Effect of early allograft dysfunction on outcomes following liver transplantation

Early allograft dysfunction (EAD) following liver transplantation (LT) remains a challenge for patients and clinicians. We retrospectively analyzed the effect of pre‐defined EAD on outcomes in a 10‐year cohort of deceased‐donor LT recipients with clearly defined exclusion criteria. EAD was defined by at least one of the following: AST or ALT >2000 IU/L within first‐week post‐LT, total bilirubin ≥10 mg/dL, and/or INR ≥1.6 on post‐operative day 7. Ten patients developed primary graft failure and were analyzed separately. EAD occurred in 86 (36%) recipients in a final cohort of 239 patients. In univariate and multivariate analyses, EAD was significantly associated with mechanical ventilation ≥2 days or death on days 0, 1, PACU/SICU stay >2 days or death on days 0‐2 and renal failure (RF) at time of hospital discharge (all P<.05). EAD was also significantly associated with higher one‐year graft loss in both uni‐ and multivariate Cox hazard analyses (P=.0203 and .0248, respectively). There was no difference in patient mortality between groups in either of the Cox proportional hazard models. In conclusion, we observed significant effects of EAD on short‐term post‐LT outcomes and lower graft survival.     

Significance of subclinical rejection in early renal allograft biopsies for chronic allograft dysfunction

To determine the significance of early subclinical rejection of renal allografts, we reviewed 127 biopsy specimens obtained soon after transplantation. Histological finding was categorized according to a modification of the Banff scheme as: acute rejection (AR), borderline changes (BL); non-specific inflammatory changes, (NI) and no rejection (NR). Subclinical rejection was defined as AR, BL or NI. Patients with BL or NI were divided into two groups; one was treated with high-dose methylprednisolone (MP), the other remained untreated. Freedom from chronic allograft dysfunction (defined as non-doubling of serum creatinine 5 yr after transplantation) was significantly more frequent in the NR group (89%) than in the BL (70%) and AR (64%) groups. At 1 yr after transplantation, mean serum creatinine had increased significantly only in the untreated group (p < 0.05), and re-biopsy showed that interstitial fibrosis had developed to a significantly greater extent in the untreated group than in the treated group (p < 0.01). Subclinical rejection in the early protocol biopsies correlated closely with subsequent allograft dysfunction. High-dose MP treatment for early subclinical rejection may be effective in suppressing the development of interstitial fibrosis at 1 yr after transplantation.     

The pathology of chronic allograft dysfunction

Chronic allograft dysfunction is associated with a variety of fibrosing/sclerosing changes in the allograft. Fibrosis is multifactorial, a final pathway following varying types of injury. Using a range of diagnostic criteria, the pathologist can and should define specific lesions enabling identification of pathogenic processes affecting the allograft. Although some cases remain 'interstitial fibrosis and tubular atrophy, no specific cause', specific diagnoses can be made in most cases. Drug toxicity, bacterial or viral infection, hypertension, obstruction, recurrent or de novo renal diseases, and acute and chronic cell- and/or antibody-mediated rejection can be diagnosed in this setting. Of particular concern is a combination of persistent inflammation and fibrosis, which has repeatedly been shown to be correlated with poor graft outcomes. Identification of ongoing activity, and the stage of evolution of fibrosis/sclerosis provides important diagnostic and therapeutic information for patient management. Histological, immunohistological, ultrastructural, and molecular studies may be needed to adequately assess the kidney in the setting of chronic allograft dysfunction. Protocol biopsies may provide diagnostic insights in early stages of late graft deterioration, or even before evident dysfunction develops.     

The impact of posterior approach for total hip arthroplasty on early complications

The optimal approach for total hip arthroplasty is hotly debated. We analysed 121 consecutive patients who underwent primary total hip arthroplasty during the first three years of practice of a newly appointed consultant. Patients were analysed for pain scores (1-6), function scores (1-6) and satisfaction levels (1-5). All complications, during and after surgery, were noted with special emphasis on incidence of dislocation and factors contributing to it. The results were gratifying and were comparable with major series of total hip replacement via the posterior approach. No patient had a dislocation. One hundred and five patients (89%) had no or minimal pain after the surgery. Eighty-six patients (73%) were mobilising without a stick. There were no major intra-operative complications and most (84%) patients rated the operation 'very good' at one year follow-up. We conclude that the posterior approach, already known to cause less blood loss and optimum component positioning, is compatible with a low overall rate of early complications especially dislocation.     

