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Background and Objective: Axial spondyloarthritis (axSpA) includes thoracic manifestations and changes in respiratory function that require a comprehensive understanding for effective treatment. This review aims to investigate these manifestations and evaluate the role of ultrasound in detecting diaphragmatic changes to provide insights for improved diagnosis and treatment strategies in axSpA patients. Methods: A systematic search was conducted in Index Medicus and Scopus from 2003 to 2023. Inclusion criteria included primary and secondary publications, with a focus on high-quality evidence such as randomised controlled trials and systematic reviews with or without meta-analysis. Keywords spondyloarthritis, respiratory, chest, thoracic, diaphragm and ultrasound were used in the search. A total of 22 articles were identified after duplicates, and inadequate papers were removed. Key Content and Findings: The review included the prevalence, classification and extra-articular manifestations of axSpA, highlighting the impact on respiratory function. Thoracic manifestations and the potential impact of pharmacological interventions were detailed, and various conditions affecting respiratory dynamics were discussed. In addition, the utility of ultrasonography in assessing diaphragmatic function was explained and the techniques, parameters and measurements used to assess diaphragmatic movement, muscle thickness and respiratory mobility were described. The results illustrate the changes in diaphragmatic function in axSpA patients and their correlation with disease activity. Conclusions: This narrative review highlights the intricate relationship between axSpA and respiratory manifestations and emphasises the significant impact on thoracic function and diaphragmatic dynamics. The utility of ultrasound in assessing diaphragmatic function offers a promising avenue for objective evaluation that provides insight into disease activity and potential therapeutic responses. This review emphasises the critical role of early diagnosis and vigilant monitoring, and advocates a multidisciplinary approach that integrates non-pharmacological interventions, particularly tailored physical activity, to maintain and improve respiratory function in axSpA patients. Increased research initiatives and awareness of pulmonary complications in axSpA are essential to optimise medical care and improve treatment outcomes in this patient group.
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Spondyloarthritis (SpA) is a group of inflammatory disorders, including axial SpA (axSpA), characterized by inflammation in the spine and sacroiliac joints. Healthcare professionals have a crucial role in diagnosing and managing axSpA. Assessing their knowledge, perceptions, and practices is essential to enhance patient care. The objective of this study is to evaluate these factors by conducting an online survey. This online survey was performed using SurveyMonkey.com to assess healthcare professionals' knowledge, perceptions, and practices related to axSpA diagnosis, management, and monitoring. The questionnaire included questions about definitions, management strategies, monitoring approaches, treatment options, and barriers to care. Convenience sampling was used, and the data were analyzed descriptively by Microsoft Excel. One hundred sixty-four healthcare professionals participated; most respondents were rheumatologists from various geographic locations (27 countries). Most participants were familiar with axSpA definitions and diagnostic criteria, demonstrating high expertise. Variations were seen in follow-up intervals and diagnostic preferences, reflecting clinical heterogeneity. Seventy-two (43.9%) individuals had a multidisciplinary team, frequently including rheumatologists, physiotherapists, and radiologists. Of the participants, 73 (44.5%) had online/telephone follow-up sessions. The pharmacological and non-pharmacological treatment approaches varied, pointing to the importance of personalized care. Glucocorticoid use varied among countries. Recognizing inflammatory back pain, interpreting radiographs, and diagnosing early was essential to medical education. This study provides beneficial data on healthcare professionals' knowledge, perceptions, and practices regarding axSpA. While diagnostic familiarity and multidisciplinary approach are positives, there is a potential to standardize management, improve telemedicine services, remove barriers to physical activity, and optimize treatment options.
