33 results on '"Thürmel K"'
Search Results
2. Fisher-Lewis Kidney Transplantation Model as a Tool for Investigation of Transplantation-Induced Cardiomyopathy
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Baumann, M., Chang, J., Thürmel, K., Roos, M., von Eynatten, M., Sollinger, D., Lutz, J., and Heemann, U.
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- 2009
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3. 195P Risk factors in patients with hepatocellular carcinoma: A German claims data analysis.
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Becht, S., Berger-Thürmel, K., von Bergwelt, M., Buggisch, P., Hofmann, W-P., Marschall, U., Mayerle, J., Orabi, S., Philipp, A.B., Schrodi, S., Trojan, J., De Toni, E.N., and Ben Khaled, N.
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DISEASE risk factors , *DATA analysis , *HEPATOCELLULAR carcinoma - Published
- 2024
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4. Anti-inflammatory treatment strategies for ischemia/reperfusion injury in transplantation
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Heemann Uwe, Thürmel Klaus, and Lutz Jens
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Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Inflammatory reactions in the graft have a pivotal influence on acute as well as long-term graft function. The main reasons for an inflammatory reaction of the graft tissue are rejection episodes, infections as well as ischemia/reperfusion (I/R) injury. The latter is of particular interest as it affects every solid organ during the process of transplantation. I/R injury impairs acute as well as long-term graft function and is associated with an increased number of acute rejection episodes that again affect long-term graft outcome. I/R injury is the result of ATP depletion during prolonged hypoxia. Further tissue damage results from the reperfusion of the tissue after the ischemic insult. Adaptive cellular responses activate the innate immune system with its Toll-like receptors and the complement system as well as the adaptive immune system. This results in a profound inflammatory tissue reaction with immune cells infiltrating the tissue. The damage is mediated by various cytokines, chemokines, adhesion molecules, and compounds of the extracellular matrix. The expression of these factors is regulated by specific transcription factors with NF-κB being one of the key modulators of inflammation. Strategies to prevent or treat I/R injury include blockade of cytokines/chemokines, adhesion molecules, NF-κB, specific MAP kinases, metalloproteinases, induction of protective genes, and modulation of the innate immune system. Furthermore, preconditioning of the donor is an area of intense research. Here pharmacological treatment as well as new additives to conventional cold storage solutions have been analyzed together with new techniques for the perfusion of grafts, or methods of normothermic storage that would avoid the problem of cold damage and graft ischemia. However, the number of clinical trials in the field of I/R injury is limited as compared to the large body of experimental knowledge that accumulated during recent years in the field of I/R injury. Future activities in the treatment of I/R injury should focus on the translation of experimental protocols into clinical trials in order to reduce I/R injury and, thus, improve short- as well as long-term graft outcome.
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- 2010
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5. Three-dimensional fat-saturated T1-weighted Cartesian volumetric interpolated breath-hold examination (VIBE) for the diagnosis of aortitis in patients with suspected large vessel vasculitis: a comparative study with 18F-FDG PET applying fully integrated PET/MRI.
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Einspieler, I., Henninger, M., Mergen, V., Wendorff, H., Haller, B., Eiber, M., Rummeny, E.J., Schwaiger, M., Moog, P., and Thürmel, K.
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VASCULITIS , *IONIZING radiation , *MAGNETIC resonance imaging , *LIKERT scale , *COMPARATIVE studies , *TRANSLOCATOR proteins , *FAT content of food - Abstract
Aim: To evaluate the feasibility of T1-weighted (T1W) three-dimensional (3D) fat saturated Cartesian volumetric interpolated breath-hold examination (VIBE) magnetic resonance imaging (MRI) sequence for the diagnosis of aortitis in patients with suspected large vessel vasculitis (LVV) applying fully integrated 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/MRI.Material and Methods: Fourteen patients with aortitis and 14 patients with a negative study for aortitis using 18F-FDG PET as the standard of reference for the evaluation of inflammatory aortic involvement were included retrospectively. All patients were imaged at 3 T using T1W VIBE pre- and post-contrast. Four aortic segments were evaluated for image quality (IQ), diagnostic confidence (DC), and the degree of inflammatory activity (IA) using a Likert scale. Binomial and generalised estimating equation model tests were used to assess the diagnostic performance of T1W VIBE. Cohen's k was applied to test for interobserver reproducibility with respect to IA. Spearman's rank correlation coefficient was calculated to examine correlations between IQ, DC, IA, and PET results.Results: On a patient- and segment-based analysis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 85.7% and 59.8%, 100% and 100%, 100% and 100%, 87.5% and 68%, and 92.9% and 82.1%, respectively. IQ and DC were acceptable to good in all examinations and substantial interobserver agreement was observed for IA (Cohen's k = 0.69). IQ and DC as well as IA and 18F-FDG vessel wall uptake were significantly correlated (r=0.763 and 0.679, respectively; p<0.0001).Conclusion: T1W 3D fat saturated VIBE MRI allows diagnosis of aortitis and may aid in the management of patients with suspected LVV. [ABSTRACT FROM AUTHOR]- Published
- 2019
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6. Management of Rheumatic Diseases During Pregnancy and Breastfeeding: Position Paper of the Working Group for Obstetrics and Prenatal Medicine in the German Society for Gynecology and Obstetrics e. V. (AGG - Section Maternal Diseases in Pregnancy).
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Kuschel B, Schäfer-Graf UM, Schmidt M, Kühnert M, Hagenbeck C, and Thürmel K
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Purpose These recommendations issued by the AGG (Section Maternal Diseases in Pregnancy) were developed as a rapid orientation on maternal rheumatic diseases for counselling and disease management in pregnancy and breastfeeding. Methods The standard literature, consensus and position papers, guidelines and recommendations by other specialist associations were evaluated by a task force of the Section and summarized in these recommendations following a joint consensus process. Recommendations This paper provides an orientating overview of the physiology, pathophysiology and definitions of rheumatic diseases which is relevant for gynecologists and obstetricians. The recommendations focus on the maternal, fetal and neonatal diagnostic workup in cases with underlying maternal rheumatic disease., Competing Interests: Conflict of Interest/Interessenkonflikt The authors state that they have no conflict of interest./Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)
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- 2024
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7. Enhancing Transsectoral Interdisciplinary Patient-Centered Care for Patients With Rare Cancers: Protocol for a Mixed Methods Process Evaluation.
