Immunological aspects of allogeneic pancreatic islet transplantation: a comparison between mouse and human

Pancreatic islet allotransplantation is a treatment for patients with severe forms of type 1 diabetes. As long‐term graft function and survival are not yet optimal, additional studies are warranted in order to continue improving transplant outcomes. The mechanisms of islet graft loss and tolerance induction are often studied in murine diabetes models. Despite numerous islet transplantation studies successfully performed over recent years, translation from experimental mouse models to human clinical application remains elusive. This review aims at critically discussing the strengths and limitations of current mouse models of diabetes and experimental islet transplantation. In particular, we will analyze the causes leading to diabetes and compare the immunological mechanisms responsible for rejection between mouse and human. A better understanding of the experimental mouse models should facilitate translation to human clinical application.     

同种异体肌腱移植修复手部肌腱缺损及指功能重建的疗效

目的探讨应用同种异体肌腱移植修复手部肌腱缺损及重建屈/伸指功能的临床效果。方法 2015年3月至2017年6月间,我科应用同种异体肌腱移植修复手部肌腱缺损18例22指,男12例,女6例;年龄为20-45岁,平均(32.9±8.3)岁。其中伸肌腱缺损6例8指,屈肌腱缺损12例14指。手部伸肌腱缺损范围6-10cm,平均(7.8±2.1)cm;屈肌腱缺损范围5-8cm,平均(6.6±1.3)cm。患者受伤至手术时间为1.5-8个月,平均(5.0±2.8)个月。术前皮肤软组织缺损者行皮瓣转移修复,骨折及骨缺损者行切开复位或植骨内固定术,手部各指间或掌指关节积极行锻炼至被动活动正常,若关节挛缩则行关节松解术。伸肌腱缝合方法采用编织缝合法,屈肌腱缝合方法采用津下套圈或编织缝合法,屈肌腱滑车缺损者在手术同时重建滑车。术后应用抗生素预防感染,伤口定期换药,所有病例均没有使用免疫抑制剂。术后3d-4周伸肌腱移植者以主动屈曲、被动伸直锻炼为主,屈肌腱移植者以主动伸直、被动屈曲锻炼为主,每天活动3次。4周后逐渐增加活动次数及强度,以主动伸屈活动为主。采用国际手外科联合会制定的手指关节总活动度(total active movement,TAM)评定标准评价手部功能。结果 3例术后出现伤口脂肪液化,细菌培养证实为无菌性渗出,予以伤口定期换药后均于术后20d内愈合;其余病例伤口均一期愈合。3例5指因屈肌腱黏连行肌腱松解术。术后随访8-24个月,平均(14.7±4.8)个月。TAM评价结果,优9指,良7指,可3指,差3指,优良率为72.7%。结论同种异体肌腱移植是代替自体肌建移植修复手部肌腱缺损及重建屈/伸指功能的较好方法之一,具有手部功能恢复满意、临床效果显著等优点,但仍存在术后肌腱黏连导致手功能优良率降低,伤口局部存在无菌性渗出导致愈合时间延长等问题,上述问题需在日后的临床应用过程中加以研究解决。     

The Use of Reinfusion Drains after Total Knee Arthroplasty in Patients Treated with Low Molecular Weight Heparin for Thromboembolic Prophylaxis

The effect of closed-suction drainage with red-cell reinfusion on patients receiving low molecular weight heparin (LMWH) prophylaxis after total knee arthroplasty (TKA) has not been previously studied. Therefore, our goals were to determine the effect of reinfusion drains and LMWH on allogeneic transfusions and wound complications after TKA by comparing patients treated with and without drains. Overall, transfusion rates were lower in the drain group (40% vs 15%, P=.04). Patients with reinfusion drains had a significantly higher rate of allogeneic transfusion (15.8%) than those predonating autologous blood and no drain (5.4%, P=.0003). The drain group had lower rates of wound complications (P=not significant). We were unable to demonstrate the efficacy of red-cell reinfusion as a substitute for autologous donation in TKA.     

