Combined coronary artery bypass graft and liver/kidney transplantation in a liver failure patient with acute on chronic kidney failure and antiphospholipid syndrome.

Coexisting coronary artery disease (CAD), end-stage liver disease (ESLD), renal failure, and hypercoagulable state poses a formidable clinical challenge. Here, we discuss the first known case of a patient with antiphospholipid syndrome (APLS), ESLD complicated by hepatorenal syndrome (HRS), and severe CAD who successfully underwent combined coronary artery bypass grafting (CABG) and simultaneous liver/kidney (SLK) transplant.

Transplantation of hepatitis C virus (HCV) antibody positive, nucleic acid test negative donor kidneys to HCV negative patients frequently results in seroconversion but not HCV viremia.

Anecdotal reports have suggested that transplantation of hepatitis C virus (HCV) antibody positive (Ab+)/nucleic acid test negative (NAT-) donor kidneys into HCV negative recipients is not associated with HCV transmission. We reviewed our center's outcomes of 32 HCV negative patients who received kidney allografts from 25 donors who were HCV Ab+/NAT-. The mean recipient age was 56.9 ± 12.1 years and the mean donor age was 41.5 ± 14 years, with a median Kidney Donor Profile Index (KDPI) of 68%. Twelve donors (48%) met Public Health Service (PHS) increased risk status. All patients received antithymocyte globulin induction followed by tacrolimus, mycophenolate mofetil, and steroid maintenance immunosuppression. With a mean follow-up posttransplant of 10 ± 2.7 months, 1- and 3- month serum creatinine levels were 1.7 ± 0.8 and 1.3 ± 0.4, respectively, and patient and graft survival rates were 100% and 97%, respectively. Fourteen patients (44%) seroconverted and became HCV Ab+ posttransplant. However, all 32 patients were HCV RNA negative at 1- and 3- months posttransplant, and 27 and 8 patients tested at 6- and 12-months posttransplant, respectively, remain HCV RNA negative. In conclusion, transplantation of HCV Ab+/NAT- kidneys to HCV negative recipients frequently causes HCV Ab seroconversion but not HCV viremia.

Comparison of outcomes of hand-assisted laparoscopic to open donor nephrectomy for pediatric recipients.

The purpose of this study is to compare the outcome of pediatric recipients of kidneys procured using a hand-assisted laparoscopic (HALDN group) to an open technique (ODN group). Twenty-eight patients ≤18 yr old (HALDN group) were compared with 17 patients (ODN group). The serum creatinine for HALDN and ODN groups at discharge were 0.93 ± 0.48 and 0.94 ± 0.54 mg/dL (p = 0.917), respectively. The serum creatinine for HALDN and ODN groups at six and 12 months was 1.01 ± 0.44 and 1.11 ± 0.55, and 1.04 ± 0.52 and 1.14 ± 0.46 mg/dL (p = 0.516, p = 0.554), respectively. The eGFR for HALDN and ODN groups at discharge was 108.66 ± 37.23 and 106.1 ± 50.55 mL/min/1.73 m(2) (p = 0.845), respectively. The eGFR for HALDN and ODN groups at six and 12 months was 97.77 ± 28.25 and 81.73 ± 27.46, and 94.56 ± 28.3 and 85.74 ± 30.1 mL/min/1.73 m2 (p = 0.085, p = 0.344), respectively. The patient and graft survival for both groups were 100% at 12 months post-transplant. In conclusion, the short-term outcome of recipients of kidneys procured via HALDN is comparable to that of kidneys procured via ODN in pediatric patients.

Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma.

