Search

Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and human epidermal growth factor receptor 2 (HER2) have been considered as potential therapeutic targets in cholangiocarcinoma, but no studies have yet clarified the clinicopathological or prognostic significance of these molecules. Immunohistochemical expression of these molecules was assessed retrospectively in 236 cases of cholangiocarcinoma, as well as associations between the expression of these molecules and clinicopathological factors or clinical outcome. The proportions of positive cases for EGFR, VEGF, and HER2 overexpression were 27.4, 53.8, and 0.9% in intrahepatic cholangiocarcinoma (IHCC), and 19.2, 59.2, and 8.5% in extrahepatic cholangiocarcinoma (EHCC), respectively. Clinicopathologically, EGFR overexpression was associated with macroscopic type (P=0.0120), lymph node metastasis (P=0.0006), tumour stage (P=0.0424), lymphatic vessel invasion (P=0.0371), and perineural invasion (P=0.0459) in EHCC, and VEGF overexpression with intrahepatic metastasis (P=0.0224) in IHCC. Multivariate analysis showed that EGFR expression was a significant prognostic factor (hazard ratio (HR), 2.67; 95% confidence interval (CI), 1.52-4.69; P=0.0006) and also a risk factor for tumour recurrence (HR, 1.89; 95% CI, 1.05-3.39, P=0.0335) in IHCC. These results suggest that EGFR expression is associated with tumour progression and VEGF expression may be involved in haematogenic metastasis in cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Reactive postural control is an important component of the balance function for fall prevention. Perturbation-based balance exercises improve reactive postural control; however, these exercises require large, complex instruments and expert medical guidance. This study investigates the effects of unexpected perturbation-based balance exercises using a wearable balance exercise device (WBED) on reactive postural control. Eighteen healthy adult males participated in this study. Participants were assigned to the WBED and Sham groups. In the intervention session, participants in the WBED group randomly underwent unexpected perturbation in the mediolateral direction, while the Sham group performed the same exercises without perturbation. Before and after the intervention session, all participants underwent evaluation of reactive balance function using air cylinders. Peak displacement (D), time at peak displacement (T), peak velocity (V), and root mean square (RMS) of center of pressure (COP) data were measured. For mediolateral and anteroposterior COP (COPML and COP[Formula: see text]), the main effects of group and time factors (pre/post) were investigated through the analysis of variance for split-plot factorial design. In the WBED group, the D-COPML and V-COPML of the post-test significantly decreased compared to those of the pre-test (p = 0.017 and p = 0.003, respectively). Furthermore, the D-COPAP and RMSAP of the post-test significantly decreased compared to those of the pre-test (p = 0.036 and p = 0.015, respectively). This study proved that the perturbation-based balance exercise using WBED immediately improved reactive postural control. Therefore, wearable exercise devices, such as WBED, may contribute to the prevention of falls and fall-related injuries., (© 2023 The Authors.)

Saccharomyces cerevisiae LIP1 encodes a regulatory subunit that forms a complex with the ceramide synthase catalytic subunits, Lag1/Lac1, which is localized on the membrane of endoplasmic reticulum. To understand the underlying regulatory mechanism of sphingolipid biosynthesis, we generated strains upon replacing the chromosomal LIP1 promoter with a Tet-off promoter, which enables the expression in Dox-dependent manner. The lip1-1 strain, obtained through the promoter substitution, exhibits severe growth inhibition and remarkable decrease in sphingolipid synthesis in the presence of Dox. Using this strain, we investigated the effect of a decrease in ceramide synthesis on TOR complex 2 (TORC2)-Ypk1 signaling, which senses the complex sphingolipid level at the plasma membrane and promotes sphingolipid biosynthesis. In lip1-1 cells, Ypk1 was activated via both upstream kinases, TORC2 and yeast PDK1 homologues, Pkh1/2, thereby inducing hyperphosphorylation of Lag1, but not of another Ypk1-substrate, Orm1, which is a known negative regulator of the first step of sphingolipid metabolism, in the presence of Dox. Therefore, our data suggest that the metabolic enzyme activities at each step of the sphingolipid biosynthetic pathway are controlled through a fine regulatory mechanism., (© 2021 Federation of European Biochemical Societies.)

Background/aim: Vein-first lobectomy (VFL) in lung cancer might reduce shedding of circulating tumour cells (CTCs). This study assessed the clinical significance of VFL., Patients and Methods: Lung cancer patients undergoing lobectomy and CTC testing were evaluated. The primary evaluation item was postoperative clustered CTC detection, and the secondary outcome measures were the 2-year overall survival and recurrence-free survival rates according to the status of VFL and postoperative clustered CTC., Results: Eighty-six patients with similar backgrounds, except for lobe resection and pulmonary vein dissection time, showed postoperative clustered CTC identification rates of 43.8% and 37.9% in the VFL group (n=57) and no-VFL group (n=29), respectively. However, prognosis was not significantly different, although the presence of clustered CTC after surgery was a predictor of recurrence., Conclusion: The status of postoperative clustered CTC was similar regardless of VFL or not, although the detection of clustered CTC was a predictor of recurrence., Competing Interests: The Authors declare that they have no conflicts of interest in relation to this study., (Copyright 2021, International Institute of Anticancer Research.)

