Publications by authors named "Minoru Ono"

336 Publications

Consensus Report on Destination Therapy in Japan - From the DT Committee of the Council for Clinical Use of Ventricular Assist Device Related Academic Societies.

Circ J 2021 Aug 24. Epub 2021 Aug 24.

Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine.

Destination therapy (DT) is the indication to implant a left ventricular assist device (LVAD) in a patient with stage D heart failure who is not a candidate for heart transplantation. The implantable LVAD has been utilized in Japan since 2011 under the indication of bridge to transplant (BTT). After almost 10 year lag, DT has finally been approved and reimbursed in May 2021 in Japan. To initiate the DT program in Japan, revision of the LVAD indication from BTT is necessary. Also, in-depth discussion of caregiver issues as well as end-of-life care is indispensable. For that purpose, we assembled a DT committee of multidisciplinary members in August 2020, and started monthly discussions via web-based communication during the COVID-19 pandemic. This is a summary of the consensus reached after 6 months' discussion, and we have included as many relevant topics as possible. Clinical application of DT has just started, and we are willing to revise this consensus to meet the forthcoming issues raised during real-world clinical experience.
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http://dx.doi.org/10.1253/circj.CJ-21-0462DOI Listing
August 2021

Clinical Impact of Copy Number Variation on the Genetic Diagnosis of Syndromic Aortopathies.

Circ Genom Precis Med 2021 Aug 30;14(4):e003458. Epub 2021 Jul 30.

Department of Cardiovascular Medicine (N.T., H. Yagi, H.M., T.K., I.K.), University of Tokyo Hospital, Japan.

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http://dx.doi.org/10.1161/CIRCGEN.121.003458DOI Listing
August 2021

Neutrophil-to-lymphocyte ratio is prognostic factor of prolonged pleural effusion after pediatric cardiac surgery.

JRSM Cardiovasc Dis 2021 Jan-Dec;10:20480040211009438. Epub 2021 Apr 19.

Division of Cardiovascular Surgery, National Center for Child Health and Development, Tokyo, Japan.

Objectives: Postoperative pleural effusion (PE) is common after pediatric cardiac surgery, and if prolonged can lead to the deterioration of the general condition due to malnutrition and result in death. This study aims at identifying the prognostic factors of prolonged PE after pediatric cardiac surgery. Patients were divided into the effective (with chest tube removal within 10 days after medical therapy) and ineffective (with chest tube in place for more than 10 days) groups. The factors were compared between the two groups retrospectively.

Participants: Participants included patients who had prolonged PE after cardiac surgery in national center for child and health development between October 2014 and October 2017.

Main Outcome Measures: Baseline characteristics and procedure details were compared between the two groups to determine the predictor of prolonged PE. White blood cell count, platelet count, neutrophil-to-lymphocyte ratio, hemoglobin level, serum total protein level, serum albumin level, blood fibrinogen level, serum creatinine level, etc. were examined.

Results: Twenty patients were included. Between the two groups, no significant differences in baseline characteristics, such as age, weight, and sex were found, and significant differences were observed only in the NLR change ratio (effective group, 5.1 [4.1-8.0] versus ineffective group, 11.9 [9.9-14.1]; P = 0.01).

Conclusions: NLR change ratio is a potential prognostic factor of prolonged PE, including chylothorax, after pediatric cardiac surgery.
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http://dx.doi.org/10.1177/20480040211009438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252915PMC
April 2021

Application of mesenchymal stem cell sheet to treatment of ischemic heart disease.

Stem Cell Res Ther 2021 07 7;12(1):384. Epub 2021 Jul 7.

Department of Cardiac Surgery, The University of Tokyo Hospital, 7-3-1 Honggo, Bunkyo-ku, Tokyo, 113-8655, Japan.

In recent years, mesenchymal stem cells (MSCs) have been used to improve cardiac function and attenuate adverse ventricular remodeling of the ischemic myocardium through paracrine effects and immunoregulation functions. In combination with cell sheet technology, MSCs could be more easily transplanted to the ischemic area. The long-term retention of MSCs in the affected area was realized and significantly improved the curative effect. In this review, we summarized the research and the applications of MSC sheets to the treatment of ischemic heart tissue. At present, many types of MSCs have been considered as multipotent cells in the treatment of heart failure, such as bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose-derived mesenchymal stem cells (AD-MSCs), umbilical cord-derived mesenchymal stem cells (UC-MSCs), and skeletal myoblasts (SMs). Since UC-MSCs have few human leukocyte antigen-II and major histocompatibility complex class I molecules, and are easy to isolate and culture, UC-MSC sheets have been proposed as a candidate for clinical applications to ischemic heart disease.
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http://dx.doi.org/10.1186/s13287-021-02451-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261909PMC
July 2021

Updating guidelines: When is the best timing of upgrading recommendation for an emerging technology?

Authors:
Minoru Ono

Asian Cardiovasc Thorac Ann 2021 May;29(4):250-253

Department of Cardiovascular Surgery, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1177/02184923211006845DOI Listing
May 2021

Assessment of ocular blood flow in continuous-flow ventricular assist device by laser speckle flowgraphy.

