A Retrospective Review of Bovine Artery Graft Patency: A Single-Site Study.

BACKGROUND: The hemodialysis-dependent population is increasing in the United States. Dialysis access complications are a significant source of morbidity and mortality for patients with end-stage renal disease. A surgically created autogenous arteriovenous fistula has been the gold standard for dialysis access. However, for patients who are not candidates for arteriovenous fistula, arteriovenous grafts using various conduits have widely been used. In this study, we report the outcomes of bovine carotid artery (BCA) grafts for dialysis access at a single institution and compare these results to those for polytetrafluoroethylene (PTFE) grafts. METHODS: A single-institution, retrospective review of all patients undergoing surgical placement of a bovine carotid artery graft for dialysis access from 2017-2018 was performed under an institutional review board-approved protocol. The primary, primary-assisted, and secondary patency were calculated for the whole cohort and results determined based on gender, body mass index (BMI), and indication for use. Comparison was performed to PTFE grafts at same institution from 2013 to 2016. RESULTS: One hundred and twenty two patients were included in this study. Seventy four patients had a BCA graft placed while 48 had a PTFE graft placed. . The mean age was 59.7 ± 13.5 years in the BCA group, 55.8 ± 14.5 in the PTFE group, and the mean BMI was 29.8 ± 9.2 kg/m2 in the BCA group and 28.1 ± 9.7 in the PTFE group. Comparison of the comorbidities present in BCA/PTFE groups included hypertension (92%/100%), diabetes (57%/54%), congestive heart failure (28%/10%), lupus (5%/7%), and chronic obstructive pulmonary disease (4%/8%). The various configurations were reviewed (BCA/PTFE): interposition/access salvage (40.5%/13%), axillary-axillary (18.9%, 7%), brachial-basilic (5.4%, 6%), brachial-brachial (4.1%, 4%), brachial-cephalic (1.4%, 0%), axillary-brachial (1.4%, 0%), brachial-axillary (23%, 62%), and femoral-femoral (5.4%, 6%). Overall, 12-month primary patency was 50% in the BCA group and 18% in the PTFE group (P = 0.001). Twelve-month primary-assisted patency was 66% in the BCA group and 37% in the PTFE group (P = 0.003). Twelve-month secondary patency was 81% in the BCA group and 36% in the PTFE group (P = 0.07). When comparing BCA graft survival probability among male and female gender, males had better primary-assisted patency (P = 0.042). Secondary patency among the 2 genders was similar. There was no statistically significant difference in primary, primary-assisted, and secondary patency of BCA grafts between different BMI groups and indication for use. The average patency of a bovine graft was 17.8 ± 8 months. Sixty one percent of the BCA grafts needed intervention with 24% needing multiple interventions. There was an average of 7 ± 5 months to first intervention. The infection rate was 8.1% in the BCA group and 10.4% in the PTFE group with no statistical difference. CONCLUSIONS: Primary and primary-assisted patency rates at 12 months in our study were higher than those for PTFE at our institution. There was higher primary-assisted patency of BCA grafts among males at 12 months compared to PTFE. Obesity and indication for BCA graft use did not appear to affect patency in our population.

αvß3 Integrins Mediate Flow-Induced NF-κB Activation, Proinflammatory Gene Expression, and Early Atherogenic Inflammation.

Endothelial cell interactions with transitional matrix proteins, such as fibronectin, occur early during atherogenesis and regulate shear stress-induced endothelial cell activation. Multiple endothelial cell integrins bind transitional matrix proteins, including α5ß1, αvß3, and αvß5. However, the role these integrins play in mediating shear stress-induced endothelial cell activation remains unclear. Therefore, we sought to elucidate which integrin heterodimers mediate shear stress-induced endothelial cell activation and early atherogenesis. We now show that inhibiting αvß3 integrins (S247, siRNA), but not α5ß1 or αvß5, blunts shear stress-induced proinflammatory signaling (NF-κB, p21-activated kinase) and gene expression (ICAM1, VCAM1). Importantly, inhibiting αvß3 did not affect cytokine-induced proinflammatory responses or inhibit all shear stress-induced signaling, because Akt, endothelial nitric oxide synthase, and extracellular regulated kinase activation remained intact. Furthermore, inhibiting αv integrins (S247), but not α5 (ATN-161), in atherosclerosis-prone apolipoprotein E knockout mice significantly reduced vascular remodeling after acute induction of disturbed flow. S247 treatment similarly reduced early diet-induced atherosclerotic plaque formation associated with both diminished inflammation (expression of vascular cell adhesion molecule 1, plaque macrophage content) and reduced smooth muscle incorporation. Inducible, endothelial cell-specific αv integrin deletion similarly blunted inflammation in models of disturbed flow and diet-induced atherogenesis but did not affect smooth muscle incorporation. Our studies identify αvß3 as the primary integrin heterodimer mediating shear stress-induced proinflammatory responses and as a key contributor to early atherogenic inflammation.

