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Background In Japan, ventricular assist devices (VADs) have been used for patients with severe heart failure as a bridge to transplantation (BTT) since 1992. However, it was not until 1997, when the Organ Transplant Law was enacted, that medical devices received approval by the national health insurance system for that use. To encourage research and development of innovative medical devices, the Pharmaceuticals and Medical Devices Agency has established a public–private partnership in collaboration with academic societies, hospitals and manufacturers. Methods The Japanese registry for Mechanically Assisted Circulatory Support (J-MACS) is a prospective registry designed to be harmonized with the Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS). Participation in J-MACS is mandatory for device manufacturers to meet the conditions of approval as well as for hospitals to obtain authorization for reimbursement from the national health insurance system. Results From June 2010 to April 2015, 476 patients were registered at 31 hospitals. Of these, analysis of primary VAD patients ( n = 332) revealed that their overall 360-day survival was 91% (implantable 93%, extracorporeal 84%). Conclusions This initial report from J-MACS focuses on patients’ demographics, device types, survival, competing outcomes, adverse events and successful examples of system failure detection. [ABSTRACT FROM AUTHOR]

Background: Escherichia coli has two L-cysteine biosynthetic pathways; one is synthesized from O-acetyl L-serine (OAS) and sulfate by L-cysteine synthase (CysK), and another is produced via S-sulfocysteine (SSC) from OAS and thiosulfate by SSC synthase (CysM). SSC is converted into L-cysteine and sulfite by an uncharacterized reaction. As thioredoxins (Trx1 and Trx2) and glutaredoxins (Grx1, Grx2, Grx3, Grx4, and NrdH) are known as reductases of peptidyl disulfides, overexpression of such reductases might be a good way for improving L-cysteine production to accelerate the reduction of SSC in E. coli. Results: Because the redox enzymes can reduce the disulfide that forms on proteins, we first tested whether these enzymes catalyze the reduction of SSC to L-cysteine. All His-tagged recombinant enzymes, except for Grx4, efficiently convert SSC into L-cysteine in vitro. Overexpression of Grx1 and NrdH enhanced a 15-40% increase in the E. coli L-cysteine production. On the other hand, disruption of the cysM gene cancelled the effect caused by the overexpression of Grx1 and NrdH, suggesting that its improvement was due to the efficient reduction of SSC under the fermentative conditions. Moreover, L-cysteine production in knockout mutants of the sulfite reductase genes (△cysI and △cysJ) and the L-cysteine synthase gene (△cysK) each decreased to about 50% of that in the wild-type strain. Interestingly, there was no significant difference in L-cysteine production between wild-type strain and gene deletion mutant of the upstream pathway of sulfite (△cysC or △cysH). These results indicate that sulfite generated from the SSC reduction is available as the sulfur source to produce additional L-cysteine molecule. It was finally found that in the E. coli L-cysteine producer that co-overexpress glutaredoxin (NrdH), sulfite reductase (CysI), and L-cysteine synthase (CysK), there was the highest amount of L-cysteine produced per cell. Conclusions: In this work, we showed that Grx1 and NrdH reduce SSC to L-cysteine, and the generated sulfite is then utilized as the sulfur source to produce additional L-cysteine molecule through the sulfate pathway in E. coli. We also found that co-overexpression of NrdH, CysI, and CysK increases L-cysteine production. Our results propose that the enhancement of thioredoxin/glutaredoxin-mediated L-cysteine synthesis from SSC is a novel method for improvement of L-cysteine production. [ABSTRACT FROM AUTHOR]

Abstract  Hydrodynamic coefficients strongly affect the dynamic performance of autonomous underwater vehicles (AUVs). Thus it is important to have the true values of the coefficients in order to simulate the AUV’s dynamic performance accurately. Although these coefficients can be predicted by many methods, most are only applicable for AUVs with streamlined shapes. Computational fluid dynamics (CFD) can be applied to estimate the hydrodynamic coefficients of AUVs with complex shapes. In this study, CFD was applied to estimate the hydrodynamic coefficients of the AUV TUNA-SAND (which stands for terrain-based underwater navigable AUV for seafloor and natural resources development), which has a complex block-like structure. First, the validity of the CFD simulation was verified by comparison with experimental results. Second, the relationships between hydrodynamic loads and motions for all six degrees of freedom were analyzed using the simulated results. Third, the importance of each hydrodynamic coefficient was investigated based on these relationships. There are 16 key damping coefficients that relate to viscosity and 12 key inertial coefficients that relate to the potential flow around TUNA-SAND. Finally, the values of all the key coefficients were obtained and verified by comparing the solutions of the simulated dynamics with the experimental results. [ABSTRACT FROM AUTHOR]

Abstract: This paper uses a modified Harrodian model to understand both the long period of rapid Japanese growth and the recent period of stagnation. The model has multiple steady-growth solutions when the labour supply is highly elastic, and government intervention, we argue, took the Japanese economy onto a high-growth trajectory. Labour constraints began to appear around 1970, and a combination of high saving rates and slow population growth account for the stagnation of the 1990s. This combination produces a structural liquidity trap and threatens the sustainability of attempts to ensure near full employment through fiscal policy or by running a persistent trade surplus. [Copyright &y& Elsevier]

A stereograph of atomic arrangement was displayed directly on the screen of display-type spherical-mirror analyzer without any computer-aided conversion process for the first time. This stereoscopic photograph enables viewing three-dimensional atomic arrangement. This technique was realized taking advantage of the phenomenon of circular dichroism in photoelectron angular distribution. The azimuthal shifts of forward focusing peaks in a photoelectron angular distribution taken with left and right helicity light in a special arrangement are the same as the parallaxes in a stereo view of atoms. Hence a stereoscopic recognition of three-dimensional atomic arrangement is possible, when the left eye and the right eye respectively view the two images obtained by left and right helicity light simultaneously. [Copyright &y& Elsevier]

Abstract: Materials and Life Science Facility (MLF) of Japan Proton Accelerator Research Complex (J-PARC) is one of the facilities that provided the highest intensity pulsed neutron and muon beams. The MLF computing environment design group organizes the computing environments of MLF and instruments. It is important that the computing environment is provided by the facility side, because meta-data formats, the analysis functions and also data analysis strategy should be shared among many instruments in MLF. The C++ class library, named Manyo-lib, is a framework software for developing data reduction and analysis softwares. The framework is composed of the class library for data reduction and analysis operators, network distributed data processing modules and data containers. The class library is wrapped by the Python interface created by SWIG. All classes of the framework can be called from Python language, and Manyo-lib will be cooperated with the data acquisition and data-visualization components through the MLF-platform, a user interface unified in MLF, which is working on Python language. Raw data in the event-data format obtained by data acquisition systems will be converted into histogram format data on Manyo-lib in high performance, and data reductions and analysis are performed with user-application software developed based on Manyo-lib. We enforce standardization of data containers with Manyo-lib, and many additional fundamental data containers in Manyo-lib have been designed and developed. Experimental and analysis data in the data containers can be converted into NeXus file. Manyo-lib is the standard framework for developing analysis software in MLF, and prototypes of data-analysis softwares for each instrument are being developed by the instrument teams. [Copyright &y& Elsevier]

Abstract: We have developed a prototype data acquisition and device control system for experiment instruments at the Material and Life science Facility (MLF)/Japan-Proton Accelerator Research Complex (J-PARC). The system employs distributed computing via Ethernet, client/server architecture, modular structure and a state machine. Communication between client and server software utilizes socket protocols over TCP/IP. We have deployed this prototype software in the network distributed control system by improving the data acquisition software used at KENS, introducing the system for the SWAN at KENS/KEK. It was kept in working order throughout 2 weeks of machine operation. [Copyright &y& Elsevier]

Proposes a method of polarization analysis based on the phenomenon of strong circular dichroism in two-dimensional photoelectron diffraction patterns using a display-type spherical mirror analyzer. Design of the analyzer; Excitation source; Mechanism of the azimuthal shift.