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Hinneburg J, Zacher S, Berger-Höger B, Berger-Thürmel K, Kratzer V, Steckelberg A, and Lühnen J
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Background: Rare cancers account for approximately 24% of all new cancers. The category of rare tumor diseases includes almost 200 different entities. In particular, the treatment of patients with extensive care needs requires cooperation between service providers, both between sectors (outpatient and inpatient) and within sectors (eg, between different medical disciplines). The treatment pathway is associated with a high need for coordination and information sharing between providers. When crossing sectoral boundaries in the German health care system, interface problems between the outpatient and inpatient sectors can lead to gaps in care delivery. The multicomponent program Trans-sectoral Personalised Care Concept for Patients with Rare Cancers aims to optimize transsectoral cooperation and coordination of care to enhance patient involvement and the medical care coordination of patients with rare cancers., Objective: This process evaluation will contribute to answering questions about intervention fidelity and the implementation of transsectoral communication, identifying and describing the intended and nonintended effects of the intervention, and exploring the barriers to and facilitators of the implementation., Methods: We will include patients who participate in the intervention phase; all persons and staff involved in the development and implementation of the intervention (Onco Coach, psychologists, physicians on the contact platform, IT staff, and staff of the Bavarian Association of Statutory Health Insurance Physicians); physicians from the Ludwig-Maximilians-University Hospital Munich and the hospital of the Technical University Munich who are involved in the treatment of patients during the course of the project; and participating office-based hematologists and oncologists. Data collection will be conducted at the beginning, during, and at the end of the intervention using mixed methods. Data will be collected from questionnaires, document analyses, semistructured interviews, and structured observations and will cover different aspects of process evaluation. These include examining the context to explore existing patterns, changes in patterns, attitudes, and interactions; analyzing the implementation of intervention elements; and exploring the complex causal pathways and mediators of the intervention. Qualitative data will be analyzed using thematic analysis. The data will then be combined using between-methods triangulation., Results: This project received funding on March 1, 2022. The intervention phase and recruitment for the process evaluation began on March 1, 2023, and the recruitment is expected to end on September 30, 2025. At the time of protocol submission in June 2023, a total of 8 doctors from hematology and oncology practices were enrolled. Data collection began on March 14, 2023., Conclusions: The Trans-sectoral Personalised Care Concept for Patients with Rare Cancers project is a complex intervention that is to be implemented in an equally complex health care context. The process evaluation will help understand the influence of contextual factors and assess the mechanisms of change., Trial Registration: ISRCTN registry ISRCTN16441179; https://doi.org/10.1186/ISRCTN16441179., International Registered Report Identifier (irrid): DERR1-10.2196/49731., (©Jana Hinneburg, Sandro Zacher, Birte Berger-Höger, Karin Berger-Thürmel, Vanessa Kratzer, Anke Steckelberg, Julia Lühnen, TARGET Group. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 12.10.2023.)
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- 2023
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8. Changing treatment landscape associated with improved survival in advanced hepatocellular carcinoma: a nationwide, population-based study.
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Ben Khaled N, Mörtl B, Beier D, Reiter FP, Pawlowska-Phelan D, Teufel A, Rössler D, Schwade DF, Philipp A, Kubisch I, Ehmer U, Geier A, Lange CM, Mayerle J, Berger-Thürmel K, De Toni EN, and Munker S
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- Humans, Sorafenib therapeutic use, Phenylurea Compounds therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
- Abstract
Background and Aims: The treatment of hepatocellular carcinoma (HCC) is undergoing a historic transformation with the approval of several new systemic therapies in the last few years. This study aimed to examine the impact of this changing landscape on survival and costs in a Western nationwide, real-world cohort., Methods: A nationwide representative claims database (InGef) was screened for HCC cases between 2015 and 2020. Survival in an era with only sorafenib (period A, January 2015 to July 2018) and after approval of lenvatinib and other systemic treatments (period B, August 2018 to December 2020) was analysed. Health care costs were assessed., Results: We identified 2876 individuals with HCC in the study period. The proportion of patients receiving systemic therapy increased significantly over time, from 11.8% in 2015 to 15.1% in 2020 (p < 0.0001). The median overall survival in period B was 6.5 months (95% confidence interval [CI]: 4.9-8.9) and in period A was 5.3 months (95% CI: 4.5-6.3; p = 0.046). In period B, the median overall survival with lenvatinib was 9.7 months (95% CI: 6.3-18.4) versus 4.8 months with sorafenib (95% CI: 4.0-7.1, p = 0.008). Costs for prescription drugs per patient increased from €6150 in 2015 to €9049 in 2020 (p < 0.0001), and costs for outpatient care per patient increased from €1646 to €2149 (p = 0.0240)., Conclusion: The approval of new systemic therapies resulted in a survival benefit in patients with HCC. The magnitude of the effect is modest and associated with a moderate increase in health costs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: N.B.K. has received reimbursement of meeting attendance fees and travel expenses from EISAI and a lecture honorarium from Falk. B.M. has served as a paid consultant for Roche Diagnostics GmbH and Roche Pharma AG. D.B. and D.P.P. are employed by InGef, which received funding from LMU University for the contribution to the study. F.P.R. has received honoraria for lectures and travel support from the Falk Foundation, Gilead, Ipsen, and Novartis. A.T. has received honoraria, travel support, or/and scientific funding from Ipsen Pharma GmbH, Gilead Sciences, AbbVie Deutschland GmbH & Co. KG, F. Hoffmann-La Roche AG, Eisai GmbH, Bayer AG, Novartis AG, Intercept Pharmaceuticals, Inc., Lilly Deutschland GmbH, Alpen Pharma (Schweiz), Dr. Falk Pharma GmbH, Astra Zeneca, Sanofi-Aventis Deutschland GmbH, and Orphalan. D.R. advises Bayer and advises and has received grants from Ipsen. I.K. served as a paid consultant for Alnylam and Roche and received lecture honorarium from Takeda. U.E. has received honoraria for lectures from AstraZeneca, the Falk Foundation, IPSEN, and Novartis and travel support from AstraZeneca. She has served as advisory board or steering committee member to AstraZeneca, Bayer, EISAI, and MSD. C.M.L. has received advisory and speaker honoraria from AbbVie, AstraZeneca, Boston Scientific, CSL Behring, Eisai, Falk, Gilead, MSD, Norgine, Novartis, Roche, Shionogi, and Sobi. K.B. received a research grant from Roche Pharma AG. E.D.T. has served as a paid consultant for AstraZeneca, Bayer, BMS, EISAI, Eli Lilly & Co, Pfizer, IPSEN, and Roche. He has received reimbursement of meeting attendance fees and travel expenses from Arqule, AstraZeneca, BMS, Bayer, Celsion, and Roche and lecture honoraria from BMS and Falk. In addition, he has received third-party funding for scientific research from Arqule, AstraZeneca, BMS, Bayer, Eli Lilly, and Roche. S.M. received a research grant from Ipsen, BMBF, and the Bavarian Ministry of economic affairs and media. All the other authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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9. Health technology assessment for cancer medicines across the G7 countries and Oceania: an international, cross-sectional study.
