T-cell counts in peripheral blood at leukapheresis predict responses to subsequent CAR-T cell therapy

CAR-T細胞の「原料の質」が治療効果と相関 --細胞採取時のリンパ球数がCAR-T細胞の体内での増殖と治療効果を予測する--. 京都大学プレスリリース. 2022-11-22.Prediction of responses to chimeric antigen receptor (CAR)-T cell therapies is essential to maximize their therapeutic efficacy for diffuse large B-cell lymphoma (DLBCL). While several tumor-intrinsic risk factors of resistance and/or early relapse have been identified, clinically useful markers that determine potential activity of CAR-T cells have not been fully investigated. T-cell property at the time of leukapheresis may serve as such a marker. Therefore, we evaluated the clinical impact of CD3⁺ cell count in peripheral blood at leukapheresis on clinical outcomes of CAR-T cell therapy. In total, 44 patients with relapsed or refractory (r/r) DLBCL who received tisagenlecleucel at Kyoto University Hospital were included. According to CD3⁺ cell counts, patients were categorized into CD3[LOW] and CD3[HIGH] groups with a threshold of 553/μL, based on receiver operating characteristic curve analysis. 1-year progression-free survival was significantly higher in the CD3[HIGH] group than the CD3[LOW] group (68.3% vs. 17.3%; adjusted hazard ratio [aHR], 0.37; p = 0.042). Overall survival was also superior in the CD3[HIGH] group (aHR, 0.24; p = 0.043). Moreover, higher CD3⁺ cell counts at leukapheresis were associated with significantly higher lymphocyte counts in peripheral blood at day 7 after CAR-T cell infusion (median 860 vs. 420/μL, P = 0.021), suggesting more extensive expansion of infused CAR-T cells in vivo. In conclusion, we demonstrated that the CD3⁺ cell count at leukapheresis predicts both expansion of CAR-T cells after infusion and outcomes of CAR-T cell therapy, and are useful for building comprehensive therapeutic strategies at the time of leukapheresis

Study of the risk communication in the Geo-disaster -Report of the local government questionnaire result-

The Tenth International Symposium on Mitigation of Geo-disasters in Asia Matsue Symposium Place: Shimane Civil Center, Matsue Date: 8 October 2012The earthquake is generated suddenly. As for the lifesaving, 72 hours are said to be critical condition from an earthquake occurrence.The Geo-disaster should be able to prevent human life damage by judging information such as the rain precisely, and evacuating early. However, it is the present conditions that 20 people (average) are dead in one year. The local government sends refuge information to promote early refuge,it is important that the inhabitants take information seriously and practice a refuge action.Do not really go, and are you? This article shows the findings of the questionnaire by the information dispatch system of the local government. and I clarify the weakness of the system and the social psychology-related problems of the local government person in charge

Favorable Outcomes after Single Cord Blood Transplantation for Patients with High-Risk Hematologic Diseases: A Single-Institute Retrospective Analysis

The donor selection algorithm for cord blood (CB) with regards to matched related and unrelated donors has not been fully investigated. To assess the potential of CB transplantation (CBT) in patients with hematologic malignancies, especially for high-risk patients, we performed a single-institute retrospective analysis and compared the clinical outcomes of CBT with those of HLA-matched sibling and unrelated donor transplantation. We included 394 patients aged 16 years and older with hematologic diseases who received their first allogeneic hematopoietic cell transplantation between 1990 and 2018 at Kyoto University Hospital. These included 394 recipients of single unrelated cord blood units (UCB, n = 108), HLA-matched sibling donors (MSDs, n = 143), or HLA-matched unrelated donors (MUDs, n = 143). There was no significant difference in relapse-free survival (RFS) between UCB, MSD, and MUD recipients (P = .975). However, we found a significant interaction between transplant year and CBT outcomes (P = .010), with significantly better outcomes observed in the more recent years. Furthermore, we found that CBT showed better RFS than matched donor transplantation (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.30 to 0.84). This impact was more prominent in high-risk patients (HR, 0.35; 95% CI, 0.16 to 0.77), with lower relapse rates (HR, 0.25; 95% CI, 0.11 to 0.54), and comparable non-relapse mortality (NRM) compared to matched donor transplantation. Extensive chronic graft-versus-host disease was less frequently observed in CBT (HR, 0.58; 95% CI, 0.26 to 1.28). CBT associated with favorable outcomes, particularly in high-risk patients, with good RFS and low relapse rates without an increase in NRM in the single-institute study. Although the findings should be externally validated, CBT might serve as a reasonable donor choice, particularly in high-risk patients

