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Background: As the number of donated organs is still extremely small in Japan compared with other developed countries, in-hospital procurement transplant coordinators (In-Hp PTC) may play an important role in increasing organ donation and making the procurement procedure smoother. In this study, our education program of In-Hp PTC is described. Materials and Methods: In May 2012, our department started the In-Hp PTC Education Program. In the first semester, a 2-hour lecture is provided every 2 weeks for 5 months to 15 In-Hp PTCs working near Osaka. In the second semester, 20 lectures were provided for 3 consecutive days to 31 In Hp PTCs, more than 80% of whom work far from Osaka. Lecture topics were the history and current status of organ donation in Japan, social regulation of organ donation, care of transplant recipients, overall procedures of organ donation, the role of In-Hp PTC, donor family care, donor indications, and donor assessment and management. Lectures also included simulations of the organ donation process. Results: Participants were surveyed for their opinions after the program, Most participants were satisfied with the program, topics and duration. As most of them are not full-time In-Hp PTCs, they preferred to attend the 3-day program. Many participants are currently working as main In-Hp PTCs and establishing their own organ donation system in their hospital. Conclusions: In-Hp PTCs have an important role to play in establishing an organ procurement system and increasing organ donation in Japan. This program may help establish a systematic education program for this occupation in Japan. [ABSTRACT FROM AUTHOR]

Introduction: After the revision of the Organ Transplant Act in July 2010, brain dead organ donation increased from 13 to 45 per year, and heart donation increased. The purpose of this study was to review 166 consecutive brain dead heart donors to evaluate our strategies to identify and manage organ donors. Methods: This study reviewed 166 consecutive brain dead heart donors since the Act was issued. Whereas 69 heart donations were performed between October 1997 and July 2010 before the revision of the Act, 97 heart donations were performed for the 3 years after the revision. Since November 2002, special transplant management doctors were sent to donor hospitals to assess donor organ function and to identify which organs could be transplanted. They also intensively cared for the donors to stabilize hemodynamics and to improve cardiac function by giving intravenous antidiuretic hormones and by pulmonary toileting via bronchofiberscope. Results: The mean heart donor age increased from 41.0 to 43.9 years after the revision. Notably, 11 hearts from donors more than 60 years old were transplanted successfully after the revision. Before the revision, the cause of death was 37 cerebrovascular disease (SAH 34, stroke 1, bleeding 2), 18 head trauma, 13 asphyxia, and 2 postresuscitation brain damage. After the revision, there were 49 cerebrovascular disease (SAH 37, stroke 2, bleeding 16, and other 4), 17 head trauma, 10 asphyxia, and 11 postresuscitation brain damage. A total of 58 donors had a history of cardiac arrest, 58 required a high dose of catecholamine drip infusion, and only 1 recipient died of primary graft dysfunction. Patient survival rate at 3 years after heart transplantation was not different before and after the revision of the Act (98.6% vs 92.2%). Conclusions: Although donor age was increased and donors who died of cerebral bleeding or postresuscitation after the revision of the Act increased, the outcome after heart transplantation was not changed. [ABSTRACT FROM AUTHOR]

Endomyocardial biopsy (EMB) is a gold standard to detect acute cellar cardiac rejection (ACR), but due to its invasiveness, a new non-invasive approach is warranted. Our final goal is to identify new biomarkers corresponding to ACR severity. Using RNA-seq analysis, we found specific gene expression profiles in EMB specimens corresponding to the grades of ISHLT criteria. We also established a transcriptome analysis method utilizing an FFPE (formalin fixed paraffin embedded) EMB section remained after pathological examination. 1. Gene expression profiling in fresh frozen EMB section: 7 cardiac recipients who had pathological ACR were enrolled. They were divided into two groups: patients with before and at rejection ISHLT grade 1A (G-going; N=3) and with at and after treating rejection grade 1A (G-resolving; N=4). Transcriptome analysis was performed using a fresh frozen section (0.5 - 3 mm wide, 7 µm thickness). 2. Establishment of a 3'mRNA-seq method utilizing thin FFPE EMB section: 28 myocardial specimens (grade 0 in 7, 1A in 12, 2 in 2, 3A in 4 and quilty in 3) were analyzed. 3'mRNA-seq libraries were prepared using total RNA isolated from an FFPE section (1-2 mm wide, 5 µm) remained after pathological examination. 3. GSEA (Gene Set Enrichment Analysis) and DGE analysis: After RNA-sequencing, gene expression profiling was analyzed by GSEA and clustered by k-means. In G-going, we identified up-regulation of the genes mainly related to ACR, interferon gamma, inflammation, and ILG-JAK-STAT3 signaling, while in G-resolving, we identified down-regulation of these genes. Inflammatory responses were also observed in 3'mRNA-seq analysis using FFPE section. We also separated 270 up-regulating genes in grade3A and 229 ACR related genes associated with ISHLT criteria. In our analysis, most of these identified genes were not listed in AlloMap ®. Although these analyses were preliminary because of the 1st analysis stage, these technique for analyzing gene expressions using a tiny myocardial sample may have a role to find new biomarkers associated with ACR. [ABSTRACT FROM AUTHOR]

