Background: Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM. Methods: A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment. Results: The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups. Conclusion Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.

Background: We aimed to evaluate long-term outcomes of gamma knife radiosurgery (GKS) for cerebral cavernous malformations (CCMs). Methods: Among the 233 CCM patients who underwent GKS, 79 adult patients (96 lesions) followed for over 10 years were included and analyzed retrospectively. Annual hemorrhage rate (AHR) was analyzed the entire cohort of 233 patients and the subset of 79 enrolled patients by dividing lesions into overall CCM lesions and brainstem lesions. AHR, neurologic outcome, adverse radiation effect (ARE), and changes of lesions in magnetic resonance imaging (MRI) were compared before and after GKS. Cox-regression analysis was performed to identify risk factors for hemorrhage following GKS. Results: Mean follow-up duration of 79 enrolled patients was 14 years (range, 10–23 years).The AHR of all CCMs for entire cohort at each time point was 17.8% (pre-GKS), 5.9% (≤ 2 years post-GKS), 1.8% (≤ 10 years post-GKS). The AHR of all CCM for 79 enrolled patients was 21.4% (pre-GKS), 3.8% (2 years post-GKS), 1.4% (10 years post-GKS), and 2.3% (> 10 years post-GKS). The AHR of brainstem cavernous malformation (CM) for entire cohort at each time point was 22.4% (pre-GKS), 10.1% (≤ 2 years post-GKS), 3.2% (≤ 10 years post-GKS). The AHR of brainstem CM for 79 enrolled patients was 27.2% (pre-GKS), 5.8% (2 years post-GKS), 3.4% (10 years post-GKS), and 3.5% (> 10 years post-GKS). Out of the 79 enrolled patients, 35 presented with focal neurologic deficits at the initial clinical visit. Among these patients, 74.3% showed recovery at the last follow-up. Symptomatic ARE occurred in five (6.4%) patients. No mortality occurred. Most lesions were decreased in size at the last follow-up MRI. Previous hemorrhage history (hazard ratio [HR], 8.38; 95% confidence interval [CI], 1.07–65.88; P = 0.043), and brainstem location (HR, 3.10; 95% CI, 1.26–7.64; P = 0.014) were significant risk factors for hemorrhage event. Conclusion GKS for CCM showed favorable long-term outcomes. GKS should be considered for CCM, especially when it has a previous hemorrhage history and brainstem location.

Background: Treatment for large (> 10 mL) arteriovenous malformations (AVMs) remains highly challenging. This study evaluated long-term effect of time-staged gamma knife radiosurgery (GKS) for large AVMs. Methods: For patients with large AVMs treated by time-staged GKS over 10 years, timestaged GKS was repeated every three years targeting the entire nidus if total obliteration was not achieved. Obliteration rate and post-GKS complications were assessed based on 10 mL volume interval of AVMs. Prognostic factors for these outcomes were evaluated using Cox regression analysis. Results: Ninety-six patients were analyzed. For AVMs in the 10–20 mL subgroup, a dose ≥ 13.5Gy yielded higher obliteration rate in the first GKS. In the 20–30 mL subgroup, a second GKS significantly boosted obliteration. AVMs > 30 mL did not achieve any obliteration with the first GKS. Among 35 (36.4%) cases lost to follow-up, 7 (7.2%) were lost due to GKS complications. Kaplan-Meier analysis showed that each subgroup needed different time for achieving 50% favorable obliteration outcome rate: 3.5, 6.5, and 8.2 years for 10–20 mL, 20–30 mL, and > 30 mL subgroup, respectively. Total obliteration rate calculated by intention-to-treat method: 73%, 51.7%, 35.7%, respectively, 61.5% overall. Post-GKS hemorrhage and chronic encapsulated expanding hematoma (CEEH) occurred in 13.5% and 8.3% of cases, respectively.Two patients died. Dose and volume were significant prognostic factors for obliteration. Initial AVM volume was a significant prognostic factor of post-GKS hemorrhage and CEEH. Conclusion Time-staged GKS for large AVMs less than 30 mL has highly favorable long-term outcome and a tolerable complication rate.