The contribution of adhesion molecule expression in donor kidney biopsies to early allograft dysfunction.

BACKGROUND: Renal allograft rejection is associated with the expression of adhesion molecules on vascular endothelial and tubular epithelial cells. METHODS: To assess whether the number of cell adhesion molecules expressed in donor kidneys can predict early rejection or delayed graft function, kidney biopsies from 20 living and 53 cadaveric kidney donors were obtained before engraftment into the recipients and the expression of the cell adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and endothelial leukocyte adhesion molecule (E-selectin) were determined by immunohistochemistry. RESULTS: All biopsies from living donors showed significantly lower expression of ICAM-1 and VCAM-1 compared to biopsies from cadaveric donors. There was no difference in the expression of adhesion molecules on tubular cells between transplants with primary function compared to allografts with early rejection in living donated kidneys (ICAM-1: 2+/-8 vs. 3+/-8%; VCAM-1: 9+/-7 vs. 1+/-1%), as well as in cadaveric kidneys (ICAM-1: 38+/-29 vs. 39+/-38%; VCAM-1: 55+/-27 vs. 48+/-29%). The expression of ICAM-1 molecules on tubular cells was determined to be a predictor for the occurrence of delayed graft function in cadaveric kidneys (ICAM-1: 65+/-24* vs. 38+/-29% delayed graft versus primary graft function). No delayed graft function occurred in recipients of living donated kidneys. CONCLUSIONS: These data suggest that adhesion molecule expression in donor biopsies is not a predictor for early allograft rejection, but can be used as a marker for the development of postischemic acute renal allograft failure.     

原位肝移植术后早期肝功能不全的相关危险因素分析

目的分析原位肝移植术后早期肝功能不全(early allograft dysfunction,EAD)的发生情况,并探讨EAD发生的相关危险因素。方法回顾性分析武汉大学人民医院2016年1月至2020年12月实施的74例原位肝移植病人的临床资料,对可能导致术后EAD的围手术期相关因素进行单因素分析,然后将有显著性差异的因素纳入Logistic回归多因素分析。结果74例肝移植病人术后EAD的发生率为36.5%(27/74)。单因素分析结果显示,受者术前中性粒细胞与淋巴细胞比值(NLR)、术前血清总胆红素、术中失血量、术前肝功能Child-Pugh分级C级、术前终末期肝病模型(MELD)评分≥18分及术后出现胆道及血管并发症是EAD发生的潜在危险因素(均P<0.05);多因素Logistic回归分析结果显示,肝移植术后EAD的独立危险因素为:术前MELD评分≥18分[OR=0.045,95%CI(0.003,0.605),P=0.045];移植术后出现胆道及血管并发症[OR=0.061,95%CI(0.009.0.419),P=0.004]。结论术前MELD评分≥18分及术后出现胆道及血管并发症是影响肝移植术后EAD的独立危险因素。临床上应该通过改善受者术前较差的肝功能和提高临床医师手术技巧来降低EAD的发生率。     

Anti-B-mediated rejection of an ABO-incompatible cardiac allograft despite aggressive plasma exchange transfusion

A group A recipient received a group B cardiac allograft. Aggressive plasma exchange with replacement by group AB FFP initially reduced the recipient's anti-B titer to a low level. Once a secondary anti-B response was mounted, plasma exchange was ineffective and IgM and IgG anti-B titers rose to high levels. Associated with the increased anti-B titers, cardiac function deteriorated and on day 13 the group B heart was replaced by a group A allograft. The compatible allograft functioned well initially but was eventually rejected, and the patient died 51 days after the initial transplantation. Histologic examination of the first allograft revealed a delayed form of typical antibody-mediated rejection with destruction of the microvasculature associated with antibody deposition and acute inflammation. By contrast, the histopathology of the second compatible allograft was typical of cell-mediated allograft rejection. Extracts of myocardium from the incompatible heart contained IgM and IgG anti-B, while no anti-B alloantibody was demonstrable in the extracts of the ABO-compatible allograft and a control heart. The utility of plasma exchange with group AB FFP replacement in such a circumstance requires further study.     

