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Tamimi T.I.A.-R.,Digestive Disease Institute | Elgouhari H.M.,Transplant Institute | Alkhouri N.,Cleveland Clinic | Yerian L.M.,Cleveland Clinic | And 5 more authors.
Journal of Hepatology | Year: 2011

Background & Aims: The extrinsic death receptor-mediated pathway of apoptosis is involved in nonalcoholic steatohepatitis (NASH) development. Our aims were to create and validate a noninvasive prediction model for NASH diagnosis based on specific circulating markers of apoptosis. Methods: Our initial cohort consisted of 95 consecutive patients undergoing a liver biopsy for clinically suspected NASH. Blood was obtained from each patient at the time of liver biopsy. Plasma caspase 3 generated cytokeratin-18 fragments (CK-18), soluble Fas (sFas), and soluble Fas ligand (sFasL) were measured. Histology was assessed by an experienced hepatopathologist. The validation cohort consisted of 82 consecutive patients that underwent liver biopsy at the time of bariatric surgery. Results: Patients with NASH had significantly higher levels of CK-18 and sFas than patients in the "not NASH" group [median (25th, 75th percentile): 508 (280, 846) U/L versus 176 (131, 224) U/L (p <0.001), and 11.8 (7.8, 12.5) ng/ml versus 5.9 (4.8, 8.3) ng/ml (p <0.001), respectively]. A significant positive correlation was revealed between the apoptosis markers and liver histopathology independent of other metabolic factors. A prediction model was generated including CK-18 fragments and sFas levels that showed an AUC of 0.93 and 0.79 in the initial and validation cohorts, respectively. A cutoff value using this model predicted NASH with a sensitivity and specificity of 88% and 89%, respectively. Conclusions: Quantification of circulating levels of two apoptotic markers accurately predicts the presence of NASH, supporting the potential usefulness of these markers in clinical practice for noninvasive diagnosis of NASH. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Hardinger K.L.,University of Missouri | Hutcherson T.,University of Missouri | Preston D.,University of Missouri | Murillo D.,Transplant Institute
Pharmacotherapy | Year: 2012

Study Objective. To determine the influence of pill burden and drug cost on outcomes after renal transplantation. Design. Retrospective medical record review. Setting. Kidney and pancreas transplantation center. Patients. Sixty-eight adults who underwent kidney or kidney-pancreas transplantation during 2007. Measurements and Main Results. The median pretransplantation pill burden was 15 pills/day, which increased to 25 pills/day at 1 month after transplantation and returned to 16 pills/day by 1 year after transplantation. Pretransplantation pill burden was lower than the burden at 1, 3, 6, 12, and 24 months after transplantation (p<0.05). The mean pretransplantation drug cost of $1918/month was lower than the cost at 1 month after transplantation ($2564/mo, p=0.04) but was similar thereafter. Higher pretransplantation pill burden was associated with increased serum creatinine concentration at 6 months after transplantation (r=0.288, p=0.017). Higher pill burdens at 1 month (r=0.364, p=0.002), 3 months (r=0.332, p=0.006), and 6 months (r=0.374, p=0.002) were associated with increased 3-month serum creatinine concentration. Higher drug costs were associated with increased serum creatinine concentrations throughout the study. Conclusion. Higher pretransplantation pill burden and higher drug cost may be associated with poor renal function after transplantation. Further study addressing factors associated with nonadherence is needed. Copyright © 1999-2012 John Wiley & Sons, Inc.

