Systemic sclerosis phase III clinical trials: Hope on the horizon?

While significant progress has been made in treating systemic sclerosis, many patients still have an outcome that is far from satisfactory. For the first time in history, several drugs are now in phase III randomized controlled trials. Approaches tested include the anti-B cell antibody rituximab, the anti-interleukin-6 receptor antibody tocilizumab, the antifibrotic drugs nintedanib and pirfenidone, and the cannabinoid receptor mimetic lenabasum.

Role of the Gut⁻Liver Axis in Driving Parenteral Nutrition-Associated Injury.

For decades, parenteral nutrition (PN) has been a successful method for intravenous delivery of nutrition and remains an essential therapy for individuals with intolerance of enteral feedings or impaired gut function. Although the benefits of PN are evident, its use does not come without a significant risk of complications. For instance, parenteral nutrition-associated liver disease (PNALD)-a well-described cholestatic liver injury-and atrophic changes in the gut have both been described in patients receiving PN.

European multicentre study validates enhanced liver fibrosis test as biomarker of fibrosis in systemic sclerosis.

Objectives: To validate enhanced liver fibrosis (ELF) test and its components-amino-terminal propeptide of procollagen type III (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and HA-as biomarkers of fibrosis in SSc in an independent, international, multicentre cohort.

Methods: Two hundred and fifty-four SSc patients from six Rheumatology Centres were included. Sera were collected and stored according to EUSTAR biobanking recommendations and analysed through automated high throughput diagnostics.

Emergency Physicians' Perceived Influence of EHR Use on Clinical Workflow and Performance Metrics.

Objective: Over the last decade, electronic health records (EHRs) have shaped clinical practice. In this article, we investigated the perceived effects of EHR use on clinical workflow and meaningful use (MU) performance metrics.

Materials And Methods: Semistructured interviews were conducted with 20 (= 20) physicians at two urban emergency departments.

Efficiency of Emergency Physicians: Insights from an Observational Study using EHR Log Files.

Objective: With federal mandates and incentives since the turn of this decade, electronic health records (EHR) have been widely adopted and used for clinical care. Over the last several years, we have seen both positive and negative perspectives on its use. Using an analysis of log files of EHR use, we investigated the nature of EHR use and their effect on an emergency department's (ED) throughput and efficiency.

Proteomic Analysis of Human Scleroderma Fibroblasts Response to Transforming Growth Factor-ß.

Purpose: Systemic sclerosis (SSc) is characterized by autoimmunity, vasculopathy and fibrosis. Fibrosis is due to an activation of fibroblasts by the transforming growth factor-ß (TGF-ß). This study investigates the proteomic response of SSc fibroblasts to TGF-ß.

Major lung complications of systemic sclerosis.

Systemic sclerosis (SSc) is associated with high mortality owing to internal organ complications, and lung disease is the leading cause of SSc-associated death. The most notable lung complications in SSc are fibrosis and pulmonary arterial hypertension (PAH). A major challenge for the management of lung disease in SSc is detecting those patients with severe pathology and those patients who are likely to benefit from available treatments.

Fluid reasoning and reading difficulties among children with ADHD.

Children with attention-deficit/hyperactivity disorder (ADHD) commonly experience difficulties in reading and in fluid reasoning (G). According to Cattell's Investment Theory (1987), G is a causal factor in the development of crystallized knowledge (G) and academic skills; therefore, the co-occurrence of reading and G difficulties within ADHD may not be coincidental. In the present study with children with both ADHD and reading difficulties ( = 187; 61% male;  = 9.

Ongoing clinical trials and treatment options for patients with systemic sclerosis-associated interstitial lung disease.

SSc is a rare CTD that affects multiple organ systems, resulting in substantial morbidity and mortality. Evidence of interstitial lung disease (ILD) is seen in ∼80% of patients with SSc. Currently there is no approved disease-modifying treatment for ILD and few effective treatment options are available.

