175 results on '"Samuel S Lee"'
Search Results
2. Treatment Outcomes with Telaprevir-Based Therapy for HIV/Hepatitis C Coinfected Patients are Comparable with Hepatitis C Monoinfected Patients
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Conar R O’Neil, Jack XQ Pang, Samuel S Lee, Mark G Swain, Kelly W Burak, Patricia Klein, Robert P Myers, Jeff Kapler, Michael J Gill, Martin Labrie, and Carla S Coffin
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Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Published
- 2015
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3. Rituximab for the Treatment of Patients with Autoimmune Hepatitis Who are Refractory or Intolerant to Standard Therapy
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Kelly W Burak, Mark G Swain, Tania Santodomino-Garzon, Samuel S Lee, Stefan J Urbanski, Alexander I Aspinall, Carla S Coffin, and Robert P Myers
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
BACKGROUND: Although most patients with autoimmune hepatitis (AIH) respond to treatment with prednisone and/or azathioprine, some patients are intolerant or refractory to standard therapy. Rituximab is an anti-CD20 monoclonal antibody that depletes B cells and has demonstrated efficacy in other autoimmune conditions.
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- 2013
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4. Clinical outcomes of esophageal squamous cell carcinoma in patients with cirrhosis
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Dae Gon Ryu, Mi Sook Yun, Hongqun Liu, Samuel S. Lee, and Sangjune Laurence Lee
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Esophageal cancer ,Squamous cell carcinoma ,Cirrhosis ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Purpose: Alcohol consumption is a strong risk factor for both cirrhosis and esophageal squamous cell carcinoma (ESCC). Few studies have been conducted on the treatment of ESCC in patients with cirrhosis. This study aimed to analyze the clinical outcomes of ESCC in patients with cirrhosis. Materials and methods: Medical records of patients with esophageal cancer between January 2009 and December 2023 were retrospectively reviewed. A total of 479 patients with ESCC were included and divided into cirrhotic (n = 69) and non-cirrhotic (n = 410) groups. Clinical outcomes and survival according to treatment were compared between these groups. Results: The cirrhotic group was younger (median age 64 years vs. 69 years, p = 0.022) and had a higher proportion of male (97.1 % vs. 88.3 %, p = 0.042) than the non-cirrhotic group. Patients with cirrhosis were less likely to undergo surgery (31.9 % vs. 47.8 %, p = 0.015) and were more likely to receive no active cancer treatment (26.1 % vs. 13.7 %, p = 0.010). Overall survival was lower in the cirrhotic group (hazard ratio [HR], 1.41; 95 % confidence interval [CI], 1.01–1.99; p = 0.045), however, no difference was found between Child-Pugh class A patients and those in the non-cirrhotic group (HR, 1.04 [95 % CI, 0.69–1.56]; p = 0.864). Postoperative mortality was significantly higher in cirrhotic group (27.3 % vs. 8.7 %, p = 0.011). Upon performing concurrent chemoradiotherapy (CRT), the clinical complete response rate (84.2 % vs. 43.3 %, p = 0.004) was better in the cirrhotic group. CRT yielded better overall survival for patients with cancer in the resectable stages in the cirrhotic group compared to surgery (HR, 0.19 [95 % CI, 0.42–0.84]; p = 0.029]. Conclusions: In patient with ESCC and cirrhosis, chemoradiotherapy may be a better treatment option than surgery.
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- 2024
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5. Reply to: Correspondence on 'Cardiomyopathy in cirrhosis: From pathophysiology to clinical care'
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Hongqun Liu, Jwan A. Naser, Grace Lin, and Samuel S. Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2024
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6. Mericitabine and Either Boceprevir or Telaprevir in Combination with Peginterferon Alfa-2a plus Ribavirin for Patients with Chronic Hepatitis C Genotype 1 Infection and Prior Null Response: The Randomized DYNAMO 1 and DYNAMO 2 Studies.
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Heiner Wedemeyer, Xavier Forns, Christophe Hézode, Samuel S Lee, Astrid Scalori, Athina Voulgari, Sophie Le Pogam, Isabel Nájera, and James A Thommes
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Medicine ,Science - Abstract
Most patients with chronic hepatitis C virus (HCV) genotype 1 infection who have had a previous null response (
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- 2016
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7. Canadian Patients with Chronic Hepatitis B Cannot Access Appropriate Drug Treatments: A Call for Change
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Morris Sherman and Samuel S Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2011
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8. Retreatment with Pegylated Interferon Alpha-2a and Ribavirin in Patients with Chronic Hepatitis C Who Have Relapsed or Not Responded to a First Course of Pegylated Interferon-Based Therapy
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Eric M Yoshida, Morris Sherman, Vincent G Bain, Curtis L Cooper, Marc Deschênes, Paul J Marotta, Samuel S Lee, Mel Krajden, Helga Witt-Sullivan, Robert J Bailey, Christopher Usaty, Kevork Peltekian, and the Canadian Pegasys Study Group
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
BACKGROUND: Pegylated interferon (pegIFN) and ribavirin combination therapy remains the first-line treatment for chronic hepatitis C virus (HCV) infection. In contrast to the wealth of studies in treatment-naive patients, the effectiveness of retreatment in patients who have previously failed pegIFN-based therapy is largely unreported.
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- 2009
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9. Impact of Pharmaceutical Industry Versus University Sponsorship on Survey Response: A Randomized Trial among Canadian Hepatitis C Care Providers
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Robert P Myers, Abdel Aziz M Shaheen, and Samuel S Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
BACKGROUND: Surveys originating from universities appear to have higher response rates than those from commercial sources. In light of the growing scrutiny placed on physician-industry relations, the present study aimed to determine the impact of the pharmaceutical industry versus university sponsorship on response to a postal survey completed by Canadian hepatitis C virus (HCV) care providers.
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- 2007
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10. Correction: Hepatitis B Virus (HBV) Variants in Untreated and Tenofovir Treated Chronic Hepatitis B (CHB) Patients During Pregnancy and Post-Partum Follow-up.
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Boris Virine, Carla Osiowy, Shan Gao, Tong Wang, Eliana Castillo, Steven R Martin, Samuel S Lee, Kimberley Simmonds, Guido van Marle, and Carla S Coffin
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Medicine ,Science - Published
- 2015
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11. Hepatitis B Virus (HBV) Variants in Untreated and Tenofovir Treated Chronic Hepatitis B (CHB) Patients during Pregnancy and Post-Partum Follow-Up.
