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Objectives The aim of this AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial subgroup analysis was to examine rivaroxaban monotherapy benefits and their relation to the time between stenting and enrollment among patients after coronary stenting. Background Of 2,215 patients with atrial fibrillation and stable coronary artery disease in the AFIRE trial, rivaroxaban monotherapy was noninferior to rivaroxaban plus antiplatelet therapy (combination therapy) in terms of efficacy and superior for safety endpoints. However, thrombotic risk after antiplatelet therapy cessation remained a concern among 1,444 patients who had undergone coronary stenting >1 year before enrollment. Methods The benefits of rivaroxaban monotherapy in coronary stenting subgroups were assessed for efficacy (a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death of any cause), safety (major bleeding defined according to International Society on Thrombosis and Haemostasis criteria), ischemic endpoints, net adverse clinical event, and time between stenting and enrollment. Results Efficacy and safety endpoints for monotherapy were superior to combination therapy, with HRs of 0.70 for efficacy (95% CI: 0.50-0.98; P = 0.036) and 0.55 for safety (95% CI: 0.33-0.92; P = 0.019). For ischemic endpoints, the HR was 0.82 (95% CI: 0.58-1.15; P = 0.240). The HR became smaller with longer time between stenting and enrollment (efficacy, P for interaction = 0.158; safety, P = 0.097). Conclusions In patients with atrial fibrillation after coronary stenting, the benefits of rivaroxaban monotherapy for efficacy and safety endpoints were consistent with those in the whole AFIRE trial population. The benefits became apparent with longer time between stenting and enrollment. (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study [AFIRE]; UMIN000016612 , NCT02642419 )

Background Several comorbidities, including cardiovascular diseases or myocardial injury, are reported to be associated with poor prognosis in patients with Coronavirus disease 2019 (COVID-19). However, detailed prognostic analysis of myocardial injury by various biomarkers in COVID-19 patients is limited. Purpose This study aims to explore the prognostic values of high-sensitive Troponin I (hsTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for COVID-19 patients using Japanese real-world data. Methods The COVID-MI study is a retrospective cohort study that enrolls consecutive laboratory-confirmed COVID-19 patients admitted to the hospital from July 2020 to September 2021. We collected clinical data, including cardiac biomarker values, by chart review. If the prespecified biomarkers in concern were not available, we measured them using the institutional serum blood bank, which enrolled patients prospectively from July 2020. Patients with available biomarkers were analyzed according to the values of hsTnI or NT-proBNP, using the clinically relevant thresholds (hsTnI: 5 ng/L and 99th percentile of the upper reference limit [99%ile URL], and NT-proBNP: 125 pg/mL and 900 pg/mL). The primary outcome measure was all-cause death. Secondary outcome measures included acute respiratory distress syndrome, myocardial infarction, myocarditis/pericarditis, venous thromboembolism, cerebral infarction, and bleeding events. Results We enrolled 917 patients with COVID-19 confirmed by viral nucleic acid amplification test. The mean age was 61 years, and 591 patients (64%) were men. On admission, the number of patients classified as severe or critical COVID-19 was 515 (56%) and 85 (8.7%), respectively. Among the 544 patients with hsTnI values, 365 (67%) patients had elevated hsTnI of ≥5 ng/L, and 134 patients (25%) had TnI of ≥99%ile URL. Besides, among 546 patients with NT-proBNP values, 295 patients (54%) had elevated NT-pro-BNP of ≥125 pg/mL, and 93 patients (17%) had NT-proBNP of ≥900 pg/mL. The median follow-up period was 31 days (interquartile range: 11–90 days). In cumulative incidence analysis, higher levels of hsTnI and NT-proBNP were associated with significantly higher mortality (hsTnI: Conclusion Elevation of hsTnI or NT-proBNP was associated with poor prognosis in the current relatively severely ill COVID-19 patients. Measuring hsTnI or NT-proBNP can be an attractive option for risk stratification and deciding appropriate management in patients with COVID-19. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Institutional Research Fund at Kobe City Medical Center General Hospital

Dear Editor, Post-transplant immunoglobulin A (IgA) nephropathy is frequently observed in patients after renal transplantation for IgA nephropathy, and is associated with an increased risk of graft...

Recently, steroid reduction/withdrawal regimens have been attempted to minimize the side effects of steroids in renal transplantation. However, some recipients have experienced an increase/resumption of steroid administrations and acute graft rejection (AR). Therefore, we investigated the relationship between the individual lymphocyte sensitivity to steroids and the clinical outcome after steroid reduction/withdrawal. We cultured peripheral blood mononuclear cells (PBMCs) isolated from 24 recipients with concanavalin A (Con A) in the presence of methylprednisolone (MPSL) or cortisol (COR) for four days, and the 50% of PBMC proliferation (IC50) values and the PBMC sensitivity to steroids were calculated. Regarding the experience of steroid increase/resumption and incidence of AR within one year of steroid reduction/withdrawal, the IC50 values of these drugs before transplantation in the clinical event group were significantly higher than those in the event-free group. The cumulative incidence of steroid increase/resumption and AR in the PBMC high-sensitivity groups to these drugs before transplantation were significantly lower than those in the low-sensitivity groups. These observations suggested that an individual’s lymphocyte sensitivity to steroids could be a reliable biomarker to predict the clinical outcome after steroid reduction/withdrawal and to select the patients whose dose of steroids can be decreased and/or withdrawn after transplantation.

