基本情報
- 所属
- 自治医科大学 附属病院冠動脈集中治療部 教授
- 学位
- 医学博士(自治医科大学)
- 研究者番号
- 20382898
- J-GLOBAL ID
- 201401043350806180
- researchmap会員ID
- B000238714
- 外部リンク
主要な経歴
3受賞
3論文
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The Journal of thoracic and cardiovascular surgery 157(4) e199-e200 2019年4月
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The Journal of thoracic and cardiovascular surgery 157(3) 1071-1079 2019年3月OBJECTIVE: Sarcopenia, age-related loss of muscle mass, is an objective and comprehensive marker of frailty. We aimed to clarify the influence of sarcopenia on the outcomes after heart valve surgery. METHODS: We retrospectively reviewed 1119 patients who underwent valve surgery via median sternotomy at our institution from June 2009 to December 2013. Patients aged <70 years, urgent/emergent cases, and patients without preoperative computed tomography of the abdomen were excluded. The remaining 428 patients were included in this study. Psoas muscle area, a validated measure of sarcopenia, was measured on preoperative computed tomography. Sarcopenia was defined as the lowest sex-specific quartile in psoas muscle area. The mean follow-up period was 3.4 years. RESULTS: Overall in-hospital mortality did not differ between the sarcopenia and nonsarcopenia patient groups. However, the incidence of stroke and intra-aortic balloon pump/percutaneous cardiopulmonary support use was greater in the sarcopenia group than in the nonsarcopenia group. The patients with sarcopenia had significantly decreased long-term survival and decreased freedom from major adverse cardiac and cerebrovascular events. Multivariable analysis and inverse probability weighting revealed that sarcopenia was an independent predictor for decreased survival (hazard ratio, 2.22; 95% confidence interval, 1.26-3.92; P = .006). CONCLUSIONS: Preoperative sarcopenia defined from the psoas muscle area was associated with long-term outcomes after valve surgery. Thus, the measurement of psoas muscle area can help facilitate more accurate risk scoring in elderly patients.
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Surgery today 49(2) 130-136 2019年2月PURPOSE: To identify the perioperative factors associated with aneurysm size changes after endovascular aortic aneurysm repair (EVAR). METHODS: Between August, 2008 and December, 2014, 187 patients underwent EVAR treatment in our institution. The subjects of this study were 135 of these patients without peripheral artery disease, who were followed up with computed tomography (CT) for 3 years. Significant aneurysm size change was defined as sac size change of more than 5 mm from the baseline. RESULTS: Sac enlargement was identified in 25 patients (18.5%) and sac shrinkage was identified in 59 (43.7%) patients. The factors associated with sac enlargement were postoperative pulse wave velocity (OR: odds ratio 3.80, p = 0.047), prevalence of a type 2 endoleak 1 week after surgery (OR 4.26, p = 0.022), inner diameter (OR 1.10, p = 0.005), and distance from the lower renal artery to the terminal aorta (OR 1.05, p = 0.017). The factors associated with sac shrinkage were prevalence of a type 2 endoleak (OR 0.09, p < 0.001) and preoperative pulse wave velocity (OR 0.32, p = 0.022). The factors independently associated with type 2 endoleak were the use of an Excluder device (OR 3.99, p = 0.002) and the length of the aneurysm (OR 1.02, p = 0.027). CONCLUSION: Inner diameter, treatment length, perioperative pulse wave velocity, and type 2 endoleak were associated with sac size changes after EVAR.
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Circulation journal : official journal of the Japanese Circulation Society 83(2) 285-294 2019年1月25日BACKGROUND: Outcomes of early-onset acute type A aortic dissection (ATAAD) associated with Marfan syndrome (MFS) are known, but not with other etiologies. Methods and Results: ATAAD patients from 2 centers (n=1,001) were divided into 2 groups: age ≤45 years (n=93) and age >45 years (n=908). Although in-hospital death and 10-year survival were similar (12% vs. 7% and 62.6% vs. 67.3%), the 10-year aortic event-free survival differed (50.0% vs. 80.2%; P<0.01). ATAAD patients from 3 centers (n=132), all aged ≤45 years, were divided into 5 groups: lone hypertension (HTN, n=71), MFS (n=23), non-syndromic familial thoracic aortic aneurysm and dissection (NS-FTAAD, n=16), bicuspid aortic valve (BAV, n=11), and no known etiologic factor (n=11). The incidence of severe aortic insufficiency varied between groups (HTN: 11%, MFS: 39%, NS-FTAAD: 38%, BAV: 55%, no known factor: 46%; P<0.01), whereas in-hospital death did not (14%, 22%, 0%, 0%, and 9%; P=0.061). The 10-year survival was 52.2%, 64.7%, 83.6%, 100%, and 90.9%, respectively, and 10-year aortic event-free survival was 55.6%, 36.3%, 77.5%, 90.0%, and 30.0%. Median descending aorta growth (mm/year) was 1.1 (0.1-3.4), 2.3 (0.3-5.3), 1.9 (1.3-2.7), 0.9 (-0.1-2.0), and 1.0 (-0.2-2.9) (P=0.15), respectively. CONCLUSIONS: Late aortic events are common in young ATAAD patients. Known etiologic factors, though not BAV, negatively influence late outcomes in these patients.
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Annals of vascular diseases 11(3) 298-305 2018年9月25日Objective: To investigate the predictors of acute kidney injury (AKI) following surgery for abdominal aortic aneurysm. Materials and Methods: Subjects were 642 non-hemodialysis patients (open aortic repair [OAR] group, n=453; endovascular aortic repair [EVAR] group, n=189) who underwent elective surgery between 2009 and 2015. AKI was assessed according to the Kidney Disease Improving Global Outcomes criteria. In-hospital mortality and incidence of AKI were compared between the OAR and EVAR groups. The effect of AKI on outcomes and predictors of AKI were examined in both groups. Results: In-hospital mortalities were 0.7% (3/453) in the OAR group and 0.5% (1/189) in the EVAR group. The incidence of AKI increased in the OAR group (14.1% vs. 3.7%, P<0.01). In the OAR group, in-hospital mortality (0% vs. 4.7%, P<0.01) increased in patients with AKI. In the OAR group, hemoglobin level <10 g/dL, estimated glomerular filtration rate <60 mL/min/1.73 m2, operation time >300 min, history of ischemic heart disease, and amount of bleeding >1,000 mL were predictors of AKI. In the EVAR group, amount of transfusion>1,000 mL was a predictor of AKI, but AKI was not found to worsen outcomes. Conclusion: AKI affected outcomes of OAR. Knowledge of predictors may optimize perioperative care.
