Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.Objective: To... Show moreBackground: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.Setting: Online Delphi survey and consensus conference.Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.Outcome measurements and statistical analysis: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as >= 70% agreement and <= 15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).Results and limitations: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder canceir management until a time when further evidence is available to guide our approach.Patient summary: This report summarises findings from an international, multistake-holder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available. (C) 2019 European Society of Medical Oncology and European Association of Urology. Published by Elsevier B.V. All rights reserved. Show less
The distribution of muscle weakness in MG is highly heterogeneous and frequently shifts in patients. In 5% of patients MG was restricted to ocular weakness, whereas 7% of patients never had any... Show moreThe distribution of muscle weakness in MG is highly heterogeneous and frequently shifts in patients. In 5% of patients MG was restricted to ocular weakness, whereas 7% of patients never had any form of ocular weakness throughout their disease course. In 83% of MG patients at least one other extra-ocular muscle was involved at the second visit.Patients with late-onset MG and the presence of additional autoimmune diseases had more exacerbations (OR = 47) and emergency treatments (OR = 26) than early-onset MG patients without other autoimmune diseases.MG-ADL (patient questionnaire on ADL) was found to be relatively insensitive to changes in generalized weakness. This led to the absence of a significant treatment response on MG-ADL in the presence of a significant response on QMG (an objective measure of muscle weakness) in the eculizumab study. A new ADL outcome measure, MGII, was shown to have a higher sensitivity for generalized weakness than MG-ADL.RoVEMP, a novel neurophysiological test, was shown to be a specific measure for myasthenic extra-ocular muscle weakness. In addition, we found a significant correlation between magnitude of decrement and the time since the last intake of pyridostigmine, supporting that RoVEMP decrement reflects reversible neuromuscular transmission failure. Show less
Background Little is known about the symptoms glioma patients experience in the year before diagnosis, either or not resulting in health care usage. This study aimed to determine the incidence of... Show moreBackground Little is known about the symptoms glioma patients experience in the year before diagnosis, either or not resulting in health care usage. This study aimed to determine the incidence of symptoms glioma patients experienced in the year prior to diagnosis, and subsequent visits to a general practitioner (GP).Methods Glioma patients were asked to complete a 30-item study-specific questionnaire focusing on symptoms they experienced in the 12 months before diagnosis. For each indicated symptom, patients were asked whether they consulted the GP for this issue.Results Fifty-nine patients completed the questionnaires, 54 (93%) with input of a proxy. The median time since diagnosis was 4 months (range 1-12). The median number of symptoms experienced in the year before diagnosis was similar between gliomas with favourable and poor prognosis, i.e. 6 (range 0-24), as were the five most frequently mentioned problems: fatigue (n = 34, 58%), mental tiredness (n = 30, 51%), sleeping disorder (n = 24, 41%), headache (n = 23, 39%) and stress (n = 20, 34%). Twenty-six (44%) patients visited the GP with at least one issue. Patients who did consult their GP reported significantly more often muscle weakness (11 vs 3, p = 0.003) than patients who did not, which remained significant after correction for multiple testing, which was not the case for paralysis in hand/leg (10 vs 4), focussing (11 vs 6) or a change in awareness (9 vs 4).Conclusions Glioma patients experience a range of non-specific problems in the year prior to diagnosis, but only patients who consult the GP report more often neurological problems. Show less