We report a case of pure red cell aplasia (PRCA) caused by parvovirus B19 (PVB19) infection, which was transmitted through a kidney allograft. The patient underwent a living-donor kidney transplant from his wife at the age of 60. Despite successful engraftment with a normal creatinine level, he developed severe anemia that required frequent blood transfusions 2 months after transplantation. Renal anemia was unlikely as his serum erythropoietin level was extremely high. A bone marrow aspiration test demonstrated the existence of large proerythroblasts. Although anti-PVB19 IgM antibody levels were not increased, polymerase chain reaction (PCR) detected PVB19 DNA in his serum. Thus, he was diagnosed as having PRCA induced by PVB19 infection. PCR analysis of total DNA isolated from 0-hour biopsy sections showed the existence of PVB19 DNA. Furthermore, PVB19 proteins was detected on renal tubules of 0-hour allograft by immunoperoxidase staining. Thus, transmission of PVB19 through the allograft was confirmed. A single course of intravenous immunoglobulin (IVIG) therapy resulted in substantial improvement; however, the effect was limited, and severe anemia relapsed after 5-6 months. Several courses of IVIG with adjustment of immunosuppressive drugs resulted in long-term remission. Our case demonstrates that donor-transmitted PVB19 infection should be suspected in kidney transplant recipients who develop refractory anemia during the early post-operative phase.

Background: The perfusion areas of renal arteries in renal transplantation are assessed via subjective observations during perfusion in a bench surgery; however, this evaluation method lacks reliability and objectivity. In this study, we aimed to evaluate the perfusion area of each main and side artery kidney graft using a 3-dimensional (3D) image analysis system. Methods: We enrolled 50 patients who had undergone living kidney transplantation with multiple renal artery grafting at our center between 2005 and 2017. All computed tomography images from donors were retrospectively analyzed using a 3D image analysis system. We then calculated the artery perfusion areas associated with the artery reconstruction method used. Results: The perfusion areas of side arteries, which were evaluated after surgery, were statistically different among cases employing different reconstruction methods (P Conclusion: A 3D image analysis system could provide an accurate visual representation of the vasculature prior to living donor transplantation. It could also enable calculation of perfusion area for each artery and preoperative prediction of the need for arterial reconstruction, thereby promoting safe kidney transplantation surgery.

Background Extended-release tacrolimus (TacER), administered once daily, offers improved adherence with reduced side effects while still maintaining an immunosuppressive potency equivalent to that of conventional tacrolimus preparations. Methods The study included 83 patients who received consecutive living-donor kidney transplants at our facility from June 2013 to December 2016. Comparisons were made between 48 cases of induction with TacER and 35 cases of induction with cyclosporine (CyA). The observation period was 3 months after transplantation. Transplanted kidney function, rejection, infectious disease, lipid abnormalities, and glucose tolerance were compared. Results The 2 groups showed no significant difference in donor background or transplanted kidney function. Within the 3-month observation period, an acute rejection response was observed in 2 cases in the TacER group and in 8 cases in the CyA group. After transplantation, hyperlipidemia requiring medication was observed more frequently in the CyA group. The 2 groups did not show a marked difference in systemic infection or renal calcineurin inhibitor toxicity in histopathologic examination of the transplanted kidneys 3 months after surgery. Discussion Proactive use of TacER leads to improved adherence while yielding immunosuppressive potency equivalent to that of conventional tacrolimus preparations; however, tacrolimus has a potent blood sugar-elevating effect; thus, direct comparison with the CyA group is important for assessing the side effects. Conclusion TacER has the potential to also reduce side effects in the early stages after surgery, suggesting its potential as a drug of first choice.

Introduction The number of young women who wish to become pregnant opting for kidney transplants is increasing, as becoming pregnant under hemodialysis or peritoneal dialysis is associated with many risks. However, there have been reports indicating that these patients are subject to a higher risk of miscarriage compared to women with normal renal function. We examine and report cases of patients that experienced pregnancy after undergoing kidney transplantation at our hospital. Subjects and method Of the kidney transplantation cases that were performed at our hospital between 1985 and 2016, there were 7 cases of pregnancy. The serum creatinine levels, urine protein findings, etc, of these 7 cases were examined during the pre-pregnancy, pregnancy, childbirth, and postpartum periods. Results All 7 cases were able to give birth. There were two cases of transient postpartum hypertension. There were no cases of obvious pregnancy toxemia or fetal growth retardation. Two of the cases resulted in the failure of the transplanted kidneys. Discussion According to previous studies on pregnancy and childbirth after kidney transplantation, the presence of high blood pressure and proteinuria as well as the renal function at the time of pregnancy is closely associated with postpartum renal function. Urine protein was detected prior to pregnancy in both cases and resulted in the failure of the transplanted kidneys. The influence of immunosuppressants on the mother and fetus is also an important consideration. Conclusion We believe it is extremely important to ensure a thorough informed consent process prior to pregnancy and systematic use of immunosuppressants for young female transplant recipients.