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Espondiloartritis Axial , Conocimientos, Actitudes y Práctica en Salud , Humanos , Estudios Transversales , Masculino , Femenino , Espondiloartritis Axial/diagnóstico , Espondiloartritis Axial/terapia , Adulto , Encuestas y Cuestionarios , Persona de Mediana Edad , Reumatólogos , Personal de Salud , Pautas de la Práctica en Medicina , Actitud del Personal de Salud , Encuestas de Atención de la SaludRESUMEN
BACKGROUND: Functioning is considered a third indicator of health and a key outcome in rehabilitation. A universal practical tool for collecting functioning information is essential. This tool would be ideally based on the International Classification of Functioning, Disability and Health. AIM: To report the results of the development of country/language-specific versions of an ICF-based clinical tool in six European countries. DESIGN: Consensus process. SETTING: Expert conferences. POPULATION: Multi-professional group of rehabilitation professionals in six European countries. METHODS: 1) Developed an initial proposal by translating the published English-language version of the simple descriptions into the targeted language; 2) conducted a multi-stage consensus conference to finalize the descriptions; 3) employed a three-stage multi-professional expert panel translation back to English. The consensus conference model was modified for geographically large countries. RESULTS: Croatian, Flemish/Dutch, Greek, Polish, and Turkish versions were produced. CONCLUSIONS: The creation of the country/language-specific simple descriptions is a significant part of the "system-wide implementation of the ICF" initiative that will pave the way for the implementation of the ICF in national health systems. CLINICAL REHABILITATION IMPACT: The practical ICF-based clinical tool with country/language specific versions for standardized reporting of functioning will serve as a means of integrating functioning information in national health systems and additionally for monitoring the effects of rehabilitation interventions.
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Evaluación de la Discapacidad , Personas con Discapacidad , Humanos , Personas con Discapacidad/rehabilitación , Europa (Continente) , Actividades Cotidianas , Lenguaje , Clasificación Internacional del Funcionamiento, de la Discapacidad y de la SaludRESUMEN
OBJECTIVE: We aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations. METHODS: A working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings. RESULTS: The evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain. CONCLUSION: Evidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations.
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Antirreumáticos , Artritis Psoriásica , Inhibidores de las Cinasas Janus , Psoriasis , Humanos , Artritis Psoriásica/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Psoriasis/tratamiento farmacológico , Metotrexato/uso terapéutico , Interleucina-12 , Inhibidores de las Cinasas Janus/uso terapéuticoRESUMEN
The aim was to assess the prevalence of chronic multimorbidity in patients with chronic low back pain or other chronic back disorders (BD). We analyzed data from the population-based cross-sectional European Health Interview Survey (EHIS) performed in the Republic of Croatia 2014-2015 by the Croatian Institute of Public Health. Outcome was the point-prevalence of chronic multimorbidity defined as having ≥2 chronic illnesses out of 14 contained in the EHIS questionnaire, after adjustment for ten sociodemographic, anthropometric and lifestyle confounders. Amoung fourteen targeted illnesses were asthma, allergies, hypertension, urinary incontinence, kidney diseases, coronary heart disease or angina pectoris, neck disorder, arthrosis, chronic obstructive pulmonary disease, diabetes mellitus, myocardial infarction, stroke, depression, and the common category "other". We analyzed data on 268 participants with BD and 511 without it. Participants with BD had a significantly higher relative risk of any chronic multimorbidity (RRadj=2.12; 95% CI 1.55, 2.99; p<0.001), as well as of non-musculoskeletal chronic multimorbidity (RRadj=2.29; 95% CI 1.70, 3.08; p=0.001) than participants without BD. All chronic comorbidities except for asthma and liver cirrhosis were significantly more prevalent in participants with BD than in participants without BD. In the population with BD, the participants with multimorbidity had three to four times higher odds for unfavorable self-reported health outcomes than the participants with no comorbid conditions, whereas the existence of only one comorbidity was not significantly associated with a worse outcome compared to the population with no comorbidities. In conclusion, the population suffering from BD has a higher prevalence of chronic multimorbidity than the population without BD and this multimorbidity is associated with unfavorable health outcomes.
