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 and Objectives: Peritonsillar abscess (PTA) is an accumulation of pus between the palatine tonsil and pharyngeal constrictor muscle. It is a common cause of emergency on-call consultations among ENT doctors and occurs due to the possibility of sepsis, airway obstruction, and progression to deep neck infection. This study aims to compare the effectiveness of needle aspiration (NA) to incision & drainage (I&D) for the treatment of PTA.Subjects and Method From September 2018 to March 2020, 58 patients with PTA were admitted to our ENT Department. After a comprehensive diagnostic procedure, 38 patients were enrolled in the study and they underwent either I&D (20 patients) or NA (18 patients) treatment. Patients were discharged when edema decreased on the endoscopic findings and their symptoms improved, with a visual analogue scale (VAS) score <3 points. For each patient, we evaluated the abscess volume, age, body mass index, hypertension, diabetes mellitus, smoking and drinking history, abscess size, and duration of hospitalization. White blood cell (WBC) count, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) were estimated on the 1st, 3rd, and 5th days of hospitalization. Results: The mean age of participants was 42.8±15.5 years and 40.3±14.7 years in the I&D and NA groups, respectively. Except for ESR, the mean hospitalization duration, initial volume of abscess size, VAS pain score, WBC count and the CRP level were not different between the groups. Conclusion Our study revealed no significant differences in hospital stay duration, VAS score, WBC counts or in the CRP level among patients admitted for PTA, whether they underwent I&D or NA.

Purpose: Plasma circulating tumor DNA (ctDNA) could reflect the genetic alterations present in tumor tissues. However, there is little information about the clinical relevance of cell-free DNA genotyping in peripheral T-cell lymphoma (PTCL). Materials and Methods: After targeted sequencing plasma cell-free DNA of patients with various subtypes of PTCL (n=94), we analyzed the mutation profiles of plasma ctDNA samples and their predictive value of dynamic ctDNA monitoring for treatment outcomes. Results: Plasma ctDNA mutations were detected in 53 patients (56%, 53/94), and the detection rate of somatic mutations was highest in angioimmunoblastic T-cell lymphoma (24/31, 77%) and PTCL, not otherwise specified (18/29, 62.1%). Somatic mutations were detected in 51 of 66 genes that were sequenced, including the following top 10 ranked genes: RHOA, CREBBP, KMT2D, TP53, IDH2, ALK, MEF2B, SOCS1, CARD11, and KRAS. In the longitudinal assessment of ctDNA mutation, the difference in ctDNA mutation volume after treatment showed a significant correlation with disease relapse or progression. Thus, a ≥ 1.5-log decrease in genome equivalent (GE) between baseline and the end of treatment showed a significant association with better survival outcomes than a < 1.5-log decrease in GE. Conclusion Our results suggest the clinical relevance of plasma ctDNA analysis in patients with PTCL. However, our findings should be validated by a subsequent study with a larger study population and using a broader gene panel.

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.

Background: The nature and role of the mitochondrial stress response in adipose tissue in relation to obesity are not yet known. To determine whether the mitochondrial unfolded protein response (UPRmt) in adipose tissue is associated with obesity in humans and rodents. Methods: Visceral adipose tissue (VAT) was obtained from 48 normoglycemic women who underwent surgery. Expression levels of mRNA and proteins were measured for mitochondrial chaperones, intrinsic proteases, and components of electron-transport chains. Furthermore, we systematically analyzed metabolic phenotypes with a large panel of isogenic BXD inbred mouse strains and Genotype-Tissue Expression (GTEx) data. Results: In VAT, expression of mitochondrial chaperones and intrinsic proteases localized in inner and outer mitochondrial membranes was not associated with body mass index (BMI), except for the Lon protease homolog, mitochondrial, and the corresponding gene LONP1, which showed high-level expression in the VAT of overweight or obese individuals. Expression of LONP1 in VAT positively correlated with BMI. Analysis of the GTEx database revealed that elevation of LONP1 expression is associated with enhancement of genes involved in glucose and lipid metabolism in VAT. Mice with higher Lonp1 expression in adipose tissue had better systemic glucose metabolism than mice with lower Lonp1 expression. Conclusion Expression of mitochondrial LONP1, which is involved in the mitochondrial quality control stress response, was elevated in the VAT of obese individuals. In a bioinformatics analysis, high LONP1 expression in VAT was associated with enhanced glucose and lipid metabolism.