Introduction Elderly kidney donors have recently become more common in living related kidney transplantation in Japan. Therefore, it is important to evaluate whether kidney function in elderly donors after nephrectomy is preserved over long periods of time. Doppler ultrasonography measurement is practical for donors after nephrectomy because it involves simple and noninvasive examinations. Doppler ultrasonography can detect compensatory hypertrophy and blood flow parameters, namely resistive index (RI) and pulsatility index (PI), of the preserved kidney in living donors. Patients and Methods Our study included 58 donors, divided into 2 groups according to age; the elderly donor group was comprised of those 65 years old or older. We measured length, width, and short diameter of the preserved kidney using Doppler ultrasonography, and calculated kidney volume. Results The elderly group was comprised of 13 patients. In this group, the median preserved kidney volume was 145.0 cm 3 (101.8–193.5) before nephrectomy, and 127.6 cm 3 (99.0–183.4) and 145.5 cm 3 (141.3–148.6) at 1 and 12 months after nephrectomy, respectively. We did not observe significant compensatory hypertrophy in the preserved kidneys of elderly donors postoperatively. Both the mean PI and RI values of elderly donors increased progressively after nephrectomy. No compensatory hypertrophy occurred in the preserved kidneys of elderly donors, although the PI and RI did increase in these donors. Conclusion Our results indicate that nephrectomy caused nephrosclerosis in the preserved kidneys of elderly donors and that prevention of hypertension may be important after nephrectomy in elderly donors.

Background To increase the number of cadaveric kidney transplants in Japan, it is necessary to proactively perform transplantation from marginal donors. We had the opportunity to frequently perform kidney transplantation from expanded-criteria donors (ECDs), and it is anticipated that there will be increases in the number of ECD kidney transplants. Methods In our institution, 18 patients underwent cadaveric kidney transplantation from January 2001 to December 2011. Sixteen of those patients were classified into 2 groups according to donation after brain death (BD) or after cardiac death (CD). We also classified donors as ECDs or standard-criteria donors (SCDs). Results Kidney graft survival and engraftment were observed in all of the patients. Renal function at 1 year after transplantation was significantly better in the BD group than in the CD group. However, there was no significant difference between the groups in renal function at 3 and 5 years. Renal function at 1 and 3 years after transplantation was significantly better in the SCD group than in the ECD group, but there was no difference in renal function between the SDC and ECD groups at 5 years. Conclusions The results were good for all of the patients. There are many reports that graft survival rate at 3–5 years after transplantation from ECDs is poorer than from SCDs. However, no statistically significant difference was found in kidney function at ≥5 years between the ECD and SCD groups in our patients.

BACKGROUND Everolimus (EVL) plus tacrolimus (TAC) therapy is effective and safe in renal transplantation. However, the pharmacokinetic and pharmacodynamic information for EVL combined with TAC is limited. We investigated the pharmacodynamic drug-drug interaction between EVL and TAC at their therapeutic concentration range. MATERIAL AND METHODS Isolated peripheral blood mononuclear cells (PBMCs) from 22 healthy participants aged 22 to 24 years were cultured with concanavalin A (Con A) in the presence of EVL and/or TAC for 4 days, and the proliferation rate of the PBMCs was calculated. RESULTS TAC promoted the inhibitory efficacy of EVL against the mitogen-activated proliferation of PBMCs at the EVL therapeutic concentration range. When 0.175 ng/mL or more of TAC was combined with 30 ng/mL or more of EVL, the antagonistic effect of TAC on the inhibitory efficacy of EVL against the mitogen-activated proliferation of PBMCs was observed. Conversely, when 0.4 ng/mL TAC and 10 ng/mL or more of EVL were combined, the antagonistic effect of EVL on the inhibitory efficacy of TAC against the mitogen-activated proliferation of PBMCs was observed. CONCLUSIONS The pharmacodynamic synergistic efficacy of EVL and TAC in combination on mitogen-activated PBMCs was evident at the therapeutic concentration range, which is used in renal transplantation. However, these drugs antagonize each other to suppress the proliferation of activated PBMCs at concentrations higher than those clinically used.

In elderly kidney transplant (KT) recipients, the incidence of acute rejection is decreased, while that of fatal infections is increased. There are currently no guidelines for an upper age limit for KT, which is very difficult to determine. Here we examined several cases of elderly KT recipients.We evaluated 127 KT patients treated at our department between 2003 and 2012 and followed them for 3 years post-transplant. The subjects were divided into two groups by age: ≥60 years (elderly group; n = 24); and 59 years (non-elderly group; n = 103). The presence or absence of acute rejection and infection, dose of immunosuppressive drugs, trough calcineurin inhibitor level, renal function, and graft and patient survival rates were retrospectively examined.Our basic immunosuppressive regimen was a combination of calcineurin inhibitor, methylprednisolone, mycophenolate mofetil, and basiliximab. At 1 year post-transplantation, the average tacrolimus and cyclosporine dose and trough levels were not significantly different. The mean dose of mycophenolate mofetil in the elderly group at 1 year post-transplantation was significantly lower than that of the non-elderly group. The incidences of cytomegalovirus infection and acute rejection during follow-up did not differ significantly between groups. There were no significant differences in creatinine level between the two groups. In the elderly group, the graft survival rates at 1 and 5 years were 100% and 95.4%, respectively, while those in the non-elderly group were 98.1% and 92.5%, respectively.Using our current immunosuppressive protocol, the outcomes of patients in the elderly group were considered acceptable.

