Sexual function and pelvic floor function in men with systemic sclerosis compared to healthy controls: a cross-sectional study.

OBJECTIVES: This cross-sectional study aimed to compare the sexual function (SF) and pelvic floor function of men with systemic sclerosis (SSc) with age-matched healthy controls (HC) and to identify the implications of clinical features on SF. MATERIAL AND METHOD: Twenty SSc males and 20 HC aged 18-70 years completed eleven questionnaires assessing SF [International Index of Erectile Function (IIEF), Male Sexual Health Questionnaire (MSHQ)]; sexual quality of life: Sexual Quality of Life Questionnaire-Male (SQoL-M); pelvic floor function: Pelvic Floor Impact Questionnaire-Short Form 7 (PFIQ-7), fatigue, depression, physical fitness, functional disability, and quality of life. Clinical data were collected. RESULTS: Significantly worse SF was observed in patients (median IIEF erectile function 12 in SSc versus 29 in HC, p < 0.001), with 70% reporting erectile dysfunction (ED) compared to 15% in HC. However, no significant difference was observed regarding pelvic floor function (median PFIQ7 8.8 in SSc versus 7.0 in HC, p = 0.141). Impaired SF was associated with higher disease activity, increased systemic inflammation, more pronounced fatigue, reduced physical fitness, severe depression, impaired overall quality of life, dyspepsia, and arthralgias (p < 0.05 for all). CONCLUSIONS: Sexual dysfunction is highly prevalent in our SSc patients, whereas pelvic floor dysfunction is unlikely to be associated with these problems.

Cardiovascular risk in myositis patients compared with the general population.

OBJECTIVES: We aimed to evaluate cardiovascular (CV) risk in patients with idiopathic inflammatory myopathies (IIM) compared with healthy controls (HC) and to assess its association with disease-specific features. METHODS: Ninety IIM patients and 180 age-/sex-matched HC were included. Subjects with a history of CV disease (angina pectoris, myocardial infarction and cerebrovascular/peripheral arterial vascular events) were excluded. All participants were prospectively recruited and underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition. The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE) and its modifications. RESULTS: Compared with HC, IIM patients had a significantly higher prevalence of traditional CV risk factors, carotid artery disease (CARD), abnormal ABI and PWV. After propensity score matching (using traditional CV risk factors), the prevalence of CARD and pathological PWV remained significantly higher in IIM than HC. No significant difference in SCORE was observed. The most unfavourable CV risk profile was observed in patients with necrotizing myopathy, especially in statin-induced anti-HMGCR+ patients. The calculated CV risk scores by SCORE, SCORE2 and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to CIMT and the presence of carotid plaques. SCORE was demonstrated to be most inaccurate in predicting CV risk in IIM. Age, disease activity, lipid profile, body composition parameters and blood pressure were the most significant predictors of CV risk in IIM patients. CONCLUSION: Significantly higher prevalence of traditional risk factors and subclinical atherosclerosis was observed in IIM patients compared with HC.

Correction: Storkánová et al. Inhibition of Hsp90 Counteracts the Established Experimental Dermal Fibrosis Induced by Bleomycin. Biomedicines 2021, 9, 650.

In the original publication [...].

Effect of an 8-Week Tailored Physiotherapy Program on Sexual Health in Women with Scleroderma and Myositis: A Controlled Pilot Study.