Objective To determine the level of discrepancy between magnetic resonance imaging (MRI) and F-18-FDG PET-CT in detecting osseous metastases in patients with Ewing sarcoma. Methods Twenty patients... Show moreObjective To determine the level of discrepancy between magnetic resonance imaging (MRI) and F-18-FDG PET-CT in detecting osseous metastases in patients with Ewing sarcoma. Methods Twenty patients with histopathologically confirmed Ewing sarcoma between 2000 and 2017 who underwent F-18-FDG PET-CT and MRI within a 4-week range were included. Each imaging modality was evaluated by a separate observer. Reference diagnosis of each lesion was based on histopathology or consensus of an expert panel using all available data, including at least 6 months' follow-up. Sensitivity, specificity, and predictive values were determined. Osseous lesions were analyzed on a patient and a lesion basis. Factors possibly related to false-negative findings were evaluated using Pearson's Chi-squared or Fisher's exact test. Results A total of 112 osseous lesions were diagnosed in 13 patients, 107 malignant and 5 benign. Seven patients showed no metastases on either F-18-FDG PET-CT or MRI. Forty-one skeletal metastases (39%) detected with MRI did not show increased F-18-FDG uptake on F-18-FDG PET-CT (false-negative). Lesion-based sensitivities and specificities were 62% (95%CI 52-71%) and 100% (48-100%) for F-18-FDG PET-CT; and 99% (97-100%) and 100% (48-100%) for MRI respectively. Bone lesions were more likely to be false-negative on F-18-FDG PET-CT if hematopoietic bone marrow extension was widespread and active (p = 0.001), during or after (neo)-adjuvant treatment (p = 0.001) or when the lesion was smaller than 10 mm (p < 0.001). Conclusion Although no definite conclusions can be drawn from this small retrospective study, it shows that caution is needed when using F-18-FDG PET-CT for diagnosing skeletal metastases in Ewing sarcoma. Poor contrast between metastases and active hematopoietic bone marrow, chemotherapeutic treatment, and/or small size significantly decrease the diagnostic yield of F-18-FDG PET-CT, but not of MRI. Show less
Wynants, L.; Smeden, M. van; McLernon, D.J.; Timmerman, D.; Steyerberg, E.W.; Calster, B. van; Topic Grp Evaluating Diagnosti 2019
Transcatheter aortic valve replacement (TAVR) is a safe and efficient alternative for surgical valve aortic replacement in patients with symptomatic severe aortic stenosis who are inoperable or... Show moreTranscatheter aortic valve replacement (TAVR) is a safe and efficient alternative for surgical valve aortic replacement in patients with symptomatic severe aortic stenosis who are inoperable or have a high risk for surgery. Randomised clinical trials have shown that TAVR is not inferior to surgical aortic valve replacement in intermediate-risk patients and ongoing trials will demonstrate the effects of TAVR in asymptomatic severe aortic stenosis patients and in patients with heart failure and moderate aortic stenosis. Continuous developments in procedural and post-procedural management along with increased operator experience and technical improvements and ongoing advances in imaging modalities (particularly in three-dimensional techniques), have reduced the procedural risks and the incidence of complications such as paravalvular aortic regurgitation. Importantly, proper selection of both patient and prosthesis, procedural guidance and follow-up of prosthesis performance remain paramount for the success of the TAVR. In all these steps, echocardiography plays a crucial role. An overview of the clinical applications and current role of echocardiographic techniques in patient selection, prosthesis sizing, periprocedural guidance and postprocedural follow-up will be provided in this review article. Show less
Czepiel, J.; Drozdz, M.; Pituch, H.; Kuijper, E.J.; Perucki, W.; Mielimonka, A.; ... ; Biesiada, G. 2019
Fibrous Dysplasia / McCune Albright syndrome (FD/MAS) represents a wide spectrum of diseases due to somatic gain-of-function mutations of the GNAS gene. The mutation leads to overactivity in the... Show moreFibrous Dysplasia / McCune Albright syndrome (FD/MAS) represents a wide spectrum of diseases due to somatic gain-of-function mutations of the GNAS gene. The mutation leads to overactivity in the target tissues and to a wide phenotype of clinical features that vary in severity and age of onset. The rarity of the disease and its variable presentation to multiple specialities often leads to misdiagnosis and inappropriate variability in investigations and treatments. To address this, our international consortium of clinicians, researchers, and patients' advocates has developed pragmatic clinical guidelines for best clinical practice for the