Transplantation of en bloc pediatric kidneys when the proximal vascular cuff is too short.
Explore the source record for details and available documents.
Child↗
Biomedical subjects
Amadeo Marcos
Publications and source records attributed to Amadeo Marcos.
Persistent donor-specific alloreactivity may portend delayed liver rejection during drug minimization in children.
Immunoreactivity, immunosuppression requirement and liver graft function was assessed serially for its relationship to delayed/recurrent acute cellular rejection (ACR) after the first 60 days in 36 pediatric primary liver transplant (LTx) recipients. Subjects were classified as rejectors (n=20) or Non-Rejectors (n=16) based on the presence/absence of biopsy-proven ACR in the first 60 days. All children received anti-lymphocyte induction and steroid-free Tacrolimus or Sirolimus monotherapy, as reported previously. Median age was 4 years (0.45-18) and follow-up was 570 days (106-1144). Compared with non-rejectors, rejectors 1. took significantly longer to achieve reduced donor-specific alloreactivity by MLR (p=0.049), and "low" TAC/SRL whole blood requirements defined as TAC levels < or = 8 ng/ml (p=0.0048), 2. experienced significantly greater variation in time to achieve reduced donor-specific immunoreactivity (SEM 0.8 vs 3.85, p=0.0048), and 3. experienced greater ACR incidence during minimization of immunosuppression (35% versus 6%, p=0.032). Serial monitoring of immunoreactivity may increase the safety with which immunosuppression is minimized in pediatric LTx.
Adolescent↗
Pancreas transplantation under alemtuzumab (Campath-1H) and tacrolimus: Correlation between low T-cell responses and infection.
BACKGROUND: Alemtuzumab induction and tacrolimus-based immunosuppression has been effective in pancreas transplantation. Despite the encouraging results of this minimalistic approach to immunosuppression, infection still remains a significant cause of morbidity. The Cylex ImmuKnow [corrected] assay was used in this study to compare pancreas recipient clinical states (stable, rejection, infection) with T cell responses. METHODS: Blood samples were taken from pancreas recipients pretransplant and at approximately three-month intervals posttransplant for analysis of T cell responses. When possible, T cell responses were also quantified during changes in clinical status (infection or rejection). RESULTS: A range between 100-300 ng/ml adenosine triphosphate (ATP) was found in stable patients (mean 194+/-123, n = 51) with good graft function and no infection or rejection. A low T cell response was highly correlated with infectious states. The fourteen patients with infections/posttransplant lymphoproliferative disease had a mean ATP of 48 ng/ml. Risk hazard analysis showed that patients with ATP levels <100 ng/ml were four to seven times more susceptible to infection compared to stable patients. Four patients with rejection showed a T cell response of 550 ng/ml ATP, which was statistically significant compared to stable patients, although the sampling numbers (9) were too small to be conclusive. CONCLUSION: The Cylex ImmuKnow [corrected] assay is a valuable tool to more precisely modulate immunosuppression in pancreas transplant patients. In particular, the assay is extremely useful in detecting overly immunosuppressed patients vulnerable to infections.
Adenosine Triphosphate↗
Alemtuzumab induction and tacrolimus monotherapy in pancreas transplantation: One- and two-year outcomes.
