岩崎　清隆

ISSN：0009-7322

ISSN：0896-4327

ISSN：0470-8105

ISSN：0009-7322

ISSN：0966-8519

ISSN：1341-1098

ISSN：0002-9149

ISSN：0039-2499

ISSN：0009-7322

ISSN：0006-3495

ISSN：1936-8798

ISSN：1434-7229

ISSN：1742-7061

ISSN：09122664

ISSN：03000818

ISSN：03000818

ISSN：13449486

ISSN：13449486

ISSN：03000818

ISSN：00214728

ISSN：00214728

概要：This study aimed to investigate "malignant hemodynamics" leading to induce the wall degradation of cerebral aneurysms in an effort to find out a reliable predictor as to which aneurysms were doomed to rupture. Two blister-holding aneurysms and two bleb-holding aneurysms were computationally analyzed and compared with those of aneurysmal appearances observed during operations. The results demonstrated that the sites of flow impingement and bifurcation were well correlated with those of blisters. Such a flow pattern was confirmed to be present at the neck of bleb. The inside of bleb was found to be dominated by weak regurgitation as a result of flow bifurcation. The possible scenario for the genesis and growth of bleb was proposed. Flow impingement was concluded to play a malignant role on aneurysmal wall degradation.

概要：Autologous tendons or bone-patellar tendon-bone grafts are clinically used for reconstruction of anterior cruciate ligaments, because of unsatisfactory durability of synthetic materials. The aims of this study are to realize decellularization of 16-cm long xenogeneic tendons which have a potential to guide regeneration, and to investigate influences of decellularization on tissue mechanical properties. Bovine tendons were decellularized by combination of pulsatile flow-and-pressure circulation of 1 wt% deoxycholic acid and microwave radiation. Then, the tissues were additionally treated with endonuclease. Influences of decellularization on durability was investigated by a cyclic tensile test under 0-100 N loads. When the tissues were not ruptured, ultimate strength, elastic modulus, and ultimate strain were examined by a uniaxial tensile test. DNA of 16-cm long bovine tendons was successfully removed over 99.99% by our decellularization technology. Non-treated and decellularized tendons were not ruptured in 1000 cycles' tensile durability tests. After the cyclic tests, ultimate stress, elastic modulus, and ultimate strain of the decellularized tendons were comparable to those of non-treated tendons. We here reported, to our knowledge, the first successful decellularization of 16-cm long tendons with preserving mechanical integrity.

ISSN：00214728

概要：We aimed to develop a calcified aortic valve model for the evaluation of paravalvular leak of a transcatheter aortic valve. We fabricated a calcified aortic valve model using silicone based on a CT image of the pre-operation of the patient who received treatment with a transcatheter aortic valve. In addition, we fabricated a thoracic aorta model and an abdominal aorta model because these three dimensional morphology would affect the insertion procedure of the transcatheter valve. These models were installed into a chamber, and the other space of the models were filled with a glycerol solution with the refractive index and viscosity of 1.410±0.002 and 5.96 mPa・s respectively, in order to adjust the expansion rate of the valve annulus and to measure the expansion range by a lazer system in pulsatile flow and pressure environments. Using the test system, the maximum and minimum cross-sectional area of the valve annulus in systole and diastole in the pulsatile flow circuit could be adjusted to these in the referenced patients' data. The pulsatile flow system with patient specific aortic valve, thoracic aorta and abdominal aorta model would be useful to quantify the paravalvular leak performance of the transcatheter aortic valve.

概要：Thrombus formations in medical devices are unsolved issue. If a reliable in vitro real-time visualization method is established, it will contribute the development and improvement of anti-thrombogenic medical devices. The aim of this study is to develop a real-time thrombus visualization system with an optical coherence tomography (OCT) and to reveal an influence of local blood flow on thrombus growth. We focus on the inlet and outlet part of connecters. The circuit was consisted of a roller pump, a reservoir, and resistance. The circuit volume was 50 ml. The blood flow rate and pressure were regulated to 100 ml/min and 70 mmHg. To visualize cross-sectional imaging of thrombus, we used a SS-OCT system with center wave-length of 1330 nm. OCT images were obtained every 10 minutes for 50 minutes. Test were performed 6 times. A fresh porcine whole blood with activated clotting time of approximately 200 sec was circulated. Thrombus-formed area increased with time at the outlet part of the connecter, however, the thrombus-formed area didn't increase at the inlet part. The part where thrombus-formed are increased was related to a flow-separation area. Flow-separation would be a cause to form such an increasingly thrombus. We revealed that the local blood flow is important not only for thrombus formation but also stability of thrombus-formed at the connecter.

