Publications by authors named "Kei Akiyoshi"

12 Publications

  • Page 1 of 1

Impact of prosthesis-patient mismatch on late outcomes after bioprosthetic mitral valve replacement for mitral regurgitation.

J Artif Organs 2021 Oct 19. Epub 2021 Oct 19.

Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama-shi, Saitama, 330-8503, Japan.

Negative impact of prosthesis-patient mismatch on long-term survival after valve replacement has been reported. However, the effect of prosthesis-patient mismatch after bioprosthetic mitral valve replacement has not yet been well examined. The purpose of this study was to investigate the effect of prosthesis-patient mismatch on late outcomes after bioprosthetic mitral valve replacement for mitral regurgitation. A total of 181 patients underwent bioprosthetic mitral valve replacement between April 2008 and December 2016. After excluding patients with mitral stenosis and those with incomplete data, 128 patients were included in the study. Postoperative transthoracic echocardiography was performed before discharge for all patients and the effective orifice area of bioprosthetic mitral valve was calculated using the formula: 220/pressure half-time, and the effective orifice area index was calculated by the formula: effective orifice area/body surface area. Prosthesis-patient mismatch was defined as a postoperative effective orifice area index ≤ 1.2 cm/m. The characteristics and outcomes were compared between the groups. There were 34 patients (26.6%) with prosthesis-patient mismatch and 94 patients (73.4%) without prosthesis-patient mismatch. There were no significant differences in the in-hospital mortality and morbidities. Multivariable analysis showed that prosthesis-patient mismatch was an independent predictor of late mortality (hazard ratio 3.38; 95% confidence interval 1.69-6.75; p = 0.001) and death from heart failure (hazard ratio 31.03, 95% confidence interval 4.49-214.40, p < 0.001). Prosthesis-patient mismatch at discharge after mitral valve replacement for mitral regurgitation was associated with long-term mortality and death from heart failure.
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http://dx.doi.org/10.1007/s10047-021-01299-9DOI Listing
October 2021

Degradation of Premature-miR-181b by the Translin/Trax RNase Increases Vascular Smooth Muscle Cell Stiffness.

Hypertension 2021 Sep 26;78(3):831-839. Epub 2021 Jul 26.

Department of Anesthesiology and Critical Care Medicine (M.N., L.S., S.D.), Johns Hopkins School of Medicine, Baltimore, MD.

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363557PMC
September 2021

The association of bispectral index values and metrics of cerebral perfusion during cardiopulmonary bypass.

J Clin Anesth 2021 Nov 17;74:110395. Epub 2021 Jun 17.

Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan. Electronic address:

Study Objective: Low bispectral index (BIS) values have been associated with adverse postoperative outcomes. However, trials of optimizing BIS by titrating anesthetic administration have reported conflicting results. One potential explanation is that cerebral perfusion may also affect BIS, but the extent of this relationship is not clear. Therefore, we examined whether BIS would be associated with cerebral perfusion during cardiopulmonary bypass, when anesthetic concentration was constant.

Design: Observational cohort study.

Setting: Cardiac operating room.

Patients: Seventy-nine patients with cardiopulmonary bypass surgery were included.

Measurements: Continuous BIS, mean arterial blood pressure (MAP), cerebral blood flow velocity (CBFV), and regional cerebral oxygen saturation (rSO) were monitored, with analysis during a period of constant anesthetic. Mean flow index (Mx) was calculated as Pearson correlation between MAP and CBFV. The lower limit of autoregulation (LLA) was identified as the MAP value at which Mx increased >0.4 with decreasing blood pressure. Postoperative delirium was assessed using the 3D-Confusion Assessment Method.