Background: Laparoscopic transabdominal preperitoneal patch (TAPP) is now commonly used in the repair of inguinal hernia. Barbed suture can be a fast and effective method of peritoneal closure. We report two rare cases of small bowel obstruction and perforation caused by barbed suture after TAPP., Cases: Patient 1 is a 45-year-old man who underwent laparoscopic repair of a right inguinal hernia. Barbed suture was used to close the peritoneal defect. At 47 days after the operation, he was diagnosed with a small bowel obstruction caused by an elongated tail of the barbed suture. Emergency laparoscopic exploration was performed for removal of the embedded suture and detorsion of the volvulus. The second patient is a 50-year-old man who was admitted with a small bowel perforation one week after TAPP herniorrhaphy. Emergency exploration revealed that the tail of the barbed suture had pierced the small intestine, causing a tiny perforation. After cutting and releasing the redundant tail of the barbed suture, the serosal and muscular defect was closed with 2 absorbable single-knot sutures. Both patients have recovered well. Finally, we searched the PubMed database and reviewed the literature on the effectiveness and safety of barbed suture for TAPP., Conclusions: Surgeons should understand the characteristics of barbed suture and master the technique of peritoneum closure during TAPP in order to reduce the risk of bowel obstruction and perforation., (© 2021. The Author(s).)

Background: Hydrocele of canal of Nuck (HCN) is a rare disease in adult female. The diagnosis and treatment of HCN is still a challenge for surgeons., Case Presentation: A 56-year-old female presented with recent onset of occasional pain during exercise and an asymptomatic left groin swelling. Ultrasonography results were suspicious for left inguinal hernia incarceration and computed tomography (CT) scan showed no intestinal obstruction, which was considered as HCN. Laparoscopic hydrocelectomy of the HCN and a routine laparoscopic hernia repair via the transabdominal preperitoneal (TAPP) approach were performed. Postoperative pathology showed no malignant lesions or endometriosis., Conclusions: The preoperative diagnosis of HCN is extremely important. Surgeons should choose appropriate surgical methods for different anatomical HCNs based on the preoperative diagnosis.

Background: Accurate diagnosis and complete resection of hydrocele of canal of Nuck (HCN) is still a challenge for surgeons., Case Presentation: A 28-year-old woman presented with a suspected inguinal hernia due to swelling in her right groin and was introduced for surgical treatment. Computed tomography scan revealed local cyst formation in the right groin and eliminated intestinal incarceration. In order to further confirm the diagnosis, we used laparoscopic exploration; after excluding a combined hernia, HCN was surgically removed using a conventional anterior peritoneal approach and a mesh patch repair was not needed. Postoperative pathology results showed no endometriosis or malignancy., Conclusions: Laparoscopic assisted anterior approach provides both an accurate intraoperative diagnosis and a quick complete resection of HCN; it is the preferred treatment for women of childbearing age with pure HCN.

Background/aim: We investigated the relationship between solid component size (SS), carcinoembryonic antigen (CEA), and standardized uptake value (SUVmax) as continuous variables and postoperative clustered circulating tumor cell (C-CTC) detection in patients with pulmonary adenocarcinoma who underwent surgery., Patients and Methods: C-CTC detection was the main evaluation item, which was analyzed using the receiver operating characteristic curve to calculate areas under the curves (AUCs) for the variables. Additionally, the two-year recurrence-free survival rates (2Y-RFSRs) were analyzed., Results: Among the 84 patients examined, SS, CEA, and SUVmax had AUCs>0.7, and were independent. Their thresholds were 2.1 cm, 7.5 ng/ml, and 2.9, respectively. The 2Y-RFSR were significantly better in the non-C-CTC group (n=58) and in the group of patients without high levels of these predictors (n=32)., Conclusion: SS, CEA level, and SUVmax predicted postoperative CTC detection in pulmonary adenocarcinoma patients., (Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

While retrospective studies have compared the efficacy of anti-tumour necrosis factor (TNF) agents and tacrolimus (TAC) in ulcerative colitis (UC), information regarding first-time use of these agents is limited. The aim of our study was to investigate the short- and long-term efficacy of anti-TNF agents [adalimumab (ADA) and infliximab (IFX)] and TAC in anti-TNF agent- and TAC-naïve steroid-refractory UC patients. We evaluated 150 steroid-refractory UC patients receiving anti-TNF agents (IFX: n = 30, ADA: n = 41) or TAC (n = 79) at eight institutions in Japan. Clinical response rates at 8 weeks were 73.2% and 75.9% while remission rates were 30.1% and 25.3% in the anti-TNF and TAC groups, respectively. Logistic regression analysis showed the male sex and higher C-reactive protein to be independent factors for response to anti-TNF agents and TAC, respectively. Use of TAC was an independent factor for relapse. No differences in response to the treatment or relapse were observed between IFX and ADA. In conclusion, TAC and anti-TNF agents promoted similar short-term effects, but anti-TNF agents ensured better long-term outcomes at first-time treatment of steroid-refractory UC patients.

