Evidence for the Immunosuppressive Potential of Calcineurin Inhibitor-Sparing Regimens in Liver Transplant Recipients with Impaired Renal Function

Patients requiring liver transplantation (LT) frequently experience renal insufficiency (RI), which affects their survival. Although calcineurin inhibitor-sparing immunosuppressive regimens (CSRs) are well known to prevent RI, the immune state in recipients receiving CSR remains to be intensively investigated. Among 60 cases of living-donor LT at our institute, 68% of the patients had none to mild RI (non-RI group) and 32% of the patients had moderate to severe RI (RI group). The RI group received a CSR comprising reduced dose of tacrolimus, methylprednisolone, and mycophenolate mofetil, while the non-RI group received a regimen comprising conventional dose of tacrolimus and methylprednisolone. One year after LT, the mean estimated glomerular filtration rate (eGFR) in the RI group had significantly improved, although it was still lower than that of the non-RI group. Serial mixed lymphocyte reaction assays revealed that antidonor T-cell responses were adequately suppressed in both groups. Thus, we provide evidence that CSR leads to improvement of eGFR after LT in patients with RI, while maintaining an appropriate immunosuppressive state

Motor function of the upper-extremity after transection of the second thoracic nerve root during total en bloc spondylectomy

Background: In total en bloc spondylectomy (TES) of upper thoracic spine including the second thoracic (T2) vertebra, T2 nerve roots are usually transected. In this study, we examined the association between transection of the T2 nerve roots and upper-extremity motor function in patients with upper thoracic TES. Copyright:Methods: We assessed 16 patients who underwent upper thoracic TES with bilateral transection of the T2 nerve roots. Patients were divided into three groups: 3 patients without any processing of T1 and upper nerve roots (T2 group), 7 with extensive dissection of T1 nerve roots (T1-2 group), and 6 with extensive dissection of T1 and upper nerve roots (C-T2 group). Postoperative upper-extremity motor function was compared between the groups.Results: Postoperative deterioration of upper-extremity motor function was observed in 9 of the 16 patients (56.3%). Three of the 7 patients in the T1-2 group and all 6 patients in the C-T2 group showed deterioration of upper-extremity motor function, but there was no deterioration in the T2 group. In the T1-2 group, 3 patients showed mild deterioration that did not affect their activities of daily living and they achieved complete recovery at the latest follow-up examination. In contrast, severe dysfunction occurred frequently in the C-T2 group, without recovery at the latest follow-up.Conclusions: The transection of the T2 nerve roots alone did not result in upper-extremity motor dysfunction; rather, the dysfunction is caused by the extensive dissection of the T1 and upper nerve roots. Therefore, transection of the T2 nerve roots in upper thoracic TES seems to be an acceptable procedure with satisfactory outcomes

Evidence for the Immunosuppressive Potential of Calcineurin Inhibitor-Sparing Regimens in Liver Transplant Recipients with Impaired Renal Function

Patients requiring liver transplantation (LT) frequently experience renal insufficiency (RI), which affects their survival. Although calcineurin inhibitor-sparing immunosuppressive regimens (CSRs) are well known to prevent RI, the immune state in recipients receiving CSR remains to be intensively investigated. Among 60 cases of living-donor LT at our institute, 68% of the patients had none to mild RI (non-RI group) and 32% of the patients had moderate to severe RI (RI group). The RI group received a CSR comprising reduced dose of tacrolimus, methylprednisolone, and mycophenolate mofetil, while the non-RI group received a regimen comprising conventional dose of tacrolimus and methylprednisolone. One year after LT, the mean estimated glomerular filtration rate (eGFR) in the RI group had significantly improved, although it was still lower than that of the non-RI group. Serial mixed lymphocyte reaction assays revealed that antidonor T-cell responses were adequately suppressed in both groups. Thus, we provide evidence that CSR leads to improvement of eGFR after LT in patients with RI, while maintaining an appropriate immunosuppressive state

Implantation of Liquid Nitrogen Frozen Tumor Tissue after Posterior Decompression and Stabilization for Metastatic Spinal Tumors

