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2,539 results on '"Busuttil, Ronald W."'

206. Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction

Author

Agopian, Vatche G., primary, Markovic, Daniela, additional, Klintmalm, Goran B., additional, Saracino, Giovanna, additional, Chapman, William C., additional, Vachharajani, Neeta, additional, Florman, Sander S., additional, Tabrizian, Parissa, additional, Haydel, Brandy, additional, Nasralla, David, additional, Friend, Peter J., additional, Boteon, Yuri L., additional, Ploeg, Rutger, additional, Harlander-Locke, Michael P., additional, Xia, Victor, additional, DiNorcia, Joseph, additional, Kaldas, Fady M., additional, Yersiz, Hasan, additional, Farmer, Douglas G., additional, and Busuttil, Ronald W., additional

Published
2021
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208. The impact of marijuana use on liver transplant recipients: A 900 patient single center experience

Author

Guorgui, Jacob, primary, Ito, Takahiro, additional, Markovic, Daniela, additional, Aziz, Antony, additional, Younan, Stephanie, additional, Severance, Alyscia, additional, Lu, Michelle, additional, Lee, Jane, additional, DiNorcia, Joseph, additional, Agopian, Vatche G., additional, Farmer, Douglas G., additional, Busuttil, Ronald W., additional, and Kaldas, Fady M., additional

Published
2021
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211. Hepatocellular Carcinoma-Circulating Tumor Cells Expressing PD-L1 Are Prognostic and Potentially Associated With Response to Checkpoint Inhibitors

Author

Winograd, Paul, Hou, Shuang, Court, Colin M, Lee, Yi-Te, Chen, Pin-Jung, Zhu, Yazhen, Sadeghi, Saeed, Finn, Richard S, Teng, Pai-Chi, Wang, Jasmin J, Zhang, Zhicheng, Liu, Hongtao, Busuttil, Ronald W, Tomlinson, James S, Tseng, Hsian-Rong, and Agopian, Vatche G

Subjects
Liver Cancer, Detection, screening and diagnosis, Rare Diseases, Good Health and Well Being, Clinical Research, Liver Disease, Digestive Diseases, Cancer, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies
Abstract

Hepatocellular carcinoma (HCC) is a leading cause of mortality. Checkpoint inhibitors of programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) have shown great efficacy, but lack biomarkers that predict response. Circulating tumor cells (CTCs) have promise as a liquid-biopsy biomarker; however, data on HCC CTCs expressing PD-L1 have not been reported. We sought to detect PD-L1-expressing HCC-CTCs and investigated their role as a prognostic and predictive biomarker. Using an antibody-based platform, CTCs were enumerated/phenotyped from a prospective cohort of 87 patients with HCC (49 early-stage, 22 locally advanced, and 16 metastatic), 7 patients with cirrhosis, and 8 healthy controls. Immunocytochemistry identified total HCC CTCs (4',6-diamidino-2-phenylindole-positive [DAPI+]/cytokeratin-positive [CK+]/clusters of differentiation 45-negative [CD45-]) and a subpopulation expressing PD-L1 (DAPI+/CK+/PD-L1+/CD45-). PD-L1+ CTCs were identified in 4 of 49 (8.2%) early-stage patients, but 12 of 22 (54.5%) locally advanced and 15 of 16 (93.8%) metastatic patients, accurately discriminating early from locally advanced/metastatic HCC (sensitivity=71.1%, specificity=91.8%, area under the receiver operating characteristic curve=0.807; P&nbsp

Published
2020

212. Isoform- and Cell Type-Specific Roles of Glycogen Synthase Kinase 3 N-Terminal Serine Phosphorylation in Liver Ischemia Reperfusion Injury

Author

Ni, Ming, Zhou, Haoming, Zhang, Jing, Jin, Dan, Lu, Tianfei, Busuttil, Ronald W, Kupiec-Weglinski, Jerzy W, Wang, Xuehao, and Zhai, Yuan

Subjects
Inflammation, Male, Cell Death, Liver Diseases, Liver Disease, Chronic Liver Disease and Cirrhosis, Immunology, Immunity, Inbred C57BL, Oral and gastrointestinal, Mice, Glycogen Synthase Kinase 3, Liver, Reperfusion Injury, Mutation, Hepatocytes, Serine, Autophagy, Animals, Protein Isoforms, Innate, 2.1 Biological and endogenous factors, Phosphorylation, Aetiology, Digestive Diseases
Abstract

Glycogen synthase kinase 3 (Gsk3) α and β are both constitutively active and inhibited upon stimulation by N-terminal serine phosphorylation. Although roles of active Gsk3 in liver ischemia reperfusion injury (IRI) have been well appreciated, whether Gsk3 N-terminal serine phosphorylation has any functional significance in the disease process remains unclear. In a murine liver partial warm ischemia model, we studied Gsk3 N-terminal serine mutant knock-in (KI) mice and showed that liver IRI was decreased in Gsk3αS21A but increased in Gsk3βS9A mutant KI mice. Bone marrow chimeric experiments revealed that the Gsk3α, but not β, mutation in liver parenchyma protected from IRI, and both mutations in bone marrow-derived cells exacerbated liver injuries. Mechanistically, mutant Gsk3α protected hepatocytes from inflammatory (TNF-α) cell death by the activation of HIV-1 TAT-interactive protein 60 (TIP60)-mediated autophagy pathway. The pharmacological inhibition of TIP60 or autophagy diminished the protection of the Gsk3α mutant hepatocytes from inflammatory cell death in vitro and the Gsk3α mutant KI mice from liver IRI in vivo. Thus, Gsk3 N-terminal serine phosphorylation inhibits liver innate immune activation but suppresses hepatocyte autophagy in response to inflammation. Gsk3 αS21, but not βS9, mutation is sufficient to sustain Gsk4 activities in hepatocytes and protect livers from IRI via TIP60 activation.

Published
2020

213. Intraoperative Hypertension and Thrombocytopenia Associated With Intracranial Hemorrhage After Liver Transplantation

Author

Gao, Wei, Li, Jun, Nguyen-Buckley, Christine, Nguyen-Lee, Jennifer, Wray, Christopher, Agopian, Vatche, Busuttil, Ronald W, Steadman, Randolph H, and Xia, Victor W

Subjects
Adult, Male, Incidence, Liver Disease, Prevention, Neurosciences, Middle Aged, Thrombocytopenia, Medical and Health Sciences, Liver Transplantation, Stroke, Postoperative Complications, Good Health and Well Being, Risk Factors, Clinical Research, Hypertension, Humans, Female, Surgery, Intraoperative Complications, Digestive Diseases, Intracranial Hemorrhages, Retrospective Studies, Aged
Abstract

BackgroundIntracranial hemorrhage (ICH) is a devastating complication. Although hypertension and thrombocytopenia are well-known risk factors for ICH in the general population, their roles in ICH after liver transplantation (LT) have not been well established.MethodsWe performed a retrospective study and hypothesized that intraoperative hypertension and thrombocytopenia were associated with posttransplant ICH. New onset of spontaneous hemorrhage in the central nervous system within 30 days after LT were identified by reviewing radiologic reports and medical records. Risk factors were identified by multivariate logistic regression. Receiver operating characteristic analysis and Youden index were used to find the cutoff value with optimal sensitivity and specificity.ResultsOf 1836 adult patients undergoing LT at University of California, Los Angeles, 36 (2.0%) developed ICH within 30 days after LT. Multivariate logistic regression demonstrated that intraoperative mean arterial pressure ≥105 mm Hg (≥10 min) (odds ratio, 6.5; 95% confidence interval, 2.7-7.7; P < 0.001) and platelet counts ≤30 × 10/L (odds ratio, 3.3; 95% confidence interval, 14-7.7; P = 0.006) were associated with increased risk of postoperative ICH. Preoperative total bilirubin ≥7 mg/dL was also a risk factor. Thirty-day mortality in ICH patients was 48.3%, significantly higher compared with the non-ICH group (3.0%; P < 0.001). Patients with all 3 risk factors had a 16% chance of developing ICH.ConclusionsIn the current study, postoperative ICH was uncommon but associated with high mortality. Prolonged intraoperative hypertension and severe thrombocytopenia were associated with postoperative ICH. More studies are warranted to confirm our findings and develop a strategy to prevent this devastating posttransplant complication.