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目的观察脱细胞真皮基质（ADM）修复颊部软组织缺损的疗效。方法选择2010年11月至2012年11月在安徽医科大学附属口腔医院就诊的颊部软组织缺损患者38例,其中20例应用异种ADM治疗,18例应用异体ADM治疗。随访6个月,观察患者缺损修复治疗效果,并对2种ADM在组织相容性、引导组织再生及补片成活情况等方面进行临床效果评价。结果应用异种ADM修复的患者,修复膜完全成活18例,大部成活2例,修复区表面颜色多为粉红色,质地柔软,瘢痕轻微;应用异体ADM修复的患者,修复膜完全成活17例,1例患者术后补片与创缘边缘有约0.8cm脱离区,补片与基底组织面贴合,补片色泽呈红色,愈合尚可。38例患者均未出现明显局部或全身反应,进食基本不受影响,无明显异物感,张口度未见明显改变。结论异种及异体ADM对颊部软组织缺损的修复效果均较为满意。     

Simultaneous Bilateral Primary Total Knee Arthroplasty With TXA and Restrictive Transfusion Protocols: Still a 1 in 5 Risk of Allogeneic Transfusion

BackgroundHistorically, there was up to a 60% risk of blood transfusion for patients undergoing simultaneous bilateral total knee arthroplasty (SBTKA). As such, the goal of this study was to analyze the rate and risk factors for allogeneic blood transfusions in patients undergoing SBTKA with tranexamic acid (TXA).MethodsWe retrospectively identified 475 patients who underwent SBTKA with a double dose TXA regimen at a single institution from 2016 to 2019. Mean age was 65 years. Two hundred fifty-seven patients (54%) were female. Mean body mass index was 30 kg/m². Drains were utilized in 143 patients (30%). Mean preoperative hemoglobin (Hgb) was 13.7 g/dL. Multivariate logistic regression analysis adjusting for age ≥70 years, sex, body mass index, drain use, and preoperative Hgb of <12.5 g/dL was utilized to identify risk factors for transfusion.ResultsOne hundred six patients (22%) received an allogeneic transfusion, including 28 patients (6%) who received ≥2 units. Multivariate analysis showed that preoperative Hgb <12.5 (OR = 3.99, P < .0001), female sex (OR = 2.34, P = .002), and drain use (OR = 2.13, P = .004) were risk factors for transfusion. Forty-two patients (42/83, 51%) with a preoperative Hgb <12.5 received a transfusion compared with 64 patients (64/392, 16%) with a Hgb ≥12.5 (P < .001).ConclusionPatients undergoing SBTKA with contemporary blood management still have a 1 in 5 rate of allogeneic transfusion. Drain use independently increases transfusion risk by 2-fold and should be avoided. Patients with a preoperative Hgb <12.5 have a transfusion rate of 50% and, as such, should either not undergo SBTKA or have extensive perioperative blood optimization.     

Pharmacogenetics of steroid‐responsive acute graft‐versus‐host disease

Glucocorticoids are central to effective therapy of acute graft‐versus‐host disease (GVHD). However, only about half of the patients respond to steroids in initial therapy. Based on postulated mechanisms for anti‐inflammatory effectiveness, we explored genetic variations in glucocorticoid receptor, co‐chaperone proteins, membrane transporters, inflammatory mediators, and variants in the T‐cell receptor complex in hematopoietic cell transplant recipients with acute GVHD requiring treatment with steroids and their donors toward response at day 28 after initiation of therapy. A total of 300 recipient and donor samples were analyzed. Twenty‐three SNPs in 17 genes affecting glucocorticoid pathways were included in the analysis. In multiple regression analysis, donor SNP rs3192177 in the ZAP70 gene (O.R. 2.8, 95% CI: 1.3‐6.0, P=.008) and donor SNP rs34471628 in the DUSPI gene (O.R. 0.3, 95% CI: 0.1‐1.0, P=.048) were significantly associated with complete or partial response. However, after adjustment for multiple testing, these SNPs did not remain statistically significant. Our results, on this small, exploratory, hypothesis generating analysis suggest that common genetic variation in glucocorticoid pathways may help identify subjects with differential response to glucocorticoids. This needs further assessment in larger datasets and if validated could help identify subjects for alternative treatments and design targeted treatments to overcome steroid resistance.     

