Management Of Post-transplant Complications Research Articles

Towards Allograft Longevity: Leveraging Omics Technologies to Improve Heart Transplant Outcomes.

Heart transplantation (HT) remains the optimal therapy for patients living with end-stage heart disease. Despite recent improvements in peri-transplant management, the median survival after HT has remained relatively static, and complications of HT, including infection, rejection, and allograft dysfunction, continue to impact quality of life and long-term survival. Omics technologies are becoming increasingly accessible and can identify novel biomarkers for, and reveal the underlying biology of, several disease states. While some technologies, such as gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA), are routinely used in the clinical care of HT recipients, a number of emerging platforms, including pharmacogenomics, proteomics, and metabolomics, hold great potential for identifying biomarkers to aid in the diagnosis and management of post-transplant complications. Omics-based assays can improve patient and allograft longevity by facilitating a personalized and precision approach to post-HT care. The following article is a contemporary review of the current and future opportunities to leverage omics technologies, including genomics, transcriptomics, proteomics, and metabolomics in the field of HT.

Follow-Up of 29 Years of Renal Transplant - A Case Report

Introduction: With the increasing longevity of renal transplant patients, the long-term morbidities of these patients have also increased. Thus, a multidisciplinary team is needed to follow-up on these cases and adequately detect and manage the complications. Furthermore, pregnancy rates have increased in this set of patients. Case Report: In this report, we discuss briefly the posttransplant period of a female patient who had spontaneous conception with two live births and had complications such as recurrent tuberculosis, skin cancers, and chronic diarrhea. However, the patient is leading an active life even after 29 years posttransplant. Conclusion: Pregnancy is less reported in renal transplant patients, but it needs a multidisciplinary approach to the management. Furthermore, early detection and management of posttransplant complications are of utmost importance and needs extreme vigilance and care.

Estimated Renal Metabolomics at Reperfusion Predicts One-Year Kidney Graft Function.

Renal transplantation is the gold-standard procedure for end-stage renal disease patients, improving quality of life and life expectancy. Despite continuous advancement in the management of post-transplant complications, progress is still needed to increase the graft lifespan. Early identification of patients at risk of rapid graft failure is critical to optimize their management and slow the progression of the disease. In 42 kidney grafts undergoing protocol biopsies at reperfusion, we estimated the renal metabolome from RNAseq data. The estimated metabolites’ abundance was further used to predict the renal function within the first year of transplantation through a random forest machine learning algorithm. Using repeated K-fold cross-validation we first built and then tuned our model on a training dataset. The optimal model accurately predicted the one-year eGFR, with an out-of-bag root mean square root error (RMSE) that was 11.8 ± 7.2 mL/min/1.73 m2. The performance was similar in the test dataset, with a RMSE of 12.2 ± 3.2 mL/min/1.73 m2. This model outperformed classic statistical models. Reperfusion renal metabolome may be used to predict renal function one year after allograft kidney recipients.

SY12-3 Hematopoietic transplantation for AML

Hematopoeitic stem cell transplantation (HSCT) has been an important modality for the treatment and cure of patients with high risk acute myeloid leukemia (AML). Improved stratification of AML patients with genetic markers (e.g. FLT3, CEBPA, NPM1 and others) has allowed better selection of patients for HSCT. Outstanding results from cord blood and haploidentical transplants have also increased the availability of donors for transplantation. Novel drugs like hypomethylating agents, BCL-2 inhibitors and various FLT 3 inhibitors have also improved the remission status of patients before transplant while also facilitating post-transplant consolidation and maintenance to improve disease control. Transplantation of older patients has also been made possible by the reduction of transplant-related mortality and morbidity through improved pre-transplant conditioning regimens and better management of post-transplant complications. Cellular engineering has also made possible the expansion of hematopoietic stem and progenitor cells to improve the results of HSCT while genetic engineering and expansion of cellular subsets has facilitated targeted therapy against viruses and leukemia. The outcomes of HSCT for the treatment of AML has improved significantly due to the above measures and HSCT remains a mainstay in the treatment of this disease.