Reliability of digital ulcer definitions as proposed by the UK Scleroderma Study Group: A challenge for clinical trial design.

Introduction: The reliability of clinician grading of systemic sclerosis-related digital ulcers has been reported to be poor to moderate at best, which has important implications for clinical trial design. The aim of this study was to examine the reliability of new proposed UK Scleroderma Study Group digital ulcer definitions among UK clinicians with an interest in systemic sclerosis.

Methods: Raters graded (through a custom-built interface) 90 images (80 unique and 10 repeat) of a range of digital lesions collected from patients with systemic sclerosis.

The Scleroderma Patient-Centered Intervention Network Cohort: baseline clinical features and comparison with other large scleroderma cohorts.

Objectives: The Scleroderma Patient-centered Intervention Network (SPIN) Cohort is a web-based cohort designed to collect patient-reported outcomes at regular intervals as a framework for conducting trials of psychosocial, educational, self-management and rehabilitation interventions for patients with SSc. The aim of this study was to present baseline demographic, medical and patient-reported outcome data of the SPIN Cohort and to compare it with other large SSc cohorts.

Methods: Descriptive statistics were used to summarize SPIN Cohort characteristics; these were compared with published data of the European Scleroderma Trials and Research (EUSTAR) and Canadian Scleroderma Research Group (CSRG) cohorts.

Should all digital ulcers be included in future clinical trials of systemic sclerosis-related digital vasculopathy?

Digital ulcers (DU) are a common manifestation of systemic sclerosis (SSc) and occur at a variety of locations including the fingertips and over the extensor aspects of the hands. However, most recent clinical trials have included only fingertip DUs as these are believed to be ischaemic in aetiology, and therefore likely to benefit from treatment with vasoactive drug therapies. There is an emerging evidence base to suggest that all DUs in SSc could share an ischaemic component which is potentially responsive to vascular therapy.

Therapeutic interleukin-6 blockade reverses transforming growth factor-beta pathway activation in dermal fibroblasts: insights from the faSScinate clinical trial in systemic sclerosis.

Objectives: Skin fibrosis mediated by activated dermal fibroblasts is a hallmark of systemic sclerosis (SSc), especially in the subset of patients with diffuse disease. Transforming growth factor-beta (TGFβ) and interleukin-6 (IL-6) are key candidate mediators in SSc. Our aim was to elucidate the specific effect of IL-6 pathway blockade on the biology of SSc fibroblasts in vivo by using samples from a unique clinical experiment-the faSScinate study-in which patients with SSc were treated for 24 weeks with tocilizumab (TCZ), an IL-6 receptor-α inhibitor.

Brief Report: Smoking in Systemic Sclerosis: A Longitudinal European Scleroderma Trials and Research Group Study.

Objective: Data on the role of tobacco exposure in systemic sclerosis (SSc; scleroderma) severity and progression are scarce. We aimed to assess the effects of smoking on the evolution of pulmonary and skin manifestations, based on the European Scleroderma Trials and Research group database.

Methods: Adult SSc patients with data on smoking history and a 12-24-month follow-up visit were included.

Lysophosphatidic Acid Receptor 1 Antagonist SAR100842 for Patients With Diffuse Cutaneous Systemic Sclerosis: A Double-Blind, Randomized, Eight-Week Placebo-Controlled Study Followed by a Sixteen-Week Open-Label Extension Study.

Objective: Preclinical studies suggest a role for lysophosphatidic acid (LPA) in the pathogenesis of systemic sclerosis (SSc). We undertook this study to assess SAR100842, a potent selective oral antagonist of the LPA receptor, for safety, biomarkers, and clinical efficacy in patients with diffuse cutaneous SSc (dcSSc).

Methods: An 8-week double-blind, randomized, placebo-controlled study followed by a 16-week open-label extension with SAR100842 was performed in patients with early dcSSc who had a baseline modified Rodnan skin thickness score (MRSS) of at least 15.

Using Implementation Intentions to Prevent Relapse after Psychological Treatment for Depression - the SMArT Intervention.

