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2.
Artigo em Inglês | MEDLINE | ID: mdl-33227328

RESUMO

One of the most striking phenomena in biology is the action potential (AP), a nonlinear pulse with threshold and amplitude saturation (all-or-none-behavior) that propagates along neurons and other cells. In the classical interpretation the AP is considered to be an electrical phenomenon - a regenerating current flowing in a "biological cable". In contrast, the thermodynamic interpretation has emphasized that conservation laws necessitate pulses and that pulses must manifest as transient changes of all observables of the system (electrical, mechanical, thermal, etc.). It is a key prediction of the latter approach that the cell membrane must undergo thermodynamic state changes during an AP. In order to characterize the thermodynamic state of an excitable membrane, plant cells (Chara australis) were stained with Di-4-ANEPPDHQ. The location of the dye in the cell membrane was confirmed by confocal microscopy and changes of fluorescence emission were investigated as a function of temperature and extracellular pH. In parallel, emission of the dye was studied in artificial lipid vesicles (DMPC, DMPS) in the vicinity of the main transition temperature. In all these systems, the emission spectrum shifted as a function of membrane state. This shift became nonlinear and was maximal when the membrane underwent a transition (∂λ∂T∼(6-10)nm°C-1). In the excitable cell Di-4-ANEPPDHQ exhibited a transient blueshift by ∼7 nm during an AP. A blueshift also occurred upon cooling and extracellular acidification. These results provided evidence for a sequence of state changes during an AP in which the cellular membrane condenses followed by expansion. This finding is in line with the thermodynamic interpretation of cellular excitability. Future studies should confirm/falsify these findings with other fluorescent dyes or state-sensitive techniques.

3.
Lupus Sci Med ; 7(1)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33214160

RESUMO

Significant fatigue is reported by two-thirds of patients with SLE and severe fatigue by one-third. The assessment and treatment of fatigue remains a major challenge in SLE, especially in patients with no disease activity. Here, we suggest a practical algorithm for the management of fatigue in SLE. First, common but non-SLE-related causes of fatigue should be ruled out based on medical history, clinical and laboratory examinations. Then, presence of SLE-related disease activity or organ damage should be assessed. In patients with active disease, remission is the most appropriate therapeutic target while symptomatic support is needed in case of damage. Both anxiety and depression are major independent predictors of fatigue in SLE and require dedicated assessment and care with psychological counselling and pharmacological intervention if needed. This practical algorithm will help in improving the management of one the most common and complex patient complaints in SLE.

5.
Int J Cancer ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33113214

RESUMO

The CeTeG/NOA-09 trial showed a survival benefit for combined CCNU/TMZ therapy in MGMT-promoter-methylated glioblastoma patients (quantitative methylation-specific PCR [qMSP] ratio > 2). Here, we report on the prognostic value of the MGMT promoter methylation ratio determined by qMSP and evaluate the concordance of MGMT methylation results obtained by qMSP, pyrosequencing (PSQ) or DNA methylation arrays (MGMT-STP27). A potential association of qMSP ratio with survival was analyzed in the CeTeG/NOA-09 trial population (n = 129; log-rank tests, Cox regression analyses). The concordance of MGMT methylation assays (qMSP, PSQ and MGMT-STP27) was evaluated in 76 screened patients. Patients with tumors of qMSP ratio > 4 showed superior survival compared to those with ratios 2-4 (P = .0251, log-rank test). In multivariate analysis, the qMSP ratio was not prognostic across the study cohort (hazard ratio [HR] = 0.88; 95% CI: 0.72-1.08). With different cutoffs for qMSP ratio (4, 9, 12 or 25), the CCNU/TMZ benefit tended to be larger in subgroups with lower ratios (eg, for cutoff 9: HR 0.32 for lower subgroup, 0.73 for higher subgroup). The concordance rates with qMSP were 94.4% (PSQ) and 90.2% (MGMT-STP27). Discordant results were restricted to tumors with qMSP ratios ≤4 and PSQ mean methylation rate ≤25%. Despite a shorter survival in MGMT-promoter-methylated patients with lower methylation according to qMSP, these patients had a benefit from combined CCNU/TMZ therapy, which even tended to be stronger than in patients with higher methylation rates. With acceptable concordance rates, decisions on CCNU/TMZ therapy may also be based on PSQ or MGMT-STP27.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33029699

