Acute diverticulitis in heart transplant recipients

Immunosuppressed patients are susceptible to complicated diverticulitis, but reports of this complication are scarce in heart graft recipients. To estimate the prevalence of acute diverticulitis in heart graft recipients, we retrospectively reviewed the cases of diverticulitis in a series of 143 patients who underwent orthotopic heart transplantation in a period of 10 years. Six (4%) of these developed acute diverticulitis and required colectomy. All of them were male patients and were older than 50 years. Four patients underwent urgent laparotomy and colon resection with end colostomy (Hartmann procedure). The two other patients suffered from diverticulitis without generalized peritonitis and underwent laparoscopic sigmoidectomy with direct transanal end-to-end anastomosis. The postoperative outcomes of these six patients were satisfactory. As are other immunosuppressed patients, heart graft recipients are susceptible to diverticulitis. Early surgical management may be safe in well-compensated patients.     

心脏移植受者术后感染的防治

通过临床分析３例心脏移植受者在术后不同阶段所发生的各种感染性疾病，主要探讨心脏移植术后感染发生的规律及其防治措施。结果发现在术后１－２个月，细菌性感染及机会性真菌感染较多见，采用敏感的抗生素能够完全控制感染。术后３个月以上的患者，各种感染逐渐减少。提示在移植术后初期，应加强对感染的监测与防治。     

Unexpected low incidence of vertebral fractures in heart transplant recipients: analysis of bone turnover.

Heart transplantation (HTX) is associated with a reduction in bone mineral density (BMD). Different markers of bone metabolism have been used, and the applied immunosuppressive regimens have also changed over time. This study was performed to re-investigate bone metabolism in HTX recipients. Twenty-five HTX recipients were compared with 25 HTX candidates in respect of biochemical parameters of bone metabolism, BMD, and the frequency of fractures for 1 year. Osteopenia or osteoporosis was observed in approximately two-thirds of the HTX recipients. Nevertheless, only three (12%) HTX recipients developed a vertebral fracture within 1 year after transplantation; no peripheral fractures occurred. Compared with HTX candidates, HTX recipients had lower serum levels of osteocalcin, and higher serum levels of cross-linked-N-telopeptide of type I collagen (NTX). In HTX recipients, osteocalcin initially reached a nadir, increased during the first 3 months, and decreased thereafter. Bone-specific alkaline phosphatase initially increased and then decreased. Serum levels of NTX and parathyroid hormone remained high throughout the year. Despite a high bone turnover, an unexpectedly low rate of vertebral fractures was registered. Nevertheless, each fragility fracture is a serious complication and we need to take steps to prevent this complication.     

A pharmacokinetic comparison of cyclosporin oral solution and cyclosporin capsules in heart and lung transplant recipients

Pharmacokinetic profiles were obtained for 16 heart or lung recipients following the administration of identical doses of cyclosporin as oral solution and capsules on consecutive days. A comparison of pharmacokinetic parameters (AUC, C_max, C_min and t_max) showed that there were no significant differences between the two formulations except for the t_max, which was significantly longer for the capsules. The mean variation in day-to-day trough levels produced by the two different forms was 25.6%. A retrospective study was carried out of consecutive cyclosporin levels in patients at steady state on oral solution. The mean variation in day-to-day trough levels was 32.3%. This was not significantly different from the variation in consecutive trough levels seen in the oral solution/capsule comparison. This study shows that cyclosporin capsules can be substituted for oral solution without causing acute changes in cyclosporin blood levels, and that the pharmacokinetics of the two formulations are similar.This work was carried out in partial fulfillment of the requirements for the Master of Science Degree in Clinical Pharmacy, University of London     