Study DesignA retrospective study.PurposeTo evaluate the immunity-enhancing effect of implantation of a liquid nitrogen-treated tumor.Overview of LiteratureWe have developed a new technique of implanting a tumor frozen in liquid nitrogen after posterior decompression and stabilization, with the aim of enhancing antitumor immunity in order to prolong the survival period of the patient. In the current study, the immunity-enhancing effect of this new technique has been evaluated.MethodsThe subjects were 19 patients in whom we had earlier performed decompression and stabilization between April 2011 and September 2013. The 19 subjects were divided into two groups, namely a frozen autologous tumor tissue implantation group (n=15; "implantation group"), which consisted of patients, who underwent implantation with autologous tumor tissue frozen in liquid nitrogen, and a control group (n=4), which consisted of patients, who did not undergo autologous cancer transplantation. To evaluate the immunity-enhancing effect of the protocol, plasma cytokines (interferon [IFN]-γ and interleukin [IL]-12) were analyzed before surgery and a month after surgery.ResultsThe mean rate of increase in IFN-γ was significantly higher in the implantation group (p=0.03). Regarding IL-12, no significant difference was observed between the groups, although the implantation group exhibited increased levels of IL-12 (p=0.22).ConclusionsDecompression and stabilization combined with autologous frozen tumor cell implantation can enhance cancer immunity in metastatic spinal tumor patients. It is hypothesized that this procedure might prevent local recurrence and prolong survival period

Increased Systemic Glucose Tolerance with Increased Muscle Glucose Uptake in Transgenic Mice Overexpressing RXRγ in Skeletal Muscle

BACKGROUND: Retinoid X receptor (RXR) γ is a nuclear receptor-type transcription factor expressed mostly in skeletal muscle, and regulated by nutritional conditions. Previously, we established transgenic mice overexpressing RXRγ in skeletal muscle (RXRγ mice), which showed lower blood glucose than the control mice. Here we investigated their glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: RXRγ mice were subjected to glucose and insulin tolerance tests, and glucose transporter expression levels, hyperinsulinemic-euglycemic clamp and glucose uptake were analyzed. Microarray and bioinformatics analyses were done. The glucose tolerance test revealed higher glucose disposal in RXRγ mice than in control mice, but insulin tolerance test revealed no difference in the insulin-induced hypoglycemic response. In the hyperinsulinemic-euglycemic clamp study, the basal glucose disposal rate was higher in RXRγ mice than in control mice, indicating an insulin-independent increase in glucose uptake. There was no difference in the rate of glucose infusion needed to maintain euglycemia (glucose infusion rate) between the RXRγ and control mice, which is consistent with the result of the insulin tolerance test. Skeletal muscle from RXRγ mice showed increased Glut1 expression, with increased glucose uptake, in an insulin-independent manner. Moreover, we performed in vivo luciferase reporter analysis using Glut1 promoter (Glut1-Luc). Combination of RXRγ and PPARδ resulted in an increase in Glut1-Luc activity in skeletal muscle in vivo. Microarray data showed that RXRγ overexpression increased a diverse set of genes, including glucose metabolism genes, whose promoter contained putative PPAR-binding motifs. CONCLUSIONS/SIGNIFICANCE: Systemic glucose metabolism was increased in transgenic mice overexpressing RXRγ. The enhanced glucose tolerance in RXRγ mice may be mediated at least in part by increased Glut1 in skeletal muscle. These results show the importance of skeletal muscle gene regulation in systemic glucose metabolism. Increasing RXRγ expression may be a novel therapeutic strategy against type 2 diabetes

コウトウ キョウイク カイカク ノ ソウゴ コウイ ブンセキ : ビデオ エスノグラフィー ケンキュウ ノ ネライ ト コウガクブ トシ コウガク エンシュウ ノ ジッサイ

