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Trends and outcomes of transarterial chemoembolization in hepatocellular carcinoma:a national survey

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Hepatobiliary & Pancreatic Diseases International 2017年第6期16卷 624-630页

作者： Khalid mumtaz Nishi Patel Rohan m modi Vihang Patel Alice Hinton James Hanje sylvester m black Somashaker Krishna Division of Gastroenterology Hepatology and NutritionThe Ohio State University Wexner Medical Center Columbus OHUSA Department of Internal medicine The Ohio State University Wexner Medical Center Columbus OHUSA Department of Surgery The Ohio State University Wexner Medical Center Columbus OHUSA Division of Biostatistics College of Public Health The Ohio State University Columbus OH USA

BACKGROUND:Transarterial chemoembolization(TACE) is a palliative procedure frequently used in patients with advanced hepatocellular carcinoma(HCC). We examined the national inpatient trends of TACE and related outcomes in the United States over the last ***:We utilized the National Inpatient Sample(2002 to 2012) and performed trend analyses of TACE for HCC in all adult patients(age >18 years). multivariate analyses for the outcomes of in-hospital "procedure-related complications"(PRCs) and "post-procedure complications"(PPCs) were performed. We also compared early(2002 to 2006) and late(2007 to 2012) eras by multivariate analyses to identify predictors of complications, healthcare resource utilization and ***:Overall, 19058 patients underwent TACE for HCC where PRCs and PPCs were seen in 24.2% and 17.6% of patients, respectively. The overall trends in the use of TACE(Pmortality [adjusted Odds ratio(a OR):0.58; 95% CI:0.41, 0.82], reduced length of hospital stay(-1.87 days; 95% CI:-2.77,-0.97) and increased hospital charges($19232; 95% CI:11013, 27451) in the late era. Additionally, there was increased mortality(a OR:4.07; 95% CI:2.96, 5.59), PRCs(a OR:3.21; 95% CI:2.56, 4.02), and PPCs(a OR:2.70; 95% CI:2.11, 3.46) among patients with ***:There is an increasing trend of TACE utilization in HCC. However, the outcomes are worse in patients with coagulopathy. Although PRCs have increased, mortality has decreased in recent years. These findings should be considered during TACE evaluation in patients with HCC.

关键词： transarterial chemoembolization hepatocellular carcinoma procedural complications mortality

Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma

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World Journal of Gastroenterology 2019年第28期25卷 3704-3721页

作者： Clifford Akateh sylvester m black Lanla Conteh Eric D miller Anne Noonan Eric Elliott Timothy m Pawlik Allan Tsung Jordan m Cloyd Department of Surgery The Ohio State University Wexner Medical Center Columbus OH 43210 United States Division of Transplant Surgery Department of Surgery The Ohio State University Wexner Medical Center Columbus OH 43210 United States Division of Gastroenterology Hepatology and Nutrition Department of Internal Medicine The Ohio State University Wexner Medical Center Columbus OH 43210 United States Department of Radiation Oncology The Ohio State University Wexner Medical Center Columbus OH 43210 United States Division of medical Oncology Department of Internal Medicine The Ohio State University Wexner Medical Center Columbus OH 43210 United States Division of Diagnostic Radiology Department of Radiology The Ohio State University Wexner Medical Center Columbus OH 43210 United States Division of Surgical Oncology Department of Surgery The Ohio State University Wexner Medical Center Columbus OH 43210 United States

Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.

关键词： Hepatocellular carcinoma Neoadjuvant therapy Adjuvant therapy Neoplasm recurrence Hepatectomy Liver cirrhosis

Diagnosis of morbid obesity may not impact healthcare utilization for orthotopic liver transplantation:A propensity matched study

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World Journal of Hepatology 2017年第12期9卷 595-602页

作者： Joshua R Peck Nicholas Latchana Anthony michaels Adam J Hanje Alice Hinton Elmahdi A Elkhammas sylvester m black Khalid mumtaz Division of Gastroenterology Hepatology and Nutritionthe Ohio State University Wexner Medical Center Department of Surgery the Ohio State University Wexner Medical Center Department of Biostatistics the Ohio State University Wexner Medical Center