Heparin-induced thrombocytopenia (HIT) is an immune-mediated condition associated with thrombocytopenia and thrombotic complications. The condition is increasingly recognized in hospitalized patients including severely injured trauma patients. Because these patients may eventually be considered for organ donation, management of the HIT screen positive donor has become an important issue in transplant surgery. We describe the recent management of 2 cardiac allograft donors with HIT. At organ recovery, both male adult donors were hemodynamically stable with a normal appearing heart and no evidence of thrombosis. The donor underwent a routine multiple organ allograft recovery with argatroban infused over 15 minutes immediately before aortic cross-clamping after confirming activated clotting time (ACT) of greater than 400 sec. The cardiac allograft was flushed in the donor operating room with a total of 4 liters of cold Celsior solution. These hearts were transplanted in patients with dilated cardiomyopathy and cardiac sarcoidosis by modified bicaval anastomosis technique using heparin for anticoagulation therapy during cardiopulmonary support. Both were bridged with implantable left ventricular assist device (Heart Mate II and Jarvik 2000, respectively). This management strategy resulted in successful multiple organ transplants (Case 1: heart, two single lungs, liver, 2 kidney, case 2: heart, bilateral lung, liver, pancreas, 2 kidneys). Neither of the heart and other recipients demonstrated signs or symptoms of HIT, or neither had any postoperative thrombotic complications.. Based on this experience, a treatment algorithm for managing HIT donors using argatroban is proposed for heart donors as well as other organ donors [ABSTRACT FROM AUTHOR]

Abstract: Objective: Because the donor shortage is extremely severe in Japan because of a strict organ transplantation law, special strategies have been established to maximize heart and lung transplantations (HTs and LTs, respectively). We reviewed 100 consecutive brain-dead donors to evaluate our strategies to identify and manage heart and lung donors. Methods: We retrospectively reviewed all 100 consecutive brain-dead donors procured since the law was issued in 1997. There were 56 mens and the overall mean donor age was 43.5 years. The causes of death were cerebrovascular disease (n = 62), head trauma (n = 20), and asphyxia (n = 16): Since November 2002, special transplant management doctors were sent to donor hospitals to assess cardiac and lung functions, seeking to identify transplant opportunities. They stabilized donor hemodynamics and lung function by administering antidiuretic hormone intravenously and performing bronchofibroscopy for pulmonary toilet. Results: Seventy-nine HTs, 1 heart-lung transplantations, and 78 LTs (46 single and 32 bilateral) were performed. By applying these strategies organs per donor were increased from 4.5 to 6.8. Among heart donors, 61/80 were marginal: high inotrope requirement (n = 29), cardiopulmonary resuscitation (n = 28), and/or >55 years old (n = 20). None of the 80 HT recipients died of primary graft failure (PGF). Patient survival rate at 10 years after HT was 95.4%. Among lung donors, 48/65 were marginal: pneumonia (n = 41), chest trauma (n = 4), and >55 years old (n = 9). Only 2/78 LT recipients died of PGF. Patient survival rate at 3 years after LT was 72.2%. After inducing frequent pulmonary toilet, lung procurement and patient survival rates increased significantly after LT. Conclusions: Although the number of cases was still small, the availability of organs has been greater and the outcomes of HT/LT acceptable. [Copyright &y& Elsevier]

Abstract: Purpose: As the donor shortage is extremely severe in Japan because of a strict Organ Transplantation Act, special strategies must be established to maximize organ transplant opportunities. The purpose of this study was to evaluate our strategies to identify and manage 200 consecutive brain-dead organ donors. Methods and materials: We retrospectively reviewed the 200 donors procured since the Organ Transplantation Act was issued in 1997, including 118 males, a mean overall age of 45.1 years and cause of death being cerebrovascular disease (n = 119), head trauma (n = 37), and asphyxia (n = 44). Donor evaluation and management system: Since November in 2002, special transplant management doctors (“medical consultants”) were sent to donor hospitals to assess organ function and identify transplantable organs. They also provided intensive care to stabilize hemodynamics and improve cardiac and lung functions by administering antidiuretic hormone intravenously and providing bronchofiberscopic pulmonary toilet. Results: We obtained 146 heart, 1 heart-lung, and 154 lung (87 single and 67 bilateral), 175 liver (28 splitted liver), 142 pancreas (114 pancreas-kidney), 253 kidney and 12 small bowel grafts. Organs procured from 1 donor increased from 4.5 to 6.8 after applying these strategies. Conclusions: Although the number of cases was still small, the availability of organs and outcomes of transplantation have been acceptable. [Copyright &y& Elsevier]

Background: In surface antigen of hepatitis B virus (HBsAg)-positive carrier for anticancer treatment of malignant lymphoma, it is well recognized that reactivation of hepatitis B virus (HBV) occasionally occurs. However, there have been only a few studies of HBV reactivation in serum HBsAg-negative and hepatitis B core antigen (HBcAb)-positive occult HBV carriers. We looked at both retrospective and prospective studies to determine the prevalence, clinical course and risk factor of HBV reactivation during chemotherapy in lymphoma patients. [ABSTRACT FROM PUBLISHER]

Abstract: Introduction: Because the donor shortage is extremely severe in Japan because of a strict organ transplantation law, special strategies must be established to maximize heart transplantation (HTx) and lung transplantation (LTx) opportunities. The purpose of this study was to review our strategies to identify and manage heart and lung donors. Method: Transplantation doctors themselves assessed their own donor heart and lung function before starting the procurement operation; skillful staff surgeons harvested the organs. Since November 2002, a special transplantation consultant doctor assessed donor organ function to identify useful organs and intensively cared for the donor to improve cardiac and lung function. Results: Only 63 brain-dead donors have been available in Japan. However, 49 HTx (77.7%) and 39 LTx (19 bilateral and 20 single) were performed from 36 donors (57.1%). Thirty-six HTx donors were marginal, requring sustained high doses of inotropes (n = 26), low left ventricular ejection fraction (n = 5), cardiopulmonary resuscitation (n = 15), and age older than 55 years (n = 6). Twenty LTx donors had infected sputa or showed pneumonia using chest X-ray. None of 49 HTx recipients died of primary graft failure (PGF). Patient survival at 3 years after HTx was 98.0%. Although 5/39 LTx died early, including 2 of PGF, patient survival rate at 3 years was 66.9%. Conclusion: Although the number of cases was still small, the availability of hearts and lungs has been high and the transplantation outcomes were acceptable. These strategies may be useful to maximize HTx/LTx opportunities. [Copyright &y& Elsevier]

