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Biomedical subjects

Sue V McDiarmid

Publications and source records attributed to Sue V McDiarmid.

At least 19 recordsLinked to original sources
PubMed2006

Portocaval hemitransposition in pediatric liver transplant recipients: a single-center experience.

Few studies have reported a series of patients who have undergone portocaval hemitransposition at the time of orthotopic liver transplantation (OLT). Furthermore, no series report the outcome of pediatric patients who required the procedure. This work analyzes the experience with portocaval hemitransposition in the pediatric liver transplant population at a single center since the initial description of the procedure. We carried out a retrospective analysis of all pediatric liver transplants performed in our institution during the 8-year period from January 1, 1997, to December 31, 2004. Of 320 pediatric patients who received OLT during the study period, 7 underwent portocaval hemitransposition (2.2%). Five of the patients had biliary atresia. Four grafts were whole cadaveric livers, while the remaining 4 were left lateral segments from either in situ cadaveric split (n = 3) or living donation (n = 1). One patient received a whole cadaveric allograft and was retransplanted with a segment 2/3 graft; in both cases portocaval hemitransposition was utilized. Average warm ischemia time was 54 +/- 16 minutes. Three patients had primary nonfunction of the allograft; 2 were retransplanted with successful outcome, and the remaining patient died before retransplantation. Another patient died from recurrent disease. Four of 7 are long-term survivors and demonstrate good liver function as long as 8 years posttransplant. In conclusions, long-term survival is possible following OLT with portocaval hemitransposition in pediatric patients. However, rates of primary graft nonfunction can be high. Appropriate selection of recipient and type of donor graft are essential for good outcomes. Portocaval hemitransposition should be used cautiously and as a last resort to establish portovenous inflow.

Adult↗
PubMed2005

Disruption of P-selectin signaling modulates cell trafficking and results in improved outcomes after mouse warm intestinal ischemia and reperfusion injury.

BACKGROUND: This study analyzes the role of T lymphocytes and neutrophils (PMN) in intestinal ischemia and reperfusion injury (IRI) using either P-selectin blockade or elimination. METHODS: Using a model of severe mouse warm intestinal IRI, the following groups were performed: group 1: wild type C57BL6 no treatment; group 2: wild type treated with r-PSGL1-Ig; group 3: C57BL6 genetically deficient in P-selectin. Survival was assessed at day 7; intestine was assayed for histopathology, apoptosis, myeloperoxidase (MPO), inflammatory cytokines, hemoxygenase-1 (HO-1), and CD3 lymphocytes. Standard statistical comparison was undertaken. RESULTS: The survival was significantly (P < 0.01) improved in the treatment groups: group 1, 50%; group 2, 90%; group 3, 100%. Graded histopathology and crypt apoptosis were improved in groups 2 and 3. MPO and CD3 positive cells were significantly reduced in groups 2 and 3. A significant reduction in inflammatory/Th1-type cytokines was seen in groups 2 and 3 as compared to group 1. Conversely, a significant increase in Th2-type cytokines and HO-1 production was seen selectively in groups 2 and 3. CONCLUSIONS: This study demonstrates the importance of P-selectin signaling in warm, murine intestinal IRI in that either the blockade of or the genetic deficiency in P-selectin confers a survival advantage and reduction in tissue injury/inflammation. The mechanism involves a reduction of PMN and CD3 T cell infiltration and an alteration in the cytokine microenvironment in favor of a Th2 profile. These data implicate T lymphocyte as an important regulatory cell in this inflammatory process.

Animals↗
PubMed2005

Infectious enteritis after intestinal transplantation: incidence, timing, and outcome.

BACKGROUND: The study reviews the incidence, timing, and outcome of infectious enteritis (IE) after intestinal transplantation (ITx). METHODS: A retrospective review of all patients who underwent ITx at a single institution between 1991 and 2003 was undertaken using database and medical records. Standard statistical analyses were performed. RESULTS: Of 33 ITx recipients, 13 (39%) developed 20 culture- or biopsy-proven episodes of IE. Recipient demographics included the following: 10 males, median age 34 (10-585) months, 11 liver + intestine grafts, and two isolated intestine grafts. Infections were diagnosed a median of 76 days (32-1,800 days) after ITx. There were 14 viral (one cytomegalovirus, eight rotavirus, four adenovirus, one Epstein-Barr virus), three bacterial (Clostridium difficile), and three protozoal (one Giardia lamblia, two Cryptosporidium) infections. The bacterial infections tended to present earlier than the viral infections, and the most frequent presenting symptom was diarrhea. Complete resolution was achieved in 17 (94%) incidences with the appropriate antimicrobial or conservative therapy. It was interesting that there were seven rejection episodes documented by biopsy at the approximate time of diagnosis of IE. There were two graft losses: one because of adenoviral enteritis and one because of rejection after rotavirus enteritis. Three-year patient survival is 74% with no deaths directly attributable to IE. CONCLUSIONS: IE can occur in 39% of recipients after ITx. Viral agents are the cause in two thirds of the cases. With supportive care and appropriate treatment, resolution is possible in the majority of cases. Differentiating rejection and infection on histopathology can be difficult and relies on cultures and immunostaining.