J Artif Organs 2021 Apr 6. Epub 2021 Apr 6.

Department of Artificial Organs, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan.

Although the influence of continuous-flow left ventricular assist device (CF-LVAD) support on peripheral circulation has been widely discussed, its monitoring modalities are limited. The aim of this study was to assess the peripheral circulation using the laser speckle flowgraph (LSFG) which can quantitatively measure the ocular blood flow. We implanted a centrifugal CF-LVAD (EVAHEART; Sun Medical Technology Research Corporation, Nagano, Japan) in five adult goats (body weight 44.5 ± 2.9 kg) under general anesthesia. The waveform of the central retinal artery using the mean blur rate (MBR) for ocular blood velocity and fluctuations as a parameter of pulsatility were obtained before LVAD implantation and after LVAD full-bypass support. The MBR waveform and LSFG fluctuation data were compared with the waveform and pulsatility index of the external carotid artery using an ultrasonic flow meter to evaluate circulatory patterns at different levels. The MBR waveform pattern of the central retinal artery was pulsatile before LVAD implantation and less pulsatile under LVAD full bypass. The fluctuation was 14.7 ± 1.86 before LVAD implantation and 3.85 ± 0.61 under LVAD full bypass (p < 0.01), respectively. The fluctuations of LSFG showed a strong correlation with the pulsatility index of the external carotid artery meaning that similar changes in circulatory pattern were observed at two different levels. Measuring the ocular blood flow using LSFG has potential utility for the assessment of the status of the peripheral circulation and its pulsatility during CF-LVAD.
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http://dx.doi.org/10.1007/s10047-021-01265-5DOI Listing
April 2021

Transcatheter Aortic Valve Implantation and Surgical Aortic Valve Replacement for Aortic Stenosis in Japan - Analysis of a Nationwide Inpatient Database.

Circ Rep 2020 Dec 1;2(12):753-758. Epub 2020 Dec 1.

Department of Cardiovascular Medicine, The University of Tokyo Tokyo Japan.

Nationwide data on transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) in Japan are scarce. Using a nationwide inpatient database, we analyzed patients undergoing TAVI (n=8,338) or SAVR (n=16,298) due to aortic stenosis between 2014 and 2017. The annual number of TAVI increased rapidly from 2014 to 2017, particularly in older patients. In-hospital deaths were lower and the length of hospital stay was shorter for patients undergoing TAVI than SAVR. TAVI has been penetrating in Japan as an alternative therapeutic option for aortic stenosis and is associated with acceptable clinical outcomes.
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http://dx.doi.org/10.1253/circrep.CR-20-0116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937519PMC
December 2020

Case Report: A Case of Acute Cellular Rejection Due to Atopic Dermatitis Exacerbation 3 Years After Heart Transplantation.

Front Immunol 2021 22;12:630051. Epub 2021 Feb 22.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Little evidence has been presented about the association between previous atopic/allergic disease and graft rejection after solid organ transplantation. Thus, we present a case wherein acute cellular rejection (ACR) after heart transplantation (HTx) was noted along with exacerbation of atopic disease.

Case Summary: A 32-year-old man was admitted at our hospital for regular monitoring of graft rejection. He had undergone heart transplant 3 years prior due to dilated cardiomyopathy. Echocardiogram revealed good biventricular function, and no abnormal findings were found in blood sampling tests. However, biopsy showed moderate ACR [Grade 2R(ISHLT 2004)/3A(ISHLT 1990)], which required twice-repeated steroid pulses with intensified immunosuppression. Meanwhile, his atopic dermatitis, which was diagnosed before having heart failure, was getting worse for the past 6 months. The exacerbation of atopic dermatitis was presumed to be related to the development of the intractable cellular rejection.

Discussion: This case suggested the association of atopic disease and graft rejection after HTx. We examined 76 patients from a cohort of previous studies who underwent HTx at our hospital, which suggested that patients with atopic/allergic disorders such as atopic dermatitis and asthma tended to have a significantly higher frequency of moderate rejection than non-allergic patients. (p = 0.012; Fisher's exact test). Our case also suggests that exacerbation of atopic dermatitis might cause graft rejection of the transplanted organ, so that it is important to carefully evaluate the risk of graft rejection if there is a previous history of atopic/allergic disease.
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http://dx.doi.org/10.3389/fimmu.2021.630051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937951PMC
February 2021

Continuous measurement of surface electrical potentials from transplanted cardiomyocyte tissue derived from human-induced pluripotent stem cells under physiological conditions in vivo.

Heart Vessels 2021 Jun 8;36(6):899-909. Epub 2021 Mar 8.