Platelet activation in heart transplant recipients

An inappropriate and persistent immune activation has been suggested to contribute to long-term mortality and morbidity after heart transplantation. Several lines of evidence suggest that platelets do not only promote thrombus formation, but also act as inflammatory cells. In the present study, we investigated if long-time survivors of heart transplantation (mean time since transplantation 6.5 yr) were characterized by enhanced platelet activation as assessed by different experimental approaches. Our main findings when comparing heart transplant recipients (n = 52) and age- and sex-matched healthy controls (n = 38) were: (i) platelets from heart transplant recipients showed enhanced expression of both P-selectin and CD63 as assessed by flow cytometry; (ii) platelets from these patients also contained significantly increased levels of soluble CD40 ligand and tended to release higher levels of this cytokine upon SFLLRN stimulation as assessed by enzyme immunoassay; (iii) heart transplant recipients had increased levels of soluble P-selectin in platelet-free plasma; and (iv) the enhanced platelet activation after heart transplantation was most pronounced in those with concomitant hypertension. These findings suggest that long-term survivors of heart transplantation are characterized by enhanced activation of platelets, possibly contributing to the persistent immune activation and clinical complications in these patients.     

Cytomegalovirus infection accelerates cardiac allograft vasculopathy: correlation between angiographic and endomyocardial biopsy findings in heart transplant patients

In order to determine the impact of cytomegalovirus (CMV) infection on cardiac allograft vasculopathy (CAV), we quantitated angiograms and endomyocardial biopsy (EMB) specimens obtained from 53 heart transplant recipients. CMV infection was particularly associated with the development of discrete stenosis in major branch vessels (P<0.03). Also, the number of diffusely affected vessel segments was significantly higher in CMV patients than in CMV-free recipients after the 2nd post-operative year (P<0.05). The EMB histology correlated well with angiography. Significantly higher levels of arteriolar endothelial cell proliferation and intimal thickness were recorded in biopsies of CMV patients than in those of CMV-free recipients during the 1st postoperative year (P<0.02 and P<0.005, respectively). The CMV-associated vascular changes in EMB histology clearly preceded angiographically detectable CAV findings. Taken together, CMV infection accelerated heart allograft arteriosclerosis. The histological changes appeared prior to changes detected by coronary angiography. The CMV effect was particularly pronounced during the first 2 post-transplant years but leveled off thereafter. Thus, CMV-accelerated allograft arteriosclerosis may be linked in particular with early graft loss of CMV-infected heart transplant recipients.     

Heart transplant candidates at high risk can be identified at the time of initial evaluation

The increasing discrepancy between the numbers of patients selected for cardiac transplantation and the available donor organs requires validation of markers of high risk at the time of initial evaluation that may help to determine which patients profit from aggressive therapy. We retrospectively examined the case records of 91 heart transplant caddidates selected out of a total of 140 consecutive patients referred for evaluation. Of these 91 patients, 48 were transplanted during follow-up. Of the remaining 43 patients, 25 died after a mean survival time of 1.6±2.5 months. The causes of death were pump failure in 18 (72%) and sudden cardiac death in 7 (28%). Multivariate analysis identified 4 out of 26 parameters at initial evaluation that distinguished the 25 nonsurvivors from the 18 survivors. These were: mean arterial pressure (P=0.03), pulmonary capillary wedge pressure (P=0.002), mean pulmonary artery pressure (P=0.007). The mode of death could not be predicted. We conclude that there are prognostic markers at initial evaluation that allow more restrictive selection of patients for cardiac transplantation and mechanical bridging.     

