BACKGROUND: Eosinophilia in hemodialysis (HD) patients has been associated with allergic reactions to dialyzers and exaggerated activation of complement during HD. Complement activation can lead to cytokine production. The cause of the eosinophilia is controversial and maybe multifactorial. Eosinophilia is stimulated by T lymphocytes and maybe related to the immune dysfunction of uremic patients. The aim of this study is to elucidate the relationship between the eosinophilia and serum cytokine concentrations in maintenance HD patients and to reveal whether the eosinophilia in HD patients reflects HD-associated cytokine production. METHODS: We examined 40 HD patients who were stable for a minimum of 3 months at our hemodialysis unit. We measured eosinophil count and eosinophil percent on peripheral blood smear. Eosinophilia was defined as >or=350 cells/mm3 or >or=5% on smear. The serum concentrations of Interleukin-1beta (IL-1beta), Interleukin-2 (IL-2), Interleukin-5 (IL-5), Interleukin-6 (IL-6) were measured by ELISA before (pre) and after (post) dialysis. RESULTS: Thirteen patients with eosinophilia were compared 27 patients without eosinophilia. In patients with eosinophilia, serum concentrations of IL-1beta and IL-2 were significantly elevated after dialysis than before dialysis (p<0.05). Post-HD IL-6 concentrations also were elevated, but statistically insignificant. IL-5 concentrations were not elevated after dialysis. In patients without eosinophilia, serum concentrations of IL-1beta, IL-2 and IL-6 were significantly elevated after dialysis (p<0.05). IL-5 concentrations were not elevated after dialysis. The eosinophil counts were not correlated to age, gender, underlying disease, serum levels of blood urea nitrogen, creatinine, albumin, CRP and the levels of post dialysis cytokines. CONCLUSION: Independently on eosinophilia in HD, the serum concentrations of cytokines (IL-1beta, IL-2 and IL-6) were elevated after HD. IL-5 concentrations were not elevated after dialysis. But we could not reveal whether the eosinophilia in maintenance HD patients may be a surrogate marker for the reflection of exaggerated cellular cytokine production during HD or not by this study.
Biomarkers ; Blood Urea Nitrogen ; Complement Activation ; Complement System Proteins ; Creatinine ; Cytokines ; Dialysis ; Enzyme-Linked Immunosorbent Assay ; Eosinophilia* ; Eosinophils ; Humans ; Hypersensitivity ; Interleukin-1beta ; Interleukin-2 ; Interleukin-5 ; Interleukin-6 ; Renal Dialysis* ; T-Lymphocytes

PURPOSE: Cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 play a key role in the pathogenesis of in-stent restenosis. We investigated the effect of a short-term therapy of celecoxib, a COX-2 inhibitor, with or without doxycycline, an MMP inhibitor, after coronary stenting on inflammatory biomarkers and neointimal hyperplasia. MATERIALS AND METHODS: A total of 75 patients (86 lesions) treated with bare metal stents were randomized into three groups: 1) combination therapy (200 mg celecoxib and 20 mg doxycycline, both twice daily), 2) celecoxib (200 mg twice daily) only, and 3) non-therapy control. Celecoxib and doxycycline were administered for 3 weeks after coronary stenting. The primary endpoint was neointimal volume obstruction by intravascular ultrasound (IVUS) at 6 months. The secondary endpoints included clinical outcomes, angiographic data, and changes in blood levels of inflammatory biomarkers. RESULTS: Follow-up IVUS revealed no significant difference in the neointimal volume obstruction among the three treatment groups. There was no difference in cardiac deaths, myocardial infarctions, target lesion revascularization or stent thrombosis among the groups. Blood levels of high-sensitivity C-reactive protein, soluble CD40 ligand, and MMP-9 varied widely 48 hours and 3 weeks after coronary stenting, however, they did not show any significant difference among the groups. CONCLUSION: Our study failed to demonstrate any beneficial effects of the short-term therapy with celecoxib and doxycycline or with celecoxib alone in the suppression of inflammatory biomarkers or in the inhibition of neointimal hyperplasia. Large scale randomized trials are necessary to define the role of anti-inflammatory therapy in the inhibition of neointimal hyperplasia.
Aged ; Angioplasty, Balloon, Coronary ; Anti-Bacterial Agents/therapeutic use ; Biological Markers/metabolism ; Coronary Artery Disease/immunology/metabolism/*therapy ; Cyclooxygenase 2 Inhibitors/therapeutic use ; Doxycycline/*therapeutic use ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Male ; Metals ; Middle Aged ; Neointima/*drug therapy/*immunology/metabolism ; Pyrazoles/*therapeutic use ; Stents/*adverse effects ; Sulfonamides/*therapeutic use