INTRODUCTION: Systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM) are very rare rheumatic diseases burdened by a high prevalence of sexual dysfunctions. However, no specific treatment has been proposed to date. To our knowledge, this is the first (pilot) study aiming to investigate the effect of an 8-week tailored physiotherapy program on the sexual health of women with SSc and IIM. METHODS: In total, 12 women with SSc and 4 women with IIM were enrolled in the study. Based on the patients' capability to participate in the program, they were divided into an intervention group (IG) (mean ± SD age 46.8 ± 8.6 years) and a control group (CG) (mean ± SD age 46.3 ± 8.5 years). IG underwent the 8-week program (1 h of supervised physiotherapy twice weekly), whereas CG received no physiotherapy. At weeks 0 and 8, all patients filled in questionnaires assessing sexual function (Female Sexual Function Index [FSFI], Brief Index of Sexual Functioning for Women [BISF-W]), sexual quality of life (Sexual Quality of Life-Female [SQoL-F]), functional ability (Health Assessment Questionnaire [HAQ]), quality of life (Medical Outcomes Short Form-36 [SF-36]), and depression (Beck's Depression Inventory-II [BDI-II]). The changes were analyzed with two-way ANOVA and Friedmann's test. RESULTS: Compared to the statistically significant deterioration in CG over weeks 0-8, we found statistically significant improvements in the total scores of FSFI and BISF-W, and some of their domains, functional status, and the physical component of quality of life. CONCLUSION: Our 8-week physiotherapy program not only prevented the natural course of progressive deterioration of functional ability but also led to a significant improvement in sexual function and quality of life in women with SSc and IIM. However, due to the lack of randomization and a relatively small sample size resulting from the strict inclusion criteria, further validation of our results is needed. TRIAL REGISTRATION NUMBER: ISRCTN91200867 (prospectively registered).

Hsp90 as a Myokine: Its Association with Systemic Inflammation after Exercise Interventions in Patients with Myositis and Healthy Subjects.

Compelling evidence supports the health benefits of physical exercise on the immune system, possibly through the molecules secreted by the skeletal muscles known as myokines. Herein, we assessed the impact of exercise interventions on plasma Heat shock protein 90 (Hsp90) levels in 27 patients with idiopathic inflammatory myopathies (IIM) compared with 23 IIM patients treated with standard-of-care immunosuppressive therapy only, and in 18 healthy subjects undergoing strenuous eccentric exercise, and their associations with the traditional serum markers of muscle damage and inflammation. In contrast to IIM patients treated with pharmacotherapy only, in whom we demonstrated a significant decrease in Hsp90 over 24 weeks, the 24-week exercise program resulted in a stabilization of Hsp90 levels. These changes in Hsp90 levels were associated with changes in several inflammatory cytokines/chemokines involved in the pathogenesis of IIM or muscle regeneration in general. Strenuous eccentric exercise in healthy volunteers induced a brief increase in Hsp90 levels with a subsequent return to baseline levels at 14 days after the exercise, with less pronounced correlations to systemic inflammation. In this study, we identified Hsp90 as a potential myokine and mediator for exercise-induced immune response and as a potential biomarker predicting improvement after physiotherapy in muscle endurance in IIM.

Cardiovascular Risk in Myositis Patients Compared to the General Population: Preliminary Data From a Single-Center Cross-Sectional Study.

Background: Idiopathic inflammatory myopathies (IIM) are associated with systemic inflammation, limited mobility, and glucocorticoid therapy, all of which can lead to metabolism disturbances, atherogenesis, and increased cardiovascular (CV) risk. The aim of this study was to assess the CV risk in IIM patients and healthy controls (HC), and its association with disease-specific features. Methods: Thirty nine patients with IIM (32 females; mean age 56; mean disease duration 4.8 years; dermatomyositis: n = 16, polymyositis: n = 7, immune-mediated necrotizing myopathy: n = 8, anti-synthetase syndrome: n = 8) and 39 age-/sex-matched HC (32 females, mean age 56) without rheumatic diseases were included. In both groups, subjects with a history of CV disease (angina pectoris, myocardial infarction, cerebrovascular, and peripheral arterial vascular events) were excluded. Muscle involvement, disease activity, and tissue damage were evaluated (Manual Muscle Test-8, Myositis Intention to Treat Activity Index, Myositis Damage Index). Comorbidities and current treatment were recorded. All participants underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition (by densitometry and bioelectric impedance). The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE, charts for the European population) and its modifications. Results: Compared to HC, there was no significant difference in IIM patients regarding blood pressure, ABI, PWV, CIMT, and the risk of fatal CV events by SCORE or SCORE2, or subclinical atherosclerosis (CIMT, carotid plaques, ABI, and PWV). The calculated CV risk scores by SCORE, SCORE2, and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to the results of carotid plaque presence and CIMT; however, none of them was demonstrated to be significantly more accurate. Other significant predictors of CV risk in IIM patients included age, disease duration and activity, systemic inflammation, lipid profile, lean body mass, and blood pressure. Conclusions: No significant differences in CV risk factors between our IIM patients and HC were observed. However, in IIM, CV risk was associated with age, disease duration, duration of glucocorticoid therapy, lipid profile, and body composition. None of the currently available scoring tools (SCORE, SCORE2, mSCORE) used in this study seems more accurate in estimating CV risk in IIM.