Published
2020

214. Tissue Inhibitor of Metalloproteinase 3 Deficiency Disrupts the Hepatocyte E-Cadherin/β-Catenin Complex and Induces Cell Death in Liver Ischemia/Reperfusion Injury

Author

Fujii, Takehiro, Duarte, Sergio, Lee, Eudora, Ke, Bibo, Busuttil, Ronald W, and Coito, Ana J

Subjects
Tissue Inhibitor of Metalloproteinase-3, Liver Disease, Chronic Liver Disease and Cirrhosis, Clinical Sciences, Cadherins, Oral and gastrointestinal, Liver Transplantation, Mice, Liver, Ischemia, Reperfusion Injury, Hepatocytes, Metalloproteases, 2.1 Biological and endogenous factors, Animals, Surgery, Aetiology, Digestive Diseases, beta Catenin
Abstract

Tissue inhibitor of metalloproteinase (TIMP) 3 is a naturally occurring inhibitor of a broad range of proteases, with key roles in extracellular matrix turnover and in the pathogenesis of various diseases. In this study, we investigated the response of mice lacking TIMP3 (TIMP3-/-) to hepatic ischemia/reperfusion injury (IRI). We report here that TIMP3-/- mice showed an enhanced inflammatory response, exacerbated organ damage, and further impaired liver function after IRI when compared with their wild-type littermates. Loss of TIMP3 led to the cleavage and shedding of E-cadherin during hepatic IRI; the full-length 120-kDa E-cadherin and the ratio of 38-kDa C-terminal fragment/120-kDa E-cadherin were decreased and increased, respectively, in TIMP3-/- livers after IRI. Moreover, GI254023X, a potent inhibitor of a disintegrin and metalloprotease (ADAM) 10, was capable of partially rescuing the expression of E-cadherin in the TIMP3-null hepatocytes. The proteolysis of E-cadherin in the TIMP3-/- livers was also linked to the loss of β-catenin from the hepatocyte membranes and to an increased susceptibility to apoptosis after liver IRI. In a similar fashion, depression of the E-cadherin/β-catenin complex mediated by TIMP3 deletion and knockdown of β-catenin by small interfering RNA were both capable of inducing caspase activation in isolated hepatocytes subjected to H2 O2 oxidative stress. Hence, these results support a protective role for TIMP3 expression in sheltering the hepatocyte E-cadherin/β-catenin complex from proteolytic processing and inhibiting apoptosis after hepatic IRI.

Published
2020

217. PACAP neuropeptide promotes Hepatocellular Protection via CREB-KLF4 dependent autophagy in mouse liver Ischemia Reperfusion Injury.

Author

Xue, Zhengze, Xue, Zhengze, Zhang, Yu, Liu, Yuanxing, Zhang, Cheng, Shen, Xiu-da, Gao, Feng, Busuttil, Ronald W, Zheng, Shusen, Kupiec-Weglinski, Jerzy W, Ji, Haofeng, Xue, Zhengze, Xue, Zhengze, Zhang, Yu, Liu, Yuanxing, Zhang, Cheng, Shen, Xiu-da, Gao, Feng, Busuttil, Ronald W, Zheng, Shusen, Kupiec-Weglinski, Jerzy W, and Ji, Haofeng

Abstract

Organ ischemia reperfusion injury (IRI), associated with acute hepatocyte death, remains an unresolved problem in clinical orthotopic liver transplantation (OLT). Autophagy, an intracellular self-digesting progress, is responsible for cell reprograming required to regain post-stress homeostasis. Methods: Here, we analyzed the cytoprotective mechanism of pituitary adenylate cyclase-activating polypeptide (PACAP)-promoted hepatocellular autophagy in a clinically relevant mouse model of extended hepatic cold storage (4 °C UW solution for 20 h) followed by syngeneic OLT. Results: In contrast to 41.7% of liver graft failure by day 7 post-transplant in control group, PACAP treatment significantly improved graft survival (91.7% by day 14), and promoted autophagy-associated regeneration programs in OLT. In parallel in vitro studies, PACAP-enhanced autophagy ameliorated cellular damage (LDH/ALT levels), and diminished necrosis in H2O2-stressed primary hepatocytes. Interestingly, PACAP not only induced nuclear cAMP response element-binding protein (CREB), but also triggered reprogramming factor Kruppel-like factor 4 (KLF4) expression in IR-stressed OLT. Indeed, CREB inhibition attenuated hepatic autophagy and recreated hepatocellular injury in otherwise PACAP-protected livers. Furthermore, CREB inhibition suppressed PACAP-induced KLF4 expression, whereas KLF4 blockade abolished PACAP-promoted autophagy and neutralized PACAP-mediated hepatoprotection both in vivo and in vitro. Conclusion: Current study documents the essential neural regulation of PACAP-promoted autophagy in hepatocellular homeostasis in OLT, which provides the emerging therapeutic principle to combat hepatic IRI in OLT.

Published
2020

218. Human Antigen R (HuR): A Regulator of Heme Oxygenase-1 Cytoprotection in Mouse and Human Liver Transplant Injury.

Author

Dery, Kenneth J, Dery, Kenneth J, Nakamura, Kojiro, Kadono, Kentaro, Hirao, Hirofumi, Kageyama, Shoichi, Ito, Takahiro, Kojima, Hidenobu, Kaldas, Fady M, Busuttil, Ronald W, Kupiec-Weglinski, Jerzy W, Dery, Kenneth J, Dery, Kenneth J, Nakamura, Kojiro, Kadono, Kentaro, Hirao, Hirofumi, Kageyama, Shoichi, Ito, Takahiro, Kojima, Hidenobu, Kaldas, Fady M, Busuttil, Ronald W, and Kupiec-Weglinski, Jerzy W

Abstract

Background and aimsIschemia-reperfusion injury (IRI) represents a risk factor in liver transplantation (LT). We have shown that overexpression of heme oxygenase-1 (HO-1) mitigates hepatic IRI in LT recipients. Here, we hypothesized that human antigen R (HuR), the stabilizer of adenylate-uridylate (AU)-rich mRNAs, is required for hepatoprotection in LT.Approach and resultsIn an experimental arm, HuR/HO-1 protein expression was correlated with hepatic IRI phenotype. In an in vitro inflammation mimic model of hepatic warm IRI, induction of HuR/HO-1 and cytoplasmic localization following cytokine preconditioning were detected in primary hepatocyte cultures, whereas HuR silencing caused negative regulation of HO-1, followed by enhanced cytotoxicity. Using the HuR-inhibitor, we showed that HuR likely regulates HO-1 through its 3' untranslated region and causes neutrophil activation (CD69+/lymphocyte antigen 6 complex locus G [Ly6-G]). HuR silencing in bone marrow-derived macrophages decreased HO-1 expression, leading to the induction of proinflammatory cytokines/chemokines. RNA sequencing of HuR silenced transcripts under in vitro warm IRI revealed regulation of genes thymus cell antigen 1 (THY1), aconitate decarboxylase 1 (ACOD1), and Prostaglandin E Synthase (PTGES). HuR, but not hypoxia-inducible protein alpha, positively regulated HO-1 in warm, but not cold, hypoxia/reoxygenation conditions. HuR modulated HO-1 in primary hepatocytes, neutrophils, and macrophages under reperfusion. Adjunctive inhibition of HuR diminished microtubule-associated proteins 1A/1B light chain 3B (LC3B), a marker for autophagosome, under HO-1 regulation, suggesting a cytoprotective mechanism in hepatic IR. In a clinical arm, hepatic biopsies from 51 patients with LT were analyzed at 2 hours after reperfusion. Graft HuR expression was negatively correlated with macrophage (CD80/CD86) and neutrophil (Cathepsin G) markers. Hepatic IRI increased HuR/HO-1 expression and inflammatory genes. Hi