BACKGROUND: Alemtuzumab (Campath-1H) induction with tacrolimus monotherapy has been shown to provide effective immunosuppression for kidney, liver, lung, and small bowel transplantation. This drug combination was evaluated in pancreas transplant recipients. METHODS: Sixty consecutive pancreas transplants (30 simultaneous pancreas-kidney, 20 pancreas after kidney, and 10 pancreas alone) were carried out under this protocol between July 2003 to January 2005. The mean follow-up was 22 months (range 17-33). RESULTS: One-year patient, pancreas, and kidney allograft survival were 95%, 93%, and 90%, respectively. With 22 months follow-up, patient, pancreas, and kidney survival were 94%, 89%, and 87%, respectively. The rejection rate was 30% (18/60), with four patients (7%) experiencing steroid-resistant rejection. Major infection occurred in three (5%) patients resulting in two (3.3%) deaths from disseminated histoplasmosis and a herpes virus infection. One patient with cryptococcal meningitis was successfully treated. Seven (11.7%) patients experienced cytomegalovirus infection, all of whom responded to treatment with ganciclovir. One (1.7%) case of polymorphic posttransplant lymphoproliferative disease was seen, which regressed with a temporary discontinuation of tacrolimus and high-dose ganciclovir. The mean serum creatinine of the 30 simultaneous pancreas-kidney transplants at one year posttransplant was 1.37+/-0.33 mg/ml. The preexisting creatinine in pancreas after kidney transplants was not adversely affected by this immunosuppressive protocol. CONCLUSION: A single dose of perioperative alemtuzumab followed by daily tacrolimus monotherapy provides effective immunosuppression for pancreas transplantation, but the optimal use of this drug combination is not yet clear.
Alemtuzumab↗
Opportunistic infections in 547 organ transplant recipients receiving alemtuzumab, a humanized monoclonal CD-52 antibody.
BACKGROUND: Alemtuzumab is being increasingly used for the prevention and/or treatment of acute allograft rejection in organ transplant recipients. We assessed the risks of infection in, to our knowledge, the largest cohort and broadest range of organ transplant recipients yet reported to have received alemtuzumab. METHODS: All patients who received alemtuzumab from September 2002 through March 2004, either as induction therapy at the time of transplantation or for the treatment of rejection, were evaluated for the development of an opportunistic infection (OI) until death or for 12 months after receipt of the last dose of alemtuzumab. RESULTS: A total of 547 recipients were included, 65% of whom received alemtuzumab for induction therapy only. Overall, 56 recipients (10%) developed 62 OIs, including cytomegalovirus disease (n = 16), BK virus infection (n=12), posttransplantation lymphoproliferative disease (n=5), human herpesvirus 6 infection (n=1), parvovirus infection (n=1), esophageal candidiasis (n=12), cryptococcosis (n=2), invasive mold infection (n=4), Nocardia infection (n=4), mycobacterial infection (n=3), Balamuthia mandrillaris infection (n=1), and toxoplasmosis (n=1). Patients who received alemtuzumab for induction therapy were significantly less likely to develop an OI, compared with patients who received alemtuzumab for rejection therapy (4.5% vs. 21%; P<.001). Independent predictors of the development of an OI were administration of alemtuzumab for rejection therapy (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.8-6.8; P<.001), allograft failure (OR, 2.1; 95% CI, 1.1-4.4; P=.04), and receipt of a lung transplant (OR, 3.7; 95% CI, 1.7-8.0; P=.001) or an intestinal transplant (OR, 8.3; 95% CI, 3.5-19.5; P<.001). CONCLUSIONS: Patients who received alemtuzumab for the treatment of allograft rejection were significantly more likely to develop an OI, compared with patients who received alemtuzumab for induction therapy only. Such data have implications for new antimicrobial prophylactic strategies.
Adolescent↗
Bloodstream infections in organ transplant recipients receiving alemtuzumab: no evidence of occurrence of organisms typically associated with profound T cell depletion.
