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Risk of recurrence of primary sclerosing cholangitis after liver transplantation is associated with de novo inflammatory bowel disease

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World Journal of Gastroenterology 2018年第43期24卷 4939-4949页

作者： Lukas Bajer Antonij Slavcev Peter Macinga Eva Sticova Jan Brezina matej roder Radim Janousek Pavel Trunecka Julius Spicak Pavel Drastich Department of Gastroenterology and Hepatology Institute for Clinical and Experimental MedicinePrague Department of Immunogenetics Institute for Clinical and Experimental Medicine Department of Clinical and Transplant Pathology Institute for Clinical and Experimental MedicinePrague Department of Diagnostic and Interventional Radiology Institute for Clinical and Experimental MedicinePrague

AIM To evaluate risk factors for primary sclerosing cholangitis(PSC) recurrence(rPSC) after orthotopic liver transplantation(OLT) in patients with well-preserved colons. METHODS We retrospectively evaluated the medical records of all patients transplanted for PSC in our center between July 1994 and May 2015 and selected 47 with followup of at least 60 mo for further analysis based on strict inclusion and exclusion criteria. rPSC was confirmed by magnetic resonance or endoscopic retrograde cholangiopancreatography and liver biopsy. All patients were evaluated by protocolary pre-OLT colonoscopy with randomized mucosal biopsies. Colonoscopy was repeated annually after OLT. Both organ donors and recipients were human leukocyte antigen(HLA) typed by serological and/or DNA methods. All input data were thoroughly analyzed employing relevant statistical methods.RESULTS Altogether, 31 men and 16 women with a median(range) age of 36(15-68) years at the time of OLT and a median follow-up of 122(60-249) mo were included. rPSC was confirmed in 21/47(44.7%) of patients, a median 63(12-180) mo after transplantation. De novo colitis [rPSC in 11/12, P ≤ 0.05, hazard ratio(HR): 4.02, 95% confidence interval(CI): 1.58-10.98] and history of acute cellular rejection(rPSC in 14/25, P ≤ 0.05; HR: 2.66, 95%CI: 1.03-7.86) showed strong positive associations with rPSC. According to the univariate analysis, overlapping features of autoimmune hepatitis(r PSC in 5/5, P ≤ 0.05) and HLA-DRB1*07 in the donor(r PSC in 10/15, P ≤ 0.05) represent other potential risk factors for rPSC, while the HLA-DRB1*04(rPSC in 0/6, P ≤ 0.05), HLA-DQB1*03(rPSC in 1/11, P ≤ 0.05), and HLA-DQB1*07(rPSC in 0/7, P ≤ 0.05) recipient alleles may have protective roles.CONCLUSION De novo colitis and acute cellular rejection are clinical conditions significantly predisposed towards recurrence of PSC after liver transplantation.

关键词：风险因素肝移植大肠炎复发胆管 HLA-DQB1 HLA-DRB1 疾病

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In situ mass spectrometry of autoimmune liver diseases

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Cellular & Molecular Immunology 2011年第3期8卷 237-242页

作者： Christopher L Bowlus Erin H Seeley Joanna roder Julia Grigorieva Heinrich roder Richard M Caprioli M Eric Gershwin Division of Gastroenterology and Hepatology University of CaliforniaDavisCAUSA Mass Spectrometry Research Center Vanderbilt University School of MedicineNashvilleTNUSA Biodesix Steamboat SpringsCOUSA Division of Clinical Immunology Allergy and RheumatologyUniversity of CaliforniaDavisCAUSA

