Endovascular Treatment of Venous Outflow and Portal Venous Complications After Liver Transplantation.

Liver transplantation continues to rapidly evolve, and in 2020, 8906 orthotopic liver transplants were performed in the United States. As a technically complex surgery with multiple vascular anastomoses, stenosis and thrombosis of the venous anastomoses are among the recognized vascular complications. While rare, venous complications may be challenging to manage and can threaten the graft and the patient. In the last 20 years, endovascular approaches have been increasingly utilized to treat post-transplant venous complications. Herein, the evaluation and interventional treatment of post-transplant venous outflow complications, portal vein stenosis, portal vein thrombosis, and recurrent portal hypertension with transjugular intrahepatic portosystemic shunt (TIPS) are reviewed.

Ad honorem exhaustion: Burnout prevalence in residents from a Colombian university / Agotamiento ad honorem: prevalencia de burnout en residentes de una universidad colombiana

Abstract Introduction: The number of health professionals diagnosed with burnout syndrome is constantly increasing. Currently, in Colombia, health care institutions are not obliged to pay residents for their work during their training. Besides their living expenses, residents must also pay tuition fees, which constitutes a stressor that may contribute to the development of burnout syndrome. Objective: To measure burnout syndrome prevalence and to identify its possible association with several socioeconomic factors in residents enrolled in 2019 in the residency programs offered by the school of medicine of a public university. Materials and methods: Cross-sectional study conducted in 269 residents that had been enrolled for at least 6 months, and who were classified into two groups according to their residency program: clinical and surgical specialties. Participants were administered a survey to collect their demographic and socioeconomic data, and the Spanish version of the Maslach Burnout Inventory - Human Services Survey for Medical Personnel instrument to determine whether they had burnout syndrome or not. Data were analyzed using descriptive statistics, and associations between socioeconomic data and MBI scores were determined using the chi-squared test. Results: Burnout prevalence was 39.78%. Likewise, the presence of burnout was positively associated with lacking enough funds to pay medical specialty training associated costs (OR: 3.45, CI:2.04-5.82); having experienced recent life changing events in the last 6 months (OR: 1.84, CI: 1.07-3.14); and having had any health issue in the last 6 months (OR: 1.81, CI:1.09-3.01). Conclusion: Burnout is a prevalent condition in the study population. So, until the obligation to pay residents for their work comes fully into force in Colombia, residency programs should be aware of burnout in residents and undergo several modifications aimed at ensuring their well-being.

Resumen Introducción. El número de profesionales de la salud diagnosticados con síndrome de burnout es cada día mayor. En la actualidad, en Colombia las instituciones de salud no están obligadas a pagarles salarios durante su entrenamiento. Además, aparte de sus gastos de manutención, los residentes deben pagar matrícula, lo que puede constituir un factor de estrés que contribuye al desarrollo de burnout. Objetivo. Medir la prevalencia de síndrome de burnout e identificar su posible asociación con diversos factores socioeconómicos en residentes matriculados en programas de residencia ofrecidos por la facultad de medicina de una universidad pública en 2019. Materiales y métodos. Estudio transversal realizado en 269 residentes con un tiempo mínimo de matrícula de 6 meses, y que, según su residencia, fueron clasificados en dos grupos: especialidades clínicas y quirúrgicas. Los datos demográficos y socioeconómicos se recolectaron mediante un cuestionario diseñado para tal fin; además, para el diagnóstico de burnout se utilizó la versión en español del instrumento Maslach Burnout Inventory - Human Services Survey for Medical Personnel (MBI-HSS MP). Los datos se analizaron mediante estadística descriptiva y las asociaciones entre los datos socioeconómicos y los puntajes obtenidos en el MBI se determinaron con la prueba de chi-cuadrado. Resultados. La prevalencia de burnout fue de 39.78%. De igual forma, se observó que su ocurrencia se asoció positivamente con no tener fondos suficientes para costear los gastos asociados con la formación médica de la residencia (OR: 3.45, IC:2.04-5.82), y con haber experimentado eventos de gran importancia o haber presentado problemas de salud en los últimos seis meses (OR: 1.84, IC:1.07-3.14; y OR: 1.81, IC:1.09-3.01, respectivamente). Conclusión. El síndrome de burnout es una condición prevalente en la población estudiada. De esta forma, hasta que la obligación de pagar un salario a los residentes entre en vigencia en Colombia, los programas de residencia deben estar al tanto de este problema y realizar varias modificaciones dirigidas a asegurar su bienestar.