The performance of electric double-layer capacitors and lithium-ion batteries deteriorates with increasing humidity. The desirable effect of bound water on the energy-storage properties of physically dry cellulose nanofiber (Na-ACF) supercapacitors with sodium (Na) carboxylate radicals was investigated using infrared and near-infrared spectroscopy, and nuclear magnetic resonance spectroscopy, alternating current impedance analyses, and first-principles calculations. The storage capacity decreased gradually upon heating to 423 K and reached zero upon exceeding 483 K, accompanied by increasing electrical resistance, forming a distorted semicircle in Nyquist diagram and drawing the phase angle to zero in Bode diagram. This is attributed to the water in the hydration gel bound to the Na+-ions that cross-link the cellulose chains, evaporating as the temperature increases, and finally becoming Na2O. The increased band-gap energy from the increase in bound water prevents leakage from the supercapacitor. In contrast to ordinary batteries, bound water is necessary for developing Na-ACF supercapacitors. [ABSTRACT FROM AUTHOR]

Background Few studies have reported the outcomes of antimicrobial stewardship programs (ASPs) implemented without infectious disease (ID) physician or pharmacist specialists. We implemented interventions that included providing antimicrobial optimization recommendations through a pharmacist-led team using prospective audit and feedback. This study evaluated different types of interventions and their impact on the outcomes of ASPs in a medium-sized hospital without ID specialists. Methods This retrospective pre–post study included adult inpatients treated with intravenous antimicrobials between April 2016 and March 2020. Outcome (eg, length of hospital stay [LOS], drug cost) and process measures (eg, type of intervention, length of therapy) were compared between 2 time periods: pre-ASP (April 2016–March 2018) and post-ASP (April 2018–March 2020). Results We included 5419 and 5634 patients in the pre- and post-ASP periods, respectively. The most common types of interventions were adjusting length of therapy (49.5%), additional laboratory tests (27.1%), antimicrobial change (16.2%), and dosage of antimicrobial (7.1%). After ASP implementation, LOS significantly decreased (14.8 vs 13.8 days, P <.01), along with the length of therapy, empirical use of antipseudomonal and anti–methicillin-resistant Staphylococcus aureus drugs, and number of days to de-escalation. No significant differences were noted in 30-day mortality, 30-day readmission, or de-escalation rates. On average, the antimicrobial cost per hospitalization decreased from US$173.03 to US$120.66. Conclusions Pharmacist-led ASP interventions that focus on the length of therapy have the potential to reduce LOS in hospitals without ID specialists. Overall, this study showed that ASPs can be effectively implemented in medium-sized hospitals without ID specialists. [ABSTRACT FROM AUTHOR]

Under the revised heart allocation system in the United States, bridge to transplant (BTT) patients with left ventricular assist device (LVAD) have a longer waitlist period, as they are now lowly prioritized. However, little is known regarding the long-term trajectory of functional capacity (FC) and health-related quality of life (HR-QOL) among BTT-LVAD patients. We retrospectively analyzed 442 consecutive patients with BTT-LVAD between April 2013 and May 2019 from a Japanese nationwide registry. FC (New York Heart Association [NYHA] functional class, peak oxygen uptake [VO 2 ], and 6-min walk test [6MWT]) and HR-QOL (European Quality of Life [EQ-5D index] and Visual Analogue Scale [EQ-VAS]) were assessed at baseline and for up to 60 months after LVAD implantation. During the follow-up period of 30 months (IQR 18–42 months), 100 (22.6%) patients underwent transplantation, 37 (8.3%) died, and 14 (3.1%) underwent explantation for recovery. Mean peak VO 2 , 6MWT distance, EQ-5D index, and EQ-VAS significantly improved 3 months after LVAD implantation (p = 0.0012, p = 0.0037, p < 0.001, p < 0.001, respectively). Furthermore, these improvements were sustained for up to 60 months following LVAD implantation. Major adverse events including device failure, infection, stroke, and bleeding, which occurred within the first 3 months after LVAD implantation may have not affected FC or HR-QOL for up to 60 months (p = 0.15, p = 0.22, respectively). BTT patients showed long-term preservation of FC and HR-QOL, suggesting that BTT remains an option despite the long waiting time to HTx. • BTT-LVAD patients showed long-term preservation of functional capacity and HR-QOL. • Early major adverse events may have not affected long-term functional capacity or HR-QOL. • This study suggested that BTT remains an option despite the long waiting list time. [ABSTRACT FROM AUTHOR]

The electric charge storage properties of amorphous cellulose nanofiber (ACF) supercapacitors with different metal carboxylate radicals (COOM; M: Na(I), Ca(II), Al(III)) was investigated in terms of charging/discharging behaviours, alternating current impedance analysis, and plane-wave-based first-principles density functional calculations. Na-ACF exhibited a higher storage effect than Ca- and Al-ACFs. The charge storage mechanism for an Na-ACF supercapacitor was proposed using an electric double layer model in a C12H17O11Na electrolyte with an electrical resistivity of 6.8 × 103 Ω cm, based on the migration of protonic soliton. The supercapacitor, which demonstrated fast charging upon voltage application, could illuminate a white LED for 7 s after charging with 10 mA at 18.5 V. [ABSTRACT FROM AUTHOR]

Background: Our recent study showed that granulocyte-colony stimulating factor (G-CSF) promoted bone-marrow cells (BMC) to migrate into the infarcted heart and that they differentiated into cardiomyocytes. However, we still do not know to what degree bone-marrow-derived cardiomyocytes contribute to myocardial regeneration after injury. In this study, we verified the proportional contribution of cells from bone marrow (BM) and from non-bone marrow (n-BM) in regenerating neomyocardium after myocardial infarction.Methods: Eight C57BL/6 mice were irradiated (900 cGy), and green fluorescent protein (GFP) mouse-derived BMCs (GFP-BMC, 1 × 106 cells) were injected. Four weeks later, the left descending coronary artery was ligated. Recombinant human G-CSF (200 μg/kg/day, 8 days) was injected. At 4 weeks after ligation, hearts were fixed for histology. We calculated the proportions of cardiomyocytes derived from BM and n-BM after taking the chimeric rate into consideration.Results: The chimeric rate was 54.6% ± 5.9%. At the infarcted border area, the total cell number was 1000.3 ± 56.5/mm2, and mobilized BM-derived GFP-BMC was 103.3 ± 13.1/mm2. After compensation with the chimeric rate, we found BM-derived troponin I-positive cells at 23.9 ± 4.1/mm2, nestin-positive cells at 12.9 ± 2.6/mm2, and Ki67-positive cells at 18.3 ± 2.6/mm2, respectively. We found significant differences in the contribution of troponin I-(6.7% ± 1.7% vs 93.3% ± 1.7%), nestin- (2.4 ± 0.5 vs 97.6 ± 0.5), and Ki67-positive (3.9 ± 1.0 vs 96.1 ± 1.0) cells derived from BM and n-BM.Conclusions: Bone marrow was one of the origins of regenerated cardiomyocytes; however, the contribution of cells from BM was very small compared with those of n-BM origin in the infarction model. [Copyright &y& Elsevier]

Background: Our previous study showed that granulocyte-colony stimulating factor (G-CSF) enhanced bone-marrow-cell migration into the injured heart and that bone-marrow cells differentiated into cardiomyocytes. However, the number of bone-marrow-derived cardiomyocytes seems too small to have a direct, positive impact on pump function. Therefore, we hypothesized that G-CSF directly could affect the host myocardium through G-CSF receptors (G-CSFRs).Methods: In experiment 1, we cultured normal mouse heart cells with G-CSF at concentrations of 0, 1, 10, 50, and 100 ng/ml. In experiment 2, we cultured heart cells derived from a recipient with idiopathic cardiomyopathy (IDCM) after heart transplantation. We compared the total number of heart cells and Ki67- and troponin I (TnI)–positive cells with/without G-CSF at 50 ng/ml. We also performed immunochemical staining of the heart specimen from a recipient with IDCM using a rabbit polyclonal anti-G-CSFR antibody.Results: In experiment 1, mouse heart cells with G-CSF (50 ng/ml) proliferated maximally. In experiment 2, the total numbers of heart cells, Ki67-positive cells. TnI-positive cells, Ki67– and TnI–double-positive cells in the G-CSF group were greater than those in the non-G-CSF group at Days 14 and 28 (p < 0.05). In the IDCM heart, G-CSFRs on cardiomyocytes were expressed heterogeneously and widely.Conclusions: Granulocyte-colony stimulating factor directly enhanced the proliferation of TnI-positive cells derived from a recipient with IDCM through the G-CSFR. [Copyright &y& Elsevier]