Factors influencing blood loss and allogeneic blood transfusion practice in craniosynostosis surgery

Objective/Aims: To identify factors influencing perioperative blood loss and transfusion practice in craniosynostotic corrections. Background: Craniosynostotic corrections are associated with large amounts of blood loss and high transfusion rates. Methods: A retrospective analysis was performed of all pediatric craniosynostotic corrections during the period from January 2003 to October 2009. The primary endpoint was the receipt of an allogeneic blood transfusion (ABT) during or after surgery. Pre‐, intra‐, and postoperative data were acquired using the electronic hospital registration systems and patients’ charts. Results: Forty‐four patients were operated using open surgical techniques. The mean estimated blood loss during surgery was 55 ml·kg^?1. In 42 patients, red blood cells were administered during or after surgery with a mean of 38 ml·kg^?1. In 23 patients, fresh frozen plasma was administered with a mean of 28 ml·kg^?1. A median of two different donors per recipient was found. Longer duration of surgery and lower bodyweight were associated with significantly more blood loss and red blood cell transfusions. Higher perioperative blood loss and surgery at an early age were correlated with a longer duration of admission. Conclusions: In this study, craniosynostotic corrections were associated with large amounts of blood loss and high ABT rates. The amount of ABT could possibly be reduced by appointing a dedicated team of physicians, by using new less‐invasive surgical techniques, and by adjusting anesthetic techniques.     

同种异体软骨细胞与自体骨髓基质干细胞混合共培养构建软骨皮下移植的可行性研究

背景：软骨组织工程的种子细胞问题是目前研究的热点和难点,如何找到一种既能够避免对自体软骨进行取材又能够达到稳定软骨构建目的的方法呢？本研究尝试利用少量同种异体羊软骨细胞作为软骨诱导微环境提供者,与扩增后的羊自体BMSC混合共培养并植入皮下环境,探讨利用同种异体软骨细胞共培养构建软骨皮下移植的可行性。方法：本实验对山羊软骨细胞和BMSC分别进行取材和分离培养扩增,并将以上细胞分为以下四组进行混合并接种在PGA支架材料上：A组：100%自体软骨细胞;B组：30%自体软骨细胞＋70%自体BMSCs;C组：30%同种异体软骨细胞＋70%自体BMSCs;D组：100%同种异体软骨细胞。经过体外构建6周后植入羊皮下进行体内构建12周,对所形成的组织块进行大体观察和组织学染色等评价。结果：自体软骨细胞组和自体软骨细胞混合自体BMSC组皮下移植后可见成熟软骨组织形成,但同种异体软骨细胞参与的两组（包括同种异体软骨细胞混合自体BMSC的实验组和单纯异体软骨细胞组）在皮下环境中都因为较强的免疫反应未能形成软骨组织。结论：同种异体软骨细胞以及PGA支架材料的存在对于组织工程软骨在羊皮下环境的构建有负面影响。     

肱骨近端锁定钢板结合同种异体骨移植增强固定治疗肱骨近端骨质疏松骨折

背景:老年肱骨近端骨质疏松骨折发病率逐年增加,由于骨质疏松导致抗力性明显降低,使骨折修复产生困难.目的:肱骨近端锁定钢板结合同种异体骨移植为一种有效的增强固定方法,分析两种方法结合对肱骨近端骨质疏松骨折的修复效果.方法:纳入河北北方学院附属第二医院2013年12月至2018年11月收治的肱骨近端骨质疏松骨折老年患者50...     

Epidermal Langerhans Cells Promote Skin Allograft Rejection in Mice With NF-κB-impaired T Cells

T cells play a major role in the acute rejection of transplanted organs. Using mice transgenic for a T-cell-restricted NF-κB super-repressor (IκBαΔN-Tg mice), we have previously shown that T-cell-NF-κB is essential for the acute rejection of cardiac but not skin allografts. In this study, we investigated the mechanism by which skin grafts activate IκBαΔN-Tg T cells. Rejection was not due to residual T-cell-NF-κB activity as mice with p50/p52^−/− T cells successfully rejected skin grafts. Rather, skin but not cardiac allografts effectively induced proliferation of graft-specific IκBαΔN-Tg T cells. Rejection of skin grafts by IκBαΔN-Tg mice was in part dependent on the presence of donor Langerhans cells (LC), a type of epidermal dendritic cells (DC), as lack of LC in donor skin grafts resulted in prolongation of skin allograft survival and injection of LC at the time of cardiac transplantation was sufficient to promote cardiac allograft rejection by IκBαΔN-Tg mice. Our results suggest that LC allow NF-κB-impaired T cells to reach an activation threshold sufficient for transplant rejection. The combined blockade of T-cell-NF-κB with that of alternative pathways allowing activation of NF-κB-impaired T cells may be an effective strategy for tolerance induction to highly immunogenic organs.