Objective T cells play a key role in the pathogenesis of early systemic sclerosis. This study was undertaken to assess the safety and efficacy of abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods In this 12‐month, randomized, double‐blind, placebo‐controlled trial, participants were randomized 1:1 to receive either subcutaneous abatacept 125 mg or matching placebo, stratified by duration of dcSSc. Escape therapy was allowed at 6 months for worsening disease. The coprimary end points were change in the modified Rodnan skin thickness score (MRSS) compared to baseline and safety over 12 months. Differences in longitudinal outcomes were assessed according to treatment using linear mixed models, with outcomes censored after initiation of escape therapy. Skin tissue obtained from participants at baseline was classified into intrinsic gene expression subsets. Results Among 88 participants, the adjusted mean change in the MRSS at 12 months was −6.24 units for those receiving abatacept and −4.49 units for those receiving placebo, with an adjusted mean treatment difference of −1.75 units (P = 0.28). Outcomes for 2 secondary measures (Health Assessment Questionnaire disability index and a composite measure) were clinically and statistically significantly better with abatacept. The proportion of subjects in whom escape therapy was needed was higher in the placebo group relative to the abatacept group (36% versus 16%). In the inflammatory and normal‐like skin gene expression subsets, decline in the MRSS over 12 months was clinically and significantly greater in the abatacept group versus the placebo group (P < 0.001 and P = 0.03, respectively). In the abatacept group, adverse events occurred in 35 participants versus 40 participants in the placebo group, including 2 deaths and 1 death, respectively. Conclusion In this phase II trial, abatacept was well‐tolerated, but change in the MRSS was not statistically significant. Secondary outcome measures, including gene expression subsets, showed evidence in support of abatacept. These data should be confirmed in a phase III trial.

The early detection of wound infection in situ can dramatically improve patient care pathways and clinical outcomes. There is increasing evidence that within an infected wound the main bacterial mode of living is a biofilm: a confluent community of adherent bacteria encased in an extracellular polymeric matrix. Here we have reported the development of a prototype wound dressing, which switches on a fluorescent color when in contact with pathogenic wound biofilms. The dressing is made of a hydrated agarose film in which the fluorescent dye containing vesicles were mixed with agarose and dispersed within the hydrogel matrix. The static and dynamic models of wound biofilms, from clinical strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis, were established on nanoporous polycarbonate membrane for 24, 48, and 72 h, and the dressing response to the biofilms on the prototype dressing evaluated. The dressing indicated a clear fluorescent/color response within 4 h, only observed when in contact with biofilms produced by a pathogenic strain. The sensitivity of the dressing to biofilms was dependent on the species and strain types of the bacterial pathogens involved, but a relatively higher response was observed in strains considered good biofilm formers. There was a clear difference in the levels of dressing response, when dressings were tested on bacteria grown in biofilm or in planktonic cultures, suggesting that the level of expression of virulence factors is different depending of the growth mode. Colorimetric detection on wound biofilms of prevalent pathogens (S. aureus, P. aeruginosa, and E. faecalis) is also demonstrated using an ex vivo porcine skin model of burn wound infection.

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OPINION STATEMENT Systemic sclerosis (SSc) is an autoimmune disease initially recognized by hand involvement due to characteristic Raynaud's phenomenon (RP), puffy hands, skin thickening, and contractures resembling claw deformities. SSc contributes to hand impairment through inflammatory arthritis, joint contractures, tendon friction rubs (TFRs), RP, digital ulcers (DU), puffy hands, skin sclerosis, acro-osteolysis, and calcinosis. These manifestations, which often co-exist, can contribute to difficulty with occupational activities and activities of daily living (ADL), which can result in impaired quality of life. However, despite this knowledge, most diagnostic and treatment principles in SSc are focused on visceral manifestations due to known associations with morbidity and mortality. Treatment of inflammatory arthritis is symptom based and involves corticosteroids ≤10mg daily, methotrexate, tumor necrosis factor inhibitors, tocilizumab, and abatacept. Small joint contractures are managed by principles of occupational hand therapy and rarely surgical procedures. TFRs may be treated similar to inflammatory arthritis with corticosteroids. All patients with RP and DU should keep digits covered and warm and avoid vasoconstrictive agents. Pharmacologic management of RP begins with use of calcium channel blockers, but additional agents that may be considered are fluoxetine and phosphodiesterase 5 (PDE5) inhibitors. DU management also involves vasodilators including calcium channel blockers and PDE5 inhibitors; bosentan has also been shown to prevent DU. In patients with severe RP and active DU, intravenous epoprostenol or iloprost can be used and surgical procedures, such as botulinum injections and digital sympathectomies, may be considered. For those with early diffuse cutaneous SSc needing immunosuppression for skin sclerosis, methotrexate or mycophenolate mofetil can be used, but the agent of choice depends on co-existing manifestations, such as inflammatory arthritis and/or lung involvement. Various pharmacologic agents for calcinosis have been considered but are generally ineffective; however, surgical options, including excision of areas of calcinosis, can be considered. Overall management of hand impairment for all patients with SSc should include occupational hand therapy techniques such as range of motion exercises, paraffin wax, and devices to assist in ADL. Thus, treatment options for the various manifestations contributing to hand impairment in SSc are limited and often modestly efficacious at best. Robust studies are needed to address the manifestations of SSc that contribute to hand impairment.

