International Journal of Organ Transplantation Medicine最新文献

Background: Interferon regulatory factors (IRFs) can play a critical role in the regulation of many facets of innate and adaptive immune responses through transcriptional activation of type I interferons, other proinflammatory cytokines, and chemokines. However, their roles in transplantation immunity still remain to be elucidated.

Objective: To evaluate the time course of mRNA expression of all 9 members of IRFs family of transcription factors during liver allograft acute rejection.

Methods: Blood samples of 19 patients with autoimmune hepatitis receiving liver transplants were collected on days 1, 3, 5, and 7 post-transplantation. The patients were followed for 6 months after transplantation and divided into two groups of acute rejection (AR) (n=4) and non-acute rejection (non-AR) (n=15).

Results: All of the studied transcription factors were down-regulated in AR-group on days 3, 5, and 7 post-transplantation compared to non-AR group. The mean±SEM IRF5 on day 7 post-transplantation was significantly (p=0.005) lower in AR-group than in non-AR group (0.7±0.21 vs. 1.91±0.27, respectively); expression of other IRFs family members was not significantly different between the two groups on days 3, 5, and 7 post-transplantation.

Conclusion: IRF5 may have an important role during the acute rejection of liver transplants.

Background: Leflunomide is an immunosuppressive agent commercialized for treatment of rheumatoid arthritis. Because of its immunosuppressive and possible antiviral properties, leflunomide has been evaluated in some case series of BKVAN with favorable results, mostly in adult patients. Leflunomide targeted levels are usually between 50 and 100 mg/L in kidney transplant adult patients. Data in pediatric population are scarce.

Objective: To assess the effect of leflunomide on BKvirus in kidney-transplanted children.

Methods: Therapeutic drug monitoring of leflunomide is routinely performed by measuring its active metabolite, teriflunomide, using a simple HPLC-UV method. Pediatric kidney transplant patients with at least one teriflunomide sample between 2010 and 2017 were retrospectively included in this study. Viremia control was defined as undetectable BK viremia or a decrease of more than 1 log in the viral load from the baseline after two months of treatment. Adverse events were recorded.

Results: A total of 7 patients from 3 centers was included. 6 were only kidney transplant recipients; 1 was a lung-kidney transplant recipient with cystic fibrosis. All patients reported high load BK viremia but none developed BKVAN. For 67% of the patients, complete BK viral clearance was observed during leflunomide treatment with drastic immunosuppressive therapy reduction. Mycophenolate was indeed discontinued in almost all patients. Of note, leflunomide concentrations were significantly higher when viremia was controlled. Only 33% of the observed concentrations were >40 mg/L. The patient with cystic fibrosis had lower concentrations with higher drug doses. No hepatotoxicity was observed in this study and no patient experienced graft rejection. Leflunomide was suspected to cause hemolytic anemia and one patient experienced biological pancreatitis.

Conclusion: This study evidenced the wide interindividual variability of the exposure and supported the routine practice of leflunomide with a suggested target level of 30-40 mg/L in pediatric kidney transplanted patient. However, because of the very limited number of patients in our series, further investigations are needed to validate this suggestion.

Granulomatosis with polyangitis (GPA) is characterized by necrotizing granulomatosis of the upper and lower respiratory tract and glomerulonephritis. If GPA does not respond to appropriate management, it might result in end-stage renal disease, which may remit the disease severity. The overall impression is that immunosuppression following renal transplantation would further subside the vasculitis. However, several studies have shown that systemic vasculitis recur in 25% of patients following renal transplantation. This may indicate the perplexing nature of the immune system. One of the key factors in prevention of relapse of GPA is following up of patients by careful immunosuppressive dose adjustment and regular measurement of biomarkers for vasculitis. Herein, we describe an interesting case of biopsy-proven GPA who had a complex long history of several post-transplantation relapses in different organs with anti-neutrophil cytoplasmic antibodies seroconversion. This case emphasizes that vasculitis in particular GPA can mimic various diseases depending on which vessels and organs are affected by the inflammation and is one of the reversible causes of failure of transplanted kidney. Bearing the diagnosis in mind as one of the potential differential diagnoses of failure of renal transplantation will lead to early diagnosis and treatment of recurrent GPA.

