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In systemic sclerosis (SSc), fibrosis of the myocardium along with ongoing autoimmune inflammation can alter the electric function of the cardiac myocytes, which may increase the risk for ventricular arrhythmias and sudden cardiac death. We analyzed the electrocardiographic (ECG) variables describing ventricular repolarization such as QT interval, QT dispersion (QTd), T wave peak-to-end interval (Tpe), and arrhythmogeneity index (AIX) of 26 patients with SSc and 36 healthy controls. Furthermore, echocardiographic and laboratory parameters were examined, with a focus on inflammatory proteins like C-reactive ptotein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), and progranulin (PGRN). The CRP, sICAM-1, and sVCAM-1 levels were positively correlated with the length of the QT interval. Although the serum PGRN levels were not increased in the SSc group compared to the controls, in SSc patients, the PGRN levels were positively correlated with the QT interval and the AIX. According to our results, we conclude that there may be a potential association between autoimmune inflammation and the risk for ventricular arrhythmias in patients with SSc. We emphasize that the measurement of laboratory parameters of inflammatory activity including CRP, PGRN, sVCAM-1, and sICAM-1 could be helpful in the prediction of sudden cardiac death in patients with SSc.
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Arritmias Cardíacas , Molécula 1 de Adhesión Intercelular , Progranulinas , Esclerodermia Sistémica , Molécula 1 de Adhesión Celular Vascular , Humanos , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Molécula 1 de Adhesión Celular Vascular/sangre , Molécula 1 de Adhesión Intercelular/sangre , Arritmias Cardíacas/etiología , Arritmias Cardíacas/sangre , Progranulinas/sangre , Electrocardiografía , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Anciano , Factores de Riesgo , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisisRESUMEN
INTRODUCTION: Systemic sclerosis (SSc) is a chronic autoimmune rheumatic disease characterized by microvascular alterations, immunopathology, and widespread fibrosis involving various organs. It is considered difficult to treat due to several reasons: complex pathogenesis, heterogeneity, late diagnosis, limited treatment options for certain organ manifestations, lack of personalized medicine. AREAS COVERED: This review presents the heterogeneity, survival and organ manifestations with their risk factors of systemic sclerosis and their current treatment options, while drawing attention to difficult-to-treat forms of the disease, based on literature indexed in PubMed. EXPERT OPINION: Despite recent advances in the management of SSc over the last decades, the disease presents significant morbidity and mortality. Although available treatment protocols brought significant advancements in terms of survival in SSc-associated interstitial lung disease and pulmonary arterial hypertension, less success has been achieved in the treatment of Raynaud's phenomenon and digital ulcers and the results are modest in case of heart, gastrointestinal, and renal manifestations. There are patients who do not respond to treatment and deteriorate even with adequate therapy. They can be considered difficult-to treat (D2T) cases. We have created a possible score system based on the individual organ manifestations and highlighted treatment options for the D2T SSc category.
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Esclerodermia Sistémica , Esclerodermia Sistémica/terapia , Esclerodermia Sistémica/diagnóstico , Humanos , Enfermedades Pulmonares Intersticiales/terapia , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedad de Raynaud/terapia , Enfermedad de Raynaud/diagnóstico , Medicina de Precisión , Factores de RiesgoRESUMEN
OBJECTIVES: To untangle the association between smoking and systemic sclerosis (SSc). METHODS: In the European Scleroderma Trials and Research cohort, the autoantibody status was compared between ever-smokers and never-smokers. Time until disease progression was assessed using Kaplan-Meier curves. Cox models were built to investigate the influence of smoking over 15 years of follow-up. All analyses were performed for the total cohort and stratified for sex and for positivity of anti-centromere (ACA) and anti-topoisomerase antibodies (ATA). RESULTS: Overall, 12 314 patients were included in the study. Of these, 10 393 were women (84%), 4637 were ACA-positive (38%), 3919 were ATA-positive (32%) and 4271 (35%) were ever-smokers. In men, but not in women, smoking was associated with mortality (HR 1.63, 95% CI 1.23 to 2.16, p=0.001). Ever-smoking women were at higher risk for skin progression (HR 1.10, 95% CI 1.00 to 1.22, p=0.046) and for 'any organ progression' (HR 1.07, 95% CI 1.00 to 1.13, p=0.036). In women, 34% of never-smokers were ATA-positive compared with 21% of ever-smokers (p<0.001). In the group of ever-smokers, higher exposure rates, reflected by the number of pack-years (OR 