AIm To study mortality, length of stay, and total charges in morbidly obese adults during index hospitalization for orthotopic liver *** The Nationwide Inpatient Sample was queried to obtain demographics, healthcare utilization, post orthotopic liver transplantation(OLT) complications, and short term outcomes of OLT performed from 2003 to 2011(n = 46509). We divided patients into those with [body mass index(BmI) ≥ 40] and without(BmI morbid obesity. multivariable logistic regression analysis was performedto characterize differences in in-hospital mortality, length of stay(LOS), and charges for OLT between patients with and without morbid obesity after adjusting for significant confounders. Additionally, propensity matching was performed to further validate the *** Of the 46509 patients who underwent OLT during the study period, 818(1.8%) were morbidly obese. morbidly obese recipients were more likely to be female(46.8% vs 33.4%, P = 0.002), Caucasian(75.2% vs 67.8%, P = 0.002), in the low national income quartile(32.3% vs 22.5%, P = 0.04), and have ≥ 3 comorbidities(modified Elixhauser index; 83.9% vs 45.0%, P morbidly obese patient also had an increase in procedure related hemorrhage(P = 0.028) and respiratory complications(P = 0.043). multivariate and propensity matched analysis showed no difference in mortality(OR: 0.70; 95%CI: 0.27-1.84, P = 0.47), LOS(β:-4.44; 95%CI:-9.93, 1.05, P = 0.11) and charges for transplantation(β: $15693; 95%CI:-51622-83008, P = 0.64) between the two groups. morbidly obese patients were more likely to have transplants on weekdays(81.7%) as compared to those without morbid obesity(75.4%, P = 0.029).CONCLUSION morbid obesity may not impact in-hospital mortality and health care utilization in OLT recipients. However, morbidly obese patients may be selected after careful assessment of co-morbidities.

关键词： Deceased donors Outcome Complications Economics Selection criteria

Impact of transjugular intrahepatic porto-systemic shunt on post liver transplantation outcomes: Study based on the United Network for Organ Sharing database

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World Journal of Hepatology 2017年第2期9卷 99-105页

作者： Khalid mumtaz Sherif metwally Rohan m modi Nishi Patel Dmitry Tumin Anthony J michaels James Hanje Ashraf El-Hinnawi Don Hayes Jr sylvester m black Wexner medical Center Gastroenterology Hepatology and Nutrition Division the Ohio State University Department of Internal medicine the Ohio State University Department of Pediatrics the Ohio State University Department of Surgery the Ohio State University Section of Pulmonary medicine the Ohio State University

AImTo determine the impact of transjugular intrahepatic porto-systemic shunt (TIPS) on post liver transplantation (LT) outcomes. mETHODSUtilizing the United Network for Organ Sharing (UNOS) database, we compared patients who underwent LT from 2002 to 2013 who had underwent TIPS to those without TIPS for the management of ascites while on the LT waitlist. The impact of TIPS on 30-d mortality, length of stay (LOS), and need for re-LT were studied. For evaluation of mean differences between baseline characteristics for patients with and without TIPS, we used unpaired t-tests for continuous measures and χ2 tests for categorical measures. We estimated the impact of TIPS on each of the outcome measures. multivariate analyses were conducted on the study population to explore the effect of TIPS on 30-d mortality post-LT, need for re-LT and LOS. All covariates were included in logistic regression analysis. RESULTSWe included adult patients (age ≥ 18 years) who underwent LT from may 2002 to September 2013. Only those undergoing TIPS after listing and before liver transplant were included in the TIPS group. We excluded patients with variceal bleeding within two weeks of listing for LT and those listed for acute liver failure or hepatocellular carcinoma. Of 114770 LT in the UNOS database, 32783 (28.5%) met inclusion criteria. Of these 1366 (4.2%) had TIPS between the time of listing and LT. We found that TIPS increased the days on waitlist (408 ± 553 d) as compared to those without TIPS (183 ± 330 d), P P P = 0.001) by TIPS to LOS. CONCLUSIONTIPS did increase time on waitlist for LT. more importantly, TIPS was not associated with 30-d mortality and re-LT, but it did lengthen hospital LOS after transplantation.

