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Jorge Reyes

Publications and source records attributed to Jorge Reyes.

At least 37 records · Page 2Linked to original sources
PubMed2003

Liver transplantation in children with cystic fibrosis: a long-term longitudinal review of a single center's experience.

BACKGROUND: Improved long-term survival in cystic fibrosis (CF) has led to an increased incidence of extrapulmonary complications of this disease. Of these, end-stage liver disease is a significant cause of morbidity and mortality with liver transplantation being the only effective therapy. METHODS: Records of all CF pediatric liver transplant recipients were reviewed. RESULTS: Twelve children with CF were the recipients of 16 allografts. The 1- and 5-year survival was 91.6% and 75%, respectively. There were 5 deaths at a mean interval of 6.8 +/- 6.3 years. All of these deaths were related to pulmonary disease. Pulmonary function improved or remained stable in 8 of 9 patients tested. Despite an 83% incidence of positive sputum cultures, there was only one early mortality related to pulmonary sepsis in the setting of primary liver allograft nonfunction. CONCLUSIONS: Liver transplantation is acceptable treatment for children with CF and end-stage liver disease. Long-term survival is comparable to liver transplantation performed for other indications. Although posttransplant morbidity and mortality is related to lung disease, the authors speculate that as therapeutic improvements prolong the survival in CF, it is expected that longer survival after liver transplantation in this patient population may also be anticipated.

Adolescent↗
PubMed2003

Lymphocyte subsets may discern treatment effects in children and young adults with post-transplant lymphoproliferative disorder.

To identify potential alternatives to Epstein-Barr virus (EBV)-specific cytotoxic T-cell responses, peripheral lymphocyte subsets (PLS) (CD4+, CD8+, CD3+, CD19+, CD56+) were measured by flow cytometry in children with abdominal transplants (n = 22) and heart transplants (n = 2), with (n = 14) and without (n = 10, group C) post-transplant lymphoproliferative disorder (PTLD). PTLD resolved with reduced immunosuppression and antiviral therapy in eight children (group B). Recalcitrant PTLD was observed in six children (group A). Recalcitrant PTLD followed prior antilymphocyte therapy [monoclonal anti-CD3 antibody (OKT3) and thymoglobin (n = 3) and thymoglobin (n = 1)] for refractory rejection in four of these six children, and resolved after treatment with rituximab (anti-CD20 monoclonal antibody). Ten children without PTLD served as a control group (group C). Between group comparisons showed a numeric increase in CD8 + cells and significantly lower CD4:CD8 ratios in both PTLD groups (A and B) compared with group C. Group A children also demonstrated significant depletion of natural killer (NK) cells, and post-rituximab depletion of B-cells compared with group B (no rituximab treatment). We conclude that NK cell depletion with a reversed CD4:CD8 ratio may represent a persistent immunosuppressed state, which may result from prior antilymphocyte therapy and may predispose to recalcitrant EBV-PTLD. Clinical remission with rituximab is accompanied by B-cell depletion. Serial monitoring of PLS from the time of diagnosis of PTLD will be necessary to confirm these observations.

Adolescent↗
PubMed2003

Exfoliative rejection after intestinal transplantation in children.