0.98, 95% CI 0.97 to 0.99, p<0.001) and by smoking duration (OR 0.96, 95% CI 0.95 to 0.97, p<0.001), were associated with lower frequency of ATA. In ACA-positive patients, the risk of mortality (HR 1.29, 95% CI 1.02 to 1.63, p=0.033), cardiac involvement (HR 1.25, 95% CI 1.03 to 1.43, p=0.001), skin progression (HR 1.21, 95% CI 1.03 to 1.42, p=0.018) and 'any organ progression' (HR 1.14, 95% CI 1.05 to 1.24, p=0.002) was increased among smokers. In ATA-positive smoking patients, mortality (HR 1.40, 95% CI 1.10 to 1.78, p=0.006), skin progression (HR 1.19, 95% CI 1.03 to 1.37, p=0.020) digital ulcers (HR 1.17, 95% CI 1.02 to 1.34, p=0.029) and 'any organ progression' (HR 1.11, 95% CI 1.00 to 1.22, p=0.048) occurred more frequently. CONCLUSIONS: Our stratified analysis demonstrates that smoking is associated with an increased risk for mortality in male SSc patients but not in women. Strikingly, smoking is associated with lower prevalence of ATA positivity, in particular in women. In both ATA-positive and ACA-positive patients, smoking is a risk factor for mortality, skin progression and 'any organ progression'.
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Progresión de la Enfermedad , Esclerodermia Sistémica , Fumar , Humanos , Esclerodermia Sistémica/etiología , Esclerodermia Sistémica/epidemiología , Esclerodermia Sistémica/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Fumar/efectos adversos , Fumar/epidemiología , Adulto , Modelos de Riesgos Proporcionales , Factores de Riesgo , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Anciano , Estimación de Kaplan-Meier , Estudios de CohortesRESUMEN
Differentiation between granulomatosis with polyangiitis (GPA) limited to the upper airways and cocaine-induced midline destructive lesion (CIMDL) may be particularly difficult because of their common histopathologic features and antineutrophil cytoplasmic antibody (ANCA) profiles. We herein present a case involving a young woman with an initial diagnosis of GPA based on upper and lower airway manifestations and constitutional symptoms, histopathologic evidence of granulomas, a positive cytoplasmic ANCA indirect immunofluorescent test result, and proteinase 3 positivity by enzyme-linked immunosorbent assay (ELISA). CIMDL was confirmed based on the appearance of a hard palate perforation, positivity for methylecgonine on urine toxicology, a positive perinuclear ANCA indirect immunofluorescent test result, and subsequent human neutrophil elastase (HNE) ANCA positivity by ELISA. Finally, based on the coexistence of CIMDL, constitutional symptoms, and lower airway manifestations, the diagnosis was modified to cocaine-induced GPA mimic. Urine toxicology for cocaine and HNE ELISA are indicated in young patients with GPA who develop limited airway disease to check for the presence of CIMDL and cocaine-/levamisole-induced ANCA-associated vasculitis. Continued abstinence from cocaine is the first-choice therapy for both CIMDL and cocaine-induced GPA mimic.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Trastornos Relacionados con Cocaína , Cocaína , Granulomatosis con Poliangitis , Femenino , Humanos , Anticuerpos Anticitoplasma de Neutrófilos , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/complicaciones , Trastornos Relacionados con Cocaína/complicaciones , Trastornos Relacionados con Cocaína/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicacionesRESUMEN
OBJECTIVE: To examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment. METHODS: Patients were randomized to riociguat (n = 60) or placebo (n = 61) for 52 weeks. Skin biopsies and plasma/serum samples were obtained at baseline and week 14. Plasma cyclic guanosine monophosphate (cGMP) was assessed using radio-immunoassay. Alpha smooth muscle actin (αSMA) and skin thickness were determined by immunohistochemistry, mRNA markers of fibrosis by qRT-PCR in skin biopsies, and serum CXC motif chemokine ligand 4 (CXCL-4) and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) by enzyme-linked immunosorbent assay. RESULTS: By week 14, cGMP increased by 94 ± 78% with riociguat and 10 ± 39% with placebo (p < 0.001, riociguat vs placebo). Serum sPECAM-1 and CXCL-4 decreased with riociguat vs placebo (p = 0.004 and p = 0.008, respectively). There were no differences in skin collagen markers between the 2 groups. Higher baseline serum sPECAM-1 or the detection of αSMA-positive cells in baseline skin biopsies were associated with a larger reduction of modified Rodnan skin score from baseline at week 52 with riociguat vs placebo (interaction P-values 0.004 and 0.02, respectively). CONCLUSION: Plasma cGMP increased with riociguat, suggesting engagement with the nitric oxide-soluble guanylate cyclase-cGMP pathway. Riociguat was associated with a significant reduction in sPECAM-1 (an angiogenic biomarker) vs placebo. Elevated sPECAM-1 and the presence of αSMA-positive skin cells may help to identify patients who could benefit from riociguat in terms of skin fibrosis. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02283762.