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Boris Virine, Carla Osiowy, Shan Gao, Tong Wang, Eliana Castillo, Steven R Martin, Samuel S Lee, Kimberley Simmonds, Guido van Marle, and Carla S Coffin
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Medicine ,Science - Abstract
Chronic hepatitis B (CHB) is a dynamic disease that may be affected by immune changes in pregnancy. Guidelines suggest consideration of nucleos/tide analogs (NA), i.e., tenofovir, (TDF) in highly viremic mothers to reduce vertical transmission risk. HBV variability affects CHB outcome, but little is known about HBV genetic changes in pregnancy due to immune or NA selection.To evaluate HBV diversity in NA treated or untreated pregnant vs. post-partum CHB carriers.In plasma collected from 21 mothers (7 matching pre/post-partum), HBV serological tests, genotype and viral load were assayed. The HBV pre-surface (S) /S overlapping polymerase (P) (N = 20), pre-core (C) /C (N = 11) and/or full genome PCR amplicons (N = 3) underwent clonal sequence analysis.The median age was 31 y, 71% Asian, 68% genotype B or C, 33% HBV eAg+, 5 received TDF (median HBV DNA 8.5 log IU/ml). In untreated mothers, median antepartum vs. post-partum ALT was 21 vs. 24 U/L and HBV DNA was 2.7 vs. 2.4 log(10) IU/ml. ALT and/or HBV DNA flares occurred during pregnant and/or post-partum period in 47% (10/21). Clonal sequencing antepartum showed the presence of minor "a determinant" and/or vaccine escape mutants (VEM) but drug resistant variants were infrequent. Analysis of pregnant vs. post-partum samples showed different HBV variants and viral diversity.Differences in immune and/or by NA selective pressures during pregnancy may affect HBV evolution during pregnancy. The presence of minor VEM warrant infant follow-up.
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- 2015
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12. Emergency Management of Bleeding Esophageal Varices: Drugs, Bands or Sleep?
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Brian M Yan and Samuel S Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Variceal bleeding is a severe complication of cirrhosis leading to significant morbidity and mortality. Treatment of acute variceal bleeding has improved dramatically since the era of the mechanical balloon tamponade. These advances include endoscopic band ligation or sclerotherapy, and vasoactive pharmacological options such as somatostatin, octreotide, vasopressin and terlipressin. Evidence from a multitude of clinical trials and meta-analyses comparing endoscopic and pharmacological treatments suggests near equivalence in efficacy for initial hemostasis, mortality and rate of rebleeding. This raises the question of whether on-call gastroenterologists should be performing emergency endoscopic treatment in the middle of the night or start pharmacological treatment and delay endoscopy until optimal patient and working conditions the next morning. The present review analyzes the available comparative data between endoscopic and pharmacological treatment options. Although the literature cannot yet definitively answer the question posed, the authors suggest that delaying endoscopic treatment until the next morning may be the most reasonable practical approach.
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- 2006
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13. Acute Management and Secondary Prophylaxis of Esophageal Variceal Bleeding: A Western Canadian Survey
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Justin Cheung, Winnie Wong, Iman Zandieh, Yvette Leung, Samuel S Lee, Alnoor Ramji, and Eric M Yoshida
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
BACKGROUND: Acute esophageal variceal bleeding (EVB) is a major cause of morbidity and mortality in patients with liver cirrhosis. Guidelines have been published in 1997; however, variability in the acute management and prevention of EVB rebleeding may occur.
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- 2006
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14. Chronic Hepatitis C in Western Canada: A Survey of Practice Patterns among Gastroenterologists in Alberta and British Columbia
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Rohit Pai, Alnoor Ramji, Samuel S Lee, Winnie W Wong, and Eric M Yoshida
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
OBJECTIVE: To survey gastroenterologists in British Columbia and Alberta with regard to awareness of chronic hepatitis C virus (HCV) management and practice patterns among physicians who treat and do not treat HCV-infected patients.
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- 2014
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15. Reactivation of Hepatitis B e Antigen-Negative Chronic Hepatitis B in a Bone Marrow Transplant Recipient following Lamivudine Withdrawal
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Robert P Myers, Mark G Swain, Stefan J Urbanski, and Samuel S Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Reactivation of hepatitis B virus (HBV) is a recognized complication of bone marrow transplantation (BMT). Lamivudine is a nucleoside analogue with potent antiviral activity that has been used in the prophylaxis of HBV reactivation in at-risk BMT recipients. Currently, no data exist regarding the safety of nucleoside analogue withdrawal in these patients. A 32-year-old BMT recipient with hepatitis B e antigen (HBeAg)-negative, chronic HBV who developed a serious flare of hepatic inflammation due to a rebound in viral replication within 12 weeks of discontinuing lamivudine therapy is described. The patient remained HBeAg-negative despite high level viremia, suggesting the emergence of a mutant viral strain. The patient's acute hepatitis resolved promptly with the reinstitution of lamivudine therapy. Further studies are necessary to define the safety and efficacy of nucleoside analogues in the prevention of HBV reactivation in at-risk BMT recipients. Clinicians should consider the risk of inducing serious flares of hepatic inflammation due to abrupt nucleoside analogue withdrawal in these patients.
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- 2001
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16. Hemodynamic Characterization of Arterialized and Nonarterialized Liver Transplants in the Rat
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John Wong, Yikun Zhang, and Samuel S Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Persistent hyperkinetic circulation after liver transplantation has been described in humans, but similar changes have not been well characterized in the rat model. This study aimed to investigate the hemodynamics of the systemic and splanchnic circulations in both arterialized and nonarterialized hepatic allografts. Orthotopic liver transplantation was performed in four groups of Sprague-Dawley rats. Group A comprised sham-operated rats with hepatic artery ligation that did not receive transplants; group B comprised rats that received transplants without arterialization; group C comprised sham-operated rats with intact hepatic artery that did not receive transplants; and group D comprised rats that received transplants with arterialization. Blood flow measurements were performed three weeks after the surgical procedure, using the radioactive microsphere method. The results showed that rats that received transplants exhibited a significantly higher cardiac index and lower systemic vascular resistance than the control rats. Splanchnic hyperemia was also present with increased mesenteric blood flow. However, there was no difference in hemodynamics between rats that received arterialized transplants and those that received nonarterialized transplants. Arterial collateral vessels from adjacent tissues were observed in the nonarterialized grafts; this was confirmed histologically. It is concluded that rats that undergo orthotopic liver transplantation exhibit hyperdynamic circulation, regardless of the arterial reconstruction procedure, possibly due to extensive collateral formation in the hepatosplanchnic circulation.
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- 2001
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17. Brain-specific rescue of Clock reveals system-driven transcriptional rhythms in peripheral tissue.
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Michael E Hughes, Hee-Kyung Hong, Jason L Chong, Alejandra A Indacochea, Samuel S Lee, Michael Han, Joseph S Takahashi, and John B Hogenesch
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Genetics ,QH426-470 - Abstract
The circadian regulatory network is organized in a hierarchical fashion, with a central oscillator in the suprachiasmatic nuclei (SCN) orchestrating circadian oscillations in peripheral tissues. The nature of the relationship between central and peripheral oscillators, however, is poorly understood. We used the tetOFF expression system to specifically restore Clock function in the brains of Clock(Δ19) mice, which have compromised circadian clocks. Rescued mice showed normal locomotor rhythms in constant darkness, with activity period lengths approximating wildtype controls. We used microarray analysis to assess whether brain-specific rescue of circadian rhythmicity was sufficient to restore circadian transcriptional output in the liver. Compared to Clock mutants, Clock-rescue mice showed significantly larger numbers of cycling transcripts with appropriate phase and period lengths, including many components of the core circadian oscillator. This indicates that the SCN oscillator overcomes local circadian defects and signals directly to the molecular clock. Interestingly, the vast majority of core clock genes in liver were responsive to Clock expression in the SCN, suggesting that core clock genes in peripheral tissues are intrinsically sensitive to SCN cues. Nevertheless, most circadian output in the liver was absent or severely low-amplitude in Clock-rescue animals, demonstrating that the majority of peripheral transcriptional rhythms depend on a fully functional local circadian oscillator. We identified several new system-driven rhythmic genes in the liver, including Alas1 and Mfsd2. Finally, we show that 12-hour transcriptional rhythms (i.e., circadian "harmonics") are disrupted by Clock loss-of-function. Brain-specific rescue of Clock converted 12-hour rhythms into 24-hour rhythms, suggesting that signaling via the central circadian oscillator is required to generate one of the two daily peaks of expression. Based on these data, we conclude that 12-hour rhythms are driven by interactions between central and peripheral circadian oscillators.