The desmoplastic and complex tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) has presented tremendous challenges for developing effective therapeutic strategies. Strategies targeting tumor stroma, albeit with great potential, have met with limited success due to the lack of knowledge on the molecular dynamics within the tumor microenvironment (TME). In pursuit of a better understanding of the influence of miRNAs on TME reprogramming and to explore circulating miRNAs as diagnostic and prognostic biomarkers for PDAC, using RNA-seq, miRNA-seq, and single-cell RNA-seq (scRNA-seq), we investigated the dysregulated signaling pathways in PDAC TME modulated by miRNAs from plasma and tumor tissue. Our bulk RNA-seq in PDAC tumor tissue identified 1445 significantly differentially expressed genes with extracellular matrix and structure organization as the top enriched pathways. Our miRNA-seq identified 322 and 49 abnormally expressed miRNAs in PDAC patient plasma and tumor tissue, respectively. We found many of the TME signaling pathways were targeted by those dysregulated miRNAs in PDAC plasma. Combined with scRNA-seq from patient PDAC tumor, our results revealed that these dysregulated miRNAs were closely associated with extracellular matrix (ECM) remodeling, cell-ECM communication, epithelial-mesenchymal transition, as well as immunosuppression orchestrated by different cellular components of TME. The findings of this study could assist the development of miRNA-based stromal targeting biomarkers or therapy for PDAC patients.

Posttransplant biliary complications in the pre- and post-model for end-stage liver disease era.

Biliary complications remain a cause of morbidity after liver transplantation. The aim of this study was to determine whether changes in clinical practice in the era of the Model for End-Stage Liver Disease (MELD) has affected biliary complications after liver transplantation. We retrospectively reviewed all deceased donor liver transplants at a single center. Patients were categorized as pre- or post-MELD (transplant before or after February 28, 2002). A total of 1798 recipients underwent deceased donor liver transplants. Biliary stricture was more common in the post-MELD era (15.4% versus 6.4%, P < 0.001). The strongest risk factors for stricture development were donor age (odds ratio [OR] = 1.01), presence of a prior bile leak (OR = 2.24), use of choledochocholedochostomy (OR = 2.22), and the post-MELD era (OR = 2.30). Bile leak was more common in the pre-MELD era (7.5% versus 4.9%, P = 0.02), with use of a T-tube as the strongest risk factor (OR = 3.38). Surgical factors did not influence the biliary complication rate. In conclusion, even when employing multivariate analysis to allow for factors that may influence biliary strictures, transplant in the post-MELD era was an independent predictor for stricture development. Further studies are warranted to determine the etiology of this increase.

Utility of Framingham Score for Optimizing Preoperative Evaluation Among Patients Undergoing Liver Transplant Evaluation.

BACKGROUND: Cardiac testing of candidates for liver transplant (LT) requires balancing risks and benefits of cardiac procedures. The goal of this study was to evaluate the utility of the Framingham score (FS) for optimizing preoperative risk stratification for coronary artery disease (CAD). METHODS: In this single-center retrospective study of 615 adults undergoing LT evaluation from 2016 to 2019, data of preoperative evaluation, post-LT 1-year mortality, and post-LT cardiac events were reviewed. Patients >30 years of age with normal echocardiogram underwent FS calculation. Elevated FS (≥35%) patients were triaged to undergo angiogram for CAD evaluation; FS <35% patients underwent stress testing as initial CAD evaluation. RESULTS: Of 615 patients referred for LT, 481 underwent cardiac testing. Ninety-five were excluded from the FS pathway because of age, abnormal baseline echocardiogram, or known CAD. Of the remaining 386 patients in the FS pathway, 342 had a low FS and 44 had a high FS. In patients with low FS, 90% underwent stress testing as initial test; 16% underwent invasive testing at some time. In those with elevated FS, 59% underwent invasive testing as initial test. Listing rate and posttransplant outcomes were similar between patients with low and high FS. CONCLUSION: We demonstrated the feasibility of a simple algorithmic evaluation process using FS for optimizing pre-LT risk stratification for CAD. Although exceptions to the protocol occur, the proposed protocol allows for a streamlined approach by prioritizing testing based on cardiac risk. This approach may maximize diagnostic yield while limiting invasive procedures.

Hepatitis C recurrence is not adversely affected by the use of donation after cardiac death liver allografts.

