Andre Ibrahim David

100 Multivisceral Transplants at a Single Center

Objective:The objective of this study was to summarize the evolution of multivisceral transplantation over a decade of experience and evaluate its current status. Summary Background Data:Multivisceral transplantation can be valuable for the treatment of patients with massive abdominal catastrophes. Its major limitations have been technical and rejection of the intestinal graft. Methods:This study consisted of an outcome analysis of 98 consecutive patients who received multivisceral transplantation at our institution. This represents the largest single center experience to date. Results:The most common diseases in our population before transplant were intestinal gastroschisis and intestinal dysmotility syndromes in children, and mesenteric thrombosis and trauma in adults. Kaplan Meier estimated patient and graft survivals for all cases were 65% and 63% at 1 year, 49% and 47% at 3 years, and 49% and 47% at 5 years. Factors that adversely influenced patient survival included transplant before 1998 (P = 0.01), being hospitalized at the time of transplant (P = 0.05), and being a child who received Campath-1H induction (P = 0.03). Among 37 patients who had none of these 3 factors (15 adults and 22 children), estimated 1- and 3-year survivals were 89% and 71%, respectively. Patients transplanted since 2001 had significantly less moderate and severe rejections (31.6% vs 67.6%, P = 0.0005) with almost half of these patients never developing rejection. Conclusions:Multivisceral transplantation is now an effective treatment of patients with complex abdominal pathology. The incidences of serious acute rejection and patient survival have improved in the most recent experience. Our results show that the multivisceral graft seems to facilitate engraftment of transplanted organs and raises the possibility that there is a degree of immunologic protection afforded by this procedure.

Intestinal and Multivisceral Transplantation in Children

Objective:To describe a single-center experience of pediatric intestinal transplantation (Itx) and to provide an overview of the children who underwent this procedure along with their outcomes. Summary Background Data:Pediatric Itx presents multiple challenges because of the very young ages at which patients require transplantation and their higher susceptibility to infectious complications. Methods:We have performed 141 Itx in 123 children with a median age of 1.37 years. Primary grafts included isolated intestine (n = 28), liver and intestine (n = 27), multivisceral (n = 61), and multivisceral without the liver (n = 7). Two protocol modifications were introduced in 1998: daclizumab induction and frequent rejection surveillance. In 2001, indications for multivisceral transplantation were expanded, and induction with Campath-1H was introduced. Results:Actuarial patient survival at 1 and 3 years for group 1 (January 1994 to December 1997, n = 25), group 2 (January 1998 to March 2001, n = 29), group 3a (April 2001 to present, daclizumab, n = 51), and group 3b (April 2001 to present, Campath-1H, n = 18) was 44%/32%, 52%/38%, 83%/60%, and 44%/44%, respectively (P = 0.0003 in favor of group 3a). Severe rejection implied a dismal prognosis (65% mortality at 6 months). Observed incidence of severe rejection in groups 1, 2, 3a, and 3b was 32%, 24%, 14%, and 11%, respectively. In multivariable analysis, use of a multivisceral (with or without liver) transplant (P = 0.002), induction with daclizumab (P = 0.005), patient at home prior to transplant (P = 0.007), and age at transplant ≥1 year (P = 0.02) favorably influenced patient survival. Multivisceral transplant was protective with respect to the mortality rate due to rejection, while an older age at transplant was associated with both a lower incidence rate of developing respiratory infection and lower risk of mortality following the respiratory infection. Survivors are off parenteral nutrition and have demonstrated significant growth catch-up. Conclusions:Itx in children still is a high-risk procedure but has now become a viable option for children who otherwise have no hope for survival. Control of respiratory infection is of particular importance in the younger children.

Blood citrulline level is an exclusionary marker for significant acute rejection after intestinal transplantation.

