Baylor Regional Transplant Institute

Fort Worth, TX, United States

Baylor Regional Transplant Institute

Fort Worth, TX, United States
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Jacobson I.M.,Cornell University | Davis G.L.,Baylor Regional Transplant Institute | El-Serag H.,Baylor College of Medicine | Negro F.,University of Geneva | Trepo C.,Service de Gastro enterologie
Clinical Gastroenterology and Hepatology | Year: 2010

Hepatitis C virus (HCV) infections pose a growing challenge to health care systems. Although chronic HCV infection begins as an asymptomatic condition with few short-term effects, it can progress to cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC), and death. The rate of new HCV infections is decreasing, yet the number of infected people with complications of the disease is increasing. In the United States, people born between 1945 and 1964 (baby boomers) are developing more complications of infection. Men and African Americans have a higher prevalence of HCV infection. Progression of fibrosis can be accelerated by factors such as older age, duration of HCV infection, sex, and alcohol intake. Furthermore, insulin resistance can cause hepatic steatosis and is associated with fibrosis progression and inflammation. If more effective therapies are not adopted for HCV, more than 1 million patients could develop HCV-related cirrhosis, hepatic decompensation, or HCC by 2020, which will impact the US health care system. It is important to recognize the impact of HCV on liver disease progression and apply new therapeutic strategies. © 2010 AGA Institute.

Barri Y.M.,Baylor Regional Transplant Institute | Barri Y.M.,Baylor Research Institute | Parker T.,Dallas Nephrology Associates | Daoud Y.,Baylor Research Institute | Glassock R.J.,University of California at Los Angeles
Transplantation | Year: 2010

Background. Living kidney transplant donors generally have a favorable renal functional outcome postuninephrectomy, but concern remains that a reduced glomerular filtration rate (GFR) postuninephrectomy might have harmful effects. This study examines the short-term (3 months) effect of donor nephrectomy on GFR and the occurrence of stage 3 chronic kidney disease (CKD) postuninephrectomy. Methods. The prevalence of stage 3 CKD (Kidney Disease Quality Outcome Initiative [GFR<60 mL/min/1.73 m2]) was examined in 196 living donors by comparing preuninephrectomy and 3-month postuninephrectomy values of GFR using 125I-iothalamate GFR (iGFR), modification of diet in renal disease estimated GFR (eGFR), Cockcroft-Gault estimated creatinine clearance, and endogenous 24-hr creatinine clearance. The accuracy of GFR estimations for predicting iGFR was also studied. Results. The mean GFR before and after donation were iGFR, 105±18 and 68±13 mL/min/1.73 m2; eGFR, 98±19 and 63±12 mL/min/1.73 m; Cockcroft-Gault estimated creatinine clearance, 125±33 and 85±22 mL/min/1.73 m, and endogenous 24-hr creatinine clearance, 133±38 and 86±24 mL/min/1.73 m, respectively. Stage 3 CKD was found postuninephrectomy in 53 donors (27%) by iGFR and in 73 donors (38%) by eGFR. The prevalence of stage 3 CKD was greater with older age. GFR estimation equations did not accurately predict iGFR, particularly postuninephrectomy. Conclusions. Stage 3 CKD is commonly observed after living kidney donation, particularly in older donors. The long-term impact of stage 3 CKD postuninephrectomy is poorly understood and may not have the same implications as stage 3 CKD in other conditions. eGFR is a poor predictor of true GFR in kidney donors. © 2010 by Lippincott Williams & Wilkins.

Qin H.,Baylor Research Institute | Matsumoto S.,Baylor Research Institute | Klintmalm G.B.,Baylor Regional Transplant Institute | de vol E.B.,Baylor Research Institute
Cell Transplantation | Year: 2011

Conflicting results have been reported on the effectiveness of the two-layer method (TLM) compared with the University of Wisconsin (UW) method for preserving pancreata. The objective of this study was to compile the evidence for or against any difference in human islet yield and viability between these two. PubMed (January 2000 to May 2008) and Cochran Library searches were performed and 17 studies were included for the meta-analysis. Data on donor characteristics, preservation time, and outcomes were abstracted. Studies were subgrouped based on how TLM was used (UW + TLM or TLM alone), on mean cold ischemic time (CIT) (>20 h or <20 h), and on whether special chemical was used (yes or no). Meta-analysis of all studies and subgroups was performed and the pooled standardized mean differences (SMD) with 95% confidence intervals (CI) were reported. Overall, the use of TLM significantly increased islet yield [SMD, 0.74 (0.44-1.04)] and viability [SMD, 0.63 (0.14-1.12)]. The beneficial effects of TLM on islet yield were more evident when TLM was used following UW storage or when prolonged CIT was used. TLM used alone, shorter CIT, and no chemical use all resulted in similar islet viability between TLM and UW groups. Beneficial effects of TLM on islet viability were demonstrated only when TLM was used following UW storage, or with prolonged CIT, or with chemical use. In conclusion, the TLM was beneficial for prolonged pancreas preservation before human islet isolation however, benefit of the TLM for short-term preservation was not clear. © 2011 Cognizant Comm. Corp.

