Recurrence ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Stroke/*complications/mortality

Patients with severe stroke due to acute large cerebral artery occlusion are likely to be severely disabled or dead without timely reperfusion. Previously, intravenous tissue plasminogen activator (IV-TPA) within 4.5 hours after stroke onset was the only proven therapy, but IV-TPA alone does not sufficiently improve the outcome of patients with acute large artery occlusion. With the introduction of the advanced endovascular therapy, which enables more fast and more successful recanalization, recent randomized trials consecutively and consistently demonstrated the benefit of endovascular recanalization therapy (ERT) when added to IV-TPA. Accordingly, to update the recommendations, we assembled members of the writing committee appointed by the Korean Stroke Society, the Korean Society of Interventional Neuroradiology, and the Society of Korean Endovascular Neurosurgeons. Reviewing the evidences that have been accumulated, the writing members revised recommendations, for which formal consensus was achieved by convening a panel composed of 34 experts from the participating academic societies. The current guideline provides the evidence-based recommendations for ERT in patients with acute large cerebral artery occlusion regarding patient selection, treatment modalities, neuroimaging evaluation, and system organization.
Arteries ; Cerebral Arteries ; Consensus ; Humans ; Neuroimaging ; Patient Selection ; Reperfusion ; Stroke* ; Tissue Plasminogen Activator ; Writing

Patients with severe stroke due to acute large cerebral artery occlusion are likely to be severely disabled or dead without timely reperfusion. Previously, intravenous tissue plasminogen activator (IV-TPA) within 4.5 hours after stroke onset was the only proven therapy, but IV-TPA alone does not sufficiently improve the outcome of patients with acute large artery occlusion. With the introduction of the advanced endovascular therapy, which enables more fast and more successful recanalization, recent randomized trials consecutively and consistently demonstrated the benefit of endovascular recanalization therapy (ERT) when added to IV-TPA. Accordingly, to update the recommendations, we assembled members of the writing committee appointed by the Korean Stroke Society, the Korean Society of Interventional Neuroradiology, and the Society of Korean Endovascular Neurosurgeons. Reviewing the evidences that have been accumulated, the writing members revised recommendations, for which formal consensus was achieved by convening a panel composed of 34 experts from the participating academic societies. The current guideline provides the evidence-based recommendations for ERT in patients with acute large cerebral artery occlusion regarding patient selection, treatment modalities, neuroimaging evaluation, and system organization.
Arteries ; Cerebral Arteries ; Consensus ; Humans ; Neuroimaging ; Patient Selection ; Reperfusion ; Stroke* ; Tissue Plasminogen Activator ; Writing

Patients with severe stroke due to acute large cerebral artery occlusion are likely to be severely disabled or die if reperfusion is not achieved in a timely manner. Intravenous tissue plasminogen activator (IV-TPA) administered within 4.5 hours after stroke onset was previously the only proven therapy, but IV-TPA alone does not sufficiently improve the outcome of patients with acute large artery occlusion. With the introduction of the advanced endovascular therapy that enables faster and more successful recanalization, recent randomized trials consecutively and consistently demonstrated the benefit of adding endovascular recanalization therapy (ERT) to IV-TPA. Accordingly, to update the recommendations, we assembled members of a writing committee appointed by the Korean Stroke Society, the Korean Society of Interventional Neuroradiology, and the Society of Korean Endovascular Neurosurgeons. The writing committee revised recommendations based on a review of the accumulated evidence, and a formal consensus was achieved by convening a panel of 34 experts from the participating academic societies. The current guideline provides evidence-based recommendations for ERT in patients with acute large cerebral artery occlusion regarding patient selection, treatment modalities, neuroimaging evaluation, and system organization.
Arteries ; Cerebral Arteries ; Consensus ; Humans ; Neuroimaging ; Neurosurgeons ; Patient Selection ; Reperfusion ; Stroke* ; Tissue Plasminogen Activator ; Writing