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Cardiovascular (CV) morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Natural autoantibodies (nAAb) are involved in innate immunity, as well as autoimmunity, inflammation, and atherosclerosis. There have not been any studies assessing the effects of biologics on nAAbs in RA and AS, also in relation to vascular pathophysiology. Fifty-three anti-TNF-treated RA and AS patients were included in a 12-month follow-up study. Anti-citrate synthase (CS) and anti-topoisomerase I fragment 4 (TOPO-F4) IgM and IgG levels were determined by ELISA. Ultrasonography was performed to assess brachial artery flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV). Other variables were also evaluated at baseline and 6 and 12 months after treatment initiation. Anti-TNF therapy improved FMD in RA and PWV in AS and stabilized ccIMT. TNF inhibition increased anti-CS IgM and IgG, and possibly also anti-TOPO-F4 IgG levels. Various correlation analyses revealed that nAAbs might be independently involved in autoimmunity as well as changes in inflammation and vascular pathology over time in biologic-treated patients (p < 0.05). We also found associations between anti-TOPO-F4 IgG and anti-Hsp60 IgG (p < 0.05). Baseline nAAb levels or nAAb level changes might determine changes in CRP, disease activity, FMD, PWV, and ccIMT over time (p < 0.05). The interplay between arthritis and inflammatory atherosclerosis, as well as the effects of anti-TNF biologics on these pathologies, might independently involve nAAbs.
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Artritis Reumatoide , Aterosclerosis , Productos Biológicos , Espondilitis Anquilosante , Humanos , Espondilitis Anquilosante/tratamiento farmacológico , Grosor Intima-Media Carotídeo , Autoanticuerpos , Inhibidores del Factor de Necrosis Tumoral , Estudios de Seguimiento , Aterosclerosis/complicaciones , Inflamación/complicaciones , Inmunoglobulina G , Inmunoglobulina MRESUMEN
Systemic sclerosis (SSc) is a heterogeneous autoimmune disease, where a significant proportion of patients develop interstitial lung disease (ILD), which is the major cause of mortality. In recent years, the diagnosis of SSc-ILD has improved a lot, and caring rheumatologists, together with pulmonologists, regularly screen and follow the development and course of ILD. Considerable progress has also been made in the treatment of SSc-ILD based on several clinical trials. The recommendations for immunosuppressive treatment have been modified and supplemented with targeted agents (tocilizumab, rituximab), and antifibrotic drugs such as nintedanib registered as a new treatment for SSc-ILD. However, there are no clear recommendations regarding the start and timing of nintedanib treatment. A debate on the early introduction of nintenadib or not took place on the 7th edition of the International Congress on Controversies in Rheumatology and Autoimmunity (CORA) in March/2023, and this review summarizes the main arguments that were discussed in this session.
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Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Prevención Secundaria , Inmunosupresores/uso terapéutico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Indoles/uso terapéutico , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/tratamiento farmacológico , PulmónRESUMEN
OBJECTIVE: The outcome of patients with COVID-19 improved over the pandemic, including patients with systemic rheumatic diseases. However, data on patients with systemic sclerosis (SSc) are lacking. This study aimed to assess the outcome of patients with both SSc and COVID-19 over several waves. METHODS: Patients with both SSc and COVID-19 who were registered in the European Scleroderma Trials and Research group (EUSTAR) were collected between April 2020 and April 2021. Patients were assigned to waves 1, 2, or 3 depending on the date of their COVID-19 diagnosis. Primary endpoints were death, intensive care unit stay, or ventilatory support (severe outcome). Subgroup analyses of patients who were hospitalized or died were conducted. General and SSc-specific characteristics and treatment were compared over the waves. Descriptive statistics and multivariate logistic regression were applied. RESULTS: A total of 333 patients were included; 57 patients (17%) had a severe outcome, and 30 patients (9%) died. Compared to wave 1, significantly fewer patients with SSc suffered from severe COVID-19 in waves 2 and 3 (28.2% vs 9.8% and 12.7%; P < 0.001), fewer patients required hospitalization (46.7% vs 19.6% and 25.5%; P < 0.001) or ventilatory support (24.0% vs 8.7% and 10.9%; P = 0.001), and fewer patients died (15.7% vs 5.0% and 7.5%; P = 0.011). Patients were significantly younger, more often men, had less frequent arterial hypertension, and less SSc cardiac involvement over waves 1 to 3. Patients received significantly less medium to high doses of corticosteroids as they did SSc treatment. CONCLUSION: The outcome of patients with both SSc and COVID-19 improved significantly over time because of intrinsic and extrinsic factors.