BACKGROUND: Graft rejection is the most significant cause of allograft failure after intestinal transplantation (ITx). Severity can vary and is based on histologic criteria, the most extreme form being exfoliation of the mucosa. We present the characteristics and outcome of children who developed exfoliative rejection (ER) after ITx. METHODS: Between June 1990 and March 2002, 88 patients received 92 ITx which included isolated small bowel (SB, n = 26), combined liver-small bowel (LSB, n = 54), and multivisceral MV n = 12) allografts performed under tacrolimus and steroid immunosuppresson. ER was diagnosed by endoscopy and confirmed by biopsy. RESULTS: Thirteen (15%) of 88 patients developed 15 episodes of ER in 15 intestinal allografts, and included SB (n = 8), LSB (n = 5), and MV (n = 2). Time to ER after ITx ranged from 9 days to 45.5 months (median 22 days). Eight episodes of ER developed within 1 month after ITx. Ten episodes of ER were exacerbations of prior rejection. Five episodes occurred abruptly. All but one received OKT3. Fourteen of 15 allografts were lost; six patients underwent allograft enterectomy acutely as a salvage operation because of ER. The remainder of the allografts were either removed or lost to patient death as a consequence to infection or chronic rejection after resolution of ER. Retransplantation was performed in three patients, with subsequent recurrence of ER in two retransplanted allografts. Inclusion of a liver allograft was a protective factor toward decreasing the incidence of ER. The results of cross-matching, inclusion of a colonic segment, and simultaneous bone marrow infusion did not affect the incidence of ER. Infectious complications included post-transplant lymphoproliferative disease (n = 4), cytomegalovirus (n = 5), and adenovirus infection (n = 2). CONCLUSIONS: Exfoliative rejection is associated with a high morbidity and mortality after ITx. Strategies to improve survival may include up front anti-lymphocyte antibody therapy and, when fail to respond promptly and satisfactorily, early intestinal allograft removal.

Child, Preschool↗
PubMed2003

Liver and intestinal transplantation in a child with cystic fibrosis: a case report.

Cystic fibrosis (CF) is an inherited disorder that presents as a multisystem disease with meconium ileus being the presenting symptom in 20% of patients. Approximately half of these patients present with complicated meconium ileus mandating early surgical intervention, potentially resulting in short gut syndrome. Although liver transplantation in children with CF has been described, this is the first report of a combined liver and small bowel transplant in a recipient with CF. A 7-month-old boy with CF presented with short bowel syndrome following extensive small bowel resection for meconium ileus and progressive cholestatic liver failure from intravenous hyperalimentation. He underwent combined liver and small intestinal transplant. He was discharged home three weeks post-transplant on enteral feeds with supplemental intravenous fluid. He has had routine protocol small bowel allograft biopsies with no documented rejection episodes. He has been treated for minor respiratory infections without major sequelae. Improvements in pulmonary therapy have impacted on the survival in the CF population to the point where the need for multiorgan transplantation will be increased in the future. Extrapolating from the excellent experience of liver transplantation in children with CF, early liver and small intestinal multivisceral transplantation, if indicated, can be performed safely in children with CF.

Cystic Fibrosis↗
PubMed2003

Dendritic cell subset ratio in peripheral blood correlates with successful withdrawal of immunosuppression in liver transplant patients.

Human dendritic cell (DC) subsets appear to play distinct roles in the induction and regulation of immune responses. While monocytoid DC (DC1) induce T-helper (Th) 1-type responses, plasmacytoid DC (DC2) have been reported to selectively induce Th2 responses. In blood, their precursors (p) can be identified as HLA-DR+ lineage- cells that are further characterized as CD11c+ CD123-/lo (IL-3Ralpha-/lo) (pDC1) or as CD11c- CD123hi (pDC2) by rare event, flow cytometric analysis. We compared the incidences of pDC1 and pDC2 in peripheral blood mononuclear cell populations isolated from normal healthy controls and from 3 groups of clinically stable liver transplant patients. Group A had been successfully withdrawn from immunosuppression, whereas group B were undergoing prospective drug weaning and on minimal anti-rejection therapy. In group C, drug withdrawal had either failed or never been attempted and patients were on maintenance immunosuppression. Assessment of DC subsets and the pDC2 : pDC1 ratio showed good intra-and interassay reproducibility. Compared with patients in group C, those in groups A and B demonstrated a significantly higher relative incidence of pDC2 and a lower incidence of pDC1 - similar to those values observed in normal healthy controls. Moreover, the pDC2 : pDC1 ratio was significantly higher in patients undergoing (successful) weaning and in those off immunosuppression compared with patients on maintenance immunosuppression.

