Milk fat globule-epidermal growth factor 8 (MFGE8) prevents intestinal fibrosis.

OBJECTIVE: Intestinal fibrosis is considered an inevitable consequence of chronic IBD, leading to stricture formation and need for surgery. During the process of fibrogenesis, extracellular matrix (ECM) components critically regulate the function of mesenchymal cells. We characterised the composition and function of ECM in fibrostenosing Crohn's disease (CD) and control tissues. DESIGN: Decellularised full-thickness intestinal tissue platforms were tested using three different protocols, and ECM composition in different tissue phenotypes was explored by proteomics and validated by quantitative PCR (qPCR) and immunohistochemistry. Primary human intestinal myofibroblasts (HIMFs) treated with milk fat globule-epidermal growth factor 8 (MFGE8) were evaluated regarding the mechanism of their antifibrotic response, and the action of MFGE8 was tested in two experimental intestinal fibrosis models. RESULTS: We established and validated an optimal decellularisation protocol for intestinal IBD tissues. Matrisome analysis revealed elevated MFGE8 expression in CD strictured (CDs) tissue, which was confirmed at the mRNA and protein levels. Treatment with MFGE8 inhibited ECM production in normal control HIMF but not CDs HIMF. Next-generation sequencing uncovered functionally relevant integrin-mediated signalling pathways, and blockade of integrin αvß5 and focal adhesion kinase rendered HIMF non-responsive to MFGE8. MFGE8 prevented and reversed experimental intestinal fibrosis in vitro and in vivo. CONCLUSION: MFGE8 displays antifibrotic effects, and its administration may represent a future approach for prevention of IBD-induced intestinal strictures.

Does reusable mean green? Comparison of the environmental impact of reusable operating room bed covers and lift sheets versus single-use.

INTRODUCTION: As hospitals strive to reduce their environmental footprint, there is an ongoing debate over the environmental implications of reusable versus disposable linens in operating rooms (ORs). This research aimed to compare the environmental impact of reusable versus single-use OR bed covers and lift sheets using life cycle assessment (LCA) methodology. METHODS: LCA is an established tool with rigorous methodology that uses science-based processes to measure environmental impact. This study compared the impacts of three independent system scenarios at a single large academic hospital: reusable bed covers with 50 laundry cycles and subsequent landfill disposal (System 1), single-use bed covers with waste landfill disposal (System 2), and single-use bed covers with waste disposal using incineration (System 3). RESULTS: The total carbon footprint of System 1 for 50 uses was 19.83 â€‹kg carbon dioxide equivalents (CO2-eq). System 2 generated 64.99 â€‹kg CO2-eq. For System 3, the total carbon footprint was 108.98 â€‹kg CO2-eq. The raw material extraction for all the material to produce an equivalent 50 single-use OR bed cover kits was tenfold more carbon-intensive than the reusable bed cover. Laundering one reusable OR bed cover 50 times was more carbon intensive (12.12 â€‹kg CO2-eq) than landfill disposal of 50 single-use OR bed covers (2.52 â€‹kg CO2-eq). DISCUSSION: Our analysis demonstrates that one reusable fabric-based OR bed cover laundered 50 times, despite the carbon and water-intensive laundering process, exhibits a markedly lower carbon footprint than its single-use counterparts. The net difference is 45.16 â€‹kg CO2-eq, equivalent to driving 115 miles in an average gasoline-powered passenger vehicle. This stark contrast underscores the efficacy of adopting reusable solutions to mitigate environmental impact within healthcare facilities.

Training Future Surgeon Leaders in Environmental Stewardship: A Review of a Decade of the Health Care Sustainability Fellowship.