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Asma , Dolor de la Región Lumbar , Humanos , Multimorbilidad , Croacia/epidemiología , Dolor de la Región Lumbar/epidemiología , Estudios Transversales , Enfermedad Crónica , Prevalencia , Asma/epidemiologíaRESUMEN
OBJECTIVE: To evaluate the 12-month efficacy and safety profile of adalimumab and etanercept in patients with ankylosing spondylitis (AS) and total spinal ankylosis (TSA). TYPE OF STUDY DESIGN: Case-series follow-up study. DESIGN: Twenty-eight patients (26 men and 2 women) with active AS (BASDAI > 4) and TSA were treated as follows: 19 patients receiving adalimumab and 9 patients receiving etanercept. Twelve-month data related to the efficacy and safety of these two TNF-alpha inhibitors were evaluated. The primary endpoint was ASAS 20 (the ASsessment in AS International Working Group criteria for 20% improvement) at weeks 12 and 52. Other measures that were evaluated were function (BASFI), disease activity (BASDAI), patient's and physician's global disease assessment on visual analogue scale (VAS) and C-reactive protein. RESULTS: In both adalimumab and etanercept groups, there was a significant improvement in all observed variables (baseline compared to weeks 12 and 52). This improvement was sustained for the whole follow-up period. In the adalimumab group, at week 12, ASAS 20 was achieved in 18/19 patients and at week 52 in 17/19 patients. In the etanercept group, at week 12 ASAS 20 was achieved in all patients and at week 52 in 6/9 patients. CONCLUSION: In patients with active AS and TSA, adalimumab and etanercept treatment showed significant improvement in function and disease activity. No serious side effects or adverse effects were observed in our cohort. Key Points ⢠TNF-alpha inhibitors can be effective treatment options for patients with AS and having total spinal ankylosis. ⢠Patients with advanced AS should not be disregarded as good candidates for treatment with biologic disease-modifying antirheumatic drugs.
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Adalimumab , Antirreumáticos , Etanercept , Espondilitis Anquilosante , Adalimumab/uso terapéutico , Antirreumáticos/uso terapéutico , Croacia , Etanercept/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Espondilitis Anquilosante/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Fibrodysplasia ossificans progressiva (FOP) is an extremely rare disease in which bone tissue forms in extraskeletal sites, which is known as heterotopic ossification (HO). Extracellular vesicles (EVs) are small phospholipid-enclosed particles released by various cells which have an emerging, but not completely understood role in various (patho)physiological processes. In order to further study the pathophysiology of FOP we conducted a small observational study comparing the proteomic profiles of EV cargo, derived from pooled plasma of four patient groups: FOP patient (N = 1) during active disease phase (flare-up), FOP patients during remission (N = 2), patients after long bone fracture (N = 20) and healthy controls (N = 10). After isolation of EVs - their protein cargo was determined using liquid chromatography / mass spectrometry, after which a functional gene enrichment analysis was performed. Our results show a sizeable difference of the proteomics profiles in which EVs from the bone fracture group show significant activity of integrin interactions, Wnt, VEGF, IGF-1 and PDGF pathways; conversely, FOP patients' EVs indicate that HO occurs via processes of innate immunity and the Ephrin B signaling pathway. We hypothesize that the Ephrin B signaling (expressed in EVs) contributes to HO by aiding in mesenchymal stem cell recruitment and osteogenic differentiation, as well as by contributing to the inflammatory response, including macrophage chemotaxis and activation. This is, to our knowledge, the first published analysis of EV protein cargo in FOP.
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OBJECTIVE: To describe the development of an Environmental contextual factors (EF) Item Set (EFIS) accompanying the disease specific Assessment of SpondyloArthritis international Society Health Index (ASAS HI). METHOD: First, a candidate item pool was developed by linking items from existing questionnaires to 13 EF previously selected for the International Classification of Functioning, Disability and Health (ICF) /ASAS Core Set. Second, using data from two international surveys, which contained the EF item pool as well as the items from the ASAS HI, the number of EF items was reduced based on the correlation between the item and the ASAS HI sum score combined with expert opinion. Third, the final English EFIS was translated into 15 languages and cross-culturally validated. RESULTS: The initial item pool contained 53 EF addressing four ICF EF chapters: products and technology (e1), support and relationship (e3), attitudes (e4) and health services (e5). Based on 1754 responses of axial spondyloarthritis patients in an international survey, 44 of 53 initial items were removed based on low correlations to the ASAS HI or redundancy combined with expert opinion. Nine items of the initial item pool (range correlation 0.21-0.49) form the final EFIS. The EFIS was translated into 15 languages and field tested in 24 countries. CONCLUSIONS: An EFIS is available complementing the ASAS HI and helps to interpret the ASAS HI results by gaining an understanding of the interaction between a health condition and contextual factors. The EFIS emphasizes the importance of support and relationships, as well as attitudes of the patient and health services in relation to self-reported health.
