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The article focuses on a study on the effects of water stress, abscisic acid (ABA) and gibberellic acid on flower production and differentiation in the cleistogamous species Collomia grandiflora Doug. Collomia grandiflora produces both closed or cleistogamous (CL) self-pollinating flowers and open or chasmogamous (CH). Prior research by other workers has shown that the concentration of ABA increases in the leaves of water-stressed plants and injected ABA mimics the morphological effects of water stress. The study found that both water stress and the application of ABA reduce the total number of flowers and percentage of CH flowers relative to well-watered control plants, with CL flowers produced in positions in the inflorescence of C. grandiflora where CH flowers typically occur.

Background: Objectives were to assess the mouth opening ability (MOA) among patients with systemic sclerosis (SSc) in comparison to a healthy control population. The impact of microstomia (decrease in any of the MOA parameters) on physical performance and long-term survival was also investigated., Methods: Interincisal (ID), interlabial (LD), the intercommissural distances at both opened mouth and closed mouth (OW, CW) and the oral area (OA) and circumference (OC) all were assessed in 131 SSc patients. Microstomia was defined based on the oral aperture values of a healthy control group (n = 63) with similar median age and sex distribution. Tests evaluating functional performance were performed. Survival analysis by univariate and multivariate Cox regression analysis was performed., Results: Microstomia was present in 56.5% of the entire SSc cohort. Patients with microstomia had higher number of contractures compared to those with preserved oral aperture parameters (median 10 vs. 7, p < 0.01). LD, OA and OC correlated negatively with the number of joint contractures, both in the entire SSc cohort and separately in the diffuse (dcSSc) and limited cutaneous subsets (lcSSc), (rho: between - 0.267 and - 0.516, p < 0.05). Reduced ID was associated with worse Health Assessment Questionnaire Disability Index (HAQ-DI) only in dcSSc while reduced LD was linked to increased HAQ-DI scores in both SSc subsets. Decreased OA upon enrollment was associated with an increased risk in mortality by multivariate Cox regression analysis (HR: 2.74; 95% CI, 1.15-6.53)., Conclusions: Microstomia was associated with joint damage, and higher overall disability based on HAQ-DI. Interlabial distance was a beneficial, convenient measurable parameter to characterize oral aperture. Oral area was an independent poor prognostic factor regarding long-term survival., Competing Interests: Declarations Ethics approval and consent to participate Each participant freely submitted their written informed consent according to the Declaration of Helsinki. Ethical approval was provided by the Regional and Institutional Research Ethics Committee, Medical Center, University of Pécs (Approval No. 2720/2006 and 4906/2013) and the Hungarian National Ethics Committee (IF-6720-6/2015.). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Autoantibody production is a hallmark of systemic sclerosis (SSc) and the most extensively studied role of B cells in the pathogenesis of the disease. However, the potential involvement of innate immune molecules in B-cell dysfunction in SSc is less understood. B-cell activation is an early event in the pathogenesis of SSc and is influenced by complement receptors (CRs) and Toll-like receptors (TLRs), shaping antibody responses. CR2 and CR1 modulate B-cell activation, and the roles of CR3 and CR4 are associated with autoimmune conditions. We investigated the expression of CRs in B cells from patients with the more severe form of the disease, diffuse cutaneous SSc (dcSSc), and the effect of TLR CD180 ligation on their expression. We found no significant difference in the basal expression of CD21 and CD11c in B cells between dcSSc and healthy controls (HCs). However, reduced basal CD11b expression in B cells in dcSSc compared to HCs, accompanied by a decrease in CD35 and an increase in CD11c expression following CD180 ligation may promote plasma cell formation and autoantibody production. Additionally, we searched for correlations between dcSSc-associated anti-DNA topoisomerase I (Scl-70) autoantibody, anti-citrate synthase (CS) natural autoantibody and complement component 3 (C3) levels and found a negative correlation between C3 and anti-CS autoantibody in dcSSc but not in HCs, supporting the hypothesis that natural autoantibodies could activate the complement system contributing to tissue injury in SSc.