Rationale: Mucormycosis is a rare opportunistic fungal infection with poor prognosis. The incidence of mucormycosis has been increasing, and it is a threat to immunocompromised hosts. We present a case of gastric mucormycosis complicated by a gastropleural fistula during immunosuppressive treatment for adult-onset Still disease (AOSD)., Patient Concerns: An 82-year-old woman diagnosed with AOSD who developed gastric ulcers during the administration of an immunosuppressive therapy with corticosteroids, cyclosporine, and tocilizumab complained of melena and epigastralgia. Esophagogastroduodenoscopy showed multiple ulcers covered with grayish or greenish exudates., Diagnoses: The patient diagnosed with mucormycosis based on culture and biopsy of the ulcers, which showed nonseptate hyphae branching at wide angles. Mucor indicus was identified using polymerase chain reaction., Interventions and Outcomes: Although liposomal amphotericin B was administered, gastric mucormycosis was found to be complicated by a gastropleural fistula. The patient died because of pneumonia due to cytomegalovirus infection, and autopsy revealed the presence of Mucorales around the fistula connecting the stomach and diaphragm., Lessons: Gastric mucormycosis is refractory to treatment and fatal. Surgical resection, if possible, along with antifungal drugs can result in better outcomes.

Background: There are few reports of the efficacy of adalimumab (ADA) for clinical remission and preventing postoperative recurrence in Crohn's disease (CD) in Asian real practice settings. We conducted a Japanese multicenter retrospective observational study., Methods: We evaluated patients with CD who were treated with ADA at 11 medical institutions in Japan to investigate the clinical efficacy of remission up to 52 weeks and the associated factors to achieve remission with a CD Activity Index (CDAI) < 150. The effects of preventing postoperative recurrence were also evaluated., Results: In 62 patients, the remission rates were 33.9, 74.2, 75.8, 77.4, and 66.1 % at 0, 4, 12, 26, and 52 weeks, respectively. Although 10 patients discontinued treatment due to primary nonresponse, secondary nonresponse, or adverse events, the ongoing treatment rate at 52 weeks was 83.9 %. Comparison of remission and non-remission on univariate analysis identified colonic type and baseline CDAI value as significant associated factors (P < 0.05). In 16 patients who received ADA to prevent postoperative recurrence, the clinical remission maintenance rate was 93.8 % and the mucosal healing rate was 64.3 % during a mean postoperative follow-up period of 32.3 months., Conclusions: ADA effectively induced remission and prevented postoperative recurrence in patients with CD in a real practice setting.

BACKGROUND This study reports the pathogenesis of anal canal adenocarcinoma in a patient with longstanding Crohn's disease (CD). CASE REPORT A 50-year-old woman with a 33-year history of CD presented with perianal pain of several months' duration. She had been treated surgically for a rectovaginal fistula 26 years earlier and had been treated with infliximab (IFX) for the previous 4 years. A biopsy under anesthesia revealed an anal canal adenocarcinoma, which was removed by abdominoperineal resection. Pathological examination showed that a large part of the tumor consisted of mucinous adenocarcinoma at the same location as the rectovaginal fistula had been removed 26 years earlier. There was no evidence of recurrent rectovaginal fistula, but thick fibers surrounded the tumor, likely representing part of the previous rectovaginal fistula. Immunohistochemical analysis using antibodies against cytokeratins (CK20 and CK7) revealed that the adenocarcinoma arose from the rectal mucosa, not the anal glands. CONCLUSIONS Mucinous adenocarcinoma can arise in patients with CD, even in the absence of longstanding perianal disease, and may be associated with adenomatous transformation of the epithelial lining in a former fistula tract.

Takotsubo cardiomyopathy is a disorder characterized by left ventricular apical ballooning with preceding emotional and/or physical stressors. This condition is also an important differential diagnosis of acute coronary syndrome. We herein describe a case of Takotsubo cardiomyopathy, a significant clinical phenomenon, triggered by delayed-onset rhabdomyolysis following the administration of long-term statin treatment, without any preceding stressors or changes in the patient's medical condition, in association with complaints of non-specific muscle-related symptoms. Although an electrocardiogram showed remarkable ST-segment elevation, a careful reading of the electrocardiogram findings revealed the features of Takotsubo cardiomyopathy. Withdrawing the statin therapy improved the patient's cardiac function.