Institute of Advanced Biomedical Engineering and Science, TWIns, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

Recording the electrical potentials of bioengineered cardiac tissue after transplantation would help to monitor the maturation of the tissue and detect adverse events such as arrhythmia. However, a few studies have reported the measurement of myocardial tissue potentials in vivo under physiological conditions. In this study, human-induced pluripotent stem cell-derived cardiomyocyte (hiPSCM) sheets were stacked and ectopically transplanted into the subcutaneous tissue of rats for culture in vivo. Three months after transplantation, a flexible nanomesh sensor was implanted onto the hiPSCM tissue to record its surface electrical potentials under physiological conditions, i.e., without the need for anesthetic agents that might adversely affect cardiomyocyte function. The nanomesh sensor was able to record electrical potentials in non-sedated, ambulating animals for up to 48 h. When compared with recordings made with conventional needle electrodes in anesthetized animals, the waveforms obtained with the nanomesh sensor showed less dispersion of waveform interval and waveform duration. However, waveform amplitude tended to show greater dispersion for the nanomesh sensor than for the needle electrodes, possibly due to motion artifacts produced by movements of the animal or local tissue changes in response to surgical implantation of the sensor. The implantable nanomesh sensor utilized in this study potentially could be used for long-term monitoring of bioengineered myocardial tissue in vivo under physiological conditions.
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http://dx.doi.org/10.1007/s00380-021-01824-zDOI Listing
June 2021

Carbon Monoxide Diffusing Capacity Predicts Cardiac Readmission in Patients Undergoing Left Ventricular Assist Device Implantation in Japan.

ASAIO J 2021 Jan 11. Epub 2021 Jan 11.

From the Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Therapeutic Strategy for Heart Failure, The University of Tokyo, Tokyo, Japan Department of Organ Transplantation, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Cardiac Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Carbon monoxide diffusion capacity (DLCO) is impaired in heart failure patients; however, its clinical impact has not been well investigated in the left ventricular assist device (LVAD) population. We explored the predictive value of preoperative DLCO in the survival and cardiac readmission rates after LVAD implantation. Seventy-six patients who received continuous-flow LVAD as bridge-to-transplant therapy from November 2007 to September 2018 and underwent pulmonary function test before LVAD implantation were included. The primary study endpoints were death and readmission for heart failure or arrhythmia (cardiac readmission). Patients were stratified into two groups according to the percent of predicted DLCO (%DLCO). Pulmonary vascular resistance (PVR) was equivocal between the groups preoperatively, whereas the low DLCO group (%DLCO < 80%) showed significantly high PVR postoperatively. The mortality rate was not different between the groups. The 2 year cardiac readmission rate was 33.5% in the low DLCO group and 8.7% in the high DLCO group (%DLCO ≥ 80%) (P = 0.028). The %DLCO was associated with cardiac readmission in univariate and multivariate analyses (hazard ratio: 4.32; 95% CI: 1.50-15.9; P = 0.005). Low %DLCO was associated with high PVR postoperatively and was a risk factor for cardiac readmission after LVAD implantation.
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http://dx.doi.org/10.1097/MAT.0000000000001363DOI Listing
January 2021

Can the intermittent low-speed function of left ventricular assist device prevent aortic insufficiency?

J Artif Organs 2021 Jun 9;24(2):191-198. Epub 2021 Jan 9.

Department of Cardiac Surgery, The University of Tokyo, Tokyo, Japan.

Aortic insufficiency (AI) is known to associate with a persistently closed aortic valve during continuous-flow ventricular assist device support. Some devices carry an intermittent low-speed (ILS) function, which facilitates aortic valve opening, but whether this function prevents AI is unknown. In this study, the Jarvik 2000 device, which is programmed to reduce the pump speed each minute for 8 s, was chosen to examine this potential effect. Prospectively collected data of 85 heart transplant-eligible Jarvik 2000 recipients who met the study criteria (no pre-existing AI and aortic valve surgery) were retrospectively analyzed for the incidence, correlating factors, and clinical outcomes of de novo AI. All data were provided by the Japanese Registry for Mechanically Assisted Circulatory Support. De novo AI occurred in 58 patients, 23 of whom developed at least moderate AI during a median support duration of 23.5 months. Freedom from moderate or greater AI was 84.4%, 66.1% and 60.2% at 1, 2 and 3 years, respectively. Multivariate analyses revealed that progressive AI was correlated with decreased pulse pressure after implantation (hazard ratio 1.060, 95% confidence interval 1.001-1.127, p = 0.045). No correlation was found for mortality or other adverse events, including stroke, bleeding, infection, pump failure, hemolysis, and readmission. The benefit of the Jarvik 2000's current ILS mode against AI appears to be minimal. However, in this limited cohort where all recipients underwent implantation as a bridge to transplantation, the impact of de novo progressive AI on other clinical adversities was also minimal.
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http://dx.doi.org/10.1007/s10047-020-01234-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154761PMC
June 2021

Tumor Growth Suppression With Novel Intra-arterial Chemotherapy Using Epirubicin-entrapped Water-in-oil-in-water Emulsion .

In Vivo 2021 Jan-Feb;35(1):239-248

Institute of Engineering Innovation, School of Engineering, The University of Tokyo, Tokyo, Japan.

Background/aim: A mixture of anticancer agents and iodized poppy seed oil (IPSO) has been widely used for intra-arterial chemotherapy of hepatocellular carcinoma. However, the anticancer agents can easily separate from IPSO, so the therapeutic potential is limited. We developed epirubicin-entrapped water-in-oil-in-water emulsion (WOW-Epi) using a double-membrane emulsification technique.

Materials And Methods: We delivered WOW-Epi through a hepatic arterial injection to VX2 hepatic tumor rabbit model (1.2 mg/kg).