The purpose of the present study is to investigate functional role of the facial nerve on suckling in developing rats. The bilateral resection of facial nerves on postnatal day 1 (P1) resulted in cell loss of facial motoneurons and complete facial paralysis without any whisker movement or nictitating reflex at the end of the postnatal 3 weeks. Although the body weight of the nerve-resected rats increased gradually for the postnatal 3 weeks, they weighed less than the control rats without nerve resection. The nerve-resected rats contained less milk (0.25±0.02 g) than the control rats (0.35±0.02 g) in the stomach on P17. On P21, the body weight of the nerve-resected rats (25.33±0.32 g) was decreased by 28% compared to that of the control rats (35.08±0.57 g). Although their growth was substantially more retarded than that of the control animals, most (92%) of the nerve-resected pups could survive without facial nerve innervation. The orofacial musculature innervated by the facial nerve plays an important role in breastfeeding, but the present study shows that these muscles are not essential for the survival of neonatal rats. [Copyright &y& Elsevier]

The rostral migratory stream (RMS) is a unique forebrain structure that provides a long-distance migratory route for the neural stem cells of the periventricular region towards the olfactory bulb (OB). The purpose of the study presented here is to examine the extent of neurogenesis and gliogenesis by the neural stem cells of different origins (periventricular vs. intrabulbar) in the OB. After the RMS had been subjected to injury, the rats received intraperitoneal injections of 5-bromodeoxyuridine (BrdU) and were further reared for 2 weeks. Neuronal and glial differentiations of the BrdU(+) cells in the olfactory bulbar granule cell (OB-GCL) and the olfactory glomerular (OB-GL) layers were examined immunohistochemically using antibodies against neuronal (NeuN, neuronal nuclei) and glial (GFAP, glial fibrillary acidic protein) markers in the OBs with injured and uninjured (control) RMS. In the completely RMS-lesioned OB, where migration of the periventricular neural stem cells was inhibited, a small number of BrdU(+) NeuN(+) cells were found in both the OB-GCL and OB-GL. The BrdU(+) NeuN(+) cells accounted for a much higher percentage of the BrdU(+) cells on the control side (OB-GCL, 36.7%; OB-GL, 8.8%) than on the completely RMS-lesioned side (OB-GCL, 3.7%; OB-GL, 0.6%). The percentage of the BrdU(+) GFAP(+) cells relative to the BrdU(+) cells did not show any major difference between the control and completely RMS-lesioned sides. This study revealed differences in neurogenesis and gliogenesis between the local and migrating neural stem cells in the OB of the adult rodent. [Copyright &y& Elsevier]

Purpose Epstein-Barr Virus (EBV) is well known to be associated with posttransplant lymphoproliferative disorders (PTLD). Due to moderate immunosuppression in heart transplant (HTx) recipients, many viruses other than EBV are also infected and activated and assessment of simultaneous viral loads of other viruses is also important. In the present study, the role of simultaneous assessment of plasma and peripheral mononuclear cells for multiple viral load quantification in peripheral blood of pediatric patients after heart transplantation was elucidated. Methods In a period of 9 months (from January to October 2009) we collected 28 samples of 3 adult and 6 pediatric cardiac transplant recipients. Quantitative polymerase chain reaction for EBV, Cytomegalovirus, Parvovirus 19 (B19), BK and JC virus, and HHV6 was simultaneously performed based on the TaqMan system using DNA which isolated from peripheral mononuclear cells (PBMCs) and plasma, as described elsewhere. Phenotyping of infected lymphocytes were also done. CD8, CD19, CD45RO, CD57, etc. Results Case 1: 2-year old girl who underwent HTx at 1 year of her age, developed B cell type PTLD and died of cytokine release syndrome, showed rapid increases in EBV load in both PMBC and plasma as well as HHV 6 and B19. Case 2: 22-year female with subclinical infection for 19 years after HTx, showed sudden decrease in both in EBV load in both PMBC and plasma after conversion of everolimus to mycophenolate mofetil and both EBV loads eliminated after cytotoxic T lymphocyte (CTL) formation against EBV. Three patients (clinical in 2 and subclinical in 1) showed an increase in B19 load. Although B19 load became negative in 2 patients, B19 load sustained positive for 9 months in one patients who experienced B cell type PLTD 6 years ago and had continuous B19 infection. In one 38-year old male with steroid treatment for nephrosis and one 11-year old boy with living renal transplantation 10 years after HTx showed increases in BK and JC virus loads and an rapid decrease in both viral loads after reduction of immunosuppression. Conclusion Simultaneous multiple viral load quantifications are useful to evaluate immunosuppressive status of HTx recipients as well as monitoring of viral infection itself. [ABSTRACT FROM AUTHOR]

Abstract: We herein report a case of putative everolimus-associated chylothorax in a cardiac transplant recipient. A 17-year-old Japanese boy with dilated cardiomyopathy and severe cardiac failure requiring left ventricular assist support was determined to be a cardiac transplant candidate in 1992. He underwent overseas heart transplantation in Houston, Texas in October 1992. He was subsequently treated with immunosuppression therapy: Cyclosporine (CSA), azathioprine, and prednisolone (PRD). After several acute rejection episodes requiring steroid therapy, intravascular ultrasonography revealed a moderate degree of transplant coronary arterial vasculopathy (TCAV) with 50% stenosis in 2003. He underwent coronary stenting twice; the immunosuppressive regimen was converted to CSA, mycophenolate mofetil, everolimus (EVL), and PRD in 2006. TCAV has not progressed since then. In October 2008, chest x-ray showed bilateral pleural effusion. As we thought that the pleural effusion was caused by cardiac dysfunction due to moderate mitral regurgitation and TCAV as well as renal impairment, he was treated with diuretics and digoxin. However, the pleural effusion progressed gradually associated with exertional dyspnea and moderate edema of his lower legs. Chest computed tomography showed massive bilateral pleural effusions without evidence of malignancy in 2011. A pleural tap in 2011 revealed chylothorax. Although mammalian target of rapamycin inhibitors were major drugs for lymphoangioleimyomatosis, we believed that the chylothorax was associated with EVL. EVL was discontinued in March 2011: the chylothorax spontaneously resolved in November 2011. [Copyright &y& Elsevier]