维生素D预防和治疗肾移植术后骨质疏松的系统评价

目的 评价维生素D预防和治疗肾移植术后骨质疏松的安全性和有效性.方法 使用由国际循证医学Cochrane协作网推荐的方法,采用计算机检索1990年1月至2009年11月期间MEDLINE、EMBase、Cochrane图书馆临床对照试验数据库(CENTRAL)、中国期刊网(CNKI)等数据库,辅以手工检索及追查已纳入文献库的维生素D预防和治疗肾移植术后骨质疏松的临床随机对照试验(RCT).由2位评价者共同评价纳入的RCT质量,对符合标准的研究采用Revman 4.2软件进行Meta分析.结果 共纳入9个RCT,肾移植术后受者658例.研究质量评价结果为:A级4篇、B级2篇和C级3篇.Meta分析结果显示:维生素D治疗1年后,试验组和对照组受者比较,骨质密度值、Z值(被测人的骨密度与同性别、同年龄对照组平均骨密度的差值)或T值(被测人的骨密度与同性别年轻人对照组平均骨密度的差值)的差异均有统计学意义(P＜0.05);血清甲状旁腺激素(PTH)浓度差异有统计学意义(P＜0.01);血清钙、磷离子浓度差异无统计学意义(P＞0.05);高钙血症发生率差异无统计学意义(P＞0.05).结论 维生素D预防和治疗肾移植术后骨质疏松是安全和有效的.     

Hyperhomocysteinemia and transplant coronary artery disease in cardiac transplant recipients

BACKGROUND: In cardiac transplant recipients, long-term survival may be limited by transplant coronary artery disease (TxCAD). Hyperhomocysteinemia (Hhcy) has been associated with vascular disease and is common in transplant recipients. The objective of this study was to determine the relationship between fasting homocysteine (Hcy) concentrations and TxCAD in a cohort of cardiac transplant recipients. METHODS: Forty-eight patients more than 5 yr after transplant were recruited from a cohort of 72 consecutive patients with in-depth analysis of homocysteine levels from the Cardiac Transplant Clinic. Early morning fasting blood was obtained, and the plasma separated and frozen within 30 min. Hcy concentrations were determined by high-performance liquid chromatography (HPLC) with pulsed integrated amperometry. Coronary angiograms were reviewed in a blinded fashion. TxCAD was diagnosed, using the most recent angiogram, when a >25% lesion was present anywhere in the coronary tree. RESULTS: Forty-eight patients transplanted between 1985 and 1994 were studied. The mean Hcy concentration for the cohort was 23.5+/-5.0 micromol/L, all patients had homocysteine levels above the upper range of normal (5-15 micromol/L). Hcy concentrations were significantly higher in patients with angiographic evidence of TxCAD: 25.0+/-5.9 vs. 21.9+/-3.4 micromol/L, p=0.03. This effect persisted when covariates were taken into account using logistic regression analysis. CONCLUSIONS: Hhcy is associated with TxCAD. Prospective studies are required to confirm this association and to assess the efficacy of Hcy-lowering therapy in this patient population.     

Plasma adiponectin in heart transplant recipients

Abstract: Background: The association between plasma adiponectin and metabolic syndrome may be impaired in heart transplant recipients, since renal failure is frequent among these patients. Thus, we studied the relationship between metabolic syndrome and plasma adiponectin in transplanted heart recipients. Methods: Ninety‐five heart transplant recipients were prospectively included 8.3 ± 5.6 yr after transplantation in this cross‐sectional study. All patients had physical examination, echocardiography or routine biennial coronary angiography, and laboratory measurements. Results: Metabolic syndrome was found in 31% of these patients. Plasma adiponectin was significantly lower in patients with metabolic syndrome (12.5 ± 8.3 μg/mL) than in patients without (16.7 ± 9.4 μg/mL, p = 0.03). Adiponectin levels were usually in the normal or high range (< 4 μg/mL in only two patients). Low creatinine clearance was associated with higher plasma adiponectin (R=?0.26, p = 0.01). Plasma adiponectin was not significantly different between the 28 patients with angiographic evidence of graft vasculopathy (13.9 ± 9.5 μg/mL) and the 67 patients without (16.1 ± 9.1 μg/mL, p = 0.3). Conclusions: Contrasting with a high frequency of metabolic syndrome in these patients, adiponectin levels were usually in the normal or high range, probably as a consequence of renal failure. This suggests that adiponectin is not a major determinant for insulin resistance among these patients.     