News Article | April 11, 2016
Site: motherboard.vice.com

The promise of immortality is core to many religions, but it’s rarely as literal as it is at The Church of Perpetual Life, a zealous house of worship in Hollywood, Florida whose members have decided they don’t want to die. "We are fighting against involuntary death, and view immortality as the ultimate solution to every problem mankind faces,” said Bill Faloon, one of the church’s founders. His parishioners call themselves “immortalists.” Other monikers include transhumanists, “longevity enthusiasts,” and “people who really are committed to the anti-aging concept.” Whatever they call themselves, they all share one thing in common: They believe that science and technology will find a way for humans to live forever on Earth. Motherboard’s Claire Evans visited the church and spent time with Faloon, who also cofounded the Life Extension Foundation Inc., which sells a variety of nutritional supplements that promise to do everything from protecting against eyesight degeneration to promoting cell regeneration. The Foundation says its primary goal is to fund research into anti-aging science. Forever Young, a short documentary produced by Evans, Jaimie Sanchez, and Motherboard, explores the psychology of the church’s members, the history of transhumanism and anti-aging, and the reaction of the mainstream medical community to some of these ideas. Gerontology expert Aubrey Grey, transhumanist and Sirius XM founder Martine Rothblatt, and Dr. Dinarine Maharaj of the South Florida Stem Cell Transplant Institute also make an appearance in the film. The people Evans spoke to, including Faloon, seem genuine in their quest for eternal life. However, it’s hard to overlook the fact that the church was formed after the Life Extension Foundation had its tax-exempt status revoked by the IRS. Is the Church of Perpetual Life a fellowship of purist transhumanist devotees, or a front for shilling vitamins? Is its promise of immortality a scam that draws in wishful thinkers, or is it actually possible that one day, humans might conquer death? "Sometimes it's very difficult to draw a line about what seems crazy and what doesn't seem crazy,” Evans said, “because crazier things have happened. We went to the Moon. Where do you draw the line and say, ‘oh that's really science fiction, that's never going to happen?’"

Sintek M.A.,University of Washington | Gdowski M.,University of Washington | Lindman B.R.,University of Washington | Nassif M.,University of Washington | And 6 more authors.
Journal of Cardiac Failure | Year: 2015

Objective The aim of this work was to characterize the clinical response and identify predictors of clinical stabilization after intra-aortic balloon counterpulsation (IABP) support in patients with chronic systolic heart failure in cardiogenic shock before implantation of a left ventricular assist device (LVAD). Background Limited data exist regarding the clinical response to IABP in patients with chronic heart failure in cardiogenic shock. Methods We identified 54 patients supported with IABP before LVAD implantation. Criteria for clinical decompensation after IABP insertion and before LVAD included the need for more advanced temporary support, initiation of mechanical ventilation or dialysis, increase in vasopressors/inotropes, refractory ventricular arrhythmias, or worsening acidosis. The absence of these indicated stabilization. Results Clinical decompensation after IABP occurred in 23 patients (43%). Both patients who decompensated and those who stabilized had similar hemodynamic improvements after IABP support, but patients who decompensated required more vasopressors/inotropes. Clinical decompensation after IABP was associated with worse outcomes after LVAD implantation, including a 3-fold longer intensive care unit stay and 5-fold longer time on mechanical ventilation (P <.01 for both). Although baseline characteristics were similar between groups, right and left ventricular cardiac power indexes (cardiac power index = cardiac index × mean arterial pressure/451) identified patients who were likely to stabilize (area under the receiver operating characteristic curve = 0.82). Conclusions Among patients with chronic systolic heart failure who develop cardiogenic shock, more than one-half of patients stabilized with IABP support as a bridge to LVAD. Baseline measures of right and left ventricular cardiac power, reflecting work performed for a given flow and pressure, may allow clinicians to identify patients with sufficient contractile reserve who will be likely to stabilize with an IABP versus those who may need more aggressive ventricular support. © 2015 Elsevier Inc.

Toffanin S.,Mount Sinai Liver Cancer Program | Toffanin S.,Tisch Cancer Institute | Toffanin S.,Transplant Institute | Toffanin S.,Italian National Cancer Institute | And 12 more authors.
Hepatology | Year: 2012

Increased translocation of intestinal bacteria is a hallmark of chronic liver disease and contributes to hepatic inflammation and fibrosis. Here we tested the hypothesis that the intestinal microbiota and Toll-like receptors (TLRs) promote hepatocellular carcinoma (HCC), a long-term consequence of chronic liver injury, inflammation, and fibrosis. Hepatocarcinogenesis in chronically injured livers depended on the intestinal microbiota and TLR4 activation in non-bone-marrow-derived resident liver cells. TLR4 and the intestinal microbiota were not required for HCC initiation but for HCC promotion, mediating increased proliferation, expression of the hepatomitogen epiregulin, and prevention of apoptosis. Gut sterilization restricted to late stages of hepatocarcinogenesis reduced HCC, suggesting that the intestinal microbiota and TLR4 represent therapeutic targets for HCC prevention in advanced liver disease. © 2012 American Association for the Study of Liver Diseases.

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