α5ß1 integrin signaling mediates oxidized low-density lipoprotein-induced inflammation and early atherosclerosis.

OBJECTIVE: Endothelial cell activation drives early atherosclerotic plaque formation. Both fibronectin deposition and accumulation of oxidized low-density lipoprotein (oxLDL) occur early during atherogenesis, and both are implicated in enhanced endothelial cell activation. However, interplay between these responses has not been established. The objective of our study was to determine whether endothelial matrix composition modulates the inflammatory properties of oxLDL. APPROACH AND RESULTS: We now show that oxLDL-induced nuclear factor-κB activation, proinflammatory gene expression, and monocyte binding are significantly enhanced when endothelial cells are attached to fibronectin compared with basement membrane proteins. This enhanced response does not result from altered oxLDL receptor expression, oxLDL uptake, or reactive oxygen species production, but results from oxLDL-induced activation of the fibronectin-binding integrin α5ß1. Preventing α5ß1 signaling (blocking antibodies, knockout cells) inhibits oxLDL-induced nuclear factor-κB activation and vascular cell adhesion molecule-1 expression. Furthermore, oxLDL drives α5ß1-dependent integrin signaling through the focal adhesion kinase pathway, and focal adhesion kinase inhibition (PF-573228, small interfering RNA) blunts oxLDL-induced nuclear factor-κB activation, vascular cell adhesion molecule-1 expression, and monocyte adhesion. Last, treatment with the α5ß1 signaling inhibitor, ATN-161, significantly blunts atherosclerotic plaque development in apolipoprotein E-deficient mice, characterized by reduced vascular cell adhesion molecule-1 expression and macrophage accumulation without affecting fibrous cap size. CONCLUSIONS: Our data suggest that α5ß1-mediated cross-talk between fibronectin and oxLDL regulates inflammation in early atherogenesis and that therapeutics that inhibit α5 integrins may reduce inflammation without adversely affecting plaque structure.

EphA2 activation promotes the endothelial cell inflammatory response: a potential role in atherosclerosis.

OBJECTIVE: Endothelial cell activation results in altered cell-cell interactions with adjacent endothelial cells and with infiltrating leukocytes. Eph receptors and their ephrin ligands regulate cell-cell interactions during tissue remodeling, and multiple proinflammatory mediators induce endothelial EphA receptor and ephrinA ligand expression. Therefore, we sought to elucidate the role of EphA receptors and ephrinA ligands in endothelial cell activation and atherosclerosis. METHODS AND RESULTS: Quantitative reverse transcription-polymerase chain reaction screening for EphA/ephrinA expression in atherosclerosis-prone macrovascular endothelium identified EphA2, EphA4, and ephrinA1 as the dominant isoforms. Endothelial activation with oxidized low-density lipoprotein and proinflammatory cytokines induced EphA2 and ephrinA1 expression and sustained EphA2 activation, whereas EphA4 expression was unaffected. Atherosclerotic plaques from mice and humans showed enhanced EphA2 and ephrinA1 expression colocalizing in the endothelial cell layer. EphA2 activation with recombinant Fc-ephrinA1 induced proinflammatory gene expression (eg vascular cell adhesion molecule-1, E-selectin) and stimulated monocyte adhesion, whereas inhibiting EphA2 (small interfering RNA, pharmacological inhibitors) abrogated both ephrinA1-induced and oxidized low-density lipoprotein-induced vascular cell adhesion molecule-1 expression. CONCLUSION: The current data suggest that enhanced EphA2 signaling during endothelial cell activation perpetuates proinflammatory gene expression. Coupled with EphA2 expression in mouse and human atherosclerotic plaques, these data implicate EphA2 as a novel proinflammatory mediator and potential regulator of atherosclerotic plaque development.

Pharmaceutical validation of medication orders using an OWL Ontology and Business Rules.

In this paper we present an application of pharmaceutical validation of medication based on an OWL ontology and business rules or more specifically clinical decision rules. This application has been developed based on a prototype that enables business users to author, execute and manage their Business Rules over OWL Ontology. This prototype is based on the Business Rule Management System (BRMS) IBM WebSphere ILOG JRules.