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COVID-19 , Hipertensión , Esclerodermia Localizada , Esclerodermia Sistémica , Masculino , Humanos , Prueba de COVID-19 , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/epidemiologíaRESUMEN
BACKGROUND: A major challenge of the HEp-2 cell-based indirect immunofluorescence (IIF) assays is the correct identification of the individual anti-nuclear antibodies (ANAs) if more than one is present in a sample. We created artificial mixes by pooling two different samples with a single autoantibody in different titers. Comparison of the expected and observed patterns and titers clarifies the interference between the two tested ANAs. METHODS: Serum samples with a single homogeneous or speckled ANA pattern were serially diluted and mixed in 16 combinations, providing end-point titers of 1:5,120 to 1:80 for both patterns. These mixes were tested by a HEp-2 IIF assay and were evaluated by conventional evaluation, the EUROPattern (EPa) system and on-screen analysis. RESULTS: Homogeneous pattern can alter the identification of the speckled pattern much more than vice versa, but both has an interfering effect on the other. The effect of the interfering on the tested pattern was higher if the titer of the former one was higher. The pattern recognition efficacy of conventional and the on-screen evaluation was similar and superior compared to the EPa analysis. CONCLUSIONS: The application of artificial mixed samples can help the evaluation of the efficacy of manual and computer-aided ANA HEp-2 pattern recognition.
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Anticuerpos Antinucleares , Enfermedades Autoinmunes , Humanos , Autoanticuerpos , Técnica del Anticuerpo Fluorescente Indirecta , ComputadoresRESUMEN
Introduction: In Hungary, the HUN-VE 3 study determined the comparative effectiveness of various primary and booster vaccination strategies during the Delta COVID-19 wave. That study included more than 8 million 18-100-year-old individuals from the beginning of the pandemic. Immunocompromised (IC) individuals have increased risk for COVID-19 and disease course might be more severe in them. In this study, we wished to estimate the risk of SARS-CoV-2 infection and COVID-19 related death in IC individuals compared to healthy ones and the effectiveness of the BNT162b2 vaccine by reassessing HUN-VE 3 data. Patients and methods: Among the 8,087,988 individuals undergoing follow-up from the onset of the pandemic in the HUN-VE 3 cohort, we selected all the 263,116 patients with a diagnosis corresponding with IC and 6,128,518 controls from the second wave, before vaccinations started. The IC state was defined as two occurrences of corresponding ICD-10 codes in outpatient or inpatient claims data since 1 January, 2013. The control group included patients without chronic diseases. The data about vaccination, SARS-CoV-2 infection and COVID-19 related death were obtained from the National Public Health Center (NPHC) during the Delta wave. Cases of SARS-CoV-2 infection were reported on a daily basis using a centralized system via the National Public Health Center (NPHC). Results: Out of the 263,116 IC patients 12,055 patients (4.58%) and out of the 6,128,518 healthy controls 202,163 (3.30%) acquired SARS-CoV-2 infection. Altogether 436 IC patients and 2141 healthy controls died in relation to COVID-19. The crude incidence rate ratio (IRR) of SARS-CoV-2 infection was 1.40 (95%CI: 1.37-1.42) comparing IC patients to healthy controls. The crude mortality rate ratio was 4.75 (95%CI: 4.28-5.27). With respect to SARS-CoV-2 infection, interestingly, the BNT162b2 vaccine was more effective in IC patients compared to controls. Primary vaccine effectiveness (VE) was higher in IC patients compared to controls and the booster restored VE after waning. VE regarding COVID-19 related death was less in IC patients compared to healthy individuals. Booster vaccination increased VE against COVID-19-related death in both IC patients and healthy controls. Conclusion: There is increased risk of SARS-CoV-2 infection and COVID-19 related mortality in IC patient. Moreover, booster vaccination using BNT162b2 might restore impaired VE in these individuals.