Background: To safely implant cells into the myocardium, we must establish a volume that prevents compromising cardiac performance. We studied pressure–volume (PV) to investigate the adverse effects of direct cell implantation in the acute phase.Methods: We used 21 minipigs. In the normal heart model, we studied PV by measuring various parameters (including end-systolic pressure, end-systolic elastance, dp/dtmax, end-diastolic volume, and time constant of isovolumetric left ventricular pressure fall [Tau]). We injected solutions into the left ventricular free wall (15 cm2). Sampling points were at baseline and after injection of saline (Group I, n = 4) or of blood (Group II, n = 4) at volumes of 1 ml and 10 ml up to 30 minutes after injection. In Group II, we injected additional blood (10 ml) 4 times. In the ischemic heart model, 1 month after ligating the left anterior descending artery, we injected 1 ml saline (Group III, n = 4), bone marrow mononuclear cells (108 cells/1 ml; Group IV, n = 4), or bone marrow stromal cells (108 cells/1 ml; Group V, n = 3). We studied PV before and after injection.Results: In Group I, we found no significant changes in parameters. In Group II, end-diastolic volume after 10-ml injection (24.4 ± 3.6 ml) was smaller than end-diastolic volume at baseline (29.5 ± 5.8 ml, p < 0.01). Tau after 10-ml injection (39.4 ± 5.3 msec) was greater than at baseline (35.6 ± 4.0 msec, p < 0.01). One pig died of ventricular fibrillation after a 20-ml injection of blood. We observed no detrimental effects in Groups III, IV, and V.Conclusions: More than 10 ml cell suspension compromised diastolic function. We safely performed direct injection of bone marrow cells (1 × 108/1 ml). [Copyright &y& Elsevier]

Objectives: Cardiopulmonary bypass (CPB) induces systemic inflammatory response with neutrophil activation and subsequent lung dysfunction. Rolipram, a selective phosphodiesterase type 4 inhibitor, blocks the decrease in levels of cyclic adenosine monophosphate associated with neutrophil activation. Here, we tested the protective effect of rolipram on CPB-induced lung injury in the rat. Methods: Rats were divided into three groups: control (C), rolipram (R) and sham (S). In the C and R groups, animals underwent CPB at a flow rate of 60 ml/kg per min for 60 min followed by another 60-min observation, whereas the S group rats were sustained for 120 min only with median sternotomy and the placement of cannulae for CPB. Rolipram (40 μg/kg per min) was administered to the R group rats by continuous intravenous infusion from 10 min before the establishment of CPB to the end of the experiment. Results: The R and S groups showed significantly higher mean arterial oxygen pressure and lower mean lung wet-to-dry weight ratio compared with those observed in the C group (R: 489±44 or S: 527±55 vs. C: 287±185, and R: 5.0±0.4 or S: 4.7±0.3 vs. C: 5.9±0.5, respectively; P<0.01). Although CD11b expression levels on circulating neutrophils in the C group doubled after CPB, those in the R and S groups remained almost the same (P=0.0008). Intrapulmonary tumor necrosis factor-α concentrations (pg/μg protein) in the C group tended to be higher than those observed in the R and S groups (R: 5.2±2.1, S: 5.0±2.1 and C: 8.9±5.4; R vs. C: P=0.09 and S vs. C: P=0.08). Pathological study of lungs revealed that more alveolar hemorrhage and neutrophil accumulation were observed in the C group compared to the R and S groups. Conclusions: These results suggest that rolipram prevents acute lung injury via the inhibition of neutrophil activation during and after CPB in this setting of a rat model. [Copyright &y& Elsevier]

: ObjectivesWe investigated the feasibility of myocardial contrast echocardiography (MCE) to evaluate regional perfusion after bone marrow cell transplantation.: BackgroundThe myocardial microvessels improved by cell transplantation are too small to visualize with conventional angiography.: MethodsFourteen mini-pigs from the Nippon Institute for Biological Science were used. The proximal left anterior descending coronary artery was ligated. One month later, nine pigs survived. Six pigs received autologous cell transplantation into the left ventricular anterior wall: bone marrow mononuclear cells (BMMNCs) (n = 3) and bone marrow stromal cells (BMSCs) (n = 3). The other three pigs received saline (control group, n = 3). The pigs were sacrificed one month later. Myocardial contrast intensity (MCI) with a contrast agent was measured using the SONOS 5500 system (Philips). Capillary density (CD) and MCI were measured at four areas: anteroseptum (nontransplanted infarct area), anterior wall (transplanted infarct area), septum (border zone), and lateral wall (normal). We compared the anteroseptum with the anterior wall by MCI and CD.: ResultsIn the BMMNC and BMSC subsets, the CD of the anterior wall was higher than that of the anteroseptum (p < 0.001). There was a linear relation between MCI and CD (acoustic unit [AU2] = 0.234 CD + 0.010, r = 0.92, p < 0.001). At one month after cell transplantation, MCI of the anterior wall increased in the BMMNC and BMSC subsets (p < 0.05), although it did not change in the control group. The ratio of wall thickness (systole/diastole) in the transplanted infarct area was larger than that in the nontransplanted infarct area (p < 0.01).: ConclusionsMyocardial contrast echocardiography is useful to evaluate regional perfusion, which was enhanced by bone marrow cell transplantation. [Copyright &y& Elsevier]

: BackgroundCell transplantation is a promising therapy for treating end-stage heart failure. Bone marrow mononuclear cells (BMMNC) have been used to enhance angiogenesis in ischemic heart disease. However, the effect of BMMNC transplantation in non-ischemic dilated cardiomyopathy is unknown. In this study, we evaluated the efficacy of BMMNC transplantation in doxorubicin-induced cardiomyopathy in a rat model.: MethodsDoxorubicin (15 mg/kg, IP) was introduced into 52 Lewis rats. They were divided into 3 groups at 4 weeks after injection: transplant group (TX, BMMNC [1×106] implantation, n = 18), control group (CN, saline injection, n = 18), and sham group (SH, thoracotomy, n = 16). At 4 weeks after surgery, we used echocardiography to measure systolic left ventricular diameter (LVDs), diastolic left ventricular diameter (LVDd), fractional shortening (FS), and left ventricular wall thickness/LVDs. We used a Langendorff apparatus to measure systolic, diastolic, and developed pressures. We used radioimmunoassay to measure circulating atrial natriuretic peptide concentration, and we performed histologic study, including electron-microscopic study.: ResultsLeft ventricular wall thickness/LVDs in the TX group was the largest of all groups (p < 0.05). Systolic and developed pressures in the TX group were the greatest (p < 0.005). Systolic left ventricular diameter, FS, and end-diastolic pressure in the TX group were smaller than in the SH group (p < 0.05). These cardiac parameters did not differ significantly between TX and CN groups, but secondary changes (decreased heart weight, developed ascites, and increased atrial natriuretic peptide concentration) caused by doxorubicin-induced heart failure were most attenuated in the TX group. In the TX group, vascular density was greatest (p < 0.05) in the left ventricular free wall and in the septum. In addition, electron microscopy showed that myocardium in the TX group was most maintained.: ConclusionBone marrow mononuclear cell transplantation had beneficial effects in doxorubicin-induced cardiomyopathy. [Copyright &y& Elsevier]

Despite the intense interest in cellulose nanofibers (CNFs) for biomedical and engineering applications, no research findings about the electrical energy storage of CNF have been reported yet. Here, we present the first electroadsorption effects of an amorphous cellulose nanofiber (ACF) supercapacitor, which can store a large amount of electricity (221 mJm−2, 13.1 Wkg−1). The electric storage can be attributed to the entirely enhanced electroadsorption owing to a quantum-size effect by convexity of 17.9 nm, an offset effect caused by positive polar C6=O6 radicles, and an electrostatic effect by appearance of the localised electrons near the Na ions. The supercapacitor also captures both positive and negative electricity from the atmosphere and in vacuum. The supercapacitor could illuminate a red LED for 1 s after charging it with 2 mA at 10 V. Further gains might be attained by integrating CNF specimens with a nano-electromechanical system (NEMS). [ABSTRACT FROM AUTHOR]

Abstract: A beam interlock system with safety keys is adopted in the Materials and Life science experimental Facility (MLF) at J-PARC to protect users conducting experiments from excessive doses of radiation from neutron and muon beams. This paper outlines the interlock system from the point of view of safety, understandability and adaptability. [Copyright &y& Elsevier]