Primary biliary cirrhosis(PBC),primary sclerosing cholangitis(PSC)and autoimmune hepatitis(AIH)are the major forms of autoimmune liver diseases each characterized by the destruction of a specific liver cell type and the presence of differing auto-antibodies.We took a proteomic approach utilizing in situ matrix-assisted laser desorption/ionization mass spectrometry(MALDI MS)to obtain profiles directly from liver samples of patients with PBC,PSC,AIH and controls.The ability to precisely localize the region for acquisition of MALDI MS allowed us to obtain profiles from bile ducts,inflammatory infiltrates and hepatocytes from each biopsy sample.Analysis tools developed to identify peaks and compare peaks across diseases and cell types were used to develop models to classify the samples.Using an initial set of testing samples from PBC patients and controls,we identified unique peaks present in bile ducts,inflammatory infiltrates and hepatocytes that could classify samples in a validation cohort with 88–91%accuracy.Interestingly,profiles of PSC and AIH did not differ significantly from PBC.Identification of proteins in these peaks may represent novel autoantigens or effector molecules.These findings illustrate the potential of a proteomic approach to autoimmune diseases with in situ MALDI MS.

关键词： autoimmune hepatitis mass spectrometry primary biliary cirrhosis primary sclerosing cholangitis

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Schoolchildren from disadvantaged backgrounds present a loss of lean tissue mass and significant increase of body fat mass during the COVID-19 lockdown in Germany:results from the MEDdirect study

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World Journal of Pediatrics 2022年第5期18卷 363-367页

作者： David Muhmann Marvin Droste Jorn Schulz Frederike Linge Lea Ladewig Ursula Eisenberg Susanne roder Rainer Buscher University Hospital Essen PediatricsⅡHufelandstr.5545147 EssenGermany Be Strong for Kids E.V Sundernholz 10845134 EssenGermany Schule Am Steeler Tor Engelbertstr.445127 EssenGermany

Children from socio-economically disadvantaged backgrounds receive unequal opportunities to succeed in school,which will lead to a decreased health literacy as adults[U].This is not only directly associated with an impaired eco-nomic and mental health and wellbeing of young people,but above all with an in creased adult mortality[1-4].While this problem is well known and described,only few and even fewer pediatric studies suggest how to interrupt this downward spiral consistently[5,6].

关键词： disadvantage adult impaired

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Path-dependent backward stochastic Volterra integral equations with jumps,differentiability and duality principle

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Probability, Uncertainty and Quantitative Risk 2018年第1期3卷 109-145页

作者： Ludger Overbeck Jasmin A.L.roder Institute of Mathematics University of GießenArndtsraße 235392 GießenGermany

We study the existence and uniqueness of a solution to path-dependent backward stochastic Volterra integral equations(BSVIEs)with jumps,where path-dependence means the dependence of the free term and generator of a path of a c`adl`ag process.Furthermore,we prove path-differentiability of such a solution and establish the duality principle between a linear path-dependent forward stochastic Volterra integral equation(FSVIE)with jumps and a linear path-dependent BSVIE with jumps.As a result of the duality principle we get a comparison theorem and derive a class of dynamic coherent risk measures based on path-dependent BSVIEs with jumps.

关键词： Path-dependent backward stochastic Volterra integral equation Jump diffusion Path-differentiability Duality principle Comparison theorem Functional Ito formula Dynamic coherent risk measure

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Extent and predictors of grade upgrading and downgrading in an Australian cohort according to the new prostate cancer grade groupings

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Asian Journal of Urology 2019年第4期6卷 321-329页

作者： Kerri Beckmann Michael O’Callaghan Andrew Vincent Penelope Cohen Martin Borg David roder Sue Evans Jeremy Millar Kim Moretti Cancer Research Institute School of Health SciencesUniversity of South AustraliaAdelaideAustralia School of Cancer and Pharmaceutical Sciences King’s College LondonLondonUK Flinders Medical Centre Urology UnitAdelaideAustralia School of Medicine University of AdelaideAdelaideAustralia SA Pathology Health SAAdelaideSouth AustraliaAustralia Genesis Care University of AdelaideAdelaideAustralia Department of Epidemiology and Preventive Medicine Monash UniversityMelbourneAustralia