Results: VX2 tumor growth was selectively suppressed in the WOW-Epi-treated group compared with the control treated groups. The accumulation of WOW in nearby cancer cells was confirmed via electron-microscopy. Endocytosis seemed to be the mechanism underlying the uptake of WOW.

Conclusion: WOW-Epi led to tumour growth suppression in vivo. WOW does not cause toxicity to arterial vessels. WOW-Epi will be hopefully used for repeated intra-arterial chemotherapy to HCC patients in the near future.
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http://dx.doi.org/10.21873/invivo.12252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880746PMC
June 2021

Differences in the prognoses of patients referred to an advanced heart failure center from hospitals with different bed volumes.

Sci Rep 2020 12 3;10(1):21071. Epub 2020 Dec 3.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan.

Few reports have discussed appropriate strategies for patient referrals to advanced heart failure (HF) centers with available left ventricular assist devices (LVADs). We examined the association between the characteristics and prognoses of referred patients with advanced HF and the bed volume of the referring hospitals. This retrospective analysis evaluated 186 patients with advanced HF referred to our center for consultation about the indication of LVAD between January 1, 2015, and August 31, 2018. We divided the patients into two groups according to the bed volume of their referring hospital (high bed volume hospitals (HBHs): ≥ 500 beds in the hospital; low bed volume hospitals (LBHs): < 500 beds). We compared the primary outcome measure, a composite of LVAD implantation and all-cause death, between the patients referred from HBHs and patients referred from LBHs. The 186 patients with advanced HF referred to our hospital, who were referred from 130 hospitals (87 from LBHs and 99 from HBHs), had a mean age of 43.0 ± 12.6 years and a median left ventricular ejection fraction of 22% [15-33%]. The median follow-up duration of the patients was 583 days (119-965 days), and the primary outcome occurred during follow-up in 42 patients (43%) in the HBH group and 20 patients (23%) in the LBH group. Patients referred from HBHs tended to require catecholamine infusion on transfer more often than those referred from LBLs (36.5% (HBH), 20.2% (LBL), P = 0.021). Kaplan-Meier analysis indicates that the occurrence of the primary outcome was significantly higher in the HBH patients than in the LBH patients (log-rank P = 0.0022). Multivariate Cox proportional hazards analysis revealed that catecholamine support on transfer and long disease duration were statistically significant predictors of the primary outcome. Patients from HBHs had a greater risk of the primary outcome. However, the multivariate analysis did not indicate an association between referral from an HBH and the primary outcome. In contrast, catecholamine support on transfer, long duration of disease, and low blood pressure were independent predictors of the primary outcome. Therefore, these should be considered when determining the timing of a referral to an advanced HF center, irrespective of the bed volume of the referring hospital.
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http://dx.doi.org/10.1038/s41598-020-78162-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713124PMC
December 2020

Bridge-to-Bridge Left Ventricular Assist Device Implantation Strategy vs. Primary Left Ventricular Assist Device Implantation Strategy.

Circ J 2020 11 3;84(12):2198-2204. Epub 2020 Nov 3.

Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine.

Background: The bridge-to-bridge (BTB) strategy, a conversion to durable left ventricular assist device (LVAD) after stabilization using surgical temporary mechanical circulatory supports for a couple of months, is not uncommon in Japan. However, its effect on clinical outcomes in comparison with a primary durable LVAD implantation strategy remains unknown.Methods and Results:Data of 837 consecutive patients (median age 45, 73% males) who underwent durable LVAD implantation as BTB (n=168) or primary implant (n=669) between April 2011 and April 2019 were retrospectively reviewed from the prospective multicenter Japanese mechanically assisted circulatory support registry. The BTB group was younger and had comparable end-organ function, better hemodynamic profile, and longer operative time compared with the primary implant group at baseline. The 3-year survival was 80% vs. 87% (P=0.007) for the BTB and primary implant groups respectively, with greater observed rates of stroke and infection as the predominant causes of death. The BTB strategy was independently associated with increased 3-year mortality (hazard ratio 2.69 [1.43-5.07], P=0.002) in addition to other significant risk factors.

Conclusions: The BTB cohort had comparable baseline characteristics to the primary implant cohort at the time of durable LVAD conversion, but had lower 3-year survival. Detailed analysis clarifying the causality of this finding should improve outcomes with the BTB strategy.
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http://dx.doi.org/10.1253/circj.CJ-20-0840DOI Listing
November 2020

Association between infectious event and de novo malignancy after heart transplantation.

Heart Vessels 2021 Apr 2;36(4):499-508. Epub 2020 Nov 2.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan.