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- 2012
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18. Failure of Splenectomy to Ameliorate Portal Hypertension in Myeloproliferative Disorders
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Samuel S Lee, Guido Van Rosendaal, Thomas E Lay, James K Kelly, and Graham F Pineo
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
The correct treatment of portal hypertension associated with myeloproliferative disorders remains uncertain. Splenectomy has been advocated by some to eliminate the forward flow component of the portal hypertension and thus reduce portal pressure. The authors describe three recent cases of myeloproliferative disorder in whom splenectomy failed to achieve any significant amelioration of portal hypertension, with in-depth hemodynamic studies in one patient. Based on these experiences, the authors suggest that splenectomy is not the optimum treatment of the portal hypertension associated with myeloproliferative disorders.
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- 1994
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19. Fatal Hepatic Decompensation in a Patient with Hepatitis B Cirrhosis Following Famciclovir Withdrawal
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Robert P Myers, Rabindra Chaudhary, Kevin Fonseca, and Samuel S Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Hepatitis B virus (HBV) infection is a major cause of chronic liver disease worldwide. Famciclovir is a nucleoside analogue with potent antiviral activity that appears promising in the management of patients with HBV infection. No data exist regarding the safety of nucleoside analogue withdrawal in patients treated for HBV cirrhosis. The authors describe a 41-year-old man with compensated HBV cirrhosis who developed fatal hepatic decompensation due to a rebound in viral replication within six weeks of discontinuing famciclovir therapy. Although several mutations in the HBV DNA polymerase gene have been documented, none has been associated with famciclovir resistance or adverse clinical outcomes. Clinicians should consider the risk of inducing serious flares in hepatic inflammation as a result of abrupt nucleoside analogue withdrawal. Until further data are available regarding the safety of withdrawal of these agents, indefinite treatment may be required in patients with established cirrhosis.
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- 2000
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20. Autonomic Regulation of Splanchnic Circulation
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Kathleen A Fraser and Samuel S Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
The role of the autonomic nervous system in circulatory regulation of the splanchnic organs (stomach, small intestine, colon, liver, pancreas and spleen) is reviewed. In general, the sympathetic nervous system is primarily involved in vasoconstriction, while the parasympathetic contributes to vasodilation. Vasoconstriction in the splanchnic circulation appears to be mediated by alpha-2 receptors and vasodilation by activation of primary afferent nerves with subsequent release of vasodilatory peptides, or by stimulation of beta-adrenergic receptors. As well, an important function of the autonomic nervous system is to provide a mechanism by which splanchnic vascular reserve can be mobilized during stress to maintain overall cardiovascular homeostasis.
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- 1991
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21. Liver Transplantation for Alcoholic Liver Disease: A Devilish Dilemma
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Stephen E Congly and Samuel S Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2013
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22. Pay Now or Pay (more) Later: Tracking the Costs of Hepatitis C Infection
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Robert P Myers and Samuel S Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2010
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23. Therapies for Cirrhotic Cardiomyopathy: Current Perspectives and Future Possibilities
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Hongqun Liu, Daegon Ryu, Sangyoun Hwang, and Samuel S. Lee
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cirrhotic cardiomyopathy ,treatments ,beta blockers ,antioxidants ,anti-apoptosis ,anti-inflammation ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM significantly contributes to mortality and morbidity in patients who undergo liver transplantation and contributes to the pathogenesis of hepatorenal syndrome/acute kidney injury. There is currently no specific treatment. The traditional management for non-cirrhotic cardiomyopathies, such as vasodilators or diuretics, is not applicable because an important feature of cirrhosis is decreased systemic vascular resistance; therefore, vasodilators further worsen the peripheral vasodilatation and hypotension. Long-term diuretic use may cause electrolyte imbalances and potentially renal injury. The heart of the cirrhotic patient is insensitive to cardiac glycosides. Therefore, these types of medications are not useful in patients with CCM. Exploring the therapeutic strategies of CCM is of the utmost importance. The present review summarizes the possible treatment of CCM. We detail the current status of non-selective beta-blockers (NSBBs) in the management of cirrhotic patients and discuss the controversies surrounding NSBBs in clinical practice. Other possible therapeutic agents include drugs with antioxidant, anti-inflammatory, and anti-apoptotic functions; such effects may have potential clinical application. These drugs currently are mainly based on animal studies and include statins, taurine, spermidine, galectin inhibitors, albumin, and direct antioxidants. We conclude with speculations on the future research directions in CCM treatment.
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- 2024
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24. Cardiomyopathy in cirrhosis: From pathophysiology to clinical careKey points
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Hongqun Liu, Jwan A. Naser, Grace Lin, and Samuel S. Lee
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cardiac ,cirrhosis ,hemodynamics ,MRI ,echocardiography ,prolonged QT Interval ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Summary: Cirrhotic cardiomyopathy (CCM) is defined as systolic or diastolic dysfunction in the absence of prior heart disease or another identifiable cause in patients with cirrhosis, in whom it is an important determinant of outcome. Its underlying pathogenic/pathophysiological mechanisms are rooted in two distinct pathways: 1) factors associated with portal hypertension, hyperdynamic circulation, gut bacterial/endotoxin translocation and the resultant inflammatory phenotype; 2) hepatocellular insufficiency with altered synthesis or metabolism of substances such as proteins, lipids, carbohydrates, bile acids and hormones. Different criteria have been proposed to diagnose CCM; the first in 2005 by the World Congress of Gastroenterology, and more recently in 2019 by the Cirrhotic Cardiomyopathy Consortium. These criteria mainly utilised echocardiographic evaluation, with the latter refining the evaluation of diastolic function and integrating global longitudinal strain into the evaluation of systolic function, an important addition since the haemodynamic changes that occur in advanced cirrhosis may lead to overestimation of systolic function by left ventricular ejection fraction. Advances in cardiac imaging, such as cardiac magnetic resonance imaging and the incorporation of an exercise challenge, may help further refine the diagnosis of CCM. Over recent years, CCM has been shown to contribute to increased mortality and morbidity after major interventions, such as liver transplantation and transjugular intrahepatic portosystemic shunt insertion, and to play a pathophysiologic role in the genesis of hepatorenal syndrome. In this review, we discuss the pathogenesis/pathophysiology of CCM, its clinical implications, and the role of cardiac imaging modalities including MRI. We also compare diagnostic criteria and review the potential diagnostic role of electrocardiographic QT prolongation. At present, no definitive medical therapy exists, but some promising potential treatment strategies for CCM are reviewed.