Background To increase the number of cadaveric kidney transplants in Japan, it is necessary to proactively use organs from all donors. Since the revision of the Organ Transplant Law, the number of organ donors after cardiac death (DCD) has decreased but the number of organ donors after brain death (DBD) has increased; however, the number of donor organs and awareness of cadaveric transplantation have increased. Methods At our institution, 28 patients underwent cadaveric kidney transplantation from January 2001 to December 2016. These patients were classified into 2 groups according to DBD or DCD. Furthermore, 10 patients received transplants from expanded criteria donors (ECD) and 18 received them from standard criteria donors (SCD). Results Kidney graft survival and engraftment were observed for all patients. There were no significant differences in renal function at 6 months for DBD and DCD transplant recipients. Renal function at 1, 3, and 5 years and serum creatinine levels were better for the ECD group. Renal function at 5 years after transplantation was significantly better for the SCD group than for the ECD group; however, there was no difference in delayed graft function between the SCD and ECD groups. Comparisons of the 3 groups showed good renal function for transplants from DBDs, but there was no significant difference in survival rates. Conclusions Results were good for all patients. There were no significant differences in outcomes of our patients who received transplants from ECD or SCD.

Background: The main purpose of directly sampled endometrial cytology is to detect invasive endometrial malignancies. With this principle in mind, The Yokohama System (TYS) Working Group, composed of cytopathologists, surgical pathologists, and gynecologic oncologists met at the 2016 International Congress of Cytology, Yokohama, with the aim to publish a standardized reporting system inclusive of specific diagnostic categories and cytomorphologic criteria for uniform and reliable diagnosis of endometrial malignancies on directly sampled endometrial samples. Methods: The diagnostic cytopathologic criteria previously published in the literature by the Japanese and Greek working group on endometrial cytology (Yanoh et al. [2012] Acta Cytol. 56:233; Margari et al. [2016] Diagn Cytopathol. 44:888-901) were critically reviewed with the aim of correlating the diagnostic classes to well defined risk categories for endometrial carcinoma (EC). Moreover, two classes of “atypical” endometrial cells were correlated respectively to a low- and high risk group. Some methodological suggestions for the application of ancillary special technologies to liquid based samples were also given. Results: The TYS group conceived a new Bethesda-style classification for directly sampled endometrial cytology which correlates the cytologic diagnostic classes with definite risk categories. The cytomorphologic findings have been correlated to the molecular pathology of EC, also through the application of ancillary special techniques to liquid-based samples. Conclusions: The success of TYS will depend on the acceptance of TYS by all the relevant pathology and gynecologic oncology communities who, by their joint efforts, will adopt, critically evaluate, and optimize this method with the only aim of further improving the impact of endometrial cytology on patients’ care. © 2018 Wiley Periodicals, Inc.

Recently, the ability to analyze big data has been required for the optimization of social systems and the development of artificial intelligence. Consequently, the solution of combinatorial optimization problems has become important in recent years, especially for the suitable operation of infrastructures. However, combinatorial optimization problems have unique properties that the number of candidate solutions increases explosively as the number of parameters is increased. One possible resolution of this issue involves artificial and/or simulated Ising spin system. In this work, we have implemented such a spin system using “prompt decision logic”. The convergence operation was successfully observed in prompt decision method for spin interaction. Therefore, it is indicated that Ising computing by prompt decision logic could resolve combinatorial optimization problems.

Feedback-controlled electromigration (FCE) has been employed to control metal nanowires with quantized conductance and to create nanogaps. The setting of the experimental parameters based on experiences is a common practice in FCE. However, tuning the optimization of parameters is intractable because trying all different combinations systematically is practically impossible. Therefore, we proposed an optimization process of the FCE parameters using Ising spin model, which can search for the global optimum in a multidimensional solution space within short calculation time. The FCE parameters were determined through a convergence property of the Ising spin model. This result implies that the proposed method is an effective tool for the process optimization of FCE.

Recently, the new computing architecture using Ising spin model has been attracting considerable attention. It is well known that the Ising spin model represents the physical properties of ferromagnetic materials in terms of statistical mechanics. In this model, the spin states are varied in order to minimize the system energy automatically, by the interaction between connected adjacent spins. The new computing scheme maps combinatorial optimization problems based on Ising model and solves these problems by using ground state search operations exploiting its convergence property. In this report, a new computing architecture using Ising spin model was implemented using field-programmable gate array (FPGA), and Ising computing using FPGA was investigated to solve combinatorial optimization problems.