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COVID-19 , Vacunas , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/prevención & control , Vacuna BNT162RESUMEN
Introduction: The Renin-Angiotensin-Aldosterone system (RAAS) has been implicated in the regulation of the cardiovascular system and linked to rheumatoid arthritis (RA). Little information has become available on the effects of Janus kinase (JAK) inhibition on RAAS. Here we studied the effects of 12-month tofacitinib treatment on angiotensin converting enzyme (ACE), ACE2 production and ACE/ACE2 ratios in RA along with numerous other biomarkers. Patients and methods: Thirty RA patients were treated with tofacitinib in this prospective study. Serum ACE concentrations were assessed by ELISA. ACE2 activity was determined by a specific quenched fluorescent substrate. ACE/ACE2 ratios were calculated. We also determined common carotid intima-media thickness (ccIMT), brachial artery flow-mediated vasodilation (FMD) and carotid-femoral pulse-wave velocity (cfPWV) by ultrasound. C-reactive protein (CRP), rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) were also determined. All measurements were performed at baseline, as well as after 6 and 12 months of tofacitinib treatment. Results: After the dropout of 4 patients, 26 completed the study. Tofacitinib treatment increased ACE levels after 6 and 12 months, while ACE2 activity only transiently increased at 6 months. The ACE/ACE2 ratio increased after 1 year of therapy (p < 0.05). Logistic regression analyses identified correlations between ACE, ACE2 or ACE/ACE2 ratios and RF at various time points. Baseline disease duration also correlated with erythrocyte sedimentation rate (ESR) (p < 0.05). One-year changes of ACE or ACE2 were determined by tofacitinib treatment plus ACPA or RF, respectively (p < 0.05). Conclusion: JAK inhibition increases serum ACE and ACE/ACE2 ratio in RA. Baseline inflammation (ESR), disease duration and ACPA, as well as RF levels at various time points can be coupled to the regulation of ACE/ACE2 ratio. The effect of tofacitinib on RAAS provides a plausible explanation for the cardiovascular effects of JAK inhibition in RA.
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OBJECTIVES: Cardiovascular (CV) morbidity and mortality, and perpetuated synovial angiogenesis have been associated with RA. In our study we evaluated angiogenic factors in relation to vascular inflammation and function, and clinical markers in RA patients undergoing 1-year tofacitinib therapy. METHODS: Thirty RA patients treated with either 5 mg or 10 mg twice daily tofacitinib were included in a 12-month follow-up study. Eventually, 26 patients completed the study and were included in data analysis. Levels of various angiogenic cytokines (TNF-α, IL-6), growth factors [VEGF, basic fibroblast (bFGF), epidermal (EGF), placental (PlGF)], cathepsin K (CathK), CXC chemokine ligand 8 (CXCL8), galectin-3 (Gal-3) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) were determined at baseline, and at 6 and 12 months after initiating tofacitinib treatment. In order to assess flow-mediated vasodilation, common carotid intima-media thickness (ccIMT) and carotid-femoral pulse-wave velocity, ultrasonography was performed. Synovial and aortic inflammation was also assessed by 18F-fluorodeoxyglucose-PET/CT. RESULTS: One-year tofacitinib therapy significantly decreased IL-6, VEGF, bFGF, EGF, PlGF and CathK, while it increased Gal-3 production (P < 0.05). bFGF, PlGF and NT-proBNP levels were higher, while platelet-endothelial cell adhesion molecule 1 (PECAM-1) levels were lower in RF-seropositive patients (P < 0.05). TNF-α, bFGF and PlGF correlated with post-treatment synovial inflammation, while aortic inflammation was rather dependent on IL-6 and PECAM-1 as determined by PET/CT (P < 0.05). In the correlation analyses, NT-proBNP, CXCL8 and Cath variables correlated with ccIMT (P < 0.05). CONCLUSIONS: Decreasing production of bFGF, PlGF or IL-6 by 1-year tofacitinib therapy potentially inhibits synovial and aortic inflammation. Although NT-proBNP, CXCL8 and CathK were associated with ccIMT, their role in RA-associated atherosclerosis needs to be further evaluated.