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- 2024
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25. Acute Coinfection with Hepatitis B and Hepatitis C Viruses
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Brian M Yan and Samuel S Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Acute coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV) is rare. The few previously reported cases all describe acute HBV followed by acute HCV, leading to HBV clearance but chronic HCV. This is the first reported case of acute concurrent infection and spontaneous clearance of both HBV and HCV.
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- 2005
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26. Hepatitis C Virus Infection in Canada’S First Nations People: A Growing Problem
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Matthew D Sadler and Samuel S Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2013
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27. Vasopressin Antagonists and Dilutional Hyponatremia
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D Mohamed Babatin and Samuel S Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
The paradox of dilutional hyponatremia, as described by Ovid two millennia ago, continues to apply to patients with advanced cirrhosis today: they have unremitting thirst despite vastly increased total body water. Hyponatremia of less than 130 mmol/L occurs in 30% of cirrhotic patients (1), and is mainly due to the reduced capacity of their kidneys to excrete free water.
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- 2004
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28. Hepatitis C, Insulin Resistance and Fatty Liver: Bad Things Come in Threes
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Ayman A Abdo and Samuel S Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2012
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29. Prolonged QT Interval in Cirrhosis: Twisting Time?
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William Lee, Bert Vandenberk, Satish R. Raj, and Samuel S. Lee
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acquired long qt syndrome ,torsade de pointes ,cirrhosis ,drug interaction ,ventricular repolarization ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Approximately 30% to 70% of patients with cirrhosis have QT interval prolongation. In patients without cirrhosis, QT prolongation is associated with an increased risk of ventricular arrhythmias, such as torsade de pointes (TdP). In cirrhotic patients, there is likely a significant association between the corrected QT (QTc) interval and the severity of liver disease, and possibly with increased mortality. We present a stepwise overview of the pathophysiology and management of acquired long QT syndrome in cirrhosis. The QT interval is mainly determined by ventricular repolarization. To compare the QT interval in time it should be corrected for heart rate (QTc), preferably by the Fridericia method. A QTc interval >450 ms in males and >470 ms in females is considered prolonged. The pathophysiological mechanism remains incompletely understood, but may include metabolic, autonomic or hormonal imbalances, cirrhotic heart failure and/or genetic predisposition. Additional external risk factors for QTc prolongation include medication (IKr blockade and altered cytochrome P450 activity), bradycardia, electrolyte abnormalities, underlying cardiomyopathy and acute illness. In patients with cirrhosis, multiple hits and cardiac-hepatic interactions are often required to sufficiently erode the repolarization reserve before long QT syndrome and TdP can occur. While some risk factors are unavoidable, overall risk can be mitigated by electrocardiogram monitoring and avoiding drug interactions and electrolyte and acidbase disturbances. In cirrhotic patients with prolonged QTc interval, a joint effort by cardiologists and hepatologists may be useful and significantly improve the clinical course and outcome.
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- 2022
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30. To B or Not to B: How Is Hepatitis B Spread and What Can be Done?
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Samuel S Lee
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 1993
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31. Oxidative Mechanisms and Cardiovascular Abnormalities of Cirrhosis and Portal Hypertension
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Hongqun Liu, Henry H. Nguyen, Sang Youn Hwang, and Samuel S. Lee
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oxidative stress ,cardiovascular ,cirrhosis ,liver ,portal hypertension ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
In patients with portal hypertension, there are many complications including cardiovascular abnormalities, hepatorenal syndrome, ascites, variceal bleeding, and hepatic encephalopathy. The underlying mechanisms are not yet completely clarified. It is well known that portal hypertension causes mesenteric congestion which produces reactive oxygen species (ROS). ROS has been associated with intestinal mucosal injury, increased intestinal permeability, enhanced gut bacterial overgrowth, and translocation; all these changes result in increased endotoxin and inflammation. Portal hypertension also results in the development of collateral circulation and reduces liver mass resulting in an overall increase in endotoxin/bacteria bypassing detoxication and immune clearance in the liver. Endotoxemia can in turn aggravate oxidative stress and inflammation, leading to a cycle of gut barrier dysfunction → endotoxemia → organ injury. The phenotype of cardiovascular abnormalities includes hyperdynamic circulation and cirrhotic cardiomyopathy. Oxidative stress is often accompanied by inflammation; thus, blocking oxidative stress can minimize the systemic inflammatory response and alleviate the severity of cardiovascular diseases. The present review aims to elucidate the role of oxidative stress in cirrhosis-associated cardiovascular abnormalities and discusses possible therapeutic effects of antioxidants on cardiovascular complications of cirrhosis including hyperdynamic circulation, cirrhotic cardiomyopathy, and hepatorenal syndrome.
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- 2023
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32. Galectin-3 inhibits cardiac contractility via a tumor necrosis factor alpha-dependent mechanism in cirrhotic rats.
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Ki Tae Yoon, Hongqun Liu, Jing Zhang, Sojung Han, and Samuel S. Lee
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- 2022
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33. β-blockers in advanced cirrhosis: More friend than enemy.
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Ki Tae Yoon, Hongqun Liu, and Samuel S. Lee
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- 2021
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34. Cirrhotic cardiomyopathy: causes and consequences.
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Baik, Soon Koo and Samuel S. Lee
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CIRRHOSIS of the liver , *CARDIOMYOPATHIES , *ETIOLOGY of diseases , *ALCOHOLISM , *DISEASE complications , *LIVER diseases , *HEART diseases - Abstract
Cirrhotic cardiomyopathy is generally defined as subnormal ventricular response to stress in the face of high resting cardiac output. Although this syndrome was first noticed more than three decades ago in cirrhotic patients, it was originally ascribed to latent alcoholic cardiomyopathy. During the 1980s−1990s, it became clear that blunted ventricular contractility to stress is also present in non-alcoholic patients and animal models of cirrhosis. Mechanistic studies in experimental animal models of cirrhosis indicate that multiple factors are responsible, including abnormal biophysical membrane characteristics, impairedβ-adrenergic signal transduction and increased activity of cardiodepressant systems mediated by cGMP. Cirrhotic cardiomyopathy appears to be precipitated or worsened by liver transplantation, insertion of transjugular intrahepatic portosystemic stent-shunts and infections. It may play a role in the pathogenesis of hepatorenal syndrome. Current management recommendations are empiric, non-specific measures; further research in this area is needed. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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35. Histological Response to Interferon Alfa-Based Therapies in Hepatitis C.
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Samuel S Lee
- Published
- 2004
36. Second-Line Treatment after Failure of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Tyrosine Kinase Inhibitor, Retrial of Immunotherapy, or Locoregional Therapy?