ビデオエスノグラフィーは、当事者的知識を十分に摂取しながら行うビデオ分析であり、我々は この方法で、高等教育改革の現場を研究した。生涯学習社会の到来を受けて、日本の高等教育は現在第 2 次世界大戦直後以来の改革期にある。すなわち、「知識」より「生涯学習能力」の獲得を志向した、 自発性を尊重するような様々な取り組みがなされ始めている。この高等教育の現場に対し、ワークプレ ース研究を行った。Ｂ大学工学部都市工学演習α班を分析対象とした調査の結果、①演習の課題解釈に は「従来の指標の相対化の要求の程度」を巡って２つの解釈があり得たこと、②班内にはその２種類の 解釈に対応した葛藤・対立的相互行為が存在したこと、③にもかかわらず、班内葛藤を生きる当事者が ともに専門性（「都市工学」）を志向していたこと、④したがって、課題理解のいかんにかかわらず、 班活動の全体が「都市工学演習」と呼び得るものになっていたこと、⑤その一方で、最終審査会場（ジ ュリー）ではこの２重性が十分レリバントなものとして浮かび上がって来ていなかったこと、これらの ことがわかった。諸結果を総合すると、学生の自主的活動を尊重するタイプの、新しい学習方法の吟味・ 評価のためには、学生によるその方法の実践状況の分析が有意義であるだろうこと、また、それは、場 合によっては教員の評価のパラダイムを変える力を持つだろうことなどが予測された。なお、本報告は、 文科省科学研究費補助金「高等教育改革のコミュニケーション分析－現場における文化変容の質的検討 －」（基盤研究（Ｂ）、 課題番号 １８３３０１０５、研究代表者：樫田美雄）ほかによる研究成果 の一部である

Details on the effect of very short dual antiplatelet therapy after drug-eluting stent implantation in patients with high bleeding risk: insight from the STOPDAPT-2 trial

Previously we briefly reported the effect of 1-month dual antiplatelet therapy (DAPT) for patients with high bleeding risk (HBR) receiving percutaneous coronary intervention (PCI) in the STOPDAPT-2 trial, but full analysis data have not been available. We conducted post hoc subgroup analysis regarding the effect of very short DAPT for HBR patients in STOPDAPT-2 trial. The primary endpoint was a 1-year composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) and bleeding (TIMI major/minor bleeding) outcomes. Major secondary endpoints were 1-year cardiovascular composite endpoint and bleeding endpoint. HBR was defined by the academic research consortium (ARC) HBR criteria. Among the 3009 study patients, 1054 (35.0%) were classified as HBR and 1955 (65.0%) were as non-HBR. There were no significant interactions between HBR/non-HBR subgroups and the assigned DAPT group on the primary endpoint (HBR; 3.48% vs. 5.98%, HR 0.57, 95% CI 0.32-1.03, and non-HBR; 1.81% vs. 2.36%, HR 0.78, 95% CI 0.42-1.45; P for interaction = 0.48), the major secondary cardiovascular endpoint (HBR; 3.07% vs. 4.03%, HR 0.77, 95% CI 0.40-1.48, and non-HBR; 1.41% vs. 1.61%, HR 0.89, 95% CI 0.43-1.84; P for interaction = 0.77), and the major secondary bleeding endpoint (HBR; 0.41% vs. 2.71%, HR 0.15, 95% CI 0.03-0.65, and non-HBR; 0.40% vs. 0.85%, HR 0.48, 95% CI 0.14-1.58; P for interaction = 0.22). In conclusion, the effects of 1-month DAPT for the primary and major secondary endpoints were consistent in HBR and non-HBR patients without any significant interactions. The benefit of 1-month DAPT in reducing major bleeding was numerically greater in HBR patients.Clinical trial registration Short and optimal duration of dual antiplatelet therapy after everolimus-eluting cobalt-chromium stent-2 [STOPDAPT-2]; NCT02619760

Randomized Comparison Between Everolimus-Eluting Bioresorbable Scaffold and Metallic Stent: Multimodality Imaging Through 3 Years

Objectives: The aim of this study was to investigate the vascular responses and fates of the scaffold after bioresorbable vascular scaffold (BVS) implantation using multimodality imaging. Background: Serial comprehen