Práticas baseadas em ocupações por terapeutas ocupacionais brasileiros no acidente vascular encefálico: uma revisão sistemática / Occupation-based practices by brazilian occupational therapists in stroke: a systematic review

Introdução: Ocupações como tratamento, são umas das abordagens mais usadas na reabilitação do Acidente Vascular Encefálico (AVE); no entanto, pouco se sabe do seu impacto comparado a outras estratégias. Objetivo: Analisar o efeito de práticas baseadas em ocupações na reabilitação do AVE conduzidas por terapeutas ocupacionais brasileiros (TOBs). Métodos: Revisão sistemática baseada no Checklist PRISMA. A pergunta de pesquisa foi redigida a partir do acrônimo PICO. Termos consultados: Acidente Vascular Cerebral; Reabilitação; e Terapia Ocupacional. Os títulos identificados foram alimentados no Programa Rayyan, nas etapas de seleção e elegibilidade, com aplicação de critérios terminológicos das ocupações. A análise de viés foi feita pela Ferramenta de Colaboração Cochrane. O Teste Kappa calculou o índice de confiabilidade. Resultados: Confirmou-se que as Atividades de Vida Diária (AVDs) são as estratégias mais comuns também por TOBs. Há crescente interesse pela gameterapia nas intervenções dos TOBs. Foi encontrada consistência na condução terapêutica com desfechos favoráveis à recuperação pós-AVE, a partir das ocupações, mas com enviesamento metodológico. Conclusão: As evidências não são suficientes para afirmar categoricamente que as práticas baseadas em ocupações são mais relevantes para estabelecer a recuperação pós-AVE que outras abordagens conduzidas por TOBs. Prospero: CRD42020223565.

Introduction: Occupations, as a form of treatment, are one of the most commonly employed approaches in the rehabilitation of Cerebral Vascular Accident (CVA); though, little is known about their efficiency compared to other strategies. Objective: Investigate the effectiveness of occupations in Cerebral Vascular Accident rehabilitation carried out by Brazilian occupational therapists (BOTs). Methods: Systematic review based on PRISMA. The research question was formulated from the acronym PICO. Terms consulted: Cerebral Vascular Accident; Rehabilitation; and Occupational Therapy. The identified titles were exported to the Rayyan Program, during the selection and eligibility stages, applying terminological criteria of the occupations. Bias analysis was performed using the Cochrane Collaboration Tool. The Kappa test calculated the reliability index. Results: It was confirmed that Activities of Daily Living (ADLs) are the most common strategies also for BOTs. Interest in game therapy was shown in BOTs interventions. Consistency was found in rehabilitation with favorable outcomes for post-stroke recovery based on occupations, but methodological bias compromises the results. Conclusion: The results are not enough to definitively state that occupation-based practices are more relevant to establishing post-stroke recovery than other approaches carried out by BOTs. Prospero: CRD42020223565.

Flow patterns regulate hyperglycemia-induced subendothelial matrix remodeling during early atherogenesis.

OBJECTIVE: Altered subendothelial matrix composition regulates endothelial dysfunction and early atherosclerotic plaque formation. Hyperglycemia promotes endothelial matrix remodeling associated with multiple microvascular complications of diabetes, but a role for altered matrix composition in diabetic atherogenesis has not been described. Therefore, we sought to characterize the alterations in matrix composition during diabetic atherogenesis using both in vitro and in vivo model systems. METHODS AND RESULTS: Streptozotocin-induced diabetes in atherosclerosis-prone ApoE knockout mice promoted transitional matrix expression (fibronectin, thrombospondin-1) and deposition in intima of the aortic arch as determined by qRT-PCR array and immunohistochemistry. Early plaque formation occurs at discrete vascular sites exposed to disturbed blood flow patterns, whereas regions exposed to laminar flow are protected. Consistent with this pattern, hyperglycemia-induced transitional matrix deposition was restricted to regions of disturbed blood flow. Laminar flow significantly blunted high glucose-induced fibronectin expression (mRNA and protein) and fibronectin fibrillogenesis in endothelial cell culture models, whereas high glucose-induced fibronectin deposition was similar between disturbed flow and static conditions. CONCLUSIONS: Taken together, these data demonstrate that flow patterns and hyperglycemia coordinately regulate subendothelial fibronectin deposition during early atherogenesis.

Altered nitric oxide production mediates matrix-specific PAK2 and NF-κB activation by flow.

Shear stress generated by distinct blood flow patterns modulates endothelial cell phenotype to spatially restrict atherosclerotic plaque development. Signaling through p21-activated kinase (PAK) mediates several of the deleterious effects of shear stress, including enhanced NF-κB activation and proinflammatory gene expression. Whereas shear stress activates PAK in endothelial cells on a fibronectin matrix, basement membrane proteins limit shear-induced PAK activation and inflammation through a protein kinase A-dependent pathway; however, the mechanisms underlying this regulation were unknown. We show that basement membrane proteins limit membrane recruitment of PAK2, the dominant isoform in endothelial cells, by blocking its interaction with the adaptor protein Nck. This uncoupling response requires protein kinase A-dependent nitric oxide production and subsequent PAK2 phosphorylation on Ser-20 in the Nck-binding domain. Of importance, shear stress does not stimulate nitric oxide production in endothelial cells on fibronectin, resulting in enhanced PAK activation, NF-κB phosphorylation, ICAM-1 expression, and monocyte adhesion. These data demonstrate that differential flow-induced nitric oxide production regulates matrix-specific PAK signaling and describe a novel mechanism of nitric oxide-dependent NF-κB inhibition.