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Jenei K, Raymakers AJN, Bayle A, Berger-Thürmel K, Cherla A, Honda K, Jackson CCGA, Karikios D, Trapani D, Berry S, and Gyawali B
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- Humans, Cross-Sectional Studies, France, Oceania, Technology Assessment, Biomedical, Neoplasms drug therapy
- Abstract
Background: Criticisms have emerged that cancer medicines offer modest benefits at increasingly high prices. Reimbursement decisions made by health technology assessment (HTA) agencies have become a complex endeavour for cancer medicines. Most high-income countries (HICs) use HTA criteria to identify high-value medicines for reimbursement under public drug coverage plans. We compared HTA criteria specific for cancer medicines in economically similar HICs, to understand how these criteria contribute to reimbursement decisions., Methods: We did an international, cross-sectional analysis in collaboration with author investigators across eight HICs, from the Group of Seven (known as G7; Canada, England, France, Germany, Italy, and Japan) and Oceania (Australia and New Zealand). Publicly available data from HTA agency reports and official documentation were extracted and analysed between Aug 15, 2021, and July 31, 2022. We collected data pertaining to the decision-making criteria used by the national HTA agency; HTA reimbursement status for 34 medicine-indication pairs corresponding to 15 unique US top-selling cancer medicines; and HTA reimbursement status for 18 cancer medicine-indication pairs (13 unique medicines) with minimal clinical benefit (score of 1 on the European Society of Medical Oncology Magnitude of Clinical Benefit Scale). Descriptive statistics were used to compare HTA decision criteria and drug reimbursement recommendations (or for Germany and Japan, final reimbursement status) across the eight countries., Findings: Therapeutic impact related to clinical outcomes of the new medicine was a uniform criterion across the eight countries, whereas quality of evidence (under the remit of therapeutic impact assessment) and equity were infrequently cited criteria. Only the German HTA agency mandated that surrogate endpoints be validated in therapeutic impact assessment. All countries except Germany included formal cost-effectiveness analyses within HTA reports. England and Japan were the only countries that specified a cost-effectiveness threshold. Of the 34 medicine-indication pairs corresponding to US top-selling cancer medicines, Germany reimbursed the maximum (34 [100%]), followed by Italy (32 [94%] recommended for reimbursement), Japan (28 [82%] reimbursed), Australia, Canada, England, and France (27 [79%] recommended for reimbursement), and New Zealand (12 [35%] recommended for reimbursement). Of the 18 cancer medicine-indication pairs with marginal clinical benefit, Germany reimbursed 15 (83%) and Japan reimbursed 12 (67%). France recommended nine (50%) for reimbursement, followed by Italy (seven [39%]), Canada (five [28%]), and Australia and England (three [17%] each). New Zealand did not recommend any medicine-indications with marginal clinical benefit for reimbursement. Considering the overall cumulative proportion across the eight countries, 58 (21%) of 272 indications for the US top-selling medicines and 90 (63%) of 144 marginally beneficial medicine-indications were not recommended for reimbursement or reimbursed., Interpretation: Our findings indicate discordance in public reimbursement decisions across economically similar countries, despite overlapping HTA decision criteria. This suggests a need for improved transparency around the nuances of the criteria to ensure improved access to high-value cancer medicines, and deprioritisation of low-value cancer medicines. Health systems have opportunities to improve their HTA decision-making processes by learning from the systems in other countries., Funding: None., Competing Interests: Declaration of interests KJ is supported by a Canadian Institutes of Health Research foreign doctoral scholarship (award number 181603). AJNR reports serving as a member of the pan-Canadian Oncology Drug Review Expert Review Committee with the Canadian Agency for Drugs and Technologies in Health, and reports a postdoctoral fellowship with the Program on Regulation, Therapeutics, and Law, which is supported by a grant from Arnold Ventures. BG has received salary support from the Ontario Institute for Cancer Research, funded by the Government of Ontario, and declares consulting fees from Vivio Health unrelated to the manuscript. AB reports consulting fees from Sanofi and honoraria from Roche, unrelated to the manuscript. DK reports honoraria from Amgen and Merck, unrelated to the manuscript. KH reports grant support from Pfizer, unrelated to the manuscript. All other authors declare no competing interests. The views expressed in the publication are the views of the authors and do not reflect those of governments, commercial entities, or health technology assessment agencies., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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10. Profile of the multicenter cohort of the German Cancer Consortium's Clinical Communication Platform.
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Maier D, Vehreschild JJ, Uhl B, Meyer S, Berger-Thürmel K, Boerries M, Braren R, Grünwald V, Hadaschik B, Palm S, Singer S, Stuschke M, Juárez D, Delpy P, Lambarki M, Hummel M, Engels C, Andreas S, Gökbuget N, Ihrig K, Burock S, Keune D, Eggert A, Keilholz U, Schulz H, Büttner D, Löck S, Krause M, Esins M, Ressing F, Schuler M, Brandts C, Brucker DP, Husmann G, Oellerich T, Metzger P, Voigt F, Illert AL, Theobald M, Kindler T, Sudhof U, Reckmann A, Schwinghammer F, Nasseh D, Weichert W, von Bergwelt-Baildon M, Bitzer M, Malek N, Öner Ö, Schulze-Osthoff K, Bartels S, Haier J, Ammann R, Schmidt AF, Guenther B, Janning M, Kasper B, Loges S, Stilgenbauer S, Kuhn P, Tausch E, Runow S, Kerscher A, Neumann M, Breu M, Lablans M, and Serve H
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- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Young Adult, Middle Aged, Aged, Aged, 80 and over, Cohort Studies, Neoplasms diagnosis, Neoplasms epidemiology, Neoplasms therapy
- Abstract
Treatment concepts in oncology are becoming increasingly personalized and diverse. Successively, changes in standards of care mandate continuous monitoring of patient pathways and clinical outcomes based on large, representative real-world data. The German Cancer Consortium's (DKTK) Clinical Communication Platform (CCP) provides such opportunity. Connecting fourteen university hospital-based cancer centers, the CCP relies on a federated IT-infrastructure sourcing data from facility-based cancer registry units and biobanks. Federated analyses resulted in a cohort of 600,915 patients, out of which 232,991 were incident since 2013 and for which a comprehensive documentation is available. Next to demographic data (i.e., age at diagnosis: 2.0% 0-20 years, 8.3% 21-40 years, 30.9% 41-60 years, 50.1% 61-80 years, 8.8% 81+ years; and gender: 45.2% female, 54.7% male, 0.1% other) and diagnoses (five most frequent tumor origins: 22,523 prostate, 18,409 breast, 15,575 lung, 13,964 skin/malignant melanoma, 9005 brain), the cohort dataset contains information about therapeutic interventions and response assessments and is connected to 287,883 liquid and tissue biosamples. Focusing on diagnoses and therapy-sequences, showcase analyses of diagnosis-specific sub-cohorts (pancreas, larynx, kidney, thyroid gland) demonstrate the analytical opportunities offered by the cohort's data. Due to its data granularity and size, the cohort is a potential catalyst for translational cancer research. It provides rapid access to comprehensive patient groups and may improve the understanding of the clinical course of various (even rare) malignancies. Therefore, the cohort may serve as a decisions-making tool for clinical trial design and contributes to the evaluation of scientific findings under real-world conditions., (© 2023. The Author(s).)
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- 2023
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11. 18F-FDG PET/MRI compared with clinical and serological markers for monitoring disease activity in patients with aortitis and chronic periaortitis.
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Einspieler I, Henninger M, Mergen V, Wendorff H, Haller B, Beyer LP, Moog P, and Thürmel K
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- Aortitis blood, Fluorodeoxyglucose F18, Humans, Retroperitoneal Fibrosis blood, Retrospective Studies, Aortitis diagnostic imaging, Magnetic Resonance Imaging, Positron-Emission Tomography, Retroperitoneal Fibrosis diagnostic imaging
- Abstract
Objectives: We compared the diagnostic value of fully integrated 18F-FDG PET/MRI to that of clinical and serological markers for monitoring disease activity in patients with aortitis/chronic periaortitis (A/CPA) during immunosuppressive therapy., Methods: Patients positive for A/CPA at the initial and at least 2 consecutive PET/MRI studies were included for retrospective analysis. Imaging (qualitative and quantitative analysis), clinical, and serologic (C-reactive protein, erythrocyte sedimentation rate) assessments were determined at each visit, and their findings compared. Differences in various PET/MRI parameters, clinical symptoms, and serologic markers during therapy between first and second visits were tested for statistical significance. Spearman's rank correlation coefficient was calculated to relate imaging to serologic marker changes between the first 2 visits., Results: Serial assessments were performed in 12 patients with A/CPA, over 34 visits. PET/MRI suggested active disease in 22/34 (64.7%) studies, whereas clinical assessment and serological analysis were positive in only 18/34 (52.9%) and 17/34 (50%) cases, respectively. Disease activity assessment differed between PET/MRI, and clinical and serological markers, in 8/34 (23.5%) and 9/34 (26.5%) cases, respectively. Imaging and serologic parameters (p < 0.009) and clinical symptoms (p = 0.063) predominantly improved at the second visit. Changes from the first to the second visit were not correlated between PET/MRI and serologic markers., Conclusions: Fully integrated 18F-FDG PET/MRI provides a comprehensive imaging approach with data on vascular/perivascular inflammation that is complementary to clinical and laboratory assessments. This highlights the potential value of imaging-based disease activity monitoring, which might have a crucial impact on clinical management in patients with A/CPA.