The aim of the study was to investigate the incidence of and risk factors for de novo malignancy after heart transplantation (HTx) in a single center. We assessed 102 consecutive patients who received HTx and were followed-up in our center regularly for > 1 year from June 2006 to May 2018. We investigated the incidence of and risk factors for de novo malignancy. The cumulative incidence of each malignancy type during the follow-up period was one (0.98%) for skin cancer, four (3.92%) for nonskin solid organ cancer, and six (5.88%) for posttransplant lymphoproliferative disorder (PTLD). The percentage of patients with more than one infectious event ≤ 1 year after HTx was higher in the malignancy group than in the non-malignancy group. Furthermore, Kaplan-Meier analysis revealed that the incidence rate of infectious events was higher in patients with malignancies than in those without (log-rank P < 0.001). After dividing malignancies into a PTLD group and a solid organ malignancy group, we found that negative Epstein-Barr virus serostatus, cytomegalovirus-positive antigenemia, and the occurrence of any viral or gastrointestinal infectious event at ≤ 1 year were more frequent in patients with PTLD than in patients without it. The survival rate was significantly lower for patients with solid organ malignancy than for patients without malignancy. In conclusion, there was a correlation between infectious events and de novo malignancy, particularly in patients with PTLD. We should confirm this finding by conducting a larger cohort study.
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http://dx.doi.org/10.1007/s00380-020-01715-9DOI Listing
April 2021

Evaluation of spinal cord protective threshold of serum memantine, an NMDA receptor antagonist, in a rabbit model of paraplegia.

Indian J Thorac Cardiovasc Surg 2020 Nov 21;36(6):598-607. Epub 2020 Aug 21.

Department of Pharmacy, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655 Japan.

Purpose: To evaluate the threshold of serum memantine for prevention of spinal cord injury (SCI) in a rabbit paraplegic model.

Methods: Forty-two New Zealand white rabbits were divided into 7 groups. Preoperatively, oral memantine was given starting from 60 mg OD for 7 days in the initial group, then reducing the dose and/or duration to 60 mg OD for 5 days, 30 mg OD for 5 days, 30 mg OD for 3 days, 15 mg OD for 3 days, 30 mg single dose, and 60 mg single dose, in subsequent 6 groups. A paraplegic model was created by clamping both infrarenal aorta and inferior vena cava (IVC) for 45 min. Motor evoked potentials (MEPs), modified Tarlov score (0-5), serum memantine concentration, and histopathology of the spinal cord were evaluated.

Results: Half of all rabbits (21/42) showed spinal protection. Receiver operating characteristic (ROC) curve analysis showed serum level of 4.5 ng/ml as a cutoff value for spinal protection (sensitivity 86%, specificity 62%, area under the curve (AUC) 0.785,  = .002). Sixteen rabbits had serum level ≥ 4.5 ng/ml (group A), with 26 rabbits having < 4.5 ng/ml (group B). Further comparison was done between groups A and B. The mean modified Tarlov score at 6, 24, 48, and 72 h was 4.5 ± 0.9 and 2.4 ± 1.6, in groups A and B, respectively ( < .001). The modified Tarlov score showed positive correlation with serum memantine level (Spearman's rho = 0.618,  = .01). Results of MEP and histopathology were significantly better for group A.

Conclusions: We showed that memantine is protective against SCI at serum levels ≥ 4.5 ng/ml in a rabbit model; thus, it can be a potential adjunct for spinal protection during thoracic/thoracoabdominal aortic surgeries.
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http://dx.doi.org/10.1007/s12055-020-01026-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572946PMC
November 2020

Takotsubo syndrome in the same heart before and after heart transplantation.

ESC Heart Fail 2020 Sep 10. Epub 2020 Sep 10.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Heart transplantation is an effective therapy for patients with end-stage heart failure. In some cases, Takotsubo syndrome (TTS) was seen in the donor heart. We report a case of TTS in a 40-year-old woman with a history of epileptic seizures who underwent heart transplantation from a donor with TTS. The donor was brain-dead due to severe hypoxic encephalopathy during cardiac arrest with TTS. Fifteen months after heart transplantation, she was readmitted for epileptic seizures. Electrocardiogram showed T-wave inversion, and transthoracic echocardiography showed apical ballooning. Coronary angiography was normal, and endomyocardial biopsy was negative for rejection. Iodine-123 metaiodobenzylguanidine imaging demonstrated a low heart-to-mediastinum ratio and high washout rate. Eighteen days after admission, recovery of left ventricular dysfunction was confirmed, and she was diagnosed with TTS triggered by epileptic seizures. It is important to recognize the risk of recurrent TTS in heart transplantation patients from a donor with TTS.
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http://dx.doi.org/10.1002/ehf2.12970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754914PMC
September 2020

Aortic root destruction after aortic valvuloplasty for bicuspid aortic valve.

Gen Thorac Cardiovasc Surg 2021 Feb 25;69(2):350-352. Epub 2020 Jul 25.

Department of Cardiac Surgery, The Jikei University School of Medicine, 3-9-18, Nishi-shinbashi, Minato-ku, Tokyo, 105-8571, Japan.

Ultrasound cardiography showed severe aortic regurgitation (AR) due to bicuspid aortic valve with dilatation of the aortic annulus and sinotubular junction in a 27-year-old man hospitalized with loss of consciousness. He underwent aortic valvuloplasty combined with external suture annuloplasty using an expanded polytetrafluoroethylene (ePTFE) suture. Intraoperative findings revealed thickening and adhesion of the aortic root despite the first surgery. He developed recurrent AR 7 months later and underwent redo surgery. An ePTFE suture was found inside the aorta. Aortic root replacement with a mechanical composite graft was performed, as reconstruction appeared difficult because the aortic annulus was damaged and there were multiple holes on all cusps. Here, we report a rare case of aortic root destruction after external suture annuloplasty.
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http://dx.doi.org/10.1007/s11748-020-01448-6DOI Listing
February 2021

COVID-19: clinical issues from the Japan Surgical Society.