Results: Mean BIS was lower during periods of MAP < LLA compared with BIS when MAP>LLA (mean 49.35 ± 10.40 vs. 50.72 ± 10.04, p = 0.002, mean difference = 1.38 [standard error: 0.42]). There was a dose response effect, with the BIS proportionately decreasing as MAP decreased below LLA (β = 0.15, 95% CI for the average slope across all patients 0.07 to 0.23, p < 0.001). In contrast, BIS was relatively unchanged when MAP was above LLA (β = 0.03, 95% CI for the average slope across all patients -0.02 to 0.09, p = 0.22). Additionally, increasing CBFV and rSO were associated with increasing BIS. Patients with postoperative delirium had lower mean BIS and higher percentage of time duration with BIS <45 compared to patients without delirium.

Conclusions: There was an association of BIS and metrics of cerebral perfusion during a period of constant anesthetic administration, but the absolute magnitude of change in BIS as MAP decreased below the LLA was small.
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http://dx.doi.org/10.1016/j.jclinane.2021.110395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530850PMC
November 2021

Cerebral autoregulation in the operating room and intensive care unit after cardiac surgery.

Br J Anaesth 2021 May 23;126(5):967-974. Epub 2021 Mar 23.

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Background: Cerebral autoregulation monitoring is a proposed method to monitor perfusion during cardiac surgery. However, limited data exist from the ICU as prior studies have focused on intraoperative measurements. Our objective was to characterise cerebral autoregulation during surgery and early ICU care, and as a secondary analysis to explore associations with delirium.

Methods: In patients undergoing cardiac surgery (n=134), cerebral oximetry values and arterial BP were monitored and recorded until the morning after surgery. A moving Pearson's correlation coefficient between mean arterial proessure (MAP) and near-infrared spectroscopy signals generated the cerebral oximetry index (COx). Three metrics were derived: (1) globally impaired autoregulation, (2) MAP time and duration outside limits of autoregulation (MAP dose), and (3) average COx. Delirium was assessed using the 3-Minute Diagnostic Interview for CAM-defined Delirium (3D-CAM) and the Confusion Assessment Method for the ICU (CAM-ICU). Autoregulation metrics were compared using χ and rank-sum tests, and associations with delirium were estimated using regression models, adjusted for age, bypass time, and logEuroSCORE.

Results: The prevalence of globally impaired autoregulation was higher in the operating room vs ICU (40% vs 13%, P<0.001). The MAP dose outside limits of autoregulation was similar in the operating room and ICU (median 16.9 mm Hg×h; inter-quartile range [IQR] 10.1-38.8 vs 16.9 mm Hg×h; IQR 5.4-35.1, P=0.20). In exploratory adjusted analyses, globally impaired autoregulation in the ICU, but not the operating room, was associated with delirium. The MAP dose outside limits of autoregulation in the operating room and ICU was also associated with delirium.

Conclusions: Metrics of cerebral autoregulation are altered in the ICU, and may be clinically relevant with respect to delirium. Further studies are needed to investigate these findings and determine possible benefits of autoregulation-based MAP targeting in the ICU.
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http://dx.doi.org/10.1016/j.bja.2020.12.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132879PMC
May 2021

Determining Thresholds for Three Indices of Autoregulation to Identify the Lower Limit of Autoregulation During Cardiac Surgery.

Crit Care Med 2021 04;49(4):650-660

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Objectives: Monitoring cerebral autoregulation may help identify the lower limit of autoregulation in individual patients. Mean arterial blood pressure below lower limit of autoregulation appears to be a risk factor for postoperative acute kidney injury. Cerebral autoregulation can be monitored in real time using correlation approaches. However, the precise thresholds for different cerebral autoregulation indexes that identify the lower limit of autoregulation are unknown. We identified thresholds for intact autoregulation in patients during cardiopulmonary bypass surgery and examined the relevance of these thresholds to postoperative acute kidney injury.

Design: A single-center retrospective analysis.

Setting: Tertiary academic medical center.

Patients: Data from 59 patients was used to determine precise cerebral autoregulation thresholds for identification of the lower limit of autoregulation. These thresholds were validated in a larger cohort of 226 patients.