Background. Serum citrulline is a marker for acute cellular rejection (ACR) after intestinal transplantation; however, its clinical utility has not yet been established. The goal of this study was to determine clearcut serum levels beyond which the diagnosis of acute rejection could be supported or refuted, and predictors of citrulline levels posttransplant from which more accurate estimates of sensitivity and specificity could be obtained. Methods. Since March 2004, we obtained 2135 dried blood spot (DBS) citrulline samples from 57 intestinal transplant recipients at or beyond 3 months posttransplant. Stepwise linear regression was performed to determine the most significant multivariable predictors of the patient’s DBS citrulline level. Results. Seven characteristics were associated with a significantly lower citrulline in multivariable analysis: presence of mild, moderate, or severe ACR; presence of bacteremia or respiratory infection; pediatric age; and time from transplant to DBS sample (P<0.00001 in each case). Using a <13 vs. ≥13 &mgr;moles/L cutoff point, the sensitivity for detecting moderate or severe ACR and the negative predictive value were high (96.4% and >99% respectively). Specificity was 54% to 74% in children and 83% to 88% in adults. Conclusions. Citrulline levels <13 &mgr;moles/L should alert the clinical team that a serious problem (rejection or infection) could be looming in a previously stable intestinal recipient. Levels ≥13&mgr;moles/L practically rule out moderate or severe rejection.

Transplantation of the Spleen: Effect of Splenic Allograft in Human Multivisceral Transplantation

Objectives:To describe the effect of the splenic allograft in human multivisceral transplantation. Summary Background Data:We performed transplants of the spleen as part of a multivisceral graft in an attempt to decrease both the risk of infection from an asplenic state and the risk of rejection by a possible tolerogenic effect. To our knowledge, this is the first report of human splenic transplantation in a large series. Methods:All primary multivisceral recipients who received a donor spleen (N = 60) were compared with those who did not receive a spleen (N = 81). Results:Thirty-five of 60 (58%) are alive in the spleen group, and 39 of 81 (48%) are alive in control group (P = 0.98). In univariate analysis, splenic recipients showed superiority in freedom-from-any rejection (P = 0.02) and freedom-from-moderate or severe rejection (P = 0.007). No significant differences were observed in analyses of infectious complications between the spleen and control groups. Both platelet and leukocyte counts became normal in splenic patients, whereas these counts were significantly increased in nonsplenic recipients. Observed incidence of graft versus host disease (GVHD) was 8.25% (5 of 60) in the spleen group and 6.2% (5 of 81) in the control group (P = 0.70). Increased incidence of autoimmune hemolysis was observed in the spleen group. Conclusions:Allograft spleen can be transplanted within a multivisceral graft without significantly increasing the risk of GVHD. The allogenic spleen seems to show a protective effect on small bowel rejection. Further investigation with longitudinal follow-up is required to precisely determine the immunologic and hematologic effects of the allograft spleen.

Liver transplant outcome

OBJECTIVE To compare low and high MELD scores and investigate whether existing renal dysfunction has an effect on transplant outcome. METHODS Data was prospectively collected among 237 liver transplants (216 patients) between March 2003 and March 2009. Patients with cirrhotic disease submitted to transplantation were divided into three groups: MELD > or = 30, MELD < 30, and hepatocellular carcinoma. Renal failure was defined as a +/- 25% decline in estimated glomerular filtration rate as observed 1 week after the transplant. Median MELD scores were 35, 21, and 13 for groups MELD > or = 30, MELD < 30, and hepatocellular carcinoma, respectively. RESULTS Recipients with MELD > or = 30 had more days in Intensive Care Unit, longer hospital stay, and received more blood product transfusions. Moreover, their renal function improved after liver transplant. All other groups presented with impairment of renal function. Mortality was similar in all groups, but renal function was the most important variable associated with morbidity and length of hospital stay. CONCLUSION High MELD score recipients had an improvement in the glomerular filtration rate after 1 week of liver transplantation.