PURPOSE: Data comparing the clinical benefits of medical treatment with those of percutaneous coronary intervention (PCI) in an elderly population with angina pectoris are limited. Therefore, we evaluated the efficacy of elective PCI versus optimal medical treatment (OMT) in elderly patients (between 75 and 84 years old) with angina pectoris. MATERIALS AND METHODS: One hundred seventy-seven patients with significant coronary artery stenosis were randomly assigned to either the PCI group (n=90) or the OMT group (n=87). The primary outcome was a composite of major adverse events in the 1-year follow-up period that included cardiovascular death, non-fatal myocardial infarction, coronary revascularization, and stroke. RESULTS: Major adverse events occurred in 5 patients (5.6%) of the PCI group and in 17 patents (19.5%) of the OMT group (p=0.015). There were no significant differences between the PCI group and the OMT group in cardiac death [hazard ratio (HR) for the PCI group 0.454; 95% confidence interval (CI) 0.041-5.019, p=0.520], myocardial infarction (HR 0.399; 95% CI 0.039-4.050, p=0.437), or stroke (HR 0.919; 95% CI 0.057-14.709, p=0.952). However, the PCI group showed a significant preventive effect of the composite of major adverse events (HR 0.288; 95% CI 0.106-0.785, p=0.015) and against the need for coronary revascularization (HR 0.157; 95% CI 0.035-0.703, p=0.016). CONCLUSION: Elective PCI reduced major adverse events and was found to be an effective treatment modality in elderly patients with angina pectoris and significant coronary artery stenosis, compared to OMT.
Aged ; Aged, 80 and over ; Angina Pectoris/mortality/*therapy ; Coronary Stenosis/therapy ; Female ; Humans ; Male ; Myocardial Infarction/prevention & control/*therapy ; *Percutaneous Coronary Intervention ; Proportional Hazards Models ; Prospective Studies ; Republic of Korea ; Stroke/epidemiology ; Treatment Outcome

PURPOSE: Preoperative concurrent chemoradiation (CCRT) therapy may allow higher rates of tumor resectability and sphincter-saving procedures. Transanal endoscopic microsurgery (TEM) has become increasingly common in the management of selected patients with early rectal cancer. The aim of this study is to evaluate the clinical outcomes of selected patients with distal rectal cancer treated with TEM after CCRT. METHODS: Between June 2000 and August 2004, 7 patients with clinically T2 or T3 rectal cancer underwent TEM after CCRT. Pretreatment and preoperative clinical stages were estimated by using endorectal ultrasound or computed tomography and digital rectal exam. CCRT was performed with radiation therapy of 4,500 cGy/25 fractions over 5 weeks with 5-FU based chemosensitization. TEM was performed 4~7 weeks following the completion of therapy. RESULTS: The mean age was 54.9 (35~70) years and the median follow-up period was 23.0 (5~57) months. The lesions were located between 2 to 6 cm above the anal verge (median 3.0 cm). Pre- treatment T staging was estimated as T3 in 1 case and T2 in 6 cases, and post-treatment T staging was estimated as complete remission (CR) in 2 cases, T1 in 3 cases, and T2 in 2 patients. Pathologic evaluation revealed tumor downstaging in 6 patients, including 3 patients (42.9%) with CR. In all cases, there was no tumor on the resection margin. There have been no recurrences during the follow-up period. CONCLUSIONS: TEM after CCRT therapy appears to be an effective alternative treatment to radical resection for highly selected patients with T2 and T3 distal rectal cancer.
Fluorouracil ; Follow-Up Studies ; Humans ; Microsurgery* ; Rectal Neoplasms* ; Recurrence ; Ultrasonography

