实体器官移植术后腹泻的深度解析

腹泻: 指排便次数增多,粪质稀薄,或带有黏液、脓血或未消化的食物.具体指标:解液状便,每日 3 次以上,或每日总量> 200 g,含水量> 85％.腹泻是实体器官移植受者术后最常见的症状之一.腹泻的原因复杂,有时是多种因素共同作用的结果.腹泻在大多数情况下不会引起严重的临床后果,但如未得到及时诊治,也会导致严重后果.绝...     

The immunology of solid organ transplantation

Solid organ transplantation has progressed dramatically over the last 50 years. However, rejection still remains one of the barriers to successful transplantation. Immunological processes underlying the mechanisms of rejection are well described and numerous pharmacological agents exist to help suppress a recipient's immune system in order to prolong graft survival. Furthermore, clinician decisions and actions during both the work-up of a potential transplant recipient and in the perioperative phase can impact upon the immunological status of an individual and the likelihood of successful solid organ transplantation. In this article we aim to describe the key processes involved in solid organ immunology and their relevance in anaesthetic practice.     

The immunology of solid organ transplantation

Solid organ transplantation has progressed dramatically over the last 50 years; however, rejection still remains one of the barriers to successful transplantation. Immunological processes underlying the mechanisms of rejection are well described and numerous pharmacological agents exist to help suppress a recipient's immune system in order to prolong graft survival. Furthermore, clinician decisions and actions during both the work-up of a potential transplant recipient and in the perioperative phase can impact upon the immunological status of an individual and the likelihood of successful solid organ transplantation. In this article we aim to describe the key processes involved in solid organ immunology and their relevance in anaesthetic practice.     

The use and value of procalcitonin in solid organ transplantation

Procalcitonin (PCT) has been increasingly used as a biomarker of bacterial infection and as a tool to guide antimicrobial therapy, especially in lower respiratory tract and bloodstream infections. Despite its increased use, data in patients with solid organ transplants are limited. Even without the presence of infection, PCT increases as a result of surgical procedures during transplantation, implantation of devices, and use of induction immunosuppressive therapy. The risk of infection is also higher in solid organ transplant recipients when compared to the general population. Monitoring PCT in the early post‐transplant period seems to be a promising method for early detection of infectious complications. It has been shown that elevated PCT levels after one wk of transplantation are correlated with infectious complications. PCT may be a useful adjunctive biomarker that may improve early identification and guide appropriate treatment of infection or rejection, with the potential to further improve clinical outcomes. The use of serial PCT measurements may be more reliable than single values. It is important to recognize which factors may lead to PCT increases in the post‐transplantation period, which in turn will help understand the kinetics and utility of this biomarker in this important patient population.     

Clinical Predictors of Relapse after Treatment of Primary Gastrointestinal Cytomegalovirus Disease in Solid Organ Transplant Recipients

Primary gastrointestinal cytomegalovirus (CMV) disease after solid organ transplantation (SOT) is difficult to treat and may relapse. Herein, we reviewed the clinical records of CMV D+/R− SOT recipients with biopsy-proven gastrointestinal CMV disease to determine predictors of relapse. The population consisted of 26 kidney (13 [50%]), liver (10 [38%]) and heart (3 [12%]) transplant recipients who developed gastrointestinal CMV disease at a median of 54 (interquartile range [IQR]: 40–70) days after stopping antiviral prophylaxis. Except for one patient, all received induction intravenous ganciclovir (mean ± SD, 33.8 ± 19.3 days) followed by valganciclovir (27.5 ± 13.3 days) in 18 patients. Ten patients further received valganciclovir maintenance therapy (41.6 ± 28.6 days). The median times to CMV PCR negativity in blood was 22.5 days (IQR: 16.5–30.7) and to normal endoscopic findings was 27.0 days (IQR: 21.0–33.5). CMV relapse, which occurred in seven (27%) patients, was significantly associated with extensive disease (p = 0.03). CMV seroconversion, viral load, treatment duration, maintenance therapy and endoscopic findings at the end of therapy were not significantly associated with CMV relapse. In conclusion, an extensive involvement of the gastrointestinal tract was significantly associated with CMV relapse. However, endoscopic evidence of resolution of gastrointestinal disease did not necessarily translate into a lower risk of CMV relapse.     