Hsp90 Levels in Idiopathic Inflammatory Myopathies and Their Association With Muscle Involvement and Disease Activity: A Cross-Sectional and Longitudinal Study.

Background: Heat shock proteins (Hsp) are chaperones playing essential roles in skeletal muscle physiology, adaptation to exercise or stress, and activation of inflammatory cells. We aimed to assess Hsp90 in patients with idiopathic inflammatory myopathies (IIM) and its association with IIM-related features. Methods: Hsp90 plasma levels were analyzed in a cross-sectional cohort (277 IIM patients and 157 healthy controls [HC]) and two longitudinal cohorts to assess the effect of standard-of-care pharmacotherapy (n=39 in early disease and n=23 in established disease). Hsp90 and selected cytokines/chemokines were measured by commercially available ELISA and human Cytokine 27-plex Assay. Results: Hsp90 plasma levels were increased in IIM patients compared to HC (median [IQR]: 20.2 [14.3-40.1] vs 9.8 [7.5-13.8] ng/mL, p<0.0001). Elevated Hsp90 was found in IIM patients with pulmonary, cardiac, esophageal, and skeletal muscle involvement, with higher disease activity or damage, and with elevated muscle enzymes and crucial cytokines/chemokines involved in the pathogenesis of myositis (p<0.05 for all). Plasma Hsp90 decreased upon pharmacological treatment in both patients with early and established disease. Notably, Hsp90 plasma levels were slightly superior to traditional biomarkers, such as C-reactive protein and creatine kinase, in differentiating IIM from HC, and IIM patients with cardiac involvement and interstitial lung disease from those without these manifestations. Conclusions: Hsp90 is increased systemically in patients with IIM. Plasma Hsp90 could become an attractive soluble biomarker of disease activity and damage and a potential predictor of treatment response in IIM.

The effect of a 24-week physiotherapy and occupational therapy program in systemic sclerosis: a monocentric controlled study with follow-up.

OBJECTIVES: The structural and functional changes of the hands and face in systemic sclerosis (SSc) can be severely disabling. We aimed to assess the effect of a 24-week supervised physiotherapy and occupational therapy program (POTp) combined with home exercise on the function of hands/mouth of SSc patients, compared to a daily home exercise program in typical outpatient care. METHODS: Fifty-nine patients with SSc were consecutively and non-selectively enrolled in an intervention (IG, n=27) or control (CG, n=32) group. Only the IG underwent the POTp twice a week for 1.5 hours. At baseline, 12, 24, and 48 weeks, all patients were assessed by a blinded physiotherapist for the hands/mouth function (delta finger-to-palm, handgrip strength, Hand and Mobility in Scleroderma, interincisal/interlabial distance), and self-evaluated their hand (Cochin Hand Function Scale) and mouth function (Mouth Handicap in Systemic Sclerosis scale), disability (Health Assessment Questionnaire [HAQ], SSc HAQ), and quality of life (Short Form-36). RESULTS: At week 24, compared to the significant deterioration in the CG, we found a significant improvement in the IG in the objectively assessed hands/mouth function and in the subjectively evaluated hand function and disability. The improvement was clinically meaningful (by >20%) in a substantial proportion of patients. Although the improvement in most outcomes was still present at week 48, the maximum effect was not sustained. CONCLUSIONS: This 24-week POTp not only attenuated the progressive deterioration, but also significantly improved the function of the hands/mouth, which was clinically meaningful in a substantial proportion of patients with SSc.