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Espondiloartritis Axial , Espondiloartritis , Espondilitis Anquilosante , Humanos , Calidad de Vida , Índice de Severidad de la EnfermedadRESUMEN
The aim of the study was testing the hypothesis that body height has a moderating effect on the association of weight and chronic low back pain (LBP) induced disability, and that this moderating effect is different in women and men. We performed a nested cross-sectional analysis using data collected at baseline in a prospective cohort study conducted in 2008-2009 at a special hospital for medical rehabilitation in Croatia. The outcome was the Roland-Morris Disability Questionnaire (RMDQ) score. The independent variable was body weight. The focal moderators were body height and sex. The moderation analysis was adjusted for seven sociodemographic and clinical covariates. We analyzed data on 72 patients with a median (interquartile range) age of 50 (43-55) years, 36 (50%) of whom were women, treated for nonspecific, chronic LBP. The interaction of sex, body weight and height was a significant predictor of the RMDQ score after adjustments for all covariates (increase of R2=0.13; p=0.001; false discovery rate <5%). In both sexes, the correlation between body weight and the RMDQ score was significantly moderated by body height but in opposite ways. In conclusion, the effects of body weight on physical disability are moderated by body height, but this moderation effect differs between women and men.
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Dolor de la Región Lumbar , Masculino , Humanos , Femenino , Persona de Mediana Edad , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/rehabilitación , Estudios Prospectivos , Estudios Transversales , Estatura , Evaluación de la Discapacidad , Peso Corporal , Encuestas y CuestionariosRESUMEN
The hypothesis of the study was that polymorphisms in promoter regions -238 and -308 of TNF-α could be associated with different clinical outcomes in inflammatory bowel diseases (IBD) and immune-mediated rheumatic diseases (IMRD). The aim was to examine the possible association of both polymorphisms with concentration of C-reactive protein (CRP) and fecal calprotectin (fCAL), onset of the remission and development of the ADA in patients on therapy with anti-TNF inhibitors. The prospective study was done in patients with IBD and IMRD on infliximab (IFX) or adalimumab (ADM). Patients were genotyped for TNF-α -238 and -308 polymorphisms. The concentration of CRP, fCAL, IFX or ADM and antibodies to drugs were measured according to manufacturer's instructions and followed-up for 6 or 12 months. Out of all patients (N = 112), number of patients in remission did not differ according to genotypes (for IBD patients P = 0.509 vs 0.223; for IMRD patients P = 0.541 vs 0.132 for TNF-α -238 and -308, respectively). Initial CRP concentration was higher in IBD patients with TNF-α -308 GG than GA/AA genotypes in patients who failed to achieve remission [11.8 (4.4-39.6) vs 3.1 (1.5-6.5), P = 0.033]. In IBD patients with remission, fCAL concentration after at least 6 months of therapy was higher in TNF-α-308 GG than in GA genotype [52 (25-552) vs 20 (20-20) µg/g, P = 0.041]. Our results showed the association of TNF-α -308 GG genotype with a higher concentration of CRP and fecal calprotectin in patients with inflammatory bowel diseases on IFX or ADM therapy. Clinical remission and development of antibodies to anti-TNF drugs were not associated with TNF-α -238 and -308 polymorphisms.