关键词： Transjugular intrahepatic porto-systemic shunt Shunt Liver Transplantation Ascites model for end-stage liver disease mortality Transjugular

Effect of transplant center volume on post-transplant survival in patients listed for simultaneous liver and kidney transplantation

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World Journal of Hepatology 2018年第1期10卷 134-141页

作者： Rohan m modi Dmitry Tumin Andrew J Kruger Eliza W Beal Don Hayes Jr James Hanje Anthony J michaels Kenneth Washburn Lanla F Conteh sylvester m black Khalid mumtaz Department of Internal medicine Ohio State University Wexner Medical CenterColumbusOH 43210United States Department of Anesthesiology and Pain medicine Nationwide Children’s HospitalColumbusOH 43205United States Department of General Surgery Division of TransplantationOhio State University Wexner Medical CenterColumbusOH 43210United States Comprehensive Transplant Center Ohio State University Wexner Medical CenterColumbusOH 43210United States Section of Pulmonary medicine Nationwide Children’s HospitalColumbusOH 43205United States Department of Internal medicine Division of GastroenterologyHepatology and NutritionOhio State University Wexner Medical CenterColumbusOH 43210United States

AIm To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed *** The United Network of Organ Sharing database was queried for patients ≥ 18 years of age listed for SLKT between February 2002 and December 2015. Posttransplant survival was evaluated using stratified Cox regression with interaction between transplant type(LTA vs SLKT) and center *** During the study period, 393 of 4580 patients(9%) listed for SLKT underwent a LTA. Overall mortality was higher among LTA recipients(180/393, 46%) than SLKT recipients(1107/4187, 26%). The Cox model predicted a significant survival disadvantage for patients receiving LTA vs SLKT [hazard ratio, hazard ratio(HR) = 2.85; 95%CI: 2.21, 3.66; P ming 30 SLKT over the study period. This disadvantage was modestly attenuated as center SLKT volume increased, with a 3% reduction(HR = 0.97; 95%CI: 0.95, 0.99; P = 0.010) for every 10 SLKs *** In conclusion, LTA is associated with increased mortality among patients listed for SLKT. This difference is modestly attenuated at more experienced centers and may explain inconsistencies between smaller-center and larger registry-wide studies comparing SLKT and LTA outcomes.

关键词： Kidney transplantation Center volume mortality Liver transplantation United network for organ sharing

Animal models of ex vivo lung perfusion as a platform for transplantation research

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World Journal of Experimental medicine 2014年第2期4卷 7-15页

作者： Kevin Nelson Christopher Bobba Samir Ghadiali Don Hayes Jr sylvester m black Bryan A Whitson Department Biomedical Engineering The Ohio State UniversityColumbusOH 43210United States Department of Internal medicine Division of PulmonaryAllergyand Critical Care and Sleep MedicineThe Ohio State University Wexner Medical Center The Ohio State University Department of Pediatrics Nationwide Children’s HospitalColumbusOH 43210United States Department of Surgery Division of TransplantationColumbusOH 43210United States Department of Surgery Division of Cardiac SurgeryThe Collaboration for Organ PerfusionProtectionEngineering and Regeneration LaboratoryThe Ohio State University Wexner Medical CenterColumbusOH 43210United States

Ex vivo lung perfusion(EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventilation/perfusion variables can be studied independent of other confounding physiologic contributions. At the same time,EVLP allows for normal organ level function and real-time monitoring of pulmonary physiology and mechanics. As a result,this technique provides uniqueadvantages over in vivo and in vitro models. Small and large animal models of EVLP have been developed and each of these models has their strengths and weaknesses. In this manuscript,we provide insight into the relative strengths of each model and describe how the development of advanced EVLP protocols is leading to a novel experimental platform that can be used to answer critical questions in pulmonary physiology and transplant medicine.

