Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

In preparation for the surge of coronavirus disease 2019 (COVID-19), it is crucial to allocate medical resources efficiently for distinguishing people who remain asymptomatic until the end of the disease. Between January 27, 2020, and April 21, 2020, 517 COVID-19 cases from 13 healthcare facilities in Gyeonggi province, Korea, were identified out of which the epidemiologic and clinical information of 66 asymptomatic patients at the time of diagnosis were analyzed retrospectively. An exposure-diagnosis interval within 7 days and abnormal aspartate aminotransferase levels were identified as characteristic symptom development in asymptomatic COVID-19 patients. If asymptomatic patients without these characteristics at the time of diagnosis could be differentiated early, more medical resources could be secured for mild or moderate cases in this COVID-19 surge.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

BACKGROUND: Although satisfactory mid- to long-term results of rotational acetabular osteotomy for early osteoarthritis secondary to acetabular dysplasia have been reported, there is still controversy about the long-term effects of this surgery in more advanced osteoarthritis. The purpose of this study was to investigate the radiographic progression of osteoarthritic changes after rotational acetabular osteotomy in acetabular dysplasia according to the preoperative Tönnis grade and evaluate its effects after minimum 10-year follow-up. METHODS: We performed 71 consecutive rotational acetabular osteotomies in 64 patients with symptomatic acetabular dysplasia between November 1984 and April 2005. Of these, 46 hips (four hips with Tönnis grade 0, 30 with grade 1, and 12 with grade 2) whose clinical and radiographic findings were available after minimum 10-year follow-up were evaluated in this study. The mean age at the time of surgery was 39.0 years (range, 18 to 62 years) and the average follow-up duration was 17.3 years (range, 10.0 to 27.7 years). Clinical and radiographic evaluations were performed according to the preoperative Tönnis grade. RESULTS: The average Harris hip score improved from 71.8 (range, 58 to 89) to 85.1 (range, 62 to 98). The radiographic parameters also improved in all Tönnis grades after the index surgery. Although the improvement of radiographic parameters was not different between preoperative Tönnis grades, the incidence of osteoarthritic progression was significantly different between grades (zero in Tönnis grade 0, four in Tönnis grade 1, and 10 in Tönnis grade 2; p < 0.001). The mean age at the time of surgery was also significantly older in osteoarthritic progression patients (p < 0.002). Kaplan-Meier survivorship analysis, with radiographic progression of osteoarthritis as the endpoint, predicted a 10-year survival rate of 100% in Tönnis grade 0, 85.7% in Tönnis grade 1, and 14.3% in Tönnis grade 2 (p < 0.001). CONCLUSIONS: The outcome of rotational acetabular osteotomy in most hips with Tönnis grade 0 and 1 was satisfactory after an average of 17 years of follow-up. The incidence of osteoarthritic progression was higher in Tönnis grade 2 and older age. Our results support that early joint preserving procedure is essential in the case of symptomatic dysplastic hips.
Acetabulum* ; Follow-Up Studies* ; Hip ; Humans ; Incidence ; Joints ; Osteoarthritis* ; Osteotomy* ; Survival Rate

Few studies have compared outcomes in patients undergoing liver transplantation (LT) for hepatitis B virus (HBV) and alcoholic liver disease (ALD) in Asian countries in which living donor LT (LDLT) is dominant, where HBV is endemic and where there are no strict regulations on pre-transplant abstinence for ALD. This study compared post-LT outcomes of deceased donor LT (DDLT) in patients with ALD and HBV. Data from 220 patients who underwent primary DDLT at Seoul National University Hospital from January 2010 to December 2014, including 107 with HBV and 38 with ALD, were retrospectively analyzed. Seventy-four patients (69.2%) in the HBV group and 30 (78.9%) in the ALD group had United Network for Organ Sharing (UNOS) status 2A (P = 0.250). There were no significant differences in their 1-year (90.7% vs. 92.1%) and 3-year (82.1% vs. 82.3%) overall survival rates (P = 1.000). Multivariate analysis showed that high serum gamma glutamyltransferase concentration (≥ 70 IU/L) was independently prognostic of 1-year post-LT overall survival. Survival outcomes following DDLT were similar in Korean patients with ALD and HBV, even in the absence of strict pre-transplant abstinence from alcohol as a selection criterion.
Alcoholics* ; Asian Continental Ancestry Group ; gamma-Glutamyltransferase ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis* ; Humans ; Liver Cirrhosis ; Liver Diseases, Alcoholic* ; Liver Transplantation* ; Liver* ; Living Donors ; Multivariate Analysis ; Retrospective Studies ; Seoul ; Social Control, Formal ; Survival Rate ; Tissue Donors*