Patient Selection for Kidney Transplant.

The incidence of end-stage renal disease has continued to increase. Similarly, the number of patients living with a functioning renal allograft has also increased. Transplantation has improved with advances in surgical techniques, immunosuppression, and better control of comorbid conditions. Transplantation is transformative and offers the greatest potential for restoring a healthy, productive, and durable life to appropriately selected patients. This article describes factors to address in selection of renal transplant candidates and discusses commonly encountered perioperative events. Paramount to selecting appropriate candidates is the collaboration between a multidisciplinary team focused on a systematic process guided by protocols and common practices.

Improving the performance of virtual crossmatch results by correlating with nationally-performed physical crossmatches: Obtaining additional value from proficiency testing activities.

PURPOSE: When donor specific HLA antibodies (DSA) are identified, the predictive value of whether a certain strength of reactivity (mean fluorescence intensity, MFI) leads to a positive crossmatch is uncertain. To determine this, we compared the DSA MFI results we generated locally for nationally distributed proficiency samples against the percentage of other laboratories reporting a positive crossmatch. METHOD: DSA MFI from single antigen beads reported by our laboratory for nationally-distributed proficiency testing survey samples was compared against the aggregate percentage of participating laboratories reporting the crossmatch positive using direct, antiglobulin-enhanced microcytotoxic (CDC-AHG), or flow cytometric methods from 2011 to 2015. RESULTS: 180 surveys were analyzed. Positive CDC-AHG and flow cytometric crossmatches were associated with MFI greater than 8554 and 2748 respectively for HLA class I, and 6919 and 3707 respectively for class II. Institutional MFI less than 3000 had high positive predictive values (0.98, 0.85, 0.81) for negative direct, AHG, and flow crossmatches, while MFI greater than 8000 had high negative predictive values for a positive direct, AHG, and flow crossmatches (1.00, 1.00, 0.97). CONCLUSION: Review of locally-generated MFI results as part of participating in proficiency testing allow for predictability of crossmatch results against other laboratories, providing a replicable model for other participating centers.

Increased risk organ transplantation in the pediatric population.

IRD organs are classified by the Public Health Service to be at above-average risk for harboring human immunodeficiency virus, hepatitis C, and hepatitis B. Traditionally underutilized, there exists even greater reluctance for their use in pediatric patients. We performed a retrospective analysis via the United Network for Organ Sharing database of all pediatric renal and hepatic transplants performed from 2004 to 2008 in the United States. Primary outcomes were patient and graft survival. Proportional hazards regression was performed to control for potentially confounding factors. Waitlist time, organ acceptance rates, and infectious transmissions were analyzed. There were 1830 SRD renal, 92 IRD renal, 1695 SRD hepatic, and 59 IRD hepatic transplants. There were no statistically significant differences in allograft or patient survival in either group. Acceptance rates of IRD organs were lower for kidney (1.5% IRD vs 4.82% SRD) and liver (1.99% IRD vs 4.51% SRD). One transmission of a bloodborne pathogen involving a pediatric recipient out of 7797 unique transplants was reported from 2008 to 2015. IRD organs appear to have equivalent outcomes. Increasing their utilization may improve access to transplant while decreasing wait times and circumventing waitlist morbidity and mortality.

Pneumatosis intestinalis and pneumoperitoneum after bilateral lung transplantation in adults.