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Sang Youn Hwang, Sangjune L. Lee, Hongqun Liu, and Samuel S. Lee
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hepatocellular carcinoma ,immune checkpoint inhibitor ,second-line treatment ,tyrosine kinase inhibitor ,locoregional therapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Immune checkpoint inhibitor (ICI)-based therapy such as atezolizumab plus bevacizumab or durvalumab plus tremelimumab became mainstream first-line systemic treatment in advanced hepatocellular carcinoma (HCC) patients since remarkably superior efficacy of ICI-based therapy compared to tyrosine kinase inhibitors (TKIs) was reported in two recent randomized controlled trials (RCTs) (IMbrave150, HIMALAYA). However, the optimal second-line therapy after treatment failure of first-line ICI-based therapy remains unknown as no RCT has examined this issue. Summary: Therefore, at present, most clinicians are empirically treating patients with TKIs or retrial of ICI or locoregional treatment (LRT) modality such as transarterial therapy, radiofrequency ablation, and radiation therapy in this clinical setting without solid evidence. In this review, we will discuss current optimal strategies for second-line treatment after the failure of first-line ICI-based therapy by reviewing published studies and ongoing prospective trials. Key Messages: Clinicians should consider carefully whether to treat the patients with TKI, other ICI-based therapy, or LRT in this situation by considering several factors including liver function reserve, performance status, adverse events of previous therapy, and presence of lesion that can consider LRT such as oligoprogression and vascular invasion. In the meantime, we await the results of ongoing prospective trials to elucidate the best management options.
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- 2023
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37. Role of Galectin in Cardiovascular Conditions including Cirrhotic Cardiomyopathy
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Hongqun Liu, Sang-Youn Hwang, and Samuel S. Lee
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galectin ,lectin ,pathophysiology ,cardiac ,cirrhotic cardiomyopathy ,treatment ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Abnormal cardiac function in the setting of cirrhosis and in the absence of a primary cardiac disease is known as cirrhotic cardiomyopathy. The pathogenesis of cirrhotic cardiomyopathy is multifactorial but broadly is comprised of two pathways. The first is due to cirrhosis and synthetic liver failure with abnormal structure and function of many substances, including proteins, lipids, hormones, and carbohydrates such as lectins. The second is due to portal hypertension which invariably accompanies cirrhosis. Portal hypertension leads to a leaky, congested gut with resultant endotoxemia and systemic inflammation. This inflammatory phenotype comprises oxidative stress, cellular apoptosis, and inflammatory cell infiltration. Galectins exert all these pro-inflammatory mechanisms across many different tissues and organs, including the heart. Effective therapies for improving cardiac function in patients with cirrhosis are not available. Conventional strategies for other noncirrhotic heart diseases, including vasodilators, are not feasible because of the significant baseline vasodilation in cirrhotic patients. Therefore, exploring new treatment modalities for cirrhotic cardiomyopathy is of great importance. Galectin-3 inhibitors such as modified citrus pectin, N-acetyllactosamine, TD139 and GB0139 exert anti-apoptotic, anti-oxidative and anti-inflammatory effects and thus have potential therapeutic interest. This review briefly summarizes the physiological and pathophysiological role of galectin and specifically examines its role in cardiac disease processes. We present a more detailed discussion of galectin in cardiovascular complications of cirrhosis, particularly cirrhotic cardiomyopathy. Finally, therapeutic studies of galectin-3 inhibitors in cirrhotic cardiomyopathy are reviewed.
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- 2023
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38. Dysregulated Calcium Handling in Cirrhotic Cardiomyopathy
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Sang Youn Hwang, Hongqun Liu, and Samuel S. Lee
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cirrhotic cardiomyopathy ,L-type calcium channel ,ryanodine receptors ,cardiac contractility ,calcium transient ,Biology (General) ,QH301-705.5 - Abstract
Cirrhotic cardiomyopathy is a syndrome of blunted cardiac systolic and diastolic function in patients with cirrhosis. However, the mechanisms remain incompletely known. Since contractility and relaxation depend on cardiomyocyte calcium transients, any factors that impact cardiac contractile and relaxation functions act eventually through calcium transients. In addition, calcium transients play an important role in cardiac arrhythmias. The present review summarizes the calcium handling system and its role in cardiac function in cirrhotic cardiomyopathy and its mechanisms. The calcium handling system includes calcium channels on the sarcolemmal plasma membrane of cardiomyocytes, the intracellular calcium-regulatory apparatus, and pertinent proteins in the cytosol. L-type calcium channels, the main calcium channel in the plasma membrane of cardiomyocytes, are decreased in the cirrhotic heart, and the calcium current is decreased during the action potential both at baseline and under stimulation of beta-adrenergic receptors, which reduces the signal to calcium-induced calcium release. The study of sarcomere length fluctuations and calcium transients demonstrated that calcium leakage exists in cirrhotic cardiomyocytes, which decreases the amount of calcium storage in the sarcoplasmic reticulum (SR). The decreased storage of calcium in the SR underlies the reduced calcium released from the SR, which results in decreased cardiac contractility. Based on studies of heart failure with non-cirrhotic cardiomyopathy, it is believed that the calcium leakage is due to the destabilization of interdomain interactions (dispersion) of ryanodine receptors (RyRs). A similar dispersion of RyRs may also play an important role in reduced contractility. Multiple defects in calcium handling thus contribute to the pathogenesis of cirrhotic cardiomyopathy.
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- 2023
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39. Metabolic Stress Index Including Mitochondrial Biomarker for Noninvasive Diagnosis of Hepatic Steatosis
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Jae Seung Chang, Jhii-Hyun Ahn, Seong Hee Kang, Sang-Baek Koh, Jang-Young Kim, Soon Koo Baik, Ji Hye Huh, Samuel S. Lee, Moon Young Kim, and Kyu-Sang Park
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mitochondria ,non-alcoholic fatty liver disease ,FGF21 ,FGF19 ,adiponectin-to-leptin ratio ,central obesity ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
BackgroundMitochondrial dysfunction with oxidative stress contributes to nonalcoholic fatty liver disease (NAFLD) progression. We investigated the steatosis predictive efficacy of a novel non-invasive diagnostic panel using metabolic stress biomarkers.MethodsAltogether, 343 subjects who underwent magnetic resonance imaging-based liver examinations from a population-based general cohort, and 41 patients enrolled in a biopsy-evaluated NAFLD cohort, participated in the development and validation groups, respectively. Serologic stress biomarkers were quantitated by enzyme-linked immunosorbent assay.ResultsMultivariate regression showed that waist-to-hip ratio, fibroblast growth factor (FGF) 21, FGF19, adiponectin-to-leptin ratio, insulin, albumin, triglyceride, total-cholesterol, and alanine-aminotransferase were independent predictors of steatosis (rank-ordered by Wald). The area under receiver-operator characteristics curve [AUROC (95%CI)] of the metabolic stress index for steatosis (MSI-S) was 0.886 (0.85−0.92) and 0.825 (0.69−0.96) in development and validation groups, respectively. MSI-S had higher diagnostic accuracy (78.1%−81.1%) than other steatosis indices. MSI-S notably differentiated steatosis severities, while other indices showed less discrimination.ConclusionMSI-S, as a novel non-invasive index, based on mitochondrial stress biomarker FGF21 effectively predicted steatosis. Furthermore, MSI-S may increase the population that could be excluded from further evaluation, reducing unnecessary invasive investigations more effectively than other indices.