Background In this retrospective study, we analyzed histologic changes identified through protocol biopsy (PB) at 1 year after kidney transplantation (KT). We focused on the pathologic changes observed in patients with a history of treatment for graft rejection within 1 year of transplantation. Methods Between January 2008 and December 2011, 56 patients underwent KT at our center. We assessed the histologic findings observed at 1 year after renal transplantation using the Banff 2007 classification. At our center, PBs are performed immediately after or at 1 hour after transplantation, and at 1 year after KT. PBs were performed in 39 patients; PBs could not be performed in 17 patients because of various causes. Of the 39 patients, 29 stabilized without clinical rejection and without treatment (the NTx group); 10 patients showed pathologic changes or clinical rejection after steroid pulse therapy within 1 year (the Tx group). We compared these 2 groups with respect to baseline data, renal function, and pathologic scores. Results The interstitial fibrosis (“ci”) score, according to the Banff classification, was significantly greater in the NTx group (0.89) than in the Tx group (0.50) at 1 year after transplantation. Conclusions The currently applied early steroid withdrawal regimen may be not be ideal for preventing pathologic changes occurring after KT. In addition to the PB performed 1 year after KT, PB should be performed within 1 year of renal transplantation to identify early signs of rejection and to provide access to appropriate treatment regimes.

We have studied desorption kinetics of deuterium molecules from a Si(1 0 0) surface by means of temperature-programmed desorption (TPD) spectra and isothermal desorptions.Three desorption components, denoted as β 1 ,A , β 1 ,B , and C, can be distinguished in semi-logarithmic plots of the TPD spectra.Their peak positions and intensities are strongly affected by the surface preparation methods employed, either with or without annealing to control the initial D coverage θ D 0 .Peak C appears at the leading edge of the TPD peak.It accounts for only about 5% of the TPD peak at θ D 0 = 1 ML and it diminishes rapidly with decreasing θ D 0 , vanishing at θ D 0 = 0.5 ML .In contrast, together the β 1 ,A and β 1 ,B peaks account for the whole TPD peak at any θ D 0 less than 1.0 ML. The maximum of the β 1 ,A peak is nearly constant at around the maximum temperature of the TPD peak.On the other hand, the β 1 ,B peak appears on the high-temperature side of the TPD peak and it systematically shifts to higher temperatures with decreasing θ D 0 .These results imply that first- and second-order kinetics are operating for the β 1 ,A and β 1 ,B desorptions, respectively.Isothermal desorption experiments confirm the above predicted kinetics for a limited region, namely θ D 0 0.5 ML .From the results for the rate curve analysis, the desorption barriers are evaluated to be 1.6 ± 0.1 eV and 1.8 ± 0.1 eV for the β 1 ,A and β 1 ,B desorptions, respectively.These values are substantially lower than the widely accepted value of ∼2.5 eV. To reproduce the measured TPD spectra we take the Arrhenius-type rate equation containing the first- and second-order rate terms for the β 1 ,A and β 1 ,B desorptions.The TPD spectra measured for θ D 0 0.4 ML can be reasonably fit with the proposed rate equation when the values given above for E d ,A and E d ,B are used. For θ D 0 > 0.4 ML , however, the TPD curves are not fit with the same values; rather, the best-fit curves require values for E d ,A and E d ,B larger than those given above. Combining the present kinetics results with those obtained by STM along with the studies, the β 1 ,A and β 1 ,B peaks may be attributed to desorption along the 2H path, while peak C may be attributed to desorption along the 4H path. The atomistic desorption mechanism as well as the energy relationship between the desorption barrier and isosteric heat of adsorption are discussed.

Scattering of 300 K effusive D 2 beam from H/Si(1 0 0) surfaces has been investigated in the dynamics experiments on angular and velocity distributions of scattered molecules. The results are compared with that of the He scattering which is governed mostly by the direct inelastic scattering (DIS). Although the angular distribution of D 2 molecules is nearly cosine but it includes considerable contribution of DIS. This may be explained in terms of the geometrical corrugation of D 2 –Si surface interaction potential.

The clinical efficacy of calcineurin inhibitors administered to renal transplant patients is considered to be a strong function of the area under the concentration time curve (AUC). Interestingly, monitoring timings of blood concentrations for two similar calcineurin inhibitors, cyclosporine (CYA; Neoral®) and tacrolimus (TAC; Prograf®) are different. Namely, CYA blood concentration is usually monitored at 2 h after administration (C2) substituted for peak concentration (Cp) and TAC at trough concentration (Ct). In the literature, data describing such characteristics of CYA and TAC have been presented in the past. However, each of these patient groups had different backgrounds. We have attempted to examine the behavior of blood concentration curves simultaneously for both CYA and TAC by establishing controlled groups of renal transplant patients with similar clinical backgrounds. Furthermore, we have analyzed the correlation with Cp and Ct versus AUC implementing area under the trough level (AUTL), or area above the trough level (AATL) as new pharmacokinetic parameters, such that C2 for CYA and Ct for TAC have been verified using controlled clinical data. We have also found distinct differences in the pharmacokinetics between CYA and TAC with the relationships between AUC, Cp, and Ct.

