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Patients with psoriasis are at risk of developing psoriatic arthritis, which can lead to joint damage. While screening questionnaires have been developed, their performance varies. The objective of this study was to develop a referral tool for dermatologists to identify psoriasis patients with concomitant psoriatic arthritis for rheumatological referral. This study used data from the DAPPER study, in which psoriasis patients were screened by a rheumatologist for the presence of concomitant psoriatic arthritis. Multivariable regression analysis was used to identify predictive variables for the presence of concomitant psoriatic arthritis: treatment history with conventional systemic drugs (odds ratio (OR) 2.97, 95% confidence interval (95% CI) 1.01-8.74, p = 0.04), treatment history with biologicals/small molecule inhibitors (OR 2.90, 95% CI 1.52-5.53, p = 0.01), patient-reported history of joint pain not caused by trauma (OR 4.23, 95% CI 1.21-14.79, p = 0.01), patient-reported history of swollen joints (OR 4.25, 95% CI 2.17-8.32, p < 0.001), and patient-reported history of sausage-like swollen digits (OR 2.38, 95% CI 1.25-4.55, p = 0.01). Based on these variables, a referral tool was created with an area under the curve of 0.82. This referral tool could be used to aid dermatologists to identify psoriasis patients with concomitant psoriatic arthritis, who may benefit from rheumatological referral.
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Artrite Psoriásica , Psoríase , Doenças Reumáticas , Humanos , Artrite Psoriásica/complicações , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Estudos Prospectivos , Psoríase/complicações , Psoríase/diagnóstico , Psoríase/epidemiologia , Encaminhamento e ConsultaRESUMO
BACKGROUND: Isolated polycystic liver disease (ADPLD) is an autosomal dominant Mendelian disorder. Heterozygous PRKCSH (where PRKCSH is protein kinase C substrate 80K-H (80 kDa protein, heavy chain; MIM*177060) mutations are the most frequent cause. Routine molecular testing using Sanger sequencing identifies pathogenic variants in the PRKCSH (15%) and SEC63 (where SEC63 is Saccharomyces cerevisiae homolog 63 (MIM*608648); 6%) genes, but about approximately 80% of patients meeting the clinical ADPLD criteria carry no PRKCSH or SEC63 mutation. Cyst tissue often shows somatic deletions with loss of heterozygosity that was recently recognized as a general mechanism in ADPLD. We hypothesized that germline deletions in the PRKCSH gene may be responsible for hepatic cystogenesis in a significant number of mutation-negative ADPLD patients. METHODS: In this study, we designed a multiplex ligation-dependent probe amplification (MLPA) assay to screen for deletions of PRKCSH exons. Genomic DNA from 60 patients with an ADPLD phenotype was included. RESULTS: MLPA analysis detected no exon deletions in mutation-negative ADPLD patients. CONCLUSION: Large copy number variations on germline level are not present in patients with a clinical diagnosis of ADPLD. MLPA analysis of the PRKCSH gene should not be considered as a diagnostic method to explain hepatic cystogenesis.
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Cistos/genética , Glucosidases/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Hepatopatias/genética , Deleção de Sequência/genética , Adulto , Idoso , Proteínas de Ligação ao Cálcio , Feminino , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Chaperonas Moleculares , Reação em Cadeia da Polimerase Multiplex/métodos , Proteínas de Ligação a RNA , Estudos RetrospectivosRESUMO
PURPOSE: The Renal cell cancer: Lifestyle, prognosis and quality of life (ReLife) study is set up to obtain insight into the association of patient and tumour characteristics, lifestyle habits and circulating biomarkers with body composition features in patients with localised renal cell cancer (RCC). Further, it aims to assess the association of body composition features, lifestyle habits and circulating biomarkers with clinical outcomes, including health-related quality of life. PARTICIPANTS: The ReLife study is a multicentre prospective cohort study involving 368 patients with newly diagnosed stages I-III RCC recruited from January 2018 to June 2021 from 18 hospitals in the Netherlands. At 3 months, 1 year and 2 years after treatment, participants fill out a general questionnaire and questionnaires about their lifestyle habits (eg, diet, physical activity, smoking and alcohol consumption), medical history and health-related quality of life. At all three time points, patients wear an accelerometer and have blood samples taken. CT scans for body composition analysis are being collected. Permission is asked for collection of tumour samples. Information about disease characteristics, treatment of the primary tumour and clinical outcomes is being collected from medical records by the Netherlands Cancer Registry. FINDINGS TO DATE: A total of 836 invited patients were eligible and 368 patients were willing to participate and were included (response rate 44%). The mean age of patients was 62.5±9.0 years and 70% was male. The majority had stage I (65%) disease and were treated with radical nephrectomy (57%). Data collection at 3 months and 1 years after treatment have been finalised. FUTURE PLANS: Data collection at 2 years after treatment is expected to be finalised in June 2023 and longitudinal clinical data will continue to be collected. Results of studies based on this cohort are important to develop personalised evidence-based lifestyle advice for patients with localised RCC to enable them to get more control over their disease course.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Qualidade de Vida , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/terapia , Estudos Prospectivos , Países Baixos/epidemiologia , Estilo de Vida , Neoplasias Renais/epidemiologia , Neoplasias Renais/terapia , PrognósticoRESUMO
