Risk factors for Clostridium difficile infection in intestinal transplant recipients during the first year post-transplant.

BACKGROUND: Clostridium difficile is the most common cause of healthcare-associated infectious diarrhea. Risk factors for C. difficile infections (CDI) in intestinal transplant recipients (ITR) are not well-defined. The aim of our study was to assess specific risk factors for CDI in ITR. METHODS: This is a 1:3 case-control study that included 29 ITR who developed CDI (cases) and 87 ITR without CDI (controls) observed during the first year post-transplantation. Wilcoxon rank sum and Fisher's exact tests were used to compare variables. Univariate and multivariable conditional logistic regressions analysis were performed to identify risk factors for CDI. RESULTS: The multivariable conditional logistic regression analysis showed that proton pump inhibitors (PPI) administration (odds ratio [OR] = 0.06; 95% confidence interval [CI]: 0.007-0.52; P = .01) was the only factor associated with lower rates of CDI. Outcomes for cases vs controls: rejection episodes 24.14% vs 20.69% (P = .7), graft loss 0% vs 2.3% (P = .99), and survival rate 1 year post-transplantation 79.3% (59.6-90.1%) vs 87.2% (78.1-92.7%) (P = .38). CONCLUSIONS: Proton pump inhibitor administration might be protective for CDI in ITR. Risks factors for CDI might be different in ITR compared to other populations; anatomical differences and medications administered in the post-transplantation period may affect intestinal microbiota.

Compensating the transplant professional: time for a model change.

Compensation models for physicians are currently based primarily on the work relative value unit (wRVU) that rewards productivity by work volume. The value-based payment structure soon to be ushered in by the Centers for Medicare and Medicaid Services rewards clinical quality and outcomes. This has prompted changes in wRVU value for certain services that will result in reduced payment for specialty procedures such as transplantation. To maintain a stable and competent workforce and achieve alignment between clinical activity, growth imperatives, and cost effectiveness, compensation of transplant physicians must evolve toward a matrix of measures beyond the procedure-based activity. This personal viewpoint proposes a redesign of transplant physician compensation plans to include the "virtual RVU" to recognize and reward meaningful clinical integration defined as hospital-physician commitment to specified and measurable metrics for current non-RVU-producing activities. Transplantation has been a leader in public outcomes reporting and is well suited to meet the challenges ahead that can only be overcome with a tight collaboration and alignment between surgeons, other physicians, support staff, and their respective institution and leadership.

AST/ASTS workshop on increasing organ donation in the United States: creating an "arc of change" from removing disincentives to testing incentives.

The American Society of Transplantation (AST) and American Society of Transplant Surgeons (ASTS) convened a workshop on June 2-3, 2014, to explore increasing both living and deceased organ donation in the United States. Recent articles in the lay press on illegal organ sales and transplant tourism highlight the impact of the current black market in kidneys that accompanies the growing global organ shortage. We believe it important not to conflate the illegal market for organs, which we reject in the strongest possible terms, with the potential in the United States for concerted action to remove all remaining financial disincentives for donors and critically consider testing the impact and acceptability of incentives to increase organ availability in the United States. However, we do not support any trials of direct payments or valuable considerations to donors or families based on a process of market-assigned values of organs. This White Paper represents a summary by the authors of the deliberations of the Incentives Workshop Group and has been approved by both AST and ASTS Boards.

Intestinal transplant registry report: global activity and trends.

The Registry has gathered information on intestine transplantation (IT) since 1985. During this time, individual centers have reported progress but small case volumes potentially limit the generalizability of this information. The present study was undertaken to examine recent global IT activity. Activity was assessed with descriptive statistics, Kaplan-Meier survival curves and a multiple variable analysis. Eighty-two programs reported 2887 transplants in 2699 patients. Regional practices and outcomes are now similar worldwide. Current actuarial patient survival rates are 76%, 56% and 43% at 1, 5 and 10 years, respectively. Rates of graft loss beyond 1 year have not improved. Grafts that included a colon segment had better function. Waiting at home for IT, the use of induction immune-suppression therapy, inclusion of a liver component and maintenance therapy with rapamycin were associated with better graft survival. Outcomes of IT have modestly improved over the past decade. Case volumes have recently declined. Identifying the root reasons for late graft loss is difficult due to the low case volumes at most centers. The high participation rate in the Registry provides unique opportunities to study these issues.

Parvovirus associated fulminant hepatic failure and aplastic anemia treated successfully with liver and bone marrow transplantation. A report of two cases.