MyomiRs in cultured muscle cells from patients with idiopathic inflammatory myopathy are modulated by disease but not by 6-month exercise training.

OBJECTIVES: Idiopathic inflammatory myopathies/IIM are associated with changes in muscle-specific microRNA/miR. Exercise improves muscle function and metabolism in parallel with changes in miR expression. We investigated the effects of disease and exercise on miRs in differentiated muscle cells/myotubes from IIM patients and controls. METHODS: Samples of m. vastus lateralis were obtained by needle biopsy from IIM patients before/after 6-month training and from matched sedentary healthy controls. Muscle cell cultures were established and exposed to saturated fatty acid during differentiation. MiR-133a,-133b,-206,-1 and their target genes (qPCR), fat oxidation (FOx), lipids (chromatography) and mitochondrial oxidative phosphorylation (OxPHOS) complexes (immunoblotting) were measured. Interrelations between in vitro miRs and metabolism of myotubes as well as clinical parameters and disease activity/MITAX were explored. RESULTS: Levels of miRs were higher in myotubes derived from IIM patients compared to healthy controls (up to 3.5-fold, p<0.05). Neither 6-month training (IIM patients) nor in vitro palmitate treatment modulated myomiRs in myotubes. However, miR-133a,-133b, and miR-1 correlated negatively with FOx (p<0.01), triacylglycerols (p<0.05) and OxPHOS complex-V (p<0.05) and positively with OxPHOS complex-I (p<0.05) in myotubes. MiR-133a and miR-133b in myotubes were related to disease activity and fasting glycaemia in vivo (both p<0.05). CONCLUSIONS: Upregulation of microRNAs involved in myogenesis and regeneration in muscle cells derived from IIM patients indicates activation of compensatory epigenetic mechanisms, potentially aimed to counteract disease progression. Relationships of microRNAs with in vitro metabolic profile of muscle cells as well as with clinical parameters support the role of muscle-specific microRNAs in modulating muscle metabolism and clinical state of patients.

Female Sexual Dysfunction and Pelvic Floor Muscle Function Associated with Systemic Sclerosis: A Cross-Sectional Study.

Only a few studies have addressed sexual health in patients with systemic sclerosis (SSc). This study aimed to compare female sexual function and pelvic floor muscle function in SSc patients with healthy controls (HC) matched by age, and to identify the potential implications of clinical features on sexual function. Our cohort included 90 women with SSc and 90 HC aged 18-70 years that completed six well-established and validated questionnaires assessing sexual function (Brief Index of Sexual Function for Women, Female Sexual Function Index, Sexual Quality of Life Questionnaire-Female, Sexual Function Questionnaire) and pelvic floor function (Pelvic Floor Impact Questionnaire-Short Form 7 and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire Short Form). Results from women with SSc and HC were contrasted and correlated with relevant clinical features. The prevalence of female sexual dysfunction was 73% in SSc patients (vs. 31% in HC). Women with SSc reported significantly worse pelvic floor function and sexual function than HC. Impaired sexual function was correlated with higher disease activity, the presence of dyspnea and interstitial lung disease, increased systemic inflammation, reduced physical activity, functional disability, more severe depression, more pronounced fatigue, and impaired quality of life. We demonstrate that sexual dysfunction is highly prevalent among women with SSc. This aspect of the disease deserves more attention both in clinical care and at the level of international research collaboration.

Inhibition of Hsp90 Counteracts the Established Experimental Dermal Fibrosis Induced by Bleomycin.