RESUMO

Left ventricular ejection fraction (LVEF) is the most important parameter in the assessment of cardiac function. A machine-learning algorithm was trained to guide ultrasound-novices to acquire diagnostic echocardiography images. The artificial intelligence (AI) algorithm then estimates LVEF from the captured apical-4-chamber (AP4), apical-2-chamber (AP2), and parasternal-long-axis (PLAX) loops. We sought to test this algorithm by having first-year medical students without previous ultrasound knowledge scan real patients. Nineteen echo-naïve first-year medical students were trained in the basics of echocardiography by a 2.5 h online video tutorial. Each student then scanned three patients with the help of the AI. Image quality was graded according to the American College of Emergency Physicians scale. If rated as diagnostic quality, the AI calculated LVEF from the acquired loops (monoplane and also a "best-LVEF" considering all views acquired in the particular patient). These LVEF calculations were compared to images of the same patients captured and read by three experts (ground-truth LVEF [GT-EF]). The novices acquired diagnostic-quality images in 33/57 (58%), 49/57 (86%), and 39/57 (68%) patients in the PLAX, AP4, and AP2, respectively. At least one of the three views was obtained in 91% of the attempts. We found an excellent agreement between the machine's LVEF calculations from images acquired by the novices with the GT-EF (bias of 3.5% ± 5.6 and r = 0.92, p < 0.001 in the "best-LVEF" algorithm). This pilot study shows first evidence that a machine-learning algorithm can guide ultrasound-novices to acquire diagnostic echo loops and provide an automated LVEF calculation that is in agreement with a human expert.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33068591

RESUMO

This article attempts to review our work in the field since 2008, attempts to put it in a coherent framework and takes a courageous look vis-à-vis the bigger picture. It summarizes our approach, successes and open questions to start from physical principles when approaching living systems. It stresses the importance of conservation laws versus material and/or structural approaches to living systems commonly taken in (molecular) biology. Indeed, we claim that the crucial system in biology isn't a molecule or a molecular class whatsoever, but the interface created by biomolecules in water. It is the physical or thermodynamic state of this 2D interface and the action of conservation laws on it, which determines biological function, an approach I refer to as the "state-to-function-approach" in stark contrast to the structure-function approach.Three key ideas, all based on physical principles, particularly the 2nd law of thermodynamics and momentum conservation, are presented and experimentally confirmed. In Idea One we bridge physical state and biological function directly, e.g. by demonstrating the control of enzymatic activity and ion conductivity via thermodynamic state. Idea Two presents the role of momentum conservation in biological communication specifically applied to the principles of nerve pulse propagation. Idea Three finally introduces a physical concept of specificity, which is free of structural requirements and includs the specific interaction between pulses and enzymes.We finally discuss the extend of applicability and the universality of the mentioned ideas by presenting some impressive similarities between fairly remotely appearing biological processes, such as cell growth and pulse propagation. We close with the question in how far a thermodynamic approach can bring insight in the concept of cell adaptation, the evolution of organs or a deeper understanding of health and disease?

9.
Artigo em Inglês | MEDLINE | ID: mdl-33058943

RESUMO

The thermodynamic (TD) properties of biological membranes play a central role for living systems. It has been suggested, for instance, that nonlinear pulses such as action potentials (APs) can only exist if the membrane state is in vicinity of a TD transition. Herein, two membrane properties in living systems - excitability and velocity - are analyzed for a broad spectrum of conditions (temperature (T), 3D-pressure (p) and pH-dependence). Based on experimental data from Characean cells and a review of literature we predict parameter ranges in which a transition of the membrane is located (15-35°C below growth temperature; 1-3pH units below pH7; at ∼800atm) and propose the corresponding phase diagrams. The latter explain: (i) changes of AP velocity with T,p and pH.(ii) The existence and origin of two qualitatively different forms of loss of nonlinear excitability ("nerve block", anesthesia). (iii) The type and quantity of parameter changes that trigger APs. Finally, a quantitative comparison between the TD behavior of 2D-lipid model membranes with living systems is attempted. The typical shifts in transition temperature with pH and p of model membranes agree with values obtained from cell physiological measurements. Taken together, these results suggest that it is not specific molecules that control the excitability of living systems but rather the TD properties of the membrane interface. The approach as proposed herein can be extended to other quantities (membrane potential, calcium concentration, etc.) and makes falsifiable predictions, for example, that a transition exists within the specified parameter ranges in excitable cells.