OBJECTIVES: Gamma-aminobutyric acid (GABA) has potential benefits in counteracting the sleep disruption and potential therapeutic effects on blood pressure, stress, cancer, and inflammatory diseases. Recently, High-dose GABA can be extracted from fermented rice germ using lactic acid bacteria. This study aimed to evaluate the effects of GABA natural extracts from fermented rice-germ on sleep latency, subjective sleep quality and insomnia symptoms. METHODS: This was a prospective randomized double-blind placebo-controlled trial performed at Kyung-Hee University hospital at Gangdong from June 2013 to October 2013. Adult (age≥30) patients who was diagnosed of insomnia according to DSM-IV criteria was enrolled. They were randomized into three groups: high dose treatment group 300 mg; low-dose treatment group, 100 mg; and placebo group. Questionnaires including Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), WHO-5 Well-Being Index were performed, and 1-week actigraphy was recorded before and 1 week after the treatment. RESULTS: Total of 114 patients were randomized into 3 groups: high-dose treatment (n=37), low-dose treatment (n=38), and placebo treatment group (n=39). At 1 week after the treatment, PSQI total score and C2 (sleep latency) score significantly decreased in low-dose and high-dose treatment group than the placebo groups [Repeated measures analysis of variance (ANOVA), p=0.017, 0.004 respectively]. ISI score also decreased in the two groups in dose-dependent manner (Repeated measures ANOVA, p=0.037). There were five (4.4%) patients who reported medication adverse events. CONCLUSIONS: This study suggests that treatment of low and high-dose GABA from unpolished rice-germ decreases sleep latency and improve insomnia severity without severe adverse events.
Actigraphy ; Adult ; Bacteria ; Blood Pressure ; Diagnostic and Statistical Manual of Mental Disorders ; gamma-Aminobutyric Acid* ; Humans ; Lactic Acid ; Prospective Studies ; Sleep Initiation and Maintenance Disorders ; Therapeutic Uses

PURPOSE: To evaluate the ability of coronary computed tomographic angiography (CCTA) to predict the need of coronary revascularization in symptomatic patients with stable angina who were referred to a cardiac catheterization laboratory for coronary revascularization. MATERIALS AND METHODS: Pre-angiography CCTA findings were analyzed in 1846 consecutive symptomatic patients with stable angina, who were referred to a cardiac catheterization laboratory at six hospitals and were potential candidates for coronary revascularization between July 2011 and December 2013. The number of patients requiring revascularization was determined based on the severity of coronary stenosis as assessed by CCTA. This was compared to the actual number of revascularization procedures performed in the cardiac catheterization laboratory. RESULTS: Based on CCTA findings, coronary revascularization was indicated in 877 (48%) and not indicated in 969 (52%) patients. Of the 877 patients indicated for revascularization by CCTA, only 600 (68%) underwent the procedure, whereas 285 (29%) of the 969 patients not indicated for revascularization, as assessed by CCTA, underwent the procedure. When the coronary arteries were divided into 15 segments using the American Heart Association coronary tree model, the sensitivity, specificity, positive predictive value, and negative predictive value of CCTA for therapeutic decision making on a per-segment analysis were 42%, 96%, 40%, and 96%, respectively. CONCLUSION: CCTA-based assessment of coronary stenosis severity does not sufficiently differentiate between coronary segments requiring revascularization versus those not requiring revascularization. Conventional coronary angiography should be considered to determine the need of revascularization in symptomatic patients with stable angina.
Aged ; Angina, Stable/*diagnostic imaging ; Coronary Angiography/*methods ; Coronary Stenosis/*diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Myocardial Revascularization ; Predictive Value of Tests ; Tomography, X-Ray Computed ; United States

