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Regional and National Trends of Adult Living donor Liver Transplantation in the United States Over the Last Two decades

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Journal of Clinical and Translational Hepatology 2022年第5期10卷 814-824页

作者： Saleh A.Alqahtani Ahmet Gurakar Hani Tamim thomas d.schiano Alan Bonder Zachary Fricker Marwan Kazimi devin E.Eckhoff Michael P.Curry Behnam Saberi Johns Hopkins University Division of Gastroenterology and HepatologyBaltimoreMDUSA American University of Beirut Department of Internal MedicineBeirutLebanon Icahn School of Medicine at Mount Sinai Division of Liver DiseasesNew YorkNYUSA Beth Israel deaconess Medical Center Harvard Medical SchoolBostonMAUSA

Background and Aims:Liver organ shortage remains a major health burden in the US,with more patients being waitlisted than the number of liver transplants(LTs)*** study investigated US national and regional trends in living donor LT(LdLT)and identified factors associated with recipient ***:We retrospectively analyzed LdLT recipients and donors from the United Network Organ Sharing/Organ Procurement Transplant Network database from 1998 until 2019 for clinical characteristics,demographic differences,and survival *** and regional trends in LdLT,recipient outcomes,and predictors of survival were ***:Of the 223,571 candidates listed for an LT,57.5%received an organ,of which only 4.2%were *** adult LdLTs first peaked at 412 in 2001 but experienced a significant decline to 168 by *** then gradually increased to 445 in *** 2 had the highest LdLT numbers(n=919),while region 1 had the highest proportion(11.1%).Overall,post-LT mortality was 21.4%among LdLT ***-LdLT survival rates after 1-,5-,and 10-years were 92%,87%,and 70%,*** analysis(2004–2019)showed that patients undergoing LdLT in recent years had lower mortality than in earlier years(hazard ratio=0.81,95%confidence interval=0.75–0.88).Conclusions:Following a substantial decline after a peak in 2001,the number of adult LdLTs steadily increased from 2011 to ***,LdLTs still constitute the minority of the transplant pool in the *** policies to increase the use of LdLTs,particularly in regions of high organ demand,should be implemented.

关键词： Living donor Liver transplantation Survival UNOS Organ demand

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

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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 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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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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Sepsis during short bowel syndrome hospitalizations:Identifying trends,disparities,and clinical outcomes in the United States

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World Journal of Gastrointestinal Pathophysiology 2024年第1期15卷 26-36页

作者： dushyant Singh dahiya Jennifer Wachala Shantanu Solanki dhanshree Solanki Asim Kichloo Samantha Holcomb Uvesh Mansuri Khwaja Saad Haq Hassam Ali Manesh Kumar Gangwani Yash R Shah Teresa Varghese Hafiz Muzaffar Akbar Khan Simon Peter Horslen thomas d schiano Syed-Mohammed Jafri division of Gastroenterology Hepatology&MotilityThe University of Kansas School of MedicineKansas CityKS 66160United States department of Internal Medicine Samaritan Medical CenterWatertownNY 13601United States division of Gastroenterology Hepatology&Nutrition The University of Texas MD Anderson Cancer CenterHoustonTX 77030United States department of Medicine Institute for Foreign Medical Graduate EducationHoustonTX 77030United States department of Internal Medicine MedStar Harbor HospitalBaltimoreMD 21225United States department of Internal Medicine WellStar Spalding Regional HospitalGriffinGA 30224United States division of Gastroenterology Hepatology and NutritionEast Carolina University/Brody School of MedicineGreenvilleNC 27858United States department of Gastroenterology and Hepatology University of Arkansas for Medical SciencesLittle RockAR 72205United States department of Internal Medicine Trinity Health Oakland/Wayne State UniversityPontiacMI 48341United States division of Gastroenterology and Hepatology SUNY Upstate Medical UniversitySyracuseNY 13210United States department of Pediatrics School of Medicine and UPMC Children’s Hospital of PittsburghUniversity of PittsburghPittsburghPA 15219United States division of Liver diseases Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States division of Gastroenterology and Hepatology Henry Ford HospitalDetroitMI 48202United States