Outcomes of Clostridium difficile infection in recipients of solid abdominal organ transplants

Knowledge of outcomes of Clostridium difficile infection (CDI) in solid organ transplant (SOT) recipients is limited. To evaluate this population, we undertook a retrospective cohort study of all recipients of kidney and liver transplants diagnosed with CDI at a single center over 14 yr. Data pertaining to all episodes of CDI were collected. Multivariate analysis using logistic regression was performed to determine independent predictors of clinical cure. Overall, 170 patients developed 215 episodes of CDI. Among these patients, 162 episodes (75%) were cured, and in 103 episodes (48%), patients were cured within 14 d. In a multivariate analysis, lack of clinical cure at 14 d was predicted by recurrent episode (0.21, 95% CI 0.06–0.72, p = 0.0128), treatment with vancomycin (OR 0.27, 95% CI 0.1–0.74, p = 0.011), vasopressor support (OR 0.23, 95% CI 0.07–0.76, p = 0.0161), and CDI before the year 2004 (OR 0.44, 95% CI 0.2–0.98, p = 0.0446). The latter three factors are likely markers for severity of illness. In this cohort, 13 patients (8%) died during hospitalization, and 49 patients (29%) died within one yr. No deaths were attributed to CDI. Recurrent episode was a major predictor of treatment failure, suggesting that research into development of therapeutic options for recurrent disease is needed.     

Acute appendicitis after solid organ transplantation

Appendicitis has rarely been reported following solid organ transplantation and never following liver transplantation. We reviewed records of all patients who received solid organ transplants at UCLA between 1989 and 2002 and subsequently underwent appendectomy for presumed acute appendicitis. Of nearly 8000 transplant patients, 17 (nine male, eight female) subsequently underwent appendectomy for presumed acute appendicitis. Average age at appendectomy was 37 yrs (range 6-73 yrs). Organ transplants included liver (seven patients), heart (four), kidney (three), kidney-pancreas (two), and heart-kidney (one). The mean interval from transplant to appendectomy was 1064 d (16-2977). Presenting symptoms and signs included abdominal pain in 16 patients (94%); nausea and or vomiting in 15 (88%); right lower quadrant tenderness in 16; and leukocytosis (WBC > 10 000) in 13 (76%). Mean interval from presentation to appendectomy was 0.94 d (range 0-4). Computed tomography (CT) was performed in 16 patients and showed signs of acute appendicitis in 15. Open technique was used in all patients, preceded by laparoscopy in one. Pathology showed appendicitis in 15 patients (one with perforation), serositis in one, and a normal appendix in one. Mean duration of hospitalization was 7 d (range 1-20). Complications occurred in four patients (24%) and included intra-abdominal abscess requiring percutaneous drainage, ventral hernia, small bowel obstruction, and hematuria in one patient each. There were no deaths and no cases of acute rejection during hospitalization. Average length of follow-up was 712 d (range 3-2492). We conclude that appendicitis is relatively rare following solid organ transplantation. CT facilitates prompt diagnosis. The clinical presentation is similar to that of non-transplant patients, but complications are more frequent, and hospitalization is longer.     