OBJECTIVE: The purpose of this article is to determine the clinical features, imaging findings, and possible causes of pneumatosis intestinalis (PI) or pneumoperitoneum that developed in bilateral lung transplant recipients. MATERIALS AND METHODS: From December 2004 to July 2009, seven (2%) of 321 bilateral lung transplant recipients (two women and five men; age range, 25-66 years) who developed PI or pneumoperitoneum, or both, were identified. Medical records were reviewed to determine the clinical presentation, laboratory findings, and medications at the time of presentation of PI or pneumoperitoneum. Hospital course and time to resolution of PI or pneumoperitoneum were recorded. Common factors that might explain the cause of the PI and pneumoperitoneum were evaluated. Two experienced abdominal radiologists reviewed all imaging studies and recorded the specific findings for each patient. RESULTS: All patients had minimal or no symptoms, normal laboratory study results, and no systemic, intestinal, or proven respiratory infections. All patients but one were receiving triple immunosuppressive agents (i.e., prednisone, azathioprine, and tacrolimus). The imaging findings were similar in five of the patients with the PI dominated by a linear and cystic appearance and involving only the colon. Three of the six patients with PI had both PI and pneumoperitoneum. The mean time to resolution of PI was 24 days. No definite cause for the PI and pneumoperitoneum could be determined in the seven patients. CONCLUSION: Bilateral lung transplant recipients may develop benign PI or pneumoperitoneum after surgery. Benign PI in bilateral lung transplant recipients has a similar and specific linear and cystic appearance and is not due to ischemic bowel. No specific cause for the PI and pneumoperitoneum could be determined.

Living donor and deceased donor liver transplantation for autoimmune and cholestatic liver diseases--an analysis of the UNOS database.

INTRODUCTION: Autoimmune hepatitis and cholestatic liver diseases have more favorable outcomes after liver transplantation as compared to viral hepatitis and alcoholic liver diseases. However, there are only few reports comparing outcomes of both living donor liver transplants (LDLT) and deceased donor liver transplants (DDLT) for these conditions. AIM: We aim to study the survival outcomes of patients undergoing LT for autoimmune and cholestatic diseases and to identify possible risk factors influencing survival. Survival outcomes for LDLT vs. DDLT are also to be compared for these diseases. PATIENTS AND METHODS: A retrospective analysis of the UNOS database for patients transplanted between February 2002 until October 2006 for AIH, PSC, and PBC was performed. Survival outcomes for LDLT and DDLT patients were analyzed and factors influencing survival were identified. RESULTS: Among all recipients the estimated patient survival at 1, 3, and 5 years for LDLT was 95.5%, 93.6%,and 92.5% and for DDLT was 90.9%, 86.5%, and 84.9%, respectively (p = 0.002). The estimated graft survival at 1, 3, and 5 years for LDLT was 87.9%, 85.4%, and 84.3% and for DDLT 85.9%, 80.3%, and 78.6%, respectively (p = 0.123). On multivariate proportional hazard regression analysis after adjusting for age and MELD score, the effect of donor type was not found to be significant. CONCLUSION: The overall survival outcomes of LDLT were similar to DDLT in our patients with autoimmune and cholestatic liver diseases. It appears from our study that after adjusting for age and MELD score donor type does not significantly affect the outcome.

Temporal trends in liver transplant centre volume in the USA.

BACKGROUND: Although prior studies have suggested an inverse association between liver transplant centre volume and postoperative patient mortality, more recent analyses have failed to confirm this association. To date, all studies of the relationship between centre volume and outcomes in liver transplantation have been cross-sectional in design. OBJECTIVE: The objective of our study was to examine temporal trends in the volume-outcomes relationship for liver transplantation. METHODS: We used information obtained from the Scientific Registry of Transplant Recipients (SRTR) programme-specific data reports to examine the outcomes of adult liver transplant recipients stratified by annual centre volume. This relationship between centre volume and patient outcomes was assessed over three consecutive time periods from 2000 through 2007. RESULTS: The overall 25% increase in adult liver transplant volume in the USA from 2000 to 2007 appeared to be distributed fairly equally among existing transplant centres. In the earliest time period of our analysis, high-volume centres achieved superior risk-adjusted 1-year patient outcomes compared with low-volume centres. By the third and most recent time period of the analysis, this discrepancy between the outcomes of high- and low-volume centres was no longer statistically apparent. CONCLUSIONS: The relationship between centre volume and patient outcomes for liver transplantation in the USA has become less pronounced over time, suggesting that the use of procedure volume as a marker of liver transplant centre quality cannot be justified. The performance-based review process currently utilized in the USA may have contributed to this diminishing influence of centre volume on liver transplant recipient outcomes. This type of review process should be considered as a potential alternative to the volume-based referral initiatives that have been developed for other non-transplant, complex surgical procedures.