Association of nonalcoholic fatty liver disease and liver cancer

AIM To investigate the association between nonalcoholic fatty liver disease (NAFLD) and liver cancer, and NAFLD prevalence in different liver tumors. METHODS This is a retrospective study of the clinical, laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation, with subsequent evaluation of the explant or liver biopsy. The following criteria were used to exclude patients from the study: a history of alcohol abuse, hepatitis B or C infection, no tumor detected in the liver tissue examined by histological analysis, and the presence of chronic autoimmune hepatitis, hemochromatosis, Wilsons disease, or hepatoblastoma. The occurrence of NAFLD and the association with its known risk factors were studied. The risk factors considered were diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, body mass index, dyslipidemia, and arterial hypertension. Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Massons trichrome and silver impregnation. Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade. RESULTS No difference was found in the association of NAFLD with the general population (34.2% and 30.0% respectively, 95%CI: 25.8-43.4). Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma (OR = 3.99, 95%CI: 1.78-8.94, P < 0.001 vs OR = 0.60, 95%CI: 0.18-2.01, P = 0.406 and OR = 0.70, 95%CI: 0.18-2.80, P = 0.613, respectively). There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma (OR = 3.50, 95%CI: 1.06-11.57, P = 0.032). Evaluation of the relationship between the presence of NAFLD, nonalcoholic steatohepatitis, and liver fibrosis, and their risk factors, showed no significant statistical association for any of the tumors studied. CONCLUSION NAFLD is more common in patients with liver metastases caused by colorectal cancer.

Valor crítico da citrulina para as complicações do enxerto no transplante de intestino

OBJECITIVE: A biochemical marker for detection of acute cellular rejection following small intestine transplantation has been sought. Citrulline, a non- protein amino acid synthesized mainly by functioning enterocytes, has been proposed. Trial sensitivity has been reportedly high but with low specificity. Thus, the goal was to determine, in a sufficiently large analysis, the significant value of citrulline level in the post-transplant setting, which would correlate with complications such as rejection and infection. METHODS: Since March, 2004 2,135 dried blood spot (DBS) citrulline samples were obtained from 57 small intestine transplant recipients three months or more after post-transplant, i.e., once the expected period of recovery in the citrulline levels had occurred. RESULTS: Using a 13 µmoles/L cut off point, sensitivity of DBS citrulline for the detection of moderate or severe ACR was extremely high (96.4%). Furthermore, specificity estimates (given the absence of ACR and these particular infections), while controlling for time-to-DBS sample were reasonably high (54%-74% in children and 83%-88% in adults), and the negative predictive value (NPV) was >99%. CONCLUSION: Citrulline is a non-invasive marker to evaluate problems of the intestinal graft after three months post-transplant. Due to the high NPV, a moderate or severe ACR can be ruled out, based exclusively on knowledge of a high value for DBS citrulline.

Test beam operation of the CMS calorimeter trigger synchronization boards

The CMS experiment uses information from its electromagnetic and hadronic calorimeters and muon detectors to decide whether to read out the whole detector. For such a task to be successful, all trigger primitives pushed through the trigger decision tree must be flawlessly aligned in time for operation at 40 MHz. Both calorimeters in CMS use the Synchronization Link Board for this purpose. In this article we report on the test results of this board using the bunched beams available in the H4 electron beam line at CERN.

The CMS Electromagnetic Calorimeter Data Acquisition System at the 2006 Test Beam.

The electromagnetic calorimeter of the CMS experiment at CERN is an homogeneous calorimeter made of about 80000 Lead Tungstate crystals, that will start to operate at the LHC at the end of 2007. From June to November 2006, ten barrel Supermodules (1700 crystals each) were exposed to beam at CERN SPS, both in standalone and in association with portions of the Hadron Calorimeter. We present the description of the system used to configure and readout the calorimeter during the campaign. The full set of final readout electronics boards was employed, together with the pre-series version of the data acquisition software. During the campaign, the hardware and software concepts for the final system were validated. The system allowed the intercalibration of the ten Supermodules and allowed to perform several important studies of the detector performances, such as energy resolution, response linearity and radiation-hardness.

First beam operation of the CMS calorimeter trigger synchronization boards

The CMS experiment uses information from its electromagnetic and hadronic calorimeters and muon detectors to decide whether to readout the whole detector. For such a task to be successful, all trigger primitives pushed through the trigger decision tree must be flawlessly aligned in time for operation at 40 MHz. Both calorimeters in CMS use the Synchronization Link Board for this purpose. In this article we report on the results of tests of this board using realistic beam conditions, which demonstrate the soundness of the adopted architecture and synchronization principle.