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Holzinger, dirk

Ulrich Dührsen, Stefan Müller, Bernd Hertenstein, Henrike Thomssen, Jörg Kotzerke, Rolf Mesters, Wolfgang E Berdel, Christiane Franzius, Frank Kroschinsky, Matthias Weckesser, Dorothea Kofahl-Krause, Frank M Bengel, Jan Dürig, Johannes Matschke, Christine Schmitz, Thorsten Pöppel, Claudia Ose, Marcus Brinkmann, Paul La Rosée, Martin Freesmeyer, Andreas Hertel, Heinz-Gert Höffkes, Dirk Behringer, Gabriele Prange-Krex, Stefan Wilop, Thomas Krohn, Jens Holzinger, Martin Griesshammer, Aristoteles Giagounidis, Aruna Raghavachar, Georg Maschmeyer, Ingo Brink, Helga Bernhard, Uwe Haberkorn, Tobias Gaska, Lars Kurch, Daniëlle M E van Assema, Wolfram Klapper, Dieter Hoelzer, Lilli Geworski, Karl-Heinz Jöckel, André Scherag, Andreas Bockisch, Jan Rekowski, Andreas Hüttmann
Purpose Interim positron emission tomography (PET) using the tracer, [18 F]fluorodeoxyglucose, may predict outcomes in patients with aggressive non-Hodgkin lymphomas. We assessed whether PET can guide therapy in patients who are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Patients and Methods Newly diagnosed patients received two cycles of CHOP-plus rituximab (R-CHOP) in CD20-positive lymphomas-followed by a PET scan that was evaluated using the ΔSUVmax method. PET-positive patients were randomly assigned to receive six additional cycles of R-CHOP or six blocks of an intensive Burkitt's lymphoma protocol...
May 11, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Jason Michael Springer, Paul Monach, David Cuthbertson, Simon Carette, Nader A Khalidi, Carol A McAlear, Christian Pagnoux, Philip Seo, Kenneth J Warrington, Steven R Ytterberg, Gary Hoffman, Carol Langford, Thomas Hamilton, Dirk Foell, Thomas Vogl, Dirk Holzinger, Peter A Merkel, Johannes Roth, Rula A Hajj-Ali
No abstract text is available yet for this article.
February 22, 2018: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
Silke Niemann, Anne Bertling, Martin F Brodde, Anke C Fender, Hélène Van de Vyver, Muzaffar Hussain, Dirk Holzinger, Dirk Reinhardt, Georg Peters, Christine Heilmann, Bettina Löffler, Beate E Kehrel
Globalization and migration promote the spread of Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus strains. The toxin PVL is linked to the development of thrombosis in association with osteomyelitis. The mechanisms by which PVL drives thrombosis development are however still unknown. We demonstrate that PVL-damaged neutrophils activate platelets via neutrophil secretion products, such as α-defensins and the myeloperoxidase product HOCl, as well as the formation of HOCl-modified proteins. Neutrophil damage by PVL is blocked by anti-PVL-antibodies, explaining why especially young osteomyelitis patients with a low antibody titre against PVL suffer from thrombotic complications...
February 1, 2018: Scientific Reports
Claas H Hinze, Dirk Holzinger, Elke Lainka, Johannes-Peter Haas, Fabian Speth, Tilmann Kallinich, Nikolaus Rieber, Markus Hufnagel, Annette F Jansson, Christian Hedrich, Hanna Winowski, Thomas Berger, Ivan Foeldvari, Gerd Ganser, Anton Hospach, Hans-Iko Huppertz, Kirsten Mönkemöller, Ulrich Neudorf, Elisabeth Weißbarth-Riedel, Helmut Wittkowski, Gerd Horneff, Dirk Foell
BACKGROUND: Systemic juvenile idiopathic arthritis (SJIA) is an autoinflammatory disease associated with chronic arthritis. Early diagnosis and effective therapy of SJIA is desirable, so that complications are avoided. The PRO-KIND initiative of the German Society for Pediatric Rheumatology (GKJR) aims to define consensus-based strategies to harmonize diagnostic and therapeutic approaches in Germany. METHODS: We analyzed data on patients diagnosed with SJIA from 3 national registries in Germany...