Our previous study demonstrated that heat shock protein 90 (Hsp90) is overexpressed in the involved skin of patients with systemic sclerosis (SSc) and in experimental dermal fibrosis. Pharmacological inhibition of Hsp90 prevented the stimulatory effects of transforming growth factor-beta on collagen synthesis and the development of dermal fibrosis in three preclinical models of SSc. In the next step of the preclinical analysis, herein, we aimed to evaluate the efficacy of an Hsp90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), in the treatment of established experimental dermal fibrosis induced by bleomycin. Treatment with 17-DMAG demonstrated potent antifibrotic and anti-inflammatory properties: it decreased dermal thickening, collagen content, myofibroblast count, expression of transforming growth factor beta receptors, and pSmad3-positive cell counts, as well as leukocyte infiltration and systemic levels of crucial cytokines/chemokines involved in the pathogenesis of SSc, compared to vehicle-treated mice. 17-DMAG effectively prevented further progression and may induce regression of established bleomycin-induced dermal fibrosis to an extent comparable to nintedanib. These findings provide further evidence of the vital role of Hsp90 in the pathophysiology of SSc and characterize it as a potential target for the treatment of fibrosis with translational implications due to the availability of several Hsp90 inhibitors in clinical trials for other indications.

The effect of a 24-week training focused on activities of daily living, muscle strengthening, and stability in idiopathic inflammatory myopathies: a monocentric controlled study with follow-up.

BACKGROUND: The structural and functional changes of the skeletal muscles in idiopathic inflammatory myopathies (IIM) caused by inflammation and immune changes can be severely disabling. The objective of this study was to assess the effect of a 24-week program combining a supervised training of activities of daily living (ADL), resistance, and stability with home exercise for improving muscle function, compared to a daily home-based exercise representing the regular outpatient care. METHODS: Fifty-seven patients with IIM were consecutively and non-selectively enrolled in an intervention (IG, n = 30) or control (CG, n = 27) group. Both groups were provided a standard-of-care pharmacological treatment and follow-up. Only the IG underwent the supervised intervention twice a week for 1 h per session. At baseline, 12, 24, and 48 weeks, all patients were assessed by an assessor blinded to the intervention for primary outcomes: muscle strength (Manual Muscle Testing of eight muscle groups [MMT-8]) and endurance (Functional Index-2 [FI-2]), and secondary outcomes: stability and body composition. Secondary outcomes also included questionnaires evaluating disability (Health Assessment Questionnaire [HAQ]), quality of life (Short Form 36 [SF-36]), depression (Beck's Depression Inventory-II [BDI-II]), and fatigue (Fatigue Impact Scale [FIS]), and analysis of the systemic and local inflammatory response and perceived exertion to assess the safety of the intervention. RESULTS: Twenty-seven patients in the IG and 23 in the CG completed the entire program and follow-up. At week 24, compared to deterioration in the CG, we found a significant improvement in the IG in muscle strength (mean % improvement compared to baseline by 26%), endurance (135%), disability (39%), depression (26%), stability (11%), and basal metabolism (2%) and a stabilization of fitness for physical exercise. The improvement was clinically meaningful (a 24-week change by >20%) in most outcomes in a substantial proportion of patients. Although the improvement was still present at 48 weeks, the effect was not sustained during follow-up. No significant increase in the systemic or local expression of inflammatory markers was found throughout the intervention. CONCLUSIONS: This 24-week supervised intervention focused on ADL training proved to be safe and effective. It not only prevented the progressive deterioration, but also resulted in a significant improvement in muscle strength, endurance, stability, and disability, which was clinically meaningful in a substantial proportion of patients. TRIAL REGISTRATION: ISRCTN35925199 (retrospectively registered on 22 May 2020).

Sexual function in patients with idiopathic inflammatory myopathies: a cross-sectional study.