Published
2020

219. Purification of HCC-specific extracellular vesicles on nanosubstrates for early HCC detection by digital scoring.

Author

Sun, Na, Sun, Na, Lee, Yi-Te, Zhang, Ryan Y, Kao, Rueihung, Teng, Pai-Chi, Yang, Yingying, Yang, Peng, Wang, Jasmine J, Smalley, Matthew, Chen, Pin-Jung, Kim, Minhyung, Chou, Shih-Jie, Bao, Lirong, Wang, Jing, Zhang, Xinyue, Qi, Dongping, Palomique, Juvelyn, Nissen, Nicolas, Han, Steven-Huy B, Sadeghi, Saeed, Finn, Richard S, Saab, Sammy, Busuttil, Ronald W, Markovic, Daniela, Elashoff, David, Yu, Hsiao-Hua, Li, Huiying, Heaney, Anthony P, Posadas, Edwin, You, Sungyong, Yang, Ju Dong, Pei, Renjun, Agopian, Vatche G, Tseng, Hsian-Rong, Zhu, Yazhen, Sun, Na, Sun, Na, Lee, Yi-Te, Zhang, Ryan Y, Kao, Rueihung, Teng, Pai-Chi, Yang, Yingying, Yang, Peng, Wang, Jasmine J, Smalley, Matthew, Chen, Pin-Jung, Kim, Minhyung, Chou, Shih-Jie, Bao, Lirong, Wang, Jing, Zhang, Xinyue, Qi, Dongping, Palomique, Juvelyn, Nissen, Nicolas, Han, Steven-Huy B, Sadeghi, Saeed, Finn, Richard S, Saab, Sammy, Busuttil, Ronald W, Markovic, Daniela, Elashoff, David, Yu, Hsiao-Hua, Li, Huiying, Heaney, Anthony P, Posadas, Edwin, You, Sungyong, Yang, Ju Dong, Pei, Renjun, Agopian, Vatche G, Tseng, Hsian-Rong, and Zhu, Yazhen

Abstract

We report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific extracellular vesicle (EV) purification system for early detection of HCC by performing digital scoring on the purified EVs. Earlier detection of HCC creates more opportunities for curative therapeutic interventions. EVs are present in circulation at relatively early stages of disease, providing potential opportunities for HCC early detection. We develop an HCC EV purification system (i.e., EV Click Chips) by synergistically integrating covalent chemistry-mediated EV capture/release, multimarker antibody cocktails, nanostructured substrates, and microfluidic chaotic mixers. We then explore the translational potential of EV Click Chips using 158 plasma samples of HCC patients and control cohorts. The purified HCC EVs are subjected to reverse-transcription droplet digital PCR for quantification of 10 HCC-specific mRNA markers and computation of digital scoring. The HCC EV-derived molecular signatures exhibit great potential for noninvasive early detection of HCC from at-risk cirrhotic patients with an area under receiver operator characteristic curve of 0.93 (95% CI, 0.86 to 1.00; sensitivity = 94.4%, specificity = 88.5%).

Published
2020

220. Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells.

Author

Court, Colin M, Court, Colin M, Hou, Shuang, Liu, Lian, Winograd, Paul, DiPardo, Benjamin J, Liu, Sean X, Chen, Pin-Jung, Zhu, Yazhen, Smalley, Matthew, Zhang, Ryan, Sadeghi, Saeed, Finn, Richard S, Kaldas, Fady M, Busuttil, Ronald W, Zhou, Xianghong J, Tseng, Hsian-Rong, Tomlinson, James S, Graeber, Thomas G, Agopian, Vatche G, Court, Colin M, Court, Colin M, Hou, Shuang, Liu, Lian, Winograd, Paul, DiPardo, Benjamin J, Liu, Sean X, Chen, Pin-Jung, Zhu, Yazhen, Smalley, Matthew, Zhang, Ryan, Sadeghi, Saeed, Finn, Richard S, Kaldas, Fady M, Busuttil, Ronald W, Zhou, Xianghong J, Tseng, Hsian-Rong, Tomlinson, James S, Graeber, Thomas G, and Agopian, Vatche G

Abstract

Somatic copy number alterations (SCNAs) are important genetic drivers of many cancers. We investigated the feasibility of obtaining SCNA profiles from circulating tumor cells (CTCs) as a molecular liquid biopsy for hepatocellular carcinoma (HCC). CTCs from ten HCC patients underwent SCNA profiling. The Cancer Genome Atlas (TCGA) SCNA data were used to develop a cancer origin classification model, which was then evaluated for classifying 44 CTCs from multiple cancer types. Sequencing of 18 CTC samples (median: 4 CTCs/sample) from 10 HCC patients using a low-resolution whole-genome sequencing strategy (median: 0.88 million reads/sample) revealed frequent SCNAs in previously reported HCC regions such as 8q amplifications and 17p deletions. SCNA profiling revealed that CTCs share a median of 80% concordance with the primary tumor. CTCs had SCNAs not seen in the primary tumor, some with prognostic implications. Using a SCNA profiling model, the tissue of origin was correctly identified for 32/44 (73%) CTCs from 12/16 (75%) patients with different cancer types.

Published
2020

221. Jagged1-mediated myeloid Notch1 signaling activates HSF1/Snail and controls NLRP3 inflammasome activation in liver inflammatory injury.

Author

Jin, Yuting, Jin, Yuting, Li, Changyong, Xu, Dongwei, Zhu, Jianjun, Wei, Song, Zhong, Andrew, Sheng, Mingwei, Duarte, Sergio, Coito, Ana J, Busuttil, Ronald W, Xia, Qiang, Kupiec-Weglinski, Jerzy W, Ke, Bibo, Jin, Yuting, Jin, Yuting, Li, Changyong, Xu, Dongwei, Zhu, Jianjun, Wei, Song, Zhong, Andrew, Sheng, Mingwei, Duarte, Sergio, Coito, Ana J, Busuttil, Ronald W, Xia, Qiang, Kupiec-Weglinski, Jerzy W, and Ke, Bibo

Abstract

Notch signaling plays important roles in the regulation of immune cell functioning during the inflammatory response. Activation of the innate immune signaling receptor NLRP3 promotes inflammation in injured tissue. However, it remains unknown whether Jagged1 (JAG1)-mediated myeloid Notch1 signaling regulates NLRP3 function in acute liver injury. Here, we report that myeloid Notch1 signaling regulates the NLRP3-driven inflammatory response in ischemia/reperfusion (IR)-induced liver injury. In a mouse model of liver IR injury, Notch1-proficient (Notch1FL/FL) mice receiving recombinant JAG1 showed a reduction in IR-induced liver injury and increased Notch intracellular domain (NICD) and heat shock transcription factor 1 (HSF1) expression, whereas myeloid-specific Notch1 knockout (Notch1M-KO) aggravated hepatocellular damage even with concomitant JAG1 treatment. Compared to JAG1-treated Notch1FL/FL controls, Notch1M-KO mice showed diminished HSF1 and Snail activity but augmented NLRP3/caspase-1 activity in ischemic liver. The disruption of HSF1 reduced Snail activation and enhanced NLRP3 activation, while the adoptive transfer of HSF1-expressing macrophages to Notch1M-KO mice augmented Snail activation and mitigated IR-triggered liver inflammation. Moreover, the knockdown of Snail in JAG1-treated Notch1FL/FL livers worsened hepatocellular functioning, reduced TRX1 expression and increased TXNIP/NLRP3 expression. Ablation of myeloid Notch1 or Snail increased ASK1 activation and hepatocellular apoptosis, whereas the activation of Snail increased TRX1 expression and reduced TXNIP, NLRP3/caspase-1, and ROS production. Our findings demonstrated that JAG1-mediated myeloid Notch1 signaling promotes HSF1 and Snail activation, which in turn inhibits NLRP3 function and hepatocellular apoptosis leading to the alleviation of IR-induced liver injury. Hence, the Notch1/HSF1/Snail signaling axis represents a novel regulator of and a potential therapeutic target for liver inflammatory

Published
2020

222. Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury.