体外膜肺氧合在心脏移植术后早期移植物功能障碍中的应用

目的  分析体外膜肺氧合(ECMO)在心脏移植术后早期移植物功能障碍(EAD)中的应用效果。方法  回顾性分析614例心脏移植受者的临床资料,根据术后是否使用ECMO分为ECMO组(43例)和非ECMO组(571例)。总结ECMO组受者心脏移植术后ECMO支持治疗情况,比较两组受者的围手术期情况和远期预后。结果  43例ECMO支持受者中,17例因出血进行开胸探查,10例出现感染,4例出现下肢静脉血栓,1例出现脑卒中。26例受者成功脱离ECMO后康复出院,6例受者ECMO支持期间死亡,6例受者ECMO脱机后死亡,5例受者因无法脱离ECMO而接受再次移植,再次移植后仅1例存活。与非ECMO组比较,ECMO组术中体外循环时间较长,术后需要主动脉内球囊反搏(IABP)、肾功能不全需要透析、再次开胸止血、感染、机械通气时间≥96 h和气管切开比例较高,术后重症监护室(ICU)入住时间较长(均为P < 0.05)。ECMO组受者出院生存率和90 d生存率分别为63%和96%,低于非ECMO组的97%和100%,差异均有统计学意义(均为P < 0.05)。生存分析结果显示,ECMO组受者的远期生存率低于非ECMO组(P < 0.05); 当排除心脏移植术后90 d内死亡的受者后,两组之间的远期生存率差异无统计学意义(P > 0.05)。结论  ECMO是治疗心脏移植术后EAD有效的方法。使用ECMO的受者心脏移植术后的早期生存率低于不使用ECMO的受者,而顺利度过心脏移植术后90 d远期生存率差异无统计学意义。     

The protective effect of hepatic dysfunction on vascularized allograft survival

Recent studies have demonstrated that hepatic dysfunction, induced by experimental biliary ligation (EBL), impairs lymphocytic responsiveness to PHA stimulation in vitro and to cellular antigens in vivo. This suppression appears to be selective for T-cell mechanisms while B-cell-mediated functions remain intact. The purpose of this study was to determine whether coexisting hepatic insufficiency could exert a protective effect on vascularized or nonvascularized allograft survival in the transplanted recipient. Female Wistar-Furth (Rtlw) 225 g rats were assigned randomly to three groups: EBL, sham operation (Sham) and normal control (NC). Fourteen days following operation animals received heterotopic cardiac or skin allografts from Buffalo (Rtlb) donors. Cardiac and skin graft survival was determined daily, rejection was confirmed histologically, and technical failures were omitted from analysis. Allograft survival was expressed as median survival time +/- SEM. Serum total bilirubin (mean +/- SEM) was significantly elevated at Day 14 in EBL animals compared to Sham and NC groups (15.1 +/- 1.0 vs 0.1 +/- 0 and 0.2 +/- 0.1 mg/dl, respectively, P less than 0.01). Median cardiac allograft survival time by Probit was 10.6 +/- 2.6 vs 5.6 +/- 0.7 and 6.0 +/- 0.9 days, respectively (P less than 0.03). Skin graft survival (mean and range) was similar in all groups. These results demonstrate that EBL in the rat suppresses T-cell function and significantly prolongs vascularized allograft survival, but not skin allograft survival across the Rtl histocompatibility barrier. The mechanism whereby coexisting hepatic dysfunction exerts a protective effect on vascularized allograft survival warrants further investigation.     

公民逝世后器官捐献原位肝移植后早期肝功能不全的危险因素分析

目的 观察公民逝世后器官捐献原位肝移植术后早期肝功能不全（early allograft dysfunction,EAD）的发生情况,探讨早期肝功能不全的危险因素。方法 回顾性分析2017年1月至2019年12月间我院65例行肝移植供、受体资料。根据术后情况将患者分为EAD组（n=29）及非EAD组（n=35）。对相关因素先进行单因素分析,然后将统计学差异的因素进行多因素Logistic回归模型分析。结果 65例原位肝移植患者术后早期肝功能不全的患者有29例,发生率为44.6%。单因素分析显示EAD组与非EAD组供体血清钠[（157.53±21.71）mmol/L vs（146.06±15.24）mmol/L,P=0.019]、热缺血时间[（21.6±6.5）min vs（10.6±4.3）min,P=0.016]、冷缺血时间[（8.3±1.2）h vs（5.4±1.2）h,P=0.012]、ICU住院时间[（78.1±19.5）h vs（49.7±17.6）h,P=0.007]及受体的无肝期时间[（98.3±16.3）h vs（66.0±17.6）h,P=0.037]差异均有统计学意义。多因素Logistic回归分析结果显示影响术后早期肝功能不全的独立危险因素为供体血清钠水平（OR 18.372,95%CI 1.846～24.173,P=0.019）及热缺血时间（OR 8.105,95%CI 1.513～37.205,P=0.013）。结论 供体血清钠水平及热缺血时间是公民逝世后器官原位肝移植术后EAD的独立危险因素。     