Background: The nature and role of the mitochondrial stress response in adipose tissue in relation to obesity are not yet known. To determine whether the mitochondrial unfolded protein response (UPRmt) in adipose tissue is associated with obesity in humans and rodents. Methods: Visceral adipose tissue (VAT) was obtained from 48 normoglycemic women who underwent surgery. Expression levels of mRNA and proteins were measured for mitochondrial chaperones, intrinsic proteases, and components of electron-transport chains. Furthermore, we systematically analyzed metabolic phenotypes with a large panel of isogenic BXD inbred mouse strains and Genotype-Tissue Expression (GTEx) data. Results: In VAT, expression of mitochondrial chaperones and intrinsic proteases localized in inner and outer mitochondrial membranes was not associated with body mass index (BMI), except for the Lon protease homolog, mitochondrial, and the corresponding gene LONP1, which showed high-level expression in the VAT of overweight or obese individuals. Expression of LONP1 in VAT positively correlated with BMI. Analysis of the GTEx database revealed that elevation of LONP1 expression is associated with enhancement of genes involved in glucose and lipid metabolism in VAT. Mice with higher Lonp1 expression in adipose tissue had better systemic glucose metabolism than mice with lower Lonp1 expression. Conclusion Expression of mitochondrial LONP1, which is involved in the mitochondrial quality control stress response, was elevated in the VAT of obese individuals. In a bioinformatics analysis, high LONP1 expression in VAT was associated with enhanced glucose and lipid metabolism.

BACKGROUND AND OBJECTIVES: There are limited data regarding the clinical efficacy of the proximal optimization technique (POT) in the treatment of coronary bifurcation lesions. We investigated the influence of POT on the clinical outcomes of patients with coronary bifurcation lesions. METHODS: We enrolled a total of 1,191 patients with a bifurcation lesion with a side branch (SB) diameter ≥2.5 mm treated with a drug-eluting stent from 18 centers between January 2003 and December 2009. The primary outcome was major adverse cardiac events (MACEs: cardiac death, myocardial infarction or target lesion revascularization [TLR]). We performed one-to-many (1:N) propensity score matching with non-fixed matching ratio. RESULTS: POT was performed in 252 patients. During follow-up (median 37 months), the incidence of MACE was lower in the POT group than it was in the non-POT group (adjusted hazard ratio, 0.43; 95% confidence interval [CI], 0.24–0.79; p=0.006). After propensity score matching, these were 0.34; 95% CI, 0.17–0.69; p=0.003 for MACE and 0.37; 95% CI, 0.17–0.78; p=0.01 for TLR. The use of POT was associated with significantly lower TLR in patients treated without kissing ballooning, but was not in those who underwent kissing ballooning (p for interaction=0.03). CONCLUSIONS In coronary bifurcation lesions with a large SB, POT may be beneficial to improve long-term clinical outcome, particularly in patients treated without kissing ballooning during the procedure.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01642992

