Allograft Acceptance Despite Differential Strain-Specific Induction of TGF-β/IL-10-Mediated Immunoregulation

We examined the immune approaches that C57BI/6 and BALB/c mice take when treated to accept cardiac allografts. C57BI/6 mice accept DBA/2 cardiac allografts when treated with gallium nitrate (GN) or anti-CD40L mAb (MR1). These allograft acceptor mice fail to mount donor-reactive delayed type hypersensitivity (DTH) responses, and develop a donor-induced immunoregulatory mechanism that inhibits DTH responses. In contrast, BALB/c mice accept C57BI/6 cardiac allografts when treated with MR1 but not with GN. These allograft acceptor mice display modest donor-reactive DTH responses, and do not develop donor-induced immune regulation of DTH responses. Real-time PCR analysis of rejecting graft tissues demonstrated no strain-related skewing in the production of cytokines mRNAs. In related studies, C57BI/6 recipients of cytokine and alloantigen educated syngeneic peritoneal exudate cells (PECs) failed to mount DTH responses to the alloantigens unless neutralizing antibodies to transforming growth factor-beta (TGF-p were present at the DTH site demonstrating regulation of cell-mediated alloimmune responses. In contrast, BALB/c recipients of cytokine-and alloantigen-educated PECs expressed strong DTH responses to alloantigens demonstrating a lack of regulated alloimmunity. In conclusion, C57BI/6 mice respond to immunosuppression by accepting cardiac allografts and generating TGF-beta-related regulation of donor-reactive T cell responses, unlike BALB/c mice that do not generate these regulatory responses yet still can accept cardiac allografts.     

Management of Patients after Renal Graft Loss: An Open Question for Nephrologists

Patients undergoing renal graft failure and returning to dialysis are often regarded to like facing for the first time a substitutive treatment, without considering the technical complications, the economical impact, and the psychological implications. This review attempt, to give answers to various questions, concerning the management of vascular access, the immunosuppressive therapy, the transplantectomy, the emotional and neuropsychic aspects, and the quality of life of graft-failed patients.     

黄芪注射液治疗慢性肾衰竭合并心力衰竭的临床疗效

目的:观察黄芪注射液治疗慢性肾衰竭合并心力衰竭的疗效。方法:将60例慢性肾衰合并心力衰竭病人分为两组。对照组30例予西医治疗。治疗组30例在西医治疗基础上加用黄芪注射液30 ml溶入10％G.S 250 ml中静脉滴注,qd连用10 d。结果:治疗组心功能明显改善,总有效率90％,明显高于对照组(P<0.05);治疗组左室射血分数(LVEF)和左室短轴缩短率(ΔD％)均显著提高(P<0.05)。结论:黄芪注射液能明显改善慢性肾衰病人的心功能。     

Acute Cellular Rejection Following Human Heart Transplantation is Associated with Increased Expression of Vitronectin Receptor (Integrin αvβ3)

The vitronectin receptor (integrin alphavbeta3), a cell-surface adhesion receptor, has been shown to play a significant role in endothelial cell migration, apoptosis, atherosclerosis, and T-lymphocyte activation. This study was undertaken to test the hypothesis that cardiac allograft rejection is associated with increased expression of alphavbeta3. We also determined whether fibronectin receptor (alpha5beta1) and tissue factor are up-regulated in the presence of acute cellular rejection. We evaluated endomyocardial biopsy specimens with histologic evidence of different degrees of acute cellular rejection (grade 0, n = 10; grade 1A, n = 10; grade 2, n = 10; grade 3A, n = 10). Biopsies were obtained 2-4weeks after cardiac transplantation. Immunoperoxidase staining was performed for alphavbeta3, tissue factor, and alpha5beta1, and protein levels were further determined by Western blot analysis. Specimens with grade 2 and grade 3A rejection showed positive staining of alphavbeta3 in lymphocytic aggregates and vascular endothelial cells. By immunoblotting, we identified significantly increased expression of alphavbeta3 in the presence of acute rejection, grade 2 (3-fold, p = 0.01) and grade 3A (3.6-fold, p = 0.005) compared to grade 0 and 1 A specimens. There was no evidence of increased expression of alpha5beta1 or tissue factor. Acute cellular rejection, a process characterized by T-lymphocyte activation and release of inflammatory cytokines, is associated with increased expression of alphavbeta3.     