The energy-resolved neutron imaging system, RADEN, has been installed at the pulsed neutron source in the Materials and Life Science Experimental Facility of the Japan Proton Accelerator Research Complex. In addition to conventional neutron radiography and tomography, RADEN, the world's first imaging beam-line at a pulsed neutron source, provides three main options for new, quantitative neutron imaging techniques: Bragg-edge imaging to visualize the spatial distribution of crystallographic information, resonance absorption imaging for elemental composition and temperature information, and polarized neutron imaging for magnetic field information. This paper describes the results of characterization studies of the neutronic performance and installed devices at RADEN and shows the results of several demonstration studies for pulsed neutron imaging. [ABSTRACT FROM AUTHOR]

Patients with cardiogenic shock (CS) needing temporary circulatory support (TCS) have poor survival rates after implantation of durable ventricular assist device (dVAD). We aimed to characterize post-dVAD adverse event burden and survival rates in patients requiring pre-operative TCS. We analyzed 13,511 adults (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] Profiles 1–3) with continuous-flow dVADs in International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support (2013–2017) according to the need for pre-operative TCS (n = 5,632) vs no TCS (n = 7,879). Of these, 726 (5.4%) had biventricular assist devices (BiVAD). Furthermore, we compared prevalent rates (events/100 patient-months) of bleeding, device-related infection, hemorrhagic and ischemic cerebrovascular accidents (hemorrhagic cerebral vascular accident [hCVA], and ischemic cerebral vascular accident [iCVA]) in early (<3 months) and late (≥3 months) post-operative periods. TCS included extracorporeal membrane oxygenation (ECMO) (n = 1,138), intra-aortic balloon pump (IABP) (n = 3,901), and other TCS (n = 593). Within 3 post-operative months, there were more major bleeding and cerebrovascular accidents (CVAs) in patients with pre-operative ECMO (events/100 patient-months rates: bleeding = 19, hCVA = 1.6, iCVA = 2.8) or IABP (bleeding = 17.3, hCVA = 1.5, iCVA = 1.5) vs no TCS (bleeding = 13.2, hCVA = 1.1, iCVA = 1.2, all p < 0.05). After 3 months, adverse events were lower and similar in all groups. Patients with ECMO had the worst short- and long-term survival rates. Patients with BiVAD had the worst survival rate regardless of need for pre-operative TCS. CVA and multiorgan failures were the common causes of death for patients with TCS and patients without TCS. Patients requiring TCS before dVAD had a sicker phenotype and higher rates of early post-operative adverse events than patients without TCS. ECMO was associated with very high early ischemic stroke, bleeding, and mortality. The extreme CS phenotype needing ECMO warrants a higher-level profile status, such as INTERMACS "0." [ABSTRACT FROM AUTHOR]

Patients with advanced heart failure and cardiogenic shock (CS) often require temporary circulatory support (TCS) as a bridge to durable ventricular assist devices (dVADs). We aim to characterize longitudinal outcomes of patients with and without CS. Between 2013 and 2017, 13,813 adult patients classified as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profiles 1 to 3 with continuous flow left ventricular assist devices or biventricular assist devices were registered into the International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support. Patients were sub-grouped according to support type (extracorporeal membrane oxygenation [ECMO], intra-aortic balloon pump [IABP], and other TCS). Other TCS included all other surgical and percutaneous TCS devices. Estimated survival was compared based on need for pre-operative TCS and by profile. Pre-operative TCS was used in 5,632 (41%) cases. Of these, ECMO was used in 1,138 (20%) cases, IABP in 3,901 (69%) cases, and other TCS in 595 (11%) cases. Patients requiring ECMO had greater needs for biventricular support after dVAD (22% ECMO, 5% IABP, and 7% other TCS; p < 0.001) with longer post-implant intensive care stays (ECMO 24 days, IABP 14 days, and other TCS 12 days; p < 0.001). INTERMACS Profile 1 to 3 patients with pre-implant ECMO had the lowest longitudinal survival (82% at 1 month and 44% at 48 months) compared with IABP (93% at 1 month and 51% at 48 months), other TCS (92% at 1 month and 52% at 48 months), and non-TCS (95% at 1 months and 55 % at 48 months) (p < 0.0001). Propensity score matching analysis of the pre-implant ECMO INTERMACS Profile 1 group when compared with alternative pre-implant TCS strategies had an associated higher hazard impacting early phase survival vs other TCS (hazard ratio, 1.80; p < 0.01) and IABP (hazard ratio, 1.65; p < 0.01). In advanced heart failure with patients with CS, the use of ECMO before dVAD was associated with lower longitudinal survival and increased utilization of biventricular support compared with alternative TCS strategies. Research focused on longitudinal profiling in CS and pre-implant TCS is warranted to further understand these differences. [ABSTRACT FROM AUTHOR]

BACKGROUND Despite advances in device technology and treatment strategies, infection remains a major cause of adverse events (AEs) in mechanical circulatory support (MCS) patients. To characterize the epidemiology of MCS infection, we examined the type, location, and timing of infection in the International Society for Heart and Lung Transplantation Registry (ISHLT) for Mechanically Assisted Circulatory Support (IMACS) over 3 years, 2013 to 2015. METHODS Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) definitions were used to categorize AE infections occurring in MCS patients within IMACS. The IMACS infection variables were mapped to ISHLT definitions for infection where feasible. Three categories of MCS infection were defined as ventricular assist device (VAD) specific, VAD related, and non-VAD. RESULTS There were 10,171 patients enrolled from January 2013 through December 2015. Infection was the most common AE, with 3,788 patients (37%) experiencing ≥ 1 infection, and 6,758 AE infections reported overall. Non-VAD infection was the largest category, 4,501: 34.0% pneumonias, 30.6% non-VAD-related bloodstream infections (BSIs), 24.15% urinary tract infections (UTIs), and 10.2% gastrointestinal infections. VAD-specific infection was the second largest category, 1,756: 82.9% driveline, 12.8% pocket, and 4.3% pump/or cannula infections. VAD-related infection was the smallest category, 501: 47.5% BSIs, 47.5% mediastinitis, and 5.0% mediastinitis/pocket infections. All 3 categories were more frequently reported ≤ 3 months after implant. CONCLUSIONS Non-VAD infection, including pneumonia, BSI, UTI, and gastrointestinal infection, was the leading category of infection in MCS patients and the most frequently reported ≤ 3 months after implant. These results provide evidence to support resourcing and strengthening infection prevention strategy early after implantation in MCS. [ABSTRACT FROM AUTHOR]

Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis (CRS) that is characterized by intractable nasal polyp formation. Eosinophil-derived neurotoxin (EDN) is an eosinophil granule protein that is closely related to allergic inflammation, but the pathological implications of EDN in ECRS remain unknown. In this study, we evaluated the function of EDN in ECRS pathogenesis and assessed its potential as a disease activity marker. Serum EDN levels were significantly higher in patients with ECRS than in those with other nasal and paranasal diseases, and were positively correlated with clinical disease activity. Production of EDN from isolated human eosinophils was induced by stimulation with IL-5 in vitro. Human nasal epithelial cells were stimulated with EDN, and the resultant changes in gene expression were detected by RNA sequencing. Pathway analysis revealed that the major canonical pathway affected by EDN stimulation was 'regulation of the epithelial–mesenchymal transition pathway'; the only gene in this pathway to be up-regulated was matrix metalloproteinase 9 (MMP-9). Consistent with this, immunostaining analysis revealed intense staining of both EDN and MMP-9 in nasal polyps from patients with ECRS. In conclusion, our data demonstrate that serum EDN level is a useful marker for the evaluation of ECRS severity. Furthermore, EDN induces production of MMP-9 from the nasal epithelium, which may be involved in the pathogenesis of ECRS. [ABSTRACT FROM AUTHOR]