definition, diagnosis, staging, treatment and monitoring for FD/MAS to empower patients and support clinical teams in both general and specialised healthcare settings. With the lack of strong evidence to inform care, the guidelines were developed based on review of published literature, long-standing extensive experience of authors, input from other healthcare professionals involved in the care of FD/MAS patients and feedback from patients and patient groups across the globe. This has led to the formulation of a set of statements to inform healthcare professionals, patients, their families, carers and patient groups of the best practice of care. It is anticipated the implementation of these recommendations will lead to improvement in the care of patients with FD/MAS internationally. Show less
Corstjens, P.L.A.M.; Hooij, A. van; Fat, E.M.T.K.; Alam, K.; Vrolijk, L.B.; Dlamini, S.; ... ; Geluk, A. 2019
This thesis about deep vein thrombosis consists of two parts. The studies described in the first part of this thesis aimed to improve the diagnostic management of deep vein thrombosis (DVT) in... Show moreThis thesis about deep vein thrombosis consists of two parts. The studies described in the first part of this thesis aimed to improve the diagnostic management of deep vein thrombosis (DVT) in general, and in diagnostic challenging circumstances specifically. First, a new diagnostic safety threshold for all future diagnostic studies in deep vein thrombosis was established, adjusted to the disease prevalence in the study population. Thereafter a new simpler clinical decision rule, as first step in the diagnostic management of DVT was designed, selecting 4 items of the Wells rule. In the following chapter’s, studies using the MRI technique: Magnetic Resonance Direct Thrombus Imaging (MRDTI) were described. This is a non-contrast enhanced MRI technique by which a thrombus can be visualized directly. This technique was applied to diagnose DVT in challenging circumstances: ipsilateral recurrent DVT, DVT in pregnant woman and upper extremity DVT. The second part of this thesis describes studies that aimed to improve the prognosis of DVT by evaluation of the persistence to prescribed therapy and predictors of the development of post thrombotic syndrome (PTS). Show less
Ortolan, A.; Lunteren, M. van; Ramiro, S.; Ramonda, R.; Landewe, R.B.M.; Dagfinrud, H.; ... ; Gaalen, F.A. van 2018
Studies in this thesis focused on the use of MRI in patients with early inflammatory arthritis. Studies were focused on: the diagnostic value of MRI, predictive value of MRI findings for the... Show moreStudies in this thesis focused on the use of MRI in patients with early inflammatory arthritis. Studies were focused on: the diagnostic value of MRI, predictive value of MRI findings for the development of erosions, associations between age and MRI findings, the use of MRI for the development of new disease activity scores and patient reported outcomes in patients with rheumatoid arthritis. Show less
Diagnosing upper extremity deep vein thrombosis (UEDVT) can be challenging. Compression ultrasonography is often inconclusive because of overlying anatomic structures that hamper compressing veins.... Show moreDiagnosing upper extremity deep vein thrombosis (UEDVT) can be challenging. Compression ultrasonography is often inconclusive because of overlying anatomic structures that hamper compressing veins. Contrast venography is invasive and has a risk of contrast allergy. Magnetic Resonance Direct Thrombus Imaging (MRDTI) and Three Dimensional Turbo Spin-echo Spectral Attenuated Inversion Recovery (3D TSE-SPAIR) are both non-contrast-enhanced Magnetic Resonance Imaging (MRI) sequences that can visualize a thrombus directly by the visualization of methemoglobin, which is formed in a fresh blood clot. MRDTI has been proven to be accurate in diagnosing deep venous thrombosis (DVT) of the leg. The primary aim of this pilot study was to test the feasibility of diagnosing UEDVT with these MRI techniques. MRDTI and 3D TSE-SPAIR were performed in 3 pilot patients who were already diagnosed with UEDVT by ultrasonography or contrast venography. In all patients, UEDVT diagnosis could be confirmed by MRDTI and 3D TSE-SPAIR in all vein segments. In conclusion, this study showed that non-contrast MRDTI and 3D TSE-SPAIR sequences may be feasible tests to diagnose UEDVT. However diagnostic accuracy and management studies have to be performed before these techniques can be routinely used in clinical practice. Show less