Value of Doppler echocardiography in the detection of low-grade rejections after cardiac transplantation

Modifications of the diastolic parameters pressure half-time (PHT) and isovolumic relaxation time (IVRT), recorded using cardiac Doppler echocardiography (CDE), were studied in 23 heart transplant recipients and compared to the results of 345 endomyocardial biopsies (EMB) performed on the same day. Two different protocols, analyzing respectively (1) a decrease of 20% or more in IVRT and/or PHT with respect to the mean and (2) a decrease of 20% or more in IVRT and/or PHT with respect to its preceding value, were used to evaluate the efficiency of CDE in diagnosing mild and moderate rejections. When a mild rejection was detected by EMB, a statistically significant decrease was found in the average CDE parameter values of the patient population. However, these variations were weak and did not differ from the spontaneous variations observed in each patient in the absence of rejection. Thus, it is not surprising that the sensitivity of CDE in the detection of mild rejections was very low (45%) using the most sensitive protocol (variations of the parameters from their preceding value). We conclude that CDE alone does not seem to be sufficient to perform the noninvasive diagnosis of low-grade rejections and must be complemented by other noninvasive methods.     

Blood glutathione as a marker of cardiac allograft vasculopathy in heart transplant recipients

BACKGROUND: Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx). Between immunologic and non-immunologic factors, reactive oxygen species generation has been proposed as pathogenetic mechanism. This study was aimed at evaluating redox status in HTx recipients and verifying whether it could be independently associated with CAV. METHODS: Fifty-five consecutive male HTx recipients, median [interquartile range] age 60 yr [50, 64], underwent angiography 67 months [21, 97] after HTx to assess CAV, defined as significant stenosis in >or=1 epicardial vessel or any distal vessel attenuation. All patients underwent blood sampling 89 months [67, 119] after HTx for biochemical (glucose, creatinine, total and LDL cholesterol, and cyclosporin levels) and redox evaluation [plasma reduced and total homocysteine, cysteine, cysteinylglycine, glutathione, blood reduced glutathione (GSH(bl)) and vitamin E]. Univariate Odds Ratios (OR) with 95% confidence interval (95% CI, highest vs. lowest quartile) were estimated on the basis of a logistic regression analysis between clinical, conventional biochemical and redox data. Only the significant variables at univariate entered into multivariate analysis. RESULTS: CAV was documented in 15 (27%) patients. Univariate analysis showed that time from HTx to angiography (OR 3.97, 95% CI 1.15-14, p = 0.03) and GSH(bl) (OR 0.31, 95% CI: 0.14-0.70, p = 0.005) were significantly associated with CAV. However, multivariate analysis revealed GSH(bl) as the only independent predictor of CAV (OR 0.31, 95% CI: 0.13-0.74, p = 0.008). CONCLUSIONS: In HTx recipients reduced levels of GSH(bl) are independently associated with CAV. Given its potent intracellular scavenger properties, GSH(bl) may serve as a marker of antioxidant defence consumption, favouring CAV development.     

Coronary stenting for coronary artery narrowing in a heart transplant recipient

Transplant atherosclerotic coronary disease remains the leading cause of death in heart transplant recipients. We report the first case of coronary stent implantation in a heart graft for epicardial focal stenosis. Due to the lower rate of restenosis after stenting in the native coronary artery, we suggest that coronary stenting be considered an acceptable, first intention therapeutic option instead of angioplasty alone whenever possible.     

The influence of dose interval on the immunosuppressive potency of methylprednisolone: an experimental organ transplant study in isogenous rats

Groups of isogenous Brown-Norway rats received heterotopic heart transplants from (Brown-Norway/Wistar Furth)xF₁ hybrid rats. Methylprednisolone was administered IV in a daily dose of 5–40 mg/kg, using a dose interval of 24, 12, or 0 h (continuous infusion). Continuous infusion proved to be superior when small daily doses were used and then caused a more than threefold increase in graft survival. High daily doses created a substantial mortality with all dose intervals. Moreover, the equipment used for continuous drug administrations was unreliable beyond 4 weeks of infusion.     