Aplastic anemia (AA) has been observed in nearly a third of patients undergoing liver transplantation (LT) for non-A-E fulminant hepatic failure (FHF). Few of these patients have been successfully managed with sequential LT and bone marrow transplantation (BMT). No causative agent has been identified for the FHF or AA in these reported cases. At our center, two patients, aged 15 years and 7 years, respectively, underwent sequential living-related LT and living-unrelated BMT. These patients are 10/9 years and 5/4 years post-LT/BMT. Human parvovirus B19 (HPV-B19) was established as the causative agent for FHF in both these patients by polymerase chain reaction. This report presents the first two cases associating HPV-B19 with FHF and AA who underwent sequential LT and BMT with excellent outcomes.

Staphylococcus aureus infections after liver transplantation.

BACKGROUND: More data on the risk factors and outcomes after Staphylococcus aureus infections in liver transplantation are needed. METHODS: Liver recipients with S. aureus infections (cases) were retrospectively identified and compared to gender-, age-, and transplant type-matched (1:2) non-S. aureus-infected controls. Risk factors associated with S. aureus infections were identified by conditional logistic regression analysis. RESULTS: We evaluated 51 patients (median age 52 years). First S. aureus infections developed at a median time of 29 days after transplantation, with 52.94% of them in the first month; 88.24% were nosocomial, 41.18% were polymicrobial, and 47.06% were caused by methicillin-resistant S. aureus (MRSA). Surgical site infections represented 58.82% and bacteremia 23.53%. By univariate analysis, patients with S. aureus infections were intubated more frequently (odds ratio [OR] 26.92, 95% confidence interval [CI] 3.23-3,504.15, p = 0.0006), had a central line (OR 11.69, 95% CI 1.42-95.9, p = 0.02), or recent surgery (OR 26.92, 95% CI 3.23-3,504.15, p = 0.0006) compared with controls. By multivariate analysis, subjects who underwent surgery within 2 weeks prior to infection had a 26.9 times higher risk of developing S. aureus infection (95% CI 3.23-3,504.15, p = 0.0006); these results were adjusted for matched criteria. S. aureus infections did not affect graft or patient survival, but the study was not powered for such outcomes. CONCLUSION: Only recent surgical procedure was found to be a significant independent risk factor for S. aureus infections after liver transplantation.

Incidence, risk factors, and outcomes associated with cytomegalovirus disease in small bowel transplant recipients.

Despite improved prophylaxis, monitoring, and more efficient immunosuppression, CMV infection remains a common opportunistic infection in transplant recipients. We assessed the incidence of CMV disease in pediatric SBT recipients, the timing of CMV disease after transplantation, and its impact on patient outcome. The medical records of 98 SBT recipients were reviewed. We performed descriptive analysis, regression analysis, and Kaplan-Meier curves to determine the time-to-event after transplantation. Fifty-three percent patients were male and 47% female, with a mean age of 38.3 months. Thirty-five percent of patients received prophylactic VGC, 55% GCV, 10% a combination of GCV/VGC, and 99% CMV immunoglobulins. A total of 24.5% recipients were CMV D+/R- (CMV serostatus donor positive/recipient negative). Seven (c. 7%) patients developed CMV disease. CMV disease was associated with 2.5 times (0.52-12.1; p = 0.25) higher rate of CMV mismatch and 11.1 times (1.3-95.9; p = 0.03) higher risk of death. CMV prophylaxis increased time-to-death (p = 0.074). Time-to-CMV disease was shorter in patients with enteritis (p < 0.0001), and CMV disease was associated with shorter time-to-death after transplantation (p = 0.001). CMV disease in SBT recipients was associated with an 11-fold mortality increase and a fourfold faster time-to-death. Time-to-death was significantly shorter with CMV enteritis.

Implementation of vascularized composite allografts in the United States: recommendations from the ASTS VCA Ad Hoc Committee and the Executive Committee.

Like all other areas of transplantation, vascularized composite allografts (VCA) has the capacity to transform the lives of patients, for the better or for the worse. It is this duality that mandates VCA be performed in centers prepared for the intricacies accompanying other transplant procedures. Similarly, the complexities of VCA require that the procedures be driven by surgeons and physicians with experience in the multidisciplinary management of immunocompromised postsurgical patients. Furthermore, the grafts should be considered as organs rather than tissues from a regulatory and a biological standpoint. The ASTS supports the field of VCA and has demonstrated its support and leadership by actively formulating a strategy for its systematic development. The goal of this document is to provide a framework for the prospective, thoughtful realization of VCA in the United States from the American Society of Transplant Surgeons (ASTS) perspective.

Intestine transplantation in the United States, 1999-2008.