OBJECTIVES: To date, there is almost no information concerning the sexual health of patients with idiopathic inflammatory myopathies (IIM). This cross-sectional study aimed to compare sexual function in patients with IIM to age-/sex-matched healthy controls (HC) and determine the potential impact of clinical features on sexual function. METHODS: In total, 122 women (61 with IIM, 61 age-matched HC) and 22 men (11 with IIM, 11 age-matched HC) aged 18-80 years completed gender-specific selection of 7 well-established and validated questionnaires assessing sexual health and function (Female Sexual Function Index, Brief Index of Sexual Function for Women, Sexual Function Questionnaire, Sexual Quality of Life Questionnaire-Female, International Index of Erectile Function, Male Sexual Health Questionnaire, Sexual Quality of Life Questionnaire-Male). Results were compared between patients and HC and correlated with selected disease-related features. RESULTS: The prevalence of sexual dysfunction in IIM was 59% in women (vs 40% in HC), and 64% (vs 9% in HC) in men. Men and women with IIM reported significantly impaired sexual function compared with sex-/age-matched HC. Decreased sexual function was associated with muscle weakness, disability, physical inactivity, fatigue, depression and decreased quality of life. CONCLUSIONS: Our results suggest that sexual dysfunction is common among IIM patients and more attention should be paid to this aspect of the disease.

Plasma heat shock protein 90 levels in patients with spondyloarthritis and their relation to structural changes: a cross-sectional study.

Aim: Heat shock protein 90 (Hsp90) is a molecular chaperone regulating immune response. We aimed to assess systemic Hsp90 as a biomarker for spondyloarthritis (SpA). Materials & methods: Total of 80 axial SpA (axSpA) and 22 psoriatic arthritis patients and a corresponding number of age- and sex-matched healthy controls (HC) were included. Plasma Hsp90 levels were measured by ELISA. Results: Hsp90 was significantly increased in axSpA patients compared with HC (median interquartile range: 15.7 [10.5-19.8] vs 8.3 [6.6-11.8] ng/ml, p < 0.001). Moreover, Hsp90 was superior to C-reactive protein in differentiating axSpA (and both radiographic axSpA [r-axSpA] and nonradiographic-axSpA) from HC. Hsp90 levels correlated with bone marrow edema of sacroiliac joints in r-axSpA patients (r = 0.594, p = 0.019). Conclusion: Hsp90 could become a biomarker for active inflammation in r-axSpA, and can better distinguish axSpA patients from healthy subjects than C-reactive protein.

Plasma Hsp90 levels in patients with systemic sclerosis and relation to lung and skin involvement: a cross-sectional and longitudinal study.

Our previous study demonstrated increased expression of Heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc). We aimed to evaluate plasma Hsp90 in SSc and characterize its association with SSc-related features. Ninety-two SSc patients and 92 age-/sex-matched healthy controls were recruited for the cross-sectional analysis. The longitudinal analysis comprised 30 patients with SSc associated interstitial lung disease (ILD) routinely treated with cyclophosphamide. Hsp90 was increased in SSc compared to healthy controls. Hsp90 correlated positively with C-reactive protein and negatively with pulmonary function tests: forced vital capacity and diffusing capacity for carbon monoxide (DLCO). In patients with diffuse cutaneous (dc) SSc, Hsp90 positively correlated with the modified Rodnan skin score. In SSc-ILD patients treated with cyclophosphamide, no differences in Hsp90 were found between baseline and after 1, 6, or 12 months of therapy. However, baseline Hsp90 predicts the 12-month change in DLCO. This study shows that Hsp90 plasma levels are increased in SSc patients compared to age-/sex-matched healthy controls. Elevated Hsp90 in SSc is associated with increased inflammatory activity, worse lung functions, and in dcSSc, with the extent of skin involvement. Baseline plasma Hsp90 predicts the 12-month change in DLCO in SSc-ILD patients treated with cyclophosphamide.

Clusterin is upregulated in serum and muscle tissue in idiopathic inflammatory myopathies and associates with clinical disease activity and cytokine profile.