概要：Off-pump CABG surgery requires high level of techniques. The surgeon must complete the anastomosis of two millimeter wide arteries within ten minutes on beating condition. Due to its difficulty, an effective training platform of DRY LAB with assessments is in strong need. This study investigated the models of anastomosis configurations and a relationship between the model and the energy loss (EL) using a beating heart simulator (BEAT, EBM) and coronary artery model (YOUCAN, EBM) which were developed from this research. The models for the analysis were chosen based on the actual EL; low (X: 42 μW), medium (Y: 196 μW) and high (Z: 362 μW) values. The effective cross-sectional areas were set by taking the cross-sectional areas from the mainstreams. The calculated EL was calculated using Hagen-Poiseuille because energy loss is inversely proportional to the square of the minimum effective cross-sectional area in a Hagen-Poiseuille flow. Results indicated that the change of the velocity distribution of the area in Y and Z were greater than those in X. The minimum effective cross-sectional areas were 2.1 mm^2 (X), 1.2 mm^2 (Y), 0.8 mm^2 (Z). Therefore, it was confirmed that mainstream could not utilize the anastomosis configuration efficiently in Y and Z. In addition, it was found that the calculated EL and the actual EL had a strong correlation, and the minimum effective cross-sectional area influenced the actual EL strongly.

概要：We aimed to investigate mechanical properties of Achilles' tendon autograft after ovine anterior cruciate ligament reconstruction. Mature three female ovine were used in this study. In each ovine, the right knee underwent anterior cruciate ligament reconstruction. They were sacrificed at 13 weeks after surgery. In each ovine, both the knees were harvested, and the left knee was used to obtain the data of the native anterior cruciate ligament. Drawer test for stability evaluation and tensile test for evaluation of mechanical properties were performed. The knee was mounted on a jig with 5 degrees of freedom for tensile testing, four cycles of anterior-posterior shear loads (50 N) were applied to the knee at 30°, 60° and 90° of the flexion with a cross head speed set at 20 mm/min. The displacement of the femur relative to tibia was defined as the anterior-posterior translation of the knee. (1) Stress relaxation test (5 N, 10 min), (2) cyclic load test (0-50 N, 10 cycles, 10 mm/min), and (3) tensile test (300 mm/min) were performed in turn. Before each testing, tissue cross-sectional area was measured with the device using a laser displacement sensor. At 13 weeks after the implantation, the anterior-posterior translation of the reconstructed knee was greater than native anterior cruciate ligament. Ultimate strength and maximum Young's modulus of the femur-graft-tibia complex were smaller than native anterior cruciate ligament. These testing methods presented here is effective to gain insight into in vivo biomechanical remodeling of reconstructed tissues.

概要：In the treatment of anterior cruciate ligament rupture, anterior cruciate ligament reconstruction is performed using autologous tendon. However, there are problems in the invasiveness and limitation in the source of autologous tendon. In order to solve these problems, a decellularized and sterilized bovine tendon has been developed. The aim of this study is to investigate cell infiltration into the decellularized and sterilized bovine tendon in rat anterior cruciate ligament reconstruction. In 4 and 26 weeks after the implantation, the tissues were explanted and subjected to hematoxylin-eosin staining. In this study, rat autologous tendon were also implanted to compare cell infiltration into the reconstructed tissues between the decellularized and sterilized bovine tendon and rat autologous tendon In the implantation period of 4 weeks, the number of cells in the decellularized and sterilized bovine tendon was higher than that in the rat autologous tendon In the implantation period of 26 weeks, the number of cells in the decellularized and sterilized bovine tendon and that in the rat autologous tendon became comparable. In the implantation period of 26 weeks, the number of cells in the decellularized and sterilized bovine tendon and that in rat anterior cruciate ligament also became comparable. These data indicated that the decellularized and sterilized bovine tendon has a promise as a prosthesis for anterior cruciate ligament reconstruction.

概要：The aim of this study is to develop an accelerated fatigue tester for the Normo valve. Because the Normo valve has a unique structure similar to natural mitral valve, a novel accelerated fatigue tester which can mount the Normo valve and test in the condition recommended by the International Organization for Standardization (IS05840) was developed. We succeeded in producing the targeted closed duration percentage over the defined trans-valvular pressure gradient by adjusting the systolic and the drive frequency. The results showed that the drive condition of 10 Hz in drive frequency and 50% in systolic fraction met the requirement noted in ISO 5840.

概要：The purpose of this study is to investigate influences of multi-loads and stenosis in femoral-popliteal artery on fracture of self-expandable stent using finite element analysis. A nitinol alloy stent was selected. The three-dimensional CAD models of the stent and vessel were constructed using SolidWorks. First, the stent was compressed by four cylinder models. Second, the stent was deployed in 50%, 60% and 75% stenotic artery models. Third, cyclic multi-loads were applied to the artery model. Multi-loads were two types. One is shortening of 12.7% and torsion of 0.28 degree/mm (Average). Another is shortening of 6.9% and torsion of 0.14 degree/mm (Half of average). When average loads were applied, strain amplitude of stent were 0.61%, 0.75%, and 0.87% in 50%, 60% and 75% stenotic model. When half of average loads were applied, those were 0.36%, 0.41%, and 0.54%. According to constant-life diagrams of average loads, when the stent was deployed in over 60% stenotic artery model, risk of fracture was high. This study indicated that risk of fracture is increased by multi-loads and stenosis.