Abstract: Because of the strict Organ Transplantation Act, only 81 brain dead (BD) organ donations had been performed in Japan for 13 years since 1997. The Act was revised on July 17, 2010, allowing, organs to be donated after BD with consent from the family, if the subject had not denied organ donation previously. This act has lead to an expectation of a 6–7-fold increase in BD donation. The 82 organ procurement coordinators (OPC) in Japan include 32 belonging to the Japanese Organ Network (JOT) and the others to each administrative division. JOT has guideline manuals of standard roles and procedures of OPC during organ procurement from BD and cardiac death donors. To manage the increased organ donations after the revision of the act, we have modified the education system. First, we modified the guideline manuals for OPC to correspond to the revised Transplant Act and governmental guidelines. Second, all OPC gathered in a meeting room to learn the new organ procurement system to deal with the revised Transplant Act and guidelines. Third, a special education program for 2 months was provided for the 10 newcomers. Last, the practical training in each donor case for newcomers was performed by older OPC. Topics of the education program were the revised transplant act and guidelines, family approach to organ donation, BD diagnosis, donor evaluation and management, organ procurement and preservation, allocation system, hospital development and family care. In the future, each OPC will be divided into special categories, such as the donor family OPC, the donor management OPC, and the operating room OPC. Therefore, we need to construct separate special education programs for each category. [Copyright &y& Elsevier]

Abstract: Although organ procurement has been regulated by The Organ Transplantation Law (brain-dead donors since 1997, donors after cardiac death since 1979), there has been no law or governmental procurement network (except for cornea) in Japan. Since the late 1980s, some university hospitals have developed original banks. Finally, in 2001 guidelines for tissue procurement were established by The Japanese Society of Tissue Transplantation and Japan Tissue Transplant Network (JTTN) to coordinate tissue harvesting. Five tissue banks were joined to the tissue transplant network (skin in one, heart valves in two, and bone in two). As the number of tissue banks is small, each bank cooperates on procurement, but cannot cover the entire country. With regard to skin transplantation, only one skin bank—The Japan Skin Bank Network (JSBN), which is located in Tokyo—has organized skin procurement. Therefore, it has been difficult to procure skin in areas distant from Tokyo, especially around Osaka. In order to improve such a situation, a tissue bank collaborating with the JSBN was established at The Medical Center for Translational Research (MTR), Osaka University Hospital in April 2008. The bank has played a role in skin procurement center in western Japan and supported procurement and preservation at the time of the skin procurement. Between April 2008 and September 2009, the bank participated in eight tissue procurements in the western area. In the future, the bank is planning to procure and preserve pancreatic islets and bones. Moreover, there is a plan to set up an induced pluripotent stem cells center and stem cell bank in MTR. This tissue bank may play a role to increase tissue procurement in Japan, especially in the western area. [Copyright &y& Elsevier]

Everolimus (EVL) can be utilized after heart reduce calcineurin inhibitor (CNI) associated nephrotoxicity, due to cell cycle inhibitor adverse effects, and as adjunct therapy for rejection and cardiac allograft vasculopathy (TCAV). Since 2007, we have primarily considered converting from mycophenolate mofetil with standard-dose CNIs to EVL with low-dose CNIs for the following recipients: 1) recipients with impaired renal function; 2) those with increases in or an initially large maximal intimal thickness (MIT) on routine intravascular ultrasound (IVUS) examinations; 3) donor derived TCAV; and 4) those with MMF-related leukopenia. In the present study, mid-term safety and effectiveness of EVL on heart transplant recipients with renal dysfunction or TCAV. A single-center, retrospective cohort study was conducted including 116 adult heart transplant patients between 1999 and 2018. Sixty nine of 116 patients was started EVL and patients who was initiated EVL due to renal dysfunction (n=21) with longer than 1 year follow-up of serum creatine and TCAV (n=22) with longer than 3 years follow-up of annual MIT measurement by IVUS were enrolled in this study. The trough levels of EVL were evaluated at 1 week after initiation. Once target trough levels of EVL (6-8 ng/mL) were achieved, the CNI dose was reduced to obtain target trough levels. EVL efficacy on renal dysfunction and TCAV and safety were assessed. In 21 patients given EVL due to renal dysfunction, serum creatinine was significantly decreased from initiation of EVL to 1 year after initiation (1.44 +/- 0.32 vs 1.23 +/- 0.36 mg/dL; p=0.0004), but that did not significantly changed since then. In 22 patients given EVL due to TCAV, MIT was significantly decreased from initiation of EVL to 3 years after initiation (1.20 +/- 0.38 mm vs 1.00 +/- 0.40 mm, p<0.001), but that did not significantly changed since then. EVL with low-dose CNI might play a role in short-term improvement in renal function and TCAV in heart transplant patients. However, immunosuppressive regimen to furtherly improve renal function or TCAV mid-term after initiation of EVL should be investigated. [ABSTRACT FROM AUTHOR]