Role of Intra‐Aortic Balloon Pump and Extracorporeal Membrane Oxygenation in Early Graft Failure After Cardiac Transplantation

Early graft failure (EGF) is a major risk factor for death after heart transplantation (Htx). We investigated the predictive risk factors for moderate‐to‐severe EGF requiring an intra‐aortic balloon pump (IABP) or extracorporeal membrane oxygenation (ECMO) circulatory support as treatment after Htx. Between January 2000 and December 2014, 412 consecutive adult patients underwent isolated Htx at our institution. Moderate and severe EGF were defined as the need for IABP and ECMO support, respectively, within 24 h after Htx. All available recipient and donor variables were analyzed to assess the risk of EGF occurrence. Overall, moderate‐to‐severe EGF occurred in 46 (11.1%) patients. Twenty‐nine (63.04%) patients required peripheral or central ECMO support in the treatment of severe EGF and 17 (36.9%) patients required IABP support for the treatment of moderate EGF. The predictive risk factors for moderate‐to‐severe EGF in recipients, as assessed by logistic regression analysis, were a preoperative transpulmonary gradient > 12 mm Hg (odds ratio [OR] 5.2; P = 0.023), a preoperative inotropic score > 10 (OR 8.5; P = 0.0001), and preoperative ECMO support (OR 4.2; P = 0.012). For donors, the predictive risk factor was a donor score ≥ 17 (OR 8.3; P = 0.006). The absence of EGF was correlated with improved long‐term survival: 94% at 1 year and 81% at 5 years without EGF versus 76% and 36% at 1 year (P < 0.001), and 70% and 28% at 5 years (P < 0.001) with EGF requiring IABP and ECMO support, respectively. In‐hospital weaned and survived patients after IABP or ECMO treatment for moderate‐to‐severe EGF had a similar 5‐year conditional survival rate as transplant patients who had not suffered EGF: 88% without EGF versus 84% with EGF treated with mechanical circulatory support devices (P = 0.08). The occurrence of EGF is a multifactorial deleterious event that depends on donor and recipient profiles. IABP and ECMO support are reliable treatment strategies, depending on the grade of EGF. Furthermore, surviving patients treated with IABP or ECMO have the same long‐term conditional survival rate as patients who have not suffered EGF.     

Donor Age and Early Graft Failure After Lung Transplantation: A Cohort Study

Lungs from older adult organ donors are often unused because of concerns for increased mortality. We examined associations between donor age and transplant outcomes among 8860 adult lung transplant recipients using Organ Procurement and Transplantation Network and Lung Transplant Outcomes Group data. We used stratified Cox proportional hazard models and generalized linear mixed models to examine associations between donor age and both 1‐year graft failure and primary graft dysfunction (PGD). The rate of 1‐year graft failure was similar among recipients of lungs from donors age 18–64 years, but severely ill recipients (Lung Allocation Score [LAS] >47.7 or use of mechanical ventilation) of lungs from donors age 56–64 years had increased rates of 1‐year graft failure (p‐values for interaction = 0.04 and 0.02, respectively). Recipients of lungs from donors <18 and ≥65 years had increased rates of 1‐year graft failure (adjusted hazard ratio [HR] 1.23, 95% CI 1.01–1.50 and adjusted HR 2.15, 95% CI 1.47–3.15, respectively). Donor age was not associated with the risk of PGD. In summary, the use of lungs from donors age 56 to 64 years may be safe for adult candidates without a high LAS and the use of lungs from pediatric donors is associated with a small increase in early graft failure.     

High Risk of Graft Failure in Emerging Adult Heart Transplant Recipients

Emerging adulthood (17–24 years) is a period of high risk for graft failure in kidney transplant. Whether a similar association exists in heart transplant recipients is unknown. We sought to estimate the relative hazards of graft failure at different current ages, compared with patients between 20 and 24 years old. We evaluated 11 473 patients recorded in the Scientific Registry of Transplant Recipients who received a first transplant at <40 years old (1988–2013) and had at least 6 months of graft function. Time‐dependent Cox models were used to estimate the association between current age (time‐dependent) and failure risk, adjusted for time since transplant and other potential confounders. Failure was defined as death following graft failure or retransplant; observation was censored at death with graft function. There were 2567 failures. Crude age‐specific graft failure rates were highest in 21–24 year olds (4.2 per 100 person‐years). Compared to individuals with the same time since transplant, 21–24 year olds had significantly higher failure rates than all other age periods except 17–20 years (HR 0.92 [95%CI 0.77, 1.09]) and 25–29 years (0.86 [0.73, 1.03]). Among young first heart transplant recipients, graft failure risks are highest in the period from 17 to 29 years of age.     