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Journal of the American Heart Association 7(14) 2018年7月9日BACKGROUND: Clinical characteristics and treatment outcomes of acute type A aortic dissection with D-dimer elevation have not been clarified. METHODS AND RESULTS: D-dimer was measured preoperatively within 24 hours of symptom onset in 262 patients with acute type A aortic dissection. The median (and interquartile range) admission D-dimer concentration in our total patient group was 26.7 (8.3-85.9) μg/mL. Median (interquartile range) D-dimer concentrations were 5.0 (2.6-18.0) μg/mL for complete false lumen thrombosis (n=33), 60.9 (19.4-160.4) μg/mL for partial thrombosis (n=81), 26.5 (10.0-70.6) μg/mL for a patent false lumen (n=131), and 8.7 (3.2-26.9) μg/mL for ulcerlike projection (n=17) (P<0.01). With a D-dimer concentration of ≤8.3 μg/mL representing the lower quartile, we then investigated predictors of a low D-dimer level. Multivariate analysis showed dissection limited to the ascending aorta (P<0.01; odds ratio, 9.81) or descending aorta (P<0.01; odds ratio, 7.68), a completely thrombosed false lumen (P<0.01; odds ratio, 4.02), and absence of brain ischemia (P=0.013; odds ratio, 4.74) to be predictors of the lower D-dimer concentration. Compared with patients with a low D-dimer concentration (≤8.3 μg/mL, n=66), patients with a D-dimer concentration >8.3 μg/mL (n=196) had a reduced preoperative platelet count and increased operation time and transfusion volume. In-hospital mortality was elevated in this group (1.5% versus 11.2%; P=0.031), although 7-year survival did not differ for hospital survivors (lower versus higher, 93.1% versus 79.1%; P=0.21). CONCLUSIONS: D-dimer concentrations are strongly influenced by the extent of dissection and false lumen status. Operative risks are increased in patients with a relatively high D-dimer concentration.
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The heart surgery forum 21(4) E247-E249 2018年6月14日Giant coronary artery aneurysm (GCAA) combined with coronary artery fistula to the pulmonary artery (PA) is rare. A 79-year-old man was accidentally discovered with GCAA. He was operated on by use of aneurysmorrhaphy, and closure of the fistulae was performed. Because ischemic changes appeared, coronary artery bypass grafting was done. The postoperative course was uneventful, and the patient was discharged on postoperative day 14. We report here a case of GCAA with a size of 66 × 52 mm in diameter associated with a fistula formation into the PA. It is one of the largest sizes of GCAA that has occurred after fistula formation.
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Annals of Thoracic Surgery 105(1) 137-143 2018年1月1日 査読有りBackground Although surgical outcomes of acute type A aortic dissection (ATAAD) have improved, it is still a high-risk procedure for octogenarians. This study analyzed early and late outcomes of surgical repair of ATAAD among octogenarians. Methods From 1990 through 2016, 1,260 consecutive patients with ATAAD were emergently admitted to Jichi Medical University Hospitals. Of them, 1,026 patients who underwent emergency surgery for ATAAD within 48 hours of symptom onset were included in this retrospective study. Of these, 112 were aged 80 years or more (mean, 83.1 ± 2.7) and formed the octogenarian group and 914 were aged less than 80 years (mean, 62.0 ± 11.4) and formed the control group. Early and late outcomes were compared. Results The inhospital mortality rate was 6.3% for the octogenarian group and 7.4% for the control group (p = 0.85). No significant difference was observed in the causes of hospital death. Although the overall postoperative complication rate was not different (24.1% versus 23.0%), pneumonia was more frequent among octogenarians (p = 0.03). Multivariate analysis of hospital mortality did not indicate age 80 years or more as a risk factor. Overall postoperative survival for the octogenarian group was 84.6%, 70.5%, and 57.1% at 1, 3, and 5 years, respectively. For the control group, the rates were 89.1%, 85.6%, and 82.1%, respectively. Pneumonia and decrepitude were the major causes of remote death for the octogenarian group. Conclusions No significant difference in the hospital mortality rate or the complication rate was observed between the groups. Emergency surgery for ATAAD in octogenarians could be performed with the same low risk observed for younger patients.
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ANNALS OF THORACIC SURGERY 104(6) 1915-1922 2017年12月 査読有りBackground. The endovascular stent graft is a novel therapeutic technique that is used in the treatment of aortic aneurysms. However, the aortic arch is a still an area that requires endovascular repair. Since 2008, the authors have treated aortic arch aneurysms (AAA) in patients without an extraanatomical bypass using a fenestrated stent graft (FSG). This study aimed to evaluate the early outcomes of FSG treatment. Methods. The authors retrospectively investigated the early outcomes of 54 AAA cases that were performed in their department from January 2008 to May 2016. The early results were analyzed retrospectively. Results. The primary technical success rate was 100%. There were 2 operative deaths due to shower embolism and respiratory failure (2 of 54, 3.7%). Two patients suffered central nervous system injury (2 of 54, 3.7%) without remaining sequelae. At a mean follow-up period of 41.4 months, the survival rate was 75.0% and there were no aortic-related deaths. On follow-up, secondary intervention was necessary in 3 cases. The rate of freedom from secondary reintervention was 92.5%. Conclusions. Although further observation and prospective studies involving larger numbers of patients will be needed to validate this process, the outcomes of FSG treatment and our procedures were acceptable. This procedure has the potential to expand the indications for treatment in patients with AAA that are deemed to be suitable for this treatment. (C) 2017 by The Society of Thoracic Surgeons
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EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 52(4) 810-817 2017年10月 査読有りThe mechanisms underlying aortic dissection remain to be fully elucidated. We aimed to identify key molecules driving dissection through gene expression profiling achieved by microarray analysis and subsequent in vitro experiments using human aortic endothelial cells (HAECs) and aortic vascular smooth muscle cells (AoSMCs). Total RNA, including microRNA (miRNA), was isolated from the intima-media layer of dissected ascending aorta obtained intraoperatively from acute type A aortic dissection (ATAAD) patients without familial thoracic aortic disease (n = 8) and that of non-dissected ascending aorta obtained from transplant donors (n = 9). Gene expression profiling was performed with mRNA and miRNA microarrays, and results were confirmed by quantitative polymerase chain reaction (qPCR). Target genes and miRNA were identified by gene ontology analysis and a literature search. To reproduce the in silico results, HAECs and AoSMCs were stimulated in vitro by upstream cytokines, and expression of target genes was assessed by qPCR. Microarray analysis revealed 1536 genes (3.6%, 1536/42 545 probes) and 41 miRNAs (3.0%, 41/1368 probes) that were differentially expressed in the ATAAD group (versus donor group). The top 15 related pathways included regulation of inflammatory response, growth factor activity and extracellular matrix. Gene ontology analysis identified JAK2 (regulation of inflammatory response), PDGFA, TGFB1, VEGFA (growth factor activity) and TIMP3, TIMP4, SERPINE1 (extracellular matrix) as the target genes and miR-21-5p, a TIMP3 repressor, as target miRNA that interacts with the target genes. Validation qPCR confirmed the altered expression of all 7 target genes and miR-21-5p in dissected aorta specimens (all genes, P < 0.05). Ingenuity pathway analysis showed TNF-alpha and TGF-beta to be upstream cytokines for the target genes. In vitro experiments showed these cytokines inhibit TIMP3 expression (P < 0.05) and enhance VEGFA expression (P < 0.01) in AoSMCs but not HAECs. miR-21-5p expression increases in AoSMCs under TNF-alpha and TGF-beta stimulation (fold change: 1.36; P = 0.011). Results of our novel approach, integrating in vitro assessment into gene expression profiling, implicated chronic inflammation characterized by MMP-TIMP dysregulation, increased VEGFA expression, and TGF-beta signalling in the development of dissection. Further investigation may reveal novel diagnostic biomarkers and uncover the mechanism(s) underlying ATAAD.