Abouljoud M.,Ford Motor Company | Klintmalm G.,Baylor Regional Transplant Institute | Whitehouse S.,Ford Motor Company
American Journal of Transplantation | Year: 2012

This personal viewpoint report summarizes the responses of a survey targeting established transplant programs with a structured framework, such as center, institute, or department, and stability of leadership to assure valuable experiential observations. The 18-item survey was sent to 20 US institutions that met inclusion criteria. The response rate was 100%. Seventeen institutions had a distinct transplant governance structure. A majority of respondents perceived that their type of transplant structure was associated with enhanced recognition within their institution (85%), improved regulatory compliance (85%), transplant volume growth (75%), improved quality outcomes (75%) and increased funding for transplant-related research (75%). The prevailing themes in respondents' remarks were the perceived need for autonomy of the transplant entity, alignment among services and finances and alignment of authority with responsibility. Many respondents suggested that a dialogue be opened about effective transplant infrastructure that overcomes the boundaries of traditional academic department silos. This report of an opinion survey of 20 U.S. transplant programs outlines prevailing themes and opinions regarding the optimal structure of modern transplant practice environments. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Gonzalez S.A.,Baylor Regional Transplant Institute | Gonzalez S.A.,Baylor University
Gastroenterology and Hepatology | Year: 2010

Hepatitis C virus (HCV) is the most common indication for liver transplantation in the United States, and recurrent disease associated with HCV is a major cause of allograft loss and mortality. Up to 30% of transplant recipients with HCV will develop progressive fibrosis and cirrhosis within 5 years of transplantation. Several recipient, donor, and viral factors have been identified as risk factors for disease progression. Likewise, immunosuppression with pulse corticosteroids or T-cell-depleting therapies such as muromonab-CD3 have been linked to HCV-associated allograft failure. Antiviral therapy with peginterferon alfa and ribavirin should be considered in select transplant recipients with recurrent HCV infection, as achievement of sustained virologic response is associated with increased allograft and patient survival; however, efficacy may be limited by poor tolerability, requirement for dose reductions, and treatment discontinuation. The use of emerging therapies such as direct-acting antiviral agents and steroid-sparing immunosuppression may play a major role in further advances associated with post-transplant management of recurrent HCV infection.

Lawrence M.C.,University of Texas Southwestern Medical Center | Naziruddin B.,Baylor Regional Transplant Institute | Levy M.F.,Baylor Regional Transplant Institute | Jackson A.,Yale University | McGlynn K.,University of Texas Southwestern Medical Center
Journal of Biological Chemistry | Year: 2011

Cytokines contribute to pancreatic islet inflammation, leading to impaired glucose homeostasis and diabetic diseases. A plethora of data shows that proinflammatory cytokines are produced in pancreatic islets by infiltrating mononuclear immune cells. Here, we show that pancreatic islet α cells and β cells express tumor necrosis factor-α(TNF-α) and other cytokines capable of promoting islet inflammation when exposed to interleukin-1β(IL-1β). Cytokine expression by β cells was dependent on calcineurin (CN)/nuclear factor of activated T cells (NFAT) and MAPK signaling. NFAT associated with the TNF-α promoter in response to stimuli and synergistically activated promoter activity with ATF2 and c-Jun. In contrast, the β-cell-specific transcriptional activator MafA could repress NFAT-mediated TNF-α gene expression whenever C/EBP-β was bound to the promoter. NFAT differentially regulated the TNF-α gene depending upon the expression and MAPK-dependent activation of interacting basic leucine zipper partners in β cells. Both p38 and JNK were required for induction of TNF-α mRNA and protein expression. Collectively, the data show that glucose and IL-1β can activate signaling pathways, which control induction and repression of cytokines in pancreatic endocrine cells. Thus, by these mechanisms, pancreatic β cells themselves may contribute to islet inflammation and their own immunological destruction in the pathogenesis of diabetes. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

Gonzalez S.A.,Baylor Regional Transplant Institute | Keeffe E.B.,Stanford University
Clinics in Liver Disease | Year: 2011

Early diagnosis of hepatocellular carcinoma (HCC) has a significant impact on survival by implementation of effective treatment strategies, including hepatic resection, locoregional ablative therapy, and liver transplantation. The use of serum tumor markers and biopsy are particularly important for diagnosis of small hepatic lesions with atypical features on imaging studies. α-Fetoprotein remains the most frequently used tumor marker for the diagnosis of HCC. The development of novel serum biomarkers for HCC, identification of molecular markers for tissue immunohistochemistry, and emergence of new diagnostic techniques such as proteomic profiling may improve the early detection rate of HCC in the future. © 2011 Elsevier Inc.