BACKGROUNd Short bowel syndrome(SBS)hospitalizations are often complicated with *** is a significant paucity of data on adult SBS hospitalizations in the United States and across the *** To assess trends and outcomes of SBS hospitalizations complicated by sepsis in the United *** The National Inpatient Sample was utilized to identify all adult SBS hospitalizations between *** study cohort was further divided based on the presence or absence of *** were identified,and hospitalization characteristics and clinical outcomes were *** of mortality for SBS hospitalizations complicated with sepsis were *** Of 247097 SBS hospitalizations,21.7%were complicated by *** SBS hospitalizations had a rising trend of hospitalizations from 20.8%in 2005 to 23.5%in 2014(P trendd to non-septic SBS hospitalizations,septic SBS hospitalizations had a higher proportion of males(32.8%vs 29.3%,Pd 50-64(32.1%vs 31.1%,Pd ethnic minorities,i.e.,Blacks(12.4%vs 11.3%,Pd Hispanics(6.7%vs 5.5%,Pd a higher proportion of patients with intestinal transplantation(0.33%vs 0.22%,Pd mean length of stay(16.1 d vs 7.7 d,Pd to the non-sepsis cohort.A younger age,female gender,White race,and presence of comorbidities such as anemia and depression were identified to be independent predictors of inpatient mortality for septic SBS *** Septic SBS hospitalizations had a rising trend between 2005-2014 and were associated with higher inpatient mortality compared to non-septic SBS hospitalizations.

关键词： Short bowel syndrome Sepsis Outcomes Mortality Trends

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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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Tuning beneficial calcineurin phosphatase activation to counterα-synuclein toxicity in a yeast model of Parkinson’s disease

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Neural Regeneration Research 2025年第1期20卷 199-200页

作者： Srishti Chawla Mikael Molin thomas Nystrom Institute for Biomedicine Sahlgrenska AcademyCentre for Ageing and Health-AgeCapUniversity of GothenburgGothenburgSweden department of Life Sciences Chalmers University of TechnologyGothenburgSweden

Calcineurin(CN)is a calcium-and calmodulindependent serine/threonine that has been studied in many model organisms including yeast,filamentous fungi,plants,and *** biological functions range from ion homeostasis and virulence in lower eukaryotes to T-cell activation in humans by human nuclear factors of activated *** is a heterodimeric protein consisting of a catalytic subunit,calcineurin A(Cna1p),which contains an active site with a dinuclear metal center,and a regulatory Ca^(2+) binding subunit called calcineurin B(Cnb1p)required to activate *** calcineurin B subunit has been highly conserved through evolution:For example,the mammalian calcineurin B shows 54%identity with calcineurin B from Saccharomyces cerevisiae.

关键词： activation dinuclear conserved

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Effect of 5.25% Sodium Hypochlorite on Shear Bond Strength of Orthodontic Brackets Bonded with OBA-MCP

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Open Journal of Orthopedics 2025年第1期15卷 1-14页

作者： Nhi Le Hoda Rahimi Richard d. Bloomstein thomas J. Cangialosi Western dental and Orthodontics San Jose USA Orthodontic department Rutgers School of Dental Medicine Newark USA

Introduction: Bracket debonding is a frequent issue that clinicians encounter, leading to increased chair time, lost revenue, and material usage. In addition to patient compliance with their diet recommendations, the preparation and conditioning of teeth for bonding significantly influence bond strength and consequently impact orthodontic treatment success and efficiency. Because of OBA-MCP’s (orthodontic bonding adhesive with modified calcium phosphate) decreased shear bond strength (SBS), the purpose of this study was to evaluate the effects of conditioning with 5.25% sodium hypochlorite (NaOCl) before etching in the bonding protocol. Materials and Methods: 90 extracted teeth were divided into 3 groups to be bonded with orthodontic brackets with different bonding protocols: 1) Transbond XT with regular bonding protocol (etch + prime + adhesive);2) OBA-MCP with regular bonding protocol;and 3) OBA-MCP with NaOCl prior to acid etching in the regular bonding protocol. SBS (in Newtons) were measured using an MTS universal testing machine with a custom jig to apply a vertical force onto the bracket and ARI (adhesive remnant index) scores were recorded for each sample after de-bond to rate the amount of adhesive remaining. Results: The addition of NaOCl to the bonding protocol statistically significantly increased the SBS of OBA-MCP to comparable levels to Transbond XT. The ARI scores showed that when NaOCl was added, more adhesive remained. Conclusion: The addition of NaOCl to the bonding protocol can increase the SBS of adhesives with historically weaker bond strengths. However, the increased amount of adhesive remaining and the increased time spent during bonding must be considered. Further testing can be done in vivo to demonstrate the practicality of this new procedure.