BACKGROUND Limited data exist describing impact of body mass index (BMI) on post‒left ventricular assist device (post-LVAD) outcomes. We sought to define the relationship between body mass index (BMI) and adverse events (AEs) after LVAD implantation by examining the ISHLT Mechanically Assisted Circulatory Support (IMACS) registry. METHODS Patients implanted with a contemporary continuous flow (CF)-LVAD were stratified into 4 groups using pre-operative BMI: underweight (UW; BMI ≤18.5 kg/m2); non-obese (NO; BMI >18.5 to <30 kg/m2); obese (OB; BMI ≥30 to <40 kg/m2); and morbidly obese (MO; BMI ≥40 kg/m2). Freedom from AEs was evaluated using the Kaplan–Meier method and risk factors for development of first AE were identified using multiphase parametric hazard modeling. AEs included infection, thromboembolic events, bleeding, device malfunction, and neurologic dysfunction. RESULTS Between 2013 and 2015, a total of 9,408 patients underwent implantation of a CF-LVAD, which consisted of 368 (4%) UW, 5,719 (61%) NO, 2,770 (29%) OB, and 444 (5%) MO patients. Survival among the 4 BMI cohorts was similar at 2 years (70.8% to 75.8%, p = 0.24). MO patients were less likely to be free from a non‒VAD-related infection (p < 0.0001) or device-related infection (p = 0.0014) at 2 years (50.3%, 70.7%) when compared with OB (58.3%, 78.7%), NO (65.2%, 81.4%), and UW (68.9%, 77.4%) patients. UW (81.5%) and NO (81.3%) patients were more likely to be free from device malfunction at 2 years when compared with OB (78.3%) and MO (72.6%) (p = 0.0006). Thromboembolic events were rare and more common in the UW cohort (p = 0.026). CONCLUSIONS Although BMI was not correlated with 2-year mortality, an increased rate of infectious and device-related AEs was noted in OB and MO LVAD patients. In a group with few options for transplant, the event morbidity in obese patients can be expected to impact morbidity with longer support durations. [ABSTRACT FROM AUTHOR]

A time‐resolved time‐of‐flight neutron diffraction technique to characterize the structural properties of materials during cyclic tests has been developed for the neutron diffractometers at J‐PARC. Using this technique, diffracted neutrons and the applied cyclic conditions are recorded as event data together with time information. The amplitude and phase of the conditions of all recorded neutron signals can be specified by using the characteristics of the event data. By adopting the developed technique, the behaviors of the crystal lattice and domains of the piezoelectric material in a multilayer‐type piezoelectric actuator driven by a cyclic electric field were evaluated. The developed technique enabled the collection and processing of diffraction data for all levels of the applied electric field, as opposed to only the highest and lowest levels. The variation in diffraction intensity during the application of a cyclic electric field was obtained successfully, and the hysteresis‐like behaviors of both the lattice strain and the 90° domain switching were revealed. [ABSTRACT FROM AUTHOR]

The second annual IMACS registry report includes over 14, 000 patients from 35 countries. Survival, adverse events, and an updated risk model is presented. Continuous flow pumps continue to dominate the world’s experience. One and Two-year survival remains at 80% and 70%. Congenital heart disease and biventricular support are the most dominant risk factors. The database is poised for major novel analyses. [ABSTRACT FROM AUTHOR]

Background The Jarvik 2000 ventricular assist device features a miniaturized intraventricular pump and an intermittent low-speed function that facilitates aortic valve opening. Despite its long history, little is known about the Jarvik device with regard to post-implantation outcomes. Methods Prospectively collected data from 13 participating hospitals were extracted from the Japanese Registry for Mechanically Assisted Circulatory Support database to analyze mortality, morbidity and de-novo aortic regurgitation. Data on 83 patients who underwent implantation of the Jarvik 2000 were reviewed. Median support duration was 191 (maximum 758) days. All recipients underwent implantation as a bridge to transplantation. Results Overall survival proportions at 1 and 2 years were 85.0% and 79.3%, respectively. Nine patients were in INTERMACS Level 1, and 28 patients were on mechanical circulatory support at the time of implantation. Causes of death included stroke, infection and device malfunction. Three patients had their device removed: 2 at the time of heart transplantation and 1 after recovery of the left ventricle. Common adverse events included major bleeding (27.7%), new infection (31.3%), stroke (20.5%) and device malfunction (20.5%). De-novo aortic regurgitation was observed in 17 patients, 6 of whom developed at least moderate regurgitation during follow-up. Conclusions Mid-term survival after Jarvik 2000 implantation was satisfactory and comparable to that reported by other national and international registries (INTERMACS and IMACS) for continuous-flow LVADs. De novo aortic regurgitation occurred despite the intermittent low-speed effect of this device, with some recipients experiencing progressive worsening of aortic regurgitation within 2 years post-implantation. [ABSTRACT FROM AUTHOR]

Background: Dilated cardiomyopathy (DCM) is the most common cardiomyopathy and causes left ventricular enlargement and contractile dysfunction, with a poor prognosis. The mechanisms underlying the disease process have not been precisely identified, but recent evidence has suggested that the activation of myocardial inflammation is involved in the deterioration associated with the condition.Methods and Results: Biopsy samples from 182 consecutive DCM patients were immunohistochemically stained with antibodies specific to CD3 (T lymphocytes), CD68 (whole macrophages), and CD163 (M2 macrophages), and each type of infiltrating cell was counted. Masson's trichrome staining was used to determine the collagen area fraction (CAF) in each sample. Patients were followed up for 6.9 ± 2.4 years, and their clinical data were obtained for analysis. Median (interquartile range) numbers of myocardial CD3, CD68, and CD163-cell infiltrates were 8.1 (4.0-14.2)/mm2 , 22.3 (12.1-36.0)/mm2 , and 6.5 (2.0-14.0)/mm2 , respectively. Patients with higher counts of infiltrating CD3-, CD68-, and CD163-positive cells had significantly poorer outcomes (P = 0.007, P = 0.011, and P = 0.022, respectively). A high CD163-positive infiltrate count was independently associated with worse outcome in multivariate Cox regression analysis (hazard ratio 1.77, P = 0.004), and multivariate linear regression analysis revealed that the CD163 cell count was an independent determinant of CAF (P < 0.001).Conclusions: It was found that DCM with increased myocardial immune activation was associated with poor long-term outcome. The association between M2 macrophages and collagen formation suggests the phenotypic polarization of macrophages toward M2 may be associated with ventricular remodelling in DCM. [ABSTRACT FROM AUTHOR]

Background This study aimed to clarify the prognostic impact of partial pressure of end-tidal carbon dioxide (PETCO 2 ) in patients with advanced chronic heart failure (HF). Methods Forty-eight patients (mean age 43.1 ± 11.9 years, 32 males) with chronic HF (44 with non-ischemic and 4 with ischemic cardiomyopathy) were prospectively enrolled. Echocardiography, blood tests, pulmonary function testing, and PETCO 2 measurements were performed as noninvasive tests, whereas right heart catheterization and arterial blood gas analysis were conducted as invasive tests. The primary end point of this study was left ventricular assist device (LVAD) implantation or cardiac death. Results Eighteen patients underwent LVAD implantation at the Interagency Registry for Mechanically Circulatory Support (INTERMACS) profile 3 during the follow-up period, and no patient died. PETCO 2 was significantly lower in a stepwise manner with New York Heart Association functional class (class I or II, 34.2 ± 9.3 mmHg vs. class III or IV, 27.7 ± 2.5 mmHg; p < 0.001). Univariate and multivariate Cox proportional hazard models and time-dependent receiver operating characteristic curve analysis revealed that PETCO 2 ≤ 31 mmHg is an independent noninvasive predictor of LVAD implantation. Univariable and multivariable linear regression analyses showed that pulmonary arterial pressure was independently and highly correlated with PETCO 2 ( r 2 = − 0.512, p < 0.001). Conclusions Among various noninvasive clinical parameters investigated, PETCO 2 was the independent predictor of LVAD implantation at the INTERMACS profile 3 in patients with chronic HF. Pulmonary congestion may significantly contribute to decreases in PETCO 2 in patients with HF. [ABSTRACT FROM AUTHOR]