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Artritis Reumatoide , Grosor Intima-Media Carotídeo , Embarazo , Humanos , Femenino , Factor de Necrosis Tumoral alfa , Estudios de Seguimiento , Interleucina-6 , Factor de Crecimiento Epidérmico/uso terapéutico , Molécula-1 de Adhesión Celular Endotelial de Plaqueta , Tomografía Computarizada por Tomografía de Emisión de Positrones , Factor A de Crecimiento Endotelial Vascular , Placenta/metabolismo , Artritis Reumatoide/complicaciones , Inflamación/complicaciones , BiomarcadoresRESUMEN
Myalgia, myopathy and myositis are the most important types of muscle impairment in immune-mediated inflammatory arthropathies and connective tissue diseases. Multiple pathogenetic and histological changes occur in the striated muscles of these patients. Clinically, the most important muscle involvement is the one that causes complaints to the patients. In everyday practice, insidious symptoms present a serious problem for the clinician; in many cases, it is difficult to decide when and how to treat the muscle symptoms that are often present only subclinically. In this work, authors review the international literature on the types of muscle problems in autoimmune diseases. In scleroderma histopathological picture of muscle shows a very heterogeneous picture, necrosis and atrophy are common. In rheumatoid arthritis and systemic lupus erythematosus, myopathy is a much less defined concept, further studies are needed to describe it. According to our view, overlap myositis should be recognized as a separate entity, preferably with distinct histological and serological characteristics. More studies are needed to describe muscle impairment in autoimmune diseases which may help to explore this topic more in depth and be of clinical use.
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Artritis Reumatoide , Enfermedades Autoinmunes , Enfermedades del Tejido Conjuntivo , Lupus Eritematoso Sistémico , Enfermedades Musculares , Miositis , Esclerodermia Sistémica , Humanos , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades Autoinmunes/complicaciones , Enfermedades Musculares/etiología , Lupus Eritematoso Sistémico/complicaciones , Artritis Reumatoide/complicaciones , Músculo Esquelético/patología , Esclerodermia Sistémica/complicacionesRESUMEN
OBJECTIVES: In this prospective study, SARS-CoV-2 spike protein specific total immunoglobulin (Ig) levels were analyzed before and after BNT162 b2 mRNA booster vaccination in individuals previously administered with two doses of BBIBP-CorV vaccine in comparison to immunized participants with three doses of BNT162 b2 vaccination. METHODS: Sixty-one Caucasian volunteers (39 females, 22 males) vaccinated by BBIBP-CorV were included (mean age: 63.9 years). Sixty-one patients (41 females, 20 males) as controls were vaccinated with BNT162b2 (mean age: 59.9 years). Both groups received the third booster BNT162b2 vaccine. Total anti-SARS-CoV-2 S1-RBD Ig levels were measured by an immunoassay (Roche Diagnostics) and their calculated ratios after/before booster dose were compared between the two groups. RESULTS: At baseline, significantly lower anti-SARS-CoV-2 S1-RBD total antibody levels were determined after initial immunization by two doses of inactivated BBIBP-CorV compared to BNT62b2 mRNA vaccine (p < 0.001). After BNT162b2 boosters, similarly high total Ig levels were detected in both the heterologous (27,195 [15,604-42,754] BAU/mL, p < 0.001) and the homologous booster cohort (24,492 [13,779-42,671] BAU/mL, p < 0.001) compared to baseline. Hence, the ratio of after/before total Ig levels was significantly higher with heterologous vs homologous immunization (p < 0.001). CONCLUSION: To address the concept that basic BBIBP-CorV vaccination is not as effective as BNT162b, we analyzed the effect of heterologous vaccination with BNT162b2. Our results suggest that BNT162b2 can successfully boost the effects of two-dose BBIBP-CorV vaccination.