Adult↗
PubMed2005

CD62 blockade with P-Selectin glycoprotein ligand-immunoglobulin fusion protein reduces ischemia-reperfusion injury after rat intestinal transplantation.

BACKGROUND: Intestinal transplantation (ITx) is severely limited by ischemia-reperfusion (I/R) injury. This study investigates I/R injury and ameliorates its consequences by using a recombinant protein targeted against selectins (recombinant P-selectin glycoprotein ligand-immunoglobulin [rPSGL-Ig]). METHODS: An isogeneic model of ITx was undertaken with control animals (no therapy) and treatment animals (rPSGL-Ig). Survival was assessed. Separate groups underwent an analysis examining tissue at multiple time points after I/R injury including histopathology; myeloperoxidase staining; immunostaining for CD3 and ED2; polymerase chain reaction analysis of interleukin (IL)-8/cytokine-inducible neutrophil chemoattractant, IL1beta, IL-6, interferon-gamma, IL-2, IL-4, and IL10; and western blots for hemoxygenase-1, BCL-2, and BCL-xl. Standard statistical analysis was undertaken. RESULTS: Treatment with rPSGL-Ig resulted in significantly improved survival after ITx. Analysis demonstrated diminished injury on histopathology and reduced tissue infiltration of neutrophils and lymphocytes. Significant differences in the cytokine profile after ITx were seen between the two groups including the production of inflammatory cytokines at 24 hr and the Th1 and Th2 cytokines at 2 and 4 hr. Last, treatment resulted in increased production of hemoxygenase, BCL-2, and BCL-xl. CONCLUSION: The results of this investigation of I/R injury after ITx revealed that rPSGL-Ig treatment led to marked improvement in outcome. The mechanism of action seems to involve the blockade of neutrophil and lymphocyte infiltration leading to a decreased inflammatory response possibly driven by Th2 cytokines. The results not only lend insight into the mechanisms behind I/R injury after ITx but also demonstrate a potential therapeutic modality to ameliorate its consequences.

Animals↗
PubMed2005

Analysis of long-term outcomes of 3200 liver transplantations over two decades: a single-center experience.

OBJECTIVE: Few studies have evaluated long-term outcomes after orthotopic liver transplantation (OLT). This work analyzes the experience of nearly 2 decades by the same team in a single center. Outcomes of OLT and factors affecting survival were analyzed. METHODS: Retrospective analysis of 3200 consecutive OLTs that were performed at our institution, between February 1984 and December 31, 2001. RESULTS: Of 2662 recipients, 578 (21.7%) and 659 (24.7%) were pediatric and urgent patients, respectively. Overall 1-, 5-, 10-, and 15-year patient and graft survival estimates were 81%, 72%, 68%, 64% and 73%, 64%, 59%, 55%, respectively. Patient survival significantly improved in the second (1992-2001) versus the era I (1984-1991) of transplantation (P < 0.001). Similarly, graft survival was better in the era II of transplantation (P < 0.02). However, biliary and infectious complications increased in era II. When OLT indications were considered, best recipient survival was obtained in children with biliary atresia (82%, 79%, and 78% at 1, 5, and 10 years, respectively), while malignant disease in adult patients resulted in the worst outcomes of 68% and 43% at 1 and 5 years, post-OLT. Further, patients <18 years and nonurgent recipients exhibited superior survival when compared with recipients >18 years (P < 0.001) or urgent patients (P < 0.001). Of 13 donor and recipient variables, era of OLT, recipient age, urgent status, donor age, donor length of hospital stay, etiology of liver disease, retransplantation, warm and cold ischemia, but not graft type (whole, split, living-donor), significantly impacted patient survival. CONCLUSIONS: Long-term benefits of OLT are greatest in pediatric and nonurgent patients. Multiple factors involving the recipient, etiology of liver disease, donor characteristics, operative variables, and surgical experience influence long-term survival outcomes. By balancing and matching these factors with a given recipient, optimum results can be achieved.