Surg Today 2020 Aug 11;50(8):794-808. Epub 2020 Jul 11.

Committee for novel coronavirus disease 2019 outbreak of the Japanese Surgical Society, Tokyo, Japan.

In this unprecedented COVID-19 pandemic, several key issues must be addressed to ensure safe treatment and prevent rapid spread of the virus and a consequential medical crisis. Careful evaluation of a patient's condition is crucial for deciding the triage plan, based on the status of the disease and comorbidities. As functionality of the medical care system is greatly affected by the environmental situation, the treatment may differ according to the medical and infectious disease circumstances of the institution. Importantly, all medical staff must prevent nosocomial COVID-19 by minimizing the effects of aerosol spread and developing diagnostic and surgical procedures. Polymerase chain reaction (PCR) screening for COVID-19 infection, particularly in asymptomatic patients, should be encouraged as these patients are prone to postoperative respiratory failure. In this article, the Japan Surgical Society addresses the general principles of surgical treatment in relation to COVID-19 infection and advocates preventive measures against viral transmission during this unimaginable COVID-19 pandemic.
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http://dx.doi.org/10.1007/s00595-020-02047-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351651PMC
August 2020

Single-dose toxicity study by intra-arterial injection of BSH entrapped water-in-oil-in-water emulsion for boron neutron capture therapy to hepatocellular carcinoma.

Appl Radiat Isot 2020 Sep 13;163:109202. Epub 2020 May 13.

Institute of Engineering Innovation, School of Engineering, The University of Tokyo, Tokyo, 113-8656, Japan; Cooperative Unit of Medicine & Engineering, The University of Tokyo Hospital, Tokyo, 113-8655, Japan.

We developed a mixing medical device by attaching Shirasu porous glass Millipore membrane to prepare water-in-oil-in-water (WOW) emulsion in a shorter time to be applied as B-entrapped WOW emulsion for hepatocellular carcinoma (HCC) treatment. Single-dose toxicity studies by intra-arterial injection of BSH-entrapped WOW were performed in rabbits and pig, and no side effects were observed. We hope to proceed to the preclinical and clinical studies for further evaluation of B compound as multidisciplinary treatments for HCC.
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http://dx.doi.org/10.1016/j.apradiso.2020.109202DOI Listing
September 2020

Impact of tacrolimus versus cyclosporin A on renal function during the first year after heart transplant.

ESC Heart Fail 2020 08 23;7(4):1842-1849. Epub 2020 May 23.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Aims: Nephrotoxicity of calcineurin inhibitors (CNIs) is associated with adverse events in patients undergoing heart transplant (HTx), although studies directly comparing tacrolimus (TAC) versus cyclosporin A (CsA), especially in combination with everolimus and low-dose CNIs approach, are limited. Thus, we sought to investigate the associations of TAC and CsA with clinical outcomes in HTx recipients, with specific focus on renal function.

Methods And Results: From August 2007 to February 2017, 72 consecutive patients (39 treated with TAC vs. 33 with CsA) receiving de novo HTx in a single transplant centre were retrospectively evaluated. We used the instrumental variable method to account for unmeasured confounding. The study outcomes were percentage change in estimated glomerular filtration rates (eGFR) (safety endpoint) and biopsy-proven acute rejection (efficacy endpoint) within the first year after HTx. The enrolled patients (median age 40 years) were predominantly men (68%). There were no significant differences in baseline characteristics, including eGFR (64.8 [45.7-96.4] mL/min/1.73 m in TAC vs. 65.6 [57.9-83.0] mL/min/1.73 m for CsA; P = 0.48), other than sex (male, 49% for TAC vs. 91% for CsA; P < 0.001) between the two groups. Within the first year after HTx, 23 (59%) in the TAC group switched mycophenolate mofetil to everolimus, whereas 16 (48%) in the CsA group (P = 0.52). At 12 months, the rates of mortality and end-stage renal disease requiring renal replacement therapies were both 0%. In the instrumental variable analysis, no differences in renal function as well as graft rejection for 1 year after HTx existed between the TAC and CsA groups. These results were similar when taking into account of everolimus use.

Conclusions: Irrespective of everolimus use with low-dose CNIs, our analysis using the instrumental variable method showed no differences in renal function as well as graft rejection during the first year after HTx between HTx recipients who received TAC or CsA.
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http://dx.doi.org/10.1002/ehf2.12749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373882PMC
August 2020

"BAX602" in Preventing Surgical Adhesion after Extracorporeal Ventricular Assist Device Implantation for Refractory Congestive Heart Failure: Study Protocol for a Multicenter Randomized Clinical Trial.

Cardiovasc Drugs Ther 2020 10;34(5):651-657

Department of Cardiac Surgery, National Cerebral and Cardiovascular Center, 6-1 Kishibeshimmachi, Suita, Osaka, 564-8565, Japan.