Type I interferon (IFN-I) signaling has been shown to be upregulated in systemic sclerosis (SSc). Dysregulated B-cell functions, including antigen presentation, as well as antibody and cytokine production, all of which may be affected by IFN-I signaling, play an important role in the pathogenesis of the disease. We investigated the IFN-I signature in 71 patients with the more severe form of the disease, diffuse cutaneous SSc (dcSSc), and 33 healthy controls (HCs). Activation via Toll-like receptors (TLRs) can influence the IFN-I signaling cascade; thus, we analyzed the effects of the TLR homologue CD180 ligation on the IFN-I signature in B cells. CD180 stimulation augmented the phosphorylation of signal transducer and activator of transcription 1 (STAT1) in dcSSc B cells ( p = 0.0123). The expression of IFN-I receptor (IFNAR1) in non-switched memory B cells producing natural autoantibodies was elevated in dcSSc ( p = 0.0109), which was enhanced following anti-CD180 antibody treatment ( p = 0.0125). Autoantibodies to IFN-Is (IFN-alpha and omega) correlated (dcSSc p = 0.0003, HC p = 0.0192) and were present at similar levels in B cells from dcSSc and HC, suggesting their regulatory role as natural autoantibodies. It can be concluded that factors other than IFN-alpha may contribute to the elevated IFN-I signature of dcSSc B cells, and one possible candidate is B-cell activation via CD180.

Background: Systemic sclerosis (SSc) is a multi-organ disease with impaired health-related quality of life (HRQoL). The EULAR SSc Impact of Disease (ScleroID) is a newly introduced SSc-specific patient-reported outcome to evaluate HRQoL in SSc., Objective: To investigate the correlation between the ScleroID and the involvement of organ systems as well as disease activity/damage in a SSc cohort from a large tertiary care centre., Patients and Methods: The ScleroID and clinical characteristics including internal organ involvement and hand function were investigated in 160 consecutive patients with SSc (median age 46 (43;56) years; diffuse cutaneous SSc 55%)., Results: A strong correlation was found between the ScleroID and articular disease activity scores (DAS28-CRP, DAS28-ESR, CDAI, SDAI), a hand function performance test, the Hand Anatomy Index and muscle strength tests. Additionally, a strong significant correlation was discovered using instruments representing hand function and musculoskeletal disability including the Cochin Hand Function Scale, the Quick Questionnaire of the Disability of the Hands, Arms and the Shoulders and the Health Assessment Questionnaire Disability Index. A significant negative correlation was found between the ScleroID score and the 6-min walking test (6MWT) (rho - 0.444, p < 0.001). Clinically mild lung/heart disease did not show increased ScleroID values. The Mouth Handicap in the Scleroderma Scale and the University of California Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 also showed significant positive correlations to the ScleroID score (rho: 0.626, p < 0.001; rho: 0.646, p < 0.001, respectively). Patients experiencing oesophageal difficulties bore a significantly higher score compared to individuals with a normal functioning oesophagus (3.2/1.5;4.5/ vs. 2.2/1.0;3.2/, p = 0.011). Moreover, the ScleroID showed a significant positive correlation to the revised EUSTAR disease activity index and modified activity index., Conclusion: In a large single-centre cohort, the previously described ScleroID-related findings were confirmed. Furthermore, several organ involvement-related functional and performance tests showed a good correlation to the ScleroID including the 6MWT and gastrointestinal-related complaints. Many aspects of musculoskeletal damage, overall disease activity, pain and fatigue were also well represented in the ScleroID, which efficiently reflects the impact of organ involvement, disease activity and functional damage., (© 2023. The Author(s).)