Muscle biopsies are used in clinical trials to measure target engagement of the investigational product. With many upcoming therapies for patients with facioscapulohumeral dystrophy (FSHD), the frequency of biopsies in FSHD patients is expected to increase. Muscle biopsies were performed either in the outpatient clinic using a Bergström needle (BN-biopsy) or in a Magnetic Resonance Imaging machine (MRI-biopsy). This study assessed the FSHD patients' experience of biopsies using a customized questionnaire. The questionnaire was sent to all FSHD patients who had undergone a needle muscle biopsy for research purposes, inquiring about biopsy characteristics and burden, and willingness to undergo a subsequent biopsy. Forty-nine of 56 invited patients (88%) completed the questionnaire, reporting on 91 biopsies. The median pain score (scale 0-10) during the procedure was 5 [2-8], reducing to 3 [1-5] and 2 [1-3] after one and 24 h, respectively. Twelve biopsies (13.2%) resulted in complications, eleven resolved within 30 days. BN-biopsies were less painful compared to MRI-biopsies (median NRS: 4 [2-6] vs. 7 [3-9], p = 0.001). The burden of needle muscle biopsies in a research setting is considerate and should not be underestimated. MRI-biopsies have a higher burden compared to BN-biopsies.
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Distrofia Muscular Facioescapuloumeral , Humanos , Distrofia Muscular Facioescapuloumeral/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Biópsia , Imageamento por Ressonância Magnética/métodos , Instituições de Assistência AmbulatorialRESUMO
INTRODUCTION: Body composition has been associated with disease outcome in several cancer types. Results for localized and metastatic renal cell cancer (RCC) are limited and inconsistent. Our aim was to examine the association between body composition and survival in RCC. METHODS: We conducted a population-based historical cohort study including patients diagnosed with RCC from 2008 to 2012. Diagnostic Computed Tomography images at the third lumbar vertebra (L3) were assessed for skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI) and subcutaneous adipose tissue index (SATI). Clinical data was retrieved from medical records. Multivariable Cox regressions with restricted cubic splines were used to determine hazard ratios (HRs) and 95% confidence intervals (95%CIs) for 10-unit increases in body composition features with overall survival (OS) and recurrence-free survival (RFS). RESULTS: We included 719 stage I-III (of whom 254 (35.3%) died and 148 (21.9%) experienced recurrence) and 320 stage IV RCC patients (of whom 298 (93.1%) died). Median follow-up was 6.35 years (interquartile range; 1.41-8.23). For stage I-III, higher SMD was associated with better OS (men: HR 0.86; 95% CI 0.68-1.08; women: HR 0.69; 95% CI 0.50-0.95). Lower compared to median VATI was associated with worse OS for both men (HR 1.38; 95%CI 1.05-1.83 for VATI = 25) and women (HR 1.67; 95%CI 1.01-2.78 for VATI = 20). For stage IV, higher SMD and higher VATI were associated with better OS among men (HR 0.74; 95% CI 0.59-0.94 and HR 0.93; 95% CI 0.88-0.99, respectively). Results for women were similar but non-significant. No statistically significant associations were found for SMI or SATI. CONCLUSION: Higher SMD and higher VATI were marginally associated with better survival in RCC patients and might be useful for better prognostication. However, the added value to current prognostic scores needs to be investigated.
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Carcinoma de Células Renais/diagnóstico por imagem , Densitometria/estatística & dados numéricos , Indicadores Básicos de Saúde , Gordura Intra-Abdominal/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Idoso , Composição Corporal , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Estudos de Coortes , Feminino , Humanos , Gordura Intra-Abdominal/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Gordura Subcutânea/diagnóstico por imagem , Gordura Subcutânea/patologia , Tomografia Computadorizada por Raios XRESUMO
Background: Body mass index (BMI) and body composition have been associated with postoperative outcomes in oncological surgery. Evidence in renal cell cancer (RCC) is limited and inconsistent. Therefore, we examined BMI and body composition in relation to postoperative outcomes in patients with RCC. Methods: We conducted a multicenter population-based historical cohort study including 801 patients with RCC treated with radical (79%) or partial (21%) nephrectomy between 2008-2012. Computed Tomography images at third lumbar vertebrae were assessed for skeletal muscle (SM) index, SM density, visceral adipose tissue (VAT) index and subcutaneous adipose tissue index (SATI). Multivariable multilevel logistic regression analyses were used to examine associations between BMI, body composition and (major) postoperative complications and extended length of hospital stay (LOHS) (≥7 days). Discrimination of models for major complications was compared using receiver operating characteristics (ROC) curves. Results: In total, 19.6% of the patients had postoperative complications (6.2% Clavien grade ≥III) and 24.1% had extended LOHS. A 10-unit increase in SM density was inversely associated with extended LOHS [odds ratio (OR) 0.58; 95% confidence interval (95% CI): 0.44-0.78]. Associations of high BMI and lower SM density with risk of major complications and of higher VAT index with extended LOHS were also observed but statistical significance differed according to surgical procedure. Models predicting major complications with or without body composition parameters were not different. Conclusions: Lower SM density was associated with extended LOHS and non-significantly associated with higher risk of major postoperative complications. High BMI was associated with higher risk of major postoperative complications. Higher VAT was non-significantly associated with higher risk of extended LOHS. Results by surgical procedure were in the same direction but were only statistically significant for some subgroups. Validation of these results and investigation of the added value of body composition parameters to anatomic classification systems is needed.