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General Thoracic and Cardiovascular Surgery 65(9) 506-511 2017年9月1日 査読有りPurpose: Pulse wave velocity (PWV), which measures vascular stiffness, is a powerful predictor of cardiovascular event. Treatment of aneurysms with endovascular prosthesis has been reported to increase PWV. The purpose of this study was to evaluate whether an endoskeleton stent graft design has less effect on PWV than the exoskeleton stent graft design. Methods: Between July 2008 and September 2016, 74 patients underwent endovascular treatment of aortic arch aneurysm in our institution. PWV before and after surgery were compared between those who underwent treatment with Najuta, an endoskeleton stent graft (n = 51), and those treated with other commercially available exoskeleton stent grafts (n = 23). Results: Preoperative PWV (endoskeleton: 2004 ± 379.2 cm/s vs. exoskeleton: 2083 ± 454.5 cm/s, p = 0.47) was similar between the two groups. Factors that were associated with preoperative PWV were age (r = 0.37, 95% CI 0.15–0.56, p = 0.002) and mean arterial pressure (r = 0.53, 95% CI 0.34–0.68, p < 0.001). There was a significant increase in PWV in patients treated by exoskeleton stent grafts (before: 2083 ± 454.5 cm/s vs. after: 2305 ± 479.7 cm/s, p = 0.023) while endoskeleton stent graft showed no change in PWV (before: 2003 ± 379.2 vs. after: 2010 ± 521.1, p = 0.56). In a multivariate analysis, mean arterial pressure (coef 17.5, 95% CI 6.48–28.59, p = 0.002) and exoskeleton stent graft (coef 359.4, 95% CI 89.36–629.43, p = 0.010) were independently associated with PWV after surgery. Conclusions: Physiological changes after endovascular treatment should be considered including effect on vascular stiffness. Endoskeleton stent graft may provide aneurysm repair with minimum effect in PWV after surgery.
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SURGERY TODAY 47(9) 1163-1171 2017年9月 査読有りPurpose To investigate the clinical characteristics of acute type A aortic dissection (ATAAD) occurring during a sporting activity. Methods The subjects of this study were 615 patients who underwent surgery for ATAAD between 1990 and 2015. The patients were divided into two groups according to whether the ATAAD was associated with a sporting activity (sports group: n = 25, mean age 62.3 years; non-sports group: n = 590, mean age 63.7 years). Specific activity was assessed in the sports group, and the characteristics and outcomes were compared between the groups. Results The sports group accounted for 5% of the patients with daytime onset ATAAD (25/479). The most common sport was golf (n = 8), followed by swimming (n = 4), cycling (n = 4), and weight lifting (n = 3). The average diameter of the ascending aorta on preoperative computed tomography was 4.8 cm. The dissection characteristics of the sports group included DeBakey type I (n = 23, 92%) and malperfusion (n = 9, 36%), which were similar to those of the non-sports group. The 30-day mortality rates were 16% (4/25) for the sports group and 8% (49/590) for the non-sports group (P = 0.33). Conclusion The most common sport associated with ATAAD was golf, followed by swimming cycling, and weight lifting. The findings of this study reinforce that sports-related aortic dissection is not a unique clinical condition of young syndromic patients, but can occur in all age groups.
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Annals of vascular diseases 10(2) 119-124 2017年6月25日Objective: We investigated the characteristics and surgical outcomes of abdominal aortic aneurysm (AAA), which typically occurs in elderly persons, in Japanese patients aged 50 years or younger. Materials and Methods: Clinical records of 999 patients who underwent open or endovascular repair for AAA at our hospital between 2007 and 2015 were reviewed to identify the clinical characteristics and surgical outcomes of young patients with AAA. The cohort included 14 patients aged 50 years or younger (mean, 40.4 years; young group) and 985 patients aged older than 50 years (mean, 72.8 years; old group). Results: Marfan syndrome, prior aortic dissection, and a history of aortic surgery were more prevalent in the young group, and 50% of the patients in the young group had dissecting aneurysms. All patients in the young group underwent open repair. Overall in-hospital mortality rates were 7.1% (1/14) and 1.9% (19/985) in the young and old groups, respectively (P=0.67). Seven-year survival and aortic event-free survival rates in the young group were 82.5%±11.5%, and 71.2±14.5%, respectively. Conclusion: AAA in patients aged 50 years or younger tended to be associated with Marfan syndrome, a history of aortic surgery, and prior aortic dissection. Early outcomes of AAA among young patients are acceptable, but close postoperative monitoring is important.
