Luminal shearing forces have been shown to impact both geometric remodeling and the development of intimal hyperplasia. Less well studied is the influence of intramural wall stresses on vessel growth and adaptation. Using a vein graft-fistula configuration to isolate the impact of circumferential wall stress, we identify the reorganization of adventitial myofibroblasts as the dominant histological event that limits early outward remodeling of vein grafts in response to elevated wall stress. We hypothesize that increased production of transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) induces recruitment of myofibroblasts, promotes adventitial reorganization, and limits early outward remodeling in response to increased intramural wall stress. Vein grafts with a distal arteriovenous fistula in the neck of rabbits were constructed, resulting in a fourfold differential in circumferential wall stress. Using this model, we demonstrate 1) elevated wall stress augments the production of TGF-beta and CTGF, 2) increased TGF-beta expression and CTGF expression are correlated with the enhanced differentiation from fibroblasts to myofibroblasts, as evidenced by the significant increase in the alpha-actin-positive cells in adventitia, and 3) the levels of TGF-beta, CTGF, and alpha-actin are inversely correlated with the magnitude of outward remodeling of the graft wall. Increased wall stress after vein graft implantation appears to induce a TGF-beta- and CTGF-mediated recruitment of adventitial fibroblasts and a conversion to a myofibroblast phenotype. Although important in the maintenance of wall stability in the face of an increased mechanical load, this adventitial adaptation limits early outward remodeling of the vein conduit and may prove deleterious in maintaining long-term vein graft patency.
Purpose: To evaluate the time cost of intraoperative aberrometry (IA), to compare IA prediction error to the prediction error associated with conventional formulas using preoperative calculations (PC) and evaluate when IA provides clinically relevant benefit. Methods: This is a retrospective study of eyes that underwent cataract phacoemulsification surgery with IA at an academic eye center. IA versus PC prediction error were compared amongst various preoperative and intraoperative characteristics. Additionally, a dichotomous variable indicating clinically relevant benefit of IA, where IA absolute prediction error was less than 0.5D and PC absolute prediction error greater than 0.5D, was associated with clinical factors. Results: Five hundred eyes of 341 patients were included in the analysis. The quantitative difference between mean absolute prediction errors for IA versus PC was between 0.0D and 0.03D in most subgroups. For the 11.0% of eyes that had clinically relevant benefit to IA, the multivariable model identified the following strongest predictors: prior myopic corneal refractive surgery (Odds ratio (OR) 3.9, p<0.01 for myopic LASIK/PRK, OR 5.5, p=0.01 for radial keratotomy), toric or multifocal/EDOF lens implantation (OR 2.7, p=0.03 for toric monofocal lenses, OR 3.1, p=0.01 for EDOF/multifocal lenses), and short and long axial lengths (p<0.01). On average, IA implementation added 3.0 minutes to surgery (p<0.01). Conclusion: For greatest likelihood of a clinically meaningful improvement in outcomes despite increased surgical time, surgeons and patients should consider using IA for eyes with extremes in axial length, eyes with prior myopic corneal refractive surgery, or when implanting lenses with toric or extended-depth-of-focus/multifocal properties.
a b s t r a c tLeukocytes play a central role in vein graft neointimal hyperplasia, which is significantly augmented under low shear conditions. The current concept is that shear force regulates leukocyte adhesion predominately through up-regulation of chemokines and growth factors within the graft wall. Using rabbit and murine vein graft models, we demonstrate that CC chemokine receptor 2/monocyte chemoattractant protein-1 mediated monocyte recruitment and a low shear environment act synergistically to augment neointimal hyperplasia development and removal of either of the conditions leads to a significant reduction in neointimal thickening. We propose a novel concept that the shear stress response element phenotypically stems from the complex interplay of the biological and physical microenvironments.Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
ImportanceDry eye is a common clinical manifestation, a leading cause of eye clinic visits, and a significant societal and personal economic burden in the United States. Meibomian gland dysfunction (MGD) is a major cause of evaporative dry eye.ObjectiveTo conduct a systematic review and meta-analysis to obtain updated estimates of the prevalence and incidence of dry eye and MGD in the United States.Data SourcesOvid MEDLINE and Embase.Study SelectionA search conducted on August 16, 2021, identified studies published between January 1, 2010, and August 16, 2021, with no restrictions regarding participant age or language of publication. Case reports, case series, case-control studies, and interventional studies were excluded.Data Extraction and SynthesisThe conduct of review followed a protocol registered on PROSPERO (CRD42021256934). PRISMA guidelines were followed for reporting. Joanna Briggs Institute and Newcastle Ottawa Scale tools were used to assess risk of bias. Data extraction was conducted by 1 reviewer and verified by another for accuracy. Prevalence of dry eye and MGD were combined in separate meta-analyses using random-effects models.Main Outcomes and MeasuresPrevalence and incidence of dry eye and MGD in the United States. Summary estimates from meta-analysis of dry eye and MGD prevalence with 95% CI and 95% prediction intervals (95% PI).ResultsThirteen studies were included in the systematic review. Dry eye prevalence was reported by 10 studies, dry eye incidence by 2 studies, and MGD prevalence by 3 studies. Meta-analysis estimated a dry eye prevalence of 8.1% (95% CI, 4.9%-13.1%; 95% PI, 0%-98.9%; 3 studies; 9 808 758 participants) and MGD prevalence of 21.2% (95% CI, 7.2%-48.3%; 95% PI, 0%-100%; 3 studies; 19 648 participants). Dry eye incidence was 3.5% in a population 18 years and older and 7.8% in a population aged 68 years and older. No studies reported MGD incidence.Conclusions and RelevanceThis systematic review and meta-analysis demonstrated uncertainty about the prevalence and incidence of dry eye and MGD in the United States. Population-based epidemiological studies that use consistent and validated definitions of dry eye and MGD are needed for higher-certainty estimates of dry eye and MGD prevalence and incidence in the United States.
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