Many factors can worsen a recurrent hepatitis C virus (HCV) infection after liver transplantation (LT). We sought to determine whether the use of donation after cardiac death (DCD) livers affects HCV recurrence. From January 2000 to June 2008, 37 HCV patients underwent LT with DCD allografts. The outcomes and severity of HCV recurrence were analyzed along with those for 74 matched control patients with HCV who received donation after brain death (DBD) livers. The 2 groups had similar donor and recipient characteristics, immunosuppression regimens, rates of acute cellular rejection (ACR), and HCV profiles. DCD patients had a higher incidence of primary nonfunction (19% versus 3%, P = 0.006) and significantly higher peak aspartate aminotransferase levels in comparison with DBD subjects, suggesting a greater degree of ischemia/reperfusion injury. Although the survival rates were not significantly different, DCD recipients had lower 1- and 5-year patient survival rates (83% and 69% versus 84% and 78%, respectively, P = 0.75) and graft survival rates (70% and 61% versus 82% and 74%, respectively, P = 0.24). Three hundred fourteen protocol and clinically indicated liver biopsy procedures were performed within 6 years after transplantation, and mixed modeling analysis showed that fibrosis progression rates were similar for the 2 groups (0.6 fibrosis units/year according to the Ishak modified staging system). The rates of severe HCV recurrence (retransplantation or death due to recurrent hepatitis C and/or the development of stage 4/6 fibrosis or worse within 2 years) were similar [3 DCD patients (8%) versus 11 DBD patients (15%), P = 0.38], and cytomegalovirus infection (hazard ratio = 7.9, P = 0.002, 95% confidence interval = 2.1-28.9) and ACR (hazard ratio = 6.2, P = 0.002, 95% confidence interval = 2.0-19.7) were the only independent risk factors for severe recurrence. In summary, although there was a trend of poorer overall outcomes in DCD patients, the use of DCD livers did not appear to adversely affect HCV recurrence after LT.

Individual and environmental correlates and predictors of early adherence and outcomes after liver transplantation.

CONTEXT: Little is known about patients' contribution to health outcomes after liver transplantation. Yet, in other transplant recipients, nonadherent behavior is directly related to the leading causes of morbidity and mortality in liver transplant recipients. OBJECTIVE: To examine patient and environmental factors in relation to all aspects of adherence to the posttransplantation regimen and health outcomes in the first 6 months after transplantation. DESIGN: A descriptive analysis of individual and environmental factors in relation to adherence and health outcomes at 6 months after liver transplantation. PARTICIPANTS, SETTING: One hundred fifty-two adult liver transplant recipients at the University of Pittsburgh Medical Center. MAIN OUTCOME MEASURES: Adherence to medication taking, appointment keeping, lifestyle changes, mood, quality of life, and clinical markers of liver function. RESULTS: Nonadherence was prevalent (47% with appointments, 73% with medication); relapse to drug/alcohol use occurred among a few recipients (5.6%), all with a history of substance abuse before transplantation. Patterns of coping, decision making, attitude, and social support were correlated with adherence, clinical markers, and psychological function (r = 0.22-0.45). Avoidant coping, affective dysregulation, and caregiver support emerged as robust predictors of negative clinical and mental health outcomes (beta = .224-.363). CONCLUSION: This information about liver transplant recipients is important for researchers and clinicians. Researchers can develop guidelines by using stable but modifiable characteristics of patients to identify transplant candidates at risk of nonadherence. Such guidelines would enable clinicians to prepare patients better to manage the posttransplant regimen.

Monitoring the operationally tolerant liver allograft recipient.

