Current State of Reporting Pain Outcomes in Cochrane Reviews of Chronic Musculoskeletal Pain Conditions and Considerations for an OMERACT Research Agenda.

OBJECTIVE To assess the current state of reporting of pain outcomes in Cochrane reviews on chronic musculoskeletal painful conditions and to elicit opinions of patients, healthcare practitioners, and methodologists on presenting pain outcomes to patients, clinicians, and policymakers. METHODS We identified all reviews in the Cochrane Library of chronic musculoskeletal pain conditions from Cochrane review groups (Back, Musculoskeletal, and Pain, Palliative, and Supportive Care) that contained a summary of findings (SoF) table. We extracted data on reported pain domains and instruments and conducted a survey and interviews on considerations for SoF tables (e.g., pain domains, presentation of results). RESULTS Fifty-seven SoF tables in 133 Cochrane reviews were eligible. SoF tables reported pain in 56/57, with all presenting results for pain intensity (20 different outcome instruments), pain interference in 8 SoF tables (5 different outcome instruments), and pain frequency in 1 multiple domain instrument. Other domains like pain quality or pain affect were not reported. From the survey and interviews [response rate 80% (36/45)], we derived 4 themes for a future research agenda: pain domains, considerations for assessing truth, discrimination, and feasibility; clinically important thresholds for responder analyses and presenting results; and establishing hierarchies of outcome instruments. CONCLUSION There is a lack of standardization in the domains of pain selected and the manner that pain outcomes are reported in SoF tables, hampering efforts to synthesize evidence. Future research should focus on the themes identified, building partnerships to achieve consensus and develop guidance on best practices for reporting pain outcomes.

Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth.

Therapeutic antibodies targeting programmed cell death 1 (PD-1) activate tumor-specific immunity and have shown remarkable efficacy in the treatment of melanoma. Yet, little is known about tumor cell-intrinsic PD-1 pathway effects. Here, we show that murine and human melanomas contain PD-1-expressing cancer subpopulations and demonstrate that melanoma cell-intrinsic PD-1 promotes tumorigenesis, even in mice lacking adaptive immunity. PD-1 inhibition on melanoma cells by RNAi, blocking antibodies, or mutagenesis of melanoma-PD-1 signaling motifs suppresses tumor growth in immunocompetent, immunocompromised, and PD-1-deficient tumor graft recipient mice. Conversely, melanoma-specific PD-1 overexpression enhances tumorigenicity, as does engagement of melanoma-PD-1 by its ligand, PD-L1, whereas melanoma-PD-L1 inhibition or knockout of host-PD-L1 attenuate growth of PD-1-positive melanomas. Mechanistically, the melanoma-PD-1 receptor modulates downstream effectors of mTOR signaling. Our results identify melanoma cell-intrinsic functions of the PD-1:PD-L1 axis in tumor growth and suggest that blocking melanoma-PD-1 might contribute to the striking clinical efficacy of anti-PD-1 therapy.

ABCB5 Identifies Immunoregulatory Dermal Cells

Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5(+) DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5(+) DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy.

Le personnage de la femme-artiste chez l'écrivain polonaise Narcyza Żmichowska (1819-1876) : Helusia héritière de Corinne de Mme de Staël et de Consuelo de George Sand

Si les hommes bénéficient d’emblée de mythes (Pygmalion, Orphée) qui légitiment et motivent leur créativité, il faut attendre Corinne (1807) de Mme Staël et Consuelo (1842) de George Sand pour que le mythe de la femme créatrice trouve enfin, dans la littérature européenne, à se concrétiser et à se développer sous la forme de Künstlerromane féminins. Corinne la poétesse et Consuelo la cantatrice sont devenues des exemples littéraires non seulement pour les femmes victoriennes, comme le montre par exemple le livre de Linda Lewis intitulé Germaine de Staël, George Sand and the Victorian Woman Artist, mais également pour les femmes polonaises issues des classes favorisées - qui lisaient d’ailleurs couramment en français. En effet, même si elles ont été officiellement décriées par la critique conservatrice polonaise pour leur « immoralité », George Sand et Mme de Staël ont été lues, bien lues et même beaucoup lues par leurs contemporaines polonaises - comme le témoigne la correspondance de ces dernières, dans laquelle elles ont moins de peine à se livrer. Le thème de la femme artiste déchirée entre la carrière publique et la vie privée, tel qu’il est représenté dans Corinne et dans Consuelo, a en particulier attiré toute leur attention et suscité chez les femmes écrivains le désir d’apporter de nouvelles manières de résoudre ce conflit. Dans cet article, le Künstlerinroman polonais Książka Pamiątek (Livre des souvenirs, 1846) de Narcyza Żmichowska fait l’objet d’une analyse comparative détaillée avec les deux Künstlerinromane français dont par ailleurs il se réclame.