Author

Nakamura, Kojiro, Nakamura, Kojiro, Kageyama, Shoichi, Kaldas, Fady M, Hirao, Hirofumi, Ito, Takahiro, Kadono, Kentaro, Dery, Kenneth J, Kojima, Hidenobu, Gjertson, David W, Sosa, Rebecca A, Kujawski, Maciej, Busuttil, Ronald W, Reed, Elaine F, Kupiec-Weglinski, Jerzy W, Nakamura, Kojiro, Nakamura, Kojiro, Kageyama, Shoichi, Kaldas, Fady M, Hirao, Hirofumi, Ito, Takahiro, Kadono, Kentaro, Dery, Kenneth J, Kojima, Hidenobu, Gjertson, David W, Sosa, Rebecca A, Kujawski, Maciej, Busuttil, Ronald W, Reed, Elaine F, and Kupiec-Weglinski, Jerzy W

Abstract

Although CEACAM1 (CC1) glycoprotein resides at the interface of immune liver injury and metabolic homeostasis, its role in orthotopic liver transplantation (OLT) remains elusive. We aimed to determine whether/how CEACAM1 signaling may affect hepatic ischemia-reperfusion injury (IRI) and OLT outcomes. In the mouse, donor liver CC1 null mutation augmented IRI-OLT (CC1-KO→WT) by enhancing ROS expression and HMGB1 translocation during cold storage, data supported by in vitro studies where hepatic flush from CC1-deficient livers enhanced macrophage activation in bone marrow-derived macrophage cultures. Although hepatic CC1 deficiency augmented cold stress-triggered ASK1/p-p38 upregulation, adjunctive ASK1 inhibition alleviated IRI and improved OLT survival by suppressing p-p38 upregulation, ROS induction, and HMGB1 translocation (CC1-KO→WT), whereas ASK1 silencing (siRNA) promoted cytoprotection in cold-stressed and damage-prone CC1-deficient hepatocyte cultures. Consistent with mouse data, CEACAM1 expression in 60 human donor liver biopsies correlated negatively with activation of the ASK1/p-p38 axis, whereas low CC1 levels associated with increased ROS and HMGB1 translocation, enhanced innate and adaptive immune responses, and inferior early OLT function. Notably, reduced donor liver CEACAM1 expression was identified as one of the independent predictors for early allograft dysfunction (EAD) in human OLT patients. Thus, as a checkpoint regulator of IR stress and sterile inflammation, CEACAM1 may be considered as a denominator of donor hepatic tissue quality, and a target for therapeutic modulation in OLT recipients.

Published
2020

223. Pattern Recognition Receptor-reactivity Screening of Liver Transplant Patients: Potential for Personalized and Precise Organ Matching to Reduce Risks of Ischemia-reperfusion Injury.

Author

Sosa, Rebecca A, Sosa, Rebecca A, Rossetti, Maura, Naini, Bita V, Groysberg, Victoria M, Kaldas, Fady M, Busuttil, Ronald W, Chang, Yu-Ling, Gjertson, David W, Kupiec-Weglinski, Jerzy W, Reed, Elaine F, Sosa, Rebecca A, Sosa, Rebecca A, Rossetti, Maura, Naini, Bita V, Groysberg, Victoria M, Kaldas, Fady M, Busuttil, Ronald W, Chang, Yu-Ling, Gjertson, David W, Kupiec-Weglinski, Jerzy W, and Reed, Elaine F

Abstract

Objective and backgroundPattern recognition receptors (PRRs) on immune and parenchymal cells can detect danger-associated molecular patterns (DAMPs) released from cells damaged during ischemia-reperfusion injury (IRI), in heart attack or stroke settings, but also as an unavoidable consequence of solid organ transplantation. Despite IRI being a significant clinical problem across all solid organ transplants, there are limited therapeutics and patient-specific diagnostics currently available.MethodsWe screened portal blood samples obtained from 67 human liver transplant recipients both pre- [portal vein (PV) sample] and post-(liver flush; LF) reperfusion for their ability to activate a panel of PRRs, and analyzed this reactivity in relation to biopsy-proven IRI.ResultsPV samples from IRI+ orthotopic liver transplantation (OLT) patients (n = 35) decreased activation of hTLR4- and hTLR9-transfected cells, whereas PV from IRI- patients (n = 32) primarily increased hTLR7 and hNOD2 activation. LF samples from OLT-IRI patients significantly increased activation of hTLR4 and hTLR9 over IRI- LF. In addition, the change from baseline reactivity to hTLR4/9/NOD2 was significantly higher in IRI+ than IRI- OLT patients.ConclusionsThese results demonstrate that TLR4/7/9 and NOD2 are involved in either promoting or attenuating hepatic IRI, and suggest a diagnostic screening of portal blood for reactivity to these PRRs might prove useful for prediction and/or therapeutic intervention in OLT patients before transplantation.

Published
2020

224. Impact of Rifaximin Therapy on Ischemia/Reperfusion Injury in Liver Transplantation: A Propensity Score-Matched Analysis

Author

Ito, Takahiro, Nakamura, Kojiro, Kageyama, Shoichi, Korayem, Islam M, Hirao, Hirofumi, Kadono, Kentaro, Aziz, Justine, Younan, Stephanie, DiNorcia, Joseph, Agopian, Vatche G, Yersiz, Hasan, Farmer, Douglas G, Busuttil, Ronald W, Kupiec-Weglinski, Jerzy W, and Kaldas, Fady M

Subjects
Graft Rejection, Adult, Male, Time Factors, Biopsy, Clinical Sciences, Drug Administration Schedule, Rifaximin, Oral and gastrointestinal, Young Adult, Postoperative Complications, Liver Function Tests, Risk Factors, Preoperative Care, Humans, 2.1 Biological and endogenous factors, Aetiology, Propensity Score, Retrospective Studies, Aged, Transplantation, Liver Disease, Graft Survival, Evaluation of treatments and therapeutic interventions, Organ Transplantation, Antibiotic Prophylaxis, Middle Aged, Allografts, Liver Transplantation, Gastrointestinal Microbiome, Survival Rate, Liver, Reperfusion Injury, 6.1 Pharmaceuticals, Reperfusion, Female, Surgery, Digestive Diseases, Biomarkers
Abstract

Intestinal microbiota is thought to play an important role in hepatic ischemia/reperfusion injury (IRI) after liver transplantation (LT). Rifaximin, a nonabsorbable antibiotic used to treat encephalopathy, exhibits antibacterial activity within the gut. We report the first study examining the impact of pre-LT rifaximin use on reducing hepatic IRI and inflammatory cell infiltration after LT. This retrospective single-center study included adult LT recipients from January 2013 through June 2016. Patients were divided into 2 groups based on duration of rifaximin use before LT: rifaximin group (≥28 days) and control group (none or