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- 2022
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40. Novel variant in glycophorin c gene protects against ribavirin-induced anemia during chronic hepatitis C treatment
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Jennifer J. Lin, Catrina M. Loucks, Jessica N. Trueman, Britt I. Drögemöller, Galen E.B. Wright, Eric M. Yoshida, Jo-Ann Ford, Samuel S. Lee, Richard B. Kim, Bandar Al-Judaibi, Ute I. Schwarz, Alnoor Ramji, Edward Tam, Colin J. Ross, and Bruce C. Carleton
- Subjects
Ribavirin ,Pharmacogenomics ,Adverse reactions ,HCV ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: The current use of ribavirin in difficult-to-cure chronic hepatitis C patients (HCV) and patients with severe respiratory infections is constrained by the issue of ribavirin-induced hemolytic anemia that affects 30% of treated patients, requiring dosage modification or discontinuation. Though some genetic variants have been identified predicting this adverse effect, known clinical and genetic factors do not entirely explain the risk of ribavirin-induced anemia. Methods: We assessed the associations of previously identified variants in inosine triphosphatase (ITPA), solute carrier 28A2 (SLC28A2) and vitamin D receptor (VDR) genes with ribavirin-induced anemia defined as hemoglobin decline of ≥30 g/L on treatment, followed by a staged discovery (n = 114), replication (n = 74), and combined (n = 188) genome-wide association study to uncover potential new predictive variants. Results: We identified a novel association in the gene coding glycophorin C (rs6741425; OR:0.12, 95%CI:0.04–0.34, P = 2.94 × 10-6) that predicts protection against ribavirin-induced anemia. We also replicated the associations of ITPA and VDR genetic variants with the development of ribavirin-induced anemia (rs1127354; OR:0.13, 95%CI:0.04–0.41, P = 8.66 ×10-5; and rs1544410; OR:1.65, 95%CI:1.01–2.70, P = 0.0437). Conclusions: GYPC variation affecting erythrocyte membrane strength is important in predicting risk for developing ribavirin-induced anemia. ITPA and VDR genetic variants are also important predictors of this adverse reaction.
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- 2021
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41. Cardiovascular events after liver transplantation: MACE hurts
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Mario H. Altieri, Hongqun Liu, and Samuel S. Lee
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cardiovascular complications ,liver transplantation ,heart failure ,cirrhotic cardiomyopathy ,arrhythmias ,ventricular dysfunction ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
The curative therapy for patients with end-stage liver disease is liver transplantation. However, liver transplantation challenges the cardiovascular system, and is associated with major adverse cardiovascular events (MACE). Immediately after implantation of the liver graft, changes in cardiac preload and afterload increase the cardiac workload. Longer-term postoperatively, a more sedentary lifestyle and enhanced appetite increase obesity and body mass index. Immunosuppressants may also affect the cardiovascular system. All these factors that liver recipients encounter impact the function of the cardiovascular system. Cardiac events are the third-leading cause of death in liver recipients. This review describes the pertinent factors that predispose to development of MACE after liver transplantation, and how to predict these cardiovascular events in the post-transplant period. We review the roles of metabolic syndrome, renal dysfunction, non-alcoholic fatty liver disease, diagnostic tests such as imaging and biomarkers, and parameters such as systolic and diastolic dysfunction, and QT interval prolongation in cardiovascular events. We summarize the current literature on scoring systems to predict cardiovascular events.
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- 2022
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42. A Dynamic Model for Predicting Outcome in Patients with HBV Related Acute-On-Chronic Liver Failure
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Wei Lin, Jing Zhang, Xiaohui Liu, Hongqun Liu, Jinqiu He, Ming Li, Shuqin Zhang, Hong Chen, Changqing Zhang, Wenfang Wu, Chenggang Jin, Samuel S. Lee, Zhongping Duan, and Yuexin Zhang
- Subjects
Prognosis ,Hepatitis B ,Nucleoside analog ,Cirrhosis ,Specialties of internal medicine ,RC581-951 - Abstract
Introduction and aim. Accurately predicting the prognosis of individual patient is crucial in the management of ACLF. We aimed to establish a specific prognostic model for HBV-related ACLF patients treated with nucleoside analog (NA).Material and methods. We prospectively collected 205 ACLF cases diagnosed according to the APASL criteria. A dynamic prognostic model based on APASL criteria was established and validated. To demonstrate that the model is also applicable to those within EASL criteria, we divided the patients into two groups: met APASL criteria only (group A, n = 123); met both APASL and EASL criteria (group B, n = 82). Its prognostic accuracy was also compared with chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score in group B.Results. The model is: R = 0.94 x Bilirubin + 0.53 x evolution of Bilirubin - 0.45 x PT-A - 0.22 x evolution in PT-A -0.1 x PLT + 10 x anti-HBe. The area under receiver operating characteristic curve (AUC) of the model for predicting 90-day mortality was 0.86, which was significantly higher than that of model for end stage liver disease(MELD), MELD-Na, CLIF-SOFA, ΔMELD (7d) and ΔMELD-Na (7d), ACLIF- SOFA(7d) (all p < 0.01). The AUC of our model in the validation group was 0.79 which was superior to MELD (0.45) CLIF-SOFA (0.53) score in group B patients (p < 0.01).Conclusion. In conclusion, the model was superior to the conventional methods in predicting the outcomes of patients with HBV related ACLF treated with NA. It is the first description of a novel prognostic model using consecutive data in patients with HBV-induced acute-on-chronic liver failure (ACLF) treated by nucleoside analogs.
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- 2018
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43. Long-Term Follow-up and Quantitative Hepatitis B Surface Antigen Monitoring in North American Chronic HBV Carriers
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Conar R. O’Neil, Stephen E. Congly, M. Sarah Rose, Samuel S. Lee, Meredith A. Borman, Carmen L. Charlton, Carla Osiowy, Mark G. Swain, Kelly W. Burak, and Carla S. Coffin
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Chronic Hepatitis B ,Natural History ,Disease Phase ,Nucleoside Analogues ,Diagnostic Test ,Canada ,Specialties of internal medicine ,RC581-951 - Abstract
Introduction. Quantitative hepatitis B surface antigen (qHBsAg) combined with HBV DNA may be useful for predicting chronic hepatitis B (CHB) activity and nucleoside analogue (NA) response.Material and methods. In this retrospective cohort study we evaluated qHBsAg levels according to CHB disease phase and among patients on treatment. Random effect logistic regression analysis was used to analyze qHBsAg change with time in the NA-treated cohort.Results. 545 CHB carriers [56% M, median age 48 y (IQR 38-59), 73% Asian] had qHBsAg testing. In the untreated group (44%), 8% were classified as immune tolerant, 10% immune clearance, 40% inactive, and 43% had HBeAg- CHB and the median HBsAg levels were 4.6 (IQR 3.4-4.9), 4.0 (IQR 3.4-4.5), 2.9 (IQR 1.4-3.8), and 3.2 log IU/mL (IQR 2.6-4.0), respectively; p < 0.001. In the NA-treated group (28% entecavir, 68% tenofovir, 4% lamivudine), no significant change in qHBsAg levels occured with time. However, 19% of patients on long-term NA had sustained qHBsAg < 2 log10 IU/mL.Conclusion. qHBsAg titers were associated with CHB phase and remained stable in those on long-term NA. A significant number of treated patients had low-level qHBsAg, of which some may be eligible for treatment discontinuation without risk of flare.