Aim: Dilated cardiomyopathy (DCM) has a variety of causes, and no useful approach to predict left ventricular (LV) remodelling and long-term outcome has yet been established. Myocardial tenascin-C (TNC) is known to appear under pathological conditions, possibly to regulate cardiac remodelling. The aim of this study was to clarify the significance of myocardial TNC expression in LV remodelling and the long-term outcome in DCM.Methods and Results: One hundred and twenty-three consecutive DCM patients who underwent endomyocardial biopsy for initial diagnosis were studied. Expression of TNC in biopsy sections was analysed immunohistochemically to quantify the ratio of the TNC-positive area to the whole myocardial tissue area (TNC area). Clinical parameters associated with TNC area were investigated. The patients were divided into two groups based on receiver operating characteristic analysis of TNC area to predict death: high TNC group with TNC area ≥2.3% (22 patients) and low TNC group with TNC area <2.3% (101 patients). High TNC was associated with diabetes mellitus. Comparing echocardiographic findings between before and 9 months after endomyocardial biopsy, the low TNC group was associated with decreased LV end-diastolic diameter and increased LV ejection fraction, whereas the high TNC group was not. Survival analysis revealed a worse outcome in the high TNC group than in the low TNC group (P < 0.001). Multivariable Cox regression analysis revealed that TNC area was independently associated with poor outcome (HR = 1.347, P = 0.032).Conclusions: Increased myocardial TNC expression was associated with worse LV remodeling and long-term outcome in DCM. [ABSTRACT FROM AUTHOR]

Donor and recipient characteristics, as well as donor-recipient matching, affect clinical outcomes after heart transplantation (HTx). This study aimed to clarify how donor and recipient characteristics affect the clinical course after HTx. The medical records of all the patients who underwent HTx at the National Cerebral and Cardiovascular Center from 1999 to 2014 were retrospectively reviewed. Sixty-one patients (48 males) underwent HTx. Six recipients (9.8 %) developed primary graft dysfunction (PGD) determined by criteria recently established at a consensus conference. Development of PGD was associated with high-dose inotropic support for the donor heart and a history of stroke in the recipient ( p = 0.04 and p = 0.002, respectively). Recipients with PGD had higher right atrial pressure (RAP) and lower cardiac output (CO) compared with those without PGD at 6 months after HTx (RAP, 6.8 ± 3.6 vs. 2.8 ± 2.2 mmHg, p < 0.001; CO, 4.6 ± 0.8 l vs. 5.8 ± 1.2 l/min, p = 0.02). With respect to survival, patients with PGD had a 5-year survival rate equivalent to those without PGD (83.3 vs. 93.3 %, p = 0.23). High-dose inotropic support for the donor heart and a history of stroke in the recipient are significant predictive factors for the development of PGD. However, recipients with PGD demonstrate mid-term survival comparable to those without PGD. [ABSTRACT FROM AUTHOR]

The first annual report of the International Society for Heart and Lung Transplantation (ISHLT) Mechanically Assisted Circulatory Support (IMACS) registry provides global data on 5,942 patients from 31 countries. This initial report focuses on patient demographics, survival, device types, adverse events, competing outcomes, and a risk factor analysis. [ABSTRACT FROM AUTHOR]

Background Whether converting to everolimus (EVL) from mycophenolate mofetil (MMF) during the maintenance period after heart transplantation (HTx) reduces cardiac allograft vasculopathy (CAV) progression remains unclear. We sought to determine the effect of converting from MMF with standard-dose calcineurin inhibitors (CNIs) to EVL with low-dose CNIs on CAV progression. Methods We retrospectively reviewed the medical records of 63 HTx recipients who survived at least at 1 year after HTx. Twenty-four recipients were converted from MMF to EVL (EVL group, 2.2 ± 2.3 years after HTx), while 39 recipients were maintained on MMF (MMF group, 2.4 ± 2.2 years after HTx). The EVL group underwent three-dimensional intravascular ultrasound (3D-IVUS) analysis before and 1 year after conversion to EVL, and these data were compared with data from 2 consecutive IVUS in the MMF group. Results IVUS indices in the EVL group at 1 year after conversion did not show increased CAV development, whereas a significant increase in %plaque volume (p = 0.006) and decrease in lumen volume (p < 0.001) were observed in the MMF group. EVL conversion was significantly associated with smaller increases in %plaque volume (p = 0.004) and smaller decreases in lumen volume (p = 0.017). IVUS indices in the late EVL conversion group (≥ 2 years) also did not exhibit increased CAV development, while those in the MMF group did. Conclusions Conversion to EVL from MMF in maintenance periods after HTx may decrease the rate of CAV progression based on IVUS indices. [ABSTRACT FROM AUTHOR]

Loeffler endocarditis is a fibrous restrictive cardiomyopathy thought to be caused by persistent eosinophilia. It is difficult to diagnose, and the prognosis is often poor if the underlying eosinophilia is not promptly recognized and treated. We describe the case of a middle-aged woman treated for hypertrophic cardiomyopathy first detected during a routine check-up at age 35 years but whose symptoms gradually progressed over the next 14 years. Right ventricular biopsy showed extensive fibrosis of the endocardial tissue, and right heart catheterization revealed right heart failure and a low cardiac output state. Ultimately, she became reliant on inotropic and mechanical cardiovascular support, but we were not able to bridge her to transplant. Autopsy findings were typical of endocardial fibroelastosis, but she had not suffered from any tropical disease or traveled to high-risk areas. The presence of abnormal capillary proliferation suggested a diagnosis of Loeffler endocarditis. Nonetheless, apart from a 6-month period of eosinophilia 7 years before her death, a history of well-controlled asthma and several drug sensitivities, we were unable to definitively identify the disease trigger. It is critical to diagnose and treat the underlying eosinophilia of Loeffler endocarditis to avoid a poor prognosis. This case highlights the importance of considering the diagnosis of eosinophilic endomyocarditis in patients with an unusual pattern of apical hypertrophic cardiomyopathy (or myocardial fibrosis of unknown etiology), even when there is no apparent history of eosinophilia. [ABSTRACT FROM AUTHOR]

OBJECTIVES Although right heart failure (RVF) is an important issue in the management of patients with left ventricular assist devices (LVADs), the benefits of performing tricuspid valve repair in conjunction with LVAD implantation have not been demonstrated. METHODS We retrospectively reviewed the records of 141 patients who received LVAD implantation as a bridge to transplant from May 1999 to January 2013. We assessed short- and long-term right heart function in 69 of these patients who underwent tricuspid valve repair because of moderate-to-severe tricuspid regurgitation (TR) or severe dilatation of the tricuspid annulus. RVF was defined as the need for a right ventricular assist device or >30 days of intravenous inotropic support. TR was graded from 0 to 4, while fibrosis in myocardial biopsy samples was graded pathologically from 0 to 3. RESULTS The average duration of LVAD support was 595 days. Twenty-seven patients developed RVF and their survival rate was significantly worse than that of patients who did not develop RVF (65 vs 91% at 1 year). RVF was significantly related to high preoperative ratio of central venous pressure (CVP) to pulmonary capillary wedge pressure, high total bilirubin, high fibrosis score and high TR grade. In patients who underwent tricuspid valve repair, the TR grade was significantly reduced from 2.6 to 1.0, and this decrease was maintained for 2 years. Although patients who underwent tricuspid valve repair had significantly higher TR grades, ratios of CVP to pulmonary capillary wedge pressure and fibrosis scores preoperatively, no survival impairment was seen. CONCLUSIONS Tricuspid valve repair is a useful and durable adjuvant procedure for restoring deteriorated right ventricular function in patients requiring LVAD implantation. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy (CAV) is a major cause of mortality after transplantation. We treated a 44-year-old female with off-pump coronary artery bypass grafting (OPCAB) 4 years after heart transplantation. Annual examinations, including coronary angiography and intravenous ultrasound (IVUS), revealed a severe lesion in the left main trunk. The left internal mammary artery was successfully anastomosed to the left anterior descending artery in an off-pump manner. To ensure that patients have a good long-term outcome after heart transplantation, routine examinations, including IVUS, are crucial, because of the nature of CAV. OPCAB is a good option for a left main trunk lesion due to CAV. [ABSTRACT FROM AUTHOR]