Adolescent↗
PubMed2005

Resolution of hypophosphatemia is associated with recovery of hepatic function in children with fulminant hepatic failure.

Fulminant hepatic failure (FHF) is a rare but often fatal disease in children. Clinical and laboratory predictors of liver regeneration and recovery, however, have not been well established. We hypothesized that hypophosphatemia may indicate recovery of liver synthetic function in children with FHF. We retrospectively reviewed the medical records of children with FHF who were admitted to UCLA and recovered hepatic function either spontaneously or by liver transplantation (LTx). Serum phosphate (Ph) and prothrombin time or international normalized ratio (INR) were compared over the patient's clinical course. Records of 39 children who spontaneously recovered experienced profound hypophosphatemia that resolved as liver synthetic function improved. Similar patterns were seen in the 84 children who recovered after LTx. We found that hypophosphatemia precedes the recovery of liver synthetic function in children with FHF who recovered with or without transplantation, and that Ph levels return to normal as liver synthetic function improves. These data suggest that hypophosphatemia may be a useful laboratory indicator of recovering liver function in children with FHF.

Adolescent↗
PubMed2004

Summary report of a national conference: Evolving concepts in liver allocation in the MELD and PELD era. December 8, 2003, Washington, DC, USA.

A national conference was held to review and assess data gathered since implementation of MELD and PELD and determine future directions. The objectives of the conference were to review the current system of liver allocation with a critical analysis of its strengths and weaknesses. Conference participants used an evidence-based approach to consider whether predicted outcome after transplantation should influence allocation, to discuss the concept of minimal listing score, to revisit current and potential expansion of exception criteria, and to determine whether specific scores should be used for automatic removal of patients on the waiting list. After review of data from the first 18 months since implementation, association and society leaders, and surgeons and hepatologists with wide regional representation were invited to participate in small group discussions focusing on each of the main objectives. At the completion of the meeting, there was agreement that MELD has had a successful initial implementation, meeting the goal of providing a system of allocation that emphasizes the urgency of the candidate while diminishing the reliance on waiting time, and that it has proven to be a powerful tool for auditing the liver allocation system. It was also agreed that the data regarding the accuracy of PELD as a predictor of pretransplant mortality were less conclusive and that PELD should be considered in isolation. Recommendations for the transplant community, based on the analysis of the MELD data, were discussed and are presented in the summary document.

Adult↗
PubMed2004

Selection of pediatric candidates under the PELD system.

1. The PELD score accurately predicts the 3 month probability of waiting list death for children with chronic liver disease. 2. Comparing pre and post PELD and MELD implementation, the percent of children receiving deceased donor livers increased and the percent of children dying on the list decreased after PELD/MELD implementation. 3. Excluding children transplanted at status 1, the largest percentage of children are transplanted at a PELD score < 10. 4. Before MELD/PELD 48% of all children receiving deceased donor organs were transplanted at status 1, compared to 41% in the PELD/MELD era. Wide regional variation occurs.

Adult↗
PubMed2003

Varicella in pediatric liver transplant patients: a retrospective analysis of treatment and outcome.

BACKGROUND: Varicella is a common childhood disease that can cause morbidity and mortality among immunosuppressed patients. There have been few previous studies monitoring the course of pediatric liver transplant patients with acute varicella. The aim of this study was to evaluate the treatment, outcomes, and complications of pediatric liver transplant patients admitted with acute varicella infection. METHODS: A retrospective chart review was carried out based on discharge diagnoses of orthotopic liver transplant and varicella among pediatric patients (age range, birth-18 years) admitted to the UCLA Medical Center between 1985 and 2001. RESULTS: Five hundred fifty-six pediatric patients received liver transplantations between 1985 and 2001. Twenty-two of these patients were admitted to the UCLA Medical Center with varicella (11 females, 11 males). No patients were treated on an outpatient basis. Mean age of the patients was 6 years (range, 1-16 years). None of these patients received the varicella vaccine before hospitalization. On admission, 5 of 22 patients (23%) had received varicella zoster immunoglobulin within 96 hours of exposure. The mean length of hospitalization was 6 days (range, 2-11 days). All immunosuppression dosages were reduced during the admissions. None of the patients had been treated with high-dose corticosteroids for acute rejection before the onset of the varicella infection. Patients were treated until defervescence with intravenous acyclovir and until their varicella lesions crusted. Patients were discharged with oral acyclovir to complete a 10-day course (including the intravenous treatment). No patients had complications from the varicella infection. A complication of an elevated serum creatinine for one patient was noted with the intravenous acyclovir treatment. This patient had associated headache and nausea that resolved when the creatinine level returned to normal. CONCLUSIONS: There were no complications or dissemination of varicella infection among our pediatric liver transplant patients. Further prospective randomized trials are required to evaluate the management of pediatric liver transplant patients infected with varicella.