Methods And Main Results: Invasive mean arterial blood pressure, cerebral blood flow velocities, regional cortical oxygen saturation, and total hemoglobin were recorded simultaneously. Three cerebral autoregulation indices were calculated, including mean flow index, cerebral oximetry index, and hemoglobin volume index. Cerebral autoregulation curves for the three indices were plotted, and thresholds for each index were used to generate threshold- and index-specific lower limit of autoregulations. A reference lower limit of autoregulation could be identified in 59 patients by plotting cerebral blood flow velocity against mean arterial blood pressure to generate gold-standard Lassen curves. The lower limit of autoregulations defined at each threshold were compared with the gold-standard lower limit of autoregulation determined from Lassen curves. The results identified the following thresholds: mean flow index (0.45), cerebral oximetry index (0.35), and hemoglobin volume index (0.3). We then calculated the product of magnitude and duration of mean arterial blood pressure less than lower limit of autoregulation in a larger cohort of 226 patients. When using the lower limit of autoregulations identified by the optimal thresholds above, mean arterial blood pressure less than lower limit of autoregulation was greater in patients with acute kidney injury than in those without acute kidney injury.

Conclusions: This study identified thresholds of intact and impaired cerebral autoregulation for three indices and showed that mean arterial blood pressure below lower limit of autoregulation is a risk factor for acute kidney injury after cardiac surgery.
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http://dx.doi.org/10.1097/CCM.0000000000004737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979429PMC
April 2021

Relationship between endothelial function and vascular stiffness on lower limit of cerebral autoregulation in patients undergoing cardiovascular surgery.

Artif Organs 2021 Apr 15;45(4):382-389. Epub 2020 Dec 15.

Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan.

Hemodynamic management based on cerebral autoregulation range is a possible strategy for preserving major organ perfusion during cardiovascular surgery. The purpose of this study was to evaluate the relation of vascular properties with lower limit of cerebral autoregulation (LLA). LLA was monitored in 66 patients undergoing cardiovascular surgery using near-infrared spectroscopy. To determine the clinical importance of LLA monitoring, association of blood pressure excursions below LLA and acute kidney injury (AKI) was evaluated. Flow-mediated dilation (FMD) and pulse wave velocity (PWV) were measured for the evaluation of endothelial function and aortic stiffness. Variables associated with LLA were evaluated. Excluding patients on hemodialysis, there were 15 patients (25.9%) who developed AKI. Blood pressure excursions below LLA were higher in patients who developed AKI (4.55 mm Hg × hr vs. 1.23 mm Hg × hr, P = .017). In the univariate analysis, prevalence of ischemic heart disease (No IHD: 53 ± 13.0 mm Hg vs. IHD: 60.0 ± 13.6 mm Hg, P = .056) and FMD (r = -0.42, 95% CI -0.61 to -0.19, P < .001) were associated with LLA before cardiopulmonary bypass (CPB). During CPB, calcium channel blocker (No Ca blocker: 42 ± 10.6 mm Hg vs. Ca blocker: 49 ± 14.3 mm Hg, P = .033), diabetes (no DM: 44 ± 13.2 mm Hg vs. DM: 55 ± 10.0 mm Hg, P = .024), FMD (r = -0.32, 95% CI -0.55 to -0.05, P = .021), and PWV (r = 0.28, 95% CI 0.012 to 0.513, P = .041) were associated with LLA. Multivariate analysis showed that FMD was correlated with LLA before CPB (r = -2.19, 95% CI -3.621 to -0.755, P = .003), while PWV was correlated with LLA during CPB (r = 0.01, 95% CI 0.001-0.019, P = .023). Endothelial function and aortic stiffness may be important factors in determining LLA at different phases in cardiovascular surgery.
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http://dx.doi.org/10.1111/aor.13868DOI Listing
April 2021

Endothelial-Specific Overexpression of Histone Deacetylase 2 Protects Mice against Endothelial Dysfunction and Atherosclerosis.

Cell Physiol Biochem 2020 Sep;54(5):947-958

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA,

Background/aims: We recently described a novel regulatory role for histone deacetylase 2 (HDAC2) in protecting endothelial cells from oxidized low-density lipoprotein (OxLDL)-induced injury. In this study, we examined the effects of endothelial-specific HDAC2 overexpression on endothelial-dependent vasorelaxation and atherogenesis in vivo.