10.
Lupus ; : 961203320965690, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33081589

RESUMO

OBJECTIVE: To comprehensively assess associations of site-specific CD4+-T-cell hypomethylation of the CD40-Ligand gene (CD40L) with disease activity of women with systemic lupus erythematosus (SLE). METHODS: CpG-sites within the DNA of the promotor and two enhancer regions (n = 22) of CD40L were identified and numbered consecutively. The rate of methylated DNA in isolated CD4+-T-cells of women with SLE were quantified for each methylation site by MALDI-TOF. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). Associations of site-specific methylation rates with the SLEDAI scores were assessed by linear regression modelling. P values were adjusted according to Bonferroni-Holm as indicated. RESULTS: 60 female SLE patients participated in the study (age 45.7 ± 11.1 years, disease duration 17.0 ± 8.3 years). Significant associations to the SLEDAI were noted for CpG22 hypomethylation of the promotor (ß = -40.1, p = 0.017, adjusted p = 0.027), trends were noted for CpG17 hypomethylation of the promotor (ß = -30.5, p = 0.032, adjusted p = 0.6), and for CpG11 hypermethylation of the second enhancer (ß = 15.0, p = 0.046, adjusted p = 0.8). CONCLUSION: Site-specific hypomethylation of the CD40L promotor in CD4+-T-cells show associations with disease activity in female SLE patients.

11.
J Neurooncol ; 149(3): 421-427, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32989681

RESUMO

OBJECT: Increasing age is a known negative prognostic factor for glioblastoma. However, a multifactorial approach is necessary to achieve optimal neuro-oncological treatment. It remains unclear to what extent frailty, comorbidity burden, and obesity might exert influence on survival in geriatric glioblastoma patients. We have therefore reviewed our institutional database to assess the prognostic value of these factors in elderly glioblastoma patients. METHODS: Between 2012 and 2018, patients aged ≥ 65 years with newly diagnosed glioblastoma were included in this retrospective analysis. Patients frailty was analyzed using the modified frailty index (mFI), while patients comorbidity burden was assessed according to the Charlson comorbidity index (CCI). Body mass index (BMI) was used as categorized variable. RESULTS: A total of 110 geriatric patients with newly diagnosed glioblastoma were identified. Geriatric patients categorized as least-frail achieved a median overall survival (mOS) of 17 months, whereas most frail patients achieved a mOS of 8 months (p = 0.003). Patients with a CCI > 2 had a lower mOS of 6 months compared to patients with a lower comorbidity burden (12 months; p = 0.03). Multivariate analysis identified "subtotal resection" (p = 0.02), "unmethylated MGMT promoter status" (p = 0.03), "BMI < 30" (p = 0.04), and "frail patient (mFI ≥ 0.27)" (p = 0.03) as significant and independent predictors of 1-year mortality in geriatric patients with surgical treatment of glioblastoma (Nagelkerke's R2 0.31). CONCLUSIONS: The present study concludes that both increased frailty and comorbidity burden are significantly associated with poor OS in geriatric patients with glioblastoma. Further, the present series suggests an obesity paradox in geriatric glioblastoma patients.

