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.

Purpose: To evaluate the incidence of de novo overactive bladder (OAB) and the factors related to its occurrence following radical prostatectomy (RP) in patients with clinically localized prostate cancer (PCa). Materials and Methods: We prospectively examined 50 patients without OAB who underwent RP for clinically localized PCa in our institution from August 2019 to February 2020. We performed assessments using the International Prostate Symptom Score (IPSS), the Overactive Bladder Symptom Score (OABSS), and uroflowmetry before surgery and 3 months after RP. OAB was defined as a score of 1 or more on the urgency components of the OABSS. Three months after RP, the patients were divided into 2 groups based on the presence of de novo OAB symptoms. We evaluated the patients’ demographics and outcomes after RP according to their de novo OAB grouping. The predictive factors of de novo OAB after RP were analyzed using a multivariate logistic regression model. Results: Of the 50 patients, 22 (44%) had de novo OAB 3 months after RP. The patients in the de novo OAB group were older, had higher preoperative IPSS storage subscores, and had larger volumes of postvoid residual urine on preoperative uroflowmetry than those in the non-de novo OAB group. Multivariate analysis showed that age and preoperative IPSS storage subscores were predictive factors of de novo OAB after RP. Conclusions de novo OAB was observed in 44% of the patients 3 months after RP. Age and preoperative IPSS storage subscores were predictive factors of de novo OAB following RP.

Purpose: To evaluate the incidence of de novo overactive bladder (OAB) and the factors related to its occurrence following radical prostatectomy (RP) in patients with clinically localized prostate cancer (PCa). Materials and Methods: We prospectively examined 50 patients without OAB who underwent RP for clinically localized PCa in our institution from August 2019 to February 2020. We performed assessments using the International Prostate Symptom Score (IPSS), the Overactive Bladder Symptom Score (OABSS), and uroflowmetry before surgery and 3 months after RP. OAB was defined as a score of 1 or more on the urgency components of the OABSS. Three months after RP, the patients were divided into 2 groups based on the presence of de novo OAB symptoms. We evaluated the patients’ demographics and outcomes after RP according to their de novo OAB grouping. The predictive factors of de novo OAB after RP were analyzed using a multivariate logistic regression model. Results: Of the 50 patients, 22 (44%) had de novo OAB 3 months after RP. The patients in the de novo OAB group were older, had higher preoperative IPSS storage subscores, and had larger volumes of postvoid residual urine on preoperative uroflowmetry than those in the non-de novo OAB group. Multivariate analysis showed that age and preoperative IPSS storage subscores were predictive factors of de novo OAB after RP. Conclusions de novo OAB was observed in 44% of the patients 3 months after RP. Age and preoperative IPSS storage subscores were predictive factors of de novo OAB following RP.

Although atopic dermatitis (AD) is known to be a representative skin disorder, it also affects the systemic immune response. In a recent study, myoblasts were shown to be involved in the immune regulation, but the roles of muscle cells in AD are poorly understood. We aimed to identify the relationship between mitochondria and atopy by genome-wide analysis of skeletal muscles in mice. We induced AD-like symptoms using house dust mite (HDM) extract in NC/Nga mice. The transcriptional profiles of the untreated group and HDM-induced AD-like group were analyzed and compared using microarray, differentially expressed gene and functional pathway analyses, and protein interaction network construction. Our microarray analysis demonstrated that immune response-, calcium handling-, and mitochondrial metabolism-related genes were differentially expressed. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology pathway analyses, immune response pathways involved in cytokine interaction, nuclear factor-kappa B, and T-cell receptor signaling, calcium handling pathways, and mitochondria metabolism pathways involved in the citrate cycle were significantly upregulated. In protein interaction network analysis, chemokine family-, muscle contraction process-, and immune response-related genes were identified as hub genes with many interactions. In addition, mitochondrial pathways involved in calcium signaling, cardiac muscle contraction, tricarboxylic acid cycle, oxidation-reduction process, and calcium-mediated signaling were significantly stimulated in KEGG and Gene Ontology analyses. Our results provide a comprehensive understanding of the genome-wide transcriptional changes of HDM-induced AD-like symptoms and the indicated genes that could be used as AD clinical biomarkers.
Animals ; Biomarkers ; Calcium ; Calcium Signaling ; Citric Acid ; Citric Acid Cycle ; Cytokines ; Dermatitis, Atopic ; Gene Ontology ; Genome ; Metabolism ; Mice ; Microarray Analysis ; Mitochondria ; Muscle Cells ; Muscle Contraction ; Muscle, Skeletal ; Myoblasts ; Myocardium ; Oxidation-Reduction ; Protein Interaction Maps ; Pyroglyphidae ; Receptors, Antigen, T-Cell ; Skin

