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Utility of the low-accelerating-dose regimen in 182 liver recipients with recurrent hepatitis C virus

World Journal of Gastroenterology 2015年第20期21卷 6236-6245页

作者： Kieron BL Lim Hamid R Sima M Isabel Fiel Viktoriya Khaitova John T Doucette Maria Chernyiak Jawad Ahmad Nancy Bach Charissa Chang Priya Grewal Leona Kim-Schluger Lawrence Liu joseph odin Ponni Perumalswami Sander S Florman Thomas D Schiano Division of Liver Diseases Icahn School of Medicine at Mount Sinai Division of Gastroenterology and Hepatology National University Center for Organ TransplantationNational University Hospital Lillian and Henry M Stratton-Hans Popper Department of Pathology Icahn School of Medicine at Mount Sinai Recanati-Miller Transplantation Institute Icahn School of Medicine at Mount Sinai Department of Preventive Medicine Icahn School of Medicine at Mount Sinai

AIM: To describe our experience using a low-acceleratingdose regimen(LADR) with pegylated interferon alpha-2a and ribavirin in treatment of hepatitis C virus(HCV) recurrence. METHODS: From 2003, a protocolized LADR strategy was employed to treat liver transplant(LT) recipients with recurrent HCV at our institution. Medical records of 182 adult patients with recurrent HCV treated with LADR between 1/2003 and 1/2011 were reviewed. Histopathology from all post-LT liver biopsies were reviewed in a blinded fashion. Paired recipient and donor IL28 B status were assessed. A novel technique was employed to ascertain recipient and donor IL28B(rs12979860) Gt data using DNA extracted from archival FFPE tissue from explanted native livers and donor gallbladders respectively. The primary endpoint was SVR; secondary endpoints examined include(1) patient and graft survival;(2) effect of anti-viral therapy on liver histology(fibrosis and inflammation);(3) incidence of on-treatment development of ACR, CDR, or PCH;(4) association of recipient and donor IL28 B genotype with SVR; and(5) incidence of antiviral therapy-associated adverse events(anemia, leukopenia, thrombocytopenia, depression) and hepatic ***: The overall SVR rate was 38%(29% Gt1, 67% Gt2, 86% Gt3 and 58% Gt4). HCV Gt(P < 0.0001), donor age(P = 0.003), cytomegalovirus mismatch(P = 0.001), baseline serum bilirubin(P = 0.002), and baseline viral load(P = 0.04) were independent predictors for SVR. SVR rates were significantly higher in the recipient-CC/donor-non CC pairs(P = 0.007). Neither baseline fibrosis nor change in fibrosis stage after anti-viral therapy were associated with SVR. Fibrosis progressed in 72% of patients despite SVR. Median graft survival was 91 mo. Five-year patient survival was superior in patients who achieved SVR(97% vs 82%, P = 0.001). Pre-treatment ALP ≥ 150 U/L(P = 0.01), total bilirubin ≥ 1.5 mg/d L(P = 0.001) and creatinine ≥ 2 mg/d L(P = 0.001) were independently associated

关键词： Hepatitis C recurrence Liver transplant Low accelerating dose regimen Peginterferon α-2a IL28B

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Hepatic decompensation/serious adverse events in post-liver transplantation recipients on sofosbuvir for recurrent hepatitis C virus

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World Journal of Gastroenterology 2016年第9期22卷 2844-2854页

作者： Neal Patel Kian Bichoupan Lawrence Ku Rachana Yalamanchili Alyson Harty Donald Gardenier Michel Ng David Motamed Viktoriya Khaitova Nancy Bach Charissa Chang Priya Grewal Meena Bansal Ritu Agarwal Lawrence Liu Gene Im Jennifer Leong Leona Kim-Schluger joseph odin Jawad Ahmad Scott Friedman Douglas Dieterich Thomas Schiano Ponni Perumalswami Andrea Branch Division of Liver Diseases Icahn School of Medicine at Mount Sinai Recanati Miller Transplant Institute Icahn School of Medicine at Mount Sinai