Acyclovir↗
PubMed2002

Late-onset bacteremia in uncomplicated pediatric liver-transplant recipients after a febrile episode.

The aim of this study was to analyze the incidence and risk factors of bacteremia after a febrile episode in uncomplicated pediatric recipients more than 2 months after liver transplantation, which has not previously been studied. This cross-sectional study was conducted over a 4-year period. Patients with known risk factors for sepsis at the time of admission were excluded from the study. Seventy-one patients were hospitalized on 128 occasions, with bacteremia occurring in the case of 11 admissions (8.6%). No laboratory tests were predictive of bacteremia. The bacteremic group most frequently presented with ill appearance ( P<0.001), lethargy ( P<0.01), decreased physical activity, and a history of early-onset bacteremia after transplantation and segmental graft ( P<0.05). This study identified a significant incidence of bacteremia in uncomplicated patients many months after liver transplantation.

Bacteremia↗
PubMed2002

Development of a pediatric end-stage liver disease score to predict poor outcome in children awaiting liver transplantation.

BACKGROUND: A pediatric end-stage liver disease (PELD) score for children with chronic liver disease using easily obtainable, objective, verifiable parameters, would be useful to prioritize children awaiting liver transplantation. METHODS: Data from the Studies of Pediatric Liver Transplantation (SPLIT), a consortium of 29 U.S. and Canadian centers, were used to develop the PELD score. Two pretransplantation endpoints were evaluated: (1) death, n=884; and (2) death or moving to the intensive care unit (ICU), n=779. The analyses were restricted to children with chronic liver disease who were listed for a first transplant. Preliminary analyses of 17 possible factors yielded 6 parameters of interest: age <1 year, total bilirubin, international normalized ratio (INR), albumin, growth failure (height or weight Z score <-2), and calculated glomerular filtration rate. In a univariate Cox regression analysis, age, bilirubin, INR, and albumin were significant (P<0.01) predictors of both endpoints; glomerular filtration rate was not significant for either endpoint; and growth failure was significant for death/ICU but not death alone. In the multivariate analyses, age, bilirubin, and INR were significant for the death endpoint; and bilirubin, INR, growth failure, and albumin were significant for the death/ICU endpoint. From these results, three PELD models were evaluated to predict both outcomes at 3 and 6 months: PELD 1 (age, bilirubin, INR); PELD 2 (bilirubin, INR, albumin, growth failure); and PELD 3 (bilirubin, INR, albumin, growth failure, and age). The area under the receiver operating characteristic curve (AUC ROC) was used to compare models. For PELD 3, the most inclusive model, the AUC ROC at 3 months was 0.92 for death and 0.82 for "death-moved to ICU." A comparison of the AUC ROCs for the other models and for the model of end-stage liver disease ([MELD], the adult end-stage liver disease severity score model), none of which performed better than PELD 3, are presented. CONCLUSION: A model using five objective parameters can accurately predict death or death-moved to ICU in children awaiting liver transplantation.

Child, Preschool↗
PubMed2002

The new liver allocation system: moving toward evidence-based transplantation policy.

In 1999, the Institute of Medicine suggested that instituting a continuous disease severity score that de-emphasizes waiting time could improve the allocation of cadaveric livers for transplantation. This report describes the development and initial implementation of this new plan. The goal was to develop a continuous disease severity scale that uses objective, readily available variables to predict mortality risk in patients with end-stage liver disease and reduce the emphasis on waiting time. Mechanisms were also developed for inclusion of good transplant candidates who do not have high risk of death but for whom transplantation may be urgent. The Model for End-Stage Liver Disease (MELD) and Pediatric End-Stage Liver Disease (PELD) scores were selected as the basis for the new allocation policy because of their high degree of accuracy for predicting death in patients having a variety of liver disease etiologies and across a broad spectrum of liver disease severity. Except for the most urgent patients, all patients will be ranked continuously under the new policy by their MELD/PELD score. Waiting time is used only to prioritize patients with identical MELD/PELD scores. Patients who are not well served by the MELD/PELD scores can be prioritized through a regionalized peer review system. This new liver allocation plan is based on more objective, verifiable measures of disease severity with minimal emphasis on waiting time. Application of such risk models provides an evidenced-based approach on which to base further refinements and improve the model.

Evidence-Based Medicine↗