Background: Estimation of the amount of blood products required during liver transplantation can help provision of adequate blood supply, minimize transfusion-associated complications, and plan for preventive measures in high risk patients.

Objective: To investigate independent predictors of peri-operative blood product transfusion and its impact on short-term survival of liver transplant recipients.

Methods: In a cross-sectional study, old charts of patients who underwent liver transplantation between March 2003 and March 2013 at Namazi Hospital, Shiraz, Iran, were reviewed. The mean amount of blood product utilized during surgery and hospital stay and the related factors, including demographic characteristics, pre-transplant laboratory data, pre-transplant clinical data, operation data, and post-transplantation data were recorded.

Results: We studied 1198 patients who underwent liver transplantation. The mean±SD amounts of red blood cells, fresh frozen plasma, and platelet transfusion during surgery and hospital stay were 2.67±3.5, 2.06±3.8, and 1.6±3.8 units, respectively. The mortality rate was significantly higher in patients who received high amounts of blood products (p<0.001). The mean amount of blood products' utilized during operation was significantly (p<0.001) decreased from 2003 to 2013.The mean amount of packed cell usage during operation and hospital stay was significantly (p<0.001) correlated with age, technique of surgery, serum albumin level, cirrhosis, blood urea nitrogen, length of operation, and prothrombin time.

Conclusion: Pre-operative factors may predict blood transfusion requirements in patients undergoing liver transplantation. Therefore, evaluation of patients before operation should be considered to provide adequate blood supply and minimize transfusion-associated complications. Understanding pre-operative factors associated with rate of transfusion may help us to best utilize the limited available blood resources.

Concomitant replacement of the ascending aorta and heart transplantation are an infrequent procedure. This procedure was most often performed in patients with Marfan syndrome, however, it has its own technical difficulties. Hereby, we report on combined heart transplantation and aortic root replacement using donor's ascending aorta in a 25-year-old man diagnosed with dilated cardiomyopathy and ascending aorta aneurysm. This procedure was successful and beneficial to patients with aortopathy who are candidates for heart transplantation.

Background: After organ transplantation, many patients have diverse experiences; they face many changes in the physical and emotional aspects of their life. Patients' understandings of the post-transplantation period influence their adaptation to the changes. There is a need to improving the knowledge of patients' unique experiences of post-transplantation period and the changes occur in their life.

Objective: To explore the experiences of organ recipients in the post-transplantation period.

Methods: In a qualitative research using a hermeneutical phenomenological approach, data were collected from April 2015 to June 2016. Participants were consisted of 15 patients who received organ chosen using a purposive sampling method. In-depth semi-structured interviews were held with them. The collected data were analyzed using Diekelmann's hermeneutical analysis approach.

Results: The data analyses led to the development of 3 main themes and 17 subthemes as "back from the grave" with the subthemes of "organ as the God's deposit," "God as the source of life," and "new life"; "chapter of prosperity" with the subthemes of "the spring of the body," "recovery," "peace and joy," "benevolent and good behavior," "renewal," "opportunity of being together again," "golden age," "positive perspective," "the sense of normality," "the return of health," and "spiritual evolution"; and "the fall" with the subthemes of "a lack of energy," "the mirage of transplantation," and "hell on the earth."

Conclusion: The patients had diverse experiences of the post-transplantation period, which varied from the feeling of exhilaration and youth to losing energy and the wish for not undertaking organ transplantation.