January 22, 2018: Pediatric Rheumatology Online Journal
Faekah Gohar, Janneke Anink, Halima Moncrieffe, Lisette W A Van Suijlekom-Smit, Femke H M Prince, Marion A J van Rossum, Koert M Dolman, Esther P A H Hoppenreijs, Rebecca Ten Cate, Simona Ursu, Lucy R Wedderburn, Gerd Horneff, Michael Frosch, Dirk Foell, Dirk Holzinger
OBJECTIVE: Around one-third of patients with juvenile idiopathic arthritis (JIA) fail to respond to first-line methotrexate (MTX) or anti-tumor necrosis factor (TNF) therapy, with even fewer achieving ≥ American College of Rheumatology Pediatric 70% criteria for response (ACRpedi70), though individual responses cannot yet be accurately predicted. Because change in serum S100-protein myeloid-related protein complex 8/14 (MRP8/14) is associated with therapeutic response, we tested granulocyte-specific S100-protein S100A12 as a potential biomarker for treatment response...
April 2018: Journal of Rheumatology
Eric S Weiss, Charlotte Girard-Guyonvarc'h, Dirk Holzinger, Adriana A de Jesus, Zeshan Tariq, Jennifer Picarsic, Eduardo J Schiffrin, Dirk Foell, Alexei A Grom, Sandra Ammann, Stephan Ehl, Tomoaki Hoshino, Raphaela Goldbach-Mansky, Cem Gabay, Scott W Canna
Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening hyperferritinemic systemic inflammatory disorders. Although profound cytotoxic impairment causes familial HLH (fHLH), the mechanisms driving non-fHLH and MAS are largely unknown. MAS occurs in patients with suspected rheumatic disease, but the mechanistic basis for its distinction is unclear. Recently, a syndrome of recurrent MAS with infantile enterocolitis caused by NLRC4 inflammasome hyperactivity highlighted the potential importance of interleukin-18 (IL-18)...
March 29, 2018: Blood
Karoline Walscheid, Lisa Neekamp, Arnd Heiligenhaus, Toni Weinhage, Dirk Holzinger, Carsten Heinz, Maren Kasper, Dirk Foell
OBJECTIVE: To characterize peripheral blood monocytes in uveitis associated with juvenile idiopathic arthritis (JIAU). METHODS: Peripheral blood monocytes from children with JIA (either with (n = 18) or without uveitis (n = 11)), idiopathic anterior uveitis (IAU; n = 12) and healthy controls (n = 11) were analyzed by flow cytometry. RESULTS: Percentage of CD14 + CD86+ monocytes and CD86 expression on single cell level were significantly higher in all patient groups than in controls, whereas no major differences existed between patient groups...
May 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Elena Belelli, Chiara Passarelli, Manuela Pardeo, Dirk Holzinger, Fabrizio De Benedetti, Antonella Insalaco
OBJECTIVES: Hyperzincaemia/hypercalprotectinemia (Hz/Hc) syndrome is a recently described condition caused by a specific de novo mutation (E250K) affecting PSTPIP1 gene. It has a phenotype distinct from classical pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome that includes severe systemic and cutaneous inflammation, hepatosplenomegaly, arthritis without sequelae, pancytopenia and failure to thrive. METHODS: We describe an 8-year-old boy who presented recurrent right knee swelling mimicking septic arthritis and persistent bone marrow involvement, without cutaneous involvement...
November 2017: Clinical and Experimental Rheumatology
Christoph Kessel, Katrin Lippitz, Toni Weinhage, Claas Hinze, Helmut Wittkowski, Dirk Holzinger, Ndate Fall, Alexei A Grom, Niklas Gruen, Dirk Foell
OBJECTIVE: Systemic-onset juvenile idiopathic arthritis (JIA) is speculated to follow a biphasic course, with an initial systemic disease phase driven by innate immune mechanisms and interleukin-1β (IL-1β) as a key cytokine and a second chronic arthritic phase that may be dominated by adaptive immunity and cytokines such as IL-17A. Although a recent mouse model points to a critical role of IL-17-expressing γ/δ T cells in disease pathology, in humans, both the prevalence of IL-17 and the role of IL-17-producing cells are still unclear...