Published
2019

225. Hippo Signaling Controls NLR Family Pyrin Domain Containing 3 Activation and Governs Immunoregulation of Mesenchymal Stem Cells in Mouse Liver Injury

Author

Li, Changyong, Jin, Yuting, Wei, Song, Sun, Yishuang, Jiang, Longfeng, Zhu, Qiang, Farmer, Douglas G, Busuttil, Ronald W, Kupiec-Weglinski, Jerzy W, and Ke, Bibo

Subjects
Cultured, Gastroenterology & Hepatology, Cells, Macrophages, Clinical Sciences, Immunology, Signal Transducing, Adaptor Proteins, Mesenchymal Stem Cells, Cell Cycle Proteins, NLR Family, Medical Biochemistry and Metabolomics, Pyrin Domain-Containing 3 Protein, Mice, Liver, Reperfusion Injury, Animals, Signal Transduction
Abstract

The Hippo pathway, an evolutionarily conserved protein kinase cascade, tightly regulates cell growth and survival. Activation of yes-associated protein (YAP), a downstream effector of the Hippo pathway, has been shown to modulate tissue inflammation. However, it remains unknown as to whether and how the Hippo-YAP signaling may control NLR family pyrin domain containing 3 (NLRP3) activation in mesenchymal stem cell (MSC)-mediated immune regulation during liver inflammation. In a mouse model of ischemia/reperfusion (IR)-induced liver sterile inflammatory injury, we found that adoptive transfer of MSCs reduced hepatocellular damage, shifted macrophage polarization from M1 to M2 phenotype, and diminished inflammatory mediators. MSC treatment reduced mammalian Ste20-like kinase 1/2 and large tumor suppressor 1 phosphorylation but augmented YAP and β-catenin expression with increased prostaglandin E2 production in ischemic livers. However, disruption of myeloid YAP or β-catenin in MSC-transferred mice exacerbated IR-triggered liver inflammation, enhanced NLRP3/caspase-1 activity, and reduced M2 macrophage phenotype. Using MSC/macrophage coculture system, we found that MSCs increased macrophage YAP and β-catenin nuclear translocation. Importantly, YAP and β-catenin colocalize in the nucleus while YAP interacts with β-catenin and regulates its target gene X-box binding protein 1 (XBP1), leading to reduced NLRP3/caspase-1 activity after coculture. Moreover, macrophage YAP or β-catenin deficiency augmented XBP1/NLRP3 while XBP1 deletion diminished NLRP3/caspase-1 activity. Increasing NLRP3 expression reduced M2 macrophage arginase1 but augmented M1 macrophage inducible nitric oxide synthase expression accompanied by increased interleukin-1β release. Conclusion: MSCs promote macrophage Hippo pathway, which in turn controls NLRP3 activation through a direct interaction between YAP and β-catenin and regulates XBP1-mediated NLRP3 activation, leading to reprograming macrophage polarization toward an anti-inflammatory M2 phenotype. Moreover, YAP functions as a transcriptional coactivator of β-catenin in MSC-mediated immune regulation. Our findings suggest a therapeutic target in MSC-mediated immunotherapy of liver sterile inflammatory injury.

Published
2019

229. Functional crosstalk between myeloid Foxo1–β-catenin axis and Hedgehog/Gli1 signaling in oxidative stress response

Author

Li, Changyong, primary, Sheng, Mingwei, additional, Lin, Yuanbang, additional, Xu, Dongwei, additional, Tian, Yizhu, additional, Zhan, Yongqiang, additional, Jiang, Longfeng, additional, Coito, Ana J., additional, Busuttil, Ronald W., additional, Farmer, Douglas G., additional, Kupiec-Weglinski, Jerzy W., additional, and Ke, Bibo, additional

Published
2020
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230. Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria

Author

Kardashian, Ani, primary, Florman, Sander S., additional, Haydel, Brandy, additional, Ruiz, Richard M., additional, Klintmalm, Goran B., additional, Lee, David D., additional, Taner, C. Burcin, additional, Aucejo, Federico, additional, Tevar, Amit D., additional, Humar, Abhinav, additional, Verna, Elizabeth C., additional, Halazun, Karim J., additional, Chapman, William C., additional, Vachharajani, Neeta, additional, Hoteit, Maarouf, additional, Levine, Matthew H., additional, Nguyen, Mindie H., additional, Melcher, Marc L., additional, Langnas, Alan N., additional, Carney, Carol A., additional, Mobley, Constance, additional, Ghobrial, Mark, additional, Amundsen, Beth, additional, Markmann, James F., additional, Sudan, Debra L., additional, Jones, Christopher M., additional, Berumen, Jennifer, additional, Hemming, Alan W., additional, Hong, Johnny C., additional, Kim, Joohyun, additional, Zimmerman, Michael A., additional, Nydam, Trevor L., additional, Rana, Abbas, additional, Kueht, Michael L., additional, Fishbein, Thomas M., additional, Markovic, Daniela, additional, Busuttil, Ronald W., additional, and Agopian, Vatche G., additional

Published
2020
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235. Contributors