持续脉冲加压冷疗对全膝关节置换术后早期功能障碍的影响

目的观察持续脉冲加压冷疗对全膝关节置换术（TKA）后患者早期功能障碍的影响。方法采用随机、双盲法将2010年8月至2011年6月在广州军区广州总医院因膝关节骨性关节炎行TKA治疗的40例患者分为常规组与加压组,每组各20例。常规组采用生理盐水冰袋;加压组采用持续脉冲加压冷疗。评估患者术后早期膝关节肿胀程度、引流量、关节活动度及HSS评分等指标。结果加压组患者术后72h膝关节肿胀值和术后48h引流量较常规组减少（P〈0.05）;术后72h、2周主动关节活动度较常规组增加（P〈0.05）;术后2周HSS评分较常规组提高（P〈0.05）。结论持续脉冲加压冷疗有助于TKA术后患者早期消肿、减少引流量、增加关节活动范围、提高耐受性,可促进膝关节功能的整体康复。     

Efficacy and safety of total lymphoid irradiation in different chronic lung allograft dysfunction phenotypes

Total lymphoid irradiation (TLI) is an alternative treatment for chronic lung allograft dysfunction (CLAD). However, data regarding its efficacy and tolerance are scarce. This study included patients with CLAD treated with TLI at our center between 2011 and 2018. Clinical characteristics before and after TLI and related complications were analyzed. Forty patients with CLAD (twenty-nine bronchiolitis obliterans syndrome [BOS], nine restrictive allograft syndrome [RAS], and two mixed) were included. Significant attenuation of the forced expiratory volume in 1-sec (FEV₁) decline slope was observed in all phenotypes, in both the BOS and RAS. The median FEV₁ 12, 6, and 3 months pre-TLI were as follows: 1980 (IQR 1720-2560), 1665 (IQR 1300-2340) and 1300 (IQR 1040-1740) ml (p < .001), while the median FEV₁ at 3, 6, and 12 months post-TLI was 1110 (IQR 810–1440), 1130 (IQR 860–1470), and 1115 (IQR 865–1490) ml (p = .769). No dropouts due to radiation toxicity were observed. The mean survival according to the Karnofsky Performance Status Scale (KPS) >70 or ≤70 at baseline was 1837 (IQR 259–2522) versus 298 (IQR 128–554) days (p < .0001), respectively. In conclusion, TLI may stop FEV₁ decline in both BOS and RAS. Moreover, a good KPS score may be an important prognostic factor.     

肝移植患者术中血糖变异系数对术后早期移植物功能障碍的影响

目的 探讨肝移植患者术中血糖变异系数（Glu_cv）对术后早期移植物功能障碍（EAD）的影响。
方法 选择2018年2月至2020年1月接受原位异体肝移植术的患者126例,男99例,女27例,年龄28～73岁,BMI 15.2～38.2 kg/m²,ASA Ⅱ—Ⅴ级。通过医院信息系统及电话随访收集患者数据,根据术中Glu_cv将患者分为两组：L组（Glu_cv＜29.8%,n=52）和H组（Glu_cv≥29.8%,n=74）。记录两组患者术后EAD的发生情况、术后7 d内C反应蛋白（CRP）最高值、ICU停留时间、术后30 d生存情况。
结果 与H组比较,L组EAD发生率明显降低（P<0.05）,ICU停留时间明显缩短（P<0.05）。两组患者术后7 d内CRP最高值、术后30 d生存率差异无统计学意义。
结论 肝移植术中低血糖变异系数的患者术后早期移植物功能障碍发生率更低,ICU停留时间更短,肝移植术中应减少血糖波动以改善预后。