Objective: The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea. Methods: At the treating physicians’ discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months. Results: Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs −0.18, −0.38, and −0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus antiTNF therapy than with multiple cDMARDs (BGD −0.18, −0.19, and −0.19 points, respectively; all p≤0.024). Conclusion In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.

Species in the genus Trametes (Basidiomycota, Polyporales) have been used in natural medicine for a long time. Many studies reported that mycelia or fruiting bodies of Trametes spp. exhibited effects of antioxidant, anti-inflammatory, anticancer, and antimicrobial activities.However, comparative analysis in this genus is scarce due to limitation of morphological identification and the sample number. In this study, the 19 strains of seven Trametes species were chosen to generate a five-gene-based phylogeny with the 31 global references. In addition, 39 culture extracts were prepared for 13 strains to test for anticancer and antibacterial activities. Strong anticancer activities were found in several extracts from T. hirsuta and T. suaveolens. Anticancer activities of T. suaveolens, T. cf. junipericola and T. trogii were first described here. The antibacterial ability of T. versicolor and T. hirsuta extracts has been confirmed. The antibacterial activities of T. suaveolens have been reported at the first time in this study. These results suggest an efficient application of the genus Trametes as the drug resources especially for anticancer agents.

Background: Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy. To define the altered pathway in GDM placenta, we investigated the transcriptomic profiles from human placenta between GDM and controls. Methods: Clinical parameters and postpartum complications were reviewed in all participants.Differentially expressed canonical pathways were analyzed between the GDM and control groups based on transcriptomic analysis. CD4 + T, CD8 + T, and senescent T cell subsets were determined by flow cytometry based on staining for specific intracellular cytokines. Results: Gene ontology analysis revealed that the placenta of GDM revealed upregulation of diverse mitochondria or DNA replication related pathways and downregulation of T-cell immunity related pathways. The maternal placenta of the GDM group had a higher proportion of CD4 + T and CD8 + T cells than the control group. Interestingly, senescent CD4 + T cells tended to increase and CD8 + T cells were significantly increased in GDM compared to controls, along with increased programmed cell death-1 (CD274 + ) expression. Programmed death-ligand 1 expression in syncytotrophoblasts was also significantly increased in patients with GDM. Conclusion This study demonstrated increased proinflammatory T cells, senescent T cells and immune-check point molecules in GDM placentas, suggesting that changes in senescent T cells and immune-escape signaling might be related to the pathophysiology of GDM.

Objective: : High-dose radiation is well known to induce and modulate the immune system. This study was performed to evaluate the correlation between clinical outcomes and changes in natural killer cell activity (NKA) after Gamma Knife Radiosurgery (GKS) in patients with brain cancer. Methods: : We performed an open-label, prospective, cross-sectional study of 38 patients who were treated with GKS for brain tumors, including metastatic and benign brain tumors. All of the patients underwent GKS, and blood samples were collected before and after GKS. NKA was measured using an enzyme-linked immunosorbent assay kit, to measure interferon-gamma (IFNγ) secreted by ex vivo-stimulated NK cells from whole blood. We explored the correlations between NK cell-produced IFNγ (NKA-IFNγ) levels and clinical parameters of patients who were treated with GKS for brain tumors. Results: : NKA-IFNγ levels were decreased in metastatic brain tumor patients compared to those with benign brain tumors (p<0.0001). All the patients who used steroid treatment to reduce brain swelling after GKS had an NKA-IFNγ level of zero except one patient. High NKA-IFNγ levels were not associated with a rapid decrease in brain metastasis and did not increase after GKS. Conclusion : The activity of NK cells in metastatic brain tumors decreased more than that in benign brain tumors after GKS.