(1) Background: Systemic sclerosis (SSc) is characterized by significant fatigue, causing diminished quality of life (QoL). The aim of this study was to examine fatigue levels and their associations with clinical factors and determine the minimal clinically important difference (MCID) value for the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-FS). (2) Methods: A total of 160 SSc patients and 62 individuals without SSc were followed-up over a 12-month period by measuring the FACIT-FS and the Visual Analogue Scale and the Short Form 36 Vitality Score analyzing changes in exhaustion. (3) Results: Fatigue was strongly correlated with HRQoL, level of pain, emotional disorders, physical capability and functionality. The MCID values for FACIT-FS were calculated as -3 for deterioration and +4 for improvement after a 12-month follow-up. The predictors of improvement of fatigue from baseline parameters were the significant disease activity, the patients' poorer functionality and the short disease duration. Patients with scleroderma-related interstitial lung disease at baseline had approximately tripled risks for worsening fatigue. The independent influential factors regarding the changing of FACIT-FS were improving or worsening in the same direction in reference to physical condition, gastrointestinal and emotional factors. (4) Conclusions: Fatigue is a multi-dimensional symptom, which is strongly correlated to HRQoL. MCID values of FACIT-FS can be useful tools in monitoring the changes of HRQoL in clinical trials and in daily practice among patients with SSc.

The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) pathways are known to play a key role in B-cell activation and fibrosis in systemic sclerosis (SSc). Receptors of B-cell activator factor (BAFF) utilize these pathways, which can be influenced by Toll-like receptors (TLRs), as TLRs can alter the expression of BAFF-binding receptors. Our results show that B-cell stimulation via TLR homologue CD180 phosphorylates Akt in diffuse cutaneous SSc (dcSSc) to a lower extent than in healthy controls (HCs). We found basal downregulated BAFF receptor (BAFF-R) and enhanced transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) expression in dcSSc B cells, which might enhance the formation of autoantibody-secreting plasma cells. Moreover, this pathological shift was observed in naive B cells, emphasizing the importance of their increase in SSc. Additionally, we measured higher serum levels of autoantibodies to BAFF in dcSSc patients, suggesting that an imbalance in the complex system of BAFF/anti-BAFF autoantibodies/BAFF-binding receptors may contribute to the development of SSc. Anti-CD180 antibody treatment had opposite effects on the expression of BAFF-R and TACI in HC B cells, resulting in similar levels as observed in SSc B cells without stimulation, which argues against the usefulness of such therapy in SSc.

Background: Preliminary criteria for the very early diagnosis of systemic sclerosis (VEDOSS) have been previously proposed to identify signs and symptoms in patients with Raynaud's phenomenon. Patients with all signs or symptoms of the VEDOSS criteria already fulfil the 2013 American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) classification criteria for systemic sclerosis. However, prospective data for the evolution to fulfilling these criteria do not exist. We therefore aimed to determine the clinical value of the VEDOSS criteria to identify patients with Raynaud's phenomenon who progress to systemic sclerosis within 5 years., Methods: The VEDOSS project was a multicentre, longitudinal registry study done in 42 European Scleroderma Trial and Research group centres located in 20 countries in Europe, North America, and South America. Patients with Raynaud's phenomenon were eligible for enrolment. Those who had fulfilled the 1980 ACR or the 2013 ACR-EULAR classification criteria for systemic sclerosis, as well as of any other ACR or EULAR classification criteria for other definite connective tissue diseases at enrolment were excluded. Data were recorded each year during follow-up visits and included the four VEDOSS criteria (ie, positivity for antinuclear antibodies [ANAs], puffy fingers, systemic sclerosis-specific autoantibodies, and abnormal nailfold capillaroscopy). The primary endpoint was the fulfilment of the 2013 ACR-EULAR classification criteria for systemic sclerosis (ie, progression from enrolment to follow-up). Proportion of progressors and VEDOSS criteria interaction were reported descriptively. Predictors of progression of the distinct VEDOSS criteria interactions were determined based on the point prevalence at 5 years. To investigate the intermediate course of progression of the distinct VEDOSS criteria and their combinations, Kaplan-Meier analysis was done., Results: Between March 1, 2010, and Oct 4, 2018, we enrolled 1150 patients with Raynaud's phenomenon in the VEDOSS database. 