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[...]inflammation represents the perfect subject for scientific collaborations between early career researchers. [...]as in other fields of research, the experimental evidence needs to find clinical translation. [...]we hope that the readers appreciate the varied research included in this Research Topic, “Rising Stars in Inflammation”.

Background The aging of migrant populations across Europe challenges researchers in palliative care to produce knowledge that can be used to respond to the needs of the growing group of patients with a migration background and address ethnic disparities in palliative care. The aim of this study was to identify what factors influence researchers’ efforts to address responsiveness of palliative care to patients with a migration background and other underserved populations in their projects. Methods We conducted semi-structured interviews with 11 researchers involved in seven projects under the Dutch national program for palliative care innovation. Results Researchers’ efforts to address responsiveness of palliative care in their projects were influenced by individual factors, i.e. awareness of the need for responsiveness to patients with a migration background; experience with responsiveness; and, differences in perceptions on responsiveness in palliative care. Researchers’ efforts were furthermore influenced by institutional factors, i.e. the interaction with healthcare institutions and healthcare professionals as they rely on their ability to identify the palliative patient with a migration background, address the topic of palliative care, and enrol these patients in research; scientific standards that limit the flexibility needed for responsive research; and, the responsiveness requirements set by funding agencies. Conclusion Researchers play a key role in ensuring research addresses responsiveness to patients with a migration background. Such responsiveness may also benefit other underserved populations. However, at times researchers lack the knowledge and experience needed for responsive research. To address this we recommend training in responsiveness for researchers in the field of palliative care. We also recommend training for healthcare professionals involved in research projects to increase enrolment of patients with a migration background and other underrepresented populations. Lastly, we encourage researchers as well as research institutions and funding agencies to allow flexibility in research practices and set a standard for responsive research practice.

Background A key aim of palliative care is to improve the quality of life of patients and their families. To help ensure quality of life for the families of patients with migrant backgrounds, this study sought insights into the dignity of informal caregivers in migrant communities. This could improve understanding of family-centered care for migrant patients. Methods Twenty semi-structured interviews with informal caregivers of Turkish, Moroccan, or Surinamese background living in the Netherlands were analyzed thematically. Results The dignity of the patient and that of their informal caregivers were found to be strongly interrelated. Most important for the dignity of caregivers was ensuring good care for their patients and preserving the patients’ dignity. Ensuring good care involved advocating for good and dignified care and for satisfaction of a patient’s wishes. For many informal caregivers, it also included delivering care to the patient by themselves or together with other family members, despite having to give up part of their own lives. Providing care themselves was part of maintaining a good relationship with the patient; the care was to cater to the patient’s preferences and help preserve the patient’s dignity, and it could be accompanied by valuable aspects such as times for good conversations. Positive interaction between an informal caregiver and a patient positively influenced the informal caregiver’s dignity. Informal caregiver and patient dignity were often compromised simultaneously; when informal caregivers felt healthcare professionals were undermining a patient’s dignity, their own dignity suffered. According to informal caregivers, healthcare professionals can help them preserve dignity by taking seriously their advice about the patient, keeping them informed about the prognosis of the disease and of the patient, and dealing respectfully with differences in values at the end of life. Conclusion The dignity of migrant patients’ informal caregivers in the last phase of a patient’s life is closely entwined with ensuring good care and dignity for the patient. Healthcare professionals can strengthen the dignity of informal caregivers by supporting their caregiving role.

Background European migrant populations are aging and will increasingly be in need of palliative and end of life care. However, migrant patients are often underrepresented in palliative care research populations. This poses a number of drawbacks, such as the inability to generalize findings or check the appropriateness of care innovations amongst migrant patients. The aim of this study was to develop a self-assessment instrument to help palliative care researchers assess and find ways to improve their projects’ diversity responsiveness in light of the aging migrant population, and determine whether in addition to older migrants other groups should be included in the instrument’s focus. Methods After developing a concept instrument based on the standards for equity in healthcare for migrants and other vulnerable groups, literature review and interviews with palliative care researchers, we conducted a Delphi study to establish the content of the self-assessment instrument and used think aloud methods in a study involving seven projects for usability testing of the self-assessment instrument. Results A Delphi panel of 22 experts responded to a questionnaire consisting of 3 items concerning the target group and 30 items on diversity responsiveness measures. Using an a priori set consensus rate of 75% to include items in the self-assessment instrument, experts reached consensus on 25 out of 30 items on diversity responsiveness measures. Findings furthermore indicate that underserved groups in palliative care other than migrant patients should be included in the instrument’s focus. This was stressed by both the experts involved in the Delphi study and the researchers engaged in usability testing. Usability testing additionally provided insights into learnability, error-rate, satisfaction and applicability of the instrument, which were used to revise the self-assessment instrument. Conclusions The final self-assessment instrument includes a list of 23 diversity responsiveness measures to be taken at varying stages of a project, and targets all groups at risk of being underrepresented. This instrument can be used in palliative care research to assess diversity responsiveness of projects and instigate action for improvement.

