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Tsujita K.,Kumamoto University | Sugiyama S.,Jinnouchi Hospital | Sumida H.,Kumamoto Central Hospital | Shimomura H.,Fukuoka Tokushukai Medical Center | And 23 more authors.
Journal of the American College of Cardiology | Year: 2015

Background Despite standard statin therapy, a majority of patients retain a high "residual risk" of cardiovascular events. Objectives The aim of this study was to evaluate the effects of ezetimibe plus atorvastatin versus atorvastatin monotherapy on the lipid profile and coronary atherosclerosis in Japanese patients who underwent percutaneous coronary intervention (PCI). Methods This trial was a prospective, randomized, controlled, multicenter study. Eligible patients who underwent PCI were randomly assigned to atorvastatin alone or atorvastatin plus ezetimibe (10 mg) daily. Atorvastatin was uptitrated with a treatment goal of low-density lipoprotein cholesterol (LDL-C) <70 mg/dl. Serial volumetric intravascular ultrasound was performed at baseline and again at 9 to 12 months to quantify the coronary plaque response in 202 patients. Results The combination of atorvastatin/ezetimibe resulted in lower levels of LDL-C than atorvastatin monotherapy (63.2 ± 16.3 mg/dl vs. 73.3 ± 20.3 mg/dl; p < 0.001). For the absolute change in percent atheroma volume (PAV), the mean difference between the 2 groups (-1.538%; 95% confidence interval [CI]: -3.079% to 0.003%) did not exceed the pre-defined noninferiority margin of 3%, but the absolute change in PAV did show superiority for the dual lipid-lowering strategy (-1.4%; 95% CI: -3.4% to -0.1% vs. -0.3%; 95% CI: -1.9% to 0.9% with atorvastatin alone; p = 0.001). For PAV, a significantly greater percentage of patients who received atorvastatin/ezetimibe showed coronary plaque regression (78% vs. 58%; p = 0.004). Both strategies had acceptable side effect profiles, with a low incidence of laboratory abnormalities and cardiovascular events. Conclusions Compared with standard statin monotherapy, the combination of statin plus ezetimibe showed greater coronary plaque regression, which might be attributed to cholesterol absorption inhibition-induced aggressive lipid lowering. (Plaque Regression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound [PRECISE-IVUS]; NCT01043380) © 2015 American College of Cardiology Foundation.


PubMed | National Hospital Organization Kumamoto Medical Center, Red Cross, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto University and 13 more.
Type: Journal Article | Journal: European journal of preventive cardiology | Year: 2016

The IMPROVE-IT trial showed that the clinical benefit of statin/ezetimibe combination appeared to be pronounced in patients with prior statin therapy. We hypothesized that the antiatherosclerotic effect of atorvastatin/ezetimibe combination was pronounced in patients with statin pretreatment.In the prospective, randomized, controlled, multicenter PRECISE-IVUS trial, 246 patients undergoing intravascular ultrasound-guided percutaneous coronary intervention were randomized to atorvastatin/ezetimibe combination or atorvastatin alone. The dosage of atorvastatin was uptitrated with a treatment goal of lowering low-density lipoprotein cholesterol to below 70mg/dl in both groups. Serial volumetric intravascular ultrasound was performed at baseline and 9-12 month follow-up to quantify the coronary plaque response in 202 patients. We compared the intravascular ultrasound endpoints in all subjects, stratified by the presence or absence of statin pretreatment.The baseline low-density lipoprotein cholesterol level (100.723.1mg/dl vs. 116.425.9mg/dl, p<0.001) and lathosterol (55 (38 to 87)) g/100mg total cholesterol vs. 97 (57 to 149) g/100mg total cholesterol, p<0.001) was significantly lower, and campesterol/lathosterol ratio (3.9 (2.4 to 7.4) vs. 2.6 (1.5 to 4.1), p<0.001) was significantly increased in patients with statin pretreatment. Contrary to the patients without statin pretreatment (-1.3 (-3.1 to -0.1)% vs. -0.9 (-2.3 to 0.9)%, p=0.12), the atorvastatin/ezetimibe combination showed a significantly stronger reduction in delta percent atheroma volume, compared with atorvastatin alone, in patients with statin pretreatment (-1.8 (-3.6 to -0.3)% vs. -0.1 (-1.6 to 0.8)%, p=0.002).Compensatory increase in cholesterol absorption observed in statin-treated patients might attenuate the inhibitory effects of statins on coronary plaque progression. A low-dose statin/ezetimibe combination might be a promising option in statin-hyporesponder.