BACKGROUND AND OBJECTIVES: Sirolimus-eluting stent (SES) is very effective for preventing in-stent restenosis through the suppression of neointimal proliferation. Treatment failure cases related to stent fracture have recently been reported on, but any studies concerning the pattern or mechanism of SES fracture are very rare. SUBJECTS AND METHODS: Between December 2003 to January 2005, 457 patients underwent follow-up coronary angiography after SES implantation at three referral center. We reviewed the angiographic and procedural data for eleven of theses patients [6 males (55%), mean age: 60 year-old age, range: 43-74 years] who were proven to have experience complete SES fracture. RESULTS: The left anterior descending artery (LAD) and right coronary artery (RCA) stent fracture were 7 cases (63%) and 4 cases (37%), respectively. Myocardial bridge was shown in 6 cases with LAD fracture (86%). Overlapping stent implantation was performed in 5 cases (45%). The mean value of the maximal angulations at the fracture site before intervention was 50 degrees (range; 39-70 degrees) and the mean change between the maximal and minimal angulations was 13.2 degrees (range; 2-28 degrees). The mean stent diameter and length were 3.0 mm (range; 2.75-3.50 mm) and 40 mm (range; 23-52 mm). Stent inflation with high pressure was performed on 6 cases (54%) and it's frequency was higher in the RCA than the LAD (3 cases, 75%, mean inflation pressure: 13.1 mmHg). The mean follow-up duration was 7.2 month and only 2 cases were admitted due to the recurrent chest pain. The binary restenosis rate was 55% (6 cases) and the restenotic lesions were treated by balloon angioplasty in 2 cases and additional stenting was done in 2 cases. CONCLUSION: Our results demonstrated that SES fracture occurred in 7 cases with LAD lesion and in 4 cases with RCA lesion. Long stenting including overlapping implantation and more than 40 degrees angulated long stent implantation may be the factors for SES fracture. Our results also showed high pressure stent inflation was performed more frequently at the RCA lesion, and myocardial bridge and kinking motion was detected more frequently at the LAD lesions.
Angioplasty, Balloon ; Arteries ; Chest Pain ; Coronary Angiography ; Coronary Vessels ; Follow-Up Studies ; Humans ; Inflation, Economic ; Male ; Middle Aged ; Referral and Consultation ; Sirolimus ; Stents* ; Treatment Failure

Purpose: Platelet function test (PFT) results and genotype hold unique prognostic implications in East Asian patients. The aim of the PTRG-DES (Platelet function and genoType-Related long-term proGnosis in Drug-Eluting Stent-treated Patients with coronary artery disease) consortium is to assess the clinical impact thereof on long-term clinical outcomes in Korean patients with coronary artery disease during dual antiplatelet therapy (DAPT) including clopidogrel. Materials and Methods: Searching publications on the PubMed, we reviewed clopidogrel treatment studies with PFT and/or genotype data for potential inclusion in this study. Lead investigators were invited to share PFT/genotype results, patient characteristics, and clinical outcomes to evaluate relationships among them. Results: Nine registries from 32 academic centers participated in the PTRG-DES consortium, contributing individual patient data from 13160 patients who underwent DES implantation between July 2003 and August 2018. The PTRG-PFT cohort was composed of 11714 patients with available VerifyNow assay results. Platelet reactivity levels reached 218±79 P2Y12 reaction units (PRU), and high on-clopidogrel platelet reactivity based on a consensus-recommended cutoff (PRU >208) was observed in 55.9%. The PTRGGenotype cohort consisted of 8163 patients with candidate genotypes related with clopidogrel responsiveness. Of those with cytochrome P450 (CYP) 2C19 genotype, frequencies of carrying one and two loss-of-function allele (s) (*2 or *3) were 47.9% (intermediate metabolizers) and 14.2% (poor metabolizers), respectively. Conclusion The PTRG-DES consortium highlights unique values for on-clopidogrel platelet reactivity and CYP2C19 phenotype that may be important to developing optimal antiplatelet regimens in East Asian patients.

