Specialized pro-resolving mediators enhance the clearance of dead cells.

The failure to resolve inflammation underpins to several prevalent diseases, like atherosclerosis, and so identifying ways to boost resolution is unmet clinical needs. The resolution of inflammation is governed by several factors such as specialized pro-resolving mediators (SPMs) that counter-regulate pro-inflammatory pathways and promote tissue repair without compromising host defense. A major function of nearly all SPMs is to enhance the clearance of dead cells or efferocytosis. As such, phagocytes, such as macrophages, are essential cellular players in the resolution of inflammation because of their ability to rapidly and efficiently clear dead cells. This review highlights the role of SPMs in the clearance of apoptotic and necroptotic cells and offers insights into how targeting efferocytosis may provide new treatments for non-resolving diseases, like atherosclerosis.

Resolvin D2-G-Protein Coupled Receptor 18 Enhances Bone Marrow Function and Limits Steatosis and Hepatic Collagen Accumulation in Aging.

Aging is associated with nonresolving inflammation and tissue dysfunction. Resolvin D2 (RvD2) is a proresolving ligand that acts through the G-protein-coupled receptor called GPR18. Unbiased RNA sequencing revealed increased Gpr18 expression in macrophages from old mice, and in livers from elderly humans, which was associated with increased steatosis and fibrosis in middle-aged (MA) and old mice. MA mice that lacked GPR18 on myeloid cells had exacerbated steatosis and hepatic fibrosis, which was associated with a decline in Mac2+ macrophages. Treatment of MA mice with RvD2 reduced steatosis and decreased hepatic fibrosis, correlating with increased Mac2+ macrophages, increased monocyte-derived macrophages, and elevated numbers of monocytes in the liver, blood, and bone marrow. RvD2 acted directly on the bone marrow to increase monocyte-macrophage progenitors. A transplantation assay further demonstrated that bone marrow from old mice facilitated hepatic collagen accumulation in young mice. Transient RvD2 treatment to mice transplanted with bone marrow from old mice prevented hepatic collagen accumulation. Together, this study demonstrates that RvD2-GPR18 signaling controls steatosis and fibrosis and provides a mechanistic-based therapy for promoting liver repair in aging.

Occupational advice to help people return to work following lower limb arthroplasty: the OPAL intervention mapping study.

BACKGROUND: Hip and knee replacements are regularly carried out for patients who work. There is little evidence about these patients' needs and the factors influencing their return to work. There is a paucity of guidance to help patients return to work after surgery and a need for structured occupational advice to enable them to return to work safely and effectively. OBJECTIVES: To develop an occupational advice intervention to support early recovery to usual activities including work that is tailored to the requirements of patients undergoing hip or knee replacements. To test the acceptability, practicality and feasibility of this intervention within current care frameworks. DESIGN: An intervention mapping approach was used to develop the intervention. The research methods employed were rapid evidence synthesis, qualitative interviews with patients and stakeholders, a prospective cohort study, a survey of clinical practice and a modified Delphi consensus process. The developed intervention was implemented and assessed during the final feasibility stage of the intervention mapping process. SETTING: Orthopaedic departments in NHS secondary care. PARTICIPANTS: Patients who were in work and intending to return to work following primary elective hip or knee replacement surgery, health-care professionals and employers. INTERVENTIONS: Occupational advice intervention. MAIN OUTCOME MEASURES: Development of an occupational advice intervention, fidelity of the developed intervention when delivered in a clinical setting, patient and clinician perspectives of the intervention and preliminary assessments of intervention effectiveness and cost. RESULTS: A cohort study (154 patients), 110 stakeholder interviews, a survey of practice (152 respondents) and evidence synthesis provided the necessary information to develop the intervention. The intervention included information resources, a personalised return-to-work plan and co-ordination from the health-care team to support the delivery of 13 patient and 20 staff performance objectives. To support delivery, a range of tools (e.g. occupational checklists, patient workbooks and employer information), roles (e.g. return-to-work co-ordinator) and training resources were created. Feasibility was assessed for 21 of the 26 patients recruited from three NHS trusts. Adherence to the defined performance objectives was 75% for patient performance objectives and 74% for staff performance objectives. The intervention was generally well received, although the short time frame available for implementation and concurrent research evaluation led to some confusion among patients and those delivering the intervention regarding its purpose and the roles and responsibilities of key staff. LIMITATIONS: Implementation and uptake of the intervention was not standardised and was limited by the study time frame. Evaluation of the intervention involved a small number of patients, which limited the ability to assess it. CONCLUSIONS: The developed occupational advice intervention supports best practice. Evaluation demonstrated good rates of adherence against defined performance objectives. However, a number of operational and implementation issues require further attention. FUTURE WORK: The intervention warrants a randomised controlled trial to assess its clinical effectiveness and cost-effectiveness to improve rates and timing of sustained return to work after surgery. This research should include the development of a robust implementation strategy to ensure that adoption is sustained. STUDY REGISTRATION: Current Controlled Trials ISRCTN27426982 and PROSPERO CRD42016045235. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 45. See the NIHR Journals Library website for further project information.