PURPOSE OF REVIEW: A fundamental goal in transplantation is the establishment of allograft function without ongoing immunosuppression. Robust allograft tolerance has been established in experimental transplantation models, whereas clinical operational tolerance has been described most frequently following human liver transplantation. RECENT FINDINGS: Clinical assessment of tolerance has been limited to laboratory evaluation of organ function. Additional tools include graft monitoring through biopsy and blood sampling for biomarker analysis. Current biomarkers under assessment in recent years include dendritic cell subsets, regulatory T cells, antidonor antibodies, and gene polymorphisms. Emerging microarray analysis that is being prospectively validated will also be reviewed. A further tool in the characterization of the tolerant patient will be the accurate enrollment of such patients into a multicenter registry that will prospectively follow the natural history of the patient withdrawn from immunosuppression and help facilitate the entry of interested patients to mechanistic and immune monitoring trials. The International Solid Organ Transplant Tolerance Registry (www.transplant-tolerance.org) will be briefly described. SUMMARY: Effective biomarker characterization of the operationally tolerant liver allograft recipient would allow earlier, well tolerated, prospective drug withdrawal with the goal of extending the potential benefits of drug minimization to an increasing number of patients in a more predictable fashion.

Liver biopsy findings from healthy potential living liver donors: reasons for disqualification, silent diseases and correlation with liver injury tests.

BACKGROUND/AIMS: Liver biopsies detect silent donor disease in potential living liver donors and provide material for studies of subclinical non-alcoholic fatty liver disease (NAFLD). Our primary goal was to determine the contribution of biopsy findings to potential donor evaluation. Factors contributing to pre-clinical NAFLD and correlations between liver injury tests and histopathology have been also determined. METHODS: Patient records, laboratory tests and results of the histopathologic examination and diagnoses of 284 patients from 2001 to 2005 were retrospectively extracted from the EDIT database. Hepatic histology was correlated with liver injury tests and with general demographic characteristics in an otherwise normal healthy population. RESULTS: A minority (n=119; 42%) of biopsies from this population of 143 males/141 females (average age=36.8years; mean BMI=26.6) were completely normal. The remainder showed steatosis (n=107; 37%), steatohepatitis (n=44; 15%), or unexplained low-grade/early stage chronic hepatitis, primary biliary cirrhosis, or nodular regenerative hyperplasia (n=16; 6%). Biopsy findings disqualified 29/56 donors. Independent risk factors for NAFLD by multivariate modeling, which differed by sex, included: BMI (p=0.0001), age (p=0.003), iron (p=0.01), and ALT (p=0.004). CONCLUSIONS: Liver biopsies provide valuable information about otherwise undetectable liver disease in potential liver donors. Obesity, age and iron, which are influenced by sex, contribute to NAFLD pathogenesis. Blood tests other than standard liver profiles are needed to detect early NAFLD.

Liver transplantation in patients with nonalcoholic steatohepatitis-related hepatocellular carcinoma.

BACKGROUND & AIMS: The increasing incidence of hepatocellular carcinoma in the United States is only partially accounted for by hepatitis C virus (HCV) infections. The prevalence of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis (NASH) is not known; guidelines from the American Association for the Study of Liver Diseases do not recommend surveillance imaging. We sought to determine the prevalence of hepatocellular carcinoma among patients undergoing liver transplantation for NASH-related cirrhosis and their outcome after surgery, compared with controls. METHODS: We reviewed the records of adult patients with NASH cirrhosis who underwent liver transplantation by using a prospectively collected database from a single center. Data from patients with NASH cirrhosis were compared with matched controls who received transplantation for primary biliary cirrhosis/primary sclerosing cholangitis, alcoholic liver disease, or HCV. RESULTS: Seventeen of 98 patients (17%) with NASH cirrhosis were diagnosed with hepatocellular carcinoma. The mean age was 63 years, and 70% were male. Six patients were diagnosed with hepatocellular carcinoma incidentally on explant. Survival after liver transplantation was 88% after mean follow-up of 2.5 years. The number of NASH patients known to have hepatocellular carcinoma before liver transplantation was greater than the number of patients with primary biliary cirrhosis/primary sclerosing cholangitis and comparable to the number of patients with alcoholic liver disease and HCV. CONCLUSIONS: Patients with NASH cirrhosis are at risk for developing hepatocellular carcinoma; patients with NASH cirrhosis, especially men older than 50 years, should undergo surveillance imaging. Patients with NASH and hepatocellular carcinoma have good outcomes after liver transplantation.