Hypertrophic cardiomyopathy (HCM) has various morphological and clinical features. A decade has passed since the previous survey of the epidemiological and clinical characteristics of Japanese HCM patients. The Aichi Hypertrophic Cardiomyopathy (AHC) Registry is based on a prospective multicenter observational study of HCM patients. The clinical characteristics of 42 ambulant HCM patients followed up for up to 5 years were investigated. The primary endpoint was major adverse cardiac events (MACE), defined as death, non-fatal stroke, admission due to congestive heart failure (CHF), or episodes of sustained ventricular tachycardia/fibrillation. The MACE-free survival during the 5-year follow-up period was 76% according to Kaplan-Meier analysis. HCM-related death occurred in 3 (7%) patients and SCD occurred in 2 (5%) patients. Additionally, 3 (7%) patients were admitted to the hospital due to CHF. Meanwhile, sustained VT was detected in one (2%) of the patients who received ICD implantation and subsequently terminated with antitachycardia pacing using an ICD. The patients with HCM exhibiting left ventricular outflow obstruction (HOCM) had a slightly lower MACE-free survival rate than those with neither HOCM nor dilated-HCM (dHCM) (71% versus 81%, log-rank P = 0.581). Furthermore, the patients with dHCM demonstrated a significantly lower MACE-free survival rate than those with neither HOCM nor dHCM (33% versus 81%, log-rank P = 0.029). In the AHC Registry targeting current Japanese HCM patients, we demonstrated that many HCM patients continue to suffer from MACE despite the development of various treatments for HCM.

In repetitive measurements of flow-mediated dilatation (FMD), the duration of the interval between measurements remains controversial. In this pilot study, we conducted three sequential measurements of low-flow-mediated constriction (L-FMC), FMD and flow-mediated total dilation (FMTD; L-FMC+ FMD) at baseline and intervals of 15 and 60 min in 30 healthy males. FMD15, L-FMC15, and FMTD15 were significantly lower than the respective first measurements, but all indices showed full recovery at 60 min in all subjects. The baseline diameter was slightly increased at 15 min and restored at 60 min, but the maximum diameter, and the baseline and reactive flow velocity unchanged. We examined the relationship between recovery rate of FMTD at 15 min (FMTD-R) and cardio-ankle vascular index (CAVI). Univariate analysis showed moderate correlation between FMTD-R, and CAVI and L-FMC0. Patients were divided according to FMTD-R value; the low-FMTD-R group [below the median value (-26.2%)] included a significantly higher proportion of smokers and higher CAVI values than the high-FMTD-R group. The reproducibility of FMTD and FMTD-R was evaluated in another group of 25 healthy subjects. The range of variation across measurements was 1.1% for FMTD and 4.6% for FMTD-R; with intraclass correlation coefficients of 0.93 and 0.95, respectively. The present study demonstrated blunted recovery of FMD within 15 min, suggesting the need for selection of a more adequate interval between measurements to avoid underestimation of FMD in subsequent measurements. The findings demonstrated the reproducibility of FMTD-R and FMTD measurements, and that FMTD-R might be involved in arterial stiffness and early vascular impairment in the healthy subjects.

Background: Indoxyl sulfate (IS), a uremic toxin, has cardiovascular as well as uremic toxicity. We evaluated the prognostic value of blood IS level for long-term outcome., Methods and Results: This study followed 311 patients with coronary artery disease. Plasma IS level and estimated glomerular filtration rate (eGFR) were determined. The endpoint was a major adverse cardiac event (MACE). Median follow-up was 759 days. IS was significantly higher in patients with MACE than in those without (P<0.001). Patients were divided according to quartiles (Q) of plasma IS level (Q1, Q2, Q3, and Q4). On Kaplan-Meier analysis a significantly lower MACE-free rate was obtained for Q4 compared with the other quartiles (P<0.001). In patients with eGFR ≥90, 89-60, 59-30, 29-15, and <15 ml·min(-1)·1.73 m(-2), the percentage of patients in Q4 was 0%, 13%, 29%, 100%, and 100%, respectively. In patients with eGFR 89-60 ml·min(-1)·1.73 m(-2), there was no significant difference in MACE-free rate between Q4 and the other quartiles; in patients with eGFR 59-30 ml·min(-1)·1.73 m(-2), a significantly lower MACE-free rate was obtained for Q4 compared with the other quartiles (P=0.832 and P=0.015, respectively)., Conclusions: Plasma IS level is a significant predictor of MACE, especially in patients with eGFR 59-30 ml·min(-1)·1.73 m(-2).