Adolescent↗
PubMed2003

Ex vivo priming of naïve T cells into EBV-specific Th1/Tc1 effector cells by mature autologous DC loaded with apoptotic/necrotic LCL.

Posttransplant lymphoproliferative disorders (PTLDs) represent life-threatening complications of bone marrow and solid organ transplantation (SOTx). These are B-cell malignancies triggered by Epstein-Barr Virus (EBV) infection in chronically immunosuppressed (IS) recipients. Immunosuppressed EBV seronegative (EBV(-)) organ recipients are at highest risk of developing PTLD owing to the lack of anti-EBV memory T cells to control subsequent EBV challenges. Our aim is to establish effective anti-EBV T-cell generation protocols for prevention or treatment of PTLD encountered in SOTx. We have used autologous dendritic cells (DCs) loaded with apoptotic/necrotic lymphoblastoid cell lines (LCLs) to evaluate the ability of such an approach to activate naïve T cells in vitro. In EBV(-) individuals, both CD8+ and CD4+ T-cell responses were amplified by this approach, as detected by IFN-gamma ELISPOT and cytotoxicity assays. The CD8+ T cells were poly-specific anti-EBNA3 A, -LMP2 and -BMLF1, with uniform reversion to a CD45RO+/RA-phenotype, decreased CD62L expression, and up-regulation of the activation markers CD28 and CD69. Addition of rhIL-12 improved anti-viral T-cell responses and reduced the functional differences observed between EBV(+) and EBV(-) responders. In conclusion, the DC/LCL method promotes cross-presentation of EBV-associated epitopes and may serve as an effective protocol for the adoptive immunotherapy of PTLD in EBV(-) SOTx patients.

Antigen Presentation↗
PubMed2003

Liver transplantation for growing teratoma syndrome: report of a case.

Liver transplantation is a well-established treatment for liver failure and for a selected group of patients with hepatic tumors. The growing teratoma syndrome refers to the phenomenon whereby germ cell tumors enlarge after chemotherapy despite complete eradication of malignant cells and normalization of serum tumor markers. We present the case of a young patient with rapidly growing teratomatous masses in his liver who was treated with liver transplantation from a live donor. We discuss his postoperative management, follow-up, and briefly review literature on the subject.

Adult↗
PubMed2002

Causes of mortality beyond 1 year after primary pediatric liver transplant under tacrolimus.

BACKGROUND: Success of pediatric liver transplantation has improved significantly. Most posttransplant deaths occur early and are related to surgical complications or recipient status at the time of transplantation. The causes of mortality beyond the first year have not been well described. METHODS: Three hundred twenty-six pediatric liver transplants were performed between November 1989 and April 1998 using tacrolimus-based immunosuppression. Patients were followed until March 2002. Mean follow-up was 9.2+/-2.4 years. RESULTS: At 1 year, 279 patients (85.5%) were alive. In the subsequent 12.5 years, 10 of the remaining children died (3.58%) at a mean interval of 3.68+/-1.69 years after transplant. The mean age at transplant was 5.62+/-6.3 years. Six patients had infections as a major contributor to mortality, including two patients with posttransplant lymphoproliferative disorder (PTLD) and one patient that died after retransplantation for hepatitis. Two patients had recurrent malignancy. Other deaths were attributable to chronic rejection, liver failure after being lost to follow-up, and complications of cystic fibrosis. CONCLUSIONS: Pediatric liver transplantation using tacrolimus-based immunosuppression has demonstrated excellent success, with 1- and 10-year survival rates of 85.5% and 82.9%, respectively. Late mortality after pediatric liver transplantation overall remains low, with a rate of 0.32% per year. The most common cause of death was infection (60%), including PTLD-related disease (20%). However, in the recent cohort of patients who underwent transplantation after September 1995, there were no fatal cases of Epstein-Barr virus or PTLD or late mortality thus far, suggesting a benefit from improved infectious disease surveillance using currently available modalities. Mortality from chronic rejection and noncompliance under tacrolimus has been exceedingly rare.