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Adalimumab/administración & dosificación , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/administración & dosificación , Enfermedades Reumáticas/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/administración & dosificación , Adulto , Anciano , Biomarcadores/análisis , Proteína C-Reactiva/análisis , Femenino , Humanos , Complejo de Antígeno L1 de Leucocito/análisis , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Inducción de Remisión , Factor de Necrosis Tumoral alfaRESUMEN
Fibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable course characterized by occasional flare-ups of heterotopic ossification (HO) in soft tissues that are followed by swelling, stiffness, pain and warmth. Here, we report for the first time a case of a 45-year-old female patient with known FOP recovering from COVID-19 with disease progression potentially linked with the viral illness. In December 2020 the patient contracted a mild form of COVID-19 infection without need for hospital admission. Since January 2021, the patient felt unwell, with occasional abdominal pain which progressively intensified. In March 2021 she presented with new onset of HO, complaining of pain, swelling and thickening sensation in the lower abdomen and left part of the neck. Computerized tomography (CT) and cytokine analysis were performed. CT scan revealed new heterotopic bone formation in multiple soft tissue areas of the neck indicating clear radiological progression. Radiotherapy, which has proven to be an efficient tool to control HO in this patient, was not able to halt HO formation after COVID-19 infection. Cytokine analysis of a plasma sample obtained during a flare-up after COVID-19 infection showed a significantly elevated pro-inflammatory cytokines compared to a flare-up panel prior to infection. Of the 23 analyzed levels of cytokines, a staggering number of 21 were above normal levels. This case is the first confirmation of uncontrolled post-COVID-19 effects in a FOP patient, which manifested with flare-ups followed by progressive HO, possibly caused by a thus far, never described form of post-COVID syndrome.
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COVID-19/inmunología , Citocinas/sangre , Mediadores de Inflamación/sangre , Miositis Osificante/inmunología , Osificación Heterotópica/inmunología , SARS-CoV-2/inmunología , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/virología , Femenino , Interacciones Huésped-Patógeno , Humanos , Persona de Mediana Edad , Miositis Osificante/diagnóstico , Miositis Osificante/virología , Osificación Heterotópica/diagnóstico , Osificación Heterotópica/virología , SARS-CoV-2/patogenicidad , Brote de los SíntomasRESUMEN
Interleukin-6 receptor antagonist tocilizumab is a biologic drug used for treating patients with active rheumatoid arthritis (RA) who failed to respond to synthetic or other biologic disease-modifying antirheumatic drugs or where they were contraindicated. Interleukin-6 receptor blockade results in a decrease of disease activity but has some potential adverse effects, the most common being infections. We present a case of a 75-year-old female patient with long-lasting RA, several comorbidities and multiple prior therapies, who developed back pain and general malaise during tocilizumab intravenous treatment. The laboratory findings were typical of toxemia, and the imaging findings revealed large psoas muscle abscess. Surgical and antibiotic treatment was performed with a good outcome. To our knowledge, this has been the first case of a psoas abscess in a patient with RA treated with tocilizumab described in the literature so far. We also present a review of the literature regarding infection, and particularly abscess formation in patients treated with biological disease-modifying antirheumatic drugs, tocilizumab included.
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Anticuerpos Monoclonales Humanizados/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Absceso del Psoas/diagnóstico por imagen , Receptores de Interleucina-6/antagonistas & inhibidores , Administración Intravenosa , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Vértebras Cervicales/diagnóstico por imagen , Femenino , Humanos , Inyecciones Intravenosas , Imagen por Resonancia Magnética , Infecciones Oportunistas/inducido químicamente , Psoriasis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Vitamin D is beneficial in patients with immune-mediated rheumatic diseases as it has been shown that it lowers the incidence risk and the level of inflammation. To examine the association between clinical outcomes and initial 25-hydroxyvitamin D [25(OH)D] concentrations in patients with the immune-mediated rheumatic diseases treated with infliximab for 9 months. This study was performed in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) treated with infliximab for at least 38 weeks. Disease activity was assessed using Disease Activity Score (DAS28) for RA and PsA and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS, while the global assessment was performed using the Visual Analogue Scale (VAS). Patients were divided into 2 groups according to 25(OH)D concentration which was classified as deficient or non-deficient (below and above 50 nmol/L, respectively). Concentrations of infliximab (IFX) and C-reactive protein (CRP) were measured according to the manufacturer's instructions.This study was performed in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) treated with infliximab for at least 38 weeks. Disease activity was assessed using Disease Activity Score (DAS28) for RA and PsA and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS, while the global assessment was performed using the Visual Analogue Scale (VAS). Patients were divided into 2 groups according to 25(OH)D concentration which was classified as deficient or non-deficient (below and above 50 nmol/L, respectively). Concentrations of infliximab (IFX) and C-reactive protein (CRP) were measured according to the manufacturer's instructions. The study included 23 patients (14 with RA, 6 with AS and 3 with PsA), median age 54 years, 15 females. Vitamin D deficient and non-deficient groups had median initial concentrations of 38 and 61 nmol/L, respectively. DAS28 and pain on VAS calculated at the 2nd and 38th week showed a statistically significant decrease only in RA and PsA patients with vitamin D deficiency (P = 0.02 and 0.06, respectively). Lower initial concentration of 25(OH)D in patients treated with infliximab was associated with better improvement of clinical measures (DAS28 and VAS) of disease after 9 months of therapy.