Aims: The pathogenesis of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains unclear. The purpose of this study is to analyse tissue characterizations of neointima in restenosis lesions after sirolimus-eluting stent (SES), comparing with those after bare metal stent (BMS) using integrated backscatter intravascular ultrasound (IB-IVUS)., Methods and Results: A total of 54 consecutive patients who had ISR lesions after SES (n = 20) or BMS (n = 34) implantation were enrolled. For tissue characterization of neointima, IB-IVUS was performed by cross-sectional (at the minimum lumen area) and volumetric (within the stented segment) analyses. In addition, angiographic patterns of restenosis were evaluated with division into focal and diffuse. The focal angiographic pattern of restenosis was predominantly observed in the SES group (SES vs. BMS; 80.0 vs. 26.5%; P = 0.0001), whereas the diffuse pattern was more common in the BMS group (SES vs. BMS; 20.0 vs. 73.5%; P = 0.0001). On both cross-sectional and volumetric IB-IVUS analyses, the neointimal tissue in restenosis lesions after SES implantation had a significantly larger percentage of lipid tissue (cross-sectional: 23.3 ± 12.7 vs. 15.7 ± 11.9%; P = 0.033; volumetric: 22.8 ± 10.4 vs. 16.3 ± 7.0%; P = 0.008) and a significantly smaller percentage of fibrous tissue compared with that after BMS implantation (cross-sectional: 73.6 ± 11.6 vs. 82.0 ± 11.2%; P = 0.011, volumetric: 73.8 ± 9.5 vs. 80.5 ± 6.7%; P = 0.004)., Conclusion: This IB-IVUS study indicates that larger amounts of lipid tissue are present in neointima of SES when compared with BMS, suggesting that neoatherosclerosis may in part be responsible for ISR after SES implantation.

Background: The purpose of the present study was to compare the 5-year clinical outcomes after implantation of drug-eluting stent (DES) and bare-metal stent (BMS) in Japanese patients with acute myocardial infarction (AMI)., Methods and Results: This study was a subgroup analysis of the Nagoya Acute Myocardial Infarction Study (NAMIS). It included 658 AMI patients, of which 280 were treated with a DES and 378 with a BMS. The major adverse cardiac event (MACE)-free rates during the 5-year follow-up period were similar between the 2 groups (95.7% vs. 96.8%, P=0.482). A significant difference was seen, however, in the target lesion revascularization (TLR) rates (7.9% vs. 17.7%, P<0.0001). Interestingly, there was no significant difference between the 2 groups from year 1 to 5 with regard to late TLR (2.5% vs. 2.1%, P=0.906), despite the markedly lower incidence of TLR within the first year in the DES group compared with the BMS group (5.4% vs. 15.6%, P<0.0001)., Conclusions: In this long-term follow-up analysis of DES compared to BMS in Japanese patients with AMI, there was no significant difference in the incidence of MACE. Although a lower rate of TLR was observed in DES group within the first year, the superiority of DES in relation to the incidence of TLR disappeared after the first year following primary percutaneous coronary intervention.

Background: After abdominal aortic aneurysm (AAA) repair, relatively low survival during long-term follow-up remains an unresolved issue. Stress myocardial perfusion single-photon emission computed tomography (SPECT) well predicts future mortality overall, as well as providing diagnoses of coronary artery disease. The prognostic value of myocardial SPECT findings after AAA repair, however, remains unclear., Methods and Results: This study followed 285 patients, all undergoing preoperative pharmacologic stress myocardial perfusion SPECT to determine summed stress score (SSS), then elective AAA repair by open AAA repair or endovascular aneurysm repair. The endpoint of the study was cardiac death. The median follow-up duration was 925 days (range, 541-1,095 days). Twenty-four (8%) died during follow-up. Kaplan-Meier analysis showed that patients with SSS≥9 had a significantly poorer prognosis than those with SSS<9 (76% vs. 93%, P=0.003). Multivariate Cox proportional hazards analysis indicated that SSS≥9, diabetes, and chronic kidney disease≥stage 3 could significantly and independently predict long-term cardiovascular mortality in patients after AAA repair (hazard ratio [HR], 4.2; 95% confidence interval [CI]: 1.8-9.7, P=0.001; HR, 3.0; 95% CI: 1.2-7.4, P=0.020; and HR, 4.1; 95% CI: 1.7-10.1, P=0.029, respectively)., Conclusions: Preoperative pharmacologic stress myocardial perfusion SPECT is a useful method to predict long-term cardiovascular mortality for patients undergoing elective AAA repair.