A threaded Java concurrent implementation of the Monte-Carlo Metropolis Ising model.

This paper describes a concurrent Java implementation of the Metropolis Monte-Carlo algorithm that is used in 2D Ising model simulations. The presented method uses threads, monitors, shared variables and high level concurrent constructs that hide the low level details. In our algorithm we assign one thread to handle one spin flip attempt at a time. We use special lattice site selection algorithm to avoid two or more threads working concurently in the region of the lattice that "belongs" to two or more different spins undergoing spin-flip transformation. Our approach does not depend on the current platform and maximizes concurrent use of the available resources.

Relationship between provider volume and outcomes for orthotopic liver transplantation.

INTRODUCTION: Recent data suggests that the previously demonstrable relationship between hospital volume and outcomes for liver transplant procedures may no longer exist. Furthermore, to our knowledge, no study has been published examining whether individual surgeon volume is associated with outcomes in liver transplantation. MATERIALS AND METHODS: The Nationwide Inpatient Sample database was used to obtain early clinical outcome and resource utilization data for liver transplant procedures performed in the USA from 1988 through 2003. The relationship between surgeon and hospital volume and early clinical outcomes was analyzed with and without adjustment for certain confounding variables such as patient age and presence of co-morbid disease. RESULTS: The in-hospital mortality rate, major postoperative complication rate, and length of hospital stay after liver transplantation did not differ significantly based on hospital procedural volume. These outcome variables did, however, exhibit a statistically significant inverse relationship with individual surgeon volume of liver transplant procedures. A significant relationship between procedure volume and outcomes for liver transplantation cannot be demonstrated at the level of transplant center, but does appear to exist at the level of the individual transplant center. CONCLUSION: Minimal volume requirements for individual liver transplant surgeons may be justified, pending validation of this volume-outcomes relationship using a clinical data source.

Regionalization of hepatic resections is associated with increasing disparities among some patient populations in use of high-volume providers.

BACKGROUND: The goal of our study was to determine the temporal trends in provider volume for liver resection procedures. STUDY DESIGN: The Nationwide Inpatient Sample database for 1988 through 2003 was used to determine temporal trends in hospital and surgeon volume of liver resection procedures. We also examined whether these trends in provider volume were associated with any changes in postoperative outcomes or in patients' access to high-volume providers. RESULTS: Regionalization of liver resection procedures to high-volume surgeons and hospitals has been occurring since 1988 and, in the most recent time period assessed, 25.8% of patients underwent hepatic resection by high-volume surgeons (> or = 17 procedures per year) and 29.9% of patients underwent resection in high-volume hospitals (> or = 45 procedures per year). Unadjusted mortality data suggest that these trends might be associated with a strengthening of the inverse relationship between hospital volume of hepatic resection and postoperative mortality and with an increasing disparity for some patient populations in use of high-volume hospitals. CONCLUSIONS: Regionalization of liver resections is occurring at both the level of the individual surgeon and the hospitals where these procedures are performed. These trends in provider volume might be associated with increasing discrepancies in outcomes and patient demographics among different volume categories of hospitals.

Extended hepatic resection for gallbladder cancer.