Heart transplantation started in Japan in 1999. Since then, 50 transplants have been performed at our center. We performed histopathological analyses of the 50 explanted hearts and the post-transplant biopsy specimens. The median age of recipients was 39 years. The primary diseases before transplant were idiopathic dilated cardiomyopathy in 33 patients (66%), hypertrophic cardiomyopathy in seven (14%), restrictive cardiomyopathy in one, arrhythmogenic right ventricular cardiomyopathy in one, and secondary cardiomyopathy in eight (16%). Before transplantation, 47 patients (94%) had left ventricular assist devices. No severe cardiovascular failure due to allograft rejection occurred. The post-transplant survival rate was 97.6% at 1 year and 93.1% at 10 years. One recipient was lost to sepsis from myelodysplastic syndrome in the fourth year, one died of multiple organ failure and peritonitis 8 months after transplant. Another patient died of recurrent post-transplant lymphoproliferative disorders ( PTLD). Mild cardiac dysfunction occurred in seven recipients in the early postoperative period. Moderate acute cellular rejection occurred in six patients (12%), and antibody-mediated rejection occurred in three (6%). The number of heart transplants performed in Japan is very small. However, the outstanding 10-year survival rate is due to donor evaluation and post-transplant care resulting in low grade rejection. Pathological evaluation has also greatly contributed to the results. [ABSTRACT FROM AUTHOR]

OBJECTIVES Aortic insufficiency (AI) often develops during left ventricular assist device (LVAD) support and is related to a poor prognosis. As LVAD implantation and the support duration increase, the risk of acquired aortic valve lesions may increase. We investigated the pathological changes in the aortic valve and its function after long-term LVAD support. METHODS Thirty-five hearts removed at heart transplantation were investigated. Thirty-one patients were supported by extracorporeal pulsatile devices, and 4 were supported by implantable devices. We compared the histological changes in the aortic valve with the echocardiogram results. RESULTS The mean duration of LVAD support was 961 days. Before device implantation, all patients had a normal aortic valve opening, and only 5 had trivial AI. After LVAD support, trivial AI was observed in 18 patients, mild AI in 4 and mild-to-moderate AI in 2. Pathological examination revealed that the aortic valve had become thinner in all patients, ranging from 120 to 1400 µm. The aortic wall had also become thinner in most patients, ranging from 830 to 2220 µm. Left ventricular wall thickness was ranging from 4 to 13 mm, and aortic annular diameter was ranging from 17 to 27 mm. Partial aortic valve fusion was seen in 17 (48.6%) recipients, and curling with leaflet shortening was detected in 22 (62.9%) patients. Dense collagen accumulation in the spongiosa layer was also present. All aortic valves of the patients with mild and mild-to-moderate AI showed a scarce or no opening before explantation. Conversely, the AI grade of patients whose aortic valve frequently opened remained none or trivial. There was no close correlation between these pathological findings and the development of AI independently. CONCLUSIONS Degenerative aortic valve changes were recognized after long-term LVAD support. There was also an increasing prevalence of mild and mild-to-moderate AI, which may have been associated with continuous aortic valve closure. An optimal strategy to prevent AI development should be determined, and careful periodic echocardiographic follow-up is essential. [ABSTRACT FROM AUTHOR]

Background: The EVAHEART left ventricular assist device was approved in 2010 by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for bridge to heart transplantation (BTT). However, its effectiveness has not been evaluated since approval. In this study we evaluated the EVAHEART device in a commercial setting in Japan. Methods: Ninety-six consecutive patients enrolled in the Japanese Registry for Mechanically Assisted Circulatory Support (J-MACS), who were listed for transplant or likely to be listed and who received an EVAHEART device, were enrolled from 2011 to 2013 at 14 Japanese centers. Patients’ survival rates, adverse events and quality-of-life data were obtained from the J-MACS Registry. Results: Patients’ median age was 43 years (85% male). The Interagency Registry for Mechanically Assisted Circulatory Support profiles revealed 12 patients in Level 1, 45 in Level 2, 37 in Level 3 and 1 in Level 4. The mean support duration was 384.7 days, with a cumulative duration of 101.2 years. The Kaplan–Meier survival rate during support was 93.4% at 6 months, 87.4% at 1 year and 87.4% at 2 years. Seventy-seven patients (80.2%) currently remain on support, 7 received a transplant and 10 died during support. Major adverse events included drive-line infection (14.6%) and neurologic events such as ischemic stroke (17.7%), hemorrhage (13.5%), transient ischemic attack (3.1%), pump thrombosis (1%) and hemolysis (1%). There was no gastrointestinal (GI) bleeding or right heart failure requiring right ventricular assist device (RVAD). There was no pump exchange due to mechanical failure. Conclusions: The EVAHEART device provides safe, reliable and long-term circulatory support with improved survival in commercial settings of BTT in Japan, where the transplant waiting period is much longer. Incidences of GI bleeding, hemolysis, right ventricular failure, device thrombosis and mechanical failure were extremely rare in patients on EVAHEART devices. [ABSTRACT FROM AUTHOR]

The simultaneous measurement of Fouriertransform infrared (FTIR)transmission spectra and 2-dimensional wide-angle X-ray diffraction(WAXD) and small-angle X-ray scattering (SAXS) patterns has been performedsuccessfully to investigate the hierarchical structure changes occurringin the stress-induced phase transition phenomenon of uniaxially orientedpoly(tetramethylene terephthalate) film. The molar fraction of theβ-crystal form, evaluated from the IR and WAXD data analyses,increased steeply in the plateru region of the stress–straincurve as already known well. The 2D SAXS data have revealed the remarkableand reversible change in the stacked lamellar structure just afterthe α-to-β phase transition was completed, where the tiltingangle of the stacked lamellae measured from the draw axis of the orientedsample became zero, and the lamellar thickness increased due to theinclusion of amorphous region located in the boundary part of thecrystalline lamellae. In parallel, the X-ray reflection spots in awider diffraction angle region became diffuse in the observed WAXDpattern of the β form, indicating the packing disorder of themechanically stressed chains. In this way, the simultaneous combinationof the 3 different types of equipments has allowed us to deduce thedetailed structural change from the various levels: the stress-inducedα–β transition was found to occur not only withthe remarkable changes in the molecular chain conformation and chainpacking mode in the crystal lattice, but also with the large and reversiblechange in the lamellar stacking structure. The stress-induced changesin lamellar thickness and long period were simulated using a mechanicalmodel with these hierarchical structure changes taken into account,giving relatively good reproduction of the observed data. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Erlotinib and pemetrexed have been approved for the second-line and maintenance treatment of non-small cell lung cancer (NSCLC). With the recommended doses determined by our previous phase I study, we conducted a phase II study to evaluate the efficacy and safety of combination of the two agents in pretreated non-squamous NSCLC patients. Methods: This study was performed in patients with stage IIIB/IV or post-surgically recurrent non-squamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. Patients received 500mg/m2 of intravenous pemetrexed every 21 days and 150mg of oral erlotinib on days 2–16 until disease progression, unacceptable toxicity, or withdrawal of consent. The expected response rate and threshold were defined as 33.5% and 10%, respectively. Assuming a one-sided alpha of 5%, a power of 80%, the possible deviation from assessment, 26 patients were necessary. Results: A total of 27 patients, 16 males and 11 females were recruited. Patients had the median age of 70 years (range, 48–80 years) and included 21 stage IV diseases, 22 adenocarcinomas. Epidermal growth factor receptor (EGFR) mutations were examined in all patients. One patient had positive EGFR mutation, but the other 26 patients had wild-type EGFR. The median number of treatment courses was 3 (range, 1 to over 19). The best overall response rate and disease control rate were 11.1% and 63.0%, respectively. The median progression-free survival and overall survival were 2.8 months (95% confidence interval (CI); 1.9–7.5 months) and 15.8 months (95% CI; 9.3 months to not available), respectively. Dermal, hepatic, gastrointestinal and hematological disorders were the frequently observed adverse events. One patient experienced grade 3 drug-induced interstitial lung disease. Conclusions: We could not demonstrate the add-on effect of intermittent erlotinib on pemetrexed in a second-line setting for patients with non-squamous NSCLC without EGFR mutations. [Copyright &y& Elsevier]

