Sirtuins (SIRTs) belong to the nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase family. They are key regulators of cellular and physiological processes, such as cell survival, senescence, differentiation, DNA damage and stress response, cellular metabolism, and aging. SIRTs also influence carcinogenesis, making them potential targets for anticancer therapeutic strategies. In this study, we investigated the anticancer properties and underlying molecular mechanisms of a novel SIRT1 inhibitor, MHY2251, in human colorectal cancer (CRC) cells. MHY2251 reduced the viability of various human CRC cell lines, especially those with wild-type TP53. MHY2251 inhibited SIRT1 activity and SIRT1/2 protein expression, while promoting p53 acetylation, which is a target of SIRT1 in HCT116 cells. MHY2251 treatment triggered apoptosis in HCT116 cells. It increased the percentage of late apoptotic cells and the sub-G1 fraction (as detected by flow cytometric analysis) and induced DNA fragmentation. In addition, MHY2251 upregulated the expression of FasL and Fas, altered the ratio of Bax/Bcl-2, downregulated the levels of pro-caspase-8, -9, and -3 proteins, and induced subsequent poly(ADP-ribose) polymerase cleavage. The induction of apoptosis by MHY2251 was related to the activation of the caspase cascade, which was significantly attenuated by pre-treatment with ZVAD-FMK, a pan-caspase inhibitor. Furthermore, MHY2251 stimulated the phosphorylation of c-Jun N-terminal kinase (JNK), and MHY2251-triggered apoptosis was blocked by pre-treatment with SP600125, a JNK inhibitor. This finding indicated the specific involvement of JNK in MHY2251-induced apoptosis. MHY2251 shows considerable potential as a therapeutic agent for targeting human CRC via the inhibition of SIRT1 and activation of JNK/p53 pathway.

Background: The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy. Methods: The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed. Results: The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients. Conclusions The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.

Background: The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy. Methods: The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed. Results: The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients. Conclusions The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.

OBJECTIVE: To evaluate the feasibility of angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular liver tumors abutting abdominal wall, in order to traverse normal liver parenchyma, and thereby, obtain favorable configuration of ablation margin. MATERIALS AND METHODS: In this study, we retrospectively analyzed 15 small superficial subcapsular liver tumors abutting abdominal wall in 15 patients, treated with radiofrequency ablation from March 2013 to June 2015 using a cool-tip electrode manually modified to create 25-35° angle at the junction between exposed and insulated segments. The tumors were hepatocellular carcinoma (n = 13) and metastases (n = 2: cholangiocellular carcinoma and rectosigmoid cancer), with maximum diameter of 10-26 mm (mean, 15.68 ± 5.29 mm). Under ultrasonographic guidance, the electrode tip was advanced to the depth of the tumors' epicenter about 1 cm from the margin. The tip was re-directed to penetrate the tumor for radiofrequency ablation. Minimal ablation margin was measured at immediate post-treatment CT. Radiological images and medical records were evaluated for success rate, length of minimal ablation margin and complications. RESULTS: Technical success rate of obtaining complete necrosis of the tumors was 100%, with no procedure-related complication. Minimal ablation margin ranged from 3-12 mm (mean, 7.07 ± 2.23 mm). CT/MRI follow-up at 21-1022 days (mean, 519.47 ± 304.51 days) revealed no local recurrence, but distant recurrence in 9 patients. CONCLUSION: Using an angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular tumors abutting abdominal wall may be a feasible technique for obtaining adequate ablation margin and lower complication rate.
Abdominal Wall ; Carcinoma, Hepatocellular ; Catheter Ablation* ; Cholangiocarcinoma ; Electrodes* ; Feasibility Studies* ; Follow-Up Studies ; Humans ; Liver* ; Medical Records ; Necrosis ; Neoplasm Metastasis ; Recurrence ; Retrospective Studies