Neurologic complications after solid organ transplantation

Neurologic complications are common after solid organ transplantation and are associated with significant morbidity. Approximately one-third of transplant recipients experiences neurologic alterations with incidence ranging from 10% to 59%. The complications can be divided into such of those common to all types of transplant and others of those specific to transplanted organ. The most common complication seen with all types of transplanted organ is neurotoxicity attributable to immunosuppressive drugs, followed by seizures, opportunistic central nervous system (CNS) infections, cardiovascular events, encephalopathy and de novo CNS neoplasms. Amongst immunosuppressants, calcineurin inhibitors are the main drugs involved in neurotoxicity, leading to complications which ranges from mild symptoms, such as tremors and paresthesia to severe symptoms, such as disabling pain syndrome and leukoencephalopathy. Neurologic complications of liver transplantation are more common than that of other solid organ transplants (13–47%); encephalopathy is the most common CNS complication, followed by seizures; however, central pontine myelinolysis can appear in 1–8% of the patients leading to permanent disabilities or death. In kidney transplanted patients, stroke is the most common neurologic complication, whereas cerebral infarction and bleeding are more typical after heart transplantation. Metabolic, electrolyte and infectious anomalies represent common risk factors; however, identification of specific causes and early diagnosis are still difficult, because of patient's poor clinical status and concomitant systemic and metabolic disorders, which may obscure symptoms.     

Clinical outcome of norovirus infection in renal transplant patients

Transplant patients are at increased risk for developing severe norovirus (NoV) infections with secondary complications such as rejection episodes and acute transplant failure. This single‐center retrospective study included all kidney transplant patients tested positive for NoV RNA between January 2007 and December 2011. Data were compared to a control group of 528 kidney transplant patients without NoV infection. Sixty‐five kidney transplant patients were recorded NoV RNA positive. Of these, 26 patients (40%) presented with acute transplant failure (AKI). In 43 patients (66.2%), dose reduction in immunosuppression was performed, and of 22 patients receiving tacrolimus, four patients (18.2%) showed toxic trough levels above 15 ng/mL at time of diagnosis. In three patients (4.6%), indicated therapeutic procedures had to be postponed due to prolonged severe diarrhea. Ten patients (15.4%) developed chronic NoV infection. One‐year patient and graft survival in NoV patients and controls was 92.3% and 96.4%, respectively (n.s.). Compared to controls, eGFR was already significantly lower before NoV infection and loss of eGFR relative to baseline over 12 and 36 months was significantly higher in NoV‐infected patients. In particular, patients initially presenting with AKI experienced a long‐term loss of transplant function. Risk factors for NoV infection were immunosuppression containing steroids and antirejection therapy.     

Quality of life after solid organ transplantation

In patients who receive a solid organ transplant, interest at present centers on long-term results and is directed more toward patient and graft survival and health-related quality of life (HRQoL). Improvement in HRQoL after receiving a transplant is a fact; but the studies should be treated with caution, as only some of them correct the results for different confounding variables and the fluctuations of the case-mix variables in the different samples and treatment groups counsel prudence.Several factors, especially those attributable to medication, affect the HRQoL of transplanted patients; and their identification and evaluation open up new possibilities for actions designed to modify their impact and improve HRQoL. In addition, some variables predict HRQoL in solid organ transplanted patients.There exist several modalities of economic evaluation. Cost-utility analysis is one of these and uses years of life adjusted for quality for measuring the results in nonmonetary units, simultaneously incorporating the increment in the quantity of life (reduction in mortality) and the increase in quality of life.     

New-onset diabetes mellitus after solid organ transplantation

New-onset diabetes mellitus is a common complication of solid organ transplantation and is likely to become even more common with the current epidemic of obesity in some countries. It has become clear that both new-onset diabetes and prediabetic states (impaired fasting glucose and impaired glucose tolerance) negatively influence graft and patient survival after transplantation. This observation forms the basis for recommending meticulous screening for glucose intolerance before and after transplantation. Although a number of clinical factors including age, weight, ethnicity, family history, and infection with hepatitis C are closely associated with the new-onset diabetes mellitus, immunosuppression with corticosteroids, calcineurin inhibitors and possibly sirolimus plays a dominant role in its pathogenesis. Management of new-onset diabetes after transplantation generally conforms to the guidelines for treatment of type 2 diabetes mellitus in the general population. However, further studies are needed to determine the optimal immunosuppressive regimens for patients with this disorder.     