概要：Hemofilters are medical devices for assisting deteriorated renal functions, which purify the blood by removing pathogen and wastes. For continuous hemofilters, antithronbogenecity is one of the most important requirements. The aim of this study is to investigate the key parameters for the establishment of a reliable in vitro thrombogenecity testing methodology for continuous hemofilters using human blood from healthy volunteers. This study used adjusted activated clotting time of human blood drawn from healthy volunteers to 150-200 sec using heparin. The blood was circulated in the air-contactless circuit with flow and pressure in a clinical situation was reproduces. The tests were terminated when the inlet pressure elevated to 150 mmHg from the initiation pressure of 70 mmHg at the inlet. The average circulation duration was 6.5±1.7 hours(n=4). The circulation duration using human blood from healthy volunteers were shorter than using porcine blood which was previously reported. Hematocrit of porcine blood was lower than the human blood from healthy volunteers, whereas the hematocrit of porcine blood was comparable to dialysis patients. These data indicated the importance of hematocrit of blood in the assessment of the thrombogenecity of continuous hemofilters.

概要：Thrombus formation at the interface between left ventricular wall and the inflow cannula of left ventricular assist device (LVAD) remains to be an unsolved problem that induces complications in clinical practice. The aim of this study is to develop an in vitro airless circuit which produces flow and pressure environments in patients with a LVAD, and to investigate an influence of MPC coating of the inflow cannula of EVAHEART^[○!R] LVAD (Sun Medical Technology Research Co., Japan) on thrombus detachment from the inflow cannula. In the thrombogenicity test, two identical circuits except for the cannula were prepared to form a comparative study. Heparinized blood from a single porcine with activated clotting time ranged within 130-210 sec was circulated for 4.5 hours. The tests were performed under the combinations of the total flow rate of 4 L/min or 5 L/min, and the pump rotational speed of 1800, 1900 or 2000 rpm, respectively. It was elucidated that higher amount of thrombus formed on the MPC non-coated cannula compared with MPC coated cannula. However, there was no difference in the amount of thrombus detached between the two cannula (Student's t-test, p=0.91). From these results, it was elucidated that the MPC non-coated cannula yielded significantly lower proportion of thrombus detachment to thrombus formation than the MPC coated cannula (Student's t-test, p<0.05).

概要：We have developed in vitro test methodologies modeling in vivo practical-use situations, to quantitatively assess safety and effectiveness of innovative medical devices. We believe that expediting development of these in vitro methodology not only reinforce preclinical evaluation and enhance timely access to innovative medical devices for patients but also reduce potential risk when used in real-world clinical practice, because controlled clinical trials have certain limitation in fully demonstrating benefit and risk. With the grant from Ministry of Health, Labour and Welfare intended for "Promotional Project for Practical Application of Innovative Pharmaceutical, Medical Device, and Tissue Engineering Products", we have developed drafts on in vitro test guideline for "Durability testing methods for coronary artery stent", "Durability testing methods for vascular stent intended for Superficial femoral - Popliteal artery", and "Method for in vitro thrombogenicity testing for inflow cannula of left ventricular assist system". Further 5 guideline drafts are under preparation. Here, we introduce impacts of in vitro test methods modeling in vivo intended-use situations on expediting availability of new medical devices and timely assessment and management of risk.

概要：We have developed a navigation system for the blood vessel prosthesis replacement of aortic aneurysms, and have used it in clinical practice. This system supports surgeons to identify a target intercostal artery by using patient image. The patient image and real body are matched by registration. Reference points of registration are anatomical landmarks of skeleton such as jugular notch, sternal angle, left anterior superior iliac spine, pubis, and spinous process. However, identification of spinous process was hard to doctors in operation. We developed a new registration method which X, Y and Z axis correspond to the Head-Foot, Right-Left and Anterior-Posterior directions. The specific feature is that identification of spinous process is not necessary. We evaluated errors with the new registration method using the retrospective 6 clinical data. We calculated fiducial localization error. As a result, errors of anterior points in the Head-Foot direction were less than 10 mm. We aimed to reduce the Head-Foot error as less than 20 mm because the ribs exist at intervals of approximately 40 mm in the Head-Foot direction. The new registration method was confirmed to be effective in the decision of approach to the target artery. Moreover, even when the point of the spinous process changed to the next spinous process of the set spinous processes, error was equivalent to the original point, therefore, using the present system, the identification of the spinous process can be unnecessary. It was concluded that newly-developed registration algorism is effective for doctors in identification of intercostal artery.