Background Because tissue transplantation (TTx) has not been familiar to the general public or even to medical staffs in Japan, awareness of TTx is very important to increase tissue donation. Our primary aim was to describe the current status of awareness of TTx in medical staffs and in the general public around Osaka. Methods Between July 2014 and February 2015, 1015 general public citizens, 203 medical staff members working in emergency hospitals, and 168 cardiothoracic surgeons were invited to complete a letter or web-based survey through the use of a self-designed questionnaire. Results In the general public citizens, only 25.1% knew about TTx, whereas 54.7% knew about organ transplantation (OTx); 25.4% agreed to donate their organs or tissues and 17.3% disagreed to donate their organs or tissues. In medical staff members working in emergency hospitals, 58.7% knew about TTx; 82.3% agreed to support organ or tissue procurement and 10.8% disagreed to do so. Among cardiothoracic surgeons, 78.7% knew about TTx; 33.2% had used valve or vascular homografts and 57.4% wanted to use them if possible. Conclusions According to these surveys, public awareness of TTx has been less than that of OTx, but willingness to donate tissue was not different from that of donating organs. Awareness of TTx in medical staffs in emergency hospitals was higher but still not satisfactory. To increase tissue donation in Japan, the East and West Japan Tissue Transplant Network, in collaboration with cardiothoracic surgeons, should make more effort to carry out dissemination and awareness regarding TTx to the general public and to medical staffs. [ABSTRACT FROM AUTHOR]

Contact tracing for COVID-19 relies heavily on the cooperation of individuals with authorities to provide information of contact persons. However, few studies have clarified willingness to cooperate and motivation to provide information for contact tracing. This study sought to describe willingness to cooperate and motivation to report contact persons for COVID-19 contact tracing among citizens in Japan, and to assess any associated sociodemographic factors. Cross-sectional study. This was an online-based survey using quota sampling. Participants were asked about their willingness to cooperate in reporting contacts for COVID-19 contact tracing if they tested positive. Participants also responded to questions regarding their reasons for cooperating or not cooperating and provided sociodemographic data. Multiple logistic regression analysis was performed to clarify associations between sociodemographic factors and willingness to cooperate. This study included 2844 participants. The proportion of participants who were not willing to cooperate in reporting contacts was 27.6%, with their main reasons being concerns about causing trouble for the other person and being criticised for revealing their names. Willingness to cooperate was lower among men, young adults and those with an educational level less than a university degree. To improve the effectiveness of contact tracing, educational campaigns, such as reducing the fear and stigma associated with COVID-19, may be important. Furthermore, it is essential to understand that individuals may have contacts whom they do not wish to disclose to others and to be considerate when handling such situations. [ABSTRACT FROM AUTHOR]

Abstract: Background: As there is only one skin procurement organization in Japan the Japan Skin Bank Network (JSBN), all skin grafts procured in Japan are sent by a commercialized delivery system. Preliminarily, bottles containing saline were transported in a cardboard box using a so-called “cooled home delivery service” using a truck with a refrigerated cargo container. During transportation the temperature in the cardboard box increased to 18°C in summer and decreased to −5°C in winter. For these reasons, we investigated whether a newly developed container “Medi Cube” would be useful to transport skin grafts. Objectives: Four bottles with a capacity of 300 mL containing 150 mL of saline in a Medi Cube container were transported from Osaka to the JSBN in Tokyo between 4 PM and 10 AM using a commercialized cooled home delivery service. Two bottles were transported in a Medi Cube container without phase change materials (PCM) in winter and summer, respectively. Another two bottles were transported in the Medi Cube with PCMs in winter. The temperatures inside saline, inside a transportation container, and outside the container, and air temperature were monitored continuously with a recordable thermometer. Results: The temperatures inside saline and inside a Medi Cube container were maintained between 3 and 6°C, even when the temperature outside the container increased during parking. The temperature inside a Medi Cube container without PCM decreased to −3°C when the inside of the cargo container was overcooled in winter. However, the temperatures inside saline and inside a Medi Cube container with PCM were between 3 and 6°C, even when the temperature outside the container decreased to below 0°C in winter. Conclusion: A Medi Cube container with PCM provided a safe, easy, and cost-effective method for overnight transportation of skin grafts. [Copyright &y& Elsevier]

The present study was undertaken to determine the neuronal population essential for normal and minimal facial function of young adult rats that had received various degrees of crush injuries to the facial nerve in the neonatal period. Using a neuronal tracer, it was found in young adult rats receiving neonatal injuries that the minimum number of tracer-labeled facial motor neurons necessary for normal facial function corresponded to 13–14% of the neurons (2540±64) of the age-matched control animals, whereas the minimum number of neurons necessary for minimal facial function corresponded to 5%. On the other hand, the minimum numbers of tracer-labeled facial motor neurons necessary for normal and minimal facial function of young adult rats that received various degrees of crush injuries corresponded to 61 and 27–30%, respectively, of the neurons (2540±64) of the uninjured control animals. These results indicate that the facial function of animals with nerves crushed at the neonatal stage can be adequately maintained by a very small population of neurons, implying a great potential of neonatal neurons for neural plasticity. [Copyright &y& Elsevier]