Improving short-term results with intestine transplantation have allowed more patients to benefit with nearly 700 patients alive in the United States with a functioning allograft at the end of 2007. This success has led to an increase in demand. Time to transplant and waiting list mortality have significantly improved over the decade, but mortality remains high, especially for infants and adults with concomitant liver failure. The approximately 200 intestines recovered annually from deceased donors represent less than 3% of donors who have at least one organ recovered. Consent practice varies widely by OPTN region. Opportunities for improving intestine recovery and utilization include improving consent rates and standardizing donor selection criteria. One-year patient and intestine graft survival is 89% and 79% for intestine-only recipients and 72% and 69% for liver-intestine recipients, respectively. By 10 years, patient and intestine survival falls to 46% and 29% for intestine-only recipients, and 42% and 39% for liver-intestine, respectively. Immunosuppression practice employs peri-operative antibody induction therapy in 60% of cases; acute rejection is reported in 30%-40% of recipients at one year. Data on long-term nutritional outcomes and morbidities are limited, while the cause and therapy for late graft loss from chronic rejection are areas of ongoing investigation.

Incidence and outcome of fungal infections in pediatric small bowel transplant recipients.

BACKGROUND: Data on the incidence, timing, and outcome of fungal infections in pediatric small bowel transplantation (SBT) are lacking. METHODS: Cases of pediatric SBT from January 2003 through December 2007 were collected. Standard induction was with thymoglobulin and/or basiliximab and maintenance immunosuppression was a tacrolimus-based regimen. Chi-square was used for categorical variables and Kaplan-Meier for survival analyses. RESULTS: A total 98 recipients were included; 25 patients developed 59 episodes of Candida infections and 4 episodes of invasive aspergillosis (incidence 25.5%, 95% confidence interval [CI] 17%, 34%). Of the Candida species, 37.3% were Candida albicans and 62.7% non-albicans Candida. Of all yeast infections, 66.1% were fungemia, 28.8% intra-abdominal infections, 1.7% empyema, and 3.4% urinary tract infection. Of the Candida intra-abdominal infections, 41.2% developed in the first month post transplantation, while 79.5% of candidemia developed after >6 months. Median time from transplantation to fungal infection was significantly shorter for abdominal infections compared with fungemia (9 versus 163 days; P=0.004). All-cause mortality was not significantly different between patients with and without fungal infections (32.3% versus 29.8%; odds ratio=1.12, 95% CI 0.45, 2.8). CONCLUSION: Fungal infections occurred in 25% of SBT recipients and C. albicans was the most common species. Intra-abdominal fungal infections occurred earlier (<1 month) than fungemia (>6 months) post transplantation.

The Declaration of Istanbul: review and commentary by the American Society of Transplant Surgeons Ethics Committee and Executive Committee.

The American Society of Transplant Surgeons (ASTS) was asked to endorse the 'The Declaration of Istanbul on Organ Trafficking and Transplant Tourism.' The document has been reviewed by the ASTS Ethics Committee and their ensuing report was presented, discussed and approved by the ASTS Council. The ASTS vigorously supports the principles outlined in the Declaration and details specific current obstacles to implementation of some of its proposals in the United States.

The viability of microorganisms in preservation solutions.

In 1988 the University of Wisconsin solution was introduced into clinical transplantation. This solution is unique in that it contains no glucose but rather raffinose, lactobionate, and hydroxyethyl starch. In addition, it contains two antibiotics, penicillin and bactrim. Prior studies have shown that other preservation solutions allow the transmission of bacterial contamination from organ donor to recipient. However, there are no data on whether UW solution, with its unique composition and extended preservation times, allows bacterial transmission. We undertook the present study to establish if bacteria remain viable in UW solution at extended preservation times. Cultures of both aerobic (Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa) and anaerobic (Bacteroides fragilis) bacteria were suspended at 10(5), 10(4), 10(2), and 10(1) org./ml (calibrated from a .5 Macfarland turbidity standard) in both Eurocollins and UW preservation solutions. Samples were then stored in an ice bath to stimulate organ preservation. The organisms were removed and plated on blood and chocolate agar at 0, 6, 12, 18, 24, and 36 hr postsuspension. The samples were then incubated at 37 degrees C and read for growth at 24-48 hr after plating. Our results showed growth of all organisms except S epi in both preservation solutions, at all dilutions and preservation times. S epi grew in the Eurocollins solution at all dilutions and preservation times but did not grow in the UW solution. When the experiment was repeated omitting penicillin from the UW solution, S epi grew at all dilutions and preservation times. These results demonstrate that in spite of the inclusion of two different antibiotics, the majority of the common bacterial contaminants of the organ donor remain viable in UW solution with extended preservation times. It may be possible therefore to omit these antibiotics from the UW solution and obtain similar results. It is also important to note that routine culturing remains an expensive but necessary part of organ procurement and preservation.