- Published
- 2020
12. Mortality prediction in stable hemodialysis patients is refined by YKL-40, a 40-kDa glycoprotein associated with inflammation.
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Lorenz G, Schmalenberg M, Kemmner S, Haller B, Steubl D, Pham D, Schreiegg A, Bachmann Q, Schmidt A, Haderer S, Huber M, Angermann S, Günthner R, Braunisch M, Hauser C, Reichelt AL, Matschkal J, Suttmann Y, Moog P, Stock K, Küchle C, Thürmel K, Renders L, Bauer A, Baumann M, Heemann U, Luppa PB, and Schmaderer C
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- Aged, Biomarkers blood, Cross-Sectional Studies, Female, Humans, Kidney Failure, Chronic blood, Kidney Failure, Chronic diagnosis, Male, Middle Aged, Predictive Value of Tests, Renal Dialysis adverse effects, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Chitinase-3-Like Protein 1 blood, Inflammation Mediators blood, Kidney Failure, Chronic mortality, Kidney Failure, Chronic therapy, Renal Dialysis mortality
- Abstract
Chronic inflammation contributes to increased mortality in hemodialysis (HD) patients. YKL-40 is a novel marker of inflammation, tissue remodeling, and highly expressed in macrophages inside vascular lesions. Elevated levels of YKL-40 have been reported for HD patients but how it integrates into the proinflammatory mediator network as a predictor of mortality remains elusive. We studied serum YKL-40, Interleukin-6 (IL-6), high-sensitivity C-reactive protein, monocyte chemotactic protein-1 (MCP-1), and interferon-gamma induced protein-10 (IP-10) in 475 chronic hemodialysis patients. Patients were followed for mortality for a median of 37 [interquartile range: 25-49] months and checked for interrelation of the measured mediators. To plot cumulative incidence functions, patients were stratified into terciles per YKL-40, IL-6, MCP-1, and IP-10 levels. Multivariable Cox regression models were built to examine associations of YKL-40, IP-10, and MCP-1 with all-cause and cause-specific mortality. Net reclassification improvement was calculated for the final models containing YKL-40 and IL-6. Increased YKL-40 was independently associated with age, IP-10, and IL-6 serum levels. After adjustment for demographic and laboratory parameters, comorbidities, and IL-6, only YKL-40 significantly improved risk prediction for all-cause (hazard ratio 1.4; 95% confidence interval 1.1-1.8) and cardiovascular mortality (hazard ratio 1.5; 95% confidence interval 1.03-2.2). Thus, in contrast to other biomarkers of aberrant macrophage activation, YKL-40 reflects inflammatory activity, which is not covered by IL-6. Mechanistic and prospective studies are needed to test for causal involvement of YKL-40 and whether it might qualify as a therapeutic target., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
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- 2018
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13. Affection of the cardiovascular system by IgG4-related disease.
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Ibrahim T, Muenzel D, Babaryka G, Barthel P, and Thürmel K
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- Aged, Arteritis pathology, Autoimmune Diseases pathology, Biopsy, Needle, Cardiovascular Diseases diagnostic imaging, Cardiovascular Diseases pathology, Coronary Angiography methods, Coronary Stenosis immunology, Coronary Stenosis pathology, Disease Progression, Fatal Outcome, Humans, Immunoglobulin G blood, Immunohistochemistry, Magnetic Resonance Imaging methods, Male, Positron Emission Tomography Computed Tomography methods, Risk Assessment, Arteritis diagnostic imaging, Autoimmune Diseases diagnostic imaging, Coronary Stenosis diagnostic imaging, Immunoglobulin G immunology
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- 2017
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14. A novel arthritis in vivo fluorescence optical imaging technology pushed to the limits continued-unravelling the signals: quantitative analysis does not distinguish inflammatory skin lesions from active synovitis.
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Finsterer S, Moog P, Meier R, and Thürmel K
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- Arthritis, Rheumatoid, Humans, Magnetic Resonance Imaging, Optical Imaging, Arthritis, Synovitis
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- 2016
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15. Fully integrated whole-body [18F]-fludeoxyglucose positron emission tomography/magnetic resonance imaging in therapy monitoring of giant cell arteritis.
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Einspieler I, Thürmel K, and Eiber M
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- Aged, Anti-Inflammatory Agents therapeutic use, Drug Therapy, Combination, Fluorodeoxyglucose F18, Giant Cell Arteritis pathology, Glucocorticoids therapeutic use, Humans, Magnetic Resonance Angiography methods, Male, Methotrexate therapeutic use, Multimodal Imaging methods, Positron-Emission Tomography methods, Radiopharmaceuticals, Giant Cell Arteritis drug therapy
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- 2016
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16. Diagnostic utility of Acoustic Radiation Force Impulse (ARFI) imaging in primary Sjoegren`s syndrome.
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Knopf A, Hofauer B, Thürmel K, Meier R, Stock K, Bas M, and Manour N
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- Adult, Aged, Aged, 80 and over, Early Diagnosis, Female, Humans, Male, Middle Aged, Parotid Gland diagnostic imaging, Prospective Studies, Sensitivity and Specificity, Young Adult, Elasticity Imaging Techniques, Sjogren's Syndrome diagnostic imaging
- Abstract
Objectives: The purpose of the study was to assess the diagnostic utility of acoustic radiation force impulse (ARFI) imaging in primary Sjögren's syndrome (pSS)., Methods: One hundred fifty-seven patients with sicca symptoms and/or salivary gland swelling were included. Sicca symptoms, Schirmer test, unstimulated whole saliva (UWS), SS-A/B antibodies, and histology were assessed according to American-European Consensus group (AECG) criteria. All patients underwent high-resolution ultrasound and ARFI imaging of the parotid (PG) and submandibular glands (SMG)., Results: Seventy patients were classified as having pSS. The remaining 87 patients suffered from idiopathic sicca (n = 24), rheumatoid arthritis (n = 12), sarcoidosis (n = 9), cutaneous/systemic lupus erythematosus (n = 7), scleroderma (n = 2), dermatomyositis (n = 1), HBV/HCV (n = 2), and panarteritis nodosa (n = 1), and disorders in 29 patients were classified as not otherwise specified. ARFI values of the PG were significantly higher in the pSS versus non-pSS groups (2.86 ± 0.07 m/s vs. 2.15 ± 0.11 m/s, p < 0.0001). ARFI imaging demonstrated diagnostic sensitivity and specificity of 81 % and 67 %, respectively., Conclusions: In addition to histology, ARFI imaging was the most important diagnostic tool for identifying early pSS., Key Points: • Early stages in Sjögren's syndrome become apparent with major salivary gland enlargements. • Schirmer and unstimulated whole saliva tests demonstrated insufficient sensitivity/specificity for early-stage diagnosis. • Acoustic radiation force impulse imaging is a reliable tool for diagnosing early disease stages.