BACKGROUND: Alemtuzumab is a humanized monoclonal antibody directed against CD52, a cell surface antigen expressed on B and T lymphocytes, monocytes and NK cells. Its use results in a profound decrease in CD4 positive T lymphocytes. Alemtuzumab is used as induction immunosuppression and therapy for rejection in organ transplant recipients in some centers. We followed a cohort of 449 consecutive transplant recipients who received alemtuzumab to determine the occurrence of bloodstream infections, particularly those previously associated with decrease in CD4 positive T lymphocytes. PATIENTS AND METHODS: Fifteen percent (69/449) patients had at least one episode of bloodstream infection. However, no patient had bacteremia with Streptococcus pneumoniae, Listeria monocytogenes, non-typhoidal Salmonella or Mycobacterium avium complex. Fungaemia was rare, occurring in 1.5% of patients. The most common organisms isolated from the blood were Staphylococcus aureus (21 episodes), coagulase negative Staphylococcus (14 episodes), Klebsiella pneumoniae (12 episodes), Enterococcus faecium (11 episodes), Pseudomonas aeruginosa (10 episodes), Enterococcus faecalis (9 episodes) and Escherichia coli (7 episodes). DISCUSSION: We conclude that although alemtuzumab use is associated with profound CD4 positive T lymphocyte depletion, alemtuzumab does not seem to be associated with an increased risk of bloodstream infection with pathogens typically seen in other disorders of CD4 cell depletion, such as acquired immunodeficiency syndrome.
Adolescent↗
Liver biopsy interpretation for causes of late liver allograft dysfunction.
Evaluation of needle biopsies and extensive clinicopathological correlation play an important role in the determination of liver allograft dysfunction occurring more than 1 year after transplantation. Interpretation of these biopsies can be quite difficult because of the high incidence of recurrent diseases that show histopathological, clinical, and serological features that overlap with each other and with rejection. Also, more than one insult can contribute to allograft injury. In an attempt to enable centers to compare and pool results, improve therapy, and better understand pathophysiological disease mechanisms, the Banff Working Group on Liver Allograft Pathology herein proposes a set of consensus criteria for the most common and problematic causes of late liver allograft dysfunction, including late-onset acute and chronic rejection, recurrent and new-onset viral and autoimmune hepatitis, biliary strictures, and recurrent primary biliary cirrhosis and primary sclerosing cholangitis. A discussion of differential diagnosis is also presented.
Biopsy, Needle↗
Caroli's disease and orthotopic liver transplantation.
Caroli's disease is a rare congenital hepatic disease, characterized by segmental dilatation of the biliary tree. Patients who have recurrent bouts of biliary infection, particularly those with complications related to portal hypertension, may require orthotopic liver transplantation (OLT). Few case reports have described the outcome of OLT in patients with Caroli's disease and to date there is no large series reported in the literature. We retrospectively analyzed the outcome of OLT in patients with Caroli's disease who underwent OLT between 1982 and 2002 at Starzl Transplantation Institute, University of Pittsburgh. Patients were identified and data was collected by computerized search of the electronic database system. All patients had confirmation of diagnosis by histopathology of explanted liver. A total of 33 patients with Caroli's disease were listed for liver transplantation, 3 of whom were excluded, as they were not transplanted. A total of 90% had signs of hepatic decompensation at the time of OLT. Median posttransplantation follow-up was 7.7 yr. Short-term graft and patient survival at 1 month was 83% and 86%, whereas overall long-term graft survival rates at 1, 5, and 10 yr were 73%, 62%, and 53%, respectively, and patient survival rates were 76%, 65%, and 56%, respectively. Long-term outcome in patients who survived the first year after transplantation was significantly better. Their survival rate at 5 and 10 yr was 90% and 78%. On univariable analysis, recipient age, donor male gender, coexistent congenital hepatic fibrosis, and re-OLT were associated with poor patient survival. Eight patients were retransplanted, 3 of whom had primary nonfunction. A total of 13 patients died; the most common cause of death being sepsis and cardiovascular complications. Patients who died of sepsis had cholangitis pre-OLT. In conclusion, OLT is a form of curative and life-saving therapy in patients with Caroli's disease, especially in those with decompensated liver disease. Overall survival is better with liver transplantation and is comparable with the survival of recipients who undergo OLT for other etiologies of chronic liver disease. Survival was poor in patients with congenital hepatic fibrosis (Caroli's syndrome) and in those who had cholangitis at the time OLT.
Adult↗
MELD and prediction of post-liver transplantation survival.