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Limited data are available on the predisposing factors to fractures and falls of patients with psoriatic arthritis (PsA). Our study intended to explore the differences between PsA patients and controls, concerning bone mineral density (BMD), the 10-year fracture risk, the number of prevalent fractures, the frequency of falls and to investigate the association of the same factors with PsA disease characteristics within the PsA group. Medical reports of 61 PsA patients and 69 consecutive, age-matched controls were analyzed, physical examination and bone mineral density (BMD, and T-score) were performed, and the 10-year fracture risk was calculated. The results were subjected to statistical analysis. Femoral neck BMD, as well as vertebral and femoral neck T-scores were lower, the odds ratio (OR) for low BMD and the 10-year risk of hip fracture was higher (p = 0.0029; 0.0002, p < 0.0001, OR = 21,9, p = 0.014) in the PsA group. The PsA patients were more predisposed to prevalent fractures, including peripheral fractures, and vertebral fractures as well as falls (OR 3.42; 2.26; 13.33; 3.95, respectively), compared to controls. Within the PsA group (beyond the age) scalp psoriasis and late-onset psoriasis, were significantly associated with a greater number of prevalent fractures (p = 0.0049; 0.029), while the number of falls per year correlated with late-onset psoriasis and the flexural psoriasis (p = 0.007; 0.023). Our results suggest that PsA is an independent risk factor for reduced bone density and falls hence to related bone fractures. Patients with late-onset psoriasis are more likely to suffer falls and related fractures, especially if their disease is characterized by the involvement of the hairy scalp and body folds.
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Artritis Psoriásica , Fracturas Óseas , Osteoporosis , Psoriasis , Humanos , Artritis Psoriásica/complicaciones , Artritis Psoriásica/epidemiología , Osteoporosis/epidemiología , Osteoporosis/complicaciones , Fracturas Óseas/epidemiología , Fracturas Óseas/etiología , Densidad Ósea , Psoriasis/complicaciones , Factores de RiesgoRESUMEN
OBJECTIVES: The early trajectory of skin fibrosis provides insights into the disease course of systemic sclerosis (SSc) including mortality; however, little is known about late skin fibrosis. The aims of our study were to ascertain the prevalence and characteristics of late skin fibrosis in SSc. METHODS: We developed and tested three conceptual scenarios of late (>5 years after first non-RP feature) skin fibrosis including new worsening of skin disease, and failure to improve after worsening within 5-year window. We defined skin worsening as change in modified Rodnan skin score (mRSS) ≥5 units or ≥25%. Using strict inclusion criteria including complete mRSS, we identified 1,043 (out of 19 115) patients within the EUSTAR database for our analysis. We further restricted analysis within 887 (out of 1043) patients who had lcSSc or dcSSc at baseline. RESULTS: One-fifth of patients among the whole cohort (n = 208/1043, 19.9%) experienced mRSS worsening, including in patients with lcSSc or dcSSc at baseline (n = 193/887, 21.8%). This was largely due to new skin worsening after the 5-year window or failure to improve with worsening within the 5-year window. Patients with lower baseline mRSS and lcSSc were more likely to develop late skin fibrosis. Anti-Scl-70 was associated with progression from baseline lcSSc to dcSSc, and anticentromere was protective. CONCLUSIONS: Late skin fibrosis is not uncommon in SSc. We have identified different patterns relevant to clinical practice and trial design. Late skin fibrosis is a neglected manifestation of SSc and warrants further investigation including to determine clinical outcomes and optimal therapeutic strategy.
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Esclerodermia Difusa , Esclerodermia Sistémica , Enfermedades de la Piel , Humanos , Esclerodermia Difusa/complicaciones , Esclerodermia Difusa/patología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/epidemiología , Esclerodermia Sistémica/patología , Fibrosis , Enfermedades de la Piel/patología , Piel/patologíaRESUMEN
BACKGROUND: The phase 2b Riociguat Safety and Efficacy in Patients with Diffuse Cutaneous Systemic Sclerosis (RISE-SSc) trial investigated riociguat versus placebo in early diffuse cutaneous systemic sclerosis. The long-term extension evaluated safety and exploratory treatment effects for an additional year. METHODS: Patients were enrolled to RISE-SSc between Jan 15, 2015, and Dec 8, 2016. Those who completed the 52-week, randomised, parallel-group, placebo-controlled, double-blind phase were eligible for the long-term extension. Patients originally assigned to riociguat continued therapy (riociguat-riociguat group). Those originally assigned to placebo were switched to riociguat (placebo-riociguat group), adjusted up to 2·5 mg three times daily in a 10-week, double-blind dose-adjustment phase, followed by an open-label phase. Statistical analyses were descriptive. Safety including adverse events and serious adverse events was assessed in the long-term safety analysis set (all patients randomly assigned and treated with study medication in the double-blind phase who continued study medication in the long-term extension). The RISE-SSc trial is registered with ClinicalTrials.gov, NCT02283762. FINDINGS: In total, 87 (72%) of 121 patients in the main RISE-SSc study entered the long-term extension (riociguat-riociguat, n=42; placebo-riociguat, n=45). 65 (75%) of 87 patients were women, 22 (25%) were men, and 62 (71%) were White. Overall, 82 (94%) of 87 patients in the long-term extension had an adverse event; most (66 [76%] of 87) were of mild to moderate severity, with no increase in pulmonary-related serious adverse events in patients with interstitial lung disease. INTERPRETATION: No new safety signals were observed with long-term riociguat in patients with early diffuse cutaneous systemic sclerosis. Study limitations include the absence of a comparator group in this open-label extension study. FUNDING: Bayer and Merck Sharp & Dohme.