BACKGROUND: Although radical cholecystectomy is the standard of care for gallbladder cancers that invade perimuscular connective tissue or perforate visceral peritoneum, the role of extended right hepatectomy in achieving negative resection margins is not clear. METHODS: Clinicopathologic, perioperative, and long-term outcome data were reviewed from patients who underwent hepatic resection for gallbladder cancer. RESULTS: From 1995 to 2005, 22 consecutive patients underwent hepatic resection for gallbladder cancer, and 11 underwent extended hepatectomy. Negative resection margins were achieved in all patients. There were no significant differences in postoperative morbidity, mortality, and long-term survival after extended and minor hepatectomy. T3 tumors negatively predicted overall and recurrence-free survival. COMMENTS: Extended hepatectomy achieves negative resection margins for patients with gallbladder cancer and is associated with acceptable morbidity and long-term survival.

Temporal trends in early clinical outcomes and health care resource utilization for liver transplantation in the United States.

INTRODUCTION: Procedures such as liver transplantation, which entail large costs while benefiting only a small percentage of the population, are being increasingly scrutinized by third-party payors. The purpose of our study was to conduct a longitudinal analysis of the early clinical outcomes and health care resource utilization for liver transplantation in the United States. METHODS: The Nationwide Inpatient Sample database was used to conduct a longitudinal analysis of the clinical outcome and resource utilization data for liver transplantation procedures in adult recipients performed in the United States over three time periods (Period I: 1988-1993; Period II: 1994-1998: Period III: 1999-2003). RESULTS: Compared to Period I, adult liver transplant recipients were more likely to be male, older, and non-White in Period III. Recipients were more likely to have at least one major comorbidity preoperatively than in Period I. The in-hospital mortality rate after liver transplantation decreased significantly from Period I to Period III, but the major intraoperative and postoperative complication rates increased over the same time period. Mean length of hospital stay decreased over the 15-year period, but the percentage of patients with a non-routine discharge status increased. CONCLUSION: Our findings indicate that the rate of postoperative complications and non-routine discharges after liver transplantation is increasing. However, these negative changes in the cost-outcomes relationship for liver transplantation are balanced by improving postoperative survival rates and reductions in the length of hospital stay.

Resection of noncolorectal nonneuroendocrine liver metastases: a comparative analysis.

BACKGROUND: Although established for metastatic colorectal (CR) and neuroendocrine (NE) malignancies, the role of partial hepatectomy in management of metastases from other primaries (NCRNE) is not well-defined. STUDY DESIGN: The objective of this retrospective study is to compare outcomes after partial hepatectomy for NCRNE, NE, and CR metastases and to identify factors associated with longterm survival for patients with NCRNE diseases. Tumor characteristics, treatments, and outcomes of 360 consecutive patients undergoing resection of NCRNE (n = 82), CR (n = 245), and NE (n = 33) hepatic metastases from 1995 to 2005 were analyzed. NCRNE tumors included breast (n = 20), sarcomas (n = 19), genitourinary (n = 18), melanoma (n = 11), and other (n = 14) cancers. The start date for follow-up and survival analyses was the date of partial hepatectomy. RESULTS: For patients with NCRNE, CR, and NE tumors, there were no marked differences in postoperative mortality (4%, 4%, and 9%) or complication (30%, 42%, and 42%) rates. Median overall survival was longest for NE patients (not yet reached) versus NCRNE and CR (both 44 months) patients (p < 0.05, log-rank test). NCRNE patients had shorter disease-free survival than CR counterparts (13 versus 16 months), p < 0.05 (log-rank test). After median followup of 59 months for NCRNE patients, actuarial 5-year overall and disease-free survival was 37% and 16%, respectively, with 15 5-year survivors. Multivariable analysis suggests that interval from discovery of liver metastases to resection > 6 months (p = 0.08) and administration of chemoradiotherapy after resection (p = 0.06) might be associated with improved overall survival. CONCLUSIONS: In selected patients, resection of NCRNE liver metastases can be done safely with survival similar to CR metastases. Delay of liver resection for at least 6 months and treatment with chemoradiotherapy after resection might be associated with improved longterm survival after partial hepatectomy.

Ets-1 and runx2 regulate transcription of a metastatic gene, osteopontin, in murine colorectal cancer cells.