Vallejo-Vaz A.J.,St George's, University of London | Kondapally Seshasai S.R.,St George's, University of London | Kurogi K.,Miyazaki Prefectural Nobeoka Hospital | Michishita I.,Yokohama Sakae Kyosai Hospital | And 5 more authors.
Atherosclerosis | Year: 2015

Aims: Whether adverse effect of statins on glycaemic indices is common to all statins remains controversial and as yet data for pitavastatin are limited. We sought to assess the effects of pitavastatin on glycaemia and new-onset diabetes (NOD) in non-diabetic individuals using data from RCT pooled together by means of a meta-analysis. Materials and methods: We searched Medline, Cochrane, Embase and clinical trials registries websites until November-2014 for ≥12-week follow-up placebo or statin-controlled RCT of pitavastatin that included participants without diabetes and reported on fasting blood glucose (FBG), HbA1c or NOD. We additionally sought studies by consulting with Kowa Ph. Ltd. The association of pitavastatin with the outcomes were estimated by random-effects meta-analyses. Heterogeneity was assessed by the I2 statistic and sensitivity and subgroup analyses, and publication bias with funnel plots and Egger and Harbord Tests. Results: 15 studies (approx. 1600 person-years) were included. No significant differences associated with pitavastatin (vs. control) were observed for FBG (MD -0.01 mg/dL [95%CI -0.77, 0.74], I2 = 0%), HbA1c (MD -0.03% [95%CI -0.11, 0.05], I2 = 43%) or NOD (RR 0.70 [95%CI 0.30, 1.61]; RD 0.0 [95%CI -0.004, 0.003]; I2 = 0%). Sensitivity and subgroup analyses (including type of control [placebo or other statin], pitavastatin dose or follow-up] did not yield significant results. Potential publication bias may occur for NOD. Conclusions: In the present meta-analysis pitavastatin did not adversely affect glucose metabolism or diabetes development compared with placebo or other statins. © 2015 Elsevier Ireland Ltd.


Ishihara A.,Miyazaki Prefectural Nobeoka Hospital | Yamashita Y.,Miyazaki Prefectural Nobeoka Hospital | Takamori H.,Miyazaki Prefectural Nobeoka Hospital | Kuroda N.,Red Cross
Pathology International | Year: 2011

An extremely rare adult example of renal carcinoma with t(6;11)(p21;q12 or q13) is presented here. The tumor of a 45-year-old Japanese male, excised under the diagnosis of renal cell carcinoma, was a well circumscribed 7cm mass with light brown sectioned surfaces. Histologically, it was composed of a major population of large polygonal epithelioid cells in a nested alveolar growth and a subpopulation of smaller cells clustering around hyaline basement membrane material. The former cells possessed ample, clear to eosinophilic granular cytoplasm with well-defined cell borders and the latter was frequently accompanied by psammomatous calcification. These tumor cells exhibited immunoreactivity for melanoma markers, transcription factor EB and cathepsin K, but were not reactive for epithelial markers and transcription factor E3. While pulmonary metastatic foci that were noted preoperatively progressed rapidly following interferon-based therapy, subsequent sunitinib malate yielded a partial response and stabilized the lung metastasis for 6months after surgery. We could trace 20 cases of 6p21 translocation renal carcinoma, among which only four were in individuals older than 40years. Description of a new case like this is important since little is known about the prognosis and treatment of adult patients with this condition. © 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.


Kurogi K.,Kumamoto University | Kurogi K.,Miyazaki Prefectural Nobeoka Hospital | Sugiyama S.,Kumamoto University | Sakamoto K.,Kumamoto University | And 5 more authors.
Journal of Cardiology | Year: 2013

Background: Many large-scale clinical trials have confirmed that statins are effective in reducing low-density lipoprotein cholesterol (LDL-C) level, resulting in reducing cardiovascular events. Recent studies have focused on the effects of statins on high-density lipoprotein cholesterol (HDL-C). Here we compared the effects of two statins on lipid profile and other metabolic parameters. Methods: The study population included 129 patients with stable coronary artery disease, hypercholesterolemia, and hypo-HDL-cholesterolemia (HDL-C < 50 mg/dl). They were randomly allocated to treatment by pitavastatin 2-4. mg/day or atorvastatin 10-20. mg/day and followed-up for 30 months. The primary endpoint was percent changes in HDL-C and adiponectin during the study. The secondary endpoints were percent and absolute changes in markers of glucose metabolism, serum lipids, and apolipoproteins. Results: The effects of 30-month treatment with pitavastatin on HDL-C were significantly greater than those of atorvastatin (%change: pitavastatin: 20.1 ± 25.7%, atorvastatin: 6.3 ± 19.8%, p= 0.01; absolute change: pitavastatin: 7.3 ± 9.1. mg/dl, atorvastatin: 2.3 ± 8.0. mg/dl, p= 0.02). A similar trend was seen with regard to apolipoprotein-AI (ApoAI) (%change: pitavastatin: 20.8 ± 19.3%, atorvastatin: 11.4 ± 17.6%, p= 0.03; absolute change: pitavastatin: 23.1 ± 20.2. mg/dl, atorvastatin: 12.1 ± 19.4. mg/dl, p= 0.02). Treatment with pitavastatin, but not atorvastatin, significantly increased adiponectin levels. Neither statin had a significant effect on hemoglobin A1c. No severe adverse events were registered during the study. Conclusion: Long-term treatment with pitavastatin resulted in significantly greater increases in serum HDL-C and ApoAI levels without adverse effects on glucose metabolism, compared with atorvastatin. © 2013.


