Autoimmune antibody profiling plays a prominent role in both classification and prognosis of systemic sclerosis (SSc). In the last years novel autoantibodies have been discovered and have become available in diagnostic assays. However, standardization in autoimmune serology is lacking, which may have a negative impact on the added value of autoantibodies in diagnosis and prognosis of SSc. In this paper we describe the comparison of commercially available diagnostic assays for the detection of SSc-associated autoantibodies and explored the coexistence of multiple SSc-associated autoantibodies within patients.
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Objectives: Pulmonary hypertension is one of the leading causes of death in systemic sclerosis. Early detection and treatment of pulmonary hypertension in systemic sclerosis is crucial. Nailfold capillaroscopy microscopy, vascular autoantibodies AT1R and ETAR, and several candidate-biomarkers have the potential to serve as noninvasive tools to identify systemic sclerosis patients at risk for developing pulmonary hypertension. Here, we explore the classifying potential of nailfold capillaroscopy microscopy characteristics and serum levels of selected candidate-biomarkers in a sample of systemic sclerosis patients with and without different forms of pulmonary hypertension.Methods: A total of 81 consecutive systemic sclerosis patients were included, 40 with systemic sclerosis pulmonary hypertension and 41 with no pulmonary hypertension. In each group, quantitative and qualitative nailfold capillaroscopy microscopy characteristics, vascular autoantibodies AT1R and ETAR, and serum levels of 24 soluble serum factors were determined. For evaluation of the nailfold capillaroscopy microscopy characteristics, linear regression analysis accounting for age, sex, and diffusing capacity of the lungs for carbon monoxide percentage predicted was used. Autoantibodies and soluble serum factor levels were compared using two-sample t test with equal variances.Results: No statistically significant differences were observed in quantitative or qualitative nailfold capillaroscopy microscopy characteristics, or vascular autoantibody ETAR and AT1R titer between systemic sclerosis-pulmonary hypertension and systemic sclerosis-no pulmonary hypertension. In contrast, several serum levels of soluble factors differed between groups: Endostatin, sVCAM, and VEGFD were increased, and CXCL4, sVEGFR2, and PDGF-AB/BB were decreased in systemic sclerosis-pulmonary hypertension. Random forest classification identified Endostatin and CXCL4 as the most predictive classifiers to distinguish systemic sclerosispulmonary hypertension from systemic sclerosis-no pulmonary hypertension.Conclusion: This study shows the potential for several soluble serum factors to distinguish systemic sclerosis-pulmonary hypertension from systemic sclerosis-no pulmonary hypertension. We found no classifying potential for qualitative or quantitative nailfold capillaroscopy microscopy characteristics, or vascular autoantibodies.
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Systemic sclerosis (SSc) is an autoimmune disease which is characterized by vasculopathy, tissue fibrosis and activation of the innate and adaptive immune system. Clinical features of the disease consists of skin thickening and internal organ involvement. Due to the heterogeneous nature of the disease it is difficult to predict disease progression and complications. Despite the discovery of novel autoantibodies associated with SSc, there is an unmet need for biomarkers for diagnosis, disease progression and response to treatment. To date, the use of single (surrogate) biomarkers for these purposes has been unsuccessful. Combining multiple biomarkers in to predictive panels or ultimately algorithms could be more precise. Given the limited therapeutic options and poor prognosis of many SSc patients, a better understanding of the immune-pathofysiological profiles might aid to an adjusted therapeutic approach. Therefore, we set out to explore immunological fingerprints in various clinically defined forms of SSc. We used multilayer profiling to identify unique immune profiles underlying distinct autoantibody signatures. These immune profiles could fill the unmet need for prognosis and response to therapy in SSc. Here, we present 3 pathophysiological fingerprints in SSc based on the expression of circulating antibodies, vascular markers and immunomodulatory mediators.