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OBJECTIVE: Early detection and preemptive treatment of patients at risk is of great importance in reducing the excess risk of cardiovascular (CV) disease in rheumatoid arthritis (RA). However, it is unclear how much screening is cost-effective in RA. The objective is to assess whether CV screening in RA proves to be cost-effective from a medical perspective, using different scenarios based on different guidelines. METHODS: A Markov chain model was used with a time horizon of 10 years. Parameter values were mainly obtained from literature and from RA patients screened for CV diseases at the Radboud University Medical Centre, Nijmegen, The Netherlands. The primary outcome was incremental cost-effectiveness expressed as costs per quality-adjusted life year (QALY) gained. Probabilistic sensitivity analysis was performed and described in willingness-to-pay curves; several scenarios were built. RESULTS: In the base case scenario, in 82% of the simulations, screening proved to be dominant compared to no screening. The mean QALY gain was 0.09 (95% percentile -0.07, 0.27), and the mean cost savings were -1,057 (95% percentile -2,825, 333). Different scenarios showed small differences in cost-effectiveness; the probability that screening is dominant remained high with the lowest probability being 50% for a very conservative scenario. CONCLUSION: Screening for CV events in RA patients was estimated to be cost-effective with high chances of being less expensive and more effective. These results support endorsement of screening for CV risk in patients with RA.
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Artrite Reumatoide/complicações , Doenças Cardiovasculares/diagnóstico , Diagnóstico Precoce , Programas de Rastreamento/economia , Adulto , Idoso , Artrite Reumatoide/economia , Doenças Cardiovasculares/economia , Doenças Cardiovasculares/etiologia , Análise Custo-Benefício , Feminino , Humanos , Masculino , Cadeias de Markov , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Modelos Econômicos , Países Baixos , Anos de Vida Ajustados por Qualidade de VidaRESUMO
OBJECTIVE: For patients with metastatic renal cell cancer (mRCC), treatment choice is mainly based on clinical parameters. With many treatments available and the limited response to treatment and associated toxicities, there is much interest in identifying better biomarkers for personalized treatment. EuroTARGET aims to identify and characterize host- and tumor-related biomarkers for prediction of response to tyrosine kinase inhibitor therapy in mRCC. Here, we describe the EuroTARGET mRCC patient cohort. METHODS AND MATERIALS: EuroTARGET is a European collaborative project designed as an observational study for which patients with mRCC were recruited prospectively in 62 centers. In addition, 462 patients with mRCC from previous studies were included. Detailed clinical information (baseline and follow-up) from all patients was entered in web-based case record forms. Blood was collected for germline DNA and pharmacokinetic/pharmacodynamic analyses and, where available, fresh-frozen tumor material was collected to perform tumor DNA, RNA, kinome, and methylome analyses. RESULTS: In total, 1,210 patients with mRCC were included. Of these, 920 received a tyrosine kinase inhibitor as first-line targeted treatment (sunitinib [N = 713, 78%], sorafenib [N = 41, 4%], or pazopanib [N = 166, 18%]) and had at least 6 months of outcome assessment (median follow-up 15.3 months [interquartile range: 8.5-30.2 months]). Germline DNA samples were available from 824 of these patients, fresh-frozen tumor material from 142 patients, fresh-frozen normal kidney tissue from 95 patients, and tissue microarrays created from formalin-fixed paraffin-embedded tumor material from 247 patients. Of the 920 patients, germline DNA variant chip data were successfully generated for 811 patients (Illumina HumanOmniExpress BeadChip). For 80 patients, next-generation exome sequencing of germline and tumor DNA was performed, tumor RNA sequencing was performed for 124 patients, kinome activity measured and processed for 121 patients (PamChip), and methylome data (Illumina Infinium HumanMethylation450 BeadChip) were created for 116 RCC tissues (and 23 normal kidney tissues). For 73 out of the 920 patients, all platform data types were generated. In addition, 40 patients were included in a pharmacokinetic/pharmacodynamic phase IV substudy. CONCLUSIONS: Analysis of EuroTARGET cohort data will contribute to personalization of therapy for patients with mRCC. The extensive clinical data and multiplatform EuroTARGET data will be freely available.