Background and Purpose: Percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) is one of the standard treatments for patients with stable angina pectoris (AP). In spite of a notable effect in preventing restenosis after PCI, DES cannot improve the mortality of patients compared to a bare-metal stent (BMS). On the other hand, periprocedural myocardial injury (PMI) is related to poor prognosis in patients undergoing PCI. We compared DES to BMS in the incidence of PMI in patients with stable AP., Methods and Subjects: We enrolled 265 consecutive patients with AP undergoing successful stent implantation. A blood sample was obtained from all patients immediately before and 24h after PCI. PMI was defined as an increase in creatine kinase-myocardial band isozyme fraction (CK-MB) greater than the upper limit of reference range 24h after PCI. During the study period, sirolimus- and paclitaxel-eluting stents were used as DES. The strategy of PCI including the type of stent to implant was left to the discretion of the operator., Results: Patients were divided into two groups (DES group, n=136 and BMS group, n=129). The incidence of PMI was significantly higher in the DES group than in the BMS group (24% vs. 12%, p=0.015). Use of DES remained an independent predictor of PMI on multivariate logistic regression analysis after adjustment for confounding factors (odds ratio 2.20, 95% CI, 1.07-4.51, p=0.032)., Conclusions: Implantation of the first-generation DES including sirolimus- and paclitaxel-eluting stents was associated with a higher incidence of PMI in patients with AP compared to BMS., (Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Coronary calcification is proportional to the extent and severity of atherosclerotic disease, and is a predictor of cardiac events. Furthermore, coronary calcification protruding into the lumen is considered as one type of vulnerable plaque. Optical coherence tomography (OCT) can provide in vivo imaging of the detailed vessel wall structure of the coronary artery with high resolution, as in the histological approach. We analyzed coronary calcification in that fashion using OCT in vivo. This study consisted of 70 superficial coronary calcifications of 39 consecutive patients who underwent percutaneous coronary intervention. After revascularization, OCT was performed in the treated vessel. We analyzed morphologic characteristics and the quantification of OCT-determined coronary calcification. Superficial coronary calcifications were classified into two groups depending on whether they did not intrude the lumen (type I) or did (type II). The distance from the lumen and the volume of each calcification were then measured. Superficial coronary calcifications were classified into two groups; type I, n = 39 (56%) and type II, n = 31 (44%). Type II calcifications were located significantly closer to the lumen [80 microm (60-130) vs.130 microm (90-260), p = 0.015], and tended to be smaller, but did not show a significant difference [0.65 (0.2631.3) mm3 vs. 1.2 (0.47-1.9) mm3, p = 0.153] compared to those of type I. In conclusion, OCT could visualize superficial coronary calcifications in detail and enable us to evaluate in vivo morphologic characterizations and quantify them.

Background: It is well known that chronic kidney disease is a strong independent predictor of adverse outcomes after percutaneous coronary intervention in patients with ischemic heart disease. Recently, peri-procedural myocardial injury has been associated with adverse cardiac events. The aim of this study was to investigate the relationship between renal function and peri-procedural myocardial injury in patients undergoing elective stent implantation., Methods: This study comprised 273 consecutive patients who underwent elective stent implantation. They were divided into two groups: estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m(2) and eGFR ≥60 mL/min/1.73m(2). Peri-procedural TnT levels higher than three times the normal limit were defined as peri-procedural myocardial injury., Results: Patients with eGFR <60 mL/min/1.73m(2) showed a higher incidence of peri-procedural myocardial injury compared to patients with eGFR ≥60 mL/min/1.73m(2) (4.3 versus 20.9%, P < 0.0001). Even after a multivariate adjustment, the eGFR level predicted peri-procedural myocardial injury [odds ratio 0.92, 95% confidence interval (CI): 0.89-0.95, P < 0.0001]. Total stent length was also an independent predictor of peri-procedural myocardial injury (odds ratio 1.09, 95% CI: 1.02-1.16, P = 0.009). Using a receiver-operating curve analysis, eGFR level of 62.1 mL/min/1.73m(2) (sensitivity 93.3%, specificity 57.2%) was the best value (area under the curve = 0.803) to maximize the power of eGFR levels in predicting peri-procedural myocardial injury., Conclusions: Patients with eGFR <60 mL/min/1.73m(2) were strongly associated with peri-procedural myocardial injury after elective stent implantation. Therefore, eGFR may be a simple and convenient predictor of peri-procedural myocardial injury.

Background/aims: Although contrast-induced acute kidney injury (CIAKI) is a major complication associated with angiography, the prophylaxis is not well established. Use of a low dose of carperitide for preventing CIAKI remains controversial. We examined the protective effect of carperitide on CIAKI after coronary angiography with a small contrast volume in chronic kidney disease (CKD) patients with coronary artery disease., Methods: We randomly assigned 112 consecutive patients to a carperitide or a control group. The contrast volume was kept under 150 ml. The primary endpoint was the incidence of CIAKI defined by a serum creatinine of ≥25% or a serum creatinine of ≥0.5 mg/dl from baseline within 48 h. The secondary endpoint was a change in renal function at 1 week after the procedure., Results: The baseline characteristics and contrast volumes (carperitide group: 67.4 ± 38.2 ml vs. control group: 64.8 ± 20.5 ml, p = 0.661) were comparable in the two groups. The incidence of CIAKI was similar in the two groups (carperitide group: 8.5% vs. control group: 5.7%, p = 0.564). A multivariate analysis revealed that a hypotension ≥20 mm Hg was a significant predictor of developing CIAKI in the carperitide group (p = 0.015). The incidence of CIAKI in the carperitide group without hypotension was rare, but not significantly different (carperitide group: 2.4% vs. control group: 5.7%, p = 0.432)., Conclusions: This study indicated that the use of a small contrast volume suppressed the incidence of CIAKI and that carperitide had no prophylactic effect against CIAKI. Our results also revealed the impact of hypotension on the development of CIAKI in the carperitide group.