Visfatin serum concentration is associated with cardiac allograft vasculopathy in heart transplant recipients

Cardiac allograft vasculopathy (CAV) still is one of the most important limiting factors of long‐term survival following heart transplant (HT). This study aimed to investigate the association between proinflammatory adipokine‐visfatin and the incidence of CAV in HT recipients. After HT, 182 patients who had a follow‐up visit at the Transplantation Clinic between 2016 and 2017 were analyzed. The median age was 60.5 years, and 76.4% were men. The incidence of CAV was 54.9%. According to the multivariable proportional hazard regression analysis, visfatin level (1.795 [1.539‐2.094]; P < .001) was significantly associated with CAV, and statin use was protective against CAV (0.504 [0.32‐0.793]; P = .003). The area under the receiver operating characteristic curve indicated an excellent discriminatory power of visfatin (0.9548 [0.9281‐0.9816]) for CAV detection. The cutoff value of 5.42 ng/mL for visfatin yielded a sensitivity of 89% and specificity of 91%. This is the first study to demonstrate that visfatin serum concentrations are independently associated with the incidence of CAV in HT recipients. Visfatin allows for simple and cheap detection of CAV given its excellent discriminatory ability and high sensitivity and specificity. In addition, we have found an independent association between the statin use and a lower risk of CAV.     

心脏移植患者服用微乳化环孢素A后的血药浓度C2值监测及意义

目的 评估心脏移植患者口服微乳化环孢素A(CsA)后2 h时的血药浓度(C2)作为临床监测指标的安全性和准确性.方法 107例心脏移植受者,除29例研究阶段移植的患者外,其余为定期随访患者.心脏移植术后口服微乳化CsA(以下"CsA"均指微乳化CsA)预防排斥反应,其中54例以服用CsA前即刻血药浓度(C0)为监测指标(C0组),另53例以C2为监测指标(C2组),所有患者入组时血肌酐(Cr)<150 tmaol/L,丙氨酸转氨酶(ALT)<80 U/L.在测定血药浓度的同时,检查心脏及肝、肾功能.结果 C0组和C2组肝损害发生率分别为25.0%(13/52)和10.0%(5/50);肾损害发生率分别为5.8%(3/52)和8.0%(4/50);急性排斥反应发生率分别为11.5%(6/52)和6.0%(3/50).C0组中,未发生排斥反应者的C2为(0.131±0.074)μmol/L,低于发生排斥反应者的(0.133±0.078)μmol/L,但二者间的差异无统计学意义(P0.05);发生不良反应(肝、肾毒性)者的C0为(0.133±0.075)μmol/L,无不良反应者的C0为(0.131±0.073)tanol/L,二者间的差异无统计学意义(P0.05).C2组中,未发生排斥反应者的C2为(0.659±0.296)μmol/L,高于发生排斥反应者的(0.516±0.217)μmol/L(P<0.05);发生不良反应者的C2为(0.719±0.288)μmol/L,无不良反应者的C2为(0.579±0.271)tanol/L,后者明显低于前者(P<0.05).结论在提示急性排斥反应和CsA所致不良反应的准确性方面,C2均明显优于C0.     

肾移植术后患者骨代谢的改变

目的:研究肾移植术后患者骨代谢生化指标的改变.方法:采用竞争性放射免疫分析法测定30例肾移植患者和25例健康献血者的血清骨代谢生化指标:骨钙素(BGP)、降钙素(CT)、甲状旁腺激素(PTH)和25羟基维生素D(25-OH-D)、Ⅰ型胶原羧基端交联肽原(ICTP)和Ⅰ型前胶原氨基端伸展肽(PINP)水平.结果:肾移植术后患者的BGP、PINP和ICTP水平明显高于正常对照组(P＜0.01),但两组的CT、25-OH-D和PTH水平差异无统计学意义(P＞0.05).结论:肾移植术后患者出现明显的骨代谢紊乱,主要表现为血清成骨细胞活性增强,同时伴有破骨细胞功能增强,骨转换活跃,其发病机制可能主要与术后长期使用免疫抑制剂有关.