Object:To determine the extent and impact of upgrading and downgrading among men who underwent radical prostatectomy(RP)according to new grade groupings and to identify predictors of upgrading from biopsy grade Group Ⅰ and Ⅱ,and downgrading to grade Group I,in a community setting.Methods:Study participants included 2279 men with non-metastatic prostate cancer diagnosed 2006-2015 who underwent prostatectomy,from the multi-institutional South Australia Prostate Cancer Clinical Outcomes Collaborative registry.Extent of up-or down-grading was assessed by comparing biopsy and prostatectomy grade groupings.Risk of biochemical recurrence(BCR)with upgrading was assessed using multivariable competing risk regression.Binomial logistic regression was used to identify pre-treatment predictors of upgrading from grade Groups Ⅰ and Ⅱ,and risk group reclassification among men with low risk disease.Results:Upgrading occurred in 35%of cases,while downgrading occurred in 13%of cases.Sixty percent with grade Group I disease were upgraded following prostatectomy.Upgrading from grade Group I was associated with greater risk of BCR compared with concordant grading(Hazard ratio:3.1,95%confidence interval:1.7-6.0).Older age,higher prostate-specific antigen levels(PSA),fewer biopsy cores,higher number of positive cores and more recent diagnosis predicted upgrading from grade Group Ⅰ,while higher PSA and clinical stage predicted upgrading from grade Group Ⅱ.No clinical risk factors for reclassification were identified.Conclusion:Biopsy sampling errors may play an important role in upgrading from grade Group I.Improved clinical assessment of grade is needed to encourage greater uptake of active surveillance.

关键词： Prostate cancer Grade misclassification Biopsy Radical prostatectomy Pathology

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Brain metastasis in advanced colorectal cancer： results from the South Australian metastatic colorectal cancer (SAmCRC) registry

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Cancer Biology & Medicine 2017年第4期14卷 371-376页

作者： Gonzalo Tapia Rico Timothy J. Price Christos Karapetis Cynthia Piantadosi Rob Padbury Amitesh Roy Guy Maddern James Moore Scott Carruthers David roder Amanda R. Townsend Department of Medical Oncology The Queen Elizabeth Hospital and University of Adelaide Adelaide SA 5011 Australia Department of Medical Oncology Flinders Medical Center and Flinders University Adelaide SA 5042 Australia Department of Surgery Flinders Medical Center Bedford Park SA 5042 Australia Department of Surgery The Queen Elizabeth Hospital Adelaide SA 5011 Australia Department of Surgery University of South Australia Adelaide SA 5005 Australia Department of Surgery Royal Adelaide Hospital Adelaide SA 5000 Australia Department of Radiation Oncology Royal Adelaide Hospital Adelaide SA 5000 Australia Department of Epidemiology University of South Australia Adelaide SA 5005 Australia

Objective:Brain metastasis is considered rare in metastatic colorectal cancer(mCRC);thus,surveillance imaging does not routinely include the brain.The reported incidence of brain metastases ranges from 0.6% to 3.2%.Methods:The South Australian mCRC Registry(SAmCRC)was analyzed to assess the number of patients presenting with brain metastasis during their lifetime.Due to small numbers,a descriptive analysis is presented.Results:Only 59 patients of 4,100 on the registry at the time of analysis had developed brain metastasis(1.4%).The clinical characteristics of those with brain metastasis were as follows:the median age was 65.3 years and 51% were female.Where the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS)mutation status of the tumor was known,the majority harbored a KRAS mutation(55%);31(53%)underwent craniotomy and 55(93%)underwent whole-brain radiotherapy.The median survival time from diagnosis of brain metastasis was 4.2 months(95% confidence interval 2.9–5.5).Patients who underwent craniotomy and radiotherapy had superior survival compared to those who underwent whole-brain radiotherapy(8.5 months vs.2.2 months,respectively).Data from the SAmCRC(a population-based registry)confirm that brain metastases are rare and the median time to development is approximately 2 years.Conclusions:Brain metastasis is a rare outcome in advanced CRC.Patients within the registry tended to be female,young in age,and harbored with higher rates of KRAS mutations.Whether routine surveillance brain scanning should be considered remains controversial given the relative rarity of developing brain metastases in mCRC and ultimately,most patients with central nervous system involvement die from their extracranial disease.