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- 2015
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17. Rapidly progressive intracranial artery stenosis in primary antiphospholipid syndrome.
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Seifert CL, Kowarik MC, Thürmel K, Berthele A, Prothmann S, and Wunderlich S
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Antiphospholipid antibody syndrome (APS) is usually a disease of young adults. In elderly stroke patients APS was not associated with progressive intracerebral stenosis in the past. Here, we report a 65-year-old patient who presented with recurrent ischemic strokes associated with progressive stenosis of the right middle cerebral artery. Antiphospholipid antibodies were detected and treatment with plasma exchange, tapered steroids, and anticoagulants was successful. This case demonstrates that APS should be considered also in elderly stroke patients. This is of particular relevance since APS confers a significant risk to angioplasty and stenting procedures which therefore should be avoided in APS.
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- 2015
- Full Text
- View/download PDF
18. Imaging large vessel vasculitis with fully integrated PET/MRI: a pilot study.
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Einspieler I, Thürmel K, Pyka T, Eiber M, Wolfram S, Moog P, Reeps C, and Essler M
- Subjects
- Adult, Aged, Aged, 80 and over, Aorta diagnostic imaging, Female, Fluorodeoxyglucose F18, Humans, Male, Middle Aged, Pilot Projects, Radiopharmaceuticals, Vasculitis diagnosis, Magnetic Resonance Imaging, Multimodal Imaging, Positron-Emission Tomography, Tomography, X-Ray Computed, Vasculitis diagnostic imaging
- Abstract
Purpose: The aim of this study was to evaluate the feasibility of hybrid [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/MRI in patients with large vessel vasculitis (LVV) by comparing visual and quantitative parameters to that of PET/CT. Furthermore, the value of PET/MRI in disease activity and extent of LVV was assessed., Methods: A total of 16 [(18)F]FDG PET/MRI and 12 [(18)F]-FDG PET/CT examinations were performed in 12 patients with LVV. MRI of the vessel wall by T1-weighted and T2-weighted sequences was used for anatomical localization of FDG uptake and identification of morphological changes associated with LVV. In addition, contrast-enhanced (CE) magnetic resonance angiography (MRA) was performed. The vascular FDG uptake in the vasculitis group was compared to a reference group of 16 patients using a four-point visual score. Visual scores and quantitative parameters [maximum standardized uptake value (SUVmax) and target to background ratio (TBR)] were compared between PET/MRI and PET/CT. Furthermore, correlations between C-reactive protein (CRP) and quantitative PET results, as well the extent of vasculitis in PET, MRI/CE-MRA and combined PET/MRI, were analysed., Results: TBRs, SUVmax values and visual scores correlated well between PET/MRI and PET/CT (r = 0.92, r = 0.91; r = 0.84, p < 0.05). There was no significant difference between both modalities concerning SUVmax measurements and visual scores. In PET/MRI, PET alone revealed abnormal FDG uptake in 86 vascular regions. MRI/CE-MRA indicated 49 vessel segments with morphological changes related to vasculitis, leading to a total number of 95 vasculitis regions in combination with PET. Strong and significant correlations between CRP and disease extent in PET alone (r = 0.75, p = 0.0067) and PET/MRI (r = 0.92, p < 0.0001) in contrast to MRI/CE-MRA only were observed. Regarding disease activity, no significant correlations were seen between quantitative PET results and CRP, although there was a trend towards significance (r = 0.55, p = 0.0651). PET/MRI also showed active LVV in 15/16 examinations., Conclusion: Hybrid PET/MRI is feasible in LVV and holds promise for precisely determining disease extent and disease activity.
- Published
- 2015
- Full Text
- View/download PDF
19. Comment on: induction treatment of ANCA-associated vasculitis with a single dose of rituximab.
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Moog P, Schulze-Koops H, and Thürmel K
- Subjects
- Female, Humans, Male, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis drug therapy, Antibodies, Monoclonal, Murine-Derived therapeutic use, Immunologic Factors therapeutic use
- Published
- 2015
- Full Text
- View/download PDF
20. Clinical aspects of granulomatosis with polyangiitis affecting the head and neck.
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Knopf A, Chaker A, Stark T, Hofauer B, Lahmer T, Thürmel K, and Bas M
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biopsy, Female, Granulomatosis with Polyangiitis therapy, Head, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neck, Retrospective Studies, Young Adult, Disease Management, Granulomatosis with Polyangiitis diagnosis
- Abstract
There are many controversies in head and neck granulomatosis with polyangiitis (HN-GPA). Diagnostic/therapeutic regimens vary due to limited knowledge about the special properties of HN-GPA. 28 patients were diagnosed with GPA accordingly. Anti-neutrophil-cytoplasmatic-antibody (ANCA), anti-peroxidase-antibody (anti-PR3) and biopsies were performed for all patients and set into clinical context. 14 patients had sinonasal symptoms. Otological (n = 8) and laryngeal (n = 2) symptoms were usually associated with complex disease activity. Pulmonary and/or renal impairment was present in 14 patients at the time of diagnosis and developed in a further nine patients within 1 year. 21 patients with systemic disease displayed elevated ANCA/anti-PR3. In contrast, those with persistent isolated HN manifestations (n = 6) lacked auto-antibodies. These patients underwent multiple biopsies to diagnose GPA. Interestingly, five patients without clinical HN manifestations but elevated auto-antibodies were identified by nasal "blind" biopsy. Clinical examination, auto-antibody testing, and histology are effective diagnostic tools in HN-GPA. Histological diagnosis remains the gold standard in patients with persistent isolated head and neck manifestations but missing auto-antibodies. Based on our findings, we suggest early and sufficient systemic therapy for all HN-GPA. Nasal mucosal "blind" biopsy should be performed in patients with elevated auto-antibodies but lacking clinical head and neck manifestations.