The biology of interleukin-2 efficacy in the treatment of patients with renal cell carcinoma.

Renal cell carcinoma (RCC) is the eighth most common malignancy in adults in the United States. More than 50% of individuals present with metastatic disease and conventional chemotherapeutic strategies have been associated with poor response rates. Immunotherapy with Interleukin (IL)-2, however, induces durable remission, achieving >10 year recurrence free survival in 5-10% of patients with advanced RCC. First described as a T cell growth factor, IL-2 has a wide spectrum of effects in the immune system. Some of the possible mechanisms by which IL-2 carries out its anticancer effects include the augmentation of cytotoxic immune cell functions and reversal of T cell anergy, enabling delivery of immune cells and possibly serum components into tumor. IL-2 indirectly limits tumor escape mechanisms such as defective tumor cell expression of Class I or Class II molecules or expansion of regulatory T cells. Indirect effects on the tumor microenvironment are also likely and associated with rather dramatic T cell infiltration during the global delayed type hypersensitivity response that is associated with systemic IL-2 administration. The IL-2 signaling pathway, its effects on immune cells, and its role in various independent mechanisms of tumor surveillance likely play a role but little substantive data defining a clear phenotype or genotype of IL-2 responders distinguishing them from nonresponders has emerged in the last 25 years since IL-2 therapy was initiated. At best, we can only speculate that the disturbed homeostatic host/tumor interaction is reset in a small subset of patients allowing an antitumor response to recover or ensue.

How a Donor Nephrectomy Population Can Help Give Perspective to the Effects of Renal Parenchymal Preservation During Partial Nephrectomy.

Introduction: Volume of renal parenchymal loss is known to affect postoperative renal function after partial nephrectomy (PN). We utilize a novel comparison using donor nephrectomy (DN) patients to demonstrate the primary effect parenchymal volume loss plays on postoperative renal function following PN. Materials and Methods: Records of 250 living donor (DN) and 118 PN patients were retrospectively reviewed. Baseline characteristics and preoperative estimated glomerular filtration rate (eGFR)s were recorded. Percent changes in eGFR and incidences of surgically induced chronic kidney disease (CKD-S) in short, intermediate, and long-term postoperative periods were compared. Univariate and multivariate analyses of prognostic factors for development of CKD-S were performed. The PN group was further divided into subgroups with different lengths of warm ischemia time (WIT) and compared with DN patients. Results: At baseline, DN patients were younger, less likely to be male, had lower body mass index, lower American Society of Anesthesiologists, and higher preoperative eGFR (all p < 0.001). At hospital discharge, intermediate follow-up, and latest follow-up, renal function changes in DN and PN groups were -40.5% vs. -3.6%, -34.1% vs. -5.5%, and -33.2% vs. -4.4%, respectively (all p < 0.001). More DN than PN patients developed CKD-S (p < 0.001). DN was a significant risk factor for the development of chronic kidney disease on univariate and multivariate analyses (p < 0.001). On subgroup analysis, both subgroups with WIT 1 to 30 minutes and 31 to 60 minutes had less renal function decline at all time points compared with DN (p < 0.001). Conclusions: Volume of renal parenchyma retained is the dominant driver of postoperative renal function after nephrectomy, compared with all other factors. Surgeons should minimize parenchymal loss during PN to optimize postoperative renal function.

Should donors who have used marijuana be considered candidates for living kidney donation?