We estimated the effect of various immunosuppressants (ISs) and metformin (M) to provide theoretical background of optimal therapeutic strategy for de novo colon cancer after liver transplantation (LT). Three colon cancer cell lines (HT29, SW620, and HCT116) were used in in vitro studies. HT29 was also used in BALB/c-nude mice animal models. Following groups were used in both in vitro and in vivo studies: sirolimus (S), tacrolimus (T), cyclosporin A (CsA), M, metformin/sirolimus (Met/S), metformin/tacrolimus (Met/T), and metformin/cyclosporin A (Met/CsA). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed and western blot analyses were performed for mTOR pathway proteins, apoptosis proteins, and epithelial-mesenchymal-transition (EMT) proteins. Tumor volume was measured for 4 weeks after inoculation. MTT-assay revealed significant cell viability inhibition in all 3 colon cancer cell lines in groups of S, M, and Met/S. Of note, group Met/S showed synergistic effect compare to M or S group. Western blot analysis showed significant low levels of all investigated proteins in groups of S and Met/S in both in vitro and in vivo experiment. Tumor growth was significantly inhibited only in the Met/S group. Combination of Met and S showed the most potent inhibition in all colon cancer cell lines. This finding might have application for de novo colon cancer.
Animals ; Apoptosis ; Blotting, Western ; Cell Line ; Cell Survival ; Colon* ; Colonic Neoplasms* ; Cyclosporine ; Immunosuppression ; Immunosuppressive Agents ; In Vitro Techniques* ; Liver Transplantation ; Metformin* ; Mice ; Models, Animal ; Sirolimus* ; Tacrolimus ; Tumor Burden

PURPOSE: Liver volumetry is a vital component in living donor liver transplantation to determine an adequate graft volume that meets the metabolic demands of the recipient and at the same time ensures donor safety. Most institutions use preoperative contrast-enhanced CT image-based software programs to estimate graft volume. The objective of this study was to evaluate the accuracy of 2 liver volumetry programs (Rapidia vs. Dr. Liver) in preoperative right liver graft estimation compared with real graft weight. METHODS: Data from 215 consecutive right lobe living donors between October 2013 and August 2015 were retrospectively reviewed. One hundred seven patients were enrolled in Rapidia group and 108 patients were included in the Dr. Liver group. Estimated graft volumes generated by both software programs were compared with real graft weight measured during surgery, and further classified into minimal difference (≤15%) and big difference (>15%). Correlation coefficients and degree of difference were determined. Linear regressions were calculated and results depicted as scatterplots. RESULTS: Minimal difference was observed in 69.4% of cases from Dr. Liver group and big difference was seen in 44.9% of cases from Rapidia group (P = 0.035). Linear regression analysis showed positive correlation in both groups (P < 0.01). However, the correlation coefficient was better for the Dr. Liver group (R² = 0.719), than for the Rapidia group (R² = 0.688). CONCLUSION: Dr. Liver can accurately predict right liver graft size better and faster than Rapidia, and can facilitate preoperative planning in living donor liver transplantation.
Donor Selection ; Humans ; Linear Models ; Liver ; Liver Transplantation ; Living Donors ; Organ Size ; Retrospective Studies ; Tissue Donors ; Tomography, X-Ray Computed ; Transplants*

The diagnosis of hepatocellular carcinoma (HCC) is based on imaging studies particularly in high-risk patients without histologic confirmation. This study evaluated the prevalence and characteristics of false-positively diagnosed HCC in a liver resection cohort for HCC. A retrospective review was performed of 837 liver resection cases for clinically diagnosed HCC between 2005 and 2010 at our institute. High-risk patients with tumors > 1 cm with one or two image findings consistent with HCC and tumors < 1 cm with two or more image findings consistent with HCC with persistently increased serum alpha-fetoprotein (AFP) levels above the normal range with underlying inhibited hepatitis activity underwent liver resection. The false-positive rate was 2.2% (n = 18). Of the 18 patients, 7 patients (0.8%) were diagnosed with benign conditions (one each of hemangioma, inflammation, cortical adenoma, dysplastic nodule, angiomyolipoma, bile duct adenoma, and non-neoplastic liver parenchyme) and 11 patients (1.3%) were diagnosed with malignancies (cholangiocarcinoma [n = 6], hepatoblastoma [n = 2], and one each of lymphoepithelioma-like carcinoma, ovarian cystadenocarcinoma, and nasopharynx carcinoma metastasis). The clinical characteristics of pathologically diagnosed HCC patients were similar (P > 0.05) compared to non-HCC patients except for higher rate of history of alcoholism (P < 0.05) observed in non-HCC patients. Four of 18 non-HCC patients (22.2%) showed diagnostic discordance on the dynamic imaging study. Despite the recent progression in diagnostic imaging techniques, 2.2% of cases were false-positively diagnosed as HCC in a liver resection patient cohort; and the final diagnosis was benign disease in 0.8% of liver resection patients clinically diagnosed with HCC.
Adenoma ; Adenoma, Bile Duct ; Alcoholism ; alpha-Fetoproteins ; Angiomyolipoma ; Carcinoma, Hepatocellular* ; Cohort Studies ; Cystadenocarcinoma ; Diagnosis* ; Diagnostic Imaging ; Hemangioma ; Hepatitis ; Hepatoblastoma ; Humans ; Inflammation ; Liver* ; Nasopharynx ; Prevalence ; Reference Values ; Retrospective Studies