Asunto(s)
Pirimidinas , Esclerodermia Difusa , Femenino , Humanos , Masculino , Pacientes , Pirazoles/efectos adversos , Proyectos de Investigación , Esclerodermia Difusa/tratamiento farmacológicoRESUMEN
Introduction: Rheumatoid arthritis (RA) has been associated with changes in lipid, arginine and NO metabolism with increased cardiovascular (CV) risk. The aim of this study is to evaluate the effect of tofacitinib, a Janus kinase (JAK) inhibitor, on arginine and methionine metabolism in correlation with inflammation, functional and pathological vascular changes during one-year treatment of patients with RA. Materials and methods: Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) levels. We assessed brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) by ultrasound at baseline and after 6 and 12 months. We also determined plasma L-arginine, L-citrulline, L-ornithine, inducible nitric oxide synthase (iNOS), asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-N-monomethyl-arginine (L-NMMA), cysteine, homocysteine, and methionine levels at these time points. Results: Twenty-six patients (13 on each arm) completed the study. CRP, ESR and DAS28 decreased significantly during one-year treatment with tofacitinib. Arginine and ADMA showed a negative univariate correlation with CRP but not with FMD, PWV or IMT. Tofacitinib at 10 mg bid significantly increased L-arginine, L-ornithine, iNOS and methionine levels after 12 months. ADMA and SDMA levels did not change in our study. Methionine showed negative correlation with FMD at baseline and positive correlation with PWV after 12 months. No change was observed in FMD and PWV but a significant increase was measured in IMT at 6 and 12 months. Multivariate analysis indicated variable correlations of L-arginine, L-citrulline, ADMA, L-NMMA, homocysteine and methionine with DAS28, CRP, ESR and RF but not with anti-CCP after one-year treatment. With respect to vascular pathophysiology, only PWV and methionine correlated with each other. Conclusion: One-year tofacitinib treatment suppressed systemic inflammation and improved functional status in RA. FMD, PWV have not been affected by one-year tofacitinib treatment., while IMT increased further despite treatment. Increased arginine and methionine might contribute to the anti-inflammatory effects of tofacitinib. Increased arginine availability with no changing ADMA may protect FMD and PWV from deterioration. The increase of IMT in the anti-inflammatory environment cannot be explained by arginine or methionine metabolism in this study.
RESUMEN
BACKGROUND/AIM: Despite remission or low disease activity non-inflammatory complaints like exhaustion, fatigue, and pain persist in a significant proportion of patients with systemic lupus erythematosus (SLE) and have a considerable impact on health-related quality of life. This study evaluated the effects of balneotherapy on non-inflammatory complaints, quality of life, and work productivity of patients with SLE. PATIENTS AND METHODS: SLE patients in remission/low disease activity in three rheumatology centers were included in this randomized, controlled, follow-up study. In addition to the standard of care (SOC), sixteen out of the thirty patients with SLE received balneotherapy (3-week period, 15 times, for 30 min) and fourteen patients received the SOC only. Pre-validated survey instruments including Lupus Quality of Life (LupusQoL), Short-Form Health Survey (SF-36), Work Productivity, and Activity Impairment-Lupus (WPAI-Lupus) questionnaires were used. RESULTS: Based on the SF-36 questionnaires, several subdomains of physical condition improved significantly after the course; the improvement remained durable (p=0.019). General health improved significantly by the end of the course (p=0.001). According to the LupusQoL questionnaire, physical health and pain showed a tendency of improvement shortly after the spa treatment. Changes in the WPAI-lupus questionnaire indicated a short-term improvement of the daily activity by the end of the observation period. No adverse reactions were observed. CONCLUSION: Thermal water therapy may be an effective, well-tolerated, complementary non-pharmacological approach for non-inflammatory complaints of patients with SLE. Physical condition improved in the short-term, whereas fatigue worsened despite treatment.