• Direct numerical simulations of fully developed turbulent Taylor-Couette flows controlled by a traveling wave-like blowing and suction are performed. • In the inner cylinder control, the torque reduction is obtained when the wave travels in the co-rotating direction with the inner cylinder. • In the outer cylinder control, the torque reduction is obtained when the wave propagates in the opposite direction. • Although the torque is reduced, the Taylor vortex remains. In wall turbulence, a traveling wave-like control is known to decrease the skin-friction drag and induce the relaminarization phenomenon. Because it is noteworthy to investigate the control effect in other canonical flows, direct numerical simulations of fully developed turbulent Taylor–Couette flows are performed. The Reynolds number, based on the wall velocity of a rotating inner cylinder and the radius of a centerline between cylinders, is set to 84,000. The traveling wave-like blowing and suction is imposed on the inner or outer cylinder wall, and the control effect is parametrically investigated. In the inner cylinder control, the torque reduction is obtained when the wave travels in the co-rotating direction with the inner cylinder, and its wavespeed is faster than the rotation. In the outer cylinder control, in contrast, the torque reduction is obtained when the wave propagates in the opposite direction. While the control is imposed on one side wall (i.e., inner or outer cylinder), the control affects the entire flow region. The Taylor vortex remains, while the traveling wave affects its strength. The three-component decomposition analysis shows that the traveling wave creates the coherent contribution on the torque, while the random contribution on it is reduced. Accordingly, a major factor of the torque reduction in the Taylor–Couette flow is the reduction of the random contribution. In addition, for the faster wavespeed cases with the small wavenumber (i.e., the long wavelength), the drag reduction larger than 60% is obtained and the relaminarization occurs in these cases. [ABSTRACT FROM AUTHOR]

Abstract Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized and potentially fatal complication of cardiac transplantation that commonly involves the gastrointestinal tract. Herein, we report a case of life-threatening gastrointestinal bleeding from recurrent terminal ileac ulcers mimicking PTLD in a heart recipient treated with everolimus (EVL). A 40-year-old man underwent heart transplantation for dilated cardiomyopathy 3 years prior to the current admission and was treated with tacrolimus and EVL. He was admitted to a local hospital because of fever, abdominal pain, and diarrhea. His symptoms persisted and, 3 weeks later, hematochezia occurred; thus, he was transferred to our hospital. As computed tomography and 18F-fluorodeoxyglucose positron emission tomography showed bowel-wall thickening of the terminal ileum, gastrointestinal PTLD was initially suspected. However, although colonoscopy— performed after switching EVL to mycophenolate mofetil (MMF)—showed terminal ileac ulcers, the histologic examination revealed no findings corresponding to PTLD. As EVL may delay ulcer healing, MMF was maintained for 3 months. After repeated colonoscopy showed ulcer healing, MMF was switched back to EVL for cardiac allograft vasculopathy prevention. Three weeks later, he was emergently admitted to a local hospital for life-threatening gastrointestinal bleeding from a recurrent terminal ileal ulcer, which required hemostatic forceps hemostasis. As EVL is suspected to be associated with recurrent ileal ulcers, EVL was again switched back to MMF. The ileal ulcers resolved, without recurrence in 3 months of clinical follow-up. This case demonstrates that cases of life-threatening gastrointestinal bleeding from recurrent terminal ileac ulcers can mimic PTLD in a heart recipient treated with EVL. Highlights • PTLD is a potentially fatal complication of cardiac transplantation. • Imaging findings suggested gastrointestinal PTLD in a heart recipient. • Repeated histologic examinations ruled out gastrointestinal PTLD. • EVL treatment may have delayed mucosal healing. [ABSTRACT FROM AUTHOR]

Abstract Background Left ventricular assist device (LVAD) therapy is the "gold standard" alternative therapy for patients with advanced heart failure. However, LVAD therapy is still uncommon in the Asia-Pacific region. Therefore, we aimed to elucidate the clinical outcomes of patients from Japan supported with the HeartMate II (HM-II) LVAD at our institution. Methods Ninety-two patients (mean 44.3 ± 12.1 years, 68 men, average body mass index 1.65 ± 0.28 m2; 81 with nonischemic cardiomyopathy) who underwent HM-II implantation for bridge to transplantation (n = 91) or for destination therapy in a clinical study (n = 1) at the National Cerebral and Cardiovascular Center between April 2013 and October 2017 were enrolled in this analysis. Preoperatively, most patients (n = 73, 79%) had an INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile of between level 2 and 4. Postoperatively, the average pump speed was 8602 ± 258 rpm and the hemodynamics were well compensated. Results Adverse events consisted of 38 (41.3%) hemolysis, 30 (32.6%) major infection, 27 (29.3%) major bleeding (6 [6.5%] with gastrointestinal bleeding), and 18 (19.6%) neurologic dysfunction events. Eighteen patients underwent heart transplantation (HTx) after an average of 32.9 ± 8.9 months of VAD support, and overall survival at both 6 months and 3 years was 96.3%. Conclusion Clinical outcome among patients with HM-II at our institution is satisfactory for both survival and adverse events. The HM-II can provide effective hemodynamic support during the extremely long waiting period for HTx in Japan. Highlights • This study has assessed the current status of HeartMate II patients in Japan. • Study patients were young and had a nonischemic etiology and small body size. • Japanese patients with the HeartMate II have shown good survival and few adverse events. • Japanese patients with the HeartMate II device had frequent hemolytic events. • Long waiting periods for heart transplantation is an important clinical issue in Japan. [ABSTRACT FROM AUTHOR]

Background Reversible cerebral vasoconstriction syndrome (RCVS) is a transient cerebrovascular disorder putatively caused by some immunosuppressive agents. Case Report We recently encountered a 47-year-old female patient diagnosed with dilated cardiomyopathy who developed RCVS after heart transplantation. A triple-drug regimen consisting of tacrolimus, mycophenolate mofetil, and a corticosteroid was started after surgery. On postoperative day (POD) 11, the patient developed a severe headache, although computed tomography of the head demonstrated no signs of hemorrhage or infarction. At first, both a painkiller and migraine drugs were regularly administered to the patient. On POD 21, however, she developed an unbearable headache with a visual field defect and mild hemiparesis of the right hand. Magnetic resonance imaging (MRI) of the brain revealed a cerebral infarction in the left occipital lobe with diffuse vasoconstriction of both the middle and posterior cerebral arteries. A diagnosis of RCVS was made and tacrolimus, a drug suspected to cause RCVS, was discontinued. In its place, two doses of basiliximab followed by everolimus, both of which are alternatives for tacrolimus, were given. The corticosteroid dose was also increased. Furthermore, to release vasoconstriction, both verapamil and diltiazem were administered. On POD 27, cerebrovascular constrictions were shown to be relieved on brain MRI and the patient's neurological symptoms subsequently almost completely diminished. Conclusion RCVS should always be considered as a cause of headache in heart transplant recipients because tacrolimus, an immunosuppressive agent, may trigger RCVS. This will allow rapid intervention that is essential for avoiding irreversible neurological deficits. [ABSTRACT FROM AUTHOR]