AIM: To determine the safety profile of new hepatitis C virus (HCV) treatments in liver transplant (LT) recipients with recurrent HCV ***: Forty-two patients were identified with recurrent HCV infection that underwent LT at least 12 mo prior to initiating treatment with a Sofosbuvir-based regimen during December 2013-June 2014. Cases were patients who experienced hepatic decompensation and/or serious adverse events (SAE) during or within one month of completing treatment. Controls had no evidence of hepatic decompensation and/or SAE. HIV-infected patients were excluded. Cumulative incidence of decompensation/SAE was calculated using the Kaplan Meier method. Exact logistic regression analysis was used to identify factors associated with the composite ***: Median age of the 42 patients was 60 years [Interquartile Range (IQR): 56-65 years], 33% (14/42) were female, 21% (9/42) were Hispanic, and 9% (4/42) were Black. The median time from transplant to treatment initiation was 5.4 years (IQR: 2.1-8.8 years). Thirteen patients experienced one or more episodes of hepatic decompensation and/or SAE. Anemia requiring transfusion, the most common event, occurred in 62% (8/13) patients, while 54% (7/13) decompensated. The cumulative incidence of hepatic decompensation/SAE was 31% (95%CI: 16%-41%). Risk factors for decompensation/SAE included lower pre-treatment hemoglobin (OR = 0.61 per g/dL, 95%CI: 0.40-0.88, P 2, 95%CI: 0.90-0.99, P = 0.01), and higher baseline serum total bilirubin (OR = 2.43 per mg/dL, 95%CI: 1.17-8.65, P < 0.01). The sustained virological response rate for the cohort of 42 patients was 45%, while it was 31% for ***: Sofosbuvir/ribavirin will continue to be used in the post-transplant population, including those with HCV genotypes 2 and 3. Management of anemia remains an important clinical challenge.

关键词： Hepatitis C virus Sofosbuvir Ribavirin Anemia Hepatic decompensation Serious adverse event Liver transplant

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Factors associated with success of telaprevir-and boceprevir-based triple therapy for hepatitis C virus infection

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World Journal of Hepatology 2017年第11期9卷 551-561页

作者： Kian Bichoupan Neeta Tandon Valerie Martel-Laferriere Neal M Patel David Sachs Michel Ng Emily A Schonfeld Alexis Pappas James Crismale Alicia Stivala Viktoriya Khaitova Donald Gardenier Michael Linderman William Olson Ponni V Perumalswami Thomas D Schiano joseph a odin Lawrence U Liu Douglas T Dieterich Andrea D Branch Division of Liver Diseases Icahn School of Medicine at Mount Sinai Icahn Medical Instititute Janssen Pharmaceuticals Com-panies Division of Janssen Scientific Affairs Inc. Genetics and Genomics Icahn School of Medicine at Mount Sinai

To evaluate new therapies for hepatitis C virus (HCV), data about real-world outcomes are needed. METHODSOutcomes of 223 patients with genotype 1 HCV who started telaprevir- or boceprevir-based triple therapy (May 2011-March 2012) at the Mount Sinai Medical Center were analyzed. Human immunodeficiency virus-positive patients and patients who received a liver transplant were excluded. Factors associated with sustained virological response (SVR24) and relapse were analyzed by univariable and multivariable logistic regression as well as classification and regression trees. Fast virological response (FVR) was defined as undetectable HCV RNA at week-4 (telaprevir) or week-8 (boceprevir). RESULTSThe median age was 57 years, 18% were black, 44% had advanced fibrosis/cirrhosis (FIB-4 ≥ 3.25). Only 42% (94/223) of patients achieved SVR24 on an intention-to-treat basis. In a model that included platelets, SVR24 was associated with white race [odds ratio (OR) = 5.92, 95% confidence interval (CI): 2.34-14.96], HCV sub-genotype 1b (OR = 2.81, 95%CI: 1.45-5.44), platelet count (OR = 1.10, per x 104 cells/μL, 95%CI: 1.05-1.16), and IL28B CC genotype (OR = 3.54, 95%CI: 1.19-10.53). Platelet counts > 135 x 103/μL were the strongest predictor of SVR by classification and regression tree. Relapse occurred in 25% (27/104) of patients with an end-of-treatment response and was associated with non-FVR (OR = 4.77, 95%CI: 1.68-13.56), HCV sub-genotype 1a (OR = 5.20; 95%CI: 1.40-18.97), and FIB-4 ≥ 3.25 (OR = 2.77; 95%CI: 1.07-7.22). CONCLUSIONThe SVR rate was 42% with telaprevir- or boceprevir-based triple therapy in real-world practice. Low platelets and advanced fibrosis were associated with treatment failure and relapse.