OBJECTIVES: The aim of this cross-sectional study was to explore the circulating and skeletal muscle expression of clusterin (CLU) in inflammatory myopathies (IIM) and its potential implication in pathogenetic mechanisms of the disease. METHODS: A total of 85 IIM patients and 86 healthy controls (HC) were recruited. In addition, 20 IIM patients and 21 HC underwent a muscle biopsy. Circulating CLU was measured by ELISA. Serum cytokine profile of patients and HC was assessed by Cytokine 27-plex Assay. Immunohistochemical localisation of CLU was assessed in 10 IIM and 4 control muscle tissue specimens. The expression of CLU and myositis related cytokines in muscle was determined by qPCR. RESULTS: Serum levels of CLU were significantly increased in IIM patients compared to controls (86.2 (71.6-99.0) vs. 59.6 (52.6-68.4) µg/mL, p<0.0001) and positively correlated with myositis disease activity assessment (MYOACT) (r=0.337, p=0.008), myositis intention-to-treat activity index (MITAX) (r=0.357, p=0.004) and global disease assessment evaluated by physician (r=0.309, p=0.015). Moreover, serum CLU correlated with cytokines and chemokines involved in IIM and their combined effect on disease activity was revealed by multivariate redundancy analysis. In muscle tissue, CLU mRNA was increased in IIM patients compared to controls (p=0.032) and CLU accumulated in the cytoplasm of regenerating myofibres. CONCLUSIONS: We suggest that the up-regulation of clusterin in circulation and skeletal muscle of IIM patients may be an inflammation and atrophy induced response of the organism intended to limit the environment, favouring further muscle damage.

Manual Therapy (Postisometric Relaxation and Joint Mobilization) in Knee Pain and Function Experienced by Patients with Rheumatoid Arthritis: A Randomized Clinical Pilot Study.

OBJECTIVES: The purpose of this study was to evaluate the impact of manual therapy on the management of rheumatoid arthritis (RA) patients with knee pain. MATERIALS AND METHODS: This was a small, randomized clinical pilot study. Subjects were 46 patients with diagnosed RA, randomly assigned to the manual therapy group (postisometric relaxation and joint mobilization) or control group (standard exercise). Subjects in each group had 10 sessions of interventions, once a day with one day break after the sixth day. Outcomes included the pain intensity of knee, Knee Society Score, Oxford Knee Score, and Health Assessment Questionnaire. RESULTS: There were no statistically significant differences between groups, except for the pain intensity of the knee. CONCLUSIONS: This study suggests that manual therapy (postisometric relaxation and joint mobilization) may have clinical benefits for treating knee pain and function in rheumatoid patients. Further extended studies are expected to determine the effectiveness of manual therapy in RA patients with knee pain.

Alterations in activin A-myostatin-follistatin system associate with disease activity in inflammatory myopathies.

OBJECTIVES: The aim of this study was to investigate the systemic and skeletal muscle levels of atrophy-associated myokines in patients with idiopathic inflammatory myopathies (IIM) and their association with clinical characteristics of myositis. METHODS: A total of 94 IIM patients and 162 healthy controls were recruited. Of those, 20 IIM patients and 28 healthy controls underwent a muscle biopsy. Circulating concentrations of myostatin, follistatin, activin A and TGF-ß1 were assessed by ELISA. The expression of myokines and associated genes involved in the myostatin signalling pathway in muscle tissue was determined by real-time PCR. RESULTS: We report decreased levels of circulating myostatin (median 1817 vs 2659 pg/ml; P = 0.003) and increased follistatin (1319 vs 1055 pg/ml; P = 0.028) in IIM compared with healthy controls. Activin A levels were also higher in IIM (414 vs 309 pg/ml; P = 0.0005) compared with controls. Myostatin was negatively correlated to muscle disease activity assessed by physician on visual analogue scale (MDA) (r = -0.289, P = 0.015) and positively to manual muscle testing of eight muscles (r = 0.366, P = 0.002). On the other hand, follistatin correlated positively with MDA (r = 0.235, P = 0.047). Gene expression analysis showed higher follistatin (P = 0.003) and myostatin inhibitor follistatin-like 3 protein (FSTL3) (P = 0.008) and lower expression of activin receptor type 1B (ALK4) (P = 0.034), signal transducer SMAD3 (P = 0.023) and atrophy marker atrogin-1 (P = 0.0009) in IIM muscle tissue compared with controls. CONCLUSION: This study shows lower myostatin and higher follistatin levels in circulation and attenuated expression of myostatin pathway signalling components in skeletal muscle of patients with myositis, a newly emerging pattern of the activin A-myostatin-follistatin system in muscle wasting diseases.