Procurement and preparation of human isolated small intestinal grafts for transplantation.

We have developed a donor operation that incorporates en bloc removal of the liver and intestine with a limited surgical resection in vivo. Over the past 18 months, we have used the following technique for the retrieval and preparation of seven isolated small intestinal allografts. The donor operation and bench preparation can be divided into three phases. During the first phase, the small intestine is removed with the liver, pancreas, and an aortic segment. In the second phase performed ex vivo, the donor liver can be separated from the specimen. The third phase involves additional bench dissection to yield an isolated intestinal allograft. The principle advantage of this technique is that it reduces potential liver injury by minimizing the surgical dissection required in vivo. Also, dividing the liver from the intestine ex vivo allows the organs to be separated in a bloodless field under controlled conditions that may be especially important when two different surgical teams are involved.

The spectrum of Pneumocystis carinii infection after liver transplantation in children.

We report the experience with Pneumocystis carinii lung infections in the 109 children undergoing liver transplantation at our hospital between August, 1985 and May, 1989. PCP developed in 9 of the 86 patients (10%) surviving > or = 6 weeks after transplantation and not receiving P carinii chemoprophylaxis. Of the 59 patients undergoing BAL 2 or more weeks after transplantation there were 16 specimens from 14 patients (24%) positive for P carinii. These patients had a spectrum of illness ranging from asymptomatic to severe pneumonia requiring mechanical ventilation. The mean interval from first transplantation to bronchoalveolar lavage positive for P carinii was 24.9 weeks and the mean interval to first PCP was 28.0 weeks. The earliest and latest occurrences of PCP were 7 weeks and 73 weeks, respectively, after transplantation. There were no complications attributed to BAL.

Transfusion-induced graft-versus-host disease after liver transplantation. Documentation using polymerase chain reaction with HLA-DR sequence-specific primers.

Graft-versus-host disease (GVHD) occurring after liver transplantation can pose a difficult diagnostic dilemma. Similar clinical and pathologic skin and gastrointestinal manifestations can result from other causes (i.e., drugs, infections). Treatment for each of these entities differs, and the high mortality associated with GVHD makes this distinction critical. GVHD has been assumed to result from the cotransplantation of donor lymphoid tissue along with the allograft. In most instances, the patient also receives blood products during the operation, and occasionally during the postoperative period, and the lymphoid cells in these products are also a potential source of concern. In this report, we describe a patient who developed GVHD after liver transplantation. Using molecular diagnostic techniques, we determined that the source for this GVHD was not the organ donor, but was most likely nonirradiated blood products received during the hospital course. Our results suggest that transplant recipients with concomitant hematopoietic dysfunction would benefit from irradiated blood products to reduce the likelihood of this complication.

Hepatic allograft rescue following arterial thrombosis. Role of urgent revascularization.

Hepatic artery thrombosis is a continuing source of morbidity and mortality following orthotopic liver transplantation. The cornerstone of therapy has been urgent retransplantation that is limited by organ availability. For this reason we developed a policy of urgent revascularization for allograft rescue. Hepatic artery thrombosis developed following 15 transplants of which 11 underwent urgent rearterialization. The diagnosis was made a mean of 4.8 days (range 1-10) following transplantation. Duplex ultrasonography was diagnostic in all patients and confirmed by angiography in 4 (36%). Three patients with hepatic artery thrombosis were identified following screening ultrasonography and were clinically unsuspected. Upon reexploration, a specific technical reason for hepatic artery was found in 4 patients (36%). Twelve arterial revascularization procedures were performed in 11 patients including: thrombectomy alone (n = 4); revision of anastomosis with thrombectomy (n = 5); and thrombectomy with placement of vascular conduit (n = 3). Following revascularization, 8 patients maintained hepatic artery patency. Three patients eventually required retransplantation secondary to biliary sepsis. Biliary tract complications developed in 6 patients, at a mean of 23 days following revascularization and included: breakdown of the biliary anastomosis (n = 4); stricture (n = 1); and sludge formation (n = 1). The overall graft and patient survival are 74% and 82% respectively, with a mean follow-up of 6.8 months. Hepatic allograft rescue with the use of urgent revascularization following hepatic artery thrombosis appears to be an effective means of either avoiding retransplantation or providing a bridge until a suitable donor becomes available.

Frozen section evaluation of donor livers before transplantation.