Objectives: Core outcome set (COS) development often begins with a systematic review to identify outcomes. Reviews frequently show heterogeneity in numbers of outcomes reported across trials. Contributing to this is a lack of a uniform definition for an outcome. This study proposes a first working definition for a unique trial outcome to support reporting a quantitative assessment of outcome reporting heterogeneity (ORH).Study Design and Setting: Eligible COS literature (development papers, protocols, and reviews) were identified using the COMET database, Ovid MEDLINE, and PubMed. Outcome numbers, definitions, timing, and grouping methodology were examined.Results: One hundred and thirty two studies were included. 82 (88.1%) studies (excluding protocols) reported a total number of unique outcomes (median, 82; range, 12-5776; IQR, 261). Timing of assessment was reported in 32 (31.4%) studies. Methods to group similar outcomes were reported in 8 (7.8%) articles. No study defined how outcomes were agreed as different and how final numbers of unique outcomes were determined. It is proposed that a unique outcome requires original meaning and context. Thus ORH is suggested to be the reporting of multiple unique outcomes across trials related to one health care condition.Conclusion: This review identified inconsistencies in how authors define, extract, group, and count trial outcomes. Further work is needed to refine our proposed definitions to optimize COS development and allow a quantifiable measure of ORH.

We used a modified educational method to estimate clinically relevant cut-points to classify severity for PROMIS measures This allows for meaningful interpretation of PROMIS measures in a clinical setting of RD population.

The detection of increased cerebral oxygenation secondary to cerebral hyperaemia, induced by hypercapnia has been studied in anaesthetised patients using a near infrared, reflectance mode, cerebral oxygenation monitor (Invos 3100 Somanetics, Troy, Michigan, USA). Two studies were performed, with and without a pneumatic scalp tourniquet, to distinguish between extracranial and intracranial changes in tissue oxygenation. In the control study a mean increase in end tidal CO2 of 23-1 mm Hg was accompanied by a mean increase in middle cerebral artery flow velocity of 116%. Regional cerebral oxygen saturation (rSo,) measured transcutaneously in the frontal distribution of the middle cerebral artery increased significandy from 70*5% to 74*6% (p = 0.001). During the second study with a scalp tourniquet inflated to maintain the extracranial tissues in a state of stable ischaemia a mean increase in end tidal CO2 of 22-3 mm Hg was accompanied by a mean increase in middle cerebral artery flow velocity of 121%. The change in rSo2 from 62-6% to 64-5% was not significant (p = 0.085).There was no correlation between the change in middle cerebral artery flow velocity and rSo2 in the control or scalp ischaemia group. This study shows that the Invos 3100 monitor is sensitive to tissue oxygenation but does not reliably detect changes in cerebral oxygenation as a result of profound cerebral hyperaemia. The contribution of extracerebral tissue to the attenuation of near infrared light and the lack of spatial resolution remain major problems to be overcome before this or other near infrared spectroscopy instruments can be introduced into clinical practice.(

To test theoretical assumptions supporting the use of near-infrared spectroscopy (NIRS) in clinical practice, we examined the behaviour of NIR light transmission and attenuation in the human head. Sterile probes for emitting and detecting NIR light at a fixed separation of 40 mm were placed in turn on intact skin, skull, dura and cerebral cortex of 10 patients undergoing elective neurosurgery. In the first five patients, the detecting probe was moved through successive extracerebral layers with the emitter on the skin surface. In the second five patients, the process was reversed, with the emitting probe moved and the detector in the same place on the scalp. NIR intensity was measured at each tissue interface and compared with the intensity measured at the skin surface with all layers intact. Removal of bone and dura from the light path caused a significant reduction in detected intensity. The largest mean reduction in light intensity was a 14-fold decrease with removal of bone (unadjusted P < 0.0001; paired t test). The assumptions that extracerebral tissues contribute little to attenuation of NIR light in the adult head and that most of this attenuation occurs superficially in the scalp are drawn into question by this study. We postulate that the skull and/or its interface with other layers may act as an optical 'channel', distorting the behaviour of NIR light in the human head.