According to the Texas Department of State Health Services, there ar.pdf

According to the Texas Department of State Health Services, there ar.pdf

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  According to theTexas Department of State Health Services, there are approximately 17.7 million adults (age 18+) living in Texas, of which 1.47 million have diabetes. In 2010, 341,430 adult Texans were diagnosed with diabetes for the first time. What is the incidence of diabetes in Texas? Express your answer in units of per 1000 persons per year. Solution 191 Patients with hepatocellular carcinoma (HCC) within Milan criteria receive priority on the liver transplant(LT) waiting list(WL) and compete with non-HCC candidates. We compared dropout from the WL using a competing risks approach to assess the relative access to transplant for these two groups. The cohort consists of all candidates listed 4/14/04 - 12/31/2007 with HCC candidates identifi ed via initial exception application. Status 1 and pediatric patients were excluded. Dropouts included removals for candidate death, too sick, and for other. A multivariable waiting list analysis was performed using a Cox model of time to dropout and competing risks model. Results: Non-HCC patients had a signifi cantly higher dropout rate from the WL compared with HCC patients over one year after listing/exception. This was reproducible across all regions. Ablation had little infl uence on HCC dropout. Larger tumor size, higher MELD score and/or AFP were associated with increased dropout. Multivariable analysis with competing risks showed that MELD, log AFP, max tumor size were of signifi cance in predicting dropout for HCC patients. % dropout Days after Listing 30 60 90 180 365 Non-HCC All MELD 6.5 9 10.6 13.9 17.9 No Ablation 2.2 4 6 9.2 11.8 Ablation 1.4 3.1 4.7 8 11.2 Non-HCC MELD <21 1.4 2.9 4.4 8.1 13.1 HCC + MELD < 8 0.6 1.4 1.9 4 6.6 HCC + MELD 8-11 0.9 2.4 3.7 6.1 8.5 HCC + MELD 11-14 1 2.8 4.3 7.8 10.3 HCC + MELD >14 3.9 6.6 9.4 13.9 17.7 Tumor < 2 cm 0.9 2.6 4.9 8.2 11.2 2-2.6 1.8 3.4 5.1 8 10.4 2.6-3.3 2.3 3.8 5.2 8.4 11.1 > 3.3 2 4.4 6.3 10 13.4 AFP < 500 1.7 3.2 4.8 7.5 10.2 500-1000 2.8 6.4 9.2 15.3 18.2 >1000 4 8.3 13 21.8 27.8 Conclusions: HCC patients appear to be advantaged in the current allocation scheme as shown by lower dropout rates. This advantage is consistent through the UNOS regions. A continuous score incorporating MELD, AFP and tumor size would help prioritize HCC with non-HCC patients to help equate dropout rates and equalize the allocation scheme. Abstract# 4 Primary Outcomes from a Randomized, Phase III Study of Belatacept vs Cyclosporine in Kidney Transplant Recipients (BENEFIT Study). F. Vincenti,1 J. M. Grinyo,2 B. Charpentier,3 J. D. Medina-Pestana,4 L. Rostaing,5 Y. Vanrenterghem,6 G. B. Di Russo,7 P. Garg,7 C.-S. Lin,7 C. Larsen.8 1UCSF; 2Univ Hospital of Bellvitge; 3Hopital Bicetre; 4Hospital do Rim e Hipertensao Unifesp; 5CHU Ranguell; 6Univ Hospital Kuleuven; 7Bristol-Myers Squibb; 8Emory Univ
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  School of Medicine.Introduction: Belatacept, a co-stimulation blocker, is being developed as an immunosuppressant for kidney transplant recipients to avoid the renal and extrarenal toxicities of calcineurin inhibitors (CNIs) that impact long-term patient/graft survival. BENEFIT assessed belatacept-based regimens vs a cyclosporine-based regimen (CsA) in kidney transplant recipients. Methods: BENEFIT is a 3-year, randomized, phase III study in adults receiving a kidney transplant from a living or deceased donor with an anticipated cold ischemia A. Carver College of Medicine, University of Iowa, VA Medical Center, Iowa City, IA. Type 1 diabetes can be successfully treated by islet transplantation. However, acute shortage of organ donors, lifelong immunosuppression and chronic graft rejection currently limit the treatment of diabetic patients. Pluripotent embryonic stem (ES) cells offer a potentially novel approach for the treatment of type 1 diabetes. We investigated whether ES cells genetically reprogrammed to express a pancreatic b cell specifi c transcription factor Pdx1 leads to enhanced in vivo differentiation into insulin producing cells. We generated a double stable ES cell line R1 Pdx1 simultaneously co-expressing EF1a promoter driven Pdx1AcGFP fusion protein and rat