概要：Transcatheter aortic valve replacement (TAVI) is a less invasive therapy and the number of operations is increasing. In some operations of TAVI, valve annulus rupture and failure were happened. Strain measurement method in the blood vessel has not been established and there is no way to evaluate the strain distribution experimentally. It is difficult to measure large deformation of the blood vessel using conventional digital volume correlation with computed tomography. This study presents a new strain measurement method of an elastic blood vessel model using the displacement distribution measured by tomographic particle image velocimetry. Tracer particles were distributed in the blood vessel model and displacement distribution was measured by tracking the particles. The displacement measuring accuracy affected by the amount of displacement and spatial resolutions was assessed. The strain yielded in the blood vessel model, when it was 10% expanded, was measured in the optimal condition determined by the accuracy measurement. In this study, the optimal displacement spatial resolutions and displacement condition were 64 X 64 X 64 voxel^3 and 90-150 μm respectively. This experimental investigation revealed that the higher strain was yielded in the inner wall of the blood vessel model and the strain becomes lower toward the outer wall.

ISSN：1347-443X

概要：Percutaneous coronary intervention (PCI) for ischemic heart disease became a common therapy. The improvement of treatment results was caused by invention of drug-eluting stent (DES) but its implantation procedure for pressure and inflation time has not been discussed. 3-time-balloon-inflation method is proved to be an effective method for inflation in in vitro experiments and it was practiced in the clinical field. The purpose of this study is to determine the effectiveness of the 3-time-balloon-inflation method and investigate the factors that cause suppression of stent expansion. From January 2011 to March 2012, PCI with drug-eluting stent (XIENCE V) were performed to 169 patients by a single-operator with 3-time-ballon-inflation method. Minimal lumen area (MLA), vessel cross-sectional area, and plaque cross-section in the MLA were measured by intravascular ultrasound (IVUS) before stent implantation. Minimum stent area (MSA) was measured after stent implantation. Stent expansion ratio (SER) was calculated from assumed area and MSA. Area acquisition ratio (AAR) was calculated from MSA and MLA. Subsequently, the ratio of calcification in the lesion was measured using the color mapping function mounted on the IVUS. The stent diameter used in this study was 2.89±0.35[mm] (mean±SD), stent length was 20.5±6.2[mm] (mean±SD), and the stent expansion pressure was 10.3±2.4[atm] (mean±SD). There was no difference in SER by stent size, target vessels, and MLA. Significant difference was seen in the calcification ratio between the group without pre-dilatation (n=27) and the group with pre-dilatation (n=142), but no difference in SER between the two groups. It was suggested that calcification ratio is one of the factors that causes the suppression of stent expansion because significance of calcification ratio came out in AAR.

ISSN：1347-443X

概要：A durability test of the implantable Left Ventricular Assist System EVAHEART was conducted to demonstrate that the EVAHEART Blood Pump can be run for 2 years without failing. This testing was useful to indicate potential for BTT and possibly DT applications. We developed a custom durability test mock circulation loop which generates a pulsatile flow simulating the native left ventricle. This mock circulation loop includes components which mimic the left ventricle (LV chamber) and compliance in the aorta (aortic column), and a loop which connects the blood pump to both the LV chamber (inlet) and the aortic column (outlet). The LV chamber has two one-way valves and a linear motor connected to a rolling seal, allowing it to generate pulsatile flow. The blood pump speed was tuned to achieve clinically relevant flow, based on the need to supplement a failing heart. The simulated heart rate (stroke rate of the linear actuator) cycled through 3 different settings each day to simulate changes in patient activity level. The sample size for the durability test was set to 18, and the test duration was 2 years. During the test, no critical blood pump failures were observed. There were no indications of significant decrease in pump performance or seal performance. Furthermore, no symptoms of failure, such as abnormal wear, were observed. In conclusion, the durability test successfully demonstrated that the EVAHEART Blood Pump achieved component reliability at a minimum of 90% reliability and 88% confidence interval over a mission life of two years.

ISSN：2185-7113

概要：冠動脈ステントの破断は, 再狭窄やステント血栓症のリスクとして認識されている. しかし, 実際の発生頻度は明確になっていない. 本研究は, 査読付き論文を調査することによって国内におけるステント破断の発生状況を評価し, 不具合報告の現状を明らかにすることを目的としている. 2014年4月1日にPubMedおよび医学中央雑誌 (医中誌) を用いてステント破断の発生に関する文献分析を実施した. PubMedでは, 「stent fracture」を検索単語として使用した. 医中誌では, 「冠動脈」「ステント」「fracture」「破断」「破損」を検索単語として使用した. PubMed検索で895報が検索された. これらの中で, 日本以外の施設にて実施された文献が792報, 冠動脈が対象ではない文献が45報, ステント破断とは関係のない文献が17報, 同一症例を対象としていると考えられる文献が11報あった. これらを除外し, 14報の観察研究および16報の症例報告で合計30報を解析対象とした. 査読付き論文では643病変でのステント破断, 不具合報告では105病変でのステント破断が報告されていた. 14報の観察研究から, ステント破断の発生頻度は5.4% (10,927病変中595病変) であった. 不具合報告から得られたステント破断の発生件数は, 文献分析によって得られた発生件数より6.1倍少なかった. これらの結果から, 不具合報告によって把握できる発生状況は, 実臨床で発生している状況の一部分を表しているに過ぎないことが定量的に示された.