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INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY 24(6) 944-950 2017年6月 査読有りOBJECTIVES: With the introduction of endovascular stent graft technology, a variety of surgical options are available for patients with aortic aneurysms. We sought to evaluate early-term and mid-term outcomes of patients undergoing endovascular and open surgical repair for non-dissected aortic arch aneurysm. METHODS: Overall, 200 patients underwent treatment for isolated non-dissected aortic arch aneurysm between January 2008 and February 2016: 133 patients had open surgery and 67, endovascular repair. Early-term and mid-term outcomes were compared. RESULTS: Seventy percent (n = 47) needing endovascular repair underwent fenestrated stent graft and 30% (n = 20) underwent the debranched technique. Patients in the open surgery group were younger (71 vs 75 years, P < 0.001) and had a lower prevalence of ischaemic heart disease (11% vs 35%, P < 0.001). Intensive care unit stay (1 vs 3 days, P < 0.001), hospital stay (11 vs 17 days, P < 0.001) and surgical time (208 vs 390 min, P < 0.001) were lower in the endovascular repair group than in the open surgery group. There were 3 in-hospital deaths each in the open surgery and endovascular groups (2% vs 5%, respectively, P = 0.40). Mid-term survival (P < 0.001) and freedom from reintervention (P = 0.009) were better in the open surgery than in the endovascular repair group. No aneurysm-related deaths were observed. The propensity-matched comparison (n = 58) demonstrated that survival was better in the open surgery group (P = 0.011); no significant difference was seen in the reintervention rate (P = 0.28). CONCLUSIONS: Close follow-up for re-intervention may reduce the risk for aneurysm-related deaths and provide acceptable outcomes in patients undergoing endovascular repair.
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INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY 24(5) 670-676 2017年5月 査読有りOBJECTIVES: Aortic valve bypass (AVB) (apico-aortic conduit) remains an effective surgical alternative for patients in whom surgical aortic valve replacement or transcatheter aortic valve implantation is not feasible. However, specific complications include thrombus formation, possibly caused by stagnation arising from flow competition between the antegrade and retrograde flow, but this has not been fully investigated. The aim of this study was to analyse flow characteristics after AVB and to elucidate mechanisms of intra-aortic thrombus using computational fluid dynamics (CFD). METHODS: Flow simulation was performed on data obtained from a 73-year-old postoperative AVB patient. Three-dimensional cine phase-contrast magnetic resonance imaging at 3 Tesla was used to acquire flow data and to set up the simulation. The vascular geometry was reconstructed using computed tomography angiograms. Flow simulations were implemented at various ratios of the flow rate between the ascending aorta and the graft. Results were visualized by streamline and particle tracing. RESULTS: CFD demonstrated stagnation in the ascending aorta-arch when retrograde flow was dominant, indicating that the risk of thrombus formation exists in the ascending arch in cases with severe aortic stenosis and/or poor left ventricular function. Meanwhile, stagnation was observed in the proximal descending aorta when the antegrade and retrograde flow were equivalent, suggesting that the descending aorta is critical when aortic stenosis is not severe. CONCLUSIONS: Flow stagnation in the aorta which may cause thrombus was observed when retrograde flow was dominant and antegrade/retrograde flows were equivalent. Our results suggest that anticoagulants might be recommended even in patients who receive biological valves.
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JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 153(4) S52-+ 2017年4月 査読有りObjective: Hemodynamics related to eccentric blood flow may factor into the development of bicuspid aortic valve aortopathy. We investigated wall shear stress distribution by means of magnetic resonance imaging-based computational fluid dynamics in patients with a bicuspid aortic valve. Methods: Included were 12 patients with a bicuspid aortic valve (aortic stenosis, n = 11; root enlargement, n = 1). Three patients with a normal tricuspid aortic valve (arch aneurysm, n = 1; descending aortic aneurysm, n = 2) were included for comparison. The thoracic aorta geometry was reconstructed by means of 3-dimensional computed tomography angiography, and the bicuspid aortic valve orifice was modeled. Flow rates at the sinotubular junction and 3 aortic branches were measured at various time points by cine phase-contrast magnetic resonance imaging to define boundary conditions for computational fluid dynamics, and the flow was simulated. Results: Bicuspid aortic valve cusp configurations were type 0 lateral (n = 4), type 0 anterior-posterior (n = 2), type 1 L-R (n = 4), and type 1 R-N (n = 2). Abnormal aortic helical flow was seen in the ascending aorta and transverse arch in all patients with bicuspid aortic valves and was right handed in 11 patients (91%). No such flow was seen in the patients with tricuspid aortic valves. The patients with bicuspid aortic valves were likely to have jet flow/wall impingement against the greater curvature of the proximal ascending aorta, resulting in remarkably increased wall shear stress around the impingement area. Conclusions: Computational fluid dynamics simulation is useful for precise evaluation of hemodynamics related to bicuspid aortic valve aortopathy. Such evaluation will advance our understanding of the disease pathophysiology and may facilitate molecular biological investigation.
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Annals of Vascular Diseases 10(3) 242-245 2017年<p>A 76-year-old woman with a 2-week history of dyspnea on exertion was admitted to our hospital. A computed tomography scan showed a 70-mm diameter aortic arch aneurysm containing a large thrombus that was compressing the pulmonary artery. Echocardiography showed severe pulmonary stenosis and no shunt flow. Operative findings revealed an aneurysmal thrombus protruding into the lumen of the pulmonary artery through a foramen. A ductus arteriosus aneurysm was diagnosed. After the thrombus removal, arch replacement and ductus closure with a prosthetic patch were performed. Histological examination showed that the thrombus had no vascular components. The patient's symptoms were relieved, and she was discharged.</p>
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Long-Term Survival in Patients With Acute Kidney Injury After Acute Type A Aortic Dissection Repair.The Annals of thoracic surgery 102(6) 2003-2009 2016年12月 査読有り
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General Thoracic and Cardiovascular Surgery 64(9) 552-557 2016年9月1日 査読有りRight-sided aortic arch (RAA) is a rare congenital disorder. We describe herein two cases of thoracic aortic aneurysm with a right aortic arch and right-sided descending aorta treated with thoracic endovascular aortic repair (TEVAR). In one case, a 70-year-old man with Edwards type 1 RAA underwent TEVAR using a Relay stent-graft (Bolton Medical, Barcelona, Spain). In another case, a 72-year-old woman with Edwards type 3 RAA underwent TEVAR using a Kawasumi Najuta stent-graft (Kawasumi Laboratories, Inc., Tokyo, Japan) with the “buffalo horn chimney technique”, our original method for left subclavian artery flow preservation. The postoperative courses were uneventful. Postoperative computed tomography showed complete exclusion of the aneurysm without endoleakage. Compared to conventional open surgical repair, TEVAR is challenging in patients with a RAA and right-sided descending aorta. However, our results showed that TEVAR might be feasible and a treatment option even in a patient with a RAA and right-sided descending aorta.