Early recovery from shock improves prognosis in patients with severe sepsis and septic shock. During this period, cytokine imbalances mediate the development of organ damage and mortality. In Japan, we have access to hemoperfusion using an immobilized polymyxin B fiber column for endotoxin removal (PMX-DHP) and continuous hemodiafiltration (CHDF) as artificial support for patients with septic shock, with the aim of improving hemodynamics and organ dysfunction caused by elevated inflammatory cytokines and mediators. In this Short communication, we discuss recent findings showing anti-inflammatory treatment following these continuous renal replacement therapies in sepsis.

Background: We have often observed that the blood trough concentration (Ct) of the once-daily, prolonged-release formulation of tacrolimus (Graceptor®; GRC) becomes unstable, and it is difficult to adjust it in the early period after transplantation. Consequently, we compared the relationships between pharmacokinetic parameters and influencing factors in a group of GRC-treated patients compared with those in a group of Prograf® (PRG)-treated patients. Methods: The study included 8 patients who were newly treated with GRC and 44 patients who were newly treated with PRG. We performed 24-hour therapeutic drug monitoring to compare the relationships between pharmacokinetic parameters, including the area under the curve (AUC), the ratio of the area under the trough level (AUTL)/AUC to indicate the relationships among AUCs, peak concentration (Cp), and Ct. The Cp/Ct values, and dose/body weight (UC/ [D/BW]) values reflected bioavailability and the influencing factors; number of days after transplantation and Dose/BW in the GRC-treated and PRG-treated patients. Results: The Cp/Ct values were higher and the AUTL/AUC and AUC corrected by dose/body weight (AUC/[D/BW]) values were lower with a low number of days after transplantation (particularly within 20 days) and a large dose than a high number of days after transplantation and a small dose in the GRC-treated patients. No such associations were observed in the PRG-treated patients. Conclusion: Care is required when using GRC as there is a tendency for Cp to increase owing to rapid absorption within 20 days after transplantation. Blood levels may be unstable and side effects may be more prevalent in some patients. Moreover, the utilization rate is low and the dose is high in such patients; therefore, unstable gastrointestinal function caused by a variety of factors may play a role in the early period after transplantation.

ABO-incompatible kidney transplantation has increased the possibility of finding suitable living donors for patients with renal failure. However, there are inevitable immunological risks, including a high risk of early post-transplantation complications. The purpose of this study was to evaluate recipient outcomes following ABO-incompatible kidney transplantation.Seventy-one patients who had undergone living-donor kidney transplantation (LDKT) at our center between January 2008 and December 2013 were divided into ABO-incompatible (ABOi; n = 21) and ABO-compatible (ABOc; n = 50) groups. Baseline data, graft function, immunosuppressant use, and the results of biopsy 1 year after LDKT were compared between the groups.Recipient preemptive LDKT rates were significantly different between groups (P = .017). Graft function, incidence of infection, and rates of T-cell-mediated rejection and borderline changes requiring medication were not significantly different. There was no acute antibody-mediated rejection. Selectivity of the immunosuppressant, tacrolimus, was significantly different between groups (P .01); however, steroid withdrawal rates, mycophenolate mofetil doses, and calcineurin inhibitor trough levels were not different. Regarding biopsy data, interstitial fibrosis scores were significantly different between groups (P = .011), as were interstitial fibrosis and tubular atrophy scores (P = .045) and arteriolar hyalinosis score (P = .022).ABOi LDKT was relatively safe, with no significant difference in the incidence of rejection compared to ABOc LDKT. Managing chronic pathological changes and arteriolar hyalinosis prophylaxis after ABOi LDKT may result in more successful outcomes.

Objective Adiponectin (ADPN), a collagen-like protein of the collectin family produced by adipocytes, may play a crucial role in the association between inflammation, atherosclerosis, and IR. Plasma ADPN is also down-regulated in association with obesity-linked diseases including coronary artery diseases. Although reports have shown that ADPN increases during maintenance hemodialysis (HD) and decreases following successful renal transplantation, there is no evidence about whether ADPN causes the deterioration of vasculitis. Methods To determine if ADPN causes inflammation and insulin resistance, we examined the differences in serum concentrations of serum amyloid A (SAA), homeostasis model assessment value for insulin resistance (HOMA-R), and ADPN in patients who had undergone both maintenance HD and who had later received a renal transplant. Results The mean SAA (27.7 ± 8.3 g/mL) and ADPN (20.8 ± 11 g/mL) levels in the patients while they underwent HD were high. ADPN increased after an HD session (30.2 ± 10.5 g/mL). Patients with diabetes mellitus (DM) who had low ADPN concentrations of at least 20 g/mL had higher body mass index (BMI), HOMA-R, and SAA values. One month after the patients received kidney transplantation, plasma ADPN decreased to 15.2 ± 1.3 g/mL, and mean SAA increased (14.6 ± 4.8 vs. 89.5 ± 23.5 g/mL before and after treatment, respectively). Conclusions Both the serum ADPN and SAA levels of the patients while they underwent were high, and their ADPN levels decreased after successful kidney transplantation. Conversely, their SAA levels increased after kidney transplantation. These results suggest a correlation between ADPN level and vasculitis. Also, this is the first time it has been shown that ADPN and SAA increase simultaneously.