Cause of Death↗
PubMed2002

Case report of combined pediatric heart-lung-liver transplantation.

We present the youngest successful patient with combined heart-lung-liver transplantation. The patient was a 2.5-year-old child with Alagille syndrome suffering from tetralogy of Fallot with pulmonary atresia and multiple aortopulmonary collaterals and familial cholestasis.

Child, Preschool↗
PubMed2002

Cytokine gene polymorphisms in children successfully withdrawn from immunosuppression after liver transplantation.

BACKGROUND: Cytokine genetic polymorphisms have been associated with transplant outcome in some experimental and clinical studies, but the cytokine profile of patients who are clinically tolerant has not been investigated. AIM: Allelic variations in tumor necrosis factor (TNF)-alpha, interferon (INF)-gamma, transforming growth factor (TGF)-beta1, interleukin (IL)-6, and IL-10 were evaluated in patients successfully withdrawn from immunosuppression. METHODS: Pediatric liver transplant recipients who were successfully withdrawn from immunosuppression (n=12) or who are on minimal immunosuppression (n=7) were genotyped. A control group of liver recipients who required maintenance immunosuppression served as a control group (n=37). RESULTS: Compared to the control group, low TNF- alpha and high/intermediate IL-10 profiles were seen in all 12 children maintained off immunosuppression and in 6 of 7 children requiring minimal immunosuppression. CONCLUSION: Children successfully maintained off immunosuppression are more likely to have a genetic predisposition toward low TNF-alpha and high/intermediate IL-10 production. Children maintained on minimal immunosuppression exhibit a similar cytokine profile to those successfully weaned.

Adolescent↗
PubMed2002

Pediatric liver transplantation. A single center experience spanning 20 years.

BACKGROUND: Survival after liver transplantation has improved significantly over the last decade with pediatric recipients faring better than adults. The 20-year experience of pediatric liver transplantation at Children's Hospital of Pittsburgh is reported in terms of patient survival; graft survival in relation to age, gender, and immunosuppressive protocols; causes of death; and indications for retransplantation. METHOD: From March 1981 to April 1998, 808 children received liver transplants at Children's Hospital of Pittsburgh. All patients were followed until March 2001, with a mean follow-up of 12.2+/-3.9 years (median=12.6; range=2.9-20). There were 405 female (50.2%) and 403 male (49.8%) pediatric recipients. Mean age at transplant was 5.3+/-4.9 years (mean=3.3; range 0.04-17.95), with 285 children (25.3%) being less than 2 years of age at transplant. Cyclosporine (CsA)-based immunosuppression was used before November 1989 in 482 children (50.7%), and the subsequent 326 recipients (40.3%) were treated with tacrolimus-based immunosuppression. Actuarial survival was calculated using the Kaplan-Meier statistical method. Differences in survival were calculated by log-rank analysis. RESULTS: Overall patient survival at 1, 5, 10, 15, and 20 years was 77.1%, 72.6%, 69.4%, 65.8%, and 64.4%, respectively. There was no difference in survival for male or female patients at any time point. At up to 10 years posttransplant, the survival for children greater than 2 years of age (79.5%, 75.7%, and 71.6% at 1, 5, and 10 years, respectively) was slightly higher than those at less than 2 years of age (72.6%, 66.9%, and 65.3% at 1, 5, and 10 years, respectively). However, at 15 and 20 years posttransplant, survival rates were similar (>2 years=67.3% and 65.8%; <2 years=64.1% and 64.1%). A significant difference in survival was seen in CsA-based immunosuppression (71.2%, 68.1%, 65.4%, and 61%) versus tacrolimus-based immunosuppression (85.8%, 84.7%, 83.3%, and 82.9%) at 1, 3, 5, and 10 years, respectively (P=0.0001). The maximum difference in survival was noted in the first 3 months between CsA and tacrolimus; thus, indicating there may have been other factors (nonimmunological factors) involved in terms of donor and recipient selection and technical issues. The mean annual death rate beyond 2 years posttransplant was 0.47%, with the mean annual death rate for patients who received tacrolimus-based immunosuppression being significantly lower than those who received CsA-based immunosuppression (0.14% vs. 0.8%; P=0.001). The most common etiologies of graft loss were hepatic artery thrombosis (33.4%), acute or chronic rejection (26.6%), and primary nonfunction (16.7%). Of note, retransplantation for graft loss because of acute or chronic rejection occurred only in those patients who received CsA-based immuno-suppression. CONCLUSION: The overall 20-year actuarial survival for pediatric liver transplantation is 64%. Survival has increased by 20% in the last 12 years with tacrolimus-based immunosuppression. Although this improvement may be the result of several factors, retransplantation as a result of acute or chronic rejection has been completely eliminated in patients treated with tacrolimus.