- Published
- 2015
- Full Text
- View/download PDF
21. Fluorescence-aided tomographic imaging of synovitis in the human finger.
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Mohajerani P, Koch M, Thürmel K, Haller B, Rummeny EJ, Ntziachristos V, and Meier R
- Subjects
- Female, Humans, Male, Middle Aged, Reproducibility of Results, Sensitivity and Specificity, Finger Joint pathology, Image Enhancement methods, Imaging, Three-Dimensional methods, Microscopy, Fluorescence methods, Synovitis pathology, Tomography, Optical methods
- Abstract
Purpose: To propose and evaluate indocyanine green (ICG)-enhanced tomographic optical imaging for detection and characterization of synovitis in affected finger joints of patients with rheumatoid arthritis and differentiation from healthy joints in comparison to 3-T magnetic resonance (MR) imaging., Materials and Methods: This prospective pilot study was approved by the institutional ethics committee. Six arthritic proximal interphalangeal (PIP) joints in six patients (five women and one man; mean age ± standard deviation, 62.6 years ± 13.3) with clinically determined rheumatoid arthritis and six healthy PIP joints from six volunteers (four women and two men; mean age, 41.5 years ± 20.2) were examined with an ICG-enhanced fluorescence molecular tomography (FMT) system and 3-T MR imaging as the standard of reference. The degree of inflammation was graded semiquantitatively on a four-point ordinate scale according to the Outcome Measures in Rheumatology Clinical Trials Rheumatoid Arthritis MR Imaging Score, or OMERACT RAMRIS. FMT reconstructions were coregistered with the MR images. Groups were compared by using a two-sided t test, and a weighted κ coefficient was used for comparing FMT and MR imaging semiquantitative scores, as well as assessing intrareader agreement., Results: FMT was used to detect synovitis in all arthritic joints. The reconstructed FMT signal correlated with MR imaging findings in intensity and spatial, transverse profile. Semiquantitative scoring of FMT correlated well with MR imaging findings (weighted κ coefficient = 0.90). The reconstructed quantitative FMT signal, denoting synovial hyperperfusion, was used to differentiate between synovitis and healthy joints (healthy joints, 1.25 ± 0.59; arthritic joints, 3.13 ± 1.03; P < .001)., Conclusion: FMT enhanced with ICG provided depth-resolved imaging of synovitis in PIP joints. FMT may help detect synovitis in patients with rheumatoid arthritis.
- Published
- 2014
- Full Text
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22. Haemostasis in chronic kidney disease.
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Lutz J, Menke J, Sollinger D, Schinzel H, and Thürmel K
- Subjects
- Antibodies, Antiphospholipid analysis, Anticoagulants adverse effects, Anticoagulants pharmacokinetics, Anticoagulants therapeutic use, Blood Coagulation physiology, Blood Platelets physiology, Endothelium, Vascular physiology, Hemorrhage complications, Hemostasis, Humans, Oxidative Stress physiology, Renal Insufficiency complications, Renal Insufficiency, Chronic complications, Thrombosis epidemiology, Thrombosis physiopathology, Blood Coagulation Disorders physiopathology, Renal Insufficiency, Chronic physiopathology
- Abstract
The coagulation system has gained much interest again as new anticoagulatory substances have been introduced into clinical practice. Especially patients with renal failure are likely candidates for such a therapy as they often experience significant comorbidity including cardiovascular diseases that require anticoagulation. Patients with renal failure on new anticoagulants have experienced excessive bleeding which can be related to a changed pharmacokinetic profile of the compounds. However, the coagulation system itself, even without any interference with coagulation modifying drugs, is already profoundly changed during renal failure. Coagulation disorders with either episodes of severe bleeding or thrombosis represent an important cause for the morbidity and mortality of such patients. The underlying reasons for these coagulation disorders involve the changed interaction of different components of the coagulation system such as the coagulation cascade, the platelets and the vessel wall in the metabolic conditions of renal failure. Recent work provides evidence that new factors such as microparticles (MPs) can influence the coagulation system in patients with renal insufficiency through their potent procoagulatory effects. Interestingly, MPs may also contain microRNAs thus inhibiting the function of platelets, resulting in bleeding episodes. This review comprises the findings on the complex pathophysiology of coagulation disorders including new factors such as MPs and microRNAs in patients with renal insufficiency.
- Published
- 2014
- Full Text
- View/download PDF
23. First experience of imaging large vessel vasculitis with fully integrated positron emission tomography/MRI.
- Author
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Einspieler I, Thürmel K, Eiber M, and Essler M
- Subjects
- Diagnosis, Differential, Female, Humans, Middle Aged, Aorta, Abdominal, Aortitis diagnosis, Magnetic Resonance Imaging methods, Positron-Emission Tomography methods
- Published
- 2013
- Full Text
- View/download PDF
24. Comparison of fluorine-18-deoxyglucose positron emission tomography/computed tomography and contrast-enhanced ultrasound in a patient with chronic periaortitis.
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Steubl D, Thürmel K, Moog P, Essler M, Heemann U, and Stock KF
- Subjects
- Aged, Humans, Immunosuppressive Agents therapeutic use, Male, Predictive Value of Tests, Radionuclide Imaging, Retroperitoneal Fibrosis diagnostic imaging, Retroperitoneal Fibrosis drug therapy, Treatment Outcome, Contrast Media, Fluorodeoxyglucose F18, Multimodal Imaging, Phospholipids, Radiopharmaceuticals, Retroperitoneal Fibrosis diagnosis, Sulfur Hexafluoride, Ultrasonography, Interventional
- Published
- 2013
- Full Text
- View/download PDF
25. Head and neck sarcoidosis, from wait and see to tumor necrosis factor alpha therapy: a pilot study.
- Author
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Knopf A, Lahmer T, Chaker A, Stark T, Hofauer B, Pickhard A, Thürmel K, and Bas M
- Subjects
- Adalimumab, Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Pilot Projects, Pulse Therapy, Drug, Remission Induction, Sarcoidosis, Pulmonary drug therapy, Watchful Waiting, Young Adult, Adrenal Cortex Hormones administration & dosage, Anti-Inflammatory Agents therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Head, Neck, Prednisone administration & dosage, Sarcoidosis therapy, Tumor Necrosis Factor-alpha therapeutic use
- Abstract
Background: To suggest treatment modalities with respect to the specific requirements of head and neck sarcoidosis., Methods: Head and neck sarcoidosis was diagnosed in 31 patients. Treatment regimes comprised wait and see, corticosteroid-pulse, stable-dose corticosteroids, or adalimumab., Results: In all, 21 patients had isolated head and neck sarcoidosis and a further 8 patients showed concomitant pulmonary sarcoidosis. Two patients with pulmonary sarcoidosis developed subsequent head and neck manifestation. Most patients with isolated head and neck sarcoidosis did not receive systemic therapy. None exhibited relapsing disease. Three patients with head and neck manifestation underwent corticosteroid pulse. Complete remission (CR) was detected for all after 5 months. Six patients were treated with stable-dose corticosteroids. Five of 6 showed CR after 12 months and 1 of 6 patients partial remission (PR) after 24 months. Five of 6 patients exhibited relapses. Two patients underwent adalimumab therapy and showed PR after 65 or CR after 26 months, respectively., Conclusions: Most patients with head and neck sarcoidosis did not require systemic therapy. We suggest corticosteroid-pulse therapy for patients with severe head and neck manifestation. Adalimumab might be potent for nonresponder., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2013
- Full Text
- View/download PDF
26. Detection of synovitis in the hands of patients with rheumatologic disorders: diagnostic performance of optical imaging in comparison with magnetic resonance imaging.