Background: The high surgical risk in redo cardiac surgery is largely attributed to adhesions around the epicardium and the great vessels. BAX602 is an adhesion prevention reagent composed of two synthetic polyethylene glycols. Spraying BAX602 over the epicardium and the great vessels reportedly contributes to adhesion prevention after pediatric cardiac surgery. The present study aims to evaluate the safety and effectiveness of BAX602 spray in patients undergoing extracorporeal ventricular assist device implantation surgery to treat refractory congestive heart failure.

Methods And Design: This investigator-initiated, multicenter, pivotal, two-arm, open-label, randomized trial will include a total of 30 patients. The primary outcome measure is the severity of adhesions, which will be evaluated during re-sternotomy surgery performed 2-12 weeks after the primary extracorporeal ventricular assist device implantation surgery. The adhesion severity will be evaluated at five predefined sites using a four-grade adhesion evaluation score (0 = no adhesion; 1 = filmy and avascular adhesion; 2 = dense/vascular adhesion; 3 = cohesive adhesion). This measure will be summarized in two ways to evaluate the effect of BAX602: (1) the total score of the severity of adhesions at all five sites (ranging from 0 to 15), and (2) the total number of sites with dense/vascular or cohesive adhesions (ranging from 0 to 5).

Ethics And Dissemination: The study findings will be disseminated at regional, national, and international conferences and through peer-reviewed scientific journals.

Trial Registration: The trial was registered in the UMIN Clinical Trials Registry (UMIN-CTR: UMIN000038998) on 6 January 2020.
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http://dx.doi.org/10.1007/s10557-020-06990-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497303PMC
October 2020

Hemocompatibility-related Adverse Events Following HeartMate II Left Ventricular Assist Device Implantation between Japan and United States.

Medicina (Kaunas) 2020 Mar 13;56(3). Epub 2020 Mar 13.

Department of Medicine, University of Chicago Medical Center, IL 60637, USA.

: Left ventricular assist device (LVAD) therapy has improved the clinical outcomes in advanced heart failure patients, however, this may differ between countries. We aimed to compare outcomes between Japanese and US LVAD cohorts. : For 416 consecutive LVAD patients who received HeartMate II LVAD implantation and completed a one-year follow-up, age-matched Japanese patients (the Japanese registry for mechanically assisted circulatory support (J-MACS) group) and the US patients were compared for their clinical outcomes. : 154 J-MACS patients and 77 US patients were compared. Survival, free from hemocompatibility-related adverse events (HRAEs) in the J-MACS was statistically comparable with the US (75% vs. 63%, = 0.79). J-MACS had more disabling strokes than the US (0.221 vs. 0.052/patient-year, = 0.005), whereas there was less nonsurgical bleeding (0.045 vs. 0.117/patient-year, = 0.024). The net hemocompatibility score was statistically comparable between the groups (1.54 vs. 1.19 points/patient, = 0.99). Post-LVAD prothrombin time with international normalized ratio (INR) <1.5 (odds ratio 4.07) was a risk factor for HRAEs in J-MACS, whereas INR >3.0 (odds ratio 5.71) was a risk factor in the US ( < 0.05 for both). : In the age-matched cohorts, the J-MACS group experienced more strokes, while the US group had more bleedings. "Tailor-made" therapeutic strategy might be required for each country, given the unique variation of HRAE incidence among each country.
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http://dx.doi.org/10.3390/medicina56030126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142632PMC
March 2020

A superior vena cava to right pulmonary artery shunt for severe right ventricular outflow tract stenosis caused by an unresectable cardiac tumor.

J Cardiol Cases 2020 Mar 13;21(3):97-100. Epub 2019 Nov 13.

Department of Cardiac Surgery, The University of Tokyo, Tokyo, Japan.

We report the case of a 47-year-old man who was diagnosed with severe right ventricular outflow tract (RVOT) stenosis due to a space-occupying lesion; the diagnosis was made using computed tomography. He underwent mass reduction, pulmonary valve replacement, and RVOT reconstruction with a bovine pericardial patch. The pathological diagnosis was undifferentiated pleomorphic sarcoma originating from the myocardium. As the mass resection was incomplete, he received heavy particle therapy. He did not want to receive adjuvant chemotherapy. Four months later, severe RVOT stenosis recurred because the residual mass had invaded the prosthetic valve in the pulmonic position and one of the cusps was fixed in the closed position. He presented with dyspnea and marked lower leg edema. We performed superior vena cava (SVC) to right pulmonary artery (RPA) shunting as a palliative operation to improve his heart failure symptoms. After surgery, his symptoms improved; his hemodynamics have been stable for one year. SVC-RPA shunting is a palliative operation but can be used to effectively treat severe RVOT stenosis caused by unresectable cardiac tumors. < Malignant primary cardiac tumors commonly recur after complete surgical resection and they have the potential to obstruct intracardiac blood flow. The superior vena cava to right pulmonary artery shunt may be useful for treating right ventricular outflow tract stenosis due to unresectable cardiac tumors.>.
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http://dx.doi.org/10.1016/j.jccase.2019.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054662PMC
March 2020

Generation of a large-scale vascular bed for the creation of three-dimensional cardiac tissue.