Background: It is recognized that a significant proportion of people with depression are prone to relapse, even after successful treatment, and that self-management interventions should be developed and provided. There is evidence that implementation intentions (IMPS) can be successfully applied to health-related behaviours but their application to self-management of mental health problems has been limited.

Aims: This paper describes the design and initial evaluation of a Self-Management After Therapy (SMArT) intervention, which incorporated IMPS and followed psychological therapy for depression.

Cardiac fibroblast-specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin-6 signaling mechanism.

Recent studies suggest that cardiac fibroblast-specific p38α MAPK contributes to the development of cardiac hypertrophy, but the underlying mechanism is unknown. Our study used a novel fibroblast-specific, tamoxifen-inducible p38α knockout (KO) mouse line to characterize the role of fibroblast p38α in modulating cardiac hypertrophy, and we elucidated the mechanism. Myocardial injury was induced in tamoxifen-treated Cre-positive p38α KO mice or control littermates via chronic infusion of the β-adrenergic receptor agonist isoproterenol.

Incidence of pulmonary hypertension and determining factors in patients with systemic sclerosis.

The objective of this study was to evaluate the incidence of pulmonary hypertension (PH) and determining factors in patients with systemic sclerosis (SSc) and a diffusing capacity of the lung for carbon monoxide () <60% predicted.In this bicentric, prospective cohort study, patients with SSc were clinically assessed at baseline and after 3 years, including right heart catheterisation (RHC). Analysis of determining factors for the development of PH was performed using univariate and multivariate analyses.

The novel use of botulinum toxin A for the treatment of Raynaud's phenomenon in the toes.

Raynaud's phenomenon is a vasospastic disorder of the digital vessels triggered by exposure to cold or stress. It is most commonly observed in the hands, but also frequently affects the toes. We present three cases of patients with severe Raynaud's phenomenon in the toes, secondary to scleroderma.

Distinctive clinical phenotype of anti-centromere antibody-positive diffuse systemic sclerosis.

Objectives: The aim was to define clinical characteristics and long-term survival of patients with dcSSc and positive ACA.

Methods: We identified all cases of ACA SSc in our cohort ( = 1313). Those with dcSSc (ACA diffuse) were compared with representative groups of consecutive ACA patients with limited subset (ACA limited) and ACA dcSSc (non-ACA diffuse).

Development of systemic sclerosis in transgender females: a case series and review of the literature.

Objectives: Systemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease with a female predominance. The reason for the female predilection in SSc may relate to the difference in hormones between the genders. There are no current data on the influence male-to-female sex transition may have in the development of SSc.

A Multicenter Study of the Validity and Reliability of Responses to Hand Cold Challenge as Measured by Laser Speckle Contrast Imaging and Thermography: Outcome Measures for Systemic Sclerosis-Related Raynaud's Phenomenon.

Objective: Reliable and objective outcome measures to facilitate clinical trials of novel treatments for systemic sclerosis (SSc)-related Raynaud's phenomenon (RP) are badly needed. Laser speckle contrast imaging (LSCI) and thermography are noninvasive measures of perfusion that have shown excellent potential. This multicenter study was undertaken to determine the reliability and validity of a hand cold challenge protocol using LSCI, standard thermography, and low-cost cell phone/mobile phone thermography (henceforth referred to as mobile thermography) in patients with SSc-related RP.

Factors influencing early referral, early diagnosis and management in patients with diffuse cutaneous systemic sclerosis.

Objective: To gain insight into clinical practice regarding referral, early diagnosis and other aspects of the management of patients with dcSSc in Europe and the USA.

Methods: Semi-structured interviews were conducted with 84 rheumatologists (or internal medicine physicians) and 40 dermatologists in different countries (the UK, France, Germany, Italy, Spain and the USA). Physicians were asked to identify key steps in the patient pathway relating to patient presentation, diagnosis and referral, in addition to other treatment and follow-up processes.