Background: Percutaneous coronary intervention (PCI) with drug-eluting stent (DES) is widely performed in patients with coronary artery disease, but the high restenosis rate remains a major clinical problem after implantation of DES in patients on hemodialysis (HD). Until now, there are limited reports regarding the long-term clinical outcome after implantation of DES in this patient population., Methods and Results: We compared bare metal stent (BMS) and DES for long-term clinical outcomes, such as target lesion revascularization (TLR), in HD patients undergoing PCI. BMS and DES were implanted in 204 and 301 patients, respectively. Baseline and lesion characteristics were comparable between the 2 groups. By Kaplan-Meier analysis, event rates of major adverse cardiac events for 6 years were significantly lower in the DES group than in the BMS group (42.5% vs. 58.0%, P=0.036). Although there were no significant differences in TLR rates between patients treated with DES and those with BMS at 1 year after PCI (17.8% vs. 21.3%, P=0.32), patients treated with DES had significantly lower rates of TLR compared with those treated with BMS beyond the 1-year follow-up after PCI (16.4% vs. 30.9%, P=0.019)., Conclusions: In patients on HD, implantation of DES might be more effective for preventing TLR in the medium to long follow-up period than BMS, although restenosis after PCI with DES is common in the short term.

Background: Microvascular impairment is associated with a poor prognosis even after successful percutaneous coronary intervention (PCI) in acute myocardial infarction. The aim of the present study was to examine the impact of metabolic syndrome (MetS) on various aspects of microvascular function and clinical outcomes., Methods and Results: In 216 consecutive patients with ST-segment elevation myocardial infarction (STEMI) after successful primary PCI, data were collected and analyzed on epicardial coronary flow, ST-segment resolution (STR) on electrocardiography, maximum serum creatine kinase levels, and the incidence of major adverse cardiac events (MACE). The prevalence of MetS was 40.7% (88 patients). Corrected Thrombolysis In Myocardial Infarction frame count was significantly higher in the MetS group than in the non-MetS group (28.1±9.4 vs. 24.7±7.9, P=0.04). STR ≥50% was observed in 51.1% and 69.5%, respectively (P=0.01). Patients with MetS also had higher maximum creatine kinase levels (3,470±2,320IU/L vs. 2,664±1,850IU/L, P=0.01). On logistic regression analysis after adjustment for confounders, MetS was an independent negative predictor of complete STR (odds ratio, 0.49; 95% confidence interval [CI]: 0.25-0.95, P=0.03). On Cox multivariate analysis, MetS was an independent predictor for MACE (hazard ratio, 4.85; 95% CI: 1.28-18.3, P=0.02)., Conclusions: MetS may damage microcirculation after direct PCI in patients with STEMI and lead to poor prognosis.

Background: Vascular endothelial growth factor (VEGF) is induced by myocardial ischemia and is thought to facilitate cardiovascular repair after acute myocardial infarction (AMI). However, the association between the plasma VEGF levels and clinical outcome in AMI patients is unclear., Methods and Results: We evaluated 879 AMI patients undergoing successful primary revascularization within 24h of symptom onset. The patients were classified into 3 groups according to tertiles of plasma VEGF levels at 7 days after the onset of AMI. Major adverse cardiovascular and cerebrovascular events (MACCE), defined as cardiac death, recurrent acute coronary syndrome, hospital readmission for heart failure, or stroke, were assessed during the 6-month follow-up period. The incidence of MACCE was the least frequent in the middle tertile. Compared to the middle tertile, patients in the low tertile were at a significantly higher risk for MACCE even after adjusting for baseline characteristics (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.18-6.06, P=0.019). An absence of statin treatment before onset and a younger age (HR 0.54, 0.87; 95%CI 0.33-0.90, 0.76-0.99; P=0.017, 0.037; respectively) were significantly associated with low VEGF., Conclusions: Low plasma VEGF levels at 7 days after the onset of AMI were associated with a significantly increased risk for MACCE during 6 months of follow-up.

Objective: Eicosapentaenoic acid (EPA) of the omega-3 polyunsaturated fatty acids (ω-3 PUFA) family plays important roles in the prevention of cardiovascular disease (CVD), while, arachidonic acid (AA) of the ω-6 PUFA family promotes inflammatory and prothrombotic influences. The complexity of coronary lesions represents the vulnerability of patients. The aim of this study was to investigate the association between the plasma EPA/AA ratio and the prevalence of complex coronary lesion morphology., Methods: This study consisted of 206 consecutive patients with stable angina pectoris (sAP). Each coronary lesion was determined either as complex or simple based on angiographic findings. To examine the plasma fatty acid level, blood samples were obtained. Patients were divided into three groups according to the obtained plasma EPA/AA ratio: the highest tertile, n=67, the 2nd tertile, n=70, or the lowest tertile, n=69., Results: A higher incidence of complex coronary lesion was obtained from patients with a lower plasma EPA/AA ratio [43 (62%) vs. 31 (44%) vs. 25 (37%), p=0.011]. High-sensitivity CRP levels and a low plasma EPA/AA ratio could independently predict the prevalence of complex coronary lesions on multivariate logistic regression analysis [odds ratio 1.83 (95%CI 1.03-3.25), p=0.038 and odds ratio 2.10 (95%CI 1.11-3.94), p=0.02)]., Conclusion: In patients with sAP, a low plasma EPA/AA ratio was significantly associated with a high prevalence of complex coronary lesions.