关键词： Brain metastasis colorectal cancer survival surveillance

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“I Am Getting Healthier”. Perceptions of Urban Aboriginal and Torres Strait Islander People in a Chronic Disease Self-Management and Rehabilitation Program

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Health 2016年第6期8卷 538-547页

作者： Alison Nelson Kyly Mills Samara Dargan Chantel roder The Institute for Urban Indigenous Health Bowen Hills Australia Queensland University of Technology Brisbane Australia

Chronic disease is a main contributor to the disproportionately high burden of illness experienced by Aboriginal and Torres Strait Islander Australians. However, there are very few programs addressing chronic disease self-management and rehabilitation which are designed specifically for urban Aboriginal and Torres Strait Islander people. This paper aims to explore client and staff perceptions of the Work It out Program, a chronic disease rehabilitation and self-management program designed for urban Aboriginal and Torres Strait Islander people. The study used a mixed methods approach to explore the success, barriers and self-reported outcomes of the program. Quantitative data were collected through a structured survey, comprising social and demographic data. Qualitative data were collected through interviews using Most Significant Change theory. Twenty-eight participants were recruited, 6 staff and 22 clients (M = 7, F = 21) with an age range between 21 and 79 years of age (Mean = 59.00, SD = 17.63). Interviews were completed in 2013 across four Work It out locations in Southeast Queensland. Semi-structured interviews were conducted either individually or in groups of two or three, depending on the participants’ preference. Thematic analysis of the data revealed six main themes;physical changes, lifestyle improvements, social and emotional well-being, perceptions about the successful features of the program, perceived barriers to the program and changes for the future. This exploratory study found that clients and staff involved in the Work It out Program perceived it as an effective self-management and rehabilitation program for urban Aboriginal and Torres Strait Islander Australians. Further evaluation with a larger sample size is warranted in order to establish further outcomes of the program.

关键词： Indigenous Health Chronic Disease Self-Management Rehabilitation

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Structural and nucleic acid binding properties of hepatitis delta virus small antigen

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World Journal of Virology 2017年第2期6卷 26-35页

作者： Carolina Alves Hong Cheng Joao Paulo Tavanez Ana Casaca Severin Gudima Heinrich roder Celso Cunha Global Health and Tropical Medicine GHTMInstituto de Higiene e Medicina Tropical IHMTUniversidade Nova de Lisboa Institute for Cancer Research Fox Chase Cancer Center Global Health and Tropical Medicine GHTM Instituto de Higiene e Medicina Tropical IHMT Universidade Nova de Lisboa Department of Microbiology Molecular Genetics and ImmunologyKansas University Medical Center

AIM To further characterize the structure and nucleic acid binding properties of the 195 amino acid small delta antigen, S-HDAg, a study was made of a truncated form of S-HDAg, comprising amino acids 61-195(?60HDAg), thus lacking the domain considered necessary for dimerization and higher order multimerization.METHODS Circular dichroism, and nuclear magnetic resonance experiments were used to assess the structure of ?60HDAg. Nucleic acid binding properties were investigated by gel retardation assays. RESULTS Results showed that the truncated ?60HDAg protein is intrinsically disordered but compact, whereas the RNA binding domain, comprising residues 94-146, adopts a dynamic helical conformation. We also found that ?60HDAg fails to multimerize but still contains nucleic acid binding activity, indicating that multimerization is not essential for nucleic acid binding. Moreover, in agreement with what has been previously reported for full-length protein, no apparent specificity was found for the truncated protein regarding nucleic acid binding.CONCLUSION Taken together these results allowed concluding that ?60HDAg is intrinsically disordered but compact; ?60HDAg is not a multimer but is still capable of nucleic acid binding albeit without apparent specificity.