The model for end-stage liver disease (MELD) was developed to predict short-term mortality in patients with cirrhosis. It has since become the standard tool to prioritize patients for liver transplantation. We assessed the value of pretransplant MELD in the prediction of posttransplant survival. We identified adult patients who underwent liver transplantation at our institution during 1991-2002. Among 2,009 recipients, 1,472 met the inclusion criteria. Based on pretransplant MELD scores, recipients were stratified as low risk (< or = 15), medium risk (16-25), and high risk (>25). The primary endpoints were patient and graft survival. Mean posttransplant follow-up was 5.5 years. One-, 5- and 10-year patient survival was 83%, 72%, and 58%, respectively, and graft survival was 76%, 65%, and 53%, respectively. In univariable analysis, patient and donor age, patient sex, MELD score, disease etiology, and retransplantation were associated with posttransplantation patient and graft survival. In multivariable analysis adjusted for year of transplantation, patient age >65 years, donor age >50 years, male sex, and retransplantation and pretransplant MELD scores >25 were associated with poor patient and graft survival. The impact of MELD score >25 was maximal during the first year posttransplant. In conclusion, older patient and donor age, male sex of recipient, retransplantation, and high pretransplant MELD score are associated with poor posttransplant outcome. Pretransplant MELD scores correlate inversely with posttransplant survival. However, better prognostic models are needed that would provide an overall assessment of transplant benefit relative to the severity of hepatic dysfunction.
Adult↗
Tolerance for organ recipients: a clash of paradigms.
Explore the source record for details and available documents.
Antilymphocyte Serum↗
Antilymphoid antibody preconditioning and tacrolimus monotherapy for pediatric kidney transplantation.
OBJECTIVE: Heavy post-transplant immunosuppression may contribute to long-term immunosuppression dependence by subverting tolerogenic mechanisms; thus, we sought to determine if this undesirable consequence could be mitigated by pretransplant lymphoid depletion and minimalistic post-transplant monotherapy. STUDY DESIGN: Lymphoid depletion in 17 unselected pediatric recipients of live (n = 14) or deceased donor kidneys (n = 3) was accomplished with antithymocyte globulin (ATG) (n = 8) or alemtuzumab (n = 9). Tacrolimus was begun post-transplantation with subsequent lengthening of intervals between doses (spaced weaning). Maintenance immunosuppression, morbidity, graft function, and patient/graft survival were collated. RESULTS: Steroids were added temporarily to treat rejection in two patients (both ATG subgroup) or to treat hemolytic anemia in two others. After 16 to 31 months (mean 22), patient and graft survival was 100% and 94%, respectively. The only graft loss was in a nonweaned noncompliant recipient. In the other 16, serum creatinine was 0.85 +/- 0.35 mg/dL and creatinine clearance was 90.8 +/- 22.1 mL/1.73 m2. All 16 patients are on monotherapy (15 tacrolimus, one sirolimus), and 14 receive every other day or 3 times per week doses. There were no wound or other infections. Two patients developed insulin-dependent diabetes. CONCLUSION: The strategy of lymphoid depletion and minimum post-transplant immunosuppression appears safe and effective for pediatric kidney recipients.
Adolescent↗
Infections after living-donor liver transplantation.
BACKGROUND: Despite greater awareness of organ donation among the general public, the supply of cadaveric organs has fallen short of identified needs. Living-donor liver transplantation (LDLT) is an effective means of overcoming the shortage of adult organs, as outcomes are now comparable to those of cadaveric donor liver transplantation. METHODS: From January, 2002 through January, 2006, 40 LDLTs were performed at our center. With two exceptions, the donor was a first-degree relative of the recipient; all donors were in excellent health with good hepatic function and morphology. All but two donors contributed the right lobe. Infections in the donors and recipients were analyzed. RESULTS: Clinically relevant infections occurred in three donors. In the recipients, the infections did not differ significantly from those experienced by recipients of cadaveric organs in terms of risk factors (e.g., poor graft function, re-transplantation, surgical complications such as bile duct stenosis, or vascular anastomotic stenosis) or type of infection. Cholangitis was the most frequent infection, leading to septic shock in five of the 14 patients with infections; intra-abdominal infections related to surgical complications led to septic shock in three additional patients. The other most commonly observed infections were urinary tract infections (n=10) and pneumonia (n=3). CONCLUSIONS: Living-donor liver transplantation offers hope to patients with end-stage liver disease in geographic areas where the waiting time mortality is high and available organs from deceased donors fall short of the population's need.