Background: Oxidized low-density lipoprotein (LDL) cholesterol is a sensitive lipid marker for predicting atherosclerosis. Ezetimibe and statins are reported to decrease both LDL cholesterol and oxidized LDL cholesterol. This prospective randomized open-label crossover study compared combination therapy with atorvastatin plus ezetimibe versus high-dose atorvastatin monotherapy. Changes in serum lipids, including malondialdehyde-modified LDL (MDA-LDL) as a representative form of oxidized LDL cholesterol, and glucose metabolism were assessed., Methods and Results: The subjects were 39 Japanese patients with coronary artery disease and type 2 diabetes or impaired glucose tolerance who were taking 10 mg/day of atorvastatin (30 men and 9 women with a mean age of 67.8 years). They were randomized to a group that first received add-on ezetimibe (10 mg/day) or a group that first received atorvastatin monotherapy at a higher dose of 20 mg/day. Both treatments were given for 12 weeks each in a crossover fashion. Add-on ezetimibe significantly decreased MDA-LDL (109.0 ± 31.9 mg/dl to 87.7 ± 29.4 mg/dl, p=0.0009), while up-titration of atorvastatin did not. The decrease with add-on ezetimibe was significantly greater than with up-titration of atorvastatin (p=0.0006). Total cholesterol and LDL cholesterol were significantly decreased by both treatments, but the percent reduction with add-on ezetimibe was significantly greater (p<0.05). High-density lipoprotein cholesterol was significantly increased by both treatments and there was no significant difference between them. The apolipoprotein B/apolipoprotein A-I ratio and remnant-like particle cholesterol were only significantly decreased by add-on ezetimibe. Both treatments caused similar elevation of hemoglobin A(1c)., Conclusion: In Japanese patients with type 2 diabetes or impaired glucose tolerance and coronary artery disease, adding ezetimibe (10 mg/day) to atorvastatin (10 mg/day) significantly improved the lipid profile compared with atorvastatin monotherapy at 20 mg/day., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Even in the drug-eluting stent era, adverse cardiac events, including restenosis after percutaneous coronary intervention (PCI), have been more frequently seen in patients on hemodialysis (HD) than in non-HD patients. The objective of this study was to compare the sirolimus-eluting stent (SES) and everolimus-eluting stent (EES) for prevention of adverse cardiac events, including restenosis, in HD patients., Methods and Results: A total of 100 consecutive patients on HD who underwent PCI were enrolled and randomly assigned to receive SES or EES. Although there was no difference between the 2 groups in baseline patient and lesion characteristics, the angiographic restenosis rate at 8-month follow-up was 21.2% in the SES group and 8.7% in the EES group (P = 0.041). Significant differences were also seen in % diameter stenosis (%DS), minimal lumen diameter, and late lumen loss at 8-month follow-up (P = 0.0024, P = 0.0040, and P = 0.033, respectively). During the 1-year follow-up, major adverse cardiac events occurred in 11 (22.0%) patients in the SES group and in 5 (10.0%) patients in the EES group (P = 0.10)., Conclusions: The use of EES was as safe as that of SES. Moreover, EES significantly prevented restenosis in patients on maintenance HD compared with SES.

Background: A high low-density lipoprotein cholesterol (LDL-C) to a high-density lipoprotein cholesterol (HDL-C) ratio is associated with cardiac events, while the left main coronary artery (LMCA) is considered to be an important target of atherosclerotic plaque accumulation. This aim of the present study was to investigate the relationship between a LDL-C/HDL-C ratio and the characteristics of tissue components of LMCA plaque., Methods and Results: One-hundred-twenty consecutive patients with stable angina pectoris who received chronic statin treatment underwent percutaneous coronary intervention for the left coronary artery. We prospectively performed integrated backscatter (IB) intravascular ultrasound (IVUS) to their LMCAs and evaluated the tissue characteristics. According to the median value of their LDL-C/HDL-C ratios (2.4), they were divided into 2 groups [high LDL-C/HDL-C ratio (>2.4) (n=60) or low LDL-C/HDL-C ratio (≤ 2.4) (n=60)]. There was no significant difference in the data analyzed using conventional IVUS between the 2 groups. In the IB-IVUS analysis, patients with a high LDL-C/HDL-C ratio had a larger lipid volume and a smaller fibrous volume compared to patients with a low LDL-C/HDL-C ratio (52 ± 10% vs. 48 ± 10%, P=0.014 and 45 ± 9% vs. 50 ± 10%, P=0.010)., Conclusions: A high LDL-C/HDL-C ratio was associated with a high percentage of lipid volume and a low percentage of fibrous volume in LMCA lesions. Our findings might well suggest the increased risk of cardiovascular events in patients with a high LDL-C/HDL-C ratio.