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- 2018
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44. A 3-year follow-up study after treatment with simeprevir in combination with pegylated interferon-α and ribavirin for chronic hepatitis C virus infection
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Fabien Zoulim, Christophe Moreno, Samuel S. Lee, Peter Buggisch, Andrzej Horban, Eric Lawitz, Chris Corbett, Oliver Lenz, Bart Fevery, Thierry Verbinnen, Umesh Shukla, and Wolfgang Jessner
- Subjects
Direct-acting antivirals ,Hepatitis C virus ,Pegylated interferon ,Simeprevir ,Sustained virologic response ,NS3 amino acid substitutions ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Simeprevir is approved with pegylated interferon and ribavirin (PR) for chronic hepatitis C virus (HCV) genotype (GT) 1 and GT4 infection in the USA and the European Union. Methods This 3-year follow-up study assessed the durability of sustained virologic response (SVR) (undetectable HCV RNA 12 or 24 weeks after treatment end), and evaluated the persistence of treatment-emergent NS3/4A protease inhibitor resistance in patients not achieving SVR following treatment with simeprevir plus PR in the parent study. The maintenance of SVR after the last post-therapy follow-up visit of the parent study (LPVPS) was assessed using HCV RNA measurements. The persistence of treatment-emergent NS3 amino acid substitutions in patients with no SVR at LPVPS was assessed using population sequencing. No study medications were administered. Results Overall, 249 patients were enrolled (200 with SVR at LPVPS; 49 with no SVR at LPVPS); 40 patients discontinued prematurely (18 with SVR; 22 with no SVR). All 200 enrolled patients who achieved SVR in the parent study maintained SVR until the last available visit in this study (median follow-up time: 35.8 months). The treatment-emergent NS3 amino acid substitutions detected at time of failure in the parent study in 43/49 enrolled patients were no longer detected in 37/43 (86.0%) at the end of this study (median follow-up time: 179.9 weeks [41.3 months]). Conclusion This 3-year follow-up study provides evidence for the long-term durability of SVR (100%) after successful treatment with simeprevir plus PR. Treatment-emergent NS3 amino acid substitutions became undetectable in the majority of patients. Trial registration NCT01349465; ClinicalTrials.gov.
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- 2018
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45. A Gene-Based Analysis of Acoustic Startle Latency
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Alicia K. Smith, Tanja Jovanovic, Varun Kilaru, Adriana Lori, Lauren Gensler, Samuel S. Lee, Seth Davin Norrholm, Nicholas Massa, Bruce Cuthbert, Bekh Bradley, Kerry J. Ressler, and Erica Duncan
- Subjects
acoustic startle ,latency ,genetics ,schizophrenia ,endophenotype ,Psychiatry ,RC435-571 - Abstract
Latency of the acoustic startle response is the time required from the presentation of startling auditory stimulus until the startle response is elicited and provides an index of neural processing speed. Latency is prolonged in subjects with schizophrenia compared to controls in some but not all studies and is 68–90% heritable in baseline startle trials. In order to determine the genetic association with latency as a potential inroad into genetically based vulnerability to psychosis, we conducted a gene-based study of latency followed by an independent replication study of significant gene findings with a single-nucleotide polymorphism (SNP)-based analysis of schizophrenia and control subjects. 313 subjects from an urban population of low socioeconomic status with mixed psychiatric diagnoses were included in the gene-based study. Startle testing was conducted using a Biopac M150 system according to our published methods. Genotyping was performed with the Omni-Quad 1M or the Omni Express BeadChip. The replication study was conducted on 154 schizophrenia subjects and 123 psychiatric controls. Genetic analyses were conducted with Illumina Human Omni1-Quad and OmniExpress BeadChips. Twenty-nine SNPs were selected from four genes that were significant in the gene-based analysis and also associated with startle and/or schizophrenia in the literature. Linear regressions on latency were conducted, controlling for age, race, and diagnosis as a dichotomous variable. In the gene-based study, 2,870 genes demonstrated the evidence of association after correction for multiple comparisons (false discovery rate
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- 2017
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46. Is pre-treatment liver biopsy necessary for all hepatitis C genotypes?
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Kevork M. Peltekian, Dr., Vincent G. Bain, Samuel S. Lee, Morris Sherman, Curtis L. Cooper, Eric M. Yoshida, Paul J. Marotta, Mel Krajden, Robert Balshaw, and Marc Deschênes
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Chronic hepatitis C ,Liver biopsy ,Outcomes research ,Practice guidelines ,Antiviral therapy ,Adherence ,Specialties of internal medicine ,RC581-951 - Abstract
Background. Current practice guidelines recommend liver biopsy prior to treatment of hepatitis C genotype-1 but not for genotype-2/3; this is based on expert opinion, not on published evidence. Methods. In retrospective analysis of a large trial database prior to the publication of recent guidelines, we compared outcomes in 985 treatment-naïve patients with hepatitis C who did or did not undergo liver biopsy before starting peginterferon alfa-2a plus ribavirin. Results. Physicians elected to treat 141/654 (21.6%) genotype-1 patients and 126/331 (38.1%) genotype-2/3 patients without liver biopsy. There were no differences in baseline characteristics among those with or without pre-treatment liver biopsy, except for female preponderance in genotype-1 patients with liver biopsy. The sustained viral response (SVR) rate was no different amongst genotype-2/3 patients who had a biopsy before treatment with 66.3% SVR vs. 69.8% of those treated without biopsy (p = 0.546), but significantly higher among genotype-1 patients with pre-treatment liver biopsy at 54.6 vs. 44.0% for those treated without a liver biopsy (p = 0.029). In genotype-1 patients with liver biopsy, more patients with cirrhosis had dose adjustments (p = 0.0057) rather than drug discontinuation. There was tendency for earlier discontinuation among patients without pre-treatment liver biopsy. Conclusions. Pre-treatment liver biopsy was associated with better SVR amongst genotype-1 patients. This improvement may reflect ongoing commitment to completing the treatment course by both patient and physician. In genotype-2/3 patients, pre-treatment liver biopsy may not be essential to maximize SVR rates. This study validates the recommendations of the most recent treatment guidelines for hepatitis C.
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- 2011
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47. Cirrhotic Cardiomyopathy
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Waleed Al Hamoudi and Samuel S. Lee
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Cirrhosis ,cardiac complications ,heart failure ,QT interval ,diastolic function ,systolic function ,Specialties of internal medicine ,RC581-951 - Abstract
Liver cirrhosis is associated with a wide range of cardiovascular abnormalities. These abnormalities include hyperdynamic circulation characterized by an increase in cardiac output and a decrease in peripheral vascular resistance. Despite the increased cardiac output, impaired ventricular contractility in response to both physiological and pharmacological stimuli has been described. Other cardiac abnormalities include structural changes including enlargement or hypertrophy of different cardiac chambers and electrophysiological changes such as QT prolongation. This constellation of cardiac abnormalities is termed cirrhotic cardiomyopathy. The pathogenic mechanisms of cirrhotic cardiomyopathy are multifactorial and include cardiomyocyte plasma membrane physico-chemical changes, attenuated stimulatory pathways, and enhanced activity of inhibitory systems. Accumulating evidence suggests that cirrhotic cardiomyopathy plays a major role in the pathogenesis of cardiac dysfunction following liver transplantation or transjugular intrahepatic portosystemic shunt placement. Recent research also strongly suggests that cirrhotic cardiomyopathy contributes to the pathogenesis of hepatorenal syndrome, especially following infections such as spontaneous bacterial peritonitis. Treatment of this syndrome remains largely empirical. Successful liver transplantation is thought to improve all the organ-related hemodynamic dysfunctions, including hepatopulmonary syndrome, cerebral hypoperfusion, hepatorenal syndrome, and cirrhotic cardiomyopathy. The prolonged QT interval normalizes following liver transplantation. Thus, liver transplantation appears to be the ultimate treatment for the cardiovascular complications of cirrhosis.