Background: In Japan ABO-incompatible liver transplantation has been done on >100 occasions up to 2003. However

Welding technology between 9Cr-ODS martensitic cladding and end-plugs has been developed by means of the pressurized resistance welding (PRW) method under solid state condition. The method is based on electrical resistance heating of the components while maintaining a continuous force sufficient to forge weld without melting. The appropriate conditions, e.g., electric current, voltage and contact force, were selected. For the PRW welded specimens, the tensile, internal burst and creep rupture tests were conducted and its integrity was confirmed. In addition, a non-destructive ultrasonic inspection method has been developed to assure the integrity of the weld between cladding and end-plug. The PRW was conducted to fabricate the ODS fuel pins in a JNC-Russia collaboration work, and the integrity accomplishment of the welded parts was verified through dimensional and leak testing, mechanical testing and micrographic examination.

A new technology has been developed using the atomic layer etching (ALE) and atomic layer deposition (ALD) concepts. It has been applied to self-aligned contacts (SAC) and patterning processes, for the sub 7 nm technology generation. In the SAC process, ultra-high selectivity of SiO2 etching towards SiN is required, for which we have developed quasi-ALE technique for SiO2 etching. We were able to significantly improve the trade-off between the etching ability of SiO2 on the micro slit portions and SiN selectivity. Quasi-ALE precisely controls the reaction layer thickness of the surface, by controlling the radical flux and ion flux independently, and hence enables etching at lower ion energies (E i < 250 eV). On the other hand, in the patterning processes, the shrinking of critical dimensions (CD) without loading is mandatory. Therefore, we developed a new process flow that combines ALD technique and etching. With this method, we were able to achieve CD shrinking at atomic-layer level precision for various patterns, without causing CD loading. In addition, we were also able to uniformly control the CD shrinkage amount across the whole wafer. This is because this technique takes advantage of the deposition step which is independent of the pattern density and the location on the wafer by self-limited reactions.

The steroid receptor (SR) complex contains FKBP51 and FKBP52, which bind to tacrolimus (TAC) and cyclophilin 40, which, in turn, bind to cyclosporine (CYA); these influence the intranuclear mobility of steroid–SR complexes. Pharmacodynamic interactions are thought to exist between steroids and calcineurin inhibitors (CNIs) on the SR complex. We examined the effect of CNIs on steroid sensitivity. Methylprednisolone (MPSL) sensitivity was estimated as the concentration inhibiting mitosis in 50% (IC50) of peripheral blood mononuclear cells and as the area under the MPSL concentration–proliferation suppressive rate curves (CPS-AUC) in 30 healthy subjects. MPSL sensitivity was compared between the additive group (AG) as the MPSL sensitivity that was a result of addition of the proliferation suppressive rate of CNIs to that of MPSL and the mixed culture group (MCG) as MPSL sensitivity of mixed culture with both MPSL and CNIs in identical patients. IC50 values of MPSL and cortisol sensitivity were examined before and 2 months after CNI administration in 23 renal transplant recipients. IC50 and CPS-AUC values of MPSL were lower in the MCG than in the AG with administration of TAC and CYA. The CPS-AUC ratio of MCG and AG was lower in the TAC group. IC50 values of MPSL and cortisol tended to be lower after administration of TAC and CYA, and a significant difference was observed in the IC50 of cortisol after TAC administration. Steroid sensitivity increased with both TAC and CYA. Furthermore, TAC had a greater effect on increasing sensitivity. Thus, concomitant administration of CNIs and steroids can increase steroid sensitivity.

Clinical practice guidelines for pancreatic cancer based on evidence-based medicine (2006) were published by the Japan Pancreas Society (Committee for revision of clinical guidelines for pancreatic cancer) in March 2009 in Japanese, revised to Clinical Practice Guidelines for Pancreatic Cancer based on evidence-based medicine (2009) in July 2009 in Japanese and further revised to Clinical Practice Guidelines for Pancreatic Cancer (2013) in October 2013 in Japanese. These guidelines were established according to evidence-based medicine. A total of 629 papers were collected from among 4612 reports concerning pancreatic cancer listed in PubMed and Igakuchuo Zasshi between May 2007 and January 2011. This new set of guidelines was written by members of the Committee for the Revision of Clinical Practice Guidelines for Pancreatic Cancer in the Japan Pancreas Society. The guidelines provide an algorithm for the diagnosis (Fig. 1) and treatment (Fig. 2) of pancreatic cancer and address six subjects (Diagnosis, Surgery, Adjuvant therapy, Radiation therapy, Chemotherapy and stent therapy), with 35 clinical questions and 57 recommendations.