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EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 50(3) 520-527 2016年9月 査読有りOBJECTIVES: Use of the left internal mammary artery in patients with diabetes mellitus and multivessel coronary artery disease is known to improve survival after coronary artery bypass grafting (CABG); however, the survival benefit of multiple arterial grafts (MAGs) in diabetic patients is debated. We investigated the efficacy of CABG performed with MAGs in diabetic patients. METHODS: The overall patient group comprised 2618 consecutive patients who underwent isolated CABG at our hospital between 1990 and 2014. Perioperative characteristics, in-hospital outcomes and long-term outcomes were compared between diabetic (n = 1110) and non-diabetic patients (n = 1508). The long-term outcomes of diabetic and non-diabetic patients were analysed between those who received a single arterial graft (SAG) and those who received MAGs. Both full unmatched patient population and propensity-matched patient population analyses (diabetic cohort = 431 pairs, non-diabetic cohort = 577 pairs) were performed. RESULTS: Preoperative comorbidities were much more common in the diabetic patients than in the non-diabetic patients; however, comorbidities were not associated with in-hospital outcomes (diabetes versus non-diabetes group, in-hospital mortality: 2.2 vs 1.5%; deep sternal wound infection: 2.2 vs 1.8%, P > 0.05). Although survival and freedom from major cardiac and cerebrovascular events (MACCEs) at 15 years were lower in the diabetes group than in the non-diabetes group (survival: 48.6 vs 55.0%, P = 0.019; MACCE-free survival: 40.8 vs 46.1%, P = 0.02), cardiac death-free survival at 15 years was similar (81.7 vs 83.9%, P = 0.24). Overall, 12-year survival was higher in both diabetic and non-diabetic patients treated with MAGs than in those treated with an SAG (64.9 vs 56.8%, P = 0.006, and 71.9 vs 60.5%, P < 0.001). Propensity-matched patient cohort analysis revealed improved 12-year survival with MAGs versus SAG in both the diabetes group (64.9 vs 58.8%, P = 0.041) and non-diabetes group (71.4 vs 63.8%, P = 0.014). Similarly, MACCE-free survival was improved in both groups. CONCLUSIONS: A long-term survival advantage, with no increase in perioperative morbidity, is conferred with the use of multiple arterial bypass grafts not only in non-diabetic patients but also in diabetic patients.
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JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 152(3) 801-+ 2016年9月 査読有りObjective: In patients with acute type A aortic dissection involving the innominate artery, it is unclear whether right axillary artery cannulation for arterial inflow is safe. We evaluated the surgical outcomes of patients with dissected innominate artery according to different arterial cannulation sites. Methods: From 2005 to 2014, of 416 patients with acute type A aortic dissection and preoperative computed tomography angiography in 2 centers, 186 (aged 63 +/- 13 years; 43% were female; 95% with DeBakey type I) had dissected innominate artery (84%, 9%, and 7% involving its entire length or more or less than half of its length, respectively). Neurologic complications, in-hospital mortality, and survival were compared between patients with right axillary (N = 84) and non-right axillary (N = 102) cannulation sites. Median follow-up was 30 months (range, 0-130 months). Results: In-hospital mortality was 9.5% and 10.8% (P =.97) for patients with right and non-right axillary cannulation, respectively. Seven patients (8.3%) with right axillary cannulation and 9 patients (8.8%; P =.89) with non-right axillary cannulation had a new-onset postoperative stroke. The axillary artery was cannulated (although dissected) in 8 patients. None of them had a new-onset stroke or died perioperatively. The innominate artery remodeling was observed on follow-up computed tomography in 12% of right axillary cases and 14% of non-right axillary cases (P =.82). Survival did not differ between right axillary and non-right axillary cases, and measured 92% +/- 3% versus 87% +/- 4% and 85% +/- 5% versus 73% +/- 9% at 1 and 5 years, respectively (log rank, P =.29). Conclusions: The right axillary artery is safe to cannulate for arterial inflow in patients with type A aortic dissection with dissected innominate artery.
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CIRCULATION JOURNAL 80(8) 1756-+ 2016年8月 査読有りBackground: Although bilateral internal mammary artery (BIMA) grafting is performed with increasing regularity in elderly patients, whether it is truly beneficial, and therefore indicated, in these patients remains uncertain. We retrospectively investigated early and late outcomes of BIMA grafting in patients aged >= 75 years. Methods and Results: We identified 460 patients aged >= 75 years from among 2,618 patients who underwent either single internal mammary artery (SIMA) grafting (n=293) or BIMA grafting (n=107). Early outcomes did not differ between the SIMA and BIMA patients (30-day mortality: 1.7% vs. 0%, P=0.39; sternal wound infection: 1.0% vs. 4.7%; P=0.057). Late outcomes, 10-year survival in particular, were improved in the BIMA group (36.6% vs. 48.1%, P=0.033). In the analysis of the results in propensity score-matched groups (196 patients in the SIMA group, 98 patients in the BIMA group), improved 10-year survival was documented in the BIMA group (34.8% vs. 47.6%, P=0.030). Cox proportional regression analysis showed SIMA usage (non-use of BIMA) to be a predictor for late mortality (hazard ratio: 0.65, 95% confidence interval: 0.43-0.98, P=0.042). We further compared outcomes between the total non-elderly patients (n=2,158) and total elderly patients (n=460). BIMA usage was similar, as was 30-day mortality (1.0% vs. 1.3%, respectively). Conclusions: A survival advantage, with no increase in early mortality, can be expected from BIMA grafting in patients aged >= 75 years.
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Kyobu geka. The Japanese journal of thoracic surgery 69(6) 481-4 2016年6月Standard full median sternotomy for total aortic arch replacement in patients with tracheostomy has higher risks for mediastinitis and graft infection. To avoid surgical site infection, it is necessary to keep a sufficient distance between the tracheostomy and the site of surgical skin incision. We herein report a case of a 74-year-old man with permanent tracheostomy after total laryngectomy, who underwent total aortic arch replacement for an aneurysm. Antero-lateral thoracotomy in the 2nd intercostal space with lower partial sternotomy( ALPS approach) provided an enough distance between the tracheostomy and the surgical field. It also provided a good view for surgical procedure and enabled the standard setup of cardiopulmonary bypass with ascending aortic cannulation, venous drainage from the right atrium and the left ventricular venting through the upper right pulmonary vein. The operation was completed in 345 minutes and the patient was discharged on the 11th postoperative day without any complications.