Posttransplant Complications: Biliary and Vascular

Since it was first described, the overall patient and graft survival after liver transplant have improved with advances in immunosuppression and surgical and anesthetic techniques. Despite this improvement, there continues to be both biliary and vascular complications associated with this life-saving operation, which can lead to further procedures, reoperation, and retransplant. Advances in endoscopic and percutaneous techniques have had a significant impact on the perioperative management of posttransplant complications, resulting in a reduction in reoperations and retransplants. Changes in intraoperative management with the use of thrombolytic therapy have allowed for the expansion of the donor pool, allowing the use of donation after cardiac death with increased safety and decreased risk of ischemic biliary tract injury. This article serves to highlight the vascular and biliary complications following transplant, their etiology, diagnosis, and management. This review contains 9 figures, 1 table, and 33 references. Key Words: bile leak, biliary stricture, deceased donor liver transplant, donation after brain death (DBD), donation after cardiac death, hepatic artery thrombosis, ischemic cholangiopathy, living donor liver transplant, portal vein thrombosis, thrombolytic therapy, venous outflow obstruction.

Posttransplant Complications: Biliary and Vascular

Since it was first described, the overall patient and graft survival after liver transplant have improved with advances in immunosuppression and surgical and anesthetic techniques. Despite this improvement, there continues to be both biliary and vascular complications associated with this life-saving operation, which can lead to further procedures, reoperation, and retransplant. Advances in endoscopic and percutaneous techniques have had a significant impact on the perioperative management of posttransplant complications, resulting in a reduction in reoperations and retransplants. Changes in intraoperative management with the use of thrombolytic therapy have allowed for the expansion of the donor pool, allowing the use of donation after cardiac death with increased safety and decreased risk of ischemic biliary tract injury. This article serves to highlight the vascular and biliary complications following transplant, their etiology, diagnosis, and management. This review contains 9 figures, 1 table, and 33 references. Key Words: bile leak, biliary stricture, deceased donor liver transplant, donation after brain death (DBD), donation after cardiac death, hepatic artery thrombosis, ischemic cholangiopathy, living donor liver transplant, portal vein thrombosis, thrombolytic therapy, venous outflow obstruction.

Exocrine drainage of the transplanted pancreas: A review

Pancreas transplant is an important treatment option for insulin dependent diabetic patients as it may result in physiologic euglycemia. Improvements in surgical technique, graft preservation, immunosuppression, diagnosis and management of rejection, and management of post-transplant complications have led to improved patient survival.There are several technical variables to consider when performing a pancreas transplant. One is the type of exocrine drainage to be used. The most common types of exocrine drainage are enteric or bladder drainage. Gastric- exocrine drainage has also been recently introduced. The most commonly cited complications associated with bladder drainage include metabolic complications, urologic complications and the need for enteric conversion.Many complications related to bladder drainage can be managed non-operatively with Foley catheter drainage. For those complications that cannot be managed in this manner, enteric conversion is an option. Complications associated with enteric drainage include anastomotic leak and intra-abdominal abscess, although at rates lower than cited in the early literature on the topic. Bladder drainage of exocrine secretions and enteric drainage of exocrine secretions, or a staged procedure with bladder drainage followed by indicated or elective enteric conversion are reasonable options for drainage of the exocrine secretions of the pancreas. Gastric-exocrine drainage is a promising therapy deserving of future exploration.