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The aim of the study was to evaluate whether multiple sclerosis (MS) is associated with risk of cataract or glaucoma. We conducted a population-based cohort study utilizing the UK General Practice Research Database (1987–2009) linked to the national hospital registry of England (1997–2008). Incident MS patients (5576 cases) were identified and each was matched to six patients without MS (controls) by age, gender, and practice. Cox proportional hazard models were used to estimate hazard ratios (HRs) of incident cataract and glaucoma in MS. Time-dependent adjustments were made for age, history of diseases and drug use.
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Background: Multiple sclerosis often leads to fatigue and changes in physical behavior (PB). Changes in PB are often assumed as a consequence of fatigue, but effects of interventions that aim to reduce fatigue by improving PB are not sufficient. Since the heterogeneous nature of MS related symptoms, levels of PB of fatigued patients at the start of interventions might vary substantially. Better understanding of the variability by identification of PB subtypes in fatigued patients may help to develop more effective personalized rehabilitation programs in the future. This study aimed to identify PB subtypes in fatigued patients with multiple sclerosis based on multidimensional PB outcome measures. Methods: Baseline accelerometer (Actigraph) data, demographics and clinical characteristics of the TREFAMS-ACE participants (n = 212) were used for secondary analysis. All patients were ambulatory and diagnosed with severe fatigue based on a score of ≥35 on the fatigue subscale of the Checklist Individual Strength (CIS20r). Fifteen PB measures were used derived from 7 day measurements with an accelerometer. Principal component analysis was performed to define key outcome measures for PB and two-step cluster analysis was used to identify PB types. Results: Analysis revealed five key outcome measures: percentage sedentary behavior, total time in prolonged moderate-to-vigorous physical activity, number of sedentary bouts, and two types of change scores between day parts (morning, afternoon and evening). Based on these outcomes three valid PB clusters were derived. Conclusions: Patients with severe MS-related fatigue show three distinct and homogeneous PB subtypes. These PB subtypes, based on a unique set of PB outcome measures, may offer an opportunity to design more individually-tailored interventions in rehabilitation.
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Sicca syndrome (dry mouth and dry eyes) occurs predominantly due to the side effects of medication, systemic diseases (Sjögren’s disease), and radiotherapy of the head and neck region. Sicca complaints decrease the quality of life, cause sleep disturbances, and affect overall health. This systematic literature review investigates the correlation and/or association between dry mouth and dry eyes. A comprehensive search was conducted through PubMed and Web of Science databases up to November 2024. English-language research studies investigating the association and/or correlation between dry mouth and dry eyes were included. Study quality was assessed using NIH quality assessment tools. Data on publication details, participant characteristics, assessment methods, and outcomes was extracted and synthesised based on the type of outcome (objective and/or subjective assessments) and cohort type.