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日本心臓血管外科学会学術総会抄録集 46回 PR14-1 2016年2月
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Annals of Vascular Diseases 9(3) 205-208 2016年We investigated the clinical picture of non-traumatic acute aortic dissection (AAD) occurring behind the wheel. Between 1990 and 2014, AAD had occurred in 11 patients while driving (nine men, mean age; 58.3 years, seven commercial drivers). The symptoms included chest and/or back pain (n = 9) and syncope (n = 2). One patient with syncope caused a traffic accident. Ten patients had type A dissection (DeBakey type I) and 1 type B dissection. In-hospital mortality was 9.9% (1/11). Our data showed if affected drivers are transported to a hospital in a timely fashion, a good surgical outcome can be expected.
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ANNALS OF THORACIC SURGERY 100(3) 827-832 2015年9月 査読有りBackground. There are no data on the fate of the preserved bicuspid aortic valve (BAV) in patients with acute type A aortic dissection. We investigated surgical outcomes in BAV patients who had undergone aortic valve resuspension versus replacement for dissection type A. Methods. Among 1,500 consecutive patients operated on for acute type A dissection between 1993 and 2013 at 3 tertiary centers, 66 had BAV (68% males, median age 60 +/- 15 years). Thirteen BAV resuspension patients were compared with 53 BAV replacement patients. Median follow-up was 5.0 +/- 4.7 years. Results. The ages of both groups were similar (resuspension 62 +/- 13 vs replacement 57 +/- 15 years, p = 0.62), and both presented similar risk-factor profiles. Moderate-to-severe aortic valve regurgitation was observed in 15% of the resuspension and 45% of the replacement patients (p = 0.06). Resuspension patients required shorter cardiopulmonary bypass and cross-clamp times (153 +/- 48 vs 224 +/- 76 min, p < 0.01; 106 +/- 33 vs 172 +/- 57 min, p < 0.01, respectively). In-hospital mortality was observed in 15.4% of the resuspension and 15.1% of the replacement patients (p = 1). One replacement patient underwent a proximal reoperation. The resuspension group experienced no severe aortic regurgitation, nor any need for proximal reintervention. Overall survival was 68% +/- 13% vs 65% +/- 7% at 5 years in resuspension and replacement groups, respectively (log-rank, p = 0.97). Conclusions. The BAV resuspension in type A dissection patients showed good short-and mid-term results. It is doable with acceptable results, and full root replacement is not always necessary. (C) 2015 by The Society of Thoracic Surgeons
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HEART AND VESSELS 30(3) 355-361 2015年5月 査読有りLittle evidence exists regarding the need for a reduction in postoperative heart rate after repair of type A acute aortic dissection. This single-center retrospective study was conducted to determine if lower heart rate during the early postoperative phase is associated with improved long-term outcomes after surgery for patients with type A acute aortic dissection. We reviewed 434 patients who underwent aortic repair between 1990 and 2011. Based on the average heart rate on postoperative days 1, 3, 5, and 7, 434 patients were divided into four groups, less than 70, 70-79, 80-89, and greater than 90 beats per minute. The mean age was 63.3 +/- 12.1 years. During a median follow-up of 52 months (range 16-102), 10-year survival in all groups was 67 %, and the 10-year aortic event-free rate was 79 %. The probability of survival and being aortic event-free using Kaplan-Meier estimates reveal that there is no significant difference when stratified by heart rate. Cox proportional regression analysis for 10-year mortality shows that significant predictors of mortality are age [Hazard Ratio (HR) 1.04; 95 % confidence interval (CI) 1.07-1.06; p = 0.001] and perioperative stroke (HR 2.30; 95 % CI 1.18-4.50; p = 0.024). Neither stratified heart rate around the time of surgery nor beta-blocker use at the time of discharge was significant. There is no association between stratified heart rate in the perioperative period with long-term outcomes after repair of type A acute aortic dissection. These findings need clarification with further clinical trials.
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Kyobu geka. The Japanese journal of thoracic surgery 68(5) 371-4 2015年5月A 74-year-old female patient experienced sudden and severe pain in her lower back and both legs. Upon examination, her femoral pulses were weak, and her legs were pale. Computed tomography revealed a 66-mm thoracic aneurysm in the distal arch and type B aortic dissection. Stenosis was present from the terminal aorta to the iliac arteries. The left common iliac artery was occluded at its bifurcation, and both lower limbs were ischemic. We performed bilateral axillary-femoral artery bypass, which improved blood flow to both limbs. The next day, it was apparent that compartment syndrome had developed in the patient's left leg. Rehabilitation therapy was effective for the compartment syndrome, the patient's symptoms resolved, and she was discharged. We later performed two-stage total arch replacement, and the subsequent clinical course has been without incident.
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Kyobu geka. The Japanese journal of thoracic surgery 68(2) 129-32 2015年2月A 71-year-old woman presented with heart failure due to aortic and mitral valve regurgitation. She had developed midiastinitis and graft infection, 15 months before, following replacement of the ascending aorta for acute aortic dissection. Omentum flap operation had been performed and the infection had been controlled. This time, she underwent re-thoracotomy, and replacement of ascending aorta, aortic valve replacement and mitral valve plasty were performed. The omenal tissue was exfoliated without any damage to the heart or the great vessels by using an ultrasonic scalpel. As the omental tissue was viable, it was placed back in the mediastinal space.
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JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 149(2) S91-U298 2015年2月 査読有り
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Annals of vascular diseases 8(2) 116-9 2015年We report a case of deep femoral artery (DFA) aneurysm associated with pre-vasculo-Behcet status. A 34-year-old man with a history of recurring oral and genital ulcers was admitted complaining of worsening left thigh pain over the previous 30 days. Computed tomography showed a left DFA aneurysm (60 mm × 70 mm), concomitant aneurysms in the popliteal and carotid arteries, and deep vein thrombosis. Active pre-vasculo-Behcet status was diagnosed, and DFA ligation was performed urgently. Remission was achieved with postoperative prednisolone and colchicine without vascular complications. DFA aneurysm and vascular pathologies were successfully managed by ligation surgery and medical therapy.
