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1.
Z Rheumatol ; 83(3): 217-228, 2024 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-38498147

RESUMO

Sjögren's syndrome (SjS) is the most common connective tissue disease with a prevalence of 1:200. Predominantly affecting women, SjS is associated with destruction of the exocrine glands, leading to xerophthalmia and xerostomia. In over 50% of patients, there are also extraglandular manifestations, leading to multiple organ manifestations including polyneuropathies and interstitial lung disease as well as symptoms such as fatigue and arthralgia. Diagnostic procedures include biomarkers, in particular anti-SS-A/Ro antibodies, histology of salivary glands, and salivary gland sonography. There are currently no licensed immunosuppressive drugs for SjS, so current treatment is often based on off-label use of drugs. The European League Against Rheumatism (EULAR) has recently published treatment recommendations based on the prevailing organ manifestations. Several promising controlled trials with novel compounds and concepts are currently in progress.


Assuntos
Doenças Reumáticas , Síndrome de Sjogren , Humanos , Feminino , Síndrome de Sjogren/diagnóstico , Glândulas Salivares/patologia , Imunossupressores/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Biomarcadores
2.
Dtsch Med Wochenschr ; 149(12): 734-739, 2024 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-38781999

RESUMO

In the diagnosis of Sjögren's syndrome the Salivary gland sonography (SGUS) has become established and can lead to a higher specificity of the applicable classification criteria. The OMERACT score is used to objectify the SGUS findings. In laboratory diagnostics, the subspecification of anti-SSA/Ro antibodies, but possibly also new biomarkers, are becoming increasingly important regarding diagnostic safety and the expected manifestations. When it comes to prevention, it has been shown that not only psychological stress, but also cardiovascular risk and the risk of lymphoma allow high-risk patients to be identified more precisely in the future. Using cluster analyses, various phenotype groups could be identified to which clinical parameters could be assigned. In 2020, therapy recommendations were published that are based on the clinical manifestations of SjS and recommend medications that are also used in the treatment of systemic lupus erythematosus (SLE) or rheumatoid arthritis. A particularly large number of therapeutic approaches are dedicated to the B cell: Rituximab and Belimumab have been included in the EULAR recommendations for serious manifestations and Ianalumab has a promising effect. Another focus of current research is the inhibition of co-stimulation between immune cells. After recent disappointing results for Abatacept, clinical trials show promising effects on Iscalimab and Dazodalibep.


Assuntos
Síndrome de Sjogren , Síndrome de Sjogren/terapia , Síndrome de Sjogren/diagnóstico , Humanos , Glândulas Salivares/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Rituximab/uso terapêutico , Ultrassonografia , Biomarcadores/sangue
3.
RMD Open ; 10(3)2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39179256

RESUMO

BACKGROUND: MicroRNAs (miRNAs) can regulate gene expression, controlling numerous cellular processes. Dysregulation of miRNA function is linked to various diseases, making them attractive diagnostic and therapeutic targets. Examples include hsa-miR-92a-3p, hsa-miR-126-3p, hsa-miR-143-3p, hsa-miR-145-5p and hsa-miR-204-5p, which are associated with endothelial function. Their prevalence in Sjögren's disease (SjD) is unknown. We assessed the prevalence of these miRNAs in serum of patients with SjD, correlating levels with cardiovascular risk factors and carotid intima-media thickness (cIMT) to evaluate their utility in risk stratification. METHODS: 199 patients with SjD and 100 age and sex-matched healthy controls (HC) were included in the study. Five different miRNAs (hsa-miR-92a-3p; hsa-miR-126-3p; hsa-miR143-3p; hsa-miR-145-5p; hsa-miR-204-5p) were analysed by quantitative real-time PCR. The miRNA results were compared with known clinical and disease-related parameters. RESULTS: Four miRNAs showed significantly different expressions compared with HC. MiR-92a-3p was upregulated (p=0.025) and miR-126-3p (p=0.044), miR-143-3p (p=0.006) and miR-204-5p (p=0.009) downregulated in SjD compared with HC. The comparison between HC and SjD with/without organ involvement revealed descriptively increased miR-92a-3p levels in patients with SjD with organ involvement (p=0.087). Furthermore, miR-92a-3p levels correlated positively with cIMT as an expression of subclinical atherosclerosis (r=0.148, p=0.04). CONCLUSION: In conclusion, patients with SjD demonstrated differences in their expression of miRNAs linked to regulation of endothelial function. Reduction of specific miRNAs was associated with increased cardiovascular risk, suggesting a potentially protective role for these miRNAs. Furthermore, miR-92a-3p could be helpful for molecular detection of early-stage atherosclerosis and increased cardiovascular risk in SjD.


Assuntos
Aterosclerose , Biomarcadores , Espessura Intima-Media Carotídea , MicroRNAs , Síndrome de Sjogren , Humanos , MicroRNAs/genética , MicroRNAs/sangue , Feminino , Pessoa de Meia-Idade , Masculino , Aterosclerose/etiologia , Aterosclerose/diagnóstico , Aterosclerose/genética , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/genética , Síndrome de Sjogren/sangue , Estudos de Casos e Controles , Adulto , Perfilação da Expressão Gênica , Idoso , Regulação da Expressão Gênica
4.
RMD Open ; 10(2)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38663882