12.
J Neurooncol ; 149(3): 455-461, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32990861

RESUMO

INTRODUCTION: Supra-total resection in terms of anterior temporal lobectomy (ATL) has gained growing attention with regard to superior long-term disease control for temporal-located glioblastoma. However, aggressive onco-surgical approaches-geared beyond conventional gross total resections (GTR)-may be associated with peri- and postoperative unfavorable events which significantly worsen initial favorable postoperative outcome. In the current study we analyzed our institutional database with regard to patient safety indicators (PSIs), hospital-acquired conditions (HACs) and specific cranial surgery-related complications (CSC) as high standard quality metric profiles in patients that had undergone surgery for temporal glioblastoma. METHODS: Between 2012 and 2018, 61 patients with temporal glioblastoma underwent GTR or temporal lobectomy at the authors' institution. Both groups of differing resection modalities were analyzed with regard to the incidence of PSIs, HACs and CSCs. RESULTS: Overall, we found 6 PSI and 2 HAC events. Postoperative hemorrhage (3 out of 61 patients; 5%) and catheter-associated urinary tract infection (2 out 61 patients; 3%) were identified as the most frequent PSIs and HACs. PSIs were present in 1 out of 41 patients (5%) for the temporal GTR and 2 out of 20 patients for the lobectomy group (p = 1.0). Respective rates for PSIs were 5 of 41 (12%) and 1 of 20 (5%) (p = 0.7). Further, CSCs did not yield significant differences between these two resection modalities (p = 1.0). CONCLUSION: With regard to ATL and GTR as differing onco-surgical approaches these data suggest ATL in terms of an aggressive supra-total resection strategy to preserve perioperative standard safety metric profiles.

13.
RMD Open ; 6(2): 0, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32868449

RESUMO

INTRODUCTION: The European Reference Network (ERN) ReCONNET is the ERN aimed at improving the management of rare and complex connective tissue and musculoskeletal diseases (rCTDs) across the European Union (EU). In the mission of ERN ReCONNET, clinical practice guidelines (CPGs) play a crucial role, representing a valid tool towards the harmonisation of the management of rCTDs while improving effectiveness and quality of care delivered to patients. METHODS: ERN ReCONNET developed two surveys to map the adherence to rCTDs CPGs among healthcare providers and to assess the knowledge and awareness of CPGs for their diseases among patients, family members and caregivers. RESULTS: The results of the surveys highlighted that healthcare professionals find it useful to apply CPGs in clinical practice (93%), while 62% of them experience difficulties and barriers in the application in their centres. Healthcare professionals also highlighted the need to develop CPGs for all rCTDs and to implement the use of the existing CPGs in clinical practice. On the other hand, patients, families and caregivers are relatively aware of the purpose of CPGs (51%) and 62% of them were aware of the existence of CPGs for their disease. Patient-friendly versions of CPGs and patients' lifestyle guidelines should be systematically developed contributing to the empowerment of patients in the disease management. CONCLUSION: ERN ReCONNET is addressing the main issues identified in the results of the survey, promoting practical actions for the local adaptation of CPGs across Europe, improving their routine clinical use and increasing the awareness on CPGs among rCTDs patients, family members and caregivers.

14.
Cell Death Dis ; 11(8): 714, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873774

RESUMO

Cannabidiol (CBD) is a non-intoxicating phytocannabinoid from cannabis sativa that has demonstrated anti-inflammatory effects in several inflammatory conditions including arthritis. However, CBD binds to several receptors and enzymes and, therefore, its mode of action remains elusive. In this study, we show that CBD increases intracellular calcium levels, reduces cell viability and IL-6/IL-8/MMP-3 production of rheumatoid arthritis synovial fibroblasts (RASF). These effects were pronounced under inflammatory conditions by activating transient receptor potential ankyrin (TRPA1), and by opening of the mitochondrial permeability transition pore. Changes in intracellular calcium and cell viability were determined by using the fluorescent dyes Cal-520/PoPo3 together with cell titer blue and the luminescent dye RealTime-glo. Cell-based impedance measurements were conducted with the XCELLigence system and TRPA1 protein was detected by flow cytometry. Cytokine production was evaluated by ELISA. CBD reduced cell viability, proliferation, and IL-6/IL-8 production of RASF. Moreover, CBD increased intracellular calcium and uptake of the cationic viability dye PoPo3 in RASF, which was enhanced by pre-treatment with TNF. Concomitant incubation of CBD with the TRPA1 antagonist A967079 but not the TRPV1 antagonist capsazepine reduced the effects of CBD on calcium and PoPo3 uptake. In addition, an inhibitor of the mitochondrial permeability transition pore, cyclosporin A, also blocked the effects of CBD on cell viability and IL-8 production. PoPo3 uptake was inhibited by the voltage-dependent anion-selective channel inhibitor DIDS and Decynium-22, an inhibitor for all organic cation transporter isoforms. CBD increases intracellular calcium levels, reduces cell viability, and IL-6/IL-8/MMP-3 production of RASF by activating TRPA1 and mitochondrial targets. This effect was enhanced by pre-treatment with TNF suggesting that CBD preferentially targets activated, pro-inflammatory RASF. Thus, CBD possesses anti-arthritic activity and might ameliorate arthritis via targeting synovial fibroblasts under inflammatory conditions.