Abdominal Abscess↗
Pathophysiologic observations and histopathologic recognition of the portal hyperperfusion or small-for-size syndrome.
In an attempt to more completely define the histopathologic features of the portal vein hyperperfusion or small-for-size syndrome (PHP/SFSS), we strictly identified 5 PHP/SFSS cases among 39 (5/39; 13%) adult living donor liver transplants (ALDLT) completed between 11/01 and 09/03. Living donor segments consisting of 3 right lobes, 1 left lobe, and 1 left lateral segment, with a mean allograft-to-recipient weight ratio (GRWR) of 1.0 +/- 0.3 (range 0.6 to 1.4), were transplanted without complications, initially, into 6 relatively healthy 25 to 63-year-old recipients. However, all recipients developed otherwise unexplained jaundice, coagulopathy, and ascites within 5 days after transplantation. Examination of sequential posttransplant biopsies and 3 failed allografts with clinicopathologic correlation was used in an attempt to reconstruct the sequence of events. Early findings included: (1) portal hyperperfusion resulting in portal vein and periportal sinusoidal endothelial denudation and focal hemorrhage into the portal tract connective tissue, which dissected into the periportal hepatic parenchyma when severe; and (2) poor hepatic arterial flow and vasospasm, which in severe cases, led to functional dearterialization, ischemic cholangitis, and parenchymal infarcts. Late sequelae in grafts surviving the initial events included small portal vein branch thrombosis with occasional luminal obliteration or recanalization, nodular regenerative hyperplasia, and biliary strictures. These findings suggest that portal hyperperfusion, venous pathology, and the arterial buffer response importantly contribute to early and late clinical and histopathologic manifestations of the small-for-size syndrome.
Adult↗
Thrombotic and nonthrombotic hepatic artery complications in adults and children following primary liver transplantation with long-term follow-up in 1000 consecutive patients.
Arterial complications have a major impact on survival after liver transplantation (LTx). The aim of this study was to examine arterial complications in adults and children after LTx. A total of 1000 consecutive primary LTx patients [mean age 40.5 years: 600 males, 400 females, 834 adults; 166 children (age <18 years)] were studied. Forty-two patients (4.2%; 31 adults, 11 children) developed hepatic artery thrombosis (HAT). Thrombosis in children occurred significantly early (mean 5.4 days) compared with adults (mean 418.7 days, P = 0.0001). Nonthrombotic complications occurred in 30 patients (29 adults, one child). Overall, 13-year patient survival after HAT was 43.2% (72.7% children, 32.9% adults). For nonthrombotic complications, 54.3% of adults died and 69.4% grafts were lost. An overall incidence of 4.2% thrombotic and 3.2% nonthrombotic complications was observed. Rate of HAT was higher in children, but survival was better compared with adults.
Adolescent↗
Wound healing in the biliary tree of liver allografts.