764 (66·4%) of 1150 patients met the VEDOSS criteria for study inclusion. Of the 764 patients, 553 (72·4%) had at least one available follow-up visit and the median duration of follow-up was 3·6 years (IQR 1·7-5·8). The mean age was 45·9 years (SD 15·0), 507 (91·7%) of 553 participants were female, and the median time since the onset of Raynaud's phenomenon was 4·0 years (IQR 1·7-10·0). At baseline, 401 (73·7%) of 544 patients with Raynaud's phenomenon had detectable ANA, with 208 (39·5%) of 527 patients positive for systemic sclerosis-specific autoantibodies. Nailfold capillaroscopy abnormalities were present in 182 (36·0%) of 505 patients and puffy fingers were detected in 96 (17·8%) of 540 at baseline. 1885 follow-up visits were recorded. 254 (45·9%) of 553 patients completed the study with progression or a 5-year follow-up; of whom, 133 reached the primary endpoint, resulting in an overall progression rate of 52·4%. The absence of ANA at baseline was the factor most strongly associated with a lack of progression within 5 years, with only four (10·8%) of 37 ANA-negative patients progressing. Conversely, positivity at baseline for systemic sclerosis-specific autoantibodies and puffy fingers was the combination having the highest risk of progression (16 [94·1%] of 17)., Interpretation: Our results from the VEDOSS project offers a useful tool for a stratified risk approach to patients with Raynaud's phenomenon. The absence of ANA is a strong protective factor that identifies patients with very low risk of developing systemic sclerosis whereas the presence of one or two VEDOSS criteria in patients with Raynaud's phenomenon confers a progressively higher risk for systemic sclerosis over time. This stratification tool can be used both for clinical management and to inform early interventional trials., Funding: European Scleroderma Trial And Research and World Scleroderma Foundation., Competing Interests: Declaration of interests LC has had consultancy relationships with Boehringer Ingelheim, Actelion, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Lilly. FdG has had consultancy relationships or has received research funding, or both, from Actelion, AstraZeneca, Boehringer Ingelheim, Capella Biosciences, Chemomab, GlaxoSmithKline, Kymab, and Mitsubishi-Tanabe in the area of potential treatments of scleroderma and its complications. DEF has received grant or research support from Actelion, Amgen, BMS Corbus, CSL Behring, Galapagos Gilead, GlaxoSmithKline, National Institutes of Health, Novartis, Kadmon, PICORI, Pfizer, Sanofi, Roche–Genentech, Talaris, and Mitsubishi; and consultancy relationships with AbbVie, Acetelion, Amgen, BMS Corbus, Galapagos, Novartis, Pfizer, Talaris, R-Pharm, Sanofi, CSL Behring, and Boehringer Ingelheim; and speakers bureau from CME. YA has had consultancy relationships or has received research funding, or both, from Actelion, Bayer, Boehringer Ingelheim, Genentech–Roche, Inventiva, Medsenic, and Sanofi in the area of potential treatments of scleroderma and its complications. OD reports receiving personal fees from AbbVie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos NV, Glenmark, GlaxoSmithKline, Horizon, Inventiva, IQvia, Italfarmaco, Iqone, Kymera Therapeutics, Lilly, Medac, Medscape, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Roivant Siences, Sanofi, Serodapharm, Topadur, Target Bioscience, and UCB, during the conduct of the study; and grants from Mitsubishi Tanabe; and a patent issued mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143). MMC has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer Ingelheim, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, Merck Sharp & Dohme, Chemomab, Lilly, Pfizer, and Roche. DH has received travel funding from Actelion, Boehringer Ingelheim, and Shire. VS reports grants and personal fees from Boehringer Ingelheim and Janssen-Cilag NV; grants from Flanders, the Belgian Fund for Scientific Research in Rheumatic diseases; and personal fees from Accord Healthcare, Celgene, and UCB, outside the submitted work. VS is also the chair (unpaid) of the European League Against Rheumatism Study group on Microcirculation in Rheumatic Diseases, co-chair (unpaid) of the American College of Rheumatology Study Group on Microcirculation, co-chair (unpaid) of the Scleroderma Clinical Trials Consortium Working Group on capillaroscopy, and is a steering committee member (unpaid) of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases. TM has received honoraria and fees for lectures from Actelion, Janssen, Boehringer Ingelheim, Lilly, Pfizer, Roche, AbbVie, and Richter. CB reports personal fees from Actelion and Eli Lilly; and grants from the European Scleroderma Trial and Research group, New Horizon Fellowship, the Foundation for Research in Rheumatology, and Fondazione Italiana per la Ricerca sull’Artrite, outside the submitted work All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Disease-associated, high-affinity pathological autoantibody production is a well-described consequence of immune dysregulation affecting B cells in systemic sclerosis (SSc), including the distribution of B-cell subsets. We have previously shown that the increased relative frequency of CD19+CD27+IgD- switched memory B cells is associated with the severe form of SSc. This study sought to analyze memory B cell subsets using an extended range of markers for further subdivision based on CD19, IgD, CD27, CD38 and CD95 phenotype, to define relationship between the alterations of memory B cell subsets and the clinical features of SSc. Peripheral blood samples were obtained from 21 SSc patients, including 14 diffuse (dcSSc) and 7 limited (lcSSc) cutaneous SSc patients, with disease duration of 2.7 ( ± 1.6) years. After purification of CD19+ B cells, multiparametric flow cytometry was performed and the frequencies of CD19+IgD-CD27-CD38+ double negative (DN) 1, CD19+IgDloCD27+CD38+ unswitched, CD19+IgD-CD27+CD38+CD95- resting switched and CD19+IgD-CD27+CD38-CD95+ activated switched memory (ASM) B cells were determined, and correlated with clinical features of SSc. The dcSSc patients had a higher frequency of ASM B cells (p = 0.028) compared to lcSSc patients. The percentage of ASM B cells was elevated in anti-Scl-70 (anti-topoisomerase I) antibody positive patients compared to negative patients (p = 0.016). Additionally, the frequency of ASM B cells was also increased in patients with pulmonary fibrosis (p = 0.003) suggesting that patients with severe form of SSc have higher ASM B cell ratios. Furthermore, the ratio of DN1 B cells was decreased (p = 0.029), while the level of anti-citrate synthase IgG natural autoantibody was elevated (p = 0.028) in patients with active disease. Our observations on the increase of ASM B cells in dcSSc and in patients with pulmonary fibrosis may point to the association of this alteration with the severe form of the disease. Functionally the correlation of ASM B cells as effector memory-plasma cell precursors with anti-topoisomerase I antibody positivity could reflect their contribution to pathological autoantibody production, whereas the decrease of memory precursor DN B cells and the increase of anti-citrate synthase IgG autoantibody may have potential significance in the assessment of disease activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Simon, Balogh, Erdő-Bonyár, Böröcz, Minier, Czirják and Berki.)

B cell activation is an early event in the development of systemic sclerosis (SSc). The classical activation of B cells downstream of the B-cell receptor (BCR) involves the phosphatidylinositol-3 kinase (PI3K) pathway that integrates the effects of multiple co-stimulatory receptors. Our analysis of PI3K pathway associated molecules in peripheral blood B cells of early diffuse cutaneous SSc (dcSSc) patients showed altered mRNA expression of Toll-like receptor (TLR) homolog CD180, TLR4, complement component 3, IL-4 receptor and secreted phosphoprotein 1 (SPP1). Parallel to this, we found elevated basal SPP1 secretion in dcSSc B cells, but, with BCR + IL-4 receptor co-stimulation, we could not induce further secretion. CD180 stimulation alone resulted in NF-κB activation in more B cells than CD180 + BCR co-stimulation both in dcSSc and healthy control (HC), but the co-engagement increased the phosphorylation of NF-κB only in dcSSc B cells. Additionally, in contrast with HC B cells, the lower basal production of IL-10 by dcSSc B cells could not be elevated with CD180 stimulation. Furthermore, activation via CD180 increased the percentage of CD86+ switched memory (CD27+IgD-) B cells in dcSSc compared to HC. Our results suggest that alternative B cell activation and CD180 dysfunction cause imbalance of regulatory mechanisms in dcSSc B cells.