Background Transplant coronary arterial vasculopathy (TCAV) is a major cause of death after heart transplantation (HTx). Palliative coronary revascularization has been attempted in patients with severe TCAV; however, the outcome has not been fully elucidated. Methods Ninety-six patients who were treated after HTx at our institute between 1999 and 2015 were screened for TCAV. TCAV was defined as >70% stenosis on coronary angiography (CAG) or a maximal intimal thickness of >0.5 mm in the right or left coronary arteries on intracoronary ultrasonography (IVUS). In the present study, the outcomes of patients with severe TCAV who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) were investigated. Results TCAV containing donor-transmitted atherosclerosis was cumulatively found in 69 patients (71.9% of the total; mean age, 34.6 ± 13.1 years; 52 men; mean follow-up duration, 83.0 ± 60.4 months). Five (7.2%) and 64 (92.8%) of the 69 patients were diagnosed as having TCAV by use of CAG and IVUS, respectively. All 5 patients diagnosed by with the use of CAG underwent coronary revascularization between 1 and 236 months after HTx. Three patients underwent PCI with drug-eluting stents, with a primary success rate of 100%. No angiographic restenosis occurred in 2 patients at 31 and 36 months after PCI, respectively. Meanwhile, 2 patients underwent CABG. No peri-operative complications occurred, and all grafts were patent as assessed by use of CAG at 34 and 5 months after CABG. Conclusions Coronary revascularization was feasible and effective for severe TCAV with middle-term follow-up. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (MI) due to left main coronary artery occlusion leads to poor outcomes, despite intensive treatments using extracorporeal life support (ECLS). We hypothesized that morbidity and mortality related to this pathology may be reduced by upgrade from peripheral to central ECLS, in which inflow directly from the cardiac chamber is connected to the ascending aorta through the blood pump with or without oxygenator. This study enrolled a consecutive institutional series of 61 cases who were treated with peripheral ECLS for acute MI induced by left main coronary artery occlusion between April 2013 and October 2020. The average age was 64±14-year-old, and male patients consist of 77%. Modes of peripheral ECLS, such as IABP, Impella devices or veno-arterial ECMO were optimized according to the hemodynamics. While 39 cases received continued peripheral ECLS, the remaining 22 cases (36%) whose peripheral ECLS was suboptimum were upgraded to central ECLS following 2.9 days of peripheral ECLS. There was 22 in-hospital death (56%) in the peripheral group and 11 in the central group (50%, p=0.79). The major cause of mortality in the peripheral group was low output syndrome in 9 (53%), cerebrovascular accident (CVA) in 4 (24%). In contrast, in the central group, 3 (23%) died of CVA and 3 (23%) died of septicemia. Of 11 surviving cases in the central group, eight cases were further upgraded to the durable LVAD for bridge to transplantation. In the remaining 3 cases in the central group, ESLS was discontinued for palliative care. Cox proportional hazard regression analysis detected that high CK-MB (over 570 IU/ml) but not central ECLS was an independent risk factor of death. In conclusion, upgrade to central ECLS avoided mortality associated with suboptimum peripheral ECLS for left main occlusion-induced cardiogenic shock. Life-long mechanical circulatory support is inevitable in cases who need upgrade to central ECLS. [ABSTRACT FROM AUTHOR]

Introduction Tuberculous paradoxical reactions (PRs) are excessive immune reactions occurring after antituberculosis (TB) treatment and are commonly observed in immunocompromised hosts such as patients infected with the human immunodeficiency virus. Case Report We recently encountered a 63-year-old male heart transplant recipient who developed tuberculous PR after treatment for miliary TB. The patient had been receiving immunosuppressive therapy with cyclosporine and mycophenolate mofetil for over 15 years. The diagnosis of miliary TB was made based on the presence of intermittent fever and fatigue; thus, anti-TB treatments (isoniazid, levofloxacin, ethambutol, and pyrazinamide) were started, which led to rapid defervescence and regression of the granular shadow and pleural effusion. However, a new persistent fever and confused state developed 1 month after the anti-TB therapy was started. After excluding possible etiologies of the patient's symptom, a PR was suspected, and anti-TB drugs were continued; corticosteroids were added as anti-inflammatory agents. After that, he has shown a favorable course with long-term anti-TB chemotherapy. Conclusion A PR should always be considered when the patients' symptoms of tuberculosis re-exacerbate after an appropriate anti-TB therapy. A PR commonly occurs in patients with various immunologic conditions including heart transplant recipients. [ABSTRACT FROM AUTHOR]