An increasing need for liver transplantation requires evaluation and triage of organs harvested from "extended criteria" donors. Although there is currently no widely accepted definition, most would agree that "extended criteria" includes organs donated by individuals that are old (>65 years), obese, infected with HBV or HCV, non-heart beating (NHBD), or had an unstable blood pressure before harvesting or the organ experienced a long cold ischemic time. These organs carry a statistical risk of dysfunction early after transplantation, but in the majority of recipients, hepatic parenchymal function recovers. Later, however, a small but significant percentage of extended criteria donors develop biliary strictures within several months after transplantation. The strictures occur primarily because of preservation injury that leads to "ischemic cholangitis" or deep wounding of the bile duct wall. Subsequent partial wound healing and wound contraction, but failed restitution of the biliary epithelial cell (BEC) lining, result in biliary tract strictures that cause progressive biliary fibrosis, increased morbidity, and decreased organ half-life. Better understanding of the pathophysiologic mechanisms that lead to biliary strictures in extended criteria donors provides an ideal proving ground for regenerative medicine; it also can provide insights into other diseases, such as extrahepatic biliary atresia and primary sclerosing cholangitis, that likely share certain pathogenic mechanisms. Possible points of therapeutic intervention include limiting cold and warm ischemic times, donor and/or donor organ treatment, ex vivo, to minimize the ischemic/preservation injury, maximize blood flow after transplantation, promote BEC wound healing, and limit myofibroblasts activation and proliferation in the bile duct wall. The pathobiology of biliary wound healing and therapeutic potential of interleukin-6 (IL-6) are highlighted.
Biliary Tract↗
Rituximab (chimeric anti-CD20 antibody) for posttransplant lymphoproliferative disorder after solid organ transplantation in adults: long-term experience from a single center.
BACKGROUND: Occurrence of posttransplant lymphoproliferative disorder (PTLD) after transplantation is known. Drastic reduction or withdrawal of immunosuppression with anti-viral therapy for Ebstein-Barr virus (EBV) is the primary treatment for all PTLD. Many PTLD are B cell in origin have CD20 antigen on the cell surface. Rituximab is a chimeric anti CD20 antibody, which has been used to treat PTLD with variable success. This study aims to report long-term experience with rituximab for PTLD from a single center. METHODS: Seventeen patients (13 male, 4 female, mean age 51.2 years) received rituximab to treat PTLD. Five patients received rituximab with drastic reduction in immunosuppression (primary). Nine patients received rituximab after failure of primary therapy (rescue) and three patients received it after resolution of PTLD (prophylactic). Mean follow-up period was 60 months. RESULTS: Overall 1-, 3-, and 5-year patient survivals were 64.7%, 47.1% and 35.3%, respectively. In the primary group, three patients had complete and one had partial response; however, only two (40%) patients are currently alive. In the rescue group, none of the patients had a complete response, four patients had partial response, and only two (22%) patients are currently alive. In the prophylactic group, two patients died at 28 and 41 months due to recurrence and graft failure, respectively. CONCLUSION: Sixty percent (3 of 5) of patients who received rituximab as primary therapy had complete resolution, and 44% (4 of 9) of patients who received it as rescue therapy had partial response. Overall 5-year patient survival was a disappointing 35%.
Antibodies, Monoclonal↗
Long-term outcome of adding mycophenolate mofetil to tacrolimus for nephrotoxicity following liver transplantation.
Mycophenolate mofetil (MMF) has no known nephrotoxicity. This report examines the outcome in patients who received MMF for renal impairment on tacrolimus-based immunosuppression. From 1995 to 1996, twelve liver transplantation (LTx) patients (mean age 54.6 years) with serum creatinine >1.8 mg/dl were included in the study. MMF was introduced and tacrolimus dose was reduced by 30-50%. Each patient was followed for 6 years. Renal function showed improvement in seven patients, deterioration in four, and no change in one patient. Overall mean serum creatinine decreased from 2.5 to 1.9 mg/dl at 6 months but increased to 2.2 mg/dl at 18 to 24 months. After that, renal function remained stable for 72 months. Iothalamate clearance showed 18.5% improvement at 1 year. Three patients developed renal failure. Six patients died in the follow-up period. Addition of MMF with reduced tacrolimus dose resulted in sustained improvement in renal function in 58% of patients.
Adult↗
Hypophosphatemia and the live liver donor.
Explore the source record for details and available documents.
Humans↗