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日本血管外科学会雑誌 24(4) 767-771 2015年要旨:77 歳男性.急性A 型大動脈解離を認め,術前心タンポナーデに伴うショック状態であった.造影CT では,偽腔開存の大動脈解離を認め腹部分枝まで解離が及んでいた.緊急上行大動脈置換術を施行し,術中腸管虚血を疑う所見なく手術を終了した.術後10 時間で下血を認め緊急試験開腹手術を施行した.小腸に虚血を認めず,S 状結腸壊死を認め結腸切除を施行した.帰室後よりアシドーシスの進行と膀胱内圧軽度高値を認め,再度腸管虚血を疑い,2 回目の緊急試験開腹術を施行した.広範な小腸虚血を認めたが,切除範囲が広く切除を断念した.しかし保存的治療で腸管虚血・全身状態の改善を認め退院となった.可逆的な腸管虚血の診断は難しいが,広範な虚血のため虚血部腸管が切除できない症例でもその後虚血が回復することがあり,腸管虚血に対し試験開腹による腹腔内圧の減圧効果が治療に奏功した可能性がある.
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Annals of Vascular Diseases 2015年We report a case of total occlusion of a Zenith bifurcated stent graft 16 months after implantation. A 72-year-old man was admitted to our hospital complaining of bilateral lower extremity numbness, followed by severe rest pain 4 h after sudden onset of symptoms. Computed tomography showed total occlusion of the endograft at the mid-portion of the main body. He underwent left axillobifemoral bypass using a reinforced polytetrafluoroethylene T-shaped graft, leading to resolution of symptoms 7 h after onset. Axillobifemoral bypass successfully relieved acute lower extremity ischemia caused by total occlusion of the abdominal aortic endograft.
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AMERICAN JOURNAL OF CARDIOLOGY 113(4) 724-730 2014年2月 査読有りThe Penn classification, a risk assessment system for acute type A aortic dissection (AAAD), is based on preoperative ischemic conditions. We investigated whether Penn classes predict outcomes after surgery for AAAD. Three hundred fifty-one patients with DeBakey type I AAAD treated surgically, January 1997 to January 2011, were divided into 4 groups per Penn class: Aa (no ischemia, n = 187), Ab (localized ischemia with branch malperfusion, n = 67), Ac (generalized ischemia with circulatory collapse, n = 46), and Abc (localized and generalized ischemia, n = 51). Early and late outcomes were compared between groups. In-hospital mortality was 3% (6 of 187) for Penn Aa, 6% (4 of 67) for Penn Ab, 17% (8 of 46) for Penn Ac, and 22% (11 of 51) for Penn Abc. Multivariate logistic regression analysis showed Penn classes Ac and Abc, operation time >6 hours, and entry in the descending thoracic aorta to be risk factors for in-hospital mortality. Incidences of neurologic, respiratory, and hepatic complications differed between groups. Five-year cumulative survival was 85% in the Penn Aa group, 74% in the Penn Ab group (p = 0.027 vs Penn Aa), 78% in the Penn Ac group, and 67% in the Penn Abc group (p <0.001 vs Penn Aa). In conclusion, morbidity and mortality are high in patients with generalized ischemia. The Penn classification appears to be a useful risk assessment system for AAAD, predictive of outcomes. (C) 2014 Elsevier Inc. All rights reserved.
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ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY 20 702-704 2014年 査読有りHereditary hemorrhagic telangiectasia (HHT; Osler-Weber-Rendu syndrome) is an uncommon disease characterized by abnormal telangiectasias and arteriovenous malformations that cause recurrent bleeding. Here, we present the case of a patient with HHT, who had a history of pulmonary and hepatic arteriovenous malformations and endocarditis of a prosthetic aortic valve that was caused by methicillin-resistant Staphylococcus aureus. The patient underwent the Bentall operation after coil embolization for pulmonary arteriovenous malformations. The postoperative course was uneventful.
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General Thoracic and Cardiovascular Surgery 63(1) 30-37 2014年 査読有りObjective: Waffle procedure, a small grid-like incision of epicardium, is a surgical technique for constrictive pericarditis with epicardial thickening. Yet evidences to endorse this approach for improved outcomes are lacking. The aim of this study is to elucidate better surgical treatment strategy for constrictive pericarditis with epicardial thickening. Methods: Twenty-five patients (mean 64.1 years) who underwent pericardiectomy for constrictive pericarditis between January 1992 and July 2012 were included in this study and were classified into two groups according to the procedure they received single total pericardiectomy (Group A, n = 17) and total pericardiectomy with the Waffle procedure (Group B, n = 8). Early and mid-term outcomes were analyzed for each group. Results: No major postoperative complications or all-cause deaths at 30 days were observed in each group. Upon discharge, postoperative echocardiography showed statistically significant increase of left ventricular end-diastolic volume (from 76.6 ± 30.3 to 91.0 ± 27.3 ml p < 0.02) and systolic volume (from 44.4 ± 19.1 to 54.5 ± 17.3 ml p < 0.05) in Group B than those in Group A. The 5-year cardiac event-free rate was similar between groups [83.6 ± 10.8 % for group A and 83.3 ± 15.2 % for group B (p = NS)] as well as the mean value of NYHA classification for each at the mid-term periods (1.5 for Group A and 1.3 for Group B). Conclusion: Waffle procedure improved echocardiographic elements of diastolic function of patients with epicardial thickening more than did total pericardiectomy without additional compromises.
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JOURNAL OF EXPERIMENTAL MEDICINE 210(11) 2205-2221 2013年10月 査読有りUsing meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design.
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CIRCULATION JOURNAL 77(6) 1461-1465 2013年6月 査読有りBackground: Ischemic mitral regurgitation (IMR) with ischemic cardiomyopathy (ICM) was treated with surgical procedures, and mitral leaflet tethering was assessed. Twenty-two patients with both ICM (left ventricular ejection fraction <0.35) and IMR (>2) underwent coronary artery bypass grafting (CABG), mitral annuloplasty (MAP) with or without surgical ventricular restoration (SVR) and procedures targeting the subvalvular apparatus. Methods and Results: Fourteen patients (group 1) underwent CABG and MAP, and the remaining 8 (group 2) underwent CABG, MAP, SVR, papillary muscle approximation (PMA), and papillary muscle suspension (PMS). PMA joined the entire papillary muscles with 3 mattress sutures. For PMS, 2 ePTFE sutures were placed between papillary muscle tips and fibrous annuli. Anterior and posterior mitral leaflet tethering angles (ALA and PLA) relative to the line connecting annuli, posterior and apical displacement of coaptation, and IMR grade were measured on echocardiography. Although preoperative ALA and PLA in group 2 were significantly larger than in group 1, there was no significant difference between groups at 1 month after surgery. At 1 year after surgery, however, the situation reversed: ALA and PLA in group 1 were significantly larger than in group 2. Conclusions: In addition to MAP, procedures targeting the subvalvular apparatus including PMA and PMS achieved persistent reduction of mitral valve leaflet tethering, which might lead to the improvement of long-term outcome.