Frozen section examination was performed on 385 donor livers before transplantation. Exclusion criteria were applied to the donor livers examined to exclude potentially dysfunctional livers. The exclusion criteria included the following: severe macrovesicular steatosis, ischemic necrosis, prominent chronic portal inflammation, prominent periductular fibrosis, granulomatous inflammation, bridging fibrosis, and malignancy. Twenty-seven of the 385 donor livers examined were excluded before transplantation. The following histologic features were present in the excluded livers: severe steatosis (22), ischemic necrosis (2), portal inflammation (1), and periductular fibrosis (2). Steatosis was present in 51 of the 385 (13.25%) organs examined, including 22 of the donor organs excluded before transplantation. Twenty-nine livers with mild to moderate steatosis were implanted into size and blood type-matched recipients. Indicators of allograft function (prothrombin time and bilirubin) and damage (aspartate aminotransferase and alanine aminotransferase) were measured daily for the first 10 days after transplant. There was no statistically significant difference between the group of nonfat livers and donor livers containing mild steatosis. Statistically significant higher posttransplant serum alanine aminotransferase and prothrombin time levels were present in the patients with livers implanted with mild versus moderate steatosis. The 1-year survival rate for patients receiving fatty versus nonfatty donor livers was not statistically different (Kaplan-Meier, P = 0.592). No significant differences were found in the clinical and laboratory characteristics of donors whose organs were implanted compared with the clinical and laboratory characteristics of donors whose organs were excluded. The primary nonfunction rate after applying the exclusion criteria was 1.4%, which is a significant decrease compared with our primary nonfunction rate of 8.5% before using frozen section examination. Frozen section examination is useful in excluding donor organs which may become dysfunctional after transplantation.

The results of reduced-size liver transplantation, including split livers, in patients with end-stage liver disease.

We initiated a policy of using RSLT in critically ill patients in June of 1988. Since that time we have performed 30 RSLTs in 29 patients, including 28 children and 1 adult. The mean age of the children was 27 months (range 1 month to 10 years) with 14 (52%) being 1 year of age or less. The mean weight was 11.3 kg (range 2-50 kg) with 20 being 10 kg or less. A total of 22 patients were in the intensive care unit at the time of RSLT including 9 who were intubated. Of the 30 RSLTs, 23 were performed as a primary transplant while 7 were retransplants. Indications for primary transplantation included biliary atresia (n = 11), fulminant hepatic failure (n = 5), neonatal hepatitis (n = 4) and others (n = 3). The RSLT was used in retransplantation for primary nonfunction (n = 2), hepatic artery thrombosis (n = 2), chronic rejection (n = 2), and herpetic hepatitis (n = 1). The size reductions included 18 left lobes, 7 left lateral segments, and 5 right lobes. This group includes the use of the split-liver technique, which was applied to 10 patients (5 livers). The median donor/recipient weight ratio for left lobe transplants was 2:1; left lateral segments was 7.3:1; and right lobes 1.6:1. One year actuarial patient and graft survivals were 68 and 65%, respectively, with a mean follow-up of 10.6 months. The number of children dying awaiting transplantation has been significantly reduced following the introduction of RSLD (3 of 115, 2.6% vs. 12 of 95, 13%; P less than 0.02).

Combined liver/small bowel transplantation using a blood group compatible but nonidentical donor.

A successful liver/small intestinal transplantation with a blood group O donor to a blood type A recipient is described. Mild graft versus host disease developed, manifested by hemolysis, but did not result in graft loss or patient mortality. This suggests that minor ABO incompatibility may be tolerated with intestinal transplantation, despite the transplantation of large amounts of lymphoid tissue.

A pilot study of soluble adhesion molecules as surrogate markers for acute liver allograft rejection.

BACKGROUND: Tissue endothelial adhesion molecule expression is increased during acute liver allograft rejection. Soluble forms exist, but their correlation to rejection and their clinical value have not been determined. METHODS: We studied endothelial adhesion molecule tissue expression and soluble levels in blood and bile and correlated these to the clinical course of 11 adult patients followed for 30 consecutive days after liver transplantation. RESULTS: Three biopsies showing acute rejection demonstrated increased intercellular adhesion molecule (ICAM)-1 but not endothelial leukocyte adhesion molecule-1 expression on hepatic endothelial cells during rejection. Vascular cell adhesion molecule (VCAM)-1 staining was focally increased in two of three specimens. Levels of soluble ICAM-1 or soluble VCAM-1 by ELISA did not distinguish acute rejection from nonrejection conditions. CONCLUSION: We confirmed that endothelial ICAM-1 expression is more intense in rejecting allografts and is more sensitive than changes in VCAM-1 or endothelial leukocyte adhesion molecule-1. However, soluble adhesion molecule determination was not useful in the accurate detection of acute rejection.