关键词： Sustained virologic response Hepatitis C virus Relapse Telaprevir Boceprevir Triple-therapy Classification and regression Adverse event Real-world

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Real-world cure rates for hepatitis C virus treatments that include simeprevir and/or sofosbuvir are comparable to clinical trial results

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World Journal of Virology 2017年第4期6卷 59-72页

作者： Kian Bichoupan Neeta Tandon James F Crismale Joshua Hartman David Del Bello Neal Patel Sweta Chekuri Alyson Harty Michel Ng Keith M Sigel Meena B Bansal Priya Grewal Charissa Y Chang Jennifer Leong Gene Y Im Lawrence U Liu joseph a odin Nancy Bach Scott L Friedman Thomas D Schiano Ponni V Perumalswami Douglas T Dieterich Andrea D Branch Division of Liver Diseases Icahn School of Medicine at Mount Sinai Janssen Scientific Affairs LLC Division of General Internal Medicine Icahn School of Medicine at Mount Sinai

AIM To assess the real-world effectiveness and cost of simeprevir(SMV), and/or sofosbuvir(SOF)-based therapy for chronic hepatitis C virus(HCV) *** The real-world performance of patients treated with SMV/SOF ± ribavirin(RBV), SOF/RBV, and SOF/RBV with pegylated-interferon(PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response-the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response(SVR) 12]-were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic *** SVR 12 rates were as follows: 86%(95%CI: 80%-91%)among 178 patients on SMV/SOF ± RBV; 62%(95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78%(95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR 12 were $174442(standard deviation: ± $18588) for SMV/SOF ± RBV; $223003(± $77946) for SOF/RBV; and $126496(± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio(OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin(OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR 12(OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. CONCLUSION SVR 12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs.

关键词： Cirrhosis Cost Sustained virological response Protease inhibitor Polymerase inhibitor

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A review from mesenchymal stem-cells and their small extracellular vesicles in tissue engineering

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BIOCELL 2022年第2期46卷 325-338页

作者： odin RAMIREZ-FERNANDEZ ESMERALDA ZUÑIGA-AGUILAR Universidad Tecnologica de Mexico-UNITEC Mexico-Campus en Linea Col.AnáhuacCiudad de México11320Mexico Department of Biomedical Engineer Universidad Politecnica de ChiapasCol.Las BrisasSuchiapa29150Mexico Department of Electrical and Computational Engineer Universidad Autónoma de Ciudad JuárezInstituto de Ingeniería y TecnologíaCiudad Juárez32310Mexico

This review aims to offer a vision of the clinical reality of cell therapy today in intensive *** this,it has been carried out a description of the properties,functions,and Mesenchymal Stem Cells(MSCS)sources to subsequently address the evidence in preclinical models and studies clinical trials with whole cells and models attributed to small extracellular vesicles(sEVs),nanoparticles made up of microvesicles secreted by cells with an effect on the extracellular matrix,and their impact as an alternative towards cell-free regenerative *** are cells that enhance the regenerative capacity which can be differentiated typically in different lineages committed as bone,cartilage,and adipose *** the other hand,small extracellular vesicles are structures that participate notoriously and crucially in intercellular communication,which has led to a change in the concept of the functions and the role that these vesicles play in living organisms,in the restoration of damaged tissues and the inflammatory response and *** present the mechanisms that are involved in the applications of MSCS as whole cells and their sEVs in cell therapy and cell-free therapy as an alternative in regenerative *** the structural loss that occurs after surgical procedures for cystic and tumoral pathology in periodontitis,as well as the maxillary atrophy that determines the rehabilitation with dental implants,it is imperative to find satisfactory *** opportunity provided by the findings in stem cells is a recent introduction in the field of oral surgery,based on the regenerative potential that these cells possess to restore defects at different levels of the oral *** review aims to discover the real applications that stem cells may have in our treatments shortly.