关键词： Shear Bond Strength Sodium Hypochlorite Orthodontic Brackets

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Microglia:a promising therapeutic target in spinal cord injury

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Neural Regeneration Research 2025年第2期20卷 454-463页

作者： Xiaowei Zha Guoli Zheng thomas Skutella Karl Kiening Andreas Unterberg Alexander Younsi department of Neurosurgery Heidelberg University HospitalHeidelbergGermany department of Neuroanatomy Institute for Anatomy and Cell BiologyHeidelberg UniversityHeidelbergGermany

Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal *** a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal *** this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor *** a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive *** review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.

关键词： astrocytes cytokines functional recovery immune regulation M1/M2 activation macrophages microglia neuroinflammation spinal cord injury therapy

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Platinum modification of metallic cobalt defect sites for efficient electrocatalytic oxidation of 5-hydroxymethylfurfural

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Journal of Energy Chemistry 2025年第2期101卷 463-473页

作者： Haoyu Zhan Baixue Cheng Yankun Lu danning Xing Xingshuai Lv Huining Huang thomas Frauenheim Tao Wang Peng Zhou State Key Laboratory of Bio-fibers and Eco-textiles College of Materials Science and Engineering Collaborative Innovation Center of Shandong Marine Biobased Fibers and Ecological Textiles Institute of Marine Biobased Materials Qingdao University Shandong Institute of Advanced Technology College of Chemistry and Chemical Engineering Ocean University of China Tianjin Key Laboratory of Advanced Functional Porous Materials Institute for New Energy Materials & Low-Carbon Technologies School of Materials Science and EngineeringTianjin University of Technology School of Science Constructor University Beijing Computational Science Research Center College of Chemistry and Molecular Engineering Qingdao University of Science and Technology

Co3O4possesses both direct and indirect oxidation effects and is considered as a promising catalyst for the oxidation of 5-hydroxymethylfurfural（HMF）.However,the enrichment and activation effects of Co3O4on OH-and HMF are weak,which limits its further *** defect engineering can regulate the electronic structure,optimize the adsorption of intermediates,and improve the catalytic activity by breaking the symmetry of the material,which is rarely involved in the upgrading of *** this work,we prepare Co3O4with metal defects and load the precious metal platinum at the defect sites（PtVco）.The results of in-situ characterizatio ns,electrochemical measurements,and theoretical calculations indicate that the reduction of Co-Co coordination number and the formation of Pt-Co bond induce the decrease of electron filling in the antibonding orbitals of Co *** resulting upward shift of the d-band center of Co combined with the characteristic adsorption of Pt species synergically enhances the enrichment and activation of organic molecules and OH species,thus exhibiting excellent HMF oxidation activity(including a lower onset potential（1.14 V） and 19 times higher current density than pure Co3O4at 1.35 V).In summary,this work explores the adsorption enhancement mechanism of metal defect sites modified by precious metal in detail,provides a new option for improving the HMF oxidation activity of cobalt-based materials,broadens the application field of metal defect based materials,and gives an innovative guidance for the functional utilization of metal defect sites in biomass conversion.

关键词： Adsorption enhancement Biomass upgrading Coordination environment Electrocatalysis Metallic defect

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Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.thomas M.Brandon Westover Can Zhang department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(Ad) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of Ad is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

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