July 2017: Arthritis & Rheumatology
Meriam Nefla, Dirk Holzinger, Francis Berenbaum, Claire Jacques
Alarmins (also known as danger signals) are endogenous molecules that are released to the extracellular milieu after infection or tissue damage. Extracellular alarmins interact with specific receptors expressed by cells that are engaged in host defence to stimulate signalling pathways that result in initiation of innate and adaptive immune responses, triggering inflammation or tissue repair. Alarmins are considered to be markers of destructive processes that occur in degenerative joint diseases (primarily osteoarthritis (OA)) and chronic inflammatory joint diseases (such as rheumatoid arthritis, psoriatic arthritis and spondylarthropathy)...
November 2016: Nature Reviews. Rheumatology
Miha Lavric, María Auxiliadora Miranda-García, Dirk Holzinger, Dirk Foell, Helmut Wittkowski
Alarmins are endogenous molecules with homeostatic roles that have reached the focus of research in inflammatory arthritis in the last two decades, mostly due to their ability to indicate tissue related damage after active or passive release from injured cells. From HMGB1, S100A8/A9 and S100A12 proteins, over heat-shock proteins (HSPs) and purine metabolites (e.g. uric acid, ATP) to altered matrix proteins and interleukin-33 (IL-33), a number of alarmins have been determined until now as having a role in rheumatoid arthritis, psoriatic and juvenile idiopathic arthritis, as well as spondyloarthritis and gout...
July 2017: Joint, Bone, Spine: Revue du Rhumatisme
Dirk Holzinger, Johannes Roth
PURPOSE OF REVIEW: To give an overview about the expanding spectrum of autoinflammatory diseases due to mutations in proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) and new insights into their pathogenesis. RECENT FINDINGS: In addition to classical pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome, PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome has been described as a distinct clinical phenotype of PSTPIP1-associated inflammatory diseases (PAID) and other entities are emerging...
September 2016: Current Opinion in Rheumatology
Faekah Gohar, Christoph Kessel, Miha Lavric, Dirk Holzinger, Dirk Foell
BACKGROUND: Diagnosing systemic juvenile idiopathic arthritis (SJIA) can be extremely challenging if typical arthritis is lacking. A variety of biomarkers have been described for the diagnosis and management of SJIA. However, very few markers have been well-validated. In addition, increasing numbers of biomarkers are identified by high throughput or multi-marker panels. METHOD: We identified diagnostic or prognostic biomarkers by systematic literature review, evaluating each according to a predefined level of verification, validation or clinical utility...
July 13, 2016: Arthritis Research & Therapy
Faekah Gohar, Banu Orak, Tilmann Kallinich, Marion Jeske, Mareike Lieber, Horst von Bernuth, Arnd Giese, Elisabeth Weissbarth-Riedel, Johannes-Peter Haas, Frank Dressler, Dirk Holzinger, Peter Lohse, Ulrich Neudorf, Elke Lainka, Claas Hinze, Katja Masjosthusmann, Christoph Kessel, Toni Weinhage, Dirk Foell, Helmut Wittkowski
OBJECTIVE: Familial Mediterranean fever (FMF) is an autoinflammatory disorder caused by pyrin-encoding MEFV mutations. Patients present with recurrent but self-limiting episodes of acute inflammation and often have persistent subclinical inflammation. The pathophysiology is only partially understood, but neutrophil overactivation is a hallmark of the disease. S100A12 is a neutrophil-derived proinflammatory danger signal that is strongly elevated in active FMF. This study was undertaken to characterize the secretory activity of neutrophils in vitro and investigate the association of S100A12 with disease activity and genotype in patients with FMF...
December 2016: Arthritis & Rheumatology
E H Pieter van Dijkhuizen, Juliëtte N Pouw, Andrea Scheuern, Boris Hügle, Sven Hardt, Gerd Ganser, Jasmin Beate Kümmerle-Deschner, Gerd Horneff, Dirk Holzinger, Maja Bulatović Ćalasan, Nico M Wulffraat
OBJECTIVES: Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug (DMARD) in juvenile idiopathic arthritis (JIA). In Dutch patients, MTX intolerance occurred frequently and was associated with subcutaneous (SC) administration. The aim of this study was to assess the prevalence of MTX intolerance and its association with the route of administration in a German cohort of JIA patients. METHODS: A cross-sectional study of JIA patients on MTX was performed...