关键词： Ex vivo lung perfusion Transplantation Rat Porcine Small animal Large animal model Ex vivo lung perfusion

Organ assessment and repair centers: The future of transplantation is near

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World Journal of Transplantation 2014年第2期4卷 40-42页

作者： Bryan A Whitson sylvester m black Division of Cardiac Surgery The Collaboration for Organ PerfusionProtectionEngineering and Regeneration (COPPER) LaboratoryThe Ohio State University Wexner Medical CenterColumbusOH 43210United States Division of Transplantation The Collaboration for Organ PerfusionProtectionEngineering and Regeneration (COPPER) LaboratoryThe Ohio State University Wexner Medical CenterColumbusOH 43210United States

Solid organ transplantation is limited by suitable donor organ availability and the geographic limitations that lead to prolonged ischemic times. Ex vivo organ perfusion is an evolving technology that enables assessment of organ function prior to transplantation. As a byproduct, overall out of body organ times are able to be extended. The future implications organ assessment and repair centers utilizing this technology are discussed.

关键词： Organ transplantation Ex vivo organ perfusion Lung Liver Kidney Heart

Development of an active-site titrant for SARS-CoV-2 main protease as an indispensable tool for evaluating enzyme kinetics

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2349-2357页

作者： Rabea Voget Julian Breidenbach Tobias Claff Alexandra Hingst Katharina sylvester Christian Steinebach Lan Phuong Vu Renato H.Weiße Ulrike Bartz Norbert Sträter Christa E.müller michael Gütschow Pharmaceutical Institute Pharmaceutical&Medicinal ChemistryUniversity of BonnBonn 53121Germany Institute of Bioanalytical Chemistry Center for Biotechnology and BiomedicineLeipzig UniversityLeipzig 04103Germany Department of Natural Sciences University of Applied Sciences Bonn-Rhein-SiegRheinbach 53359Germany

A titrant for the SARS-CoV-2 main protease(m^(pro))was developed that enables,for the first time,the exact determination of the concentration of the enzymatically active m^(pro) by active-site *** covalent binding mode of the tetrapeptidic titrant was elucidated by the determination of the crystal structure of the enzyme–titrant *** fluorogenic substrates of m^(pro),including a prototypical,internally quenched Dabcyl-EDANS peptide,were compared in terms of solubility under typical assay *** exploiting the new titrant,key kinetic parameters for the m^(pro)-catalyzed cleavage of these substrates were determined.

关键词： COVID-19 SARS-CoV-2 main protease Peptide nitriles Fluorogenic substrates Active-site titration X-ray crystallography Inner filter effect

Preservation solutions used during abdominal transplantation:Current status and outcomes

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World Journal of Transplantation 2015年第4期5卷 154-164页

作者： Nicholas Latchana Joshua R Peck Bryan A Whitson mitchell L Henry Elmahdi A Elkhammas sylvester m black Department of Surgery the Ohio State University Wexner Medical Department of Internal medicine Division of Gastroenterologythe Ohio State University Wexner Medical Center Department of Surgery Division of Cardiac Surgerythe Ohio State University Wexner Medical Center Department of Surgery Division of Transplantationthe Ohio State University Wexner Medical Center

Organ preservation remains an important contributing factor to graft and patient outcomes. During donor organ procurement and transportation, cellular injury is mitigated through the use of preservation solutions in conjunction with hypothermia. Various preservation solutions and protocols exist with widespread variability among transplant centers. In this review of abdominal organ preservation solutions, evolution of transplantation and graft preservation are discussed followed by classification of preservation solutions according to the composition of electrolytes, impermeants, buffers, antioxidants, and energy precursors. Lastly, pertinent clinical studies in the setting of hepatic, renal, pancreas, and intestinal transplantation are reviewed for patient and graft survival as well as financial considerations. In liver transplants there may be some benefit with the use of histidine-tryptophan-ketoglutarate(HTK) over University of Wisconsin solution in terms of biliary complications and potential cost savings. Renal grafts may experience increased initial graft dysfunction with the use of Euro-Collins thereby dissuading its use in support of HTK which can lead to substantial cost savings. University of Wisconsin solution and Celsior are favored in pancreas transplants given the concern for pancreatitis and graft thrombosis associated with HTK. No difference was observed with preservation solutions with respect to graft and patient survival in liver, renal, and pancreas transplants. Studies involving intestinal transplants are sparse but University of Wisconsin solution infused intraluminally in combination with an intra-vascular washout is a reasonable option until further evidence can be generated. Available literature can be used to ameliorate extensive variation across centers while potentially minimizing graft dysfunction and improving associated costs.

关键词： Graft preservation Kidney Liver Pancreas Intestine