Osteopontin (OPN) is a sialic acid-rich phosphoprotein secreted by a wide variety of cancers. We have shown previously that OPN is necessary for mediating hepatic metastasis in CT26 colorectal cancer cells. Although a variety of stimuli can induce OPN, the molecular mechanisms that regulate OPN gene transcription in colorectal cancer are unknown. We hypothesized that cis- and trans-regulatory elements determine OPN transcription in CT26 cells. OPN transcription was analyzed in CT26 cancer cells and compared with YAMC (young adult mouse colon) epithelial cells. Clonal deletion analysis of OPN promoter-luciferase constructs identified cis-regulatory regions. A specific promoter region, nucleotide (nt) -107 to -174, demonstrated a >8.0-fold increase in luciferase activity in CT26 compared with YAMC. Gel-shift assays sublocalized two cis-regulatory regions, nt -101 to -123 and nt -121 to -145, which specifically bind CT26 nuclear proteins. Competition with unlabeled mutant oligonucleotides revealed that the regions nt -115 to -118 and nt -129 to -134 were essential for protein binding. Subsequent supershift and chromatin immunoprecipitation assays confirmed the corresponding nuclear proteins to be Ets-1 and Runx2. Functional relevance was demonstrated through mutations in the Ets-1 and Runx2 consensus binding sites resulting in >60% decrease in OPN transcription. Ets-1 and Runx2 protein expression in CT26 was ablated using antisense oligonucleotides and resulted in a >7-fold decrease in OPN protein expression. Ets-1 and Runx2 are critical transcriptional regulators of OPN expression in CT26 colorectal cancer cells. Suppression of these transcription factors results in significant down-regulation of the OPN metastasis protein.

Predictive indices of morbidity and mortality after liver resection.

OBJECTIVE: To determine if use of Model for End-Stage Liver Disease (MELD) scores to elective resections accurately predicts short-term morbidity or mortality. SUMMARY BACKGROUND DATA: MELD scores have been validated in the setting of end-stage liver disease for patients awaiting transplantation or undergoing transvenous intrahepatic portosystemic shunt procedures. Its use in predicting outcomes after elective hepatic resection has not been evaluated. METHODS: Records of 587 patients who underwent elective hepatic resection and were included in the National Surgical Quality Improvement Program Database were reviewed. MELD score, CTP score, Charlson Index of Comorbidity, American Society of Anesthesiology classification, and age were evaluated for their ability to predict short-term morbidity and mortality. Morbidity was defined as the development of one or more of the following complications: pulmonary edema or embolism, myocardial infarction, stroke, renal failure or insufficiency, pneumonia, deep venous thrombosis, bleeding, deep wound infection, reoperation, or hyperbilirubinemia. The analysis was repeated with patients divided according to their procedure and their primary diagnosis. Parametric or nonparametric analyses were performed as appropriate. Also, a new index was developed by dividing the patients into a development and a validation cohort, to predict morbidity and mortality in patients undergoing elective hepatic resection. ROC curves were also constructed for each of the primary indices. RESULTS: CTP and ASA scores were superior in predicting outcome. Also, patients undergoing resection of primary malignancies had a higher rate of mortality but no difference in morbidity. CONCLUSION: MELD scores should not be used to predict outcomes in the setting of elective hepatic resection.

Nitric oxide-dependent osteopontin expression induces metastatic behavior in HepG2 cells.

Our objective was to delineate the role of nitric oxide (NO) in osteopontin (OPN)-associated metastatic properties in HepG2 cells. OPN is the major phosphoprotein secreted by malignant cells in patients with advanced metastatic cancer, is frequently overexpressed in human tumors, and has been implicated as a key mediator of tumor cell metastasis. OPN is significantly overexpressed in hepatocellular cancer (HCC) and correlates with capsular infiltration and behavior. In addition, significantly increased inducible nitric oxide synthase (iNOS) and NO expression are found in HCC. In archived human samples of normal, cirrhotic, and HCC livers, we demonstrate that iNOS and OPN protein are strongly coexpressed in hepatoma cells. In the setting of cirrhosis, hepatocytes express iNOS, but not OPN. Further in vitro studies performed with HepG2 hepatocellular cancer cells demonstrate that exogenous NO transcriptionally upregulates OPN expression. Enhanced expression of OPN in this setting is associated with increased in vitro cell adhesion and invasion. These data suggest that NO enhances HCC expression of OPN and, as a result, conveys a metastatic phenotype.