Regen Ther 2019 Dec 22;11:316-323. Epub 2019 Oct 22.

Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.

Introduction: The definitive treatment for severe heart failure is transplantation. However, only a small number of heart transplants are performed each year due to donor shortages. Therefore, novel treatment approaches based on artificial organs or regenerative therapy are being developed as alternatives. We have developed a technology known as cell sheet-based tissue engineering that enables the fabrication of functional three-dimensional (3D) tissue. Here, we report a new technique for engineering human cardiac tissue with perfusable blood vessels. Our method involved the layering of cardiac cell sheets derived from human induced pluripotent stem cells (hiPSCs) on a vascular bed derived from porcine small intestinal tissue.

Methods: For the vascular bed, a segment of porcine small intestine was harvested together with a branch of the superior mesenteric artery and a branch of the superior mesenteric vein. The small intestinal tissue was incised longitudinally, and the mucosa was resected. Human cardiomyocytes derived from hiPSCs were co-cultured with endothelial cells and fibroblasts on a temperature-responsive dish and harvested as a cardiac cell sheet. A triple-layer of cardiac cell sheets was placed onto the vascular bed, and the resulting construct was subjected to perfusion culture in a bioreactor system.

Results: The cardiac tissue on the vascular bed pulsated spontaneously and synchronously after one day of perfusion culture. Electrophysiological recordings revealed regular action potentials and a beating rate of 105 ± 13/min (n = 8). Furthermore, immunostaining experiments detected partial connection of the blood vessels between the vascular bed and cardiac cell sheets.

Conclusions: We succeeded in engineering spontaneously beating 3D cardiac tissue using human cardiac cell sheets and a vascular bed derived from porcine small intestine. Further development of this method might allow the fabrication of functional cardiac tissue that could be used in the treatment of severe heart failure.
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http://dx.doi.org/10.1016/j.reth.2019.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818334PMC
December 2019

The second official report from Japanese registry for mechanical assisted circulatory support (J-MACS): first results of bridge to bridge strategy.

Gen Thorac Cardiovasc Surg 2020 Feb 23;68(2):102-111. Epub 2019 Oct 23.

Department of Cardiac Surgery, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: The Japanese registry for mechanical assisted circulatory support (J-MACS) is a prospective registry to collect all data of implantable left ventricular assist device (LVAD) (and part of paracorporeal VAD) established in 2010. The first analytical report was published in 2017. The organization running J-MACS was used to be the pharmaceuticals and medical devices agency (PMDA), but has been changed to the council for clinical use of ventricular assist device related academic societies in 2017.

Methods: Since 2018, we changed the analytical methods as follows: first, we eliminated paracorporeal VAD from the analysis. Second, we included not only primary implantation but bridge to bridge (BTB) implantation of LVAD. Third, we added the analyses of adverse events that were not included in the previous analysis.

Results: As of Oct 2018, 711 primary LVAD implants and 168 BTB implants were enrolled. Survival rate of primary LVAD was 93% at 360 days and 91% at 720 days, and that of BTB was 86% at 360 days and 82% at 720 days.

Conclusion: We first reported the results of BTB in the second official report of J-MACS. The prognosis after LVAD implantation has been kept good in Japanese circumstances.
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http://dx.doi.org/10.1007/s11748-019-01227-yDOI Listing
February 2020

Comparison of two point of care whole blood coagulation analysis devices and conventional coagulation tests as a predicting tool of perioperative bleeding in adult cardiac surgery-a pilot prospective observational study in Japan.

Transfusion 2019 11 15;59(11):3525-3535. Epub 2019 Oct 15.

Department of Blood Transfusion, The University of Tokyo Hospital, Tokyo, Japan.

Background: It is widely accepted that Point-of Care Test (PoCT) devices are useful in the detection of coagulopathies in situations of massive bleeding such as major cardiac surgery. These devices contribute to the reduction of blood transfusion. However, their implementation remains limited in Japan because of their cost and lack of health insurance support.

Study Design And Methods: Conventional coagulation tests and thromboelastography (TEG)/Sonoclot values were measured in 50 consecutive cardiac surgery cases. Clinical background information such as operative procedures was obtained from electronic medical records, and the theoretical perioperative total blood loss was calculated by measuring the hemoglobin content and total red blood cell transfusion volume. The correlation between perioperative total blood loss and the measured laboratory values or clinical parameters was evaluated by a multivariate linear regression analysis. The risk factors of the total amount of platelet transfusion and postoperative drain bleeding volume were similarly evaluated.

Results: No significant association between the estimated perioperative total blood loss (eTBL) and the laboratory measurements including conventional coagulation tests, TEG and Sonoclot was observed. On the other hand, postoperative drain bleeding volume was significantly associated with postoperative Sonoclot CR (p = 0.039) as well as preoperative use of oral anticoagulants and cell saver treated blood volume. Platelet transfusion amount was significantly associated with post-CBP PF and time to peak value of Sonoclot (p = 0.014 and 0.001, respectively).

Conclusion: Sonoclot measurements may be useful to estimate the risks of postoperative bleeding and platelet transfusion in cardiac surgeries in Japan.
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http://dx.doi.org/10.1111/trf.15523DOI Listing
November 2019
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