BACKGROUND AND OBJECTIVES: Patients with acute myocardial infarction show varying degrees of collateral development. However, the relationships between angiogenic factors and degree of collaterals are not well known. SUBJECTS AND METHODS: Fifty-nine patients (mean age, 59+/-10 years) with ST-segment elevation myocardial infarction (STEMI) underwent primary percutaneous coronary intervention (PCI). Patients were divided into one of 2 groups: group I (Rentrop collateral grade 0/1, n=34) or group II (grade 2/3, n=25). Plasma levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sFlt-1), angiopoietin (Ang)-2, and soluble Tie-2 at baseline, 24 and 48 hours after PCI were measured. RESULTS: There were fewer diabetic patients and higher incidence of previous angina and multi-vessel disease in group II. Group II had a lower left ventricular ejection fraction and a trend toward longer pain-to-balloon time. Plasma levels of Ang-2, sFlt-1 were elevated prior to primary PCI and decreased after PCI, whereas plasma level of VEGF was relatively low initially, however rose after PCI. sTie-2 levels showed no significant interval change in group I, but decreased over time in group II. VEGF, sFlt-1, and Tie-2 levels did not differ between the groups at each time point. However, plasma levels of Ang-2 were higher in group I than in group II at baseline and at 48 hours. CONCLUSION: Presence of collaterals in STEMI patients undergoing primary PCI was associated with lesser rise in Ang-2 plasma level. VEGF showed a delayed response to acute ischemia compared to Ang-2. Clinical implications of our findings need to be investigated in further studies.
Angiogenesis Inducing Agents ; Angiogenesis Modulating Agents ; Angiopoietin-2 ; Humans ; Incidence ; Ischemia ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Plasma ; Receptors, Vascular Endothelial Growth Factor ; Stroke Volume ; Vascular Endothelial Growth Factor A

Background: Coronary artery disease patients undergoing percutaneous coronary intervention (PCI) often exhibit reduced left ventricular ejection fraction (LVEF). However, the impact of LV dysfunction status in conjunction with platelet reactivity on clinical outcomes has not been previously investigated. Methods: From the multicenter PTRG-DES (Platelet function and genoType-Related long-term prognosis in DES-treated patients) consortium, the patients were classified as preserved-EF (PEF: LVEF ≥ 50%) and reduced-EF (REF: LVEF< 5 0%) group by echocardiography. Platelet reactivity was measured using VerifyNow P2Y 12 assay and high platelet reactivity (HPR) was defined as PRU ≥ 252. The major adverse cardiac and cerebrovascular events (MACCEs) were a composite of death, myocardial infarction, stent thrombosis and stroke at 5 years after PCI. Major bleeding was defined as Bleeding Academic Research Consortium bleeding types 3–5. Results: A total of 13,160 patients from PTRG-DES, 9,319 (79.6%) patients with the results of both PRU and LVEF were analyzed. The incidence of MACCE and major bleeding was higher in REF group as compared with PEF group (MACCEs: hazard ratio [HR] 2.17, P < 0.001, 95% confidence interval [CI] 1.85–2.55; major bleeding: HR 1.78, P < 0.001, 95% CI 1.39–2.78).The highest rate of MACCEs was found in patients with REF and HPR, and the difference between the groups was statistically significant (HR 3.14 in REF(+)/HPR(+) vs. PEF(+)/HPR(-) group,P <0.01, 95% CI 2.51–3.91). The frequency of major bleeding was not associated with the HPR in either group. Conclusion LV dysfunction was associated with an increased incidence of MACCEs and major bleeding in patients who underwent PCI. The HPR status further exhibited significant increase of MACCEs in patients with LV dysfunction in a large, real-world registry.Trial Registration: ClinicalTrials.gov Identifier: NCT04734028