Adolescent↗
PubMed2002

Pediatric intestinal transplantation: historical notes, principles and controversies.

The development in technique and immunosuppressive management of the last 12 yr have made intestinal transplantation an effective treatment for children with intestinal failure. The information provided in this review support such a conclusion, but was more clearly validated by the March 2001 Medicare Report which provided a national coverage decision of the Social Security Act for intestinal transplantation. As of May 2001, there were 55 centers world-wide which have performed 696 intestinal transplants in 656 patients. (Intestinal Transplant Registry, http://www.lhsc.on.ca/itr) the majority of recipients have been children, and there has been a greater need for liver replacement in conjunction with the allograft intestine because of a higher incidence of TPN-induced cholestatic liver disease in children. Though overall long-term survival is approximately 50%, similar advances in surgical, clinical and immunosuppressive management since 1995 have improved patient survival to more than 70% in most experienced programs. Over 80% of survivors are enjoying nutrition-supporting intestinal function. The major causes of graft loss and patient demise continues to be rejection and infection. Tacrolimus remains the mainstay of immunosuppressive therapy. Further experience other induction protocols utilizing rapamycin and daclizumab, as well graft pretreatment protocols may further enhance results in the future.

Child↗
PubMed2002

Long-term nutritional outcome after pediatric intestinal transplantation.

BACKGROUND/PURPOSE: The aim of this study was to describe the long-term nutritional status of a large population of children after intestinal transplantation and to identify factors associated with nutritional outcomes. METHODS: Longitudinal anthropometric data are maintained in a database registry for all patients referred to our Intestinal Care Center (ICC). Z-scores for weight and height were calculated biannually over a maximum of 2 years, and associations between baseline and follow-up laboratory measures and growth were evaluated for patients greater than 6 months post intestinal transplant. RESULTS: Since the inception of the ICC in December 1996, 24 pediatric patients (18 boys, 18 white) received an isolated small bowel or small bowel/liver transplant (median age, 3.2 years). The majority of cases (75%) had been diagnosed with surgical short bowel syndrome and were dependent on total parenteral nutrition (TPN) at the time of transplant. Of the 23 patients who survived the initial postoperative period, 87% were weaned from TPN to an amino-acid or peptide-based enteral formula or solid food within 3 months. A positive trend in z-scores for weight and height/length was observed in only 30% and 26% of patients, respectively, during the follow-up period. Although mean albumin levels increased significantly from 2.8 to 3.1 mg/dl by 6 months posttransplant (P <.01) no difference in alkaline phosphatase was found over time. Steroid doses were weaned within 3 to 4 months after transplantation but not discontinued. The cumulative survival rate was 91% at 1 year and 86% at 2 years posttransplant, whereas those weaned from TPN achieved 100% and 94% survival, respectively. CONCLUSIONS: Attainment of positive linear growth remains a challenge in the pediatric transplant population despite successful liberation from TPN, protein anabolism, and high survival rates. Further investigation into alternative methods of nutritional evaluation and manipulation as well as the use of growth factors to enhance the growth process need to be investigated.