BACKGROUND: Recent in vivo studies indicated that R-spondin 1 (RSPO1) regulates food intake and increases insulin secretion, but its role in humans remains unknown. This study investigated the association between serum levels of RSPO1 and diverse metabolic parameters in humans. METHODS: The study population consisted of 43 subjects with newly diagnosed diabetes mellitus, and 79 non-diabetic participants. Serum levels of RSPO1 were measured using the enzyme-linked immunosorbent assay. The relationships between circulating RSPO1 and diverse metabolic parameters were analyzed. RESULTS: Circulating RSPO1 levels increased to a greater extent in the obese group than in the lean group. Moreover, serum levels of RSPO1 were higher in the insulin-resistant group than in the insulin-sensitive group. Serum levels of RSPO1 were significantly correlated with a range of metabolic parameters including body mass index, fasting C-peptide, homeostasis model assessment of insulin resistance index, and lipid profile. Moreover, levels were significantly associated with insulin resistance and obesity in non-diabetic subjects. CONCLUSION: This study demonstrated the association between serum levels of RSPO1 and a range of metabolic parameters in humans. Serum levels of RSPO1 are significantly related to obesity and insulin resistance, although the precise mechanisms remain unknown.
Biomarkers ; Body Mass Index ; C-Peptide ; Diabetes Mellitus ; Eating ; Enzyme-Linked Immunosorbent Assay ; Fasting ; Homeostasis ; Humans ; Insulin Resistance ; Insulin ; Obesity

BACKGROUND AND OBJECTIVES: There are limited data regarding the clinical efficacy of the proximal optimization technique (POT) in the treatment of coronary bifurcation lesions. We investigated the influence of POT on the clinical outcomes of patients with coronary bifurcation lesions. METHODS: We enrolled a total of 1,191 patients with a bifurcation lesion with a side branch (SB) diameter ≥2.5 mm treated with a drug-eluting stent from 18 centers between January 2003 and December 2009. The primary outcome was major adverse cardiac events (MACEs: cardiac death, myocardial infarction or target lesion revascularization [TLR]). We performed one-to-many (1:N) propensity score matching with non-fixed matching ratio. RESULTS: POT was performed in 252 patients. During follow-up (median 37 months), the incidence of MACE was lower in the POT group than it was in the non-POT group (adjusted hazard ratio, 0.43; 95% confidence interval [CI], 0.24–0.79; p=0.006). After propensity score matching, these were 0.34; 95% CI, 0.17–0.69; p=0.003 for MACE and 0.37; 95% CI, 0.17–0.78; p=0.01 for TLR. The use of POT was associated with significantly lower TLR in patients treated without kissing ballooning, but was not in those who underwent kissing ballooning (p for interaction=0.03). CONCLUSIONS: In coronary bifurcation lesions with a large SB, POT may be beneficial to improve long-term clinical outcome, particularly in patients treated without kissing ballooning during the procedure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01642992
Coronary Artery Disease ; Death ; Drug-Eluting Stents ; Follow-Up Studies ; Humans ; Incidence ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Propensity Score ; Treatment Outcome

BACKGROUND: The aim of this study was to explore the differences in the clinical characteristics and diagnostic rates of diabetes mellitus (DM) according to various criteria in different age groups and to evaluate the efficacy of each criterion for screening older patients. METHODS: We studied 515 patients and measured the fasting plasma glucose level (FPG), 2-hour plasma glucose level after the 75 g oral glucose tolerance test (2-hour postload glucose [2-h PG]), and glycosylated hemoglobin (HbA1c) for re-evaluation of hyperglycemia without a history of diabetes. Patients with newly diagnosed DM were grouped by age as younger ( < 65 years) or older (≥65 years). RESULTS: Older patients had significantly lower HbA1c, FPG, and 2-h PG levels and a higher homeostatic level of pancreatic β-cell function compared with younger patients (P < 0.001). The older group had the lowest diagnostic rate when using the FPG level (45.5%) and the highest diagnostic rate when using the 2-h PG level (84.6%). These results were mostly due to the higher frequency of isolated post-challenge hyperglycemia in the older patients than in the younger group (28.8% vs. 9.2%). The use of both the FPG and HbA1c levels significantly enhanced the low diagnostic power when employing only the FPG levels in the older group (71.2% vs. 45.5%). CONCLUSION: In the older patients, the 2-h PG level was the most accurate diagnostic criterion. When we consider the costs and convenience, a combination of the FPG and HbA1c criteria may be recommended as a screening test for DM in older people.
Blood Glucose* ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Early Diagnosis* ; Fasting ; Glucose ; Glucose Tolerance Test ; Hemoglobin A, Glycosylated ; Humans ; Hyperglycemia ; Mass Screening ; Plasma*