15.
BMC Mol Cell Biol ; 21(1): 64, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917131

RESUMO

BACKGROUND: It has been demonstrated that von Willebrand factor (VWF) mediated platelet-endothelium and platelet-platelet interactions are shear dependent. The VWF's mobility under dynamic conditions (e.g. flow) is pivotal to platelet adhesion and VWF-mediated aggregate formation in the cascade of VWF-platelet interactions in haemostasis. RESULTS: Combining microfluidic tools with fluorescence and reflection interference contrast microscopy (RICM), here we show, that specific deletions in the A-domains of the biopolymer VWF affect both, adhesion and aggregation properties independently. Intuitively, the deletion of the A1-domain led to a significant decrease in both adhesion and aggregate formation of platelets. Nevertheless, the deletion of the A2-domain revealed a completely different picture, with a significant increase in formation of rolling aggregates (gain of function). We predict that the A2-domain effectively 'masks' the potential between the platelet glycoprotein (GP) Ib and the VWF A1-domain. Furthermore, the deletion of the A3-domain led to no significant variation in either of the two functional characteristics. CONCLUSIONS: These data demonstrate that the macroscopic functional properties i.e. adhesion and aggregate formation cannot simply be assigned to the properties of one particular domain, but have to be explained by cooperative phenomena. The absence or presence of molecular entities likewise affects the properties (thermodynamic phenomenology) of its neighbours, therefore altering the macromolecular function.

16.
Skeletal Radiol ; 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32845377

RESUMO

BACKGROUND: Because of overlapping phenotypical presentations, the diagnostic differentiation of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) remains challenging. Thus, this study aimed to examine the diagnostic value of distinct imaging features obtained by high-resolution 3-T MRI for the diagnostic differentiation. MATERIALS AND METHODS: Seventeen patients with PsA and 28 patients with RA were imaged at high resolution using 3-T MRI scanners and a dedicated 16-channel hand coil. All images were analyzed according to the outcome measures in rheumatology clinical trials' (OMERACT) RAMRIS (Rheumatoid Arthritis Magnetic Resonance Imaging Score) and PsAMRIS (Psoriatic Arthritis Magnetic Resonance Imaging Score) for the presence and intensity of synovitis, flexor tenosynovitis, bone edema, bone erosion, periarticular inflammation, bone proliferation, and joint space narrowing. Next, odds ratios (OR) were calculated to determine the strength of the associations between these imaging features, demographic characteristics, and the outcome RA vs. PsA. RESULTS: PsA could be differentiated from RA by extracapsular inflammatory changes (PsAMRIS sub-score "periarticular inflammation"), with low odds for the presence of RA (OR of 0.06, p < 0.01) at all metacarpophalangeal (MCP) joints. A prediction model informed by the items that were strongest associated with the presence of RA or PsA demonstrated excellent differentiating capability with an area under the curve of 98.1%. CONCLUSION: High-resolution imaging is beneficial for the identification of relevant imaging features that may assist the clinical differentiation of inflammatory conditions of the hand. At the MCP level, extracapsular inflammatory changes were strongly associated with PsA and may consequently allow the imaging differentiation of PsA and RA.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32860806

RESUMO

Experimental observations in lipid monolayers at the air-water interface have demonstrated that solitary sound pulses can be excited. These pulses propagate electrical, chemical, and thermal variations in addition to the mechanical changes in lateral pressure and lipid density, and can interact with nearby ions, polymers, and water. In addition, it was demonstrated that sound pulses that reversibly traverse the melting transition between the so-called liquid-expanded and liquid-condensed phases display unusual nonlinear properties that are strikingly similar to those of action potentials in living cells. This review describes recent experimental and theoretical investigations of sound in lipid membranes and their potential function in biology.