Body Height↗
PubMed2002

Posttransplant lymphoproliferative disorders in liver transplantation: a 20-year experience.

OBJECTIVE: To evaluate the incidence of posttransplant lymphoproliferative disease (PTLD) and the risk factors and the impact of this complication on survival outcomes in a large cohort of liver transplant recipients at a single institution. SUMMARY BACKGROUND DATA: Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, in large part due to the availability and reliance on the use of nonspecifically directed immunosuppression. However, as predicted and subsequently verified in 1968, an increased incidence of certain de novo malignancies has been observed, particularly with regards to lymphoid neoplasms. While many reports have confirmed and clarified the nature of PTLD, the literature is fraught with conflicting experience and outcomes with PTLD. METHODS: Four thousand consecutive patients who underwent liver transplants between February 1981 and April 1998 were included in this analysis and were followed to November 2001. The effect of recipient age at the time of transplant, recipient gender, diagnosis, baseline immunosuppression, grading of PTLD, and association with Epstein-Barr virus were compared. The causes of death were also examined. Treatment for PTLD varied over the 20-year period, but all included massive reduction or elimination of baseline immunosuppression. RESULTS: The 1-year patient survival for liver transplant patients with PTLD was 85%, while the overall patient survival for the entire cohort was 53%. The actuarial 20-year survival was estimated at 45%. The overall median time to PTLD presentation was 10 months, and children had an incidence of PTLD that was threefold higher than adults. Patient survival was better in children, in patients transplanted in the era of tacrolimus immunosuppression, in patients with polymorphic PTLD, and in those with limited disease. Interestingly, neither the presence or absence of Epstein-Barr virus nor the timing of PTLD presentation appeared to influence overall patient survival. Patients transplanted for alcohol-related liver disease had a similar incidence of PTLD but had a higher risk of mortality. CONCLUSIONS: While PTLD continues to pose problems in patients receiving liver transplants, improvements in patient survival have been observed over time. While it is too early to assess the impact of new advances in prophylaxis, diagnosis, and treatment, such approaches are based on an increased knowledge of the pathophysiology of PTLD.

Adult↗
PubMed2002

Enteral formula use in children after small bowel transplant.

The ultimate goal of intestinal transplantation (ITx) is the maintenance of nutritional status enterally/orally. We retrospectively identified children who had received ITx since the inception of our Intestinal Care Center in December 1996 (n = 24; median age, 2.6 years). Two patients died within 2 months of transplant. Enteral formulas used in the remaining 22 patients included the following: amino acid, trace long chain fatty acids (LCT; n = 4); amino acid, medium chain fatty acids (MCT)/LCT fat mix (n = 13); amino acid, LCT fat (n = 1); and peptide, MCT/LCT fat mix (n = 3). Feedings were initiated on an average of 13 days after ITx. The median number of days to complete the total parenteral nutrition (TPN) wean was 30 days, and stoma output measured on an average of 37 mL/kg per day at 1 month posttransplant. Nine patients (41%) advanced to oral intake alone within 2 to 30 months, and 5 patients (23%) were diagnosed with milk allergy through the RAST test (Pharmacia, Uppsala, Sweden). No differences in the initiation of therapy, advancement to oral intake, stoma output, or TPN weaning were observed by the type of formula used. Using z-score statistics, positive linear growth was achieved in 7 of 21 children (33%) over the 1-year period, whereas linear growth velocity was maintained in an additional 6 patients (29%). Successful advancement to total enteral/oral intake and positive growth after ITx can be achieved with either an amino acid- or peptide-based, partial MCT enteral formula initiated within 2 weeks of transplant. Monitoring for posttransplant allergy is recommended because of the high rate of postoperative allergy symptomology.

Journal Article↗