Half-life analysis of pancreas and kidney transplants.

Although graft and patient survival data are available for pancreas and kidney transplants, they are rarely reported in terms of half-life. Our aim was to determine whether a more relevant measure of outcome is patient and allograft half-life. Using the data from the Organ Procurement and Transplantation Network Registry on kidney and pancreas transplants from January 1988 to December 1996, patient and graft half-life and 95% confidence intervals were calculated and demographic variables compared. No significant differences were found between demographic variables. Kidneys transplanted in diabetics as a simultaneous kidney-pancreas (SPK) fared better than diabetics receiving a kidney alone (9.6 vs. 6.3 years). Pancreatic graft survival in an SPK pair was better than pancreas after kidney transplant or pancreas transplant alone (11.2 vs. 2.5 years). Because kidney and pancreatic grafts have a longer half-life when transplanted with their mate grafts, we should consider the relative benefits of SPKs over pancreas after kidney transplant or pancreas transplant alone to limit the loss of precious resources.

Redox-mediated upregulation of hepatocyte iNOS transcription requires coactivator PC4.

BACKGROUND: Redox-mediated upregulation of transcription of hepatocyte inducible nitric oxide synthase (iNOS) requires hepatocyte nuclear factor IV-alpha (HNF-4alpha). In this setting, PC4 is often isolated with HNF-4alpha in DNA-protein pull-down studies. Transcriptional coactivator PC4 facilitates activator-dependent transcription via interactions with basal transcriptional machinery that are independent of PC4-DNA binding. We hypothesized that PC4 is a necessary component of HNF-4alpha-regulated redox-sensitive hepatocyte iNOS transcription. METHODS: Murine CCL9.1 hepatocytes were stimulated with interleukin-1beta (IL-1beta; 1000 U/mL) in the presence and absence of peroxide (H(2)O(2); 50 nmol/L). Antisense and sense oligonucleotides to HNF-4alpha and PC4 were added selectively. Coimmunoprecipitation (Co-IP) studies determined the association between HNF-4alpha and PC4. Transient transfection was performed with the use of a luciferase reporter construct containing the murine iNOS promoter (1.8 kb). Chromatin immunoprecipitation assays determined in vivo binding of PC4 and HNF-4alpha to the iNOS promoter region. RESULTS: Ablation of either HNF-4alpha or PC4 blunted the peroxide-mediated increase in the activation of the iNOS promoter. In IL-1beta+H(2)O(2) only, co-IP studies demonstrated the presence of an HNF-4alpha-PC4 protein complex, and chromatin immunoprecipitation assays demonstrated that this complex binds to the genomic iNOS promoter. CONCLUSIONS: Redox-mediated upregulation of hepatocyte iNOS transcription requires an HNF-4alpha-PC4 transcriptional complex.

Acute kidney transplant failure following transurethral bladder polyp fulguration.

Ureteral obstruction and anastomotic leak represent the most common urologic complications of kidney transplantation. Delay in diagnosis or treatment can lead to allograft loss. Obstruction of the ureter occurs in 2% of kidney transplant recipients. Although the majority of cases are immediate technical complications of the operation, subsequent manipulation of the genitourinary system can result in iatrogenic ureteral injury. We report the case of a long-term kidney transplant recipient who developed obstructive uropathy and acute renal failure requiring dialysis after undergoing cystoscopy and bladder polyp fulguration. The etiology was inadvertent thermal injury of the ureteroneocystostomy incurred during the procedure. After attempted percutaneous management, definitive open repair resulted in a return of allograft function to baseline.