PURPOSE: We investigate the outcomes of treatment of patients with severe comminuted distal radius fractures with volar plate fixation using a pronator-preserving approach. MATERIALS AND METHODS: Fourteen patients with severe comminution of the distal radius fractures for whom anatomical reduction of the fractures was deemed difficult to achieve with traditional approaches were enrolled. The gender ratio was 8 males to 6 females, and the average age of the patients was 64.9 years. According to the AO/OTA classification of fractures, 2 patients had 23-A3 fractures, 7 patients had 23-C2, and 5 patients had 23-C3. Radial length, radial inclination, and volar tilt were measured for radiologic evaluation. Modified Mayo wrist score (MMWS) was used for clinical outcome. RESULTS: Bony union was achieved in all 14 patients without signs of complications. The average time-to-union was 4.3 months (3-6 months). The radiological findings at the final follow-up were as follows: the average radial inclination was 20.5degrees; the average volar tilt, 7.57degrees; and the average radial length, 11.8 mm. At the final follow-up, the results of the MMWS were 'Fair' in 1 patient, 'Good' in 4, and 'Excellent' in 9. CONCLUSION: We propose that a pronator-preserving approach is an effective treatment for severe comminuted distal radius fracture.
Classification ; Female ; Follow-Up Studies ; Humans ; Male ; Radius Fractures* ; Palmar Plate ; Wrist

Peripheral arterial occlusive disease caused by atherosclerosis can present with intermittent claudication or critical limb ischemia. Proper diagnosis and management is warranted to improve symptoms and salvage limbs. With the introduction of new techniques and dedicated materials, endovascular recanalization is widely performed for the treatment of peripheral arterial occlusive disease because it is less invasive than surgery. However, there are various opinions regarding the appropriate indications and procedure methods for interventional recanalization according to operator and institution in Korea. Therefore, we intend to provide evidence based guidelines for interventional recanalization by multidisciplinary consensus. These guidelines are the result of a close collaboration between physicians from many different areas of expertise including interventional radiology, interventional cardiology, and vascular surgery. The goal of these guidelines is to ensure better treatment, to serve as a guide to the clinician, and consequently, to contribute to public health care.
Arterial Occlusive Diseases/radiography/*therapy ; Arteries/pathology ; Endovascular Procedures/*standards ; Humans ; Intermittent Claudication/radiography/therapy ; Limb Salvage/methods ; Lower Extremity/*blood supply ; Peripheral Arterial Disease/radiography/*therapy ; *Practice Guidelines as Topic ; Republic of Korea

PURPOSE: This study was conducted to evaluate prognostic factors and cancer-specific survival (CSS) in a cohort of 41 patients with urachal carcinoma by use of a Bayesian model-averaging approach. MATERIALS AND METHODS: Our cohort included 41 patients with urachal carcinoma who underwent extended partial cystectomy, total cystectomy, transurethral resection, chemotherapy, or radiotherapy at a single institute. All patients were classified by both the Sheldon and the Mayo staging systems according to histopathologic reports and preoperative radiologic findings. Kaplan-Meier survival curves and Cox proportional-hazards regression models were carried out to investigate prognostic factors, and a Bayesian model-averaging approach was performed to confirm the significance of each variable by using posterior probabilities. RESULTS: The mean age of the patients was 49.88+/-13.80 years and the male-to-female ratio was 24:17. The median follow-up was 5.42 years (interquartile range, 2.8-8.4 years). Five- and 10-year CSS rates were 55.9% and 43.4%, respectively. Lower Sheldon (p=0.004) and Mayo (p<0.001) stage, mucinous adenocarcinoma (p=0.005), and larger tumor size (p=0.023) were significant predictors of high survival probability on the basis of a log-rank test. By use of the Bayesian model-averaging approach, higher Mayo stage and larger tumor size were significant predictors of cancer-specific mortality in urachal carcinoma. CONCLUSIONS: The Mayo staging system might be more effective than the Sheldon staging system. In addition, the multivariate analyses suggested that tumor size may be a prognostic factor for urachal carcinoma.
Adult ; Bayes Theorem ; Carcinoma/*pathology/*therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Treatment Outcome ; Urinary Bladder Neoplasms/*pathology/*therapy