Simultaneous pancreas and kidney transplantation from organ donation after cardiac death

Background: The concept of organ donation after cardiac death (DCD) historically precedes the current practice of organ procurement from heartbeating donors meeting the brainstem death criteria. DCD has not gained widespread interest, however, due partly to initial fears that transplantation of such organs leads to suboptimal outcome. Methods: Available data on long‐term outcomes following simultaneous pancreas and kidney transplant (SPK) from DCD donors were reviewed, and it was found that the long‐term outcome is comparable to SPK from heartbeating donors. Australia’s first SPK from a DCD donor was performed. Results: The patient received a kidney and a pancreas from a young healthy donor after cardiac death, and at the time of writing was well with functioning grafts. Conclusion: SPK from donation after cardiac death is safe and should continue to be available for patients in need.     

实体器官移植术后隐球菌病的研究进展

隐球菌病是实体器官移植术后最主要的致死性真菌感染性疾病,大多数伴有中枢神经系统侵犯。由于临床症状缺乏特异性,可能导致延误诊断,预后不佳,而早期诊断和充分有效的抗真菌治疗是改善移植受体隐球菌病预后的主要策略。本文对隐球菌病的流行病学、发病机制、临床表现、诊断方法、防治措施,结合我国器官移植实际情况进行综述。     

The use of statins after solid organ transplantation

Sir, The survival benefits and safety associated with statin therapyare well established. However, statin use may be complicatedby myositis and, on rare occasions, rhabdomyolysis and its sequelae.The recent voluntary withdrawal of cerivastatin from the markethas prompted investigators to question the     

肾移植术后慢性腹泻的临床诊治分析

目的  探讨肾移植术后患者慢性腹泻的诊治方案。方法  回顾性分析2007年1月至2014年6月在西京医院泌尿外科实施同种异体肾移植术并规律随访的353例患者中发生慢性腹泻者的临床资料。观察肾移植术后慢性腹泻的发生情况(发生率、发生时间、病程、并发症),记录慢性腹泻患者的一般状况与辅助检查指标变化(体重指数、贫血情况、辅助检查指标),以及患者的治疗经过与预后。结果  353例肾移植患者中15例(4.2%)发生慢性腹泻,给予积极对症、病因治疗的时间为(15±7)d,腹泻期间死亡2例(分别死于消化道出血和严重低钾血症猝死),其余患者的腹泻均治愈。13例患者随访期间预后良好5例,死亡2例(均死于肺部感染),移植肾失功5例,移植肾功能不全1例。结论  肾移植术后慢性腹泻病因复杂,应积极对症、病因治疗,合并严重并发症者预后不良。     

Direct oral anticoagulant considerations in solid organ transplantation: A review

For more than 60 years, warfarin was the only oral anticoagulation agent available for use in the United States. In many recent clinical trials, several direct oral anticoagulants (DOACs) demonstrated similar efficacy with an equal or superior safety profile, with some other notable benefits. The DOACs have lower inter‐ and intrapatient variability, much shorter half‐lives, and less known drug‐drug and drug‐food interactions as compared to warfarin. Despite these demonstrated benefits, the use of DOACs has not gained uniform acceptance because of lack of supportive data in special patient populations, including recipients of solid organ transplants maintained on immunosuppression. This review describes the properties of several novel DOACs including their pharmacology and mechanisms of action as they relate to use among solid organ transplant recipients. We have particularly focused on (i) dosing in patients with impaired renal and hepatic function; (ii) considerations for drug‐drug interactions with immunosuppressive medications; and (iii) management of the anticoagulated patients at the time of unplanned surgery. The risks and benefits of the use of DOACs in solid organ transplant recipients should be carefully evaluated prior to the introduction of these agents in this highly distinct patient population.