关键词： Tissue engineering Mesenchymal stem cells Small extracellular vesicles Acute graft-versus-host disease Cell culture Cell differentiation

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Design and development of a dual-flow bioreactor mimicking intestinal peristalsis and permeability in epithelial tissue barriers for drug transport assessment

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BIOCELL 2019年第1期43卷 29-35页

作者： odin RAMIREZ-FERNANDEZ Ludovika CACOPARDO Benjamin LEON-MANCILLA Joana COSTA Research Centre“E.Piaggio”Department of Information Engineering University of PisaItaly Departamento de Cirugia Facultad de MedicinaUniversidad nacional Autonoma de Mexico Departamento de Ciencias Basicas Instituto Tecnologico de TlalnepantlaTecnologicos de MexicoMexico

We present a bioreactor system which combines a semi permeable membrane that simulates the osmotic nutrients interchange in the small intestine circulation and rhythmic peristaltic *** custom-designed presents a semipermeable membrane bioreactor,with peristaltic flow and compression variation that allows adjustment of luminal flow *** addition,this system is also capable of achieving the drug distribution in the small intestine model from the apical compartment to the basal compartment by the semipermeable *** dynamic bioreactor can mimic the human small intestine with increased accuracy to overcome many of the limitations and accuracy with the previously described in vitro small intestinal models,providing a more representative model of the small intestine.

关键词： Bioreactor Flow Simulation Permeability 3D Print Small Intestine

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Influence of surface modified mixed metal oxide nanoparticles on the electrochemical and mechanical properties of polyurethane matrix

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Frontiers of Chemical Science and Engineering 2023年第1期17卷 1-14页

作者： joseph Raj Xavier Department of Chemistry Saveetha School of EngineeringSaveetha Institute of Medical and Technical SciencesChennai-602105India

Newly synthesized functional nanoparticles,3-amino-1,2,4-triazole(ATA)/SiO_(2)—TiO_(2)were introduced to the polyurethane(PU)*** techniques were used to investigate the barrier properties of the synthesized PU—ATA/SiO_(2)—TiO_(2)nanocomposite coated steel *** natural seawater,electrochemical impedance spectroscopy experiments indicated outstanding protective behaviour for the PU—ATA/SiO_(2)—TiO_(2)coated *** coating resistance(Rcoat)of PU—ATA/SiO_(2)—TiO_(2)was determined to be 2956.90 kΩ·cm^(−2).The Rcoat of the PU—ATA/SiO_(2)—TiO_(2)nanocomposite coating was found to be over 50%higher than the PU *** current measured along the scratched surface of the PU—ATA/SiO_(2)—TiO_(2)coating was found to be very low(1.65 nA).The enhanced ATA/SiO_(2)—TiO_(2)nanoparticles inhibited the entry of electrolytes into the coating interface,as revealed by scanning electron microscopy/energy dispersive X-ray spectroscopy and X-ray diffraction analysis of the degradation *** contact angle testing validated the hydrophobic nature of the PU—ATA/SiO_(2)—TiO_(2)coating(θ=115.4°).When the concentration of ATA/SiO_(2)—TiO_(2)nanoparticles was 2 wt%,dynamic mechanical analysis revealed better mechanical ***,the newly synthesised PU—ATA/SiO_(2)—TiO_(2)nanocomposite provided excellent barrier and mechanical properties due to the addition of ATA/SiO_(2)—TiO_(2)nanoparticles to the polyurethane,which inhibited material degradation and aided in the prolongation of the coated steel’s life.