Author

Adams, Mark C., primary, Adibe, Obinna O., additional, Adler, Jeremy, additional, Adzick, N. Scott, additional, Albanese, Craig T., additional, Andrews, Walter S., additional, Applebaum, Harry, additional, Arca, Marjorie J., additional, Aronson, Daniel C., additional, Azizkhan, Richard G., additional, Baird, Robert, additional, Barnett, Sean, additional, Barnhart, Douglas C., additional, Barsness, Katherine A., additional, Bartlett, Robert H., additional, Baskin, Laurence S., additional, Beasley, Spencer W., additional, Bentz, Michael L., additional, Billmire, Deborah F., additional, Boulanger, Scott C., additional, Brandt, Mary L., additional, Brock, John W., additional, Brown, Rebeccah L., additional, Btaiche, Imad F., additional, Busuttil, Ronald W., additional, Caldamone, Anthony A., additional, Caniano, Donna A., additional, Caty, Michael G., additional, Chardot, Christophe, additional, Chung, Dai H., additional, Cilley, Robert E., additional, Colon, Nadja C., additional, Columbani, Paul M., additional, Coran, Arnold G., additional, Cotton, Robin T., additional, Cowles, Robert A., additional, Cox,, Charles S., additional, Dassinger, Melvin S., additional, Davidoff, Andrew M., additional, Davidson, Richard S., additional, Coppi, Paolo De, additional, Dicken, Bryan J., additional, Didelot, William, additional, DiFiore, John W., additional, Dillon, Patrick A., additional, Dillon, Peter W., additional, Donahoe, Patricia K., additional, Duchossois, Gina P., additional, Dunn, James C.Y., additional, Dutta, Sanjeev, additional, Eaton, Simon, additional, Ehrlich, Peter F., additional, Eichelberger, Martin R., additional, Elden, Lisa M., additional, Eliason, Jonathan L., additional, Emil, Sherif, additional, Escobar, Mauricio A., additional, Falcone,, Richard A., additional, Fallat, Mary E., additional, Farmer, Diana L., additional, Farmer, Douglas G., additional, Faro, Albert, additional, Fisher, Michael J., additional, Fishman, Steven J., additional, Fitzgerald, Tamara N., additional, Flake, Alan W., additional, Foglia, Robert P., additional, Ford, Henri R., additional, Franklin, Andrew, additional, Frischer, Jason S., additional, Fuller, Stephanie M.P., additional, Gandhi, Sanjiv K., additional, Garcia, Victor F., additional, Gatti, John M., additional, Gauderer, Michael W.L., additional, Geiger, James D., additional, Georgeson, Keith E., additional, Gingalewski, Cynthia A., additional, Glassberg, Kenneth I., additional, Glick, Philip L., additional, Gonzales, Kelly D., additional, Grikscheit, Tracy C., additional, Grosfeld, Jay L., additional, Groth, Travis W., additional, Gruessner, Angelika C., additional, Gruessner, Rainer W.G., additional, Gutierrez, Ivan M., additional, Guzzetta,, Philip C., additional, J. Hall, Jason, additional, Hamilton, Thomas E., additional, Harmon, Carroll M., additional, Harrison, Michael R., additional, Hayes-Jordan, Andrea, additional, Hays, Stephen R., additional, Healey, John H., additional, Hendren, W. Hardy, additional, Hering, Bernhard J., additional, Herndon, David N., additional, Hirose, Shinjiro, additional, Hirsch, Jennifer C., additional, Hirschl, Ronald B., additional, Hoganson, David M., additional, Holcomb, George W., additional, Höllwarth, Michael E., additional, Horn, B. David, additional, Huddleston, Charles B., additional, Hutchinson, Raymond J., additional, Hutson, John M., additional, Hyun, Grace, additional, Inge, Thomas H., additional, Jaksic, Tom, additional, Jea, Andrew, additional, Kaefer, Martin, additional, Kang, Kuang Horng, additional, Karsanac, Christopher J., additional, Kayes, Kosmas, additional, Kelly, Robert E., additional, Kiely, Edward M., additional, Klein, Michael D., additional, Krasin, Matthew J., additional, Krummel, Thomas M., additional, Kulungowski, Ann M., additional, Laberge, Jean-Martin, additional, Landsman, Ira S., additional, Langer, Jacob C., additional, La Quaglia, Michael P., additional, Laufer, Marc R., additional, Lee, Hanmin, additional, Lelli, Joseph L., additional, Levitt, Marc A., additional, Liau, James Y., additional, Lillehei, Craig, additional, Lindahl, Harry, additional, Liu, Gigi Y., additional, Lorenz, H. Peter, additional, Luerssen, Thomas G., additional, Lukish, Jeffrey R., additional, Lund, Dennis P., additional, Magee, John C., additional, McGahren, Eugene D., additional, McLaughlin, Eamon J., additional, McQuiston, Leslie T., additional, Meyers, Rebecka L., additional, Millar, Alastair J.W., additional, Minevich, Eugene, additional, Miranda, Edward P., additional, Mitchell, Michael E., additional, Mollen, Kevin P., additional, Moss, R. Lawrence, additional, Mouriquand, Pierre, additional, Murase, Noriko, additional, Murphy, J. Patrick, additional, Murphy, Joseph T., additional, Nance, Michael L., additional, Nathan, Saminathan S., additional, Newman, Kurt D., additional, Numanoglu, Alp, additional, Nwomeh, Benedict C., additional, Ohye, Richard G., additional, Oldham, Keith T., additional, O'Neill, James A., additional, Pakarinen, Mikko P., additional, Panait, Nicoleta, additional, Pearl, Richard H., additional, Peña, Alberto, additional, Pieretti, Rafael V., additional, Pierro, Agostino, additional, Piper, Hannah G., additional, Potsic, William P., additional, Pryor, Howard I., additional, Puligandla, Pramod S., additional, Puri, Prem, additional, Qureshi, Faisal G., additional, Rescorla, Frederick J., additional, Révillon, Yann, additional, Reyes, Jorge, additional, Reynolds, Marleta, additional, Rhee, Audrey C., additional, Rich, Barrie S., additional, Ricketts, Richard R., additional, Rink, Richard C., additional, Rintala, Risto J., additional, Rocchini, Albert P., additional, Rodeberg, David A., additional, Sadove, A. Michael, additional, Saggi, Bob H., additional, Scherer, L.R., additional, Schmid, Daniel B., additional, Scholz, Stefan, additional, Schwartz, Marshall Z., additional, Shamberger, Robert C., additional, Shapiro, Nina L., additional, Sheldon, Curtis A., additional, Shochat, Stephen J., additional, Sidell, Douglas, additional, Skinner, Michael A., additional, Smith, Jodi L., additional, Smith, Samuel D., additional, Snyder, Charles L., additional, Speer, Allison L., additional, Spitz, Lewis, additional, Spray, Thomas L., additional, Stanley, James C., additional, Starzl, Thomas E., additional, Stehr, Wolfgang, additional, Stolar, Charles J.H., additional, Storm, Phillip B., additional, Stylianos, Steven, additional, Subramaniam, Ramnath, additional, Superina, Riccardo, additional, Sutherland, David E.R., additional, Sutton, Leslie N., additional, Sydorak, Roman, additional, Sylvester, Karl G., additional, Teitelbaum, Daniel H., additional, Tepas, Joseph J., additional, Thomas, John C., additional, Thompson, Dana Mara, additional, Tovar, Juan A., additional, Upperman, Jeffrey S., additional, Vacanti, Joseph P., additional, van Aalst, John A., additional, Vane, Dennis W., additional, Allmen, Daniel Von, additional, Walkovich, Kelly, additional, Walsh, Danielle S., additional, Warner, Brad W., additional, Weber, Thomas R., additional, Weldon, Christopher B., additional, Wesson, David E., additional, Wetmore, Ralph F., additional, Willging, J. Paul, additional, Wilson, Jay M., additional, Woo, Lynn L., additional, Woo, Russell K., additional, Yerkes, Elizabeth B., additional, Ziegler, Moritz M., additional, and Zimmermann, Arthur, additional

Published
2012
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248. Contributors