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- 2006
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48. [Preclinical loading in patients with acute chest pain and acute coronary syndrome - PRELOAD survey].
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Macherey-Meyer S, Braumann S, Heyne S, Meertens MM, Tichelbäcker T, Baldus S, Lee S, and Adler C
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- Humans, Germany, Guideline Adherence, Male, Female, Non-ST Elevated Myocardial Infarction diagnosis, Non-ST Elevated Myocardial Infarction therapy, Middle Aged, Myocardial Infarction diagnosis, Chest Pain etiology, Chest Pain drug therapy, Vitamin K antagonists & inhibitors, Electrocardiography, Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome drug therapy, Aspirin administration & dosage, Aspirin therapeutic use, Anticoagulants therapeutic use, Anticoagulants administration & dosage, Anticoagulants adverse effects, ST Elevation Myocardial Infarction diagnosis, ST Elevation Myocardial Infarction therapy, Heparin therapeutic use, Heparin administration & dosage, Emergency Medical Services
- Abstract
Background: Guidelines on myocardial infarction (MI) recommend antithrombotic and anticoagulatory treatment at time of diagnosis. MI with ST segment elevation (STEMI) is mostly a certain diagnosis. Acute coronary syndrome without ST segment elevation (NSTE-ACS) has diagnostic uncertainty and remains a working diagnosis in the prehospital setting., Objective: Assessment of prehospital loading with aspirin and heparin depending on ACS subtype and pretreatment with oral anticoagulants., Methods: The PRELOAD survey was a nationwide German study. STEMI/NSTE-ACS scenarios were designed and varied in pretreatment: I) no pretreatment, II) new oral anticoagulants (NOAC), III) vitamin K antagonist (VKA). Loading strategy was assessed and included: a) aspirin (ASA), b) unfractionated heparin (UFH), c) ASA + UFH, d) no loading., Results: A total of 708 emergency physicians were included. In NSTE-ACS without pretreatment, 79% chose loading (p < 0.001). ASA + UFH (71.4%) was the preferred option. In corresponding STEMI scenario, 100% chose loading and 98.6% preferred ASA + UFH (p < 0.001). In NSTE-ACS with NOAC pretreatment, 69.8% favored loading (p < 0.001); in VKA pretreatment the corresponding rate was 72.3% (p < 0.001). In each scenario, ASA was the preferred option. In STEMI with NOAC pretreatment, 97.5% chose loading (p < 0.001); analogous rate was 96.8% in STEMI with VKA pretreatment (p < 0.001). ASA was the preferred option again., Conclusions: Prehospital loading was the preferred treatment strategy despite the diagnostic uncertainty in NSTE-ACS and guidelines recommending loading at time of diagnosis. Pretreatment with oral anticoagulants resulted in a strategy shift to loading with only aspirin. In STEMI patients, this indicates potential undertreatment., (© 2023. The Author(s).)
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- 2024
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49. Oral anticoagulation in patients with left ventricular thrombus: a systematic review and network meta-analysis with reconstructed time-to-event data.
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Heyne S, Macherey-Meyer S, Meertens MM, Finke K, Baldus S, Adler C, and Lee S
- Abstract
Background: Left ventricular thrombus (LVT) is associated with high rates of systemic embolism. Vitamin K antagonists (VKAs) are the only approved treatment for LVT. Although evidence suggests direct oral anticoagulant (DOACs) to be at least equally effective in general, the efficacy of individual DOACs remains unclear., Methods: A literature search was performed in EMBASE, MEDLINE and Web of Science looking for randomized controlled trials (RCTs) and non-randomized controlled studies of interventions (NRSI) comparing individual DOACs to VKAs for the treatment of LVT. Individual patient data was reconstructed and incorporated in a Bayesian network meta-analysis (NMA) and a Cox frailty regression model., Results: A total of 2545 patients across 19 studies (4 RCTs, 15 NRSI) were included. 1738 received VKAs, 581 received Rivaroxaban, 226 received Apixaban, 82 received Dabigatran and 2 received Edoxaban. LVT resolution was less likely with VKAs compared to Rivaroxaban in the time-to-event analysis (HR 0.66, 95% CI [0.49; 0.91], p = 0.01). There was no difference for other DOACs compared to VKAs. Rivaroxaban reduced ischemic stroke compared to VKAs (OR 0.18, 95% CrI [0.05; 0.49]), other DOACs did not., Conclusion: In this NMA, Rivaroxaban showed faster LVT resolution and consecutively lower odds of ischemic stroke than VKAs while Apixaban and Dabigatran showed at least equal efficacy. Given the quality and size of the available studies, these differences between individual DOACs should be acknowledged as hypothesis generating only. Future adequately powered randomized controlled trials are needed to assess possible time-varying effects between individual DOACs., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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50. The Effect of Tissue Inhibitor of Metalloproteinases on Scar Formation after Spinal Cord Injury.
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Mishra RR, Nielsen BE, Trudrung MA, Lee S, Bolstad LJ, Hellenbrand DJ, and Hanna AS
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- Humans, Animals, Tissue Inhibitor of Metalloproteinase-1 metabolism, Spinal Cord Injuries pathology, Spinal Cord Injuries metabolism, Cicatrix pathology, Cicatrix metabolism, Tissue Inhibitor of Metalloproteinases metabolism
- Abstract
Spinal cord injury (SCI) often results in permanent loss of motor and sensory function. After SCI, the blood-spinal cord barrier (BSCB) is disrupted, causing the infiltration of neutrophils and macrophages, which secrete several kinds of cytokines, as well as matrix metalloproteinases (MMPs). MMPs are proteases capable of degrading various extracellular matrix (ECM) proteins, as well as many non-matrix substrates. The tissue inhibitor of MMPs (TIMP)-1 is significantly upregulated post-SCI and operates via MMP-dependent and MMP-independent pathways. Through the MMP-dependent pathway, TIMP-1 directly reduces inflammation and destruction of the ECM by binding and blocking the catalytic domains of MMPs. Thus, TIMP-1 helps preserve the BSCB and reduces immune cell infiltration. The MMP-independent pathway involves TIMP-1's cytokine-like functions, in which it binds specific TIMP surface receptors. Through receptor binding, TIMP-1 can stimulate the proliferation of several types of cells, including keratinocytes, aortic smooth muscle cells, skin epithelial cells, corneal epithelial cells, and astrocytes. TIMP-1 induces astrocyte proliferation, modulates microglia activation, and increases myelination and neurite extension in the central nervous system (CNS). In addition, TIMP-1 also regulates apoptosis and promotes cell survival through direct signaling. This review provides a comprehensive assessment of TIMP-1, specifically regarding its contribution to inflammation, ECM remodeling, and scar formation after SCI.
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- 2024
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