ISSN：2185-7113

概要：

ソフトウェア医療機器 (Software as a Medical device, SaMD) は患者との接触がないため, 従来の医療機器ソフトウェア (Non-SaMD) のような直接的な危害ではなく, 間接的な危害を引き起こし得る. 本研究の目的は, 上記2種類に分類される, ソフトウェアを含む医療機器の間接的危害の実態をアメリカのリコールデータから分析することである. アメリカにおける医療機器のリコールのうち, 米国食品医薬品局がソフトウェア起因としたものを対象に, 各リコール製品がSaMDか否かに分類した. また, フィジカルなもの (Group 1), 情報に関係するもの (Group 2), データに関係するもの (Group 3), その他 (Group 4) の4つの故障モードに分類した. 2009～2014年の全リコール (6,393件) からソフトウェア起因のリコールとして抽出した712件に対して分類を行った結果, 間接的危害に繋がり得るGroup 2が408件 (57%) で第1位を占めており, 直接的危害に繋がり得るGroup 1が122件 (17%) で続いた. Group 2の408件中387件 (95%) がリコールクラスⅡとなっており, 6件 (1%) はリコールクラスⅠとなっていた. 6件のうち4件はNon-SaMDにて, 2件がSaMDにて起きていた. 本研究によって明らかになったこの事実は, 情報提示機能の安全性について今後さらに理解を深めていくことの重要性および安全対策が課題であることを示唆している.

概要：

A navigation system with high accuracy is required for performing precise surgery. To obtain high accuracy, three factors should be considered: acquiring precise image data of patient, measuring an accurate intraoperative patient position and reducing registration error. Although it spends a lot of efforts to set up the system during surgery, its performance does not always satisfy surgeons.

During this decade, we have developed a surgical navigation system for aortic aneurysm repair and utilized it in one hundred clinical cases. It has been found that this system has needed to improve the usability and the reliability in registration process to show valuable information for surgery. Our recent system adopts a two-phased approach with different goals. Before thoracotomy, it exhibits the location of a target intercostal artery in the thorax and supports a surgeon to determine an appropriate approach to repair aortic aneurysm in each patient setup and anatomy. After adhesiolysis, it narrows the range of existing area of the artery within five millimeters and assists him to identify the artery.

In 2016, its improved system is ready to use for clinical pre-trial with approval from Hospital Ethics Committee of Tokyo Women's Medical University. In the next two years, it is hoped that the improved system provides the clinical benefit.

概要：

【背景】我々の人工血管置換術用手術ナビゲーションシステムは、2006年にプロトタイプ機による臨床応用を開始した。当該システムによる100症例の臨床経験を通して、精度向上や使いやすさの工夫を重ね、新規ナビゲーションシステムが再構築された。新システムの臨床応用を2016年6月に開始したので、本稿ではその経験について報告する。【方法】新システムを胸腹部大動脈人工血管置換術6例に適用した。患者の体位決定後、消毒前に患者と事前に取得した画像データとのレジストレーションを行い、術者の目標血管へのアプローチ法を決定した。皮膚切開及び癒着部の剥離を経て、術野を確保した後、目標血管周辺に存在する特徴点に基づいて患者と画像とのずれを補正し、肋間動脈を同定した。【結果】ナビゲーションは全例でスムーズに運用できた。ナビゲーションに要した時間は、皮膚切開前のアプローチ方法の決定に9.8±1.7分、術野における血管同定に6.4±1.5分であった。皮膚切開前のナビゲーションでは左胸から目標血管へ向かう方向のアプローチを画像で確認するために十分な精度が得られ、剥離後も肋間動脈の目標血管の位置及び走行を確認できた。【結論】新システムは、現在良好に運用できている。今後は、新システムを解剖学的に特異的な症例にも適用し、ナビゲーションが広く使用できることを示していきたい。

