Thomas Daikeler

Bio: Thomas Daikeler is an academic researcher from University Hospital of Basel. The author has contributed to research in topics: Giant cell arteritis & Medicine. The author has an hindex of 30, co-authored 141 publications receiving 3309 citations. Previous affiliations of Thomas Daikeler include University of Basel & Harvard University.

Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis: A Randomized Clinical Trial

Abstract: Importance High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. Objective To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. Design, Setting, and Participants The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation–registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. Interventions HSCT vs intravenous pulse cyclophosphamide. Main Outcomes and Measures The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. Results A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Conclusions and Relevance Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit. Trial Registration isrctn.org Identifier:ISRCTN54371254

The impact of 18F-FDG PET on the management of patients with suspected large vessel vasculitis

Abstract: Purpose We aimed to assess the impact of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the management of patients with suspected large vessel vasculitis.

The ultrasound compression sign to diagnose temporal giant cell arteritis shows an excellent interobserver agreement.

Abstract: Objectives The aim of this study was to investigate the relationship between rheumatoid arthritis (RA) and the occurrence of diabetes mellitus (DM). Methods A meta-analysis was conducted to explore the risk of DM in RA patients. All relevant studies were identified by searching PUBMED, EMBASE and MEDLINE database prior to 1 January 2014. Pooled risk estimates were calculated with random-effects models using STATA 11.0. Results A total of 11 case-control studies and 8 cohort studies were included in the final analysis. The pooled risk estimate of 11 case-control studies showed a statistically significant increased risk of DM prevalence among RA individuals (OR=1.40, 95% CI: 1.34-1.47). The pooled risk estimate of 8 cohort studies also showed a statistically significant increasing risk of DM (RR=1.43, 95%CI: 1.38-1.47). In a subgroup analysis for case-control studies, the pooled risk estimate of individuals with RA increased the incidence of T1DM (type 1 diabetes mellitus) and the incidence of T2DM (type 2 diabetes mellitus) (OR, 4.78 vs. 1.41). In a subgroup analysis for cohort studies, RA was also found to have a statistically significant increasing risk of T2DM (RR=1.24, 95%CI: 1.14-1.35). Begg funnel plot and Egger test showed no evidence of publication bias. Conclusions RA is associated with increased risk of DM, including T1DM and T2DM.

Vascular involvement in patients with giant cell arteritis determined by duplex sonography of 2x11 arterial regions

Abstract: Objective To define the specificity and extent of duplex sonography (DS) findings suggestive of vessel wall inflammation in patients with giant cell arteritis (GCA) Methods Patients admitted between December 2006 and April 2009 to the University Hospital Basel with a suspicion of GCA were eligible for the study DS of 2×11 arterial regions was performed in all study participants, and American College of Rheumatology criteria were applied to classify patients into GCA or non-GCA groups Results GCA was diagnosed in 38 of the 72 participants (53%) A DS pattern suggestive of vessel wall inflammation was not observed in any of the patients in the non-GCA group but, in 21 of the 38 patients with GCA (55%), DS signs suggestive of vessel wall inflammation of ≥1 vessel region were detected In 12 of the 38 patients with GCA (32%), DS signs of large vessel vasculitis (LVV) were found in ≥1 vessel region(s) of both upper and lower limb vessels Follow-up DS was performed 6 months after the baseline examination in 9 of the 12 patients with LVV and showed the persistence of most findings despite normalised signs of systemic inflammation Conclusion DS detects changes in the vessel wall that appear to be specific for GCA; they can be present in upper and lower limb arteries of patients with GCA Surprisingly, DS-detectable LVV and signs of systemic inflammation are largely dissociated

Neurofilaments as biomarkers in neurological disorders

Abstract: Neuroaxonal damage is the pathological substrate of permanent disability in various neurological disorders. Reliable quantification and longitudinal follow-up of such damage are important for assessing disease activity, monitoring treatment responses, facilitating treatment development and determining prognosis. The neurofilament proteins have promise in this context because their levels rise upon neuroaxonal damage not only in the cerebrospinal fluid (CSF) but also in blood, and they indicate neuroaxonal injury independent of causal pathways. First-generation (immunoblot) and second-generation (enzyme-linked immunosorbent assay) neurofilament assays had limited sensitivity. Third-generation (electrochemiluminescence) and particularly fourth-generation (single-molecule array) assays enable the reliable measurement of neurofilaments throughout the range of concentrations found in blood samples. This technological advancement has paved the way to investigate neurofilaments in a range of neurological disorders. Here, we review what is known about the structure and function of neurofilaments, discuss analytical aspects and knowledge of age-dependent normal ranges of neurofilaments and provide a comprehensive overview of studies on neurofilament light chain as a marker of axonal injury in different neurological disorders, including multiple sclerosis, neurodegenerative dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson disease. We also consider work needed to explore the value of this axonal damage marker in managing neurological diseases in daily practice.

Update of EULAR recommendations for the treatment of systemic sclerosis

Abstract: The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.

EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice.

Abstract: To develop evidence-based recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV) including giant cell arteritis (GCA) and Takayasu arteritis (TAK). European League Against Rheumatism (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound, MRI, CT and [18F]-fluorodeoxyglucose positron emission tomography (PET) in LVV. Based on evidence and expert opinion, the task force consisting of 20 physicians, healthcare professionals and patients from 10 EULAR countries developed recommendations, with consensus obtained through voting. The final level of agreement was voted anonymously. A total of 12 recommendations have been formulated. The task force recommends an early imaging test in patients with suspected LVV, with ultrasound and MRI being the first choices in GCA and TAK, respectively. CT or PET may be used alternatively. In case the diagnosis is still in question after clinical examination and imaging, additional investigations including temporal artery biopsy and/or additional imaging are required. In patients with a suspected flare, imaging might help to better assess disease activity. The frequency and choice of imaging modalities for long-term monitoring of structural damage remains an individual decision; close monitoring for aortic aneurysms should be conducted in patients at risk for this complication. All imaging should be performed by a trained specialist using appropriate operational procedures and settings. These are the first EULAR recommendations providing up-to-date guidance for the role of imaging in the diagnosis and monitoring of patients with (suspected) LVV.

Ankylosing spondylitis: an overview.

Abstract: Ankylosing spondylitis (AS) is a complex, potentially debilitating disease that is insidious in onset, progressing to radiological sacroiliitis over several years. Patients with symptomatic AS lose productivity owing to work disability and unemployment, have a substantial use of healthcare resources, and reduced quality of life. The pathogenesis of AS is poorly understood. However, immune mediated mechanisms involving human leucocyte antigen (HLA)-B27, inflammatory cellular infiltrates, cytokines (for example, tumour necrosis factor α and interleukin 10), and genetic and environmental factors are thought to have key roles. The detection of sacroiliitis by radiography, magnetic resonance imaging, or computed tomography in the presence of clinical manifestations is diagnostic for AS, although the presence of inflammatory back pain plus at least two other typical features of spondyloarthropathy (for example, enthesitis and uveitis) is highly predictive of early AS. Non-steroidal anti-inflammatory drugs (NSAIDs) effectively relieve inflammatory symptoms and are presently first line drug treatment. However, NSAID treatment has only a symptomatic effect and probably does not alter the disease course. For symptoms refractory to NSAIDs, second line treatments, including corticosteroids and various disease modifying antirheumatic drugs, are employed but are of limited benefit. Emerging biological therapies target the inflammatory processes underlying AS, and thus, may favourably alter the disease process, in addition to providing symptom relief.