PURPOSE: Changes in magnesium (Mg) concentration and calcium-to-magnesium ratio (Ca/Mg) play a critical role in cancer cell proliferation. In this study, we evaluated the association between preoperative Ca/Mg ratio and clinicopathological characteristics of prostate cancer. MATERIALS AND METHODS: Preoperative serum levels of Ca and Mg, as well as the Ca/Mg ratio, were retrospectively analyzed in 319 consecutive patients with prostate cancer who underwent radical prostatectomy at our institution between February 2014 and June 2016. Blood Ca and Mg levels, together with the Ca/Mg ratio, were analyzed in relation to the patients' demographic and clinicopathological characteristics. RESULTS: Preoperative Ca/Mg ratio was significantly higher in patients with pathologic Gleason score (pGS)≥8 than in those with pGS≤7 (mean [95% confidence interval]: 4.45 [4.35–4.56] vs. 4.32 [4.27–4.38], p=0.037). The Ca/Mg ratio was positively correlated with preoperative prostate-specific antigen (PSA) levels (r=0.116, p=0.039) and PSA density (r=0.156, p=0.005). Ca/Mg ratio was a preoperative predictor of high pGS (≥8) according to multiple logistic regression analysis (odds ratio, 1.752; 95% confidence interval, 1.002–3.064; p=0.049). CONCLUSIONS: A high serum Ca/Mg ratio was closely associated with worse clinicopathological parameters (high PSA and PSA density and pGS≥8), suggesting that the Ca/Mg ratio may be a useful serological marker for further characterization of oncologic features in prostate cancer. A multicenter prospective study with long-term follow-up is recommended to further assess the utility of this cost-effective marker as a prognostic indicator of prostate cancer.
Calcium ; Cell Proliferation ; Follow-Up Studies ; Humans ; Logistic Models ; Magnesium ; Neoplasm Grading ; Prospective Studies ; Prostate-Specific Antigen ; Prostatectomy ; Prostatic Neoplasms ; Retrospective Studies

Eradication of Helicobacter pylori using first-line therapy is becoming less effective. Subjects who had been treated for H. pylori infection were prospectively enrolled through an on-line database registry from October 2010 to December 2012. Demographic data, detection methods, treatment indication, regimens, durations, compliance, adverse events, and eradication results for H. pylori infection were collected. Data of 3,700 patients from 34 hospitals were analyzed. The overall eradication rate of the first-line therapy was 73.0%. Eradication failure was significantly associated with old age, concomitant medication, and comorbidity. Regional differences in eradication rates were observed. The most common first-line therapy was proton pump inhibitor-based triple therapy (standard triple therapy, STT) for 7 days (86.8%). The eradication rates varied with regimens, being 73% in STT, 81.8% in bismuth-based quadruple therapy, 100% in sequential therapy, and 90.3% in concomitant therapy. The eradication rate in treatment-naïve patients was higher than that in patients previously treated for H. pylori infection (73.8% vs. 58.5%, P < 0.001). The overall eradication rate for second-line therapy was 84.3%. There was no statistical difference in eradication rates among various regimens. H. pylori eradication rate using STT is decreasing in Korea and has become sub-optimal, suggesting the need for alternative regimens to improve the efficacy of first-line therapy for H. pylori infection.
Adult ; Age Factors ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Databases, Factual ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy/microbiology ; Helicobacter pylori/isolation & purification ; Humans ; Internet ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Proton Pump Inhibitors/*therapeutic use ; Registries ; Republic of Korea ; Treatment Outcome