ISSN：0966-8519

概要：BACKGROUND AND AIM OF THE STUDY:The study aim was to develop a novel stentless mitral valve (SMV) and to evaluate its performance, using an original pulsatile simulator developed specifically to analyze the hydrodynamic function of the mitral valve.;METHODS:The SMV developed at the authors' institution consists of two major components: a large anterior leaflet with commissures, and a small posterior leaflet. The valve is formed by suturing the leaflets (made from bovine pericardium) to a flexible (Duran) ring. The SMV, constructed with a 27 mm flexible ring, was installed into the mitral valve simulator, after which the four papillary flaps of the two leaflets were sutured to artificial papillary muscles. The artificial ventricle was driven pneumatically at a pulse rate of 70 beats/min, with a systolic fraction of 35%. The mean flow, aortic pressure, and atrial pressure were adjusted to 4.5 1/min, 120/80 mmHg, and 10 mmHg, respectively. A 27 mm mechanical valve (MEV; St. Jude Medical Inc.) was employed as a control. The hydrodynamic performance of the SMV and MEV were investigated and compared. An echo-Doppler study was also performed.;RESULTS:The waveforms of the SMV and MEV showed a similar pattern. The mean transvalvular flow was 4.7 +/- 0.4 1/min for the SMV, and 3.55 +/- 0.13 1/min for the MEV (p < 0.001). Mitral regurgitation was 5.07 +/- 1.15 and 3.78 +/- 0.35 ml/beat, respectively (p < 0.05). Echocardiographic data indicated that the regurgitant jet towards the left atrial model was none or trivial for the SMV, and trivial for the MEV.;CONCLUSION:Within the environment of the mitral valve simulator, the novel SMV prepared from bovine pericardium demonstrated excellent performance characteristics, and may represent a potential future alternative for bioprosthetic stented mitral valves.

概要：© 2016 Iijima et al.Background Clinical studies for assessing the effectiveness and safety in a premarketing setting are conducted under time and cost constraints. In recent years, postmarketing data analysis has been given more attention. However, to our knowledge, no studies have compared the effectiveness and the safety between the pre- and postmarketing settings. In this study, we aimed to investigate the importance of the postmarketing data analysis using clinical data. Methods and Findings Studies on capsule endoscopy with rich clinical data in both pre- and postmarketing settings were selected for the analysis. For effectiveness, clinical studies published before October 10, 2015 comparing capsule endoscopy and conventional flexible endoscopy measuring the detection ratio of obscure gastrointestinal bleeding were selected (premarketing: 4 studies and postmarketing: 8 studies) from PubMed (MEDLINE), Cochrane Library, EMBASE and Web of Science. Among the 12 studies, 5 were blinded and 7 were non-blinded. A time series meta-analysis was conducted. Effectiveness (odds ratio) decreased in the postmarketing setting (premarketing: 5.19 [95% confidence interval: 3.07-8.76] vs. postmarketing: 1.48 [0.81-2.69]). The change in odds ratio was caused by the increase in the detection ratio with flexible endoscopy as the control group. The efficacy of capsule endoscopy did not change between pre- and postmarketing settings. Heterogeneity (I2 ) increased in the postmarketing setting because of one study. For safety, in terms of endoscope retention in the body, data from the approval summary and adverse event reports were analyzed. The incidence of retention decreased in the postmarketing setting (premarketing: 0.75% vs postmarketing: 0.095%). The introduction of the new patency capsule for checking the patency of the digestive tract might contribute to the decrease. Conclusions Effectiveness and safety could change in the postmarketing setting. Therefore, time series meta-analyses could be useful to continuously monitor the effectiveness of medical device in clinical practices.

ISSN：14347229

概要：© 2016, The Japanese Society for Artificial Organs. Our aim was to conduct a scoping review of the regulations for hemodialyzers in the safety evaluation in Japan and the United States, and to evaluate the criteria for premarketing clinical trials and postmarketing safety reports to inform the development of a sophisticated premarketing evaluation in Japan. Regulations for approval of hemodialyzers were identified from the databases of the Ministry of Health, Labor and Welfare in Japan and the Federal Drug Agency (FDA) in the United States (US). The criteria for premarket clinical trials and postmarketing safety reports were evaluated for both countries. Standards in Japan required evaluation of blood compatibility and reporting of acute adverse effects by a premarketing clinical trial in 6 of 86 applications with semipermeable membrane materials deemed to be different to those of previously approved devices from 1983 to 31 August 2015. By comparison, the clinical trial was required in one of 545 approvals in the US from 1976 to 29 January 2016, but blood compatibility was not the point. All postmarketing adverse effects identified in Japan were included in the set of ‘warnings’. The more stringent requirements for evaluation of blood compatibility and acute adverse effects in Japan seemed to be related to differences in the history of quality management systems for medical devices between the two countries. This study revealed that there were differences between Japan and the US in requiring the premarketing clinical trials for the hemodialyzers. Our findings could be useful for constructing sophisticated premarketing safety evaluation.