Plasma N-Terminal Atrial Natriuretic Peptide Predicts Hospitalization in Patients with Heart Failure

Abstract>

Objective. The soluble form of ST2 (sST2) is a novel laboratory parameter for cardiac risk prediction, and over the past years, several studies have tried to evaluate its utility, especially in the management of heart failure. We investigated whether increased serum levels of sST2 show a characteristic pathomorphologic pattern in 3-Tesla cardiac magnetic resonance imaging (CMRI). Methods. One hundred and fifty-six patients referred to 3T CMRI due to suspected coronary artery disease (CAD) or myocarditis were prospectively enrolled in the study. Ninety patients were diagnosed with CAD, 22 patients with myocarditis, and 44 patients, who constituted the reference group, showed no pathologic CMRI pattern. Results. There was no significant difference between the sST2 values for patients in the reference group and patients with CAD or myocarditis. The sST2 concentration showed a weak correlation with the NYHA functional class (P = 0.002, r = 0.22), but correlation of sST2 and LGE, left ventricular parameters, and LVEF could not be seen. In contrast NT-proBNP was positively correlated to left ventricular parameters, LGE, and NYHA class function (P < 0.05). Additionally, it showed an inverse relationship to LVEF (P < 0.001, r = ? 0.42). Conclusions. Soluble ST2 is not able to detect myocardial scar and should not be used alone as a parameter for detection of inflammation and myocardial scar formation.     

出院指导对预防老年心力衰竭复发的影响

目的：探讨护理干预对老年心力衰竭（心衰）病人复发再入院的影响。方法：将134例60－86岁心衰住院病人出院时随机分为观察组71例和对照组63例。观察组出院时由专职护士进行心衰相关知识健康教育、个别化用药指导、饮食指导及出院后定期护理随访指导；对照组则进行常规出院指导。观察90d内因心衰复发再入院率、两次以上再入院率和病死率。结果：90d内再入院率和两次以上再入院率，观察组分别为31．0％和9．9％，对照组为49．2％和22．2％（P＜0．05）；病死率，观察组5．6％，对照组9．5％（P＞0．05）。结论：加强心衰病人出院后的护理及健康教育有助于减少心衰复发率。     

TGF-β1 impairs homocysteine metabolism in human renal cells: possible implications for transplantation

We hypothesized that TGF-beta1 influences the metabolism of homocysteine (Hcy) and increases its cellular export, which may lead to hyperhomocysteinemia in patients with renal transplants. We exposed human renal proximal tubule epithelial cells (huRPTECs) to different concentrations of TGF-beta1, IL-1alpha, IL-10, or methionine and measured total Hcy (tHcy) in culture supernatants. We then examined the relationship between plasma levels of tHcy and TGF-beta1 in renal graft recipients. In multivariate analysis, the factors mediator (TGF-beta1, IL-1alpha, IL-10), mediator concentration, methionine concentration, and "mediator x concentration" interaction independently influenced tHcy concentrations in culture supernatants. A 31% increase in tHcy was observed after exposure of huRPTECs to TGF-beta1 compared to medium alone. However, TGF-beta1 plasma levels in kidney graft recipients showed no independent association with tHcy plasma concentrations. We demonstrated that the release of Hcy from huRPTECs is enhanced by TGF-beta1, but that TGF-beta1 plasma levels in renal graft recipients show no independent relationship with hyperhomocysteinemia.     

Correlation of Biochemical and Hematological Changes with Graft Failure Following Pig Heart and Kidney Transplantation in Baboons

We have explored biochemical and hematologic parameters that might indicate acute humoral xenograft rejection (AHXR) following pig organ transplantation in baboons. Baboons (n = 15) received an immunosuppressive regimen, and underwent a miniature swine or hDAF kidney (Group 1, n = 6) or heart (Group 2, n = 7) transplantation. Control baboons (Group 3, n = 2) received the immunosuppressive regimen without organ transplantation. Blood chemistry and hematologic parameters were measured daily. Baboon and porcine cytomegalovirus were monitored. In Groups 1 and 2, organ grafts survived for up to 29 days. A plasma fibrinogen of <80 mg/dL on 2 consecutive days, and a serum lactate dehydrogenase of >600 U/L and aspartate transaminase of >300 U/L, were associated with the development of AHXR in both heart and kidney grafts. In Group 1, a decrease in platelet count of >150,000/microL within 3 days, or a count of <50,000/microL, were associated with AHXR. In Group 2, a creatine phosphokinase of >500 U/L was associated with graft failure. In Group 3, no abnormalities were observed. The possibility that porcine CMV may play a role in graft injury could not be excluded. Noninvasive parameters were identified that have predictive potential for AHXR. Monitoring of these might enable therapeutic intervention to reverse rejection.     