OBJECTIVE: Since the inception of Ken Lee Memorial Fellowship (KLMF) in 2013, our institution has achieved 10 years of trainee led sustainability projects. The ability of health care organizations to drive sustainability depends on organizational and human capacity. This qualitative study presents the first decade of sustainability fellows' projects, the challenges associated with implementing them, and the environmental and cost impact of these initiatives. DESIGN, SETTING, PARTICIPANTS: All residents in the General Surgery residency program at the Cleveland Clinic, a quaternary hospital, regardless of postgraduate year (PGY) level, are invited to apply for the KLMF program with a short project proposal. One fellow is selected per year. Each project since the program's inception was reviewed qualitatively, relying on data derived from observation, interview of prior fellows, and supervising staff, and analysis of documentation from the annual fellow presentation and abstract, Grand Rounds recording, and fellowship leadership. RESULTS: A targeted approach by each sustainability fellow is encouraged, with the following action cycle for change implementation throughout the 1-year fellowship: identification and discovery of an issue, collaborative planning of an intervention, implementation of the intervention, and evaluation. Projects range from water and waste reduction to education of surgical staff, with positive implications for environmental stewardship in our hospital. However, multiple barriers to completing, scaling, and maintaining sustainability initiatives remain, as demonstrated by challenges faced by our Ken Lee Fellows. CONCLUSIONS: Our goal is that this intensive educational experience within the framework of a graduate medical education curriculum will ensure future generations of surgeons who are thoughtful leaders in environmental stewardship.

Radiomics to Detect Inflammation and Fibrosis on Magnetic Resonance Enterography in Stricturing Crohn's Disease.

BACKGROUND & AIMS: Non-invasive cross-sectional imaging via magnetic resonance enterography (MRE) offers excellent accuracy for the diagnosis of stricturing complications in Crohn's disease (CD) but is limited in determining the degrees of fibrosis and inflammation within a stricture. We developed and validated a radiomics-based machine-learning model for separately characterizing the degree of histopathologic inflammation and fibrosis in CD strictures and compared it to centrally read visual radiologist scoring of MRE. METHODS: This single center, cross-sectional study, included 51 CD patients (n=34 for discovery; n=17 for validation) with terminal ileal strictures confirmed on diagnostic MRE within 15 weeks of resection. Histopathological specimens were scored for inflammation and fibrosis and spatially linked with corresponding pre-surgical MRE sequences. Annotated stricture regions on MRE were scored visually by radiologists as well as underwent 3D radiomics-based machine learning analysis; both evaluated against histopathology. RESULTS: Two distinct sets of radiomic features capturing textural heterogeneity within strictures were linked with each of severe inflammation or severe fibrosis across both discovery (area under the curve (AUC)=0.69, 0.83) and validation (AUCs=0.67,0.78) cohorts. Radiologist visual scoring had an AUC=0.67 for identifying severe inflammation and AUC=0.35 for severe fibrosis. Use of combined radiomics and radiologist scoring robustly augmented identification of severe inflammation (AUC=0.79) and modestly improved assessment of severe fibrosis (AUC=0.79 for severe fibrosis) over individual approaches. CONCLUSIONS: Radiomic features of CD strictures on MRE can accurately identify severe histopathologic inflammation and severe histopathologic fibrosis, as well as augment performance of radiologist visual scoring in stricture characterization.

A global consensus on the definitions, diagnosis and management of fibrostenosing small bowel Crohn's disease in clinical practice.

Fibrostenosis of the small bowel is common in patients with Crohn's disease. No consensus recommendations on definition, diagnosis and management in clinical practice are currently available. In this Consensus Statement, we present a clinical practice RAND/UCLA appropriateness study on the definition, diagnosis and clinical management of fibrostenosing Crohn's disease. It was conducted by a panel of 28 global experts and one patient representative. Following a systematic literature review, 526 candidate items grouped into 136 questions were generated and subsequently evaluated for appropriateness. Strictures are best defined as wall thickening, luminal narrowing and prestenotic dilation. Cross-sectional imaging is required for accurate diagnosis of fibrostenosing Crohn's disease, and it is recommended before making treatment decisions. It should also assess the degree of inflammation in the bowel wall. Multiple options for medical anti-inflammatory, endoscopic and surgical therapies were suggested, including follow-up strategies following therapy. This Consensus Statement supports clinical practice through providing guidance on definitions, diagnosis and therapeutic management of patients with fibrostenosing small bowel Crohn's disease.