insulin promoter driven luciferase. The undifferentiated R1 Pdx1 ES cell line expressed the pluripotency molecular markers Oct4 and Nanog, as well as nuclear localized Pdx1AcGFP fusion protein. The undifferentiated R1 Pdx1 ES cells were treated with Activin A for eight days to generate Pdx1+CXCR4+ defi nitive endoderm (DE) cells. Purifi ed Pdx1+CXCR4+ DE cells were either directly infused or transplanted under the kidney capsule of diabetic mice. For the induction of diabetes, mice were treated with streptozotocin. Long term sustained correction of hyperglycemia was achieved using both direct infusion as well as renal transplantation of Pdx1+CXCR4+ DE cells. The blood glucose levels decreased from >500 mg/dl at day 14 post transplantation to =200 mg/dl at day 30 thereby suggesting glucose regulated insulin secretion by the transplanted Pdx1+CXCR4+ DE cells. All of the mice (N=10) either directly infused or transplanted with Pdx1+CXCR4+ DE cells achieved normoglycemia, were tumor free and survived throughout the duration of the study (>100 days) while all of the mice in the control group (N=10) died within 9 days. Using real-time non invasive in vivo bioluminescence imaging and immunohistochemical analysis, we demonstrate that direct infusion of Pdx1+CXCR4+ DE cells leads to their in vivo homing into the pancreas, de novo differentiation into functional insulin producing cells and sustained correction of hyperglycemia. Thus, in vivo differentiation of R1 Pdx1-derived DE cells into insulin producing cells offers a potentially novel approach for the treatment of type 1 diabetes. Abstract# 2 Early Results from the Clinical Trials in Organ Transplantation (CTOT-01) Trial Identify Noninvasive Markers as Correlates of 6-Month Renal Allograft Pathology. D. Hricik, E. Poggio, K. Newell, D. Rush, P. Nickerson, R. Formica, E. Akalin, J. Goebel, R. Fairchild, H. Gebel, D. Ikle, P. Heeger. CTOT-01 Consortium. CTOT01 is an NIH funded prospective observational study testing the utility of noninvasive blood and
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  urinary monitoring topredict kidney transplant injury. Adult and pediatric crossmatch negative recipients of fi rst kidney transplants from 8 centers are being enrolled, with locally determined immunosuppression. The primary endpoint is cumulative incidence of acute rejection (AR) or incremental fi brosis based on evaluation of implantation and 6 mo protocol biopsies (increase in Banff ci/ct scores >2 vs implantation). Blood and urine samples are obtained pretransplant (preTx) and serially posttransplant (postTx) for a panel of assays including HLA antibodies, IFNgamma ELISPOT, and urine infl ammatory molecule/chemokine gene and protein expression. Enrollment has reached 235 (of a projected 300) and the 6 mo biopsy has been obtained on >90% of eligible patients. Thus far, results have been analyzed on 100 patients. Mean age is 46 yrs, 60% are male, 67% obtained grafts from living donors, and 82% received induction antibodies (anti-IL2R or rATG). 17/100 patients (17%) had biopsy proven AR (Banff grade 1A or higher, including 4 detected on the 6 mo biopsy). In total, 32/100 (32%) reached the composite study endpoint. >90% of monitoring samples have been collected. No patient developed de novo donor-directed alloantibodies. Univariate analyses reveal that preTx donorreactive ELISPOT correlate with both AR (p=0.04) and the composite endpoint (p=0.02). Higher postTx mean values (obtained during mo 1-6) of several Luminexassessed urinary proteins correlated with AR (IP-10, p=0.04; MIG, p<0.02) or with the composite endpoint (IP- 10, p=0.005; MCP1, p=0.01, MIG, p<0.04). There were trends for correlations between posTx mean mRNA for granzyme B (p=0.095) and IP-10 (p=0.099) and the composite endpoint. Using logistic regression, a predictive model for the composite endpoint was developed using preTx ELISPOT, postTx mean IP-10 protein and mean mRNA for granzyme B and IP-10. Using ROC analysis, the model has an AUC of 0.86, sensitivity of 92% and specifi city of 72%. These results suggest that noninvasive blood and urine monitoring, employing multiple assays, can be used to assess risk of renal allograft injury. Once validated, analogous noninvasive monitoring should be useful for guiding individualized treatment based on likelihood of subsequent allograft injury.