- Author
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Meier R, Thürmel K, Moog P, Noël PB, Ahari C, Sievert M, Dorn F, Waldt S, Schaeffeler C, Golovko D, Haller B, Ganter C, Weckbach S, Woertler K, and Rummeny EJ
- Subjects
- Adult, Aged, Carpal Joints pathology, Female, Finger Joint pathology, Humans, Indocyanine Green, Male, Metacarpophalangeal Joint pathology, Middle Aged, Observer Variation, Prospective Studies, Sensitivity and Specificity, Synovitis etiology, Diagnostic Imaging methods, Hand Joints pathology, Magnetic Resonance Imaging methods, Optical Devices, Rheumatic Diseases complications, Synovitis diagnosis, Synovitis pathology
- Abstract
Objective: To prospectively compare an indocyanine green (ICG)-enhanced optical imaging system with contrast-enhanced magnetic resonance imaging (MRI) for the detection of synovitis in the hands of patients with rheumatologic disorders., Methods: Forty-five patients (30 women [67%], mean ± SD age 52.6 ± 13.4 years) in whom there was a clinical suspicion of an inflammatory arthropathy were examined with a commercially available device for ICG-enhanced optical imaging as well as by contrast-enhanced 3T MRI as the standard of reference. Three independent readers graded the degree of synovitis in the carpal, metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of both hands (1,350 joints), using a 4-point ordinate scale (0 = no synovitis, 1 = mild, 2 = moderate, 3 = severe). Statistical analyses were performed using a logistic generalized estimating equation approach. Agreement of optical imaging ratings made by the different readers was estimated with a weighted kappa coefficient., Results: When MRI was used as the standard of reference, optical imaging showed a sensitivity of 39.6% (95% confidence interval [95% CI] 31.1-48.7%), a specificity of 85.2% (95% CI 79.5-89.5%), and accuracy of 67.0% (95% CI 61.4-72.1%) for the detection of synovitis in patients with arthritis. Diagnostic accuracy was especially limited in the setting of mild synovitis, while it was substantially better in patients with severely inflamed joints. Moderate interreader and intrareader agreement was observed., Conclusion: The evaluated ICG-enhanced optical imaging system showed limitations for the detection of inflamed joints of the hand in comparison with MRI., (Copyright © 2012 by the American College of Rheumatology.)
- Published
- 2012
- Full Text
- View/download PDF
27. Kidney transplant after preexisting posterior reversible encephalopathy syndrome induced by Goodpasture's syndrome.
- Author
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Lahmer T, Küchle C, Schirmer L, Heemann U, Lutz J, and Thürmel K
- Subjects
- Electroencephalography, Follow-Up Studies, Humans, Male, Posterior Leukoencephalopathy Syndrome physiopathology, Preoperative Period, Treatment Outcome, Young Adult, Anti-Glomerular Basement Membrane Disease complications, Anti-Glomerular Basement Membrane Disease surgery, Kidney Transplantation, Posterior Leukoencephalopathy Syndrome etiology
- Abstract
Posterior reversible encephalopathy syndrome is characterized by varying neurologic symptoms associated with brain vasogenic edema. Posterior reversible encephalopathy syndrome can be associated with severe hypertension (eg, in eclampsia or HELLP syndrome), but it also has been observed without hypertension and in several clinical conditions including infections and autoimmune disorders. The literature offers several reports of posterior reversible encephalopathy syndrome detected or induced after bone-marrow and solid-organ transplant, or induction by immunosuppression. We describe what is, to the best of our knowledge, the first case of man who successfully underwent a kidney transplant with preexisting posterior reversible encephalopathy syndrome induced by Goodpasture's syndrome.
- Published
- 2012
- Full Text
- View/download PDF
28. Evaluation of smell and taste in patients with Wegener's granulomatosis.
- Author
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Fasunla JA, Hundt W, Lutz J, Förger F, Thürmel K, and Steinbach S
- Subjects
- Adult, Aged, Female, Granulomatosis with Polyangiitis complications, Humans, Male, Middle Aged, Olfaction Disorders etiology, Smell physiology, Taste physiology, Taste Disorders etiology, Granulomatosis with Polyangiitis physiopathology, Olfaction Disorders diagnosis, Taste Disorders diagnosis
- Abstract
Although a reduced olfactory/gustatory function affects patients in all parts of life, this problem has not received much attention in Wegener's granulomatosis (WG). The aim of this study was to assess the smell/taste function of WG patients. Demographic data of 16 WG patients (9 males, 7 females) were obtained. They all subjectively assessed their taste/smell function on visual analogue scale. Olfactory/gustatory functions of the patients were tested with 'Sniffin' Sticks and 'Taste' strips, respectively. The results were then compared with those from sex and age-matched control group (n = 16) and normative data. WG patients subjectively assessed their olfactory (p = 0.03) and gustatory (p = 0.02) function to be lower than control group. All the olfactory scores (odour identification, odour discrimination and threshold) in both genders were significantly below the scores in the control group. WG patients were hyposmic. For taste (total taste score, as well as scores for the qualities sweet, sour, salty and bitter), WG patients did not significantly differ from controls and were normogeusic. However, the gustatory scores showed the tendency of reduction as compared to the control group. In conclusion, WG patients truly suffer from olfactory/taste dysfunction, but this is worse with olfaction. It is, therefore, imperative that physicians should make their patients to be aware of these sensory dysfunctions and educate them on methods to cope with it for better quality of life.
- Published
- 2012
- Full Text
- View/download PDF
29. Rheumatic disorders affecting the head and neck: underestimated diseases.
- Author
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Knopf A, Bas M, Chaker A, Strassen U, Pickhard A, Stark T, Lahmer T, and Thürmel K
- Subjects
- Adult, Comorbidity, Female, Germany epidemiology, Granulomatosis with Polyangiitis epidemiology, Granulomatosis with Polyangiitis physiopathology, Head, Humans, Joints pathology, Joints physiopathology, Male, Middle Aged, Neck, Retrospective Studies, Rheumatic Diseases epidemiology, Rheumatic Diseases physiopathology, Salivary Glands pathology, Sarcoidosis epidemiology, Sarcoidosis physiopathology, Scleroderma, Systemic epidemiology, Scleroderma, Systemic physiopathology, Sex Factors, Granulomatosis with Polyangiitis diagnosis, Rheumatic Diseases diagnosis, Sarcoidosis diagnosis, Scleroderma, Systemic diagnosis
- Abstract
Objectives: To describe the clinical manifestations of rheumatic disorders with isolated head and neck (H&N) affection and to introduce a novel diagnostic pathway., Methods: From 2004 to 2010, 90 patients presented with isolated H&N symptoms of a rheumatic disorder were included in the study. Rheumatic disorders were classified according to the ACR criteria. In 2008, we introduced a novel diagnostic pathway to reduce under-diagnosis of primary rheumatic disorders in the H&N. Disease-related data were assessed retrospectively and set into clinical context., Results: The majority of patients suffered from SS (n = 42), granulomatosis with polyangiitis (Wegener's) (n = 13) and sarcoidosis (n = 18) with predominance for female patients (n = 65). Enlargement of the major salivary glands (n = 47), sicca symptoms (n = 41) and cervical lymphadenopathy (n = 25) represented the most frequent symptoms. Interestingly, 3% of all enlargements of salivary glands and 4% of all cervical lymphadenopathy could be contributed to rheumatic disorders. The mean time to diagnosis was 20.71 months for SS, 8.4 months for granulomatosis with polyangiitis and 57.5 months for sarcoidosis. After implementation of the newly developed diagnostic pathway in 2008, the annually diagnosed rheumatic disorders increased 5-fold., Conclusions: The majority of rheumatic diseases of the H&N can be related to SS, granulomatosis with polyangiitis and sarcoidosis. However, the lack of specific symptoms and the clinical variability of H&N manifestation may contribute to a prolonged time to diagnosis. Our retrospective study points out the variability of symptoms and suggests a diagnostic pathway to reduce the cases of undetected H&N affection in rheumatic disorders.