January 2016: Clinical and Experimental Rheumatology
Karoline Walscheid, Arnd Heiligenhaus, Dirk Holzinger, Johannes Roth, Carsten Heinz, Christoph Tappeiner, Maren Kasper, Dirk Foell
PURPOSE: Juvenile idiopathic arthritis-associated uveitis (JIAU) is the most common uveitis entity in childhood. As S100A8/A9 and S100A12 proteins are valuable biomarkers in childhood arthritis, we investigated the occurrence of these proteins in childhood uveitis. METHODS: Serum samples from patients with JIAU (n = 79) or idiopathic anterior uveitis (IAU, n = 24), as well as from nonuveitic controls (n = 24), were collected. Furthermore, aqueous humor samples (JIAU n = 17, nonuveitic controls n = 16, IAU n = 12) were obtained...
December 2015: Investigative Ophthalmology & Visual Science
Mareike Lieber, Tilmann Kallinich, Peter Lohse, Jens Klotsche, Dirk Holzinger, Dirk Foell, Helmut Wittkowski
OBJECTIVES: To assess subclinical inflammation in heterozygous carriers of Mediterranean fever (MEFV) gene mutations, analysis of classical inflammation markers and S100A12 was performed. METHODS: Exons 2, 3, and 10 of the MEFV gene, C-reactive protein (CRP), serum amyloid A protein (SAA), procalcitonin (PCT), and S100A12 concentrations, erythrocyte sedimentation rate (ESR), and differential blood count were analysed in apparently healthy parents (n=26) of homozygous children with familial Mediterranean fever (FMF)...
November 2015: Clinical and Experimental Rheumatology
Janneke Anink, Lisette W A Van Suijlekom-Smit, Marieke H Otten, Femke H M Prince, Marion A J van Rossum, Koert M Dolman, Esther P A H Hoppenreijs, Rebecca ten Cate, Simona Ursu, Lucy R Wedderburn, Gerd Horneff, Michael Frosch, Thomas Vogl, Faekah Gohar, Dirk Foell, Johannes Roth, Dirk Holzinger
INTRODUCTION: Approximately 30% of juvenile idiopathic arthritis (JIA) patients fail to respond to anti-TNF treatment. When clinical remission is induced, some patients relapse after treatment has been stopped. We tested the predictive value of MRP8/14 serum levels to identify responders to treatment and relapse after discontinuation of therapy. METHODS: Samples from 88 non-systemic JIA patients who started and 26 patients who discontinued TNF-blockers were analyzed...
August 7, 2015: Arthritis Research & Therapy
Laura B E Kienhorst, Ellen van Lochem, Wietske Kievit, Nicola Dalbeth, Marilyn E Merriman, Amanda Phipps-Green, Arnoud Loof, Waander van Heerde, Sita Vermeulen, Lisa K Stamp, Elly van Koolwijk, Jacqueline de Graaf, Dirk Holzinger, Johannes Roth, Hein J E M Janssens, Tony R Merriman, Jasper C A Broen, Matthijs Janssen, Timothy R D J Radstake
OBJECTIVE: The frequent association of gout with metabolic syndrome and cardiovascular disease (CVD) suggests that it has a systemic component. Our objective was to study whether circulating proinflammatory cytokines are associated with comorbidities in gout patients. METHODS: We studied 330 gout patients from 3 independent cohorts and compared them with 144 healthy individuals and 276 disease controls. We measured circulating levels of interleukin-8 (IL-8)/CXCL8, IL-1β, IL-6, IL-10, IL-12, and tumor necrosis factor, after which we performed proteome-wide analysis in a selection of samples to identify proteins that were possibly prognostic for the development of comorbidities...
December 2015: Arthritis & Rheumatology
Heleen D de Koning, Joost Schalkwijk, Monique Stoffels, Johanna Jongekrijg, Joannes F M Jacobs, Eugène Verwiel, Hans J P M Koenen, Frank Preijers, Dirk Holzinger, Irma Joosten, Jos W M van der Meer, Anna Simon
INTRODUCTION: Schnitzler's syndrome (SchS) is a disabling autoinflammatory disorder, characterized by a chronic urticarial rash, an M-protein, arthralgia, and other signs of systemic inflammation. Anti-interleukin-1 (IL-1) beta antibodies are highly effective, but the pathophysiology is still largely unknown. Here we studied the effect of in-vivo IL-1 inhibition on serum markers of inflammation and cellular immune responses. METHODS: Eight patients with SchS received monthly subcutaneous (s...
July 22, 2015: Arthritis Research & Therapy
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