PURPOSE: This study was conducted to evaluate prognostic factors and cancer-specific survival (CSS) in a cohort of 41 patients with urachal carcinoma by use of a Bayesian model-averaging approach. MATERIALS AND METHODS: Our cohort included 41 patients with urachal carcinoma who underwent extended partial cystectomy, total cystectomy, transurethral resection, chemotherapy, or radiotherapy at a single institute. All patients were classified by both the Sheldon and the Mayo staging systems according to histopathologic reports and preoperative radiologic findings. Kaplan-Meier survival curves and Cox proportional-hazards regression models were carried out to investigate prognostic factors, and a Bayesian model-averaging approach was performed to confirm the significance of each variable by using posterior probabilities. RESULTS: The mean age of the patients was 49.88+/-13.80 years and the male-to-female ratio was 24:17. The median follow-up was 5.42 years (interquartile range, 2.8-8.4 years). Five- and 10-year CSS rates were 55.9% and 43.4%, respectively. Lower Sheldon (p=0.004) and Mayo (p<0.001) stage, mucinous adenocarcinoma (p=0.005), and larger tumor size (p=0.023) were significant predictors of high survival probability on the basis of a log-rank test. By use of the Bayesian model-averaging approach, higher Mayo stage and larger tumor size were significant predictors of cancer-specific mortality in urachal carcinoma. CONCLUSIONS: The Mayo staging system might be more effective than the Sheldon staging system. In addition, the multivariate analyses suggested that tumor size may be a prognostic factor for urachal carcinoma.
Adult ; Bayes Theorem ; Carcinoma/*pathology/*therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Treatment Outcome ; Urinary Bladder Neoplasms/*pathology/*therapy

BACKGROUND AND OBJECTIVES: Metabolic syndrome and high sodium intake are associated with frequent cardiovascular events. Few studies have estimated sodium intake in subjects with metabolic syndrome by 24-hour urine sodium excretion. We evaluated sodium intake in individuals with metabolic syndrome. SUBJECTS AND METHODS: Participants were recruited by random selection and through advertisement. Twenty four-hour urine collection, ambulatory blood pressure measurements, and blood test were performed. Sodium intake was estimated by 24-hour urine sodium excretion. Participants receiving antihypertensive medications were excluded from analysis. RESULTS: Among the 463 participants recruited, subjects with metabolic syndrome had higher levels of 24-hour urine sodium excretion than subjects without metabolic syndrome (p=0.0001). There was a significant relationship between the number of metabolic syndrome factors and 24-hour urine sodium excretion (p=0.001). The proportion of subjects with metabolic syndrome was increased across the tertile groups of 24-hour urine sodium excretion (p<0.0001). The association of high sodium intake and metabolic syndrome was significant only among women. Among the factors related to metabolic syndrome, body mass index had an independent association with 24-hour urine sodium excretion (p<0.0001). CONCLUSION: Women with metabolic syndrome exhibited significantly higher sodium intake, suggesting that dietary education to reduce sodium consumption should be emphasized for women with metabolic syndrome.
Blood Pressure ; Body Mass Index ; Education ; Female ; Hematologic Tests ; Humans ; Hypertension ; Sodium* ; Sodium, Dietary ; Urine Specimen Collection

OBJECTIVE: To evaluate the prevalence of known risk factors for contrast-induced nephropathy (CIN) and their association with the actual occurrence of CIN in patients undergoing intravenous contrast-enhanced computed tomography (CECT) in Korea. MATERIALS AND METHODS: Patients who underwent CECT in 2008 were identified in the electronic medical records of 16 tertiary hospitals of Korea. Data on demographics, comorbidities, prescriptions and laboratory test results of patients were collected following a standard data extraction protocol. The baseline renal function was assessed using the estimated glomerular filtration rate (eGFR). We identified the prevalence of risk factors along the eGFR strata and evaluated their influence on the incidence of CIN, defined as a 0.5 mg/dL or 25% increase in serum creatinine after CECT. RESULTS: Of 432425 CECT examinations in 272136 patients, 140838 examinations in 101487 patients met the eligibility criteria for analysis. The mean age of the participants was 57.9 +/- 15.5 years; 25.1% of the patients were older than 70 years. The prevalence of diabetes mellitus was 11.9%, of hypertension 13.7%, of gout 0.55% and of heart failure was 1.7%. Preventive measures were used in 40238 CECT examinations (28.6%). The prevalence of risk factors and use of preventive measures increased as the renal function became worse. A CIN was occurred after 3103 (2.2%) CECT examinations, revealing a significant association with decreased eGFR, diabetes mellitus, and congestive heart failure after adjustment. CONCLUSION: Risk factors for CIN are prevalent among the patients undergoing CECT. Preventive measures were seemingly underutilized and a system is needed to improve preventive care.
Adult ; Aged ; Aged, 80 and over ; Comorbidity ; Contrast Media/*adverse effects ; Female ; Glomerular Filtration Rate ; Humans ; Incidence ; Kidney Diseases/*chemically induced/epidemiology/*radiography ; Male ; Middle Aged ; Prevalence ; Republic of Korea/epidemiology ; Risk Factors ; Tomography, X-Ray Computed/*methods