Background: Cardiac arrest during or after office-based cosmetic surgery is rare, and little is known about its prognosis. We assessed the clinical outcomes of patients who developed cardiac arrest during or after cosmetic surgery at office-based clinics. Methods: Between May 2009 and May 2016, 32 patients who developed cardiac arrest during or after treatment at cosmetic surgery clinics were consecutively enrolled. We compared clinical outcomes, including complications, between survivors (n=19) and non-survivors (n=13) and attempted to determine the prognostic factors of mortality. Results: All 32 of the patients were female, with a mean age of 30.40±11.87 years. Of the 32 patients, 13 (41%) died. Extracorporeal life support (ECLS) was applied in a greater percentage of non-survivors than survivors (92.3% vs. 47.4%, respectively; p=0.009). The mean duration of in-hospital cardiopulmonary resuscitation (CPR) was longer for the non-survivors than the survivors (31.55±33 minutes vs. 7.59±9.07 minutes, respectively; p=0.01).The mean Acute Physiology and Chronic Health Evaluation score was also higher among non-survivors than survivors (23.85±6.68 vs. 16.79±7.44, respectively; p=0.01). No predictor of death was identified in the patients for whom ECLS was applied. Of the 19 survivors, 10 (52.6%) had hypoxic brain damage, and 1 (5.3%) had permanent lower leg ischemia.Logistic regression analyses revealed that the estimated glomerular filtration rate was a predictor of mortality. Conclusion Patients who developed cardiac arrest during or after cosmetic surgery at office-based clinics experienced poor prognoses, even though ECLS was applied in most cases. The survivors suffered serious complications. Careful monitoring of subjects and active CPR (when necessary) in cosmetic surgery clinics may be essential.

OBJECTIVE: Contrast-induced nephropathy (CIN) frequently occurs after percutaneous intervention. Objective of this study was to investigate the usefulness of serum cystatin C, neutrophil gelatinase-associated lipocalcin (NGAL), urinary kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) as early predictors for CIN after percutaneous coronary intervention (PCI). METHODS: In 53 patients who underwent PCI were enrolled. Serum creatinine and cystatin C level were measured immediately before, and 24 hours and 48 hours after catheterization. Serum NGAL, urinary KIM-1, and IL-18 were measured immediately before, and 4 hours, 24 hours, and 48 hours after catheterization. CIN was defined as a rise in creatinine 0.5 mg/dL or 25% above baseline. RESULTS: CIN occurred in four patients (7.5%). Serum cystatin C levels were higher at 24 hours and 48 hours in CIN patients than in those without CIN (P<0.05). Serum NGAL levels were higher at 48 hours in CIN patients than in those without CIN. Urinary KIM-1 levels were higher at 48 hours in CIN patients than in those without CIN. There were no significant markers of CIN on multi-variate analysis. CONCLUSION: In this study, the occurrence of CIN after PCI was 7.5%. Although there were some time-course changes in serum cystatin C and urinary KIM-1 after PCI, there was no significant predictor for CIN after PCI.
Catheterization ; Catheters ; Contrast Media ; Creatinine ; Cystatin C ; Humans ; Interleukin-18 ; Kidney ; Neutrophils ; Percutaneous Coronary Intervention*

BACKGROUND: Type II autosomal dominant osteopetrosis (ADO II) is a rare genetically heterogeneous disorder characterized by osteosclerosis and increased bone mass, predominantly involving spine, pelvis, and skull. It is closely related to functional defect of osteoclasts caused by chloride voltage-gated channel 7 (CLCN7) gene mutations. In this study, we aimed to identify the pathogenic mutation in a Korean patient with ADO II using whole exome sequencing. METHODS: We evaluated the clinical, biochemical, and radiographic analysis of a 68-year-old woman with ADO II. We also performed whole exome sequencing to identify pathogenic mutation of a rare genetic disorder of the skeleton. Moreover, a polymorphism phenotyping program, Polymorphism Phenotyping v2 (PolyPhen-2), was used to assess the effect of the identified mutation on protein function. RESULTS: Whole exome sequencing using peripheral leukocytes revealed a heterozygous c.296A>G missense mutation in the CLCN7 gene. The mutation was also confirmed using Sanger sequencing. The mutation c.296A>G was regarded to have a pathogenic effect by PolyPhen-2 software. CONCLUSION: We detect a heterozygous mutation in CLCN7 gene of a patient with ADO II, which is the first report in Korea. Our present findings suggest that symptoms and signs of ADO II patient having a c.296A>G mutation in CLCN7 may appear at a very late age. The present study would also enrich the database of CLCN7 mutations and improve our understanding of ADO II.
Aged ; Exome ; Female* ; Humans ; Korea ; Leukocytes ; Mutation, Missense ; Osteoclasts ; Osteopetrosis* ; Osteosclerosis ; Pelvis ; Skeleton ; Skull ; Spine