Sclerodermalike syndromes (SLSs) comprise diseases with mucin deposition (eg, scleromyxedema, scleredema), with eosinophilia (eg, eosinophilic fasciitis), metabolic or biochemical abnormalities (eg, nephrogenic systemic fibrosis), or endocrine disorders (eg, POEMS syndrome, or polyneuropathy, organomegaly, endocrinopathy, monoclonal lymphoproliferative disorder, and hypothyroidism). Chronic graft-versus-host disease may also show sclerodermalike skin changes. Inherited progeria syndromes with early aging (eg, Werner syndrome) and a heterogeneous group of hereditary disorders with either skin thickening (eg, stiff skin syndrome) or atrophy and tightening (eg, acrogeria) can also imitate classic systemic sclerosis (SSc). In addition, SLSs can be provoked by several drugs, chemicals, or even physical injury (eg, trauma, vibration stress, radiation). In SLSs, the distribution of skin involvement seems to be atypical compared with SSc. The acral skin involvement is usually missing, and lack of Raynaud phenomenon, scleroderma-specific antinuclear antibodies, the absence of scleroderma capillary pattern, and internal organ manifestations indicate the presence of an SLS. Skin involvement is sometimes nodular, and the underlying tissues can also be affected. For the differential diagnosis, a skin biopsy of the deeper layers including fascia and muscle is required. Histology does not always allow differentiation between SSc and SLSs; therefore, the diagnosis is often based on the distribution, quality of cutaneous involvement, and other accompanying clinical features., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Altered expression and function of the Toll-like receptor (TLR) homologue CD180 molecule in B cells have been associated with autoimmune disorders. In this study, we report decreased expression of CD180 at protein and mRNA levels in peripheral blood B cells of diffuse cutaneous systemic sclerosis (dcSSc) patients. To analyze the effect of CD180 stimulation, together with CpG (TLR9 ligand) treatment, on the phenotype defined by CD19/CD27/IgD/CD24/CD38 staining, and function (CD69 and CD180 expression, cytokine and antibody secretion) of B cell subpopulations, we used tonsillar B cells. After stimulation, we found reduced expression of CD180 protein and mRNA in total B cells, and CD180 protein in B cell subpopulations. The frequency of CD180 + cells was the highest in the CD19 + CD27 + IgD + non-switched (NS) B cell subset, and they showed the strongest activation after anti-CD180 stimulation. Furthermore, B cell activation via CD180 induced IL-6 and natural autoantibody secretion. Treatment with the combination of anti-CD180 antibody and CpG resulted in increased IL-6 and IL-10 secretion and natural autoantibody production of B cells. Our results support the role of CD180 in the induction of natural autoantibody production, possibly by NS B cells, and suggest an imbalance between the pathologic and natural autoantibody production in SSc patients.

Cardiac involvement in systemic sclerosis (SSc) implies a worse prognosis. Little is known about the right atrial (RA) mechanics in this disease, but recent data suggest that it correlates well with the functional capacity of the patients in conditions with known right heart involvement. Thus we aimed to investigate the abnormalities of the RA function as compared with healthy subjects and to assess the potential correlations between RA mechanics and the functional capacity in SSc patients using 2D speckle tracking technique. A total of 70 SSc patients (age: 57 ± 12 years) were investigated. Functional capacity was measured with 6-minute walk test (6MWT). Echocardiographic parameters of the right ventricular (RV) systolic function (TAPSE, RVFAC), parameters of the tricuspid inflow (E, A), and tricuspid annular systolic (S), early- (e') and late- (a') diastolic myocardial velocities were measured. RV wall thickness was obtained. RA reservoir (ε R ), conduit (ε CD ), and contractile (ε CT ) strain were measured. RA stiffness was calculated as ratio of E/e' to ε R . Echocardiographic data were compared with an age- and gender-matched group of 25 healthy volunteers. RA ε R (49.3 ± 10.7 vs 59.6 ± 9.9%, p = 0.000) and ε CD (26.8 ± 8.1 vs 34.3 ± 7.3%, p = 0.000) were significantly lower in SSc patients. No significant difference was found in ε CT (22.9 ± 5.8 vs 25.3 ± 5.7%, p = 0.082). RA stiffness was significantly increased in SSc patients (0.11 ± 0.04 vs 0.08 ± 0.02, p = 0.001). 6MWT distance was 391 ± 95m. In stepwise multiple linear regression analysis RV wall thickness (r = -0.289, p = 0.030) and RA stiffness (r = -0.418, p = 0.002) became independent predictors of 6MWT distance. In conclusion, RA ε R and ε CD are impaired, while RA stiffness is increased in SSc compared with healthy subjects. Speckle tracking-derived RA stiffness is turned out to be one of the main determinants of the functional capacity in SSc patients., (Copyright © 2018. Published by Elsevier Inc.)