- Published
- 2011
- Full Text
- View/download PDF
30. If the knee hurts, don't forget the spine!
- Author
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Lahmer T, Ingerl D, Heemann U, and Thürmel K
- Subjects
- Aged, 80 and over, Cervical Vertebrae, Chondrocalcinosis complications, Chondrocalcinosis diagnostic imaging, Female, Humans, Knee Joint diagnostic imaging, Pain etiology, Spinal Diseases diagnostic imaging, Spinal Diseases etiology, Tomography, X-Ray Computed, Chondrocalcinosis pathology, Knee Joint pathology, Spinal Diseases pathology
- Abstract
Calcium pyrophosphate dihydrate crystal-deposits (CPPD) at the spine are rare but the lesions detected with CT scans or MRI are often interpreted as a spondylodiscitis or osteitis. CPPD is a disease of the elderly without major sex predominance. The diagnosis of CPPD requires typical manifestations on a radiograph and/or detection of positively birefringent crystals in the synovial fluid of (peripheral) joints by compensated polarized light microscopy. CPPD crystal deposition at the spine has been associated with clinical manifestations, typically spine stiffness, and is sometimes associated with bony ankylosis or diffuse idiopathic skeletal hyperostosis. The preferred treatment of CPPD in the acute phase is oral non-steroidal anti-inflammatory medication or alternatively oral or intravenous glucocorticoids. CPPD should be considered in patients with non-specific spinal lesions., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
31. Fetuin-A pretransplant serum levels, kidney allograft function and rejection episodes: a 3-year posttransplantation follow-up.
- Author
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Roos M, Heinemann FM, Lindemann M, Horn PA, Lutz J, Stock K, Thürmel K, Baumann M, Witzke O, and Heemann U
- Subjects
- Adult, Aged, Biomarkers blood, Female, Follow-Up Studies, Humans, Inflammation metabolism, Inflammation pathology, Inflammation physiopathology, Kidney pathology, Kidney Transplantation pathology, Male, Middle Aged, Predictive Value of Tests, Time Factors, Transplantation, Homologous pathology, Transplantation, Homologous physiology, Treatment Outcome, Graft Rejection blood, Graft Survival physiology, Kidney physiology, Kidney Transplantation physiology, alpha-2-HS-Glycoprotein metabolism
- Abstract
Background: Fetuin-A is a negative acute-phase protein, which acts as a potent calcification inhibitor and an antagonist of transforming growth factor-β. Thus, fetuin-A levels are influenced by chronic inflammation and actively affect fibrosis and calcification processes, respectively. Graft rejection, interstitial fibrosis and tubular atrophy, chronic inflammation and calcification are common causes for kidney allograft loss. This study evaluated whether pretransplant fetuin-A levels predict long-term graft survival and rejection episodes in patients after kidney transplantation., Methods: In 206 renal transplant recipients pretransplant fetuin-A levels were measured in serum by ELISA. During the 36 months' active follow-up (median 1,249 days) 13 patients died (94% patient survival) and renal allograft failure was reported in 18 patients (91% graft survival)., Results: Pretransplant fetuin-A levels did not differ among patients with incident graft failures as compared to patients with functional graft after long-term follow-up or rejection episodes (fetuin-A: 393.6 ± 46 vs. 384.4 ± 69 vs. 405 ± 27.4 μg/ml). In logistic regression analysis, pretransplant fetuin-A levels did not correlate with graft failure after 3 years' follow-up (p = 0.895). In COX regression analysis, fetuin-A levels were not associated with the time to graft loss. Moreover, fetuin-A levels correlated neither with renal and metabolic parameters nor with cellular or humoral rejection episodes., Conclusion: Pretransplant levels of fetuin-A are not a predictor for renal allograft loss or rejection episodes after 36 months' follow-up in transplant recipients., (Copyright © 2011 S. Karger AG, Basel.)
- Published
- 2011
- Full Text
- View/download PDF
32. Anti-inflammatory treatment strategies for ischemia/reperfusion injury in transplantation.
- Author
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Lutz J, Thürmel K, and Heemann U
- Abstract
Inflammatory reactions in the graft have a pivotal influence on acute as well as long-term graft function. The main reasons for an inflammatory reaction of the graft tissue are rejection episodes, infections as well as ischemia/reperfusion (I/R) injury. The latter is of particular interest as it affects every solid organ during the process of transplantation. I/R injury impairs acute as well as long-term graft function and is associated with an increased number of acute rejection episodes that again affect long-term graft outcome.I/R injury is the result of ATP depletion during prolonged hypoxia. Further tissue damage results from the reperfusion of the tissue after the ischemic insult. Adaptive cellular responses activate the innate immune system with its Toll-like receptors and the complement system as well as the adaptive immune system. This results in a profound inflammatory tissue reaction with immune cells infiltrating the tissue. The damage is mediated by various cytokines, chemokines, adhesion molecules, and compounds of the extracellular matrix. The expression of these factors is regulated by specific transcription factors with NF-kappaB being one of the key modulators of inflammation.Strategies to prevent or treat I/R injury include blockade of cytokines/chemokines, adhesion molecules, NF-kappaB, specific MAP kinases, metalloproteinases, induction of protective genes, and modulation of the innate immune system. Furthermore, preconditioning of the donor is an area of intense research. Here pharmacological treatment as well as new additives to conventional cold storage solutions have been analyzed together with new techniques for the perfusion of grafts, or methods of normothermic storage that would avoid the problem of cold damage and graft ischemia.However, the number of clinical trials in the field of I/R injury is limited as compared to the large body of experimental knowledge that accumulated during recent years in the field of I/R injury. Future activities in the treatment of I/R injury should focus on the translation of experimental protocols into clinical trials in order to reduce I/R injury and, thus, improve short- as well as long-term graft outcome.
- Published
- 2010
- Full Text
- View/download PDF
33. Treatment of severe intravenous phenytoin overdose with hemodialysis and hemoperfusion.
- Author
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Eyer F, Felgenhauer N, Pfab R, Thürmel K, and Zilker T
- Subjects
- Adult, Anticonvulsants administration & dosage, Anticonvulsants pharmacokinetics, Female, Humans, Phenytoin administration & dosage, Phenytoin pharmacokinetics, Seizures drug therapy, Anticonvulsants poisoning, Drug Overdose therapy, Hemoperfusion, Phenytoin poisoning, Renal Dialysis
- Abstract
Background: Phenytoin is a widely used anticonvulsant agent responsible for a number of intentional and unintentional overdoses. However, besides supportive care, specific treatment recommendations to enhance elimination of the parent compound have been discussed controversially and effectiveness of hemoperfusion is under debate., Case Report: A women with a prehistory of cerebral seizures was presented following a severe iatrogenic phenytoin overdose with a peak plasma concentration of 117 mg/L. A Phenytoin overdose could be contributed to both inadequate dosing and missed repeated drug monitoring. Native phenytoin body clearance failed to relevantly lower phenytoin concentration. Thus, three sessions of a four-hour long combination of activated charcoal hemoperfusion and high-flux hemodialysis were performed resulting in considerably reduced half-life during these measures of about 7-13 hours compared to the native half-life wavering between 40-100 hours. This resulted in a substantial clinical improvement in terms of central nervous system toxicity., Conclusions: Hemodiaperfusion with activated charcoal seems to be a reasonable measure for forced lowering of highly toxic phenytoin plasma concentration and should be considered especially in circumstances following intravenous overdose (e.g. inadequate iatrogenic dosing). Its narrow therapeutic range enforces strictly adequate dosing and subsequent repeated drug monitoring of phenytoin.
- Published
- 2008
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