关键词： Hepatitis delta virus Delta antigen Nuclear magnetic resonance Circular dichroism Intrinsically disordered protein

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Lifestyle intervention by group-based rehabilitation versus individual counseling in type 2 diabetes: 1-year follow-up of the Copenhagen type 2 diabetes rehabilitation project

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Journal of Diabetes Mellitus 2012年第3期2卷 308-315页

作者： Eva Soelberg Vadstrup A.Frolich H.Perrild *** M.roder Department of Endocrinology and Gastroenterology Bispebjerg University HospitalCopenhagenDenmark Department of Integrated Healthcare Bispebjerg University HospitalCopenhagenDenmark Health Care Center Oesterbro CopenhagenDenmark Department of Cardiology and Endocrinology Hillerød University HospitalHillerodDenmark

Background: Today most guidelines on the management of type 2 diabetes incorporate lifestyle intervention including patient education, physical activity and dietary modification. However, the content and organization of lifestyle intervention programs are still debatable. Aims: To compare the longer term effectiveness of a group-based rehabilitation program with an individual counseling program at improving glycemic control, cardiovascular risk factors and quality of life among type 2 diabetes patients. Methods: We randomized 143 type 2 diabetes patients to either a 6-month group-based rehabilitation program, including patient education, supervised exercise, and diet intervention, or a 6-month individual counseling program. Follow-up time was 12 months after baseline. Outcome measures were glycated hemoglobin (HbA1c), cardiovascular risk factors, quality-of-life and self-rated health. Results: In the rehabilitation group, HbA1c decreased 0.2%-point (95% confidence interval [CI] = -0.4, -0.03), systolic blood pressure decreased 6 mmHg (95% CI = -9.3, -2.5), diastolic blood pressure decreased 4 mmHg (95% CI = -6.3, -2.4), weight decreased 2.2 kg (95% CI = -3.2, -1.3), and waist circumference decreased 2.0 cm (95% CI = -2.9, -1.1). In the individual group, HbA1c decreased 0.4% (95% CI = -0.6, -0.1), systolic blood pressure decreased 3 mmHg (95% CI = -6.3, -0.7), diastolic blood pressure decreased 3 mmHg (95% CI = -4.7, -0.7), weight decreased 1.6 kg (95% CI = -2.6, -.7]), and waist circumference decreased 1.6 cm (95% CI = -2.5, -0.6). Vitality, fatigue distress, physical functioning and cardiovascular distress improved over time (P < 0.05) in the two groups combined. Repeated measurement analysis did not result in significant differences between the groups of any outcome. Conclusions: This study demonstrates that group-based rehabilitation in a primary healthcare center is a comparable alternative to individual counseling in an outpatient clinic. However, the resource use of the rehabilitation program was twice as m

关键词： Rehabilitation Lifestyle Intervention Glycemic Control Quality of Life Cardiovascular Risk Factors

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基因重组的单克隆抗体

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国外医学情报 1987年第21期 365-367页

作者： John roder 多伦多大学免疫学和医学遗传学系副教授

近年来有许多实验室用遗传工程技术和体细胞诱变方法制备新一代单克隆抗体McAb,包括嵌合抗体、酶抗体和具有新型功能的抗体等,获得了初步成果。这种抗体将更有效地用于体内诊断、治疗疾病、提高免疫化学分析及有助于分析研究抗原抗体相... 详细信息

近年来有许多实验室用遗传工程技术和体细胞诱变方法制备新一代单克隆抗体McAb,包括嵌合抗体、酶抗体和具有新型功能的抗体等,获得了初步成果。这种抗体将更有效地用于体内诊断、治疗疾病、提高免疫化学分析及有助于分析研究抗原抗体相互作用的机理。一、基本原理免疫球蛋白分子Ig是由两条相同的重链(H)和两条相同的轻链(L)组成的糖蛋白。每条链又分为恒定区(C_H、C_L)和可变区(V_H,V_L),V_H、V_L决定Ig结合抗原

关键词：单克隆抗体嵌合抗体结合抗原杂交瘤细胞杂种细胞基因重组

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