Author

Abcarian, Herand, primary, Abdullah, Fizan, additional, Abramson, Michael A., additional, Abularrage, Christopher J., additional, Adams, Reid B., additional, Adamski, John., additional, Ahrendt, Steven A., additional, Ahuja, Nita, additional, Alam, Hasan B., additional, Alverdy, John C., additional, Armstrong, David N., additional, Arnaoutakis, George J., additional, Arnold, Alejandro, additional, Arthurs, Zachary M., additional, Asbun, Horacio J., additional, Ascher, Nancy L., additional, Asgeirsson, Theodor, additional, Ashley, Stanley W., additional, Babiera, Gildy V., additional, Balcom, James H., additional, Balogh, Zsolt J., additional, Banki, Farzaneh, additional, Barbul, Adrian, additional, Barie, Philip S., additional, Bauer, Todd W., additional, Beck, David E., additional, Bedri, Mazen I., additional, Berenji, Manijeh, additional, Berger, David L., additional, Bergman, Thomas A., additional, Berry, Stepheny D., additional, Billingham, Richard P., additional, Birnbaum, Elisa H., additional, Black, James H., additional, Bland, Kirby I., additional, Bochicchio, Grant V., additional, Bouchard, Philippe, additional, Boughey, Judy C., additional, Bowers, Steven P., additional, Brady, Colin M., additional, Brandes, Steven B., additional, Brant-Zawadzki, Peter, additional, Brayman, Kenneth L., additional, Brethauer, Stacy A., additional, Brock, Malcolm V., additional, Brooke, Benjamin S., additional, Broome, James T., additional, Brown, Carl J., additional, Brunicardi, F. Charles, additional, Brushart, Thomas M., additional, Buchman, Timothy G., additional, Bulger, Eileen M., additional, Burns, J. Bracken, additional, Busuttil, Ronald W., additional, Byrne, John, additional, Callender, Glenda G., additional, Callery, Mark P., additional, Cambria, Richard P., additional, Cameron, Andrew M., additional, Cameron, John L., additional, Campsen, Jeffrey, additional, Caprini, Joseph A., additional, Carter, Jonathan, additional, Caudle, Abigail S., additional, Ceppa, Eugene P., additional, Cevasco, Marisa, additional, Chaikof, Elliot L., additional, Chalikonda, Sricharan, additional, Chandrasekhara, Vinay, additional, Chaudhry, Vivek, additional, Chen, Haiquan, additional, Chen, Herbert, additional, Cheng, Aaron M., additional, Choti, Michael A., additional, Christians, Kathleen K., additional, Christmas, A. Britton, additional, Chua, Heidi, additional, Chun, Albert K., additional, Chung, Alice, additional, Clark, Orlo H., additional, Cleary, Sean P., additional, Cocanour, Christine S., additional, Codner, Panna A., additional, Cogbill, Thomas H., additional, Collier, Patrick S., additional, Conrad, Mark F., additional, Cooper, Joel D., additional, Corning, Cybil, additional, Cortes, Vicente, additional, Coselli, Joseph S., additional, Craft, Randall O., additional, Croce, Martin A., additional, Crow, Jessica, additional, Cuff, Robert F., additional, Cullen, Joseph J., additional, Cunningham, Steven C., additional, Curet, Myriam J., additional, Dackiw, Alan P.B., additional, Dagher, Nabil N., additional, Darling, R. Clement, additional, Davidson, Nancy E., additional, Degliuomini, John J., additional, Degnim, Amy C., additional, Delaney, Conor P., additional, DeMatteo, Ronald P., additional, DeMeester, Steven R., additional, DeMeester, Tom R., additional, Dempsey, Daniel T., additional, deSouza, Ashwin L., additional, Deune, E. Gene, additional, DeVos, Wayne C., additional, Dimick, Justin B., additional, Donahue, Timothy R., additional, Dort, Jonathan M., additional, Dozois, Eric J., additional, Dreesen, Elizabeth, additional, Duh, Quan-Yang, additional, Dulchavsky, Scott A., additional, Duncan, Mark D., additional, Duvvuri, Umamaheshwar, additional, Eachempati, Soumitra R., additional, Eakin, Jeffrey, additional, Eckhauser, Frederic E., additional, Edil, Barish H., additional, Edwards, Eric D., additional, Edwards, Meghan, additional, Efron, David T., additional, Efron, Jonathan E., additional, Efron, Philip A., additional, Ellison, E. Christopher, additional, Ellison, Trevor A., additional, El Sherif, Amgad, additional, Escobar, Guillermo A., additional, Esposito, Domenic P., additional, Evans, Douglas B., additional, Evans, Heather L., additional, Fabri, Peter J., additional, Fairman, Ronald M., additional, Farres, Houssam, additional, Feins, Richard H., additional, Feliciano, David V., additional, Ferguson, Charles M., additional, Ferguson, Mark K., additional, Ferrone, Cristina R., additional, Ferzli, George S., additional, Fichera, Alessandro, additional, Fink, Aaron S., additional, Fink, David, additional, Fishel, Rhonda, additional, Fisher, Kerry, additional, Fisher, William E., additional, Fitzgibbons, Timothy C., additional, Fleshman, James W., additional, Flint, Lewis M., additional, Flohr, Tanya R., additional, Flores, Jaime I., additional, Fogarty, Sara P., additional, Foley, Paul J., additional, Fong, Yuman, additional, Friel, Charles M., additional, Frykberg, Eric R., additional, Fuller, Joseph C., additional, Gadd, Michele A., additional, Gailloud, Philippe, additional, Galanis, Charles, additional, Gallagher, James J., additional, Gallagher, Scott F., additional, Gaspard, Bryan A., additional, Gaughan, Colleen B., additional, Gearhart, Susan L., additional, Geller, David A., additional, Georgiades, Christos S., additional, Geschwind, Jean-Francois H., additional, Ghosheh, Bashar, additional, Giday, Samuel A., additional, Giuliano, Armando E., additional, Glebova, Natalia, additional, Goldberg, Nelson H., additional, Goldstone, Jerry, additional, Golla, Suman, additional, Gosnell, Jessica E., additional, Gourley, Jeffrey R., additional, Graham, Jay A., additional, Grams, Jayleen, additional, Grant, Michael P., additional, Grau, Ana M., additional, Grothey, Axel, additional, Guerrero, Marlon A., additional, Guillem, Jose G., additional, Haider, Adil H., additional, Hall, Bruce Lee, additional, Han, David C., additional, Harmon, John W., additional, Harold, Kristi L., additional, Harper, Amy P., additional, Harris, Hobart W., additional, Hashimi, Samad, additional, Hassoun, Heitham T., additional, Haut, Elliott R., additional, Hébert-Blouin, Marie-Noëlle, additional, Heitmiller, Richard F., additional, Henderson, J. Michael, additional, Heniford, B. Todd, additional, Henke, Peter K., additional, Herlong, H. Franklin, additional, Hernandez, Jonathan M., additional, Hess, Philip J., additional, Hiatt, Jonathan R., additional, Hines, O. Joe, additional, Hodin, Richard A., additional, Hoffman, John P., additional, Hong, Johnny C., additional, Hoppo, Toshitaka, additional, Horn, Jan K., additional, Hornicek, Francis J., additional, Hossain, Rydhwana, additional, Howard, Thomas J., additional, Hoyt, David B., additional, Hrabe, Jennifer E., additional, Hranjec, Tjasa, additional, Hull, Tracy L., additional, Iannettoni, Mark D., additional, Iannitti, David A., additional, Idrees, Kamran, additional, Ignacio, Elizabeth A., additional, Iseli, Tim A., additional, Ito, Hiromichi, additional, Jacene, Heather, additional, Jackson, Lana L., additional, Jacobs, Lenworth M., additional, Jacobs, Lisa K., additional, Jagannath, Sanjay, additional, Jaszczak, Nicholas, additional, Jayaraman, Vijay, additional, Jimenez, Juan Carlos, additional, Jin, Judy, additional, Jobe, Blair A., additional, Joh, Jennifer E., additional, Johnson, Eric K., additional, Johnson, Jonas T., additional, Johnson, Lynt B., additional, Johnson, Michael, additional, Jonnalagadda, Sreenivasa, additional, Jurkovich, Gregory J., additional, Kachala, Stefan S., additional, Kalloo, Anthony N., additional, Karakousis, Giorgos C., additional, Katz, Ryan D., additional, Keane, Thomas, additional, Kebebew, Electron, additional, Kent, K. Craig, additional, Kent, Tara S., additional, Khashab, Mouen, additional, Kilic, Arman, additional, Hui Kim, Elizabeth Min, additional, Kim, Yongsik, additional, King, Jonathan C., additional, King, Tari