Background: Left ventricular (LV) diastolic dysfunction is common in systemic sclerosis (SSc). Less is known, however, about left atrial (LA) mechanics in this context. The aim of this study was to investigate the correlation between LV diastolic function and LA mechanics in SSc patients with the use of volumetric and 2-dimensional speckle tracking-derived strain techniques and to compare the results with those obtained in healthy subjects., Methods and Results: Seventy-two SSc patients and 30 healthy volunteers (H) were investigated. LV diastolic function was classified as normal (I), impaired relaxation (II), and pseudonormal pattern (III). LA reservoir (H: 51.8 ± 7.4%; I: 45.1 ± 8.1%; II: 42.2 ± 6.6%; III: 36.6 ± 7.3%; analysis of variance: P < .001) and contractile strain (H: 24.8 ± 4.9%; I: 18.2 ± 4.4%; II: 21.5 ± 2.8%; III: 16.8 ± 3.6%; P < .001) already showed significant worsening in SSc patients with preserved LV diastolic function compared with healthy subjects. LA conduit strain (H: 27.1 ± 4.6%; I: 26.9 ± 5.7%; II: 20.6 ± 6.1%; III: 19.5 ± 5.3%; P < .001) was preserved in this early phase. Further deterioration of reservoir strain was pronounced in the pseudonormal group only. LA contractile strain increased significantly in the impaired relaxation group and then decreased with the further worsening of the LV diastolic function. Regarding phasic volume indices, the differences between groups were not always statistically significant., Conclusion: LA mechanics strongly reflects the changes in LV diastolic function in SSc. On the other hand, strain parameters of the LA reservoir and contractile function already show significant worsening in SSc patients with preserved LV diastolic function, suggesting that impairment of the LA mechanics is an early sign of myocardial involvement in SSc., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the efficacy of a three-week period of complex and intensive hand physical therapy on hand function in patients with systemic sclerosis (SSc)., Methods: Thirty-one patients with SSc were treated. Hand stretching exercises, ergotherapy supplemented with thermal and mud baths, whirlpool therapy and soft tissue massage were daily used during a three-week period. The control SSc group (n=22) received similar management for their large joints leaving out their hands. The primary outcomes of this study were the Health Assessment Questionnaire (HAQ) and the Disabilities of the Arm, Shoulder and Hand (DASH). Hand Anatomic Index (HAI), Cochin Hand Function (CHFT) and clinical characteristics were also assessed before starting the therapy and six months afterwards., Results: Six months after the investigation period, only the group receiving hand physical therapy showed improvement in HAQ and DASH scores compared to the baseline values (p<0.05). The improvement in median HAQ value (25%-75% quartiles) reached the clinical meaningful rate (baseline 1.125/0.625-1.625/ versus 0.75/0.25-1.5/ at six months). Visual analogue scales of global pain (p<0.01) and Raynaud's phenomenon (p<0.05) also had better results than at baseline. HAI, gripping strength and CHFT also showed some improvement, but did not reach the significance level of change by the end of the six-month observation period., Conclusions: The complex physical therapy caused favourable changes in both the HAQ and the DASH indicating that this particular program had some long-term beneficial effect on hand function in patients with SSc.