18.
Cardiology ; 145(9): 578-588, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756051

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the different components of left atrial (LA) dysfunction predictors in asymptomatic primary systemic hypertension patients with preserved left ventricular (LV) ejection fraction, particularly using LA 4-dimensional (4D) longitudinal and circumferential strain values. METHODS AND RESULTS: Patients with no left ventricular hypertrophy (NLVH) and left ventricular hypertrophy (LVH) are all asymptomatic regarding primary blood hypertension. Thirty NLVH patients and 30 LVH patients according to LV mass index and 40 controls analyzed by 4D echocardiography were prospectively enrolled. LA volumes and longitudinal and circumferential strains were measured using 4D volume-strain echocardiography with a Vivid E95 Version 203 instrument. Correlation analysis indicated a significant relation between LV 4D mass index and LA 4D longitudinal/circumferential strain (r = -0.446 to 0.381, p = 0.000-0.042). LVH patients had a reduced LA emptying fraction compared with NLVH patients and control subjects (p < 0.01). NLVH patients had an impaired LA conduit function and increased contractile function compared with the control group (p < 0.01). LVH patients had increased LA volumes and significantly decreased reservoir, conduit and contractile functions compared with the controls (p < 0.01). LVH patients had increased LA volumes and decreased reservoir and contractile functions compared with NLVH patients (p < 0.01). The clinical utility of LA 4D volume-strain measurement was verified by receiver-operating characteristic curve analysis showing larger net benefits as evaluated with NLVH, LVH and control group comparisons. Interclass correlation coefficients of interobserver and intraobserver assessments in the LV and LA 4D value evaluations were >0.75 and >0.85, respectively. CONCLUSIONS: LVH patients showed increased LA volumes and decreased LA emptying fractions. LA reservoir, conduit and contractile functions were significantly impaired in LVH patients. Decreased LA conduit function and increased contractile function were revealed in NLVH patients. LA volumetric and functional analyses with 4D volume-strain echocardiography may facilitate the recognition of subtle LA and LV dysfunctions in asymptomatic systemic hypertension patients.

19.
Z Rheumatol ; 79(7): 679-685, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32757030

RESUMO

A few days after the SARS-CoV-2 infection was declared a pandemic, the German Society for Rheumatology (DGRh) compiled first recommendations for the care of patients with inflammatory rheumatic diseases (IRD). These first recommendations were based on an expert consensus and were largely non-evidence-based. Now that the first scientific data from registers, cross-sectional studies, case reports and case series are available, the present update is intended to update the previous recommendations and to add new findings. The current recommendations are based on a literature search of publications available up to 15 June 2020 and address preventive measures (such as hygiene measures or vaccinations) and the use of immunomodulatory/immunosuppressive drugs. An important goal of the current recommendations is also to prevent harm to patients with IRD through unjustified restriction of care. The DGRh will continue to update its recommendations in the case of new aspects and will publish them as well as further information on the COVID-19 pandemic on its homepage ( www.dgrh.de ) in an ongoing process.


Assuntos
Infecções por Coronavirus/epidemiologia , Inflamação/terapia , Pneumonia Viral/epidemiologia , Doenças Reumáticas/terapia , Reumatologia/métodos , Betacoronavirus , Alemanha , Humanos , Pandemias , Sociedades Médicas
20.
Ann Rheum Dis ; 79(10): 1333-1339, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32816709

RESUMO

OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. METHODS: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. RESULTS: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%). CONCLUSIONS: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Índice de Gravidade de Doença , Feminino , Humanos , Masculino , Seleção de Pacientes , Sensibilidade e Especificidade
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