Eradication of Helicobacter pylori using first-line therapy is becoming less effective. Subjects who had been treated for H. pylori infection were prospectively enrolled through an on-line database registry from October 2010 to December 2012. Demographic data, detection methods, treatment indication, regimens, durations, compliance, adverse events, and eradication results for H. pylori infection were collected. Data of 3,700 patients from 34 hospitals were analyzed. The overall eradication rate of the first-line therapy was 73.0%. Eradication failure was significantly associated with old age, concomitant medication, and comorbidity. Regional differences in eradication rates were observed. The most common first-line therapy was proton pump inhibitor-based triple therapy (standard triple therapy, STT) for 7 days (86.8%). The eradication rates varied with regimens, being 73% in STT, 81.8% in bismuth-based quadruple therapy, 100% in sequential therapy, and 90.3% in concomitant therapy. The eradication rate in treatment-naïve patients was higher than that in patients previously treated for H. pylori infection (73.8% vs. 58.5%, P < 0.001). The overall eradication rate for second-line therapy was 84.3%. There was no statistical difference in eradication rates among various regimens. H. pylori eradication rate using STT is decreasing in Korea and has become sub-optimal, suggesting the need for alternative regimens to improve the efficacy of first-line therapy for H. pylori infection.
Adult ; Age Factors ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Databases, Factual ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy/microbiology ; Helicobacter pylori/isolation & purification ; Humans ; Internet ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Proton Pump Inhibitors/*therapeutic use ; Registries ; Republic of Korea ; Treatment Outcome

In this article, a part of fund and grant supports was omitted unintentionally.

BACKGROUND/AIMS: There is controversy about the prophylactic effect of anti-thymocyte globulin (ATG) on graft versus host disease (GVHD) in the setting of matched related-donor hematopoietic stem cell transplantation (HSCT). This study assessed the inf luences of ATG on the incidences of acute and chronic GVHD and other clinical outcomes in matched related-donor HSCT. METHODS: Sixty-one patients received allogeneic HSCT from human leukocyte antigen-matched, related donors. Patients received busulfan/fludarabine conditioning regimens and standard GVHD prophylaxis with or without additional ATG. RESULTS: There was no significant difference in the cumulative incidences of overall acute GVHD, grade II to IV acute GVHD at day 100, and chronic GVHD during the follow-up period between the ATG and non-ATG groups. Three-year overall survival rates were very similar, but three year disease-free survival of the non-ATG group was higher than that of the ATG group (56.2% for ATG vs. 63.1% for non-ATG, p = 0.597). Relapse rate at 3 years in the ATG group was slightly higher than that of the non-ATG group (37.5% vs. 20%, p = 0.29). Non-relapse mortality rate at 3 years was lower in the ATG group (6.25% vs. 15.6%, p = 0.668). CONCLUSIONS: Although the addition of ATG doesn't guarantee a reduction in the incidences of acute and chronic GVHD, pre-transplantation ATG may result in lower non-relapse mortality in the context of matched related-donor HSCT with a busulfan/fludarabine conditioning regimen. However, caution is needed when using ATG because of a possibility to increase relapse rate.
Antilymphocyte Serum* ; Disease-Free Survival ; Follow-Up Studies ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Incidence ; Leukocytes ; Mortality ; Recurrence ; Survival Rate ; Tissue Donors*

PURPOSE: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. METHODS: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. RESULTS: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). CONCLUSIONS: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.
Carcinogenesis ; Herpesviridae ; Humans ; Hyperplasia* ; Immunohistochemistry ; MicroRNAs ; Nanoparticles ; Prostate* ; Prostatic Hyperplasia ; Prostatic Neoplasms ; Real-Time Polymerase Chain Reaction