RESUMO

OBJECTIVES: Cardiovascular comorbidities are common in patients with autoimmune diseases. This study investigates the extent of subclinical atherosclerosis in patients with primary Sjögren's syndrome (pSS). Correlations with clinical factors such as organ involvement (OI) or disease activity were analysed and oxLDL antibodies (oxLDL ab) were measured as potential biomarkers of vascular damage. METHODS: Patients with pSS were consecutively included from the rheumatology outpatient clinic. Age- and sex-matched controls were recruited (2:1 ratio). Data collection was performed by a standardised questionnaire and Doppler ultrasound to evaluate the plaque extent and carotid intima-media thickness (cIMT). Propensity score matching included all cardiovascular risk (CVR) factors and corresponding laboratory markers. RESULTS: Data were available for 299 participants (199 pSS/100 controls), aged 59.4 years (50.6-65.0), 19.1% male. After matching, the pSS cohort had greater cIMT (p<0.001) and plaque extent (OR=1.82; 95% CI 1.14 to 2.95). Subgroup analyses of patients with pSS revealed that OI was associated with increased cIMT (p=0.025) and increased plaque occurrence compared with patients without OI (OR=1.74; 95% CI 1.02 to 3.01). OxLDL ab tended to be lower in patients with plaque (p=0.052). Correlations of higher Oxidized Low Density Lipoprotein (oxLDL) ab with EULAR Sjögren's Syndrome Disease Activity Index (p<0.001) and anti-Sjögren's-syndrome-related antigen A autoantibodies (SSA/Ro antibodies) (p=0.026) were observed. CONCLUSIONS: Subclinical atherosclerosis occurs earlier and more severely in patients with pSS. The difference in cIMT between pSS and controls seems mainly driven by patients with OI, suggesting that this subgroup is particularly at risk. OxLDL ab might protect against atherosclerotic progression in patients with pSS. CVR stratification and preventive medications such as Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors should be discussed and further longitudinal studies are needed.


Assuntos
Aterosclerose , Biomarcadores , Espessura Intima-Media Carotídea , Lipoproteínas LDL , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/epidemiologia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/diagnóstico , Masculino , Pessoa de Meia-Idade , Feminino , Aterosclerose/etiologia , Aterosclerose/epidemiologia , Aterosclerose/diagnóstico , Lipoproteínas LDL/sangue , Idoso , Estudos de Casos e Controles , Autoanticorpos/sangue , Autoanticorpos/imunologia , Fatores de Risco , Placa Aterosclerótica/epidemiologia
5.
Sci Rep ; 14(1): 3799, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360886

RESUMO

Ventricular tachyarrhythmia (VTA) are frequent arrhythmias in patients with hypertrophic cardiomyopathy (HCM). Representing a major risk factor for sudden cardiac death, Holter ECG at first clinical presentation appears insufficient. This study aims to investigate the ability of routinely obtained parameters associated with myocardial remodeling in stratifying for VTA in HCM. In this monocentric analysis, patients with HCM underwent 12-channel electrocardiography and echocardiography, including tissue doppler imaging. The study's primary endpoint was the documentation of non-sustained and sustained ventricular tachycardia-summarized as ventricular tachyarrhythmias (VTA) on Holter ECG or active devices. The occurrence of VTA was exploratory. Based on our collective, we developed a risk model regarding VTA. Of 140 HCM patients, 38 (27.1%) had an episode of VTA. Patients with VTA were likelier to have a history of atrial fibrillation (p < 0.001), a thicker interventricular septum (p < 0.001) and lower peak systolic mitral annular velocity (p < 0.001). The parameters were independently associated with endpoint in univariate and multivariate logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.80 (sensitivity, 63%; specificity, 88%). Our risk model including these widely available parameters is able to distinguish low and high-risk of VTA in patients with HCM.


Assuntos
Cardiomiopatia Hipertrófica , Taquicardia Ventricular , Humanos , Projetos Piloto , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Ecocardiografia/efeitos adversos , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/complicações , Fatores de Risco , Medição de Risco , Morte Súbita Cardíaca/etiologia
6.
J Neurol ; 270(6): 2987-2996, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36802030

RESUMO

OBJECTIVE: Neurological manifestations of Sjögren's syndrome can be severe but also treatment-responsive. We aimed to systematically evaluate neurological manifestations of primary Sjögren's syndrome and find clinical features allowing sufficient identification of affected patients (pSSN) among those with Sjögren's syndrome without neurological involvement (pSS). METHODS: Para-/clinical features of patients with primary Sjögren's syndrome (2016 ACR/EULAR classification criteria) were compared between pSSN and pSS. At our university-based center, patients with suggestive neurological symptoms undergo screening for Sjögren's syndrome, and newly diagnosed pSS patients are thoroughly evaluated for neurologic involvement. pSSN disease activity was rated by the Neurological Involvement of Sjögren's Syndrome Disease Activity Score (NISSDAI). RESULTS: 512 patients treated for pSS/pSSN at our site between 04/2018 and 07/2022 were included (238 pSSN patients [46%] vs. 274 pSS patients [54%], cross-sectional design). Independent predictors of neurological involvement in Sjögren's syndrome were male sex [p < 0.001], older age at disease onset [p < 0.0001], hospitalization at first presentation [p < 0.001], lower IgG levels [p = 0.04] and higher eosinophil values (treatment-naïve) [p = 0.02]. Univariate regression additionally showed older age at diagnosis [p < 0.001], lower prevalence of rheumatoid factor [p = 0.001], SSA(Ro)/SSB(La) antibodies [p = 0.03; p < 0.001], higher white blood cell count [p = 0.02] and CK levels [p = 0.02] (treatment-naïve) in pSSN. INTERPRETATION: Patients with pSSN had different clinical characteristics than patients with pSS and represented a large proportion of the cohort. Our data suggest that neurological involvement in Sjögren's syndrome has been underestimated. Intensified screening for neurologic involvement should be included in the diagnostic algorithm for Sjögren's syndrome, especially in males of older age and with severe disease course requiring hospitalization.


Assuntos
Síndrome de Sjogren , Humanos , Masculino , Feminino , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Estudos Transversais , Prevalência , Progressão da Doença
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