Simple Measures to Monitor β-Cell Mass and Assess Islet Graft Dysfunction

The aim of this study was to develop a simple test for the assessment of islet graft dysfunction based on measures involving fasting C-peptide. Calculations were made to account for the dependence of C-peptide secretion on glucose concentration (C-peptide/glucose ratio [CP/G]) and adjusted for renal function by calculating the C-peptide/glucose-creatinine ratio (CP/GCr). Values from 22 recipients were analyzed at different times post-last islet infusion. Receiver operating characteristic curves were used to determine which of these measures best predicts high 90-minute glucose (90 min-Glc; >10 mmol/L) after a Mixed Meal Tolerance Test (MMTT). In this initial analysis, CP/G was found to be superior predicting high 90 min-Glc with a larger area under the ROC curve than C-peptide (p = 0.01) and CP/GCr (p = 0.06). We then correlated C-peptide and CP/G with islet equivalents--IEQ/kg infused, 90 min-Glc after MMTT and clinical outcome (beta-score). C-peptide and CP/G in the first 3 months post-last islet infusion correlated with IEQ/kg infused. CP/G correlated with 90 min-Glc and beta-score. C-peptide and CP/G are good indicators of islet mass transplanted. CP/G is more indicative of graft dysfunction and clinical outcome than C-peptide alone. The ease of calculation and the good correlation with other tests makes this ratio a practical tool when monitoring and managing islet transplant recipients.     

Early Prediction of Cardiac Allograft Vasculopathy and Heart Transplant Failure

Early risk‐prediction is essential to prevent cardiac allograft vasculopathy (CAV) and graft failure in heart transplant patients. We developed multivariate models to identify patients likely to experience CAV, severe CAV, and failure due to CAV, at 1, 5 and 10 years. A cohort of 172 patients was followed prospectively for 6.7 ± 3.9 years. Logistic regression models were developed and cross‐validated using bootstrap resampling. Predictive markers of atherothrombosis (myocardial fibrin deposition, and loss of vascular antithrombin and tissue plasminogen activator) and arterial endothelial activation (intercellular adhesion molecule‐1 expression) were measured in serial biopsies obtained within 3 months posttransplant. Most markers were univariately associated with outcome. Multivariate models showed that loss of tissue plasminogen activator was the dominant and, in most cases, only predictor of long‐term CAV (p < 0.001), severe CAV (p < 0.001), and graft failure due to CAV (p < 0.001). The models discriminated patients having adverse outcomes, had particularly high negative predictive values (graft failure due to CAV: 99%, 99% and 95% at 1, 5 and 10 years) and predicted event incidence and time to event. Early absence of atherothrombotic risk identifies a patient subgroup that rarely develops CAV or graft failure, implying that this low‐risk subgroup could possibly be followed with fewer invasive procedures.     

慢性心力衰竭患者睡眠质量及其影响因素调查分析

目的了解慢性心力衰竭(心衰)患者住院期间的睡眠质量及其影响因素.方法采用匹兹堡睡眠质量指数(PSQI)量表,焦虑自评量表(SAS),抑郁自评量表(SDS)和睡眠影响因素调查表对100例慢性心衰患者进行问卷调查.结果 73.0%慢性心衰患者有睡眠问题,PSQI总分及7个分项得分与国内常模相比较,差异有显著性意义(均P<0.01);心功能等级、SAS、SDS和环境质量与睡眠质量呈正相关关系;影响因素依次为生理(呼吸困难、心悸、咳嗽、咳痰),心理(担心疾病、经济困难、家庭功能不良)和环境(院内噪声、夜间治疗护理)三方面.结论慢性心衰患者的睡眠质量较差,应采取有效的护理措施控制影响睡眠的各种因素.     

慢性心力哀竭患者睡眠质量及其影响因素调查分析

目的 了解慢性心力衰竭（心衰）患者住院期间的睡眠质量及其影响因素。方法 采用匹兹堡睡眠质量指数（PSQI）量表．焦虑自评量表（SAS），抑郁自评量表（SDS）和睡眠影响因素调查表对100例慢性心袭惠者进行问卷调查。结果73．0％慢性心衰患者有睡眠问题．PSQI总分及7个分项得分与国内常模相比较．差异有显著性意义（均P〈0．01）；心功能等级、SAS、SDS和环境质量与睡眠质量呈正相关关系；影响因素依次为生理（呼吸困难、心悸、咳嗽、咳痰）．心理（担心疾病、经济困难、家庭功能不良）和环境（院内噪声、夜间治疗护理）三方面。结论 慢性心衰患者的睡眠质量较差，应采取有效的护理措施控制影响睡眠的各种因素。