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Artritis Psoriásica/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Deficiencia de Vitamina D/complicaciones , Vitamina D/análogos & derivados , Adulto , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/sangre , Artritis Reumatoide/tratamiento farmacológico , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Femenino , Humanos , Infliximab/uso terapéutico , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/tratamiento farmacológico , Vitamina D/sangre , Deficiencia de Vitamina D/sangreRESUMEN
Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary disease caused by a mutation in the intracellular domain of the activin A receptor type I and is characterized by episodes (flare-ups) of progressive heterotopic endochondral ossification (HO) in the soft tissues. The mutation alone is not sufficient for the occurrence of HO since flare-ups are triggered by inflammation and activation of the innate immune system. A number of cellular and humoral mediators have been implicated in animal and in vitro models. Observations in humans support the inflammatory nature of the condition, but data on the involved mediators are variable. We hypothesize that for induction of flare-ups in patients with FOP increase in at least one of the pro-inflammatory cytokines is both essential and sufficient to trigger the entire process of the inflammatory cells influx resulting in the novel ectopic bone formation and we suggest that C-C motif ligand 5 (CCL5), a pro-inflammatory chemokine also known as Regulated on activation, normal T-cell expressed and secreted (RANTES), might be the key candidate. CCL5 is a chemoattractant for all cellular types implicated in HO and is produced by the cells of the tissue microenvironment at the sites of HO as well as by the pro-inflammatory cellular mediators. CCL5 induces ossification in cultured human pluripotent mesenchymal cells (hMSCs) and in the primary culture of monocytes from FOP patients (but not from their healthy relatives), stimulation with lipopolysaccharide induces CCL5 expression. Finally, in a pilot study we used a panel of 23 cytokines and chemokines to screen the plasma samples of three subjects: a female patient with FOP during a flare-up; a female patient with hyperostosis corticalis generalisata (van Buchem disease), another rare disease characterized by excessive bone formation at the sites where it regularly occurs that does not include inflammatory events; and a healthy woman without bone disorders. There appeared a rather clear-cut signal of a 2-fold higher level of CCL5 in the FOP patient vs. the healthy subject and the van Buchem patient. Evaluation of the hypothesis would require an international prospective study, with main motivation being the lack of a conclusive treatment as the major unmet need in FOP. A treatment targeting CCL5 receptor already exists and is used in HIV-infected patients.
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Quimiocina CCL5/sangre , Terapia Molecular Dirigida , Miositis Osificante/sangre , Osificación Heterotópica/sangre , Quimiocina CCL5/antagonistas & inhibidores , Citocinas/fisiología , Femenino , Humanos , Inflamación , Lipopolisacáridos/farmacología , Células Madre Mesenquimatosas/metabolismo , Modelos Inmunológicos , Monocitos/metabolismo , Miositis Osificante/tratamiento farmacológico , Miositis Osificante/inmunología , Osificación Heterotópica/inmunología , Osteocondrodisplasias/sangre , Células Madre Pluripotentes/metabolismoRESUMEN
Nonpharmacological interventions are one of the mainstreams of treatment for patients with spondyloarthritis (SpA). They include education, measures regarding joint protection, posture and rest, therapeutic exercise, physical therapy modalities, orthoses, and acupuncture. A key component in the rehabilitation of patients with SpA entities is therapeutic exercise, which can be performed as land-based or water-based. Positive effects of the exercises are manifested in reducing pain, maintaining mobility, improving posture, increasing aerobic capacity and improving quality of life. The best effects can be obtained when exercise is performed under the supervision of a physiotherapist at a health institution. The majority of studies on therapeutic exercise in SpA are related to ankylosing spondylitis (AS), while there is a paucity of studies devoted to other conditions. Although progress has been made in the quantity and quality of research on this topic, there are still issues regarding the quality of studies and considerable variability among them, which makes it difficult to compare different methods and harmonize and develop rehabilitation protocols according to evidence-based medicine.