Because the shortage of donor organs is especially serious in Japan, since 2002 a unique partnership between transplant consultant physicians and local physicians has been developed to maximize the organ utilization rate. Since 2011, more than 25 lung consultant physicians have been registered to specifically assess donor lungs and provide advice on intensive respiratory care to donors. In this study, we retrospectively reviewed the efficacy of this system for lung transplantation opportunities and outcomes. One hundred eighty-seven brain-dead lung donor candidates were chronologically divided into 3 phases: I (May 1998–November 2006) and II (December 2006–January 2011), before and after medical consultants requested that local physicians administer aggressive bronchial suctioning using bronchoscopy, respectively; and phase III (February 2011–January 2013), after the emergence of lung consultants. The lung utilization rate, Pa o 2 /F io 2 ratio at the first and second brain death examinations and at the tertiary assessment before recovery, and graft survival were analyzed. The lung utilization rate was significantly higher in phases II and III than in phase I. In phases I and II, the Pa o 2 /F io 2 ratio at the tertiary assessment was significantly lower than that at the first or the second brain death examination, whereas it did not worsen with time in phase III. Graft survival was significantly better in phases II and III than in phase I. Graft death due to primary graft dysfunction was significantly more frequent in phase I than in phases II and III. In conclusion, this system is effective in improving lung transplantation opportunities and outcomes. [ABSTRACT FROM AUTHOR]

Highlights: [•] No data are available on the total number of olfactory receptor neurons (ORNs). [•] Stereological analyses were applied for the total quantification of ORNs in mice. [•] We concluded that the total number of ORNs was approximately 10,000,000. [ABSTRACT FROM AUTHOR]

Left ventricular assist devices (LVADs) have emerged as an important treatment option for bridging patients with heart failure to transplant. LVADs have shown improved survival; however, the impact of LVAD type on the quality of life (QoL) while on long-term LVAD support is unknown. We aimed to evaluate the QoL of patients while supported with a LVAD in Japan. 299 patients enrolled in the Japanese Registry for Mechanically Assisted Circulatory Support (J-MACS), who were listed for transplant or likely to be listed, received a LVAD from 2010 to 2018 and had full QoL data, were enrolled. QoL data, such as visual analogue scale (VAS) and EQ-5D-3L by 5 dimensions (5D: mobility, self-care, usual activities, pain/discomfort and anxiety/depression) before and at 3- and 12-months after implantation of a LVAD were obtained from the J-MACS Registry. These patients were divided into 3 groups; primary implantable LVAD (iLVAD) (N=263), primary paracorporeal LVAD (pLVAD) (N=9) and bridge from paracorporeal to implantable LVAD (BTB) (N=27). VAS in all groups significantly increased from before to 3- and 12-months after LVAD implantation(p<0.001). VAS in pLVAD group before and 3- and 12-months after LVAD implantation were significantly lower than those in BTB and iLVAD groups (32.2±28.5, 61.4±23.2 and 62.3±23.1 in pLVAD, 42.7±19.2, 74.0±14.6 and 74.3±19.3 in BTB and 47.4±24.9, 71.1±18.2 and 72.9±18.2 in iLVAD, respectively). The proportions of some and/or extreme problems in mobility, self-care and usual activities before LVAD implantation in pLVAD group were 100%, while those in BTB and iLVAD group were lower than 87.6%. Although the proportions of some and/or extreme problems in all dimensions in pLVAD group significantly decreased from before to 3- and 12-months after LVAD implantation, the proportions of some and/or extreme problems in all dimensions except anxiety/depression in pLVAD group were still significantly higher than those in BTB and iLVAD. QoL as VAS and 5D were significantly improved after implantation of any LVAD type. However, VAS and 5D except anxiety/depression in patients with pLVAD were significantly lower and more problems than those in patients with iLVAD. These differences were eliminated by converting from pLVAD to iLVAD. BTB might be a beneficial treatment option to improve QoL as well as patient's survival. [ABSTRACT FROM AUTHOR]

Central extracorporeal life support (ECLS) has been shown to yield a sufficient flow support with unloading of heart and lung in cases having acute refractory heart failure with durable LVAD candidacy being uncertain. In contrast, subsequent implantation of durable LVAD after the bridge by the central ECLS is reportedly associated with morbidities in-hospital and long-term. This study aimed to review outcomes of this bridge strategy from central ECLS to durable LVAD, as compared to those of primary LVAD implantation. This study enrolled an institutional consecutive series of 158 cases who underwent durable LVAD implantation from April 2013 to September 2020. Of these, 43 cases (27%), who were bridged from central ECLS, were compared with 115 cases (73%) who underwent primary durable LVAD implantation. The mean age was 45.2±12.2 years and 111 cases were male. Durable LVAD included HeartMateII 120 cases, HeartMate3 in 38 cases. Before the durable LVAD implantation, there were significant intergroup differences in systolic diameter of the LV (Bridge; 51.7±2.0 vs Primary; 65.0±1.2 mm, p<0.0001), pulmonary capillary wedge pressure (11.1±1.6 vs 20.5±0.9 mmHg, p<0.0001), serum albumin (3.2±0.08 vs 3.9±0.04 g/dL, p<0.0001), and serum creatine level (0.8±0.05 vs 1.0±0.03 g/dL, p<0.0001). As for the intraoperative factors, longer operative time and a larger amount of blood products were required in the bridge group. The overall survival rates were not significantly different (p=0.11), though the rates of stroke incidence were significantly higher in the bridge group (1-year: 30% vs 8%, 5-year: 30% vs 12%, p=0.0025). Cox multivariate hazard analysis in the entire cohort showed that the bridge strategy was an independent risk factor of stroke (hazard ratio, 3.37; P=0.0012; 95% confidence interval, 1.3 - 8.7). In subgroup analysis, cases having stroke showed a smaller preoperative systolic diameter of the LV (55.5±3.1 vs 62.3±1.3 mm, P=0.044) and a larger amount of platelet product use (42.3±3.6 vs 32.7±1.5 units, P=0.017) as compared to those not having stroke. The bridge strategy yielded similar midterm outcomes as compared to the primary strategy, apart from stroke incidence which was more prominent after the bridge strategy. Perioperative care for bleeding potentials may protect from stroke after the bridge strategy. [ABSTRACT FROM AUTHOR]