Methods: Endothelial-specific HDAC2-overexpressing transgenic mice (HDAC2-Tg) were generated under control of the Tie2 promoter. An atherosclerosis model was produced by injecting HDAC2-Tg and wild-type (WT) mice with adeno-associated virus encoding a PCSK9 gain-of-function mutant under control of a liver-specific promoter and feeding them a high-fat diet for 12 weeks. Aortic stiffness in vivo was determined by measuring pulse wave velocity. Wire myography was used to measure endothelium dependent (acetylcholine) and independent (sodium nitroprusside) relaxation in isolated mice aortas. Atherosclerotic plaque burden in aortas was determined by Oil Red O staining and protein expression was determined by western blotting.

Results: At baseline, HDAC2-Tg mice had normal mean arterial blood pressure (MAP) and body weight, but pulse wave velocity (PWV), an inverse measure of vascular health and stiffness, was decreased, suggesting that their vessels were more compliant. Moreover, basal nitric oxide production was enhanced in the vessels of HDAC2-Tg mice as compared to that in WT controls, although no significant differences in acetylcholine (endothelial component)- or sodium nitroprusside (non-endothelial component)-mediated relaxation were observed. However, after exposure to OxLDL, aortas from HDAC2-Tg mice exhibited greater acetylcholine-induced relaxation than did those from WT mice. Thus, endothelial-specific vasodilator production was enhanced despite oxidative injury. Atherosclerosis induction in WT mice led to a significant increase in PWV, but in HDAC2-Tg mice, PWV and MAP remained unchanged. Further, aortic rings from HDAC2-Tg exhibited better endothelial-dependent vascular relaxation than did those from WT mice, but not when treated with nitric oxide synthase inhibitor L-NAME. Finally, plaque burden, determined by Oil red O staining, was significantly increased in WT, but not HDAC2-Tg mice, subjected to the atherogenic model. Deletion of endothelial HDAC2 led to impaired endothelial cell-dependent vascular relaxation and increased PWV, compared with those in littermate controls.

Conclusion: HDAC2 protects against endothelial dysfunction and atherogenesis induced by oxidized lipids. Hence, overexpression or activation of HDAC2 represents a novel therapy for endothelial dysfunction and atherosclerosis. HDAC2-Tg mice provide an opportunity to determine the role of endothelial HDAC2 in vascular endothelial homeostasis.
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http://dx.doi.org/10.33594/000000280DOI Listing
September 2020

[Pseudoaneurysm with Infective Endocarditis Ten Years After the Resection of Pseudoaneurysm Complicated with Myocardial Infarction;Report of a Case].

Kyobu Geka 2019 Oct;72(11):923-927

Department of Cardiovascular Surgery, Yokosuka Municipal Uwamachi Hospital, Yokosuka, Japan.

A 76-year-old female was referred to our hospital for fever and chillness. She was diagnosed with pneumonia and sepsis, and methicillin-resistant Staphylococcus aureus (MRSA)was detected by the sputum culture. Echocardiography showed mobile vegetation and left ventricular pseudoaneurysm at the apex. As she had a history of ventricular pseudoaneurysmectomy 10 years before, we considered the patient had developed infective endocarditis at the surgical site. Surgical treatment was needed because of the rapidly growing pseudoaneurysm despite the use of antibacterial agents. She successfully underwent resection of the pseudoaneurysm and MRSA was also detected in the culture of the previous vascular graft patch. Antibacterial agents were administrated for 6 weeks, and she was discharged at 53 days after operation.
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October 2019

Off-pump coronary artery bypass grafting via left anterior thoracotomy from the 4th costal space in a patient with total laryngectomy and a permanent tracheostoma.

Gen Thorac Cardiovasc Surg 2020 Jun 20;68(6):633-636. Epub 2019 May 20.