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PLOS ONE 8(2) e56657 2013年2月 査読有りDespite advanced immunosuppression, redundancy in the molecular diversity of acute rejection (AR) often results in incomplete resolution of the injury response. We present a bioinformatics based approach for identification of these redundant molecular pathways in AR and a drug repositioning approach to suppress these using FDA approved drugs currently available for non-transplant indications. Two independent microarray data-sets from human renal allograft biopsies (n = 101) from patients on majorly Th1/IFN-y immune response targeted immunosuppression, with and without AR, were profiled. Using gene-set analysis across 3305 biological pathways, significant enrichment was found for the IL17 pathway in AR in both data-sets. Recent evidence suggests IL17 pathway as an important escape mechanism when Th1/IFN-y mediated responses are suppressed. As current immunosuppressions do not specifically target the IL17 axis, 7200 molecular compounds were interrogated for FDA approved drugs with specific inhibition of this axis. A combined IL17/IFN-y suppressive role was predicted for the antilipidemic drug Fenofibrate. To assess the immunregulatory action of Fenofibrate, we conducted in-vitro treatment of anti-CD3/CD28 stimulated human peripheral blood cells (PBMC), and, as predicted, Fenofibrate reduced IL17 and IFN-gamma gene expression in stimulated PMBC. In-vivo Fenofibrate treatment of an experimental rodent model of cardiac AR reduced infiltration of total leukocytes, reduced expression of IL17/IFN-y and their pathway related genes in allografts and recipients' spleens, and extended graft survival by 21 days (p < 0.007). In conclusion, this study provides important proof of concept that meta-analyses of genomic data and drug databases can provide new insights into the redundancy of the rejection response and presents an economic methodology to reposition FDA approved drugs in organ transplantation.
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The Annals of thoracic surgery 94(2) 542-548 2012年8月 査読有り
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ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY 18(1) 18-23 2012年2月 査読有りBackground: Our surgical strategies for acute type A aortic dissection (AAAD) are prompt establishment of cardiopulmonary bypass and primary entry resection. We investigated our experience with surgery for AAAD. Methods: Between January 1997 and December 2006, 243 consecutive patients with AAAD underwent emergency surgery. Clinical and diagnostic data of these patients were analyzed retrospectively. Results: Surgical procedures included ascending aorta or hemiarch replacement (n = 212) and total or partial arch replacement (n = 31), and those for proximal reconstruction included modified Bentall procedure (n = 8), and aortic valve replacement (n = 3). Hospital mortality was 6.9%, and entry resection was performed in 74% of patients. Actuarial survival rate at 5 and 10 years was 86% +/- 14% and 77% +/- 23%, respectively. A total of 13 patients required re-operation: 5, an aortic root; 3, an aortic arch; and 5, a descending aorta. Actuarial freedom from re-operation at 5 and 10 years was 95% +/- 5%, and 81% +/- 18%, respectively. Conclusions: Our surgical strategy for AAAD seems to be pertinent with acceptable short- and long-term results. Since we lost 8 patients due to rupture of false lumen postoperatively, careful follow-up for a residual false lumen may improve the patients' prognosis.
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CIRCULATION RESEARCH 110(2) 312-+ 2012年1月 査読有りRationale: Marfan syndrome (MFS) is a systemic connective tissue disorder notable for the development of aortic root aneurysms and the subsequent life-threatening complications of aortic dissection and rupture. Underlying fibrillin-1 gene mutations cause increased transforming growth factor-beta (TGF-beta) signaling. Although TGF-beta blockade prevents aneurysms in MFS mouse models, the mechanisms through which excessive TGF-beta causes aneurysms remain ill-defined. Objective: We investigated the role of microRNA-29b (miR-29b) in aneurysm formation in MFS. Methods and Results: Using quantitative polymerase chain reaction, we discovered that miR-29b, a microRNA regulating apoptosis and extracellular matrix synthesis/deposition genes, is increased in the ascending aorta of Marfan (Fbn1(C1039G/+)) mice. Increased apoptosis, assessed by increased cleaved caspase-3 and caspase-9, enhanced caspase-3 activity, and decreased levels of the antiapoptotic proteins, Mcl-1 and Bcl-2, were found in the Fbn1(C1039G/+) aorta. Histological evidence of decreased and fragmented elastin was observed exclusively in the Fbn1(C1039G/+) ascending aorta in association with repressed elastin mRNA and increased matrix metalloproteinase-2 expression and activity, both targets of miR-29b. Evidence of decreased activation of nuclear factor kappa B, a repressor of miR-29b, and a factor suppressed by TGF-beta, was also observed in Fbn1(C1039G/+) aorta. Furthermore, administration of a nuclear factor kappa B inhibitor increased miR-29b levels, whereas TGF-beta blockade or losartan effectively decreased miR-29b levels in Fbn1(C1039G/+) mice. Finally, miR-29b blockade by locked nucleic acid antisense oligonucleotides prevented early aneurysm development, aortic wall apoptosis, and extracellular matrix deficiencies. Conclusions: We identify increased miR-29b expression as key to the pathogenesis of early aneurysm development in MFS by regulating aortic wall apoptosis and extracellular matrix abnormalities. (Circ Res. 2012;110:312-324.)
MISC
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CIRCULATION 140 2019年11月0
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CIRCULATION JOURNAL 80(11) 2413-2413 2016年11月
共同研究・競争的資金等の研究課題
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日本学術振興会 科学研究費助成事業 2023年4月 - 2026年3月
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日本学術振興会 科学研究費助成事業 2021年4月 - 2024年3月
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日本学術振興会 科学研究費助成事業 2021年4月 - 2024年3月
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日本学術振興会 科学研究費助成事業 2020年4月 - 2023年3月
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日本学術振興会 科学研究費助成事業 2018年4月 - 2023年3月