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Routine assessment of patient index data 3 (RAPID3) is a simple, valid and reliable tool designed to measure disease activity in patients with rheumatoid arthritis (RA). RA causes significant disability and diminishes health-related quality of life (HR-QoL). The aim of this study was to investigate how RAPID3 is related to HR-QoL in patients with RA. In this cross-sectional study performed at the tertiary outpatient clinic 68 consecutive patients (58 females, and 10 males) with established RA were enrolled. RAPID3 and EuroQoL-5D-3L (EQ-5D-3L) were used to measure disease activity and quality of life, respectively. Alongside, demographic and clinical data were obtained, as well as HAQ-DI as a measure of physical function, and Steinbrocker's score for radiographic damage. To test the relationships among RAPID3 and study variables we used the Pearson product-moment correlation coefficient, with the significance was set at P < 0.05. Linear and forward stepwise regression was used to show how variables of interest contributed to RAPID3. The mean value of RAPID3 (standard deviation, SD) was 14.12 (± 5.21), while the median (IQR) value of EQ-5D-3L was 0.51 (0.62-0.23). There was a high significant correlation (r = - 0.73) between RAPID3 scores and EQ-5D-3L. Among the other variables of interest, the strongest correlation was found between RAPID3 and intensity of pain (r = 0.88), while the EQ-5D-3L and pain were moderately correlated (r = - 0.68). In evaluating the influence of variables of interest on RAPID3, a forward stepwise regression model was constructed to evaluate whether VAS pain, EQ-5D-3L and EQ-VAS predicted RAPID3. The given variables significantly explained approximately 81% of the variation in RAPID3. Based on the results of this study RAPID3, a simple and practical tool to assess disease activity, reflects well HR-QoL in patients with established RA.
Asunto(s)
Artritis Reumatoide/fisiopatología , Dolor/fisiopatología , Rendimiento Físico Funcional , Calidad de Vida , Artritis Reumatoide/complicaciones , Artritis Reumatoide/psicología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor/etiología , Dolor/psicología , Evaluación del Resultado de la Atención al Paciente , Medición de Resultados Informados por el Paciente , Índice de Severidad de la EnfermedadRESUMEN
To examine the effect of endurance on the relationship between grip force and measures of functional capacity and disease activity, we performed a cross-sectional study at the University Department of Rheumatology, Physical medicine and Rehabilitation from January 2017 to August 2018. Functional capacity of the hand was measured by ABILHAND-RA questionnaire and disease activity was assessed by the Disease Activity Score (DAS-28-CRP). All participants underwent dynamometric measurements of maximal grip force and hand grip endurance during repeated gripping. We analyzed the data from 34 RA patients at the median (IQR) age of 57 (51-61), 31 (91%) of them women, and 44 healthy participants at the age of 55 (50-59), 39 (89%) of them women. The moderating effect of endurance on the correlation between maximum grip force and the ABILHAND-RA score was not significant in healthy participants (b = 0.000, 95% CI - 0.005-0.004, p = 0.862), but it was in RA patients (b = 0.003, 95% CI 0.000-0.005, p = 0.027). In RA patients, the effect of maximum grip force on the ABILHAND-RA score increased with the increase in hand grip endurance. In RA patients, the interaction between endurance and grip force significantly explained the 15% more variance of the disease activity than main effects of these two measures, age, gender and body mass index alone. Hand grip endurance during repeated gripping affects the correlation between maximum grip force and the ABILHAND-RA score in a pattern that differs in RA patients and in the healthy population. In RA patients, hand grip endurance significantly moderates the correlation between maximum grip force and the DAS-28-CRP.