PubMed | University of Miyazaki, Miyazaki Prefectural Nichinan Hospital and Miyazaki Prefectural Nobeoka Hospital
Type: Journal Article | Journal: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy | Year: 2016

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in China, Korea and Japan caused by a novel bunyavirus, SFTS virus (SFTSV). Although central nervous system manifestations are common in SFTS patients, the pathogenesis has not been elucidated; and there are few reports of myocardial dysfunction. Here we report an elderly Japanese patient with reversible myocardial dysfunction and encephalopathy. A previously healthy 65-year-old male engaged in forestry got a tick bite and developed fever and fatigue in 3 days. Three days after onset, he presented to a local hospital where the diagnosis of SFTS with hemophagocytotic syndrome was made. The blood test showed leukopenia and thrombocytopenia as well as elevated levels of alanine aminotransferase and aspartate aminotransferase. Marked hemophagocytosis was found on bone marrow smear. Peripheral blood was positive for SFTSV gene by reverse-transcription polymerase chain reaction. On day 7, the patient was transferred to our hospital. We observed disturbance of consciousness, Kernig sign and myoclonus to face and limbs. Decreased blood flow of whole cerebral cortex was detected by single photon emission computed tomography (SPECT). Chest X-ray revealed cardiomegaly and electrocardiography (ECG) showed abnormal T waves. These data suggested acute encephalopathy and myocardial dysfunction. We treated him with corticosteroid and blood transfusion, which resulted in the complete recovery of the above abnormal symptoms and laboratory data including the findings in SPECT and ECG in about a month. This case demonstrated transient myocardial dysfunction and encephalopathy can occur in addition to typical clinical manifestation of SFTS.


We encountered a patient with gastric cancer who achieved long-term quality of life( QOL) by undergoing chemotherapy with weekly administration of paclitaxel and placement of an expandable metallic stent. An 82-year-old man visited our hospital with a complaint of discomfort during swallowing. Upper gastrointestinal endoscopy revealed a type 3 tumor in the cardial part of the posterior wall of the stomach, which was pathologically diagnosed as a well-differentiated adenocarcinoma. Computed tomography scans revealed no lymph node metastasis. Considering the patient was of advanced age and had a pulmonary function disorder, we administered chemotherapy with S-1. However, the patient experienced difficulty in swallowing medication at the start of therapy. Thus, a stent was inserted to continue the administration of chemotherapy with S-1 and cisplatin( CDDP). After completion of 4 courses of chemotherapy with S-1 and CDDP, an increase in the tumor marker level was observed; hence, we initiated chemotherapy with weekly paclitaxel. Currently, the patient is undergoing medical treatment at our outpatient department. Chemotherapy after stent placement for stenosis is considered useful for intensive therapy in high-risk patients such as those of advanced age. Here, we discuss the present case in light of a review of the related literature.


Nakamura K.,Miyazaki Prefectural Nobeoka Hospital
General thoracic and cardiovascular surgery | Year: 2010

This study aimed to compare postoperative complications and the surgical outcome in patients aged <80 years versus octogenarian patients. Another aim was to evaluate the safety and efficacy of early mobilization with early cardiac rehabilitation in octogenarians. A retrospective analysis was performed in 138 consecutive patients (group Y comprised 118 patients <80 years, and group O comprised 20 octogenarians) who had undergone valve surgery at the authors' institution between July 2007 and December 2009. Furthermore, the efficacy of early mobilization with early cardiac rehabilitation and long-term results were analyzed in 40 consecutive octogenarian patients undergoing valve surgery from 2000. The late survival follow-up was 100% complete. Redo cardiac operations were more frequent (O group 15.0% vs. Y group 3.4%, P = 0.011), and the preoperative EuroSCORE was significantly higher in group O than in group Y (group O 16.4 ± 18.3 vs. group Y 7.5 ± 9.1, P = 0.001). The incidence of delirium/confusion and worsening of renal function after surgery was higher in group O. The hospital mortality was 1.7% in group Y and no hospital death in group O (P > 0.99). Early mobilization with early cardiac rehabilitation significantly reduced the incidence of postoperative delirium/confusion and increased the number of patients who could return directly home. The actuarial 5-year survival rate was 77.7% for octogenarians. Although there were more high-risk patients among the octogenarians, valve surgery was a safe, low-risk procedure with excellent long-term results. Early mobilization with early cardiac rehabilitation was significantly effective and safe for postoperative recovery in octogenarians after cardiac valve surgery.

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