Changes of patient-reported outcomes and protein fingerprint biomarkers after exercise therapy for axial spondyloarthritis.

The objective of this study was to investigate the patient-reported outcomes (PROs) and matrix metalloproteinase (MMP) derived extracellular matrix (ECM) biomarkers in non-radiographic (nr)-axial spondyloarthritis (axSpA) and radiographic (r)-axSpA after exercise intervention. Forty-six axSpA patients with stable disease and treatment underwent 24 weeks long exercise intervention. The clinical and laboratory assessments were performed at baseline and at follow-up. The PROs included evaluation of patient's global disease activity (PGDA), disease activity (DA7), pain (PAIN7) and fatigue during last week and quality of life questionnaires. ELISAs for MMP-degraded collagen type II, C-reactive protein (CRPM) and citrullinated vimentin were used. The data of 23 r-axSpA and 19 nr-axSpA were analysed. The PDGA was similar for nr-axSpA (35.2 ± 18.9) and r-axSpA (33.4 ± 22.3) at baseline, improved significantly after intervention (p < 0.01) and the change of PDGA was almost identical for nr-axSpA (- 10.0 ± 15.4) and r-axSpA (- 9.8 ± 11.9). Evaluations of DA7 and PAIN7 were significantly improved only in nr-axSpA (3.5 ± 2.3 and 34.7 ± 25.6 at baseline vs. 2.1 ± 1.9 and 21.0 ± 20.5, respectively, p < 0.01). The decline of DA7 and PAIN7 was more profound, but not significantly in nr-axSpA than in r-axSpA (- 1.4 ± 1.6 and - 13.7 ± 17.4 vs. - 0.5 ± 3.1 and - 3.7 ± 3.3, respectively). The quality of life was not changed. At baseline, increased levels of CRPM were found in r-axSpA (14.85 ± 4.10) compared to nr-axSpA (11.83 ± 3.20), p < 0.05, but all three biomarkers were not influenced by exercise therapy. We found that exercise therapy mainly in the nr-axSpA improves PROs, but not ECM turnover biomarkers. This indicates that exercise therapy is important for patients' health but does not affect ECM turnover.

Comparison of Deep Tissue Massage and Therapeutic Massage for Lower Back Pain, Disease Activity, and Functional Capacity of Ankylosing Spondylitis Patients: A Randomized Clinical Pilot Study.

OBJECTIVES: This study aims to compare the effectiveness of deep tissue massage (DTM) and therapeutic massage (TM) in the management of ankylosing spondylitis (AS) patients. MATERIALS AND METHODS: This was a small, randomized clinical pilot study. Subjects were 27 men with diagnosed AS, randomly assigned to DTM group or TM group. Subjects in each group had 10 sessions of massage. Outcomes included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), Modified Schober Test, Finger to Floor Test, chest expansion, and pain intensity of lower back. RESULTS: There are no statistical significant differences between groups, except for BASDAI and pain intensity of lower back. CONCLUSIONS: This study suggests that massage may have clinical benefits for treating ankylosing spondylitis patients. Additional scientific research in this area is warranted.