A., additional, Kirkpatrick, Andrew W., additional, Kong, Allen, additional, Kozarek, Richard A., additional, Krasna, Mark J., additional, Krontiras, Helen, additional, Kuwayama, David, additional, Lai, Edward C.S., additional, Lal, Alysandra, additional, LaMuraglia, Glenn M., additional, Lau, Kwan N., additional, Lavu, Harish, additional, Lawrence, Peter F., additional, LeBlanc, Karl A., additional, Ledgerwood, Anna M., additional, LeMaire, Scott A., additional, Lembersky, Barry C., additional, Leukhardt, William H., additional, Li, Ryan, additional, Lillemoe, Keith D., additional, Lipsett, Pamela A., additional, Lipsitz, Evan C., additional, Little, Alex G., additional, Lucas, Charles E., additional, Luketich, James D., additional, Lum, Ying Wei, additional, Lyden, Sean P., additional, MacFadyen, Bruce V., additional, Madariaga, Maria Lucia L., additional, Magnuson, Thomas H., additional, Maier, Ronald V., additional, Makary, Martin A., additional, Makhija, Rohit, additional, Malangoni, Mark A., additional, Malas, Mahmoud B., additional, Manson, Paul N., additional, Marcello, Peter W., additional, Marks, Jeffrey M., additional, Marohn, Michael R., additional, Martin, Terri R., additional, Martin, Tomas D., additional, Mathisen, Douglas J., additional, Matthews, Brent D., additional, Mazzaglia, Peter J., additional, McDermott, John E., additional, McFadden, David W., additional, McHenry, Christopher R., additional, McIntyre, Robert C., additional, McLemore, Elisabeth C., additional, McLeod, Robin S., additional, Mellinger, John D., additional, Melo, Nicholas, additional, Melton, Genevieve B., additional, Meltzer, Andrew J., additional, Melvin, W. Scott, additional, Mendoza, Maria Clara, additional, Messiner, Ryan, additional, Meyer, Anthony A., additional, Meyers, William C., additional, Michelassi, Fabrizio, additional, Millikan, Keith W., additional, Miner, Thomas J., additional, Moley, Jeffrey F., additional, Moore, Frederick A., additional, Morrow, Ellen H., additional, Morrow, Monica, additional, Moss, Angela K., additional, Moustarah, Fady, additional, Mufeed, Sami, additional, Muldoon, Roberta L., additional, Muniappan, Ashok, additional, Murphy, Erin H., additional, Muscarella, Peter, additional, Nahabedian, Maurice Y., additional, Napolitano, Lena M., additional, Nealon, William H., additional, Neideen, Todd, additional, Neumayer, Leigh A., additional, Newman, Naeem A., additional, Nguyen, Hien T., additional, Nguyen, Kevin Tri, additional, Nikfarjam, Mehrdad, additional, Norton, Jeffrey A., additional, O'Mara, Charles S., additional, Onders, Raymond P., additional, Pachter, H. Leon, additional, Pappas, Theodore N., additional, Parikh, Manish, additional, Park, Jason, additional, Pascual, Jose L., additional, Patel, Virendra I., additional, Pearl, Russell K., additional, Peitzman, Andrew B., additional, Pemberton, John H., additional, Perler, Bruce A., additional, Perrier, Nancy D., additional, Pesce, Catherine E., additional, Petelin, Joseph B., additional, Peters, Jeffrey H., additional, Petrowsky, Henrik, additional, Pfluke, Jason M., additional, Philipp, Scott R., additional, Phillips, Bradley J., additional, Piper, Greta L., additional, Pitt, Henry A., additional, Pizano, Louis R., additional, Ponsky, Jeffrey L., additional, Prescott, Jason D., additional, Pronovost, Peter J., additional, Pust, Gerd D., additional, Pustavoitau, Aliaksei, additional, Puyana, Juan Carlos, additional, Qazi, Umair, additional, Quickel, Robert R., additional, Ra, Jin H., additional, Rad, Ariel N., additional, Radvany, Martin G., additional, Rafferty, Janice F., additional, Rahbari, Reza, additional, Ramos, Margarita, additional, Ramshaw, Bruce J., additional, Rawlings, Arthur, additional, Reardon, Patrick R., additional, Reber, Howard A., additional, Reeder, Jennifer G., additional, Reidy, Tobi, additional, Reifsnyder, Andrew, additional, Reifsnyder, Thomas F., additional, Resnick, Andrew S., additional, Richards, William O., additional, Rieder, Erwin, additional, Roberts, John P., additional, Robinson, Raymond E., additional, Robinson, Thomas N., additional, Rodriguez, Aurelio, additional, Rodriguez-Paz, Jose M., additional, Rogers, Selwyn O., additional, Romig, Mark, additional, Roseborough, Glen S., additional, Rosemurgy, Alexander S., additional, Rosenthal, Eben L., additional, Rossi, Daniel C., additional, Rosson, Gedge D., additional, Safar, Bashar, additional, Salky, Barry A., additional, Santora, Rachel J., additional, Sarin, Shawn N., additional, Sawyer, Robert G., additional, Sax, Harry C., additional, Scalea, Thomas M., additional, Schauer, Philip R., additional, Schild, A. Frederick, additional, Schmidt, C. Max, additional, Schneider, John G., additional, Schreiber, Martin A., additional, Schuerer, Douglas J.E., additional, Schulick, Richard D., additional, Schwab, C. William, additional, Schweitzer, Michael A., additional, Scortino, Christopher, additional, Senagore, Anthony J., additional, Sentovich, Stephen M., additional, Sepesi, Boris, additional, Seybt, Melanie W., additional, Shah, Amit, additional, Shellito, Paul C., additional, Shepard, Alexander D., additional, Shetty, Kirti, additional, Sicklick, Jason K., additional, Silberfein, Eric J., additional, Silverman, Ronald P., additional, Simmons, Rache M., additional, Sing, Ronald F., additional, Smith, Barbara L., additional, Smith, C. Daniel, additional, Smith, Maurice A., additional, Smith, R. Stephen, additional, Snyder, Michael J., additional, Sohn, Helen, additional, Soybel, David I., additional, Spencer, Michael P., additional, Spinner, Robert J., additional, Spoerke, Nicholas J., additional, Steele, Scott R., additional, Stein, Sharon L., additional, Stevens, Kent A., additional, Sticca, Robert P., additional, Stiegmann, Gregory V., additional, Stonemetz, Jerry, additional, Strasberg, Steven M., additional, Streiff, Michael B., additional, Su, Stacey, additional, Sucher, Joseph F., additional, Sussman, Marc, additional, Sutherland, David E.R., additional, Swanstrom, Lee L., additional, Taghizadeh, Maakan, additional, Talamini, Mark A., additional, Tarpley, John L., additional, Tatli, Servet, additional, Taylor, Spence M., additional, Terris, David J., additional, Thompson, Geoffrey B., additional, Traverso, L. William, additional, Trunkey, Donald D., additional, Tsai, Peter I., additional, Tsai, Susan, additional, Tsangaris, Theodore N., additional, Udelsman, Robert, additional, Umanskiy, Konstantin, additional, Upchurch, Gilbert R., additional, Urist, Marshall M., additional, Urschel, Harold C., additional, Vagefi, Parsia A., additional, Van, Philbert Y., additional, Van Arendonk, Kyle J., additional, Vauthey, Jean-Nicolas, additional, Veeramachaneni, Nirmal K., additional, Velmahos, George C., additional, Venbrux, Anthony C., additional, Vollmer, Charles M., additional, Wacker, Frank K., additional, Wallack, Marc K., additional, Walsh, R. Matthew, additional, Wang, Grace J., additional, Wang, Jennifer Y., additional, Wang, Thomas N., additional, Waters, Joshua A., additional, Watkins, Michael T., additional, Watson, Christopher M., additional, Webb, Alexandra L.B., additional, Weigelt, John A., additional, Weiss, Eric G., additional, Whang, Edward E., additional, Whitacre, Eric B., additional, Williams, D. Brandon, additional, Wolff, Bruce G., additional, Wolfgang, Christopher, additional, Wong, Patricia, additional, Wood, Douglas E., additional, Yadav, Bhupender, additional, Yang, Stephen C., additional, Yeo, Charles J., additional, Yoon, Sam S., additional, You, Christopher J., additional, You, Y. Nancy, additional, Youssef, Yassar, additional, Zalinski, Stéphane, additional, Zamir, Gideon A., additional, Zarins, Christopher K., additional, Zeiger, Martha A., additional, Zenilman, Michael E., additional, and Zimmerman, Michael A., additional

Published
2011
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