BACKGROUND: The use of marijuana in the USA has been steadily increasing over the last 10 years. This study is the first to investigate the effect of marijuana use by live kidney donors upon outcomes in both donors and recipients. METHODS: Living kidney donor transplants performed between January 2000 and May 2016 in a single academic institution were retrospectively reviewed. Donor and recipient groups were each divided into two groups by donor marijuana usage. Outcomes in donor and recipient groups were compared using t-test, Chi-square and mixed linear analysis (P < 0.05 considered significant). RESULTS: This was 294 living renal donor medical records were reviewed including 31 marijuana-using donors (MUD) and 263 non-MUDs (NMUD). It was 230 living kidney recipient records were reviewed including 27 marijuana kidney recipients (MKRs) and 203 non-MKRs (NMKR). There was no difference in donor or recipient perioperative characteristics or postoperative outcomes based upon donor marijuana use (P > 0.05 for all comparisons). There was no difference in renal function between NMUD and MUD groups and no long-term difference in kidney allograft function between NMKR and MKR groups. CONCLUSIONS: Considering individuals with a history of marijuana use for living kidney donation could increase the donor pool and yield acceptable outcomes.

Predictors of Systolic Heart Failure and Mortality Following Orthotopic Liver Transplantation: a Single-Center Cohort.

OBJECTIVES: The purpose of this study was to identify risk factors that may predict heart failure with reduced ejection fraction (HFrEF) following orthotopic liver transplantation (OLT) and associated mortality. BACKGROUND: HFrEF following OLT is a poorly understood phenomenon, reported in 3% to 7% of transplanted patients. METHODS: This is a retrospective analysis of 176 consecutive patients who underwent OLT from 2010 to 2017. Multivariate logistic regression was used to identify associations between cardiovascular risk factors and perioperative variables with post-OLT HFrEF, defined as reduction in left ventricular ejection fraction of at least 10% and left ventricular ejection fraction less than or equal to 40% with acute heart failure symptoms. Multivariate cox proportional hazards regression (with inverse probability weighting by propensity scores) was used to evaluate effects of HFrEF on 1-year mortality. RESULTS: Of the176 patients, 14% developed HFrEF with a median of 5 days. History of heart failure (OR 10.99, 2.15-56.09; P = .04) and intraoperative transfusion of greater than 11 units of packed red blood cells (OR 3.377, 1.025-11.13; P = .045) were associated with increased incidence of HFrEF. Pre-transplant hemoglobin greater than 8.5 g/dL (OR 0.252, CI 0.0954- 0.665; P = .05) was protective against HFrEF. Thirty-three percent of HFrEF group died within 1 year (HR 7.36, 2.57-21.12; P < .001). CONCLUSIONS: The incidence of acute HFrEF post-OLT is 14% and is associated with a 7-fold increase in 1-year mortality. Cirrhotic cardiomyopathy and stress-induced cardiomyopathy maybe the underlying mechanisms. Our study identified risk factors associated with post-OLT HFrEF and should provide additional guidance for risk stratification of patients undergoing OLT.

Age, model for end-stage liver disease score, and organ functioning predict posttransplant tacrolimus neurotoxicity.

Calcineurin-inhibiting immunosuppressive medications are the mainstay of posttransplant immunosuppression. Although these highly beneficial drugs are critical for posttransplant survival, significant numbers of transplant recipients experience side effects, some requiring a switch to a different immunosuppressive regimen. Neurotoxicity is one of the most debilitating side effects because of its impact on mental status and cognition. As our center uses tacrolimus as the initial immunosuppressant for all liver transplant (LTX) recipients, we were interested in those patients who required a switch because of neurotoxic side effects. Over a 5-year period, 827 adult LTX recipients received their first graft at our center. Ninety-four patients were no longer on tacrolimus by 2 months post-LTX (86 switched because of concerns over neurotoxicity, and 8 switched because of renal function concerns). Of those experiencing neurotoxic side effects, the majority (64%) had altered mental status, and 26% had seizures (first onset post-LTX). On the basis of our prior work, we hypothesized that patients with a pre-LTX history of excessive alcohol use would be at higher risk for neurotoxic effects. We also hypothesized that the elderly and those who had more advanced illness (that is, higher Model for End-Stage Liver Disease scores) at LTX would be at risk as well. We found that patients with a pre-LTX diagnosis of alcoholic liver disease were not more likely to be switched from tacrolimus. Furthermore, we found that in addition to older age and higher Model for End-Stage Liver Disease scores, poorer hepatic functioning was significantly associated with a switch from tacrolimus. We discuss the implications of these findings and the relevance for future clinical care in these high-risk patients.