The propagation-rate constant of vinylidene chloride (VDC) was determined at 40 and 50 °C, respectively, by applying the so-called Ugelstad plot to the polymerization-rate data of the seeded and unseeded emulsion polymerizations of VDC. The values of the propagation-rate constant kp thus determined are kp = 64 dm3/mol · s at 50 °C and kp = 52 dm3/mol · s at 40 °C, respectively. From these kp values, the activation energy for propagation reaction was determined to be Ep = 4.2 kcal/mol, which is close to that of vinyl chloride (3.7 kcal/mol). © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1005–1015, 2001

Objective The incidence of biliary complications after adult living donor liver transplantation (ALDLT) are still high even though various devices have been reported to overcome them. Method From October 2000 to April 2007, we performed 52 ALDLTs which included 15 ABO-incompatible grafts. Median follow-up was 565 days. In 49 procedures, we used duct-to-duct anastmosis with a stent inserted in the recipient duct and out through the common bile duct wall as an external stent, and in 3 procedures, we used duct-to-jejunostomy anastomosis. We investigated postoperative biliary complications and their management. Results Forty-four patients received right lobe grafts and 8 received left lobe grafts. Among patients in whom duct-to-duct anastomosis was used, nine (20.5%) developed biliary complications including bile leakage in five and biliary strictures in four. All bile leakage was treated with reoperation. Three biliary strictures were treated with stent placement, and one biliary stricture was treated with magnetic compression anastomosis. Among the three patients in whom duct-to-jejunostomy was used, two (66.7%) had bile leakage and stricture, respectively. Two of four ABO-incompatible patients (50%) had hepatic artery thrombosis with biliary complications, a high incidence. Conclusion In our series of ABO-incompatible patients undergoing ALDLT, those who developed hepatic artery thrombosis exhibited a high incidence of biliary complications.

Emulsion polymerization of vinylidene chloride was carried out at 50°C using sodium lauryl sulfate as emulsifier and potassium persulfate as initiator, respectively. Contrary to the results so far reported, the stirring rate did not affect the progress of the polymerization and such an abnormal kinetic behavior as the rate of polymerization suddenly drops in the course of polymerization was not observed. The number of polymer particles produced was proportional to the 0.7 power of the concentration of emulsifier forming micelles and to the 0.3 power of the initial initiator concentration, respectively, and was independent of the initial monomer concentration. The rate of polymerization was in proportion to the 0.3 power of the concentration of emulsifier forming micelles, to the 0.5 power of the initial initiator concentration, to the 0.2 power of the initial monomer concentration, and to the 0.45 power of the number of polymer particles, respectively.

Posttransplant anemia (PTA) influences kidney graft function and prognosis; however, there is no consensus regarding target hemoglobin (Hb) levels.We examined several cases of PTA to identify any correlation between Hb levels and graft function. We evaluated 84 kidney transplant recipients (50 men and 34 women; mean age, 46.7 years) who were treated at our department between February 2004 and March 2012 and were available for a 2-year post-transplant follow-up.Hb levels and serum creatinine levels before transplantation and at 1, 3, 6, 12, and 24 months after transplantation were compared. We examined the correlation between the degree of anemia and renal function among the patients. Data were analyzed using Spearman's rank correlation coefficient and Friedman tests. The mean pretransplantation Hb level was 10.4 g/dL, whereas Hb levels at 6, 12, and 24 months after transplantation were significantly increased to 11.6, 12.2, and 12.4 g/dL, respectively, suggesting an improvement in anemia after the transplantation. Correlation analysis between anemia and kidney graft dysfunction revealed significant correlations at 1, 3, 12, and 24 months after transplantation. Subjects were stratified for correlation analysis according to Hb level at 24 months after transplantation:10, 10-10.9, 11.0-11.9, 12.0-12.9, and ≥ 13.0 g/dL. A significant improvement in kidney graft function was noted in patients with an Hb level ≥ 11 g/dL at 2 years after transplantation. Anemia improved significantly by 3 months after transplantation.A significant correlation between PTA and kidney graft function was apparent, and the prognosis for kidney graft function was poor in patients with Hb levels ≤ 11 g/dL.

The geometric structures of 7-azaindole (7-AzI) and its dimer were investigated by laser-induced fluorescence (LIF). The rotationally resolved LIF spectrum (resolution: ∼0.00003 cm-1 of 7-AzI monomer shows that (i) rotational constants are A′′ 0.13082(5), B′′ = 0.05677(2), C′′ = 0.03970(1), A′ = 0.12468(5), B′ = 0.056752(2), and C′ = 0.03911(1), and (ii) the transition dipole moment direction is tilted at an angle of ± 21(5) degrees with respect to a axis. The LIF spectrum (resolution: ∼0.06 cm-1) of the nonreactive 7-AzI dimer suggests there are three possibilities for the geometric structure, having “single bonded”, “T-shaped”, and “non-planar” structures.The ionization energy of 7-AzI was determined to be 8.1171(5) eV by using pulsed-field ionization photoelectron spectroscopy (PFI-PES). Several vibronic bands of 7-AzI cation were observed and compared with those of neutral 7-AzI in the S0 and S1 states. The electron binding energies of 7-AzI cluster anions (2 ≤ n ≤ 5) were determined by photoelectron spectroscopy.