关键词： SiO_(2)/TiO_(2)nanoparticle nanocomposite coatings dynamic mechanical analysis electrochemical techniques corrosion colloids and interfaces

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Comparison of bacterial quantities in left and right colon biopsies and faeces

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World Journal of Gastroenterology 2012年第32期18卷 4404-4411页

作者： Anna Lyra Sofia Forssten Peter Rolny Yvonne Wettergren Sampo J Lahtinen Krista Salli Lennart Cedgrd Elisabeth odin Bengt Gustavsson Arthur C Ouwehand DuPont Nutrition and Health KantvikActive Nutrition02460 KantvikFinland Department of Medicine Sahlgrenska AcademyUniversity of GothenburgS-41685 GothenburgSweden Wasa MedicalsAB Probiotic DivisionS-302 91 HalmstadSweden Department of Surgery Sahlgrenska AcademyUniversity of GothenburgS-41685 GothenburgSweden

AIM:To compare quantities of predominant and pathogenic bacteria in mucosal and faecal ***:Twenty patients undergoing diagnostic colonoscopy with endoscopically and histologically normal mucosa were recruited to the study,14 subjects of which also supplied faecal(F) samples between 15 d to 105 d post *** biopsies were taken from each subject from the midportion of the ascending colon(right side samples,RM) and the sigmoid(left side samples,LM).Predominant intestinal and mucosal bacteria including clostridial 16S rRNA gene clusters Ⅳ and ⅩⅣab,Bacteroidetes,Enterobacteriaceae,Bifidobacterium spp.,Akkermansia muciniphila(***),Veillonella spp.,Collinsella spp.,Faecalibacterium prausnitzii(***) and putative pathogens such asEscherichia coli(***),Clostridium difficile(***),Helicobacter pylori(***) and Staphylococcus aureus(***) were analysed by quantitative polymerase chain reaction(qPCR).Host DNA was quantified from the mucosal samples with human glyceraldehyde 3-phosphate dehydrogenase gene targeting *** t tests and the Pearson correlation were applied for statistical ***:The most prominent bacterial groups were clostridial groups Ⅳ and ⅩⅣa+b andBacteroidetes and bacterial species *** in both sample *** and *** were not detected and *** was detected in only one mucosal sample and three faecal *** was detected in less than half of the mucosal samples at both sites,but was present in all faecal *** detected bacteria,except Enterobacteriaceae,were present at higher levels in the faeces than in the mucosa,but the different locations in the colon presented comparable quantities(RM,LM and F followed byP 1 for RMvs F,P 2 for LMvs F andP 3 for RM vs LM:4.17 ± 0.60 log 10 /g,4.16 ± 0.56 log 10 /g,5.88 ± 1.92 log 10 /g,P 1 = 0.011,P 2 = 0.0069,P 3 = 0.9778 ***;6.25 ± 1.3 log 10 /g,6.09 ± 0.81 log 10 /g,8.84 ± 1.38 log 10 /g,P

关键词： Gastrointestinal microbiota Mucosa Faeces Real-time quantitative polymerase chain reaction Sampling

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On Two Classes of Finite Inseparable p-Groups

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Acta Mathematica Sinica,English Series 2015年第7期31卷 1203-1214页

作者： joseph KIRTL Department of Mathematics Marist College

A finite group is inseparable, it does not split over any proper nontrivial normal subgroup; that is, if it has no nontrivial semidirect product decompositions. This paper investigates two classes of finite inseparabl... 详细信息

关键词： p-group inseparable splitting

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Modelling COVID-19 Cumulative Number of Cases in Kenya Using a Negative Binomial INAR (1) Model

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Open Journal of Modelling and Simulation 2023年第1期11卷 14-36页

作者： Charity Wamwea Susan Mwelu Matabel odin Jomo Kenyatta University of Agriculture and Technology (JKUAT) Nairobi Kenya

In this paper, a Negative Binomial (NB) Integer-valued Autoregressive model of order 1, INAR (1), is used to model and forecast the cumulative number of confirmed COVID-19 infected cases in Kenya independently for the three waves starting from 14th March 2020 to 1st February 2021. The first wave was experienced from 14th March 2020 to 15th September 2020, the second wave from around 15th September 2020 to 1st February 2021 and the third wave was experienced from 1st February 2021 to 3rd June 2021. 5, 10, and 15-day-ahead forecasts are obtained for these three waves and the performance of the NB-INAR (1) model analysed.

关键词： COVID-19 Predictive Model New SARS-CoV-2 Integer Valued Autoregressive (INAR) Model

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