Department of Cardiovascular Surgery, Yokosuka Uwamachi Hospital, 2-36 Uwamachi, Yokosuka, Kanagawa, 238-8567, Japan.

Median sternotomy is the standard approach for coronary artery bypass grafting. Herein, we performed off-pump coronary artery bypass grafting via left anterior thoracotomy from the 4th costal space in an unstable angina pectoris patient with total laryngectomy and a permanent tracheostoma. In this patient, median sternotomy had high risks of surgical-site infection and tracheal injury. To avoid these risks, we selected left anterior thoracotomy. Initially, it was difficult to expose the ascending aorta and postdescending branch. With extension of the skin incision to the median area and division of the 5th and 6th ribs and costal arch, we could expose the anastomotic sites, including the ascending aorta and postdescending branch, without median sternotomy conversion. We performed multiple coronary artery bypass graft procedures safely. This approach might be an additional surgical option in patients with total laryngectomy and a permanent tracheostoma.
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http://dx.doi.org/10.1007/s11748-019-01143-1DOI Listing
June 2020

Surgical outcomes of acute type A aortic dissection in dialysis patients.

Gen Thorac Cardiovasc Surg 2019 Jun 14;67(6):501-509. Epub 2018 Dec 14.

Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, 1-847 Amanumacho, Omiya-ku, Saitama, 330-8503, Japan.

Background: Acute type A aortic dissection (ATAAD) is relatively uncommon in dialysis patients, and characteristics and repair outcomes are not fully understood.

Patients And Methods: Patients with ATAAD (n = 960) were divided into a dialysis group (n = 19) and non-dialysis group (n = 941), depending on whether they required dialysis for preoperative end-stage renal disease (ESRD). Hospital charts and imaging data were reviewed, and characteristics and outcomes were compared between the groups. Segmental aortic wall or intima/media flap calcification in the thoracic and abdominal aorta was assessed in the dialysis patients.

Results: The leading primary causes of ESRD were polycystic kidney disease (n = 5) and chronic glomerulonephritis (n = 5). There were no significant differences (dialysis group vs. non-dialysis group) in age (60.5 vs. 64.5 years), preoperative hemodynamics, or organ ischemia. Dialysis patients were more likely to have an entry tear in the aortic arch (42% vs. 15%, p = 0.003). These patients showed moderate-to-severe calcification (multiple focal or single focal calcification > 10 mm) in the ascending aorta (17%), aortic arch (61%), descending aorta (67%), and abdominal aorta (83%). Arch replacement was common in this group (37% vs. 18%, p = 0.030). Although in-hospital mortality was increased in this group (21% vs. 7%, p = 0.059), morbidities did not differ significantly. Six-year survival was 60.3 ± 13.4% and 78.8 ± 1.6%, respectively (p = 0.01).

Conclusions: Dialysis patients tend to have aortic calcification and a primary tear in the aortic arch. Outcomes are acceptable.
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http://dx.doi.org/10.1007/s11748-018-1051-6DOI Listing
June 2019

Characteristics and Treatment Outcomes of Acute Type A Aortic Dissection With Elevated D-Dimer Concentration.

J Am Heart Assoc 2018 07 9;7(14). Epub 2018 Jul 9.

Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan.

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) (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 (0.01; odds ratio, 9.81) or descending aorta (0.01; odds ratio, 7.68), a completely thrombosed false lumen (0.01; odds ratio, 4.02), and absence of brain ischemia (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%; 0.031), although 7-year survival did not differ for hospital survivors (lower versus higher, 93.1% versus 79.1%; =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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http://dx.doi.org/10.1161/JAHA.118.009144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6064831PMC
July 2018

Effect of endoskeleton stent graft design on pulse wave velocity in patients undergoing endovascular repair of the aortic arch.

Gen Thorac Cardiovasc Surg 2017 Sep 8;65(9):506-511. Epub 2017 Jun 8.

Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama, Saitama, 330-8503, Japan.

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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http://dx.doi.org/10.1007/s11748-017-0787-8DOI Listing
September 2017
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