Gonzalez S.A.,Baylor Regional Transplant Institute | Keeffe E.B.,Stanford University
Frontiers in Bioscience | Year: 2011

Viral hepatitis is a major cause of chronic liver disease, liver failure, and hepatocellular carcinoma worldwide, resulting in significant morbidity and mortality. New insights into the pathogenesis and molecular biology of hepatitis viruses have led to the discovery of novel antiviral agents. Likewise, a greater understanding of the natural history of chronic infection, predictors of disease progression, and predictors of virologic response to therapy has resulted in more effective treatment strategies. Recent data have increasingly demonstrated that the ability to achieve a successful response to antiviral therapy may significantly reduce the risk of progressive liver disease and hepatocellular carcinoma. Immunization practices and the use of potent antiviral therapy may have a major impact in reducing the burden of chronic liver disease and the incidence of hepatocellular carcinoma associated with chronic hepatitis B and chronic hepatitis D. Individualized treatment strategies and the development of direct acting antiviral agents may lead to further improvements in the ability to achieve a sustained virologic response to therapy in chronic hepatitis C. With new advances in the treatment of chronic hepatitis, efforts to optimize viral suppression while reducing the potential for antiviral drug resistance will become increasingly important.

Gonzalez S.A.,Baylor Regional Transplant Institute | Gonzalez S.A.,Baylor University | Keeffe E.B.,Stanford University
Gastroenterology and Hepatology | Year: 2011

Genome-wide association studies have recently identified single nucleotide polymorphisms in proximity to the interleukin-28B (IL-28B) gene that can predict sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection who are undergoing therapy with pegylated interferon (IFN) α and ribavirin. IL-28B encodes IFN-λ3, a type III IFN involved in host antiviral immunity. Favorable variants of the 2 most widely studied IL-28B polymorphisms, rs12979860 and rs8099917, are strong pretreatment predictors of early viral clearance and SVR in patients with genotype 1 HCV infection. Variations in the distribution of IL-28B alleles may partly explain differences in SVR rates among ethnic groups. Further investigations have implicated IL-28B in the development of chronic HCV infection versus spontaneous resolution of acute infection and suggest that IL-28B may be a key factor involved in host immunity against HCV. Clinical trials of IFN-λ as a therapeutic agent for chronic HCV infection are currently underway. The use of IL-28B polymorphisms as a predictive tool will have a major impact on treatment strategies for chronic HCV infection, particularly in the context of emerging therapies and direct-acting antiviral agents.

Onaca N.,Baylor Regional Transplant Institute | Klintmalm G.B.,Baylor Regional Transplant Institute
Journal of Hepato-Biliary-Pancreatic Sciences | Year: 2010

Background: Liver transplantation (LTX) is indicated in selected patients with hepatocellular carcinoma (HCC) and cirrhosis. Methods: We compared the outcome of LTX for patients with and without HCC in 5-year time periods between 1987 and 2007 to reflect the implementation of the Milan tumor selection criteria in 1997 and of the model for end-stage liver disease (MELD) score-based liver allocation in 2002. Results Of 2350 patients who underwent primary LTX, 330 had HCC. Five-year patient survival for HCC patients was 28.6% in 1987-1992 and 42.3% in 1992-1997, which was 41.4-31.4% lower than that in non-HCC patients (P<0.0001). After 1997, 5-year survival was 76% for HCC patients, similar to the survival for non-HCC patients (P = 0.8784). Five-year tumor recurrence dropped from 52.9% (1987-1992) and 48.2% (1992-1997) to 11.4% (1997-2002) and 8.4% (2002-2007) (P<0.0001). Multivariate analysis for tumor recurrence showed the following significant factors: tumor size >6 cm [hazard ratio (HR) 3.67], ≥5 nodules (HR 3.441), vascular invasion (HR 3.18), transplant in 1987-1992 (HR 6.772), and transplant in 1992-1997 (HR 3.059). MELD-based liver allocation reduced median waiting time for LTX for HCC versus non-HCC (35 vs. 111 days; P = 0.005) without compromise in patient outcome. Conclusions: The results of LTX for HCC continue to improve and are equal to results in patients without HCC. © Japanese Society of Hepato-Biliary-Pancreatic Surgery and Springer 2009.

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