Extrahepatic portal vein aneurysm--report of six patients and review of the literature.

Extrahepatic portal vein aneurysm is a rare condition. We report six patients with extrahepatic portal vein aneurysm, four of whom were surgically treated. In addition, a review of the literature was performed to examine natural history, management, and outcomes regarding portal vein aneurysm. Patients seen at our institution with extrahepatic portal vein aneurysm greater than 1.9 cm in diameter were reviewed (1998 to 2006). There were five females and one male; median age was 66.5 (30-77). Computed tomography (CT) scan was utilized for diagnosis in all cases. The median diameter of the aneurysm was 4.7 cm (2.7-6.0). Indications for surgery included gallstone pancreatitis, mass effect on the adjacent duodenum, a peripancreatic mass, and liver cirrhosis. Three patients underwent aneurysm resection, and one patient had an orthotropic liver transplant. Two patients were managed with observation. The median follow-up from first presentation and surgery was 50 months (9-181) and 5 months (2-73), respectively. At last follow-up, five patients were alive with radiologically proven portal vein patency. One patient died 2 months after liver transplantation. There was no case of aneurysmal rupture. One patient had intramural thrombus at presentation that resolved with conservative treatment. This report suggests that symptomatic aneurysms can be safely resected with excellent patency.

Masquerader: high mobility group box-1 and cancer.

Since its identification a third of a century ago, the high-mobility group box-1 (HMGB1) protein has been linked to varied diverse cellular processes, including release from necrotic cells and secretion by activated macrophages engulfing apoptotic cells. Initially described as solely chromatin-associated, HMGB1 was additionally discovered in the cytoplasm of several types of cultured mammalian cells 6 years later. In addition to its intracellular role, HMGB1 has been identified extracellularly as a putative leaderless cytokine and differentiation factor. In the years since its discovery, HMGB1 has also been implicated in disease states, including Alzheimer's, sepsis, ischemia-reperfusion, arthritis, and cancer. In cancer, overexpression of HMGB1, particularly in conjunction with its receptor for advanced glycation end products, has been associated with the proliferation and metastasis of many tumor types, including breast, colon, melanoma, and others. This review focuses on current knowledge and speculation on the role of HMGB1 in the development of cancer, metastasis, and potential targets for therapy.

Post-Transplant Diabetes Mellitus After Kidney Transplant in Hispanics and Caucasians Treated with Tacrolimus-Based Immunosuppression.

BACKGROUND Development of post-transplant diabetes mellitus after kidney transplant (PTDM) significantly increases kidney graft loss and mortality. Several risk factors for PTDM have been reported, including Hispanic ethnicity and the use of calcineurin inhibitors and corticosteroids. The incidence and impact of PTDM in the Hispanic kidney transplant population is unknown. MATERIAL AND METHODS We retrospectively reviewed the medical records of 155 Hispanic and 124 Caucasian patients, who were not diabetics and underwent kidney transplant between January 2006 and December 2011. We analyzed their clinical outcomes at 12 months post-transplant, including the incidence of PTDM, acute rejection rates, and patient and graft survival. RESULTS Hispanics who developed PTDM (n=22) were more than 10 years older and had higher body mass index (BMI) than Hispanics without PTDM (p<0.001 and p=0.001, respectively). Caucasians with PTDM (n=13) were non-significantly older (2.5 years) and had higher BMI than Caucasians without PTDM (p=0.526, p=0.043, respectively). The incidence of PTDM was not significantly different between Hispanics and Caucasians treated with tacrolimus-based immunosuppression (14.2% and 10.5%, respectively). CONCLUSIONS PTDM did not cause significant difference in short-term outcomes after kidney transplant in Hispanics or Caucasians. Larger multicenter prospective and long-term clinical trials are needed to validate these findings.