Emergency liver transplantation (LT) for acute liver failure (ALF) is a life-saving treatment. Occurrence of this situation in the same patient twice is very rare. Herein, we describe a patient who underwent two emergency LTs for ALF, both from living donors. When she was 26 years old, she underwent a right lobe living donor LT (LDLT) from her sister for ALF due to use of herbal weight loss medications. The next 3 years were uneventful but another ALF developed during a terminal stage pregnancy (37^th week). Despite medical treatment, her liver functions worsened, and the baby was delivered by caesarean section. The second time, her brother was the donor and she recovered after the emergency right lobe re-LDLT. Both patient and baby were well at the 2-month follow-up. As far as we know, there is no reported similar case, and we concluded that LDLT is a paramount treatment option for both primary and secondary ALFs.

Tissue engineering and cell-based therapies are promising therapeutic approaches in structural and functional defects of the trachea. Researchers have focused on these approaches to overcome the complications related to such diseases. Patients exposed to mustard gas suffer from massive damage to the respiratory system. Current treatment plans are only palliative and include anti-inflammatory drugs, broncholytics, long-acting β₂-agonists, and inhaled corticosteroids. As mustard gas exposure leads to chronic airway inflammation, it seems that tracheobronchomalacia, because of chronic inflammation and weakness of the supporting cartilage, is an important factor in the development of chronic and refractory respiratory symptoms. The previous studies show that regenerative medicine approaches have promising potential to improve the life quality of patients suffering from tracheal defects. It seems that the engineered tracheal graft may improve the respiratory function and decrease symptoms in patients who suffer from asthma-like attacks due to mustard gas exposure. There are several successful case reports on the transplantation of stem cell-based bioartificial grafts in structural airway diseases. Therefore, we hope that the reconstruction of tracheobronchial structure can lead to a decrease in respiratory difficulties in mustard gas-exposed patients who suffer from tracheomalacia. In the present review, we summarize the main aspects of tracheal tissue engineering and cell-based therapies and the possibilities of the application of these approaches in mustard gas-exposed patients.

Background: Histopathologic changes of post-reperfusion liver needle biopsies in patients with liver transplantation have rarely been reported and most of the previous reports have been in less than 200 cases.

Objective: In this study, we evaluated 408 post-perfusion liver needle biopsies for the histopathologic changes attributable to reperfusion injury and compared them with early post-liver transplantation outcome, to find out the value of these findings.

Methods: In 408 patients who underwent liver transplantation, post-perfusion liver needle biopsy was taken within one hour of vascular anastomosis. The specimens were fixed in formalin and evaluated by a hepatopathologist blinded to the outcome of transplantation for hepatocellular necrosis, apoptosis, ballooning degeneration, cholestasis, neutrophilic infiltration, and steatosis. These were compared with cold and warm ischemic time, levels of AST, ALT, alkaline phosphatase, bilirubin, presence or absence of rejection, and duration of hospital stay.

Results: Hepatocellular ballooning degeneration, apoptosis, and necrosis did not show any significant correlations with early post-transplantation outcome and reperfusion injury. However, presence of neutrophilic infiltration in the post-reperfusion liver biopsy was well correlated with liver function tests and other clinical and paraclinical findings. Presence of steatosis in post-reperfusion liver needle biopsy was also associated with high liver function tests and long hospital stay.

Conclusion: Presence of PMN leukocytes in the post-perfusion liver needle biopsy of transplanted liver is associated with poor early outcome and reperfusion injury, so it should be recorded in the pathology report and should be considered a high-risk sign for the clinicians.

Background: Acute cellular rejection (ACR), a reversible process, can affect the graft survival.

Objective: To evaluate the relation between ACR and clinical factors in recipients of allograft liver transplantation.

Methods: 47 recipients of liver were consecutively enrolled in a retrospective study. Their information were retrieved from their medical records and analyzed.

Results: Of the 47 recipients, 38 (81%) experienced acute rejection during 24 months of the transplantation. None of the studied factors for occurring transplant rejection, i.e., blood groups, sex, age, familial history of disease, receiving drugs and blood products, type of donor, Child score, and Child class, was not found to be significant.

Conclusion: During a limited follow-up period, we did not find any association between ACR and suspected risk factors.