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From teh UU repository: "Background: Oral immunotherapy (OIT) is a promising therapeutic approach to treat food allergic patients. However, there are some concerns regarding its safety and long-term efficacy. The use of non-digestible oligosaccharides might improve OIT efficacy since they are known to directly modulate intestinal epithelial and immune cells in addition to acting as prebiotics. Aim: To investigate whether a diet supplemented with plant-derived fructo-oligosaccharides (FOS) supports the efficacy of OIT in a murine cow's milk allergy model and to elucidate the potential mechanisms involved. Methods: After oral sensitization to the cow's milk protein whey, female C3H/HeOuJ mice were fed either a control diet or a diet supplemented with FOS (1% w/w) and received OIT (10 mg whey) 5 days a week for 3 weeks by gavage. Intradermal (i.d.) and intragastric (i.g.) challenges were performed to measure acute allergic symptoms and mast cell degranulation. Blood and organs were collected to measure antibody levels and T cell and dendritic cell populations. Spleen-derived T cell fractions (whole spleen-and CD25-depleted) were transferred to naive recipient mice to confirm the involvement of regulatory T cells (Tregs) in allergy protection induced by OIT + FOS. Results: OIT + FOS decreased acute allergic symptoms and mast cell degranulation upon challenge and prevented the challenge-induced increase in whey-specific IgE as observed in sensitized mice. Early induction of Tregs in the mesenteric lymph nodes (MLN) of OIT + FOS mice coincided with reduced T cell responsiveness in splenocyte cultures. CD25 depletion in OIT + FOS-derived splenocyte suspensions prior to transfer abolished protection against signs of anaphylaxis in recipients. OIT + FOS increased serum galectin-9 levels. No differences in short-chain fatty acid (SCFA) levels in the cecum were observed between the treatment groups. Concisely, FOS supplementation significantly improved OIT in the acute allergic skin response, %Foxp3+ Tregs and %LAP+ Th3 cells in MLN, and serum galectin-9 levels. Conclusion: FOS supplementation improved the efficacy of OIT in cow's milk allergic mice. Increased levels of Tregs in the MLN and abolished protection against signs of anaphylaxis upon transfer of CD25-depleted cell fractions, suggest a role for Foxp3+ Tregs in the protective effect of OIT + FOS. "
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Background: Impaired upper extremity function due to muscle paresis or paralysis has a major impact on independent living and quality of life (QoL). Assistive technology (AT) for upper extremity function (i.e. dynamic arm supports and robotic arms) can increase a client’s independence. Previous studies revealed that clients often use AT not to their full potential, due to suboptimal provision of these devices in usual care. Objective: To optimize the process of providing AT for impaired upper extremity function and to evaluate its (cost-)effectiveness compared with care as usual. Methods: Development of a protocol to guide the AT provision process in an optimized way according to generic Dutch guidelines; a quasi-experimental study with non-randomized, consecutive inclusion of a control group (n = 48) receiving care as usual and of an intervention group (optimized provision process) (n = 48); and a cost-effectiveness and cost-utility analysis from societal perspective will be performed. The primary outcome is clients’ satisfaction with the AT and related services, measured with the Quebec User Evaluation of Satisfaction with AT (Dutch version; D-QUEST). Secondary outcomes comprise complaints of the upper extremity, restrictions in activities, QoL, medical consumption and societal cost. Measurements are taken at baseline and at 3, 6 and 9 months follow-up.
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Background/Aims: This study examines the feasibility of a preoperative exercise program to improve the physical fitness of a patient before gastrointestinal surgery. Methods: An outpatient exercise program was developed to increase preoperative aerobic capacity, peripheral muscle endurance and respiratory muscle function in patients with pancreatic, liver, intestinal, gastric or esophageal cancer. During a consult at the outpatient clinic, patients were invited to participate in the exercise program when their surgery was not scheduled within 2 weeks. Results: The 115 participants followed on average 5.7 (3.5) training sessions. Adherence to the exercise program was high: 82% of the planned training sessions were attended, and no adverse events occurred. Mixed model analyses showed a significant increase of maximal inspiratory muscle strength (84.1-104.7 cm H2O; p = 0.00) and inspiratory muscle endurance (35.0-39.5 cm H2O; p = 0.00). No significant changes were found in aerobic capacity and peripheral muscle strength. Conclusion: This exercise program in patients awaiting oncological surgery is feasible in terms of participation and adherence. Inspiratory muscle function improved significantly as a result of inspiratory muscle training. The exercise program however failed to result in improved aerobic capacity and peripheral muscle strength, probably due to the limited number of training sessions as a result of the restricted time interval between screening and surgery.
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Blended behavior change interventions combine therapeutic guidance with online care. This new way of delivering health care is supposed to stimulate patients with chronic somatic disorders in taking an active role in their disease management. However, knowledge about the effectiveness of blended behavior change interventions and how they should be composed is scattered. This comprehensive systematic review aimed to provide an overview of characteristics and effectiveness of blended behavior change interventions for patients with chronic somatic disorders.
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