Preserving personal dignity is an important aim of palliative care. Little is known about how physicians perceive and preserve dignity of patients from non-western migration backgrounds. Insight in this is important given the increased demand for culturally sensitive palliative care. To gain insight in how Dutch physicians perceive and preserve dignity in the last phase of life for patients from non-western migration backgrounds. Qualitative thematic analysis of semi-structured interviews. Fifteen physicians experienced in palliative care. Physicians experienced dilemmas in preserving dignity of non-western patients in three situations: (a) relief of suffering in the terminal phase, (b) termination of interventions and treatment, and (c) disclosure of diagnosis. Physicians wanted to grant the needs of patients in the last phase of their lives, which was central to physicians' view on dignity, but dilemmas arose when this conflicted with physicians' other personal and professional values. To make the dilemmas manageable, physicians assessed whether needs of patients were authentic, but due to linguistic, cultural, and communication barriers, this was difficult with non-western patients. To find a way out of the dilemmas, physicians had three strategies: accept and go along with patient's wishes, convince or overrule the patient or family, or seek solutions that were acceptable for all. Physicians encounter dilemmas providing palliative care for people from non-western backgrounds. Future physicians can be trained in connective strategies and seeking middle grounds to optimally preserve patients' dignity while being in concordance with their personal and professional values.

ObjectiveMast cells may play a role in rheumatoid arthritis (RA), but activation of human mast cells in autoimmune settings has been little studied. Toll-like receptors (TLR) and Fcγ receptors (FcγR) are important receptors for cellular activation in the joint, but expression and stimulation of these receptors in human mast cells or the functional interplay between these pathways is poorly understood. Here, we analysed triggering of human mast cells via these receptors in the context of anti-citrullinated protein antibody-positive (ACPA+) RA.MethodsRNA and protein expression of TLRs and FcγR was quantified using PCR and flow cytometry, respectively. Mast cells were stimulated with TLR ligands (including HSP70) combined with IgG immune complexes and IgG-ACPA.ResultsHuman mast cells expressed TLRs and produced cytokines in response to TLR ligands. Both cultured and synovial mast cells expressed FcγRIIA, and triggering of this receptor by IgG immune complexes synergised with activation by TLR ligands, leading to two- to fivefold increased cytokine levels. Mast cells produced cytokines in response to ACPA immune complexes in a citrulline-specific manner, which synergised in the presence of HSP70.ConclusionsOur data show that synovial mast cells express FcγRIIA and that mast cells can be activated by IgG-ACPA and TLR ligands. Importantly, combined stimulation via TLRs and immune complexes leads to synergy in cytokine production. These findings suggest mast cells are important targets for TLR ligands and immune complexes, and that combined activation of mast cells via these pathways greatly enhances inflammation in synovial tissue of RA patients.

BackgroundMast cells have been implicated in the pathogenesis of Rheumatoid Arthritis (RA). In particular, activation of mast cells by IL-33 has been linked to the development of arthritis in animal models. Likewise, increased levels of IL-33 have been described in the sera and synovial fluid of RA patients. However, little is known about the influence of IL-33-triggered human mast cells on immune responses in RA.ObjectivesTo evaluate the activation of mast cells by IL-33 and immune complexes and their ability to modulate monocyte-mediated immune responses in the context of Anti-Citrullinated Protein Antibody-positive (ACPA+) RA.MethodsHuman mast cells were stimulated with IL-33 combined with immune complexes (IC) formed by plate bound total IgG or IgG-ACPA bound to citrullinated fibrinogen. Mast cell activation was analysed by measuring cytokine production with ELISA and a multiplex assay. By immunofluorescence, the cellular interactions of mast cells were assessed in the synovial tissue of patients with established ACPA+ RA undergoing knee joint replacement. Finally, the influence of mast cells on LPS-induced monocyte activation was evaluated by measuring cytokine production by ELISA and membrane markers by flow cytometry.ResultsIL-33 enhanced the activation of mast cells by IC, including IgG-ACPA IC, as demonstrated by a significant increase of IL-8 production. Further analysis of mast cell supernatants showed a differential activation of mast cells, with IC preferentially inducing pro-inflammatory mediators (e.g. IL-8) and IL-33 inducing significantly higher amounts of potential immunomodulatory mediators (e.g. IL-10 and histamine). Additionally, the combined stimulation with IL-33 and IgG IC showed a significant synergistic effect exclusively for the IL-33-induced immunomodulatory mediators. Ex vivo, in the synovial membrane of RA patients, mast cells were frequently found in contact with CD14+ cells. Finally, mast cells activated with IL-33 and IC inhibited, mainly via the release of IL-10 and histamine, the LPS-induced production of the prototypical pro-inflammatory cytokine TNF-α and the upregulation of the co-stimulatory molecule CD80 by monocytes.ConclusionsWe here show that human mast cells acquire an immunomodulatory phenotype when exposed to IL-33, releasing regulatory mediators even when triggered with pro-inflammatory stimuli such as immune complexes. This finding was corroborated by the evidence of mast cell-monocyte interactions at synovial level and by the functional demonstration that mast cells triggered with IL-33 and IC are able to suppress monocyte pro-inflammatory activation. Overall, our study suggests a novel immunomodulatory role for human mast cells that might have a functional relevance in the pathogenesis of RA.ReferencesGalli SJ, Grimbaldeston M, Tsai M. Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nature reviews Immunology. 2008;8(6):478-86.Brown MA, Hatfield JK. Mast Cells are Important Modifiers of Autoimmune Disease: With so Much Evidence, Why is There Still Controversy? Front Immunol. 2012;3:147.Liew FY. IL-33: a Janus cytokine. Ann Rheum Dis. 2012;71 Suppl 2:i101-4.AcknowledgementsThis research was conducted while F. Rivellese was an ARTICULUM Fellow.Disclosure of InterestNone declared