Hybrid thoracic endovascular aortic repair of ascending aortic pseudoaneurysm

We report the successful thoracic endovascular aortic repair of an ascending aortic pseudoaneurysm. Because the risk of resternotomy after conventional surgery was very high, endovascular repair with extra-anatomic reconstruction of the supra-aortic vessels was performed using the femoral artery as the donor artery. Complete exclusion of the pseudoaneurysm was achieved, with no postoperative complications or neurologic sequelae

The Anorexigenic Action of the Octadecaneuropeptide (ODN) in Goldfish is Mediated Through the MC4R- and Subsequently the CRH Receptor-Signaling Pathways

International audienceIntracerebroventricular (ICV) administration of the octadecaneuropeptide (ODN), a peptide derived from diazepam-binding inhibitor, reduces food intake in goldfish as in rodents. However, the neurochemical pathways involved in the anorexigenic action of ODN have not yet been identified in goldfish. Alpha-melanocyte-stimulating hormone (alpha-MSH), corticotropin-releasing hormone (CRH), and CRH-related peptides play a major role in the control of food consumption in goldfish. In this species, the anorexigenic action of alpha-MSH is mediated via the CRH/CRH receptor neuronal system. Therefore, in the present study, we examined whether the anorexigenic effect of ODN in goldfish could be mediated through alpha-MSH and/or CRH neuronal pathways. ICV injection of ODN (10 pmol/g body weight (BW)) significantly reduced food intake, and the anorexigenic effect of ODN was suppressed by ICV preinjection of the melanocortin 4 receptor (MC4R) antagonist HS024 (40 pmol/g BW) or the CRH receptor 1/receptor 2 antagonist alpha-helical CRH((9-41)) (100 pmol/g BW). ICV injection of ODN (10 pmol/g BW) induced a significant increase of proopiomelanocortin mRNA level but had no effect on CRH mRNA level, while ICV injection of the MC4R agonist, melanotan II (100 pmol/g BW), significantly enhanced CRH mRNA expression. These results suggest that, in goldfish, the anorexigenic action of ODN is mediated by the MC4R- and subsequently through the CRH receptor-signaling pathways

被災地域へのアンケートに基づく土砂災害における避難を促進する情報に関する基礎的研究: 和歌山県那智勝浦町にて

金沢大学理工研究域地球社会基盤学系平成23年台風12号による豪雨で，死者27名，行方不明1名の被害を出した和歌山県那智勝浦町を対象として，土砂災害における避難行動と伝達された情報に関するアンケート調査を行った．アンケート調査では，避難率が低かったことが大きな被害につながったとも考えられるため，今後，犠牲者を出さないために避難率が低かった理由を明らかにする必要がある．具体的には，避難情報に接した際の反応，避難行動の有無に対する意思決定条件，避難行動を促進あるいは抑制した情報伝達手法・周辺環境などを調査し，明らかになった結果をもとに，早期避難を促すために必要な情報，手段ならびに排除すべき阻害要因を示し，住民の安全を確保する対策の提案を行う．This study focuses on the relationship of the action and information for safe evacuation of inhabitants in geo-disaster. A questionnaire survey was performed to inhabitants in Nachikatsuura town, Wakayama prefecture where suffered severe damage by heavy rain caused by typhoon No. 12 in 2011. A relation between information given by local governments and actual situation of evacuation during the heavy rain was analyzed. The necessary information and comunication tools were discussed for safe and early evacuation of inhabitants