Hip and knee replacements are regularly carried out for patients who work. There is a lack of evidence about these patients' needs and how they return to work. Guidance to enable return to work after surgery is limited. There is, therefore, a need for structured occupational advice to help these patients. The aim of this project was to develop a multidisciplinary occupational advice intervention for this patient population and assess if it could be delivered. The study also aimed to make recommendations about its further assessment in a clinical trial. The study combined different methods of research (quantitative and qualitative) to identify the population likely to benefit, their current care, and the outcomes important to patients and health-care professionals. All of the information gathered was mapped through a framework (intervention mapping), which included a consensus process with stakeholders to develop the intervention. The intervention delivery was assessed for a small number of patients across orthopaedic departments, employer organisations and primary care networks. The study involved 154 patients, 110 stakeholders (general practitioners, surgeons, employers and health professionals/nurses) and a survey of current care (152 respondents) to develop the intervention. The intervention included information resources, a personalised return-to-work plan and co-ordination from the health-care team to support the delivery of 33 patient and staff performance objectives. To support delivery, a range of tools (e.g. occupational checklists, patient workbooks and employer information), roles (e.g. return-to-work co-ordinator) and training resources were created. The intervention was assessed in 26 patients and staff, and showed high rates of adherence to the defined performance objectives. The overall results demonstrated that the occupational advice intervention developed for hip and knee replacement patients is deliverable. The intervention warrants further research to assess its clinical effectiveness and cost-effectiveness as a tool to improve rates and timing of sustained return to work after surgery.

Short-term risk factors for a second hip fracture in a UK population.

INTRODUCTION: A hip fracture carries significant morbidity and mortality-a second fracture of the contralateral hip carries even higher complications. Most second hip fractures occur within 48 months of the first. The aim of this study was to comprehensively analyse all identifiable variables that may increase the risk of a contralateral hip fracture within this time period. METHODS: We retrospectively analysed 1242 consecutive patients with hip fractures presenting to our institution. All patient-related, surgery-related and inpatient variables were collected from the index admission. We then identified patients with a subsequent contralateral hip fracture in the following 2 years. Univariate and multivariate analyses were performed to identify risk factors associated with a second fracture. RESULTS: A total of 66 patients (5.3%) had a contralateral hip fracture in the 2 years following initial hip fracture. Mean age at first presentation was 81 years, and mean time to second fracture was 305 days. Following multivariate analysis, the patients at highest risk of a second fracture were those with dementia, acute inpatient chest infection, urinary tract infection and multiple comorbidities as measured by the Charlson score. Discharge destination after initial fracture was not associated with the risk of a second fracture. CONCLUSIONS: We have identified a number of discrete risk factors that are associated with a short- to medium-term risk of contralateral hip fracture that may be useful in screening for patients at risk and provide them with focused medical rehabilitation.