ISSN：18684300

概要：© 2016, The Author(s).Stent struts protruding into ostial side branch called “jailed strut” at bifurcation lesions is a likely cause of thrombus formation. We aimed to investigate the influences of multiple kissing balloon inflation (KBI) for stent expansion, and stent platform design, respectively, on the reduction of incomplete stent apposition area (ISA area) caused by jailed struts at a side-branch ostium, using a three-dimensional elastic left main (LM) bifurcated coronary artery model. The referenced LM bifurcation angle data of 209 patients were stratified by tertiles focusing on the angle between the LM trunk (LMT) and left anterior descending artery (LAD). A bifurcation model was fabricated with angles of 129°, 122.2°, and 76.4° for LMT–LAD, LMT–left circumflex (LCx), and LAD–LCx, respectively, and with diameters of 5, 3.75, and 3.5 mm for LMT, LAD, and LCx, respectively; these diameters fulfill Murray’s law. A 75 % stenosis was included along the LMT. One-time and three-time KBIs were conducted using two-link Nobori and three-link Xience Xpedition (n = 6 each). The ISA area was quantified using micro-CT. Three-time KBI was effective in reducing the ISA area compared with one-time KBI for both the Nobori (p = 0.05) and Xience Xpedition (p = 0.07). The ISA area was smaller in the Nobori than in the Xience Xpedition, both in one-time and three-time KBI (one-time KBI: p = 0.003; three-time KBI: p = 0.001). Our findings of this study on reducing the ISA area by focusing on an interventional technique and stent design may help to improve coronary bifurcation intervention for a possibly better long-term clinical outcome.

ISSN：14347229

概要：© 2017, The Author(s). Thrombus formation at the interface between connectors and tubes is a potential risk factor for complications. We investigated time-dependent relationships between formation of thrombus and hemodynamic factors at the interface between connectors and tubes using optical coherence tomography (OCT) under pulsatile flow. A swept-source OCT with the center wavelength of 1330 nm was employed. The sequential process of thrombus formation at the interface of connectors and tubes in the inlet and outlet was investigated. Connectors with and without tapers were tested using identical 50-ml air-contactless circuits. Fresh human blood from healthy volunteers was circulated under pulsatile flow. Thrombus initially formed at the interface between the connector tip and the tube. Geometries of thrombus growth were different between the 2 connectors, and between the inlet and the outlet. Growth of thrombus was observed at the interface between the connectors and tubes over time in 60 min circulation, except at the outlet part of connector without tapers. At the connector without tapers outlet, thrombus propagation length from the connector edge toward the flow downstream was comparable at 10 and 60 min (0.55 ± 0.35 vs. 0.51 ± 0.32 mm, p = 0.83). Analysis using particle image velocimetry showed the presence of a flow reattachment point 1.5 mm downstream from the connector edge. These results suggest that the flow reattachment point inhibits downstream thrombus growth. We quantitatively demonstrated sequential thrombus process at the interface between the connectors and tubes under pulsatile flow of human blood using OCT.

概要：© 2017 Takahashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: The mechanical interaction between blood vessels and medical devices can induce strains in these vessels. Measuring and understanding these strains is necessary to identify the causes of vascular complications. This study develops a method to measure the three-dimensional (3D) distribution of strain using tomographic particle image velocimetry (Tomo-PIV) and compares the measurement accuracy with the gauge strain in tensile tests. Methods and findings: The test system for measuring 3D strain distribution consists of two cameras, a laser, a universal testing machine, an acrylic chamber with a glycerol water solution for adjusting the refractive index with the silicone, and dumbbell-shaped specimens mixed with fluorescent tracer particles. 3D images of the particles were reconstructed from 2D images using a multiplicative algebraic reconstruction technique (MART) and motion tracking enhancement. Distributions of the 3D displacements were calculated using a digital volume correlation. To evaluate the accuracy of the measurement method in terms of particle density and interrogation voxel size, the gauge strain and one of the two cameras for Tomo-PIV were used as a video-extensometer in the tensile test. The results show that the optimal particle density and interrogation voxel size are 0.014 particles per pixel and 40 × 40 × 40 voxels with a 75% overlap. The maximum measurement error was maintained at less than 2.5% in the 4-mm-wide region of the specimen. Conclusions: We successfully developed a method to experimentally measure 3D strain distribution in an elastic silicone material using Tomo-PIV and fluorescent particles. To the best of our knowledge, this is the first report that applies Tomo-PIV to investigate 3D strain measurements in elastic materials with large deformation and validates the measurement accuracy.