Pump thrombosis is one of the major adverse events associated with the use of a left ventricular assist system ( LVAS) in patients with advanced heart failure. We investigated the clinical implication of pump replacement because of thrombus formation. This study included 87 patients who underwent implantation of a Nipro ( Toyobo) pulsatile extracorporeal LVAS intended as a bridge to transplantation and were alive more than 3 months after implantation. The pump of this device is translucent, and daily evaluation for signs of thrombus formation was performed. Pump replacement was performed for significant thrombus formation that became visible. Data collection including demographics as well as hematologic values were performed 1 day before (baseline) and 3 months after implantation, and all patients were followed for 2 years or until death. At 3 months after LVAS implantation, 41 patients (47.1%) had undergone pump replacement because of pump thrombus. Baseline body surface area <1.63 m2 was a significant predictor of pump replacement (hazard ratio [ HR] 2.15, P = 0.04). At 3 months after implantation, there was a significantly higher incidence of stroke ( P < 0.05) as well as a significantly greater decrease in body weight ( F = 4.92, P = 0.03) in patients who underwent pump replacement as compared to those without. The 2-year mortality after implantation was 26.4%. Multivariate Cox regression analysis showed that pump replacement within 3 months after implantation was an independent predictor of mortality ( HR 2.50, P = 0.03). In conclusion, pump replacement for thrombus formation may have a strong association with worse outcome. Our results reconfirm the clinical importance of device thrombus in the management of LVAS. [ABSTRACT FROM AUTHOR]

Abstract: Active hydrothermal venting from shallow seafloor (200-m depth) with talc chimneys has been discovered at the Wakamiko Crater floor in the Aira Caldera, southern Kyushu, Japan. The major chemical composition of the fluids suggests that the fluids are supplied from a single reservoir. The fluid is characterized by a low chloride concentration, low δD value, and a high δ18O value, suggesting that the endmember hydrothermal fluid is a mixture of seawater and andesitic water and possibly contribution of meteoric water and/or phase separation. Such noticeable magmatic input may be supported by high helium isotopic ratio (6.77 RA) of fumarolic gas discharging from the crater. Silica and alkaline geothermometers indicate that the fluid–rock interaction in the reservoir occurs in the temperature range of 230 to 250°C. The high alkalinity and high ammonium and dissolved organic matter concentrations in the fluid indicate interaction of the fluid with organic matter in sedimentary layers. At least three hydrothermal vents have been observed in the crater. Two of these have similar cone-shaped chimneys. The chimneys have a unique mineralogy and consist dominantly of talc (kerolite and hydrated talc) with lesser amounts of carbonate (dolomite and magnesite), anhydrite, amorphous silica, and stibnite. The precipitation temperature estimated from δ18O values of talc was almost consistent with the observed fluid temperature. Geochemical modeling calculations also support the formation of talc and carbonate upon mixing of the endmember hydrothermal fluid with seawater and suggest that the talc chimneys are currently growing from venting fluid. [Copyright &y& Elsevier]

Background: In recent years, maintenance chemotherapy is increasingly being recognized as a new treatment strategy to improve the outcome of advanced non-small cell lung cancer (NSCLC). However, the optimal maintenance strategy is still controversial. Gemcitabine is a promising candidate for single-agent maintenance therapy because of little toxicity and good tolerability. We have conducted a randomized phase II study to evaluate the validity of single-agent maintenance chemotherapy of gemcitabine and to compare continuation- and switch-maintenance. Methods: Chemonaïve patients with stage IIIB/IV NSCLC were randomly assigned 1:1 to either arm A or B. Patients received paclitaxel (200 mg/m2, day 1) plus carboplatin (AUC 6 mg/mL/min, day 1) every 3 weeks in arm A, or gemcitabine (1000 mg/m2, days 1 and 8) plus carboplatin (AUC 5 mg/mL/min, day1) every 3 weeks in arm B. Non-progressive patients following 3 cycles of induction chemotherapy received maintenance gemcitabine (1000 mg/m2, days 1 and 8) every 3 weeks. (Trial registration: UMIN000008252) Results: The study was stopped because of delayed accrual at interim analysis. Of the randomly assigned 50 patients, 49 except for one in arm B were evaluable. Median progression-free survival (PFS) was 4.6 months for arm A vs. 3.5 months for arm B (HR = 1.03; 95% CI, 0.45-2.27; p = 0.95) and median overall survival (OS) was 15.0 months for arm A vs. 14.8 months for arm B (HR = 0.79; 95% CI, 0.40-1.51; p = 0.60), showing no difference between the two arms. The response rate, disease control rate, and the transit rate to maintenance phase were 36.0% (9/25), 64.0% (16/25), and 48% (12/25) for arm A vs. 16.7% (4/24), 50.0% (12/24), and 33% (8/24) for arm B, which were also statistically similar between the two arms (p = 0.13, p = 0.32, and p = 0.30, respectively). Both induction regimens were tolerable, except that more patients experienced peripheral neuropathy in arm A. Toxicities during the maintenance phase were also minimal Conclusion: Survival and overall response were not significantly different between the two arms. Gemcitabine may be well-tolerable and feasible for maintenance therapy. [ABSTRACT FROM AUTHOR]

OBJECTIVES Due to a serious heart donor shortage, the criteria for acceptance for transplantation have been expanded. This study assesses donor-related factors associated with postoperative low output syndrome (LOS) and long-term survival of recipients. METHODS From 1999 to February 2011, 36 heart transplantations were performed at our institute, of which 28 donor hearts (78%) were considered to be marginal due to high inotropic requirement (n = 11), recent episode of cardiac arrest (n = 11), female to male transplantation (n = 11), reduced left ventricular contraction (n = 6), old age (n = 6), small donor heart (n = 5), donor–recipient size mismatch (n = 2), ventricular hypertrophy (n = 2) or prolonged ischaemic time (n = 1). St Thomas solution (n = 6) and Celsior (n = 30) were used for preservation. Ischaemic damage in post-transplant cardiac patients was graded by perioperative ischaemic myocardial injury (PIMI) score (scores 0–3). RESULTS The donor age was 39 ± 11 years old, which was not significantly different to that of the recipients. 50% of the donors were female. Thirty-three donors (92%) required catecholamine at an average of 8.0 ± 5.2 µg/hg/min and echocardiogram findings showed that left ventricular ejection fraction was 65 ± 10%. All recipients survived during the perioperative period (one patient died from sepsis at 4 years after transplantation) for a 10-year survival rate of 95%. Severe primary graft dysfunction was observed in two patients who required intra-aortic balloon pumping or veno-arterial extra-corporeal membrane oxygenation, and five other patients showed postoperative LOS (cardiac index < 2.2 l/min/m2). Left ventricular diastolic diameter smaller than 36 mm (P = 0.0002), high inotropic requirement (P = 0.0089) and left ventricular ejection fraction less than 55% (P = 0.0383) were related to post-transplant LOS. All patients recovered cardiac function and were discharged from the intensive care unit after an average of 6 days. Although preservation with Celsior was not related to LOS, it had relationships with lower CKMB level (P = 0.0013) and lower PIMI score (P = 0.0054). CONCLUSIONS Cautious donor selection is essential when the donor heart has a small ventricular diameter or requires a high level of inotropic support. However, long-term survival in recipients with marginal donor hearts can be anticipated with adequate treatment. [ABSTRACT FROM AUTHOR]

The effects of left ventricular assist system (LVAS) implantation on renal hemodynamics remains to be fully elucidated. We evaluated renal function and intrarenal blood flow in five advanced heart failure patients who had been supported with a Toyobo LVAS for bridge to heart transplantation. Renal function expressed as estimated glomerular filtration rate (eGFR) was calculated using the modified formula of Modification of Diet in Renal Disease. Mean blood velocities in the bilateral segmental arteries during systolic and diastolic perfusion were measured using duplex Doppler sonography, and renal vascular resistance (resistive index [RI]) of the segmental arteries was defined as (peak systolic velocity [PSV]-end-diastolic velocity [EDV])/PSV. All studies were performed before and after implantation (mean duration of support, 15.6 ± 10.9 months). LVAS implantation significantly improved eGFR (42.7 ± 7.9 to 64.1 ± 16.3 mL/min, P < 0.05). Beat-by-beat measurements of heart rate did not change significantly. Mean PSV decreased significantly (38.2 ± 8.9 to 28.3 ± 2.2 cm/s, P < 0.05), and mean EDV increased significantly (8.3 ± 3.2 to 11.3 ± 1.3 cm/s, P < 0.05), and thus, mean RI was significantly improved (0.79 ± 0.06 to 0.60 ± 0.04, P < 0.01). In conclusion, in advanced heart failure patients, pulsatile LVAS implantation is associated with improved renal function, and this improvement may be mediated in part through an improvement of intrarenal hemodynamics. [ABSTRACT FROM AUTHOR]