Oral Session: Liver IV: Management of Posttransplant Complications

Pediatric TransplantationVolume 21, Issue S1 p. 36-38 Oral Session: Liver IV: Management of Posttransplant ComplicationsFree Access Oral Session: Liver IV: Management of Posttransplant Complications First published: 05 May 2017 https://doi.org/10.1111/petr.12968Citations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume21, IssueS1Special Issue: IPTA 9th Congress on Pediatric TransplantationMay 2017Pages 36-38 RelatedInformation

Interstitial Lung Disease and Lung Transplantation

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias and carries the worst prognosis. Currently the best treatment option is lung transplantation. Historically patients with IPF had poor outcomes following referral for lung transplant due to high waiting-list mortality. The introduction of the lung allocation score in the United States in 2005 has reduced 1 year waiting-list mortality from 21% to 11% and also led to IPF becoming the most common diagnosis for lung transplantation. Although prioritizing all patients with IPF on the waiting list has led to a dramatic decline in waiting-list mortality, further improvements may be made by prioritizing which patients with IPF should be transplanted, with an emphasis on 6-minute walk testing, biomarkers, and the presence of pulmonary hypertension rather than traditional pulmonary function tests. The choice of surgical procedure and the prediction and management of posttransplant complications may also influence long-term outcomes.

Pediatric intestinal transplantation: Literature review 2006-2007

: The field of intestinal transplantation has rapidly progressed over the last few years, with greatly improved patient and graft survival rates. Pediatric patients actually comprise the majority of individuals referred for intestinal transplantation; therefore, most of the current literature on this subject is centered on such group of patients. Issues pertinent to patient selection, indications for transplantation and management of post-transplant complications run parallel to those issues of appropriate immunosuppressive protocols and avoidance/treatment of rejection, which is still one of the biggest causes of morbidity and mortality. This manuscript reviews what the authors view as the most innovative contributions in the field of intestinal transplantation over the last two yr (2006–2007). This review is by no means exhaustive but might serve as a starting point for those clinicians interested in the field.

Transmission of Chromosomally Integrated HHV6 by Allogeneic Peripheral Blood Stem Cell Transplantation Associated with the Development of a Fatal Macrophage Activation (Haemophagocytic) Syndrome.

It is estimated that at least 1% of the UK population have chromosomal integration of HHV6 leading to persistently high levels of detectable viral DNA (Clark DA et al, JID 2006: 193, p912–916). As far as we are aware transmission of integrated HHV6 by allogeneic stem cell transplantation has been described in the literature on only one previous occasion and this was not associated with disease (Clark DA et al, JID 2006: 193, p912–916). Indeed it remains controversial as to whether HHV6 ever causes disease in the post transplant setting. A 35-yr-old male with a past history of treated Hodgkins lymphoma (HL) developed stage 4 diffuse large B-NHL (DLBL). He achieved a CR with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) + rituximab × 8 cycles but subsequently relapsed. Following salvage chemotherapy with IVE (ifosfamide, etoposide, epirubicin) + rituximab × 3 cycles he underwent a fully HLA matched sibling allogeneic peripheral blood stem cell transplant in second CR of the DLBL using BEAM (carmustine, etoposide, cytarabine, melphalan) + alemtuzumab conditioning. On day +32 he presented with fever, pneumonitis and pancytopenia. Bone marrow examination revealed haemophagocytosis of red cells and platelets. He had a mild coagulopathy and grossly elevated ferritin (63,303 ug/l). A diagnosis of macrophage activation syndrome (MAS) probably secondary to infection was made. Cultures of blood, urine and broncho-alveolar lavage (BAL) were negative apart from HHV6 levels of 62,000 DNA copies/ml in serum. There was no clinical or radiological evidence of relapse of HL or DLBL and no evidence of CMV reactivation. He deteriorated despite intensive care unit support and treatment with broad spectrum antibiotics, aciclovir, cidofovir, caspofungin and cyclosporin-A. He showed slight improvement with high dose steroids but died on day +78. Further investigations revealed the patient was negative for serum HHV6 immediately prior to transplantation whilst his donor had very high levels of serum HHV6 (750,000 DNA copies/ml) suggestive of chromosomal integration (Ward KN et al, J Clin Microbiology 2006: 44, p1571–1574). It is, therefore, highly likely that HHV6 was transmitted via the allogeneic stem cell transplant. The case raises some difficult issues in relation to the management of post transplant complications that maybe virally driven. Chromosomally integrated HHV6 is not thought to cause active infection and it has been suggested, therefore, that post-transplant patients demonstrating high levels of HHV6 should be investigated for chromosomal integration in the donor and if present not subsequently treated with potentially toxic anti-viral drugs. However, HHV6 has been associated with MAS in the non transplant setting. In our case HHV6 was the only identifiable infectious agent during this severe illness. Given the association of HHV6 with MAS and the uncertain pathogenecity of integrated HHV6 in the context of post transplant immune dysregulation, this scenario makes diagnosis and treatment challenging.