概要：© 2017 Matsuhashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Blood-contacting devices have contributed to improving the treatment of patients. However, thrombus formation at the interface between a connector and tube is still a potential source of thrombus-related complications that induce stroke or myocardial infarction. We aimed to develop a non-blood-contacting real-time method for visualizing thrombus formation, and to experimentally investigate the time-dependent phenomenon of thrombus formation at the interface between a connector and a tube in a medical device. Methods and findings: An optical coherence tomography device with a center wavelength of 1330 nm was used to visualize thrombus formation during porcine blood circulation for 50 min in a closed 50-mL circulation system isolated from ambient air. The thrombus formation sites at the interface between a tube and connector were visualized. The area of the thrombus formation at the interface between the inlet of the connector and the tube was found to be 0.012 ± 0.011 mm 2 . Conversely, at the interface between the outlet of the connector and the tube, the area was found to be 0.637 ± 0.306 mm 2 . Thus, significantly larger amounts of thrombus were formed at the outlet interface (p < 0.01). The thrombus formation area at the outlet interface increased over time. Conversely, the area of thrombus formation showed repeated increasing and decreasing behavior at the inlet interface. Flow visualization with particle image velocimetry showed the presence of a flow separated area in the minimal f low phase at the inlet interface and a large recirculating slow flow region at the outlet interface in the minimal flow phase. These data suggested that the recirculating stagnant flow region contributed to thrombus growth. Conclusions: The method presented here was effective in quantitatively assessing time-dependent phenomena of thrombus formation at the connector-tube interface. The method may contribute to the assessment of thrombogenicity of a novel design of connector.

ISSN：09108327

概要：© 2017 Springer Japan KK, part of Springer Nature As transcatheter aortic valve implantation (TAVI) requires multidisciplinary collaboration, operators and the entire heart team must overcome a steep learning curve. A web-based screening and traditional on-site proctoring system were developed for the introduction of TAVI in Japan. To assess the learning curve involved with the introduction of TAVI under the supervision of a novel proctoring system. We divided 749 consecutive patients enrolled in the OCEAN-TAVI study between October 2013 and August 2015 into the trans-femoral (TF, n = 608) and transapical (TA, n = 141) approach groups to compare outcomes in patients who underwent TAVI during the early proctoring period (proctoring group) and after the procedures began to be performed independently (independent group). The primary endpoint was the rate of composite events regarding early safety (at 30 days) according to the valve academic research consortium-2 criteria. For TF-TAVI, the logistic EuroSCORE and the rate of peripheral artery disease were significantly lower during the independent period. The rate of device success significantly increased during the independent period (90.5 vs. 81.8%, p = 0.005). The rate of the primary endpoint was significantly reduced during the independent period compared to that during the proctoring period for TA-TAVI (21.3 vs. 37.9%, p = 0.031); however, no difference was observed for TF-TAVI (16.8 vs. 13.1%, p = 0.283). No deaths occurred within 30 days during the proctoring period for TF-TAVI. After adjustment using propensity score matching, the procedure time for TF-TAVI (88 ± 43 vs. 102 ± 36 min, p = 0.004) and the rate of life-threatening bleeding for TA-TAVI (3.6 vs. 25%, p = 0.026) reduced during the independent period compared to the values during the proctoring period. During the introduction of TAVI under the supervision of a new proctoring system in Japan, clinical outcomes and technical aspects improved significantly. There are differences in the steepness of the learning curve between TF-TAVI and TA-TAVI.

ISSN：14347229

概要：© 2018 The Japanese Society for Artificial Organs We analyzed the adverse events associated with an off-label use of arterial stents and CE-marked iliac vein stents for the treatment of iliac venous thromboembolism and investigated their relationships with the anatomical features of the iliac vein, to gain insights into the development of a better iliac vein stent. Reports of adverse events following the use of stents in the iliac vein were retrieved from the Manufacturer and User Facility Device Experience (MAUDE) database that contain suspected device-associated complications reported to the Food and Drug Administration. Data from 2006 to 2016 were investigated. The literature analysis was also conducted using PubMed, Cochrane Library, EMBASE, and Web of Science focusing on English articles published up to 4 October 2016. The analysis of 88 adverse events from the MAUDE database and 182 articles from the literature revealed that a higher number of adverse events had been reported following the use of arterial stents in the iliac vein compared to CE-marked iliac vein stents. While stent migration and shortening were reported only for the arterial stents, stent fracture and compression occurred regardless of the stent type, even though a vein does not pulsate. A study of the anatomical features of the iliac vein implies that bending, compression, and kink loads are applied to the iliac vein stents in vivo. For designing, developing, and pre-clinical testing of stents intended for use in the iliac vein, the above mechanical load environments induced by the anatomical features should be considered.

ISSN：1774024X

概要：© Europa Digital & Publishing 2018. All rights reserved. This is a consensus document from the European Bifurcation Club concerning bench testing in coronary artery bifurcations. It is intended to provide guidelines for bench assessment of stents and other strategies in coronary bifurcation treatment where the United States Food and Drug Administration (FDA) or International Organization for Standardization (ISO) guidelines are limited or absent. These recommendations provide guidelines rather than a step-by-step manual. We provide data on the anatomy of bifurcations and elastic response of coronary arteries to aid model construction. We discuss testing apparatus, bench testing endpoints and bifurcation nomenclature.

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