Resolvin D2/GPR18 signaling enhances monocytic myeloid-derived suppressor cell function to mitigate abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) formation is a chronic vascular pathology characterized by inflammation, leukocyte infiltration and vascular remodeling. The aim of this study was to delineate the protective role of Resolvin D2 (RvD2), a bioactive isoform of specialized proresolving lipid mediators, via G-protein coupled receptor 18 (GPR18) receptor signaling in attenuating AAAs. Importantly, RvD2 and GPR18 levels were significantly decreased in aortic tissue of AAA patients compared with controls. Furthermore, using an established murine model of AAA in C57BL/6 (WT) mice, we observed that treatment with RvD2 significantly attenuated aortic diameter, pro-inflammatory cytokine production, immune cell infiltration (neutrophils and macrophages), elastic fiber disruption and increased smooth muscle cell α-actin expression as well as increased TGF-ß2 and IL-10 expressions compared to untreated mice. Moreover, the RvD2-mediated protection from vascular remodeling and AAA formation was blocked when mice were previously treated with siRNA for GPR18 signifying the importance of RvD2/GPR18 signaling in vascular inflammation. Mechanistically, RvD2-mediated protection significantly enhanced infiltration and activation of monocytic myeloid-derived suppressor cells (M-MDSCs) by increasing TGF-ß2 and IL-10 secretions that mitigated smooth muscle cell activation in a GPR18-dependent manner to attenuate aortic inflammation and vascular remodeling via this intercellular crosstalk. Collectively, this study demonstrates RvD2 treatment induces an expansion of myeloid-lineage committed progenitors, such as M-MDSCs, and activates GPR18-dependent signaling to enhance TGF-ß2 and IL-10 secretion that contributes to resolution of aortic inflammation and remodeling during AAA formation.

Pediatric Ethics Consultation Services.

BACKGROUND AND OBJECTIVE: Although guidelines call for the presence of pediatric ethics consultation services (PECS), their existence in children's hospitals remains unquantified. This study determined the prevalence of PECS in children's hospitals and compared the practice environments of those with versus without PECS. METHOD: The Children's Hospital Association Annual Benchmark Report survey from 2020 and PECS data were analyzed for the association of PECS with domains of care. RESULTS: Two hundred thirty-one hospitals received survey requests, with 148 submitted and 144 reachable to determine PECS (62% response rate), inclusive of 50 states. Ninety-nine (69%) reported having ethics consultation services. Freestanding children's hospitals (28% of all hospitals) were more likely to report the presence of PECS (P <.001), making up 41% of hospitals with a PECS. The median number of staffed beds was 203 (25th quartile 119, 75th quartile 326) for those with PECS compared with 80 for those without (25th quartile 40, 75th quartile 121). Facilities with palliative care, higher trauma ratio, intensive care, and comprehensive programs were more likely to have PECS. Academic affiliation was associated with PECS presence (P <.001). Settings associated with skilled nursing facilities or long-term care programs were not more likely to have PECS. Hospitals designated as federally qualified health centers (P = .04) and accountable care organizations (P = .001) were more likely to have PECS. CONCLUSION: Although PECS function as formal means to clarify values and mitigate conflict, one-third of children's hospitals lack PECS. Future research is needed to understand barriers to PECS and improve its presence.

Pediatric Ethics Consultation Services, Scope, and Staffing.

BACKGROUND AND OBJECTIVES: National standards and guidelines call for a mechanism to address ethical concerns and conflicts in children's hospitals. The roles, responsibilities, and reach of pediatric ethics consultation services (PECS) remain unmeasured. The purpose of this study is to quantify staffing, structure, function, scope, training, and funding of PECS. METHODS: Cross-sectional online survey was shared with an ethics informant at 181 children's hospitals in the United States from March to June 2022. Data were summarized descriptively and with semantic content analyses. RESULTS: One hundred seventeen surveys were received from individual children's hospitals in 45 states and Washington DC (response rate 65%), with 104 qualifying for survey completion. Almost one-quarter of settings received 50 or more pediatric ethics consults in the past 12 months. On average, 7.4 people at each institution have responsibility for completing ethics consults. Estimated full-time equivalent salary support for ethics is on average 0.5 (range 0-3, median 0.25). One-third (33%) of facilities do not offer any salary support for ethics and three-quarters do not have an institutional budget for the ethics program. Clinical staff primarily initiate consults. End-of-life, benefits versus burdens of treatments, and staff moral distress were the most frequently consulted themes. Almost one-quarter (21%) of children's hospitals do not receive any consults from patients or families. CONLUSIONS: The findings from this study reveal wide variation in PECS practices and raise concern about the lack of financial support provided for PECS despite substantial workloads.

Demand and Supply: Association between Pediatric Ethics Consultation Volume and Protected Time for Ethics Work.

BACKGROUND: Despite national increase in pediatric ethics consultation volume over the past decade, protected time and resources for healthcare ethics consultancy work has lagged. METHODS: Correlation study investigating potential associations between ethics consult volume reported by recent national survey of consultants at children's hospitals and five programmatic domains. RESULTS: 104 children's hospitals in 45 states plus Washington DC were included. There was not a statistically significant association between pediatric ethics consult volume and hospital size, rurality of patient population, or number of consultants. Academically-affiliated children's hospitals had fewer ethics consults compared to nonacademically affiliated. Association was found between full-time equivalent (FTE) hours and number of ethics consults (p < 0.0001). Spearman rank correlation between ethics consult volume and FTE was 0.5. CONCLUSIONS: While the results of this study should be interpreted with caution, investment in protected time for ethics consultancy work may translate into increased volume of pediatric ethics consults.

The Accessibility of Inpatient Pediatric Ethics Consultation Services to Patient Caregivers.

BACKGROUND: Ethics consultation services (ECS) support clinical decision-making when there are values conflicts. Accessibility to ECS by patients and families is required to benefit from the service. Multiple national guidelines encourage ready availability of ECS to all stakeholders including patients and families. METHODS: All facilities registered with the Children's Hospital Association (n = 190) were contacted using a protocol modeled after an adult ethics consultation practice study. After an online search to identify an ethics contact, calls were made to hospital operators, and each transfer was documented as well as time to ECS contact. If no contact was identified on progression through the call protocol or on completion of the call pathway on 3 occasions each spaced by 1 week, the ECS was labeled "unreached." RESULTS: Only 36 (19%) ECS contacts were identified via online search with the remainder 154 (81%) requiring phone calls. Fewer than one-quarter of operators (n = 34/154, 22%) could identify a contact name or number for ECS. Thirty ECS (16%) remained unreachable after completion of the call pathway or 3 separate attempts. Successful ECS contact required an average of 2.9 attempts. Maximum call hold duration was 25 minutes. Callback times averaged 5.8 business days after voicemail. CONCLUSIONS: This study revealed limited reachability of ECS. ECS should make their contact information available online and improve information available to operators.