The economics and ethics of kidney transplantation: perspectives in 2006

The field of kidney transplantation has made impressive progress, which has led to marked improvements in both patient and allograft survival. The economic and ethical consequences of these advances have recently garnered increasing attention in the medical literature. This review highlights key articles published in 2005 and 2006. Major areas of focus in the health economics literature pertaining to kidney transplantation include the most cost-effective strategies for immunosuppressive therapies, the management of posttransplant complications, and the optimal utilization of the current pool of deceased-donor kidneys. Ethical challenges include various aspects of living donation, strategies to expand the donor pool, and the impact of financial policies for immunosuppressive agents on long-term patient and allograft survival. Given the rising demand for kidney transplantation within a setting of scarce resources, the economic and ethical dimensions of transplant medicine are of increasing interest to patients, providers, and payers. Research in these areas will help uncover ways to utilize this important medical technology in the most ethical and cost-effective manner.

Acute renal failure due to adenovirus-associated obstructive uropathy and necrotizing tubulointerstitial nephritis in a bone marrow transplant recipient

Management of post-transplant complications caused by severe adenoviral infection remains a major therapeutic challenge. A 17-year-old male who had undergone bone marrow transplantation for the treatment of acute lymphoblastic leukemia developed complete anuria following hemorrhagic cystitis 34 days after the transplant procedure. The computed tomogram scan revealed bilateral hydronephrosis, indicating acute renal failure because of obstructive uropathy. The emergency procedure of percutaneous nephrostomy caused massive bleeding in the left kidney, which eventually required a nephrectomy. Adenovirus-positive severe necrotizing tubulointerstitial nephritis was the histopathological diagnosis. Post-transplant acute renal failure because of hydronephrosis, which could be complicated by adenovirus-induced renal parenchymal disease, is of great concern and may cause significant problems with interventional treatment.

8 Imaging: focus on hepatocellular carcinoma and liver transplantation

The choice of management for the patient with HCC hinges on precise localization and staging of the disease process. All the major imaging modalities are employed to achieve this end. US is frequently the initial means of detection of the lesion. Since percutaneous needling may lead to tumour dissemination, the temptation to proceed to imaging-guided biopsy should be resisted until a full evaluation has been completed and it is clear that neither curative surgery nor transplantation is a therapeutic option. CT scanning is considered to be superior to ultrasound both in detection and staging of the disease. A variety of modifications to the technique, including CT arterio-portography and lipiodol-CT, is used to obtain optimum results. The role of MRI has not yet been established but initial results suggest that this may be the optimum means of scanning the patient following percutaneous or intra-arterial therapy. Angiography is generally performed prior to resection and and may be combined with the delivery of chemotherapeutic and embolic agents pre-operatively or as a definitive palliative procedure. Imaging-guided percutaneous alcohol is also a useful palliative measure where the lesion is small. In the majority of cases, resection is not feasible. In a selected few liver transplantation is an option. p]Imaging requirements of the potential liver transplant candidate depend on the nature of the underlying liver problem. A general assessment including a chest X-ray and US with Doppler imaging of the hepatic vascular structures is sufficient in the majority. In children with complex structural anomalies and in patients with bile duct disease or tumours, the full range of investigations is required. US, cholangiography CT and angiography may all be required in the diagnosis and management of post-transplant complications.