The vasculature influences the progression and resolution of tissue inflammation. Capillaries express vascular endothelial growth factor (VEGF) receptors, including neuropilins (NRPs), which regulate interstitial fluid flow. NRP2, a receptor of VEGFA and semaphorin (SEMA) 3F ligands, is expressed in the vascular and lymphatic endothelia. Previous studies have demonstrated that blocking VEGF receptor 2 attenuates VEGFA-induced vascular permeability. The inhibition of NRP2 was hypothesized to decrease vascular permeability as well. Unexpectedly, massive tissue swelling and edema were observed in Nrp2 À/À mice compared with wild-type littermates after delayed-type hypersensitivity reactions. Vascular permeability was twofold greater in inflamed blood vessels in Nrp2-deficient mice compared to those in Nrp2-intact littermates. The addition of exogenous SEMA3F protein inhibited vascular permeability in Balb/cJ mice, suggesting that the loss of endogenous Sema3F activity in the Nrp2-deficient mice was responsible for the enhanced vessel leakage. Functional lymphatic capillaries are necessary for draining excess fluid after inflammation; however, Nrp2-mutant mice lacked superficial lymphatic capillaries, leading to 2.5-fold greater fluid retention and severe lymphedema after inflammation. In conclusion, Nrp2 deficiency increased blood vessel permeability and decreased lymphatic vessel drainage during inflammation, highlighting the importance of the NRP2/SEMA3F pathway in the modulation of tissue swelling and resolution of postinflammatory edema. (Am J Pathol 2016 http://dx

Summary Neuropilin-1 (NRP1) is a receptor for vascular endothelial growth factor (VEGF). A soluble isoform of Nrp1 (sNrp1) has not been described in the mouse. Our goal was to examine the expression of mouse sNrp1 during liver development and regeneration. sNrp1 was cloned from mouse liver. The expression of sNrp1 and VEGF was examined in mouse liver during postnatal development and regeneration using northern blot, western blot, in situ hybridization, and immunohistochemical analyses. HGF/NRP1 binding was examined in vitro. A novel 588-amino acid sNrp1 isoform was found to contain the ligand binding regions of Nrp1. The adult liver expressed more sNrp1 than full-length Nrp1. In vivo, hepatocytes constitutively expressed VEGF and sNrp1 in the quiescent state. sNrp1 was highly upregulated at P20, a time point coinciding with a plateau in liver and body weights. Following hepatectomy, endogenous levels of sNrp1 decreased during the rapid growth phase; and VEGF levels were highest just prior to and during the angiogenic phase. sNrp1 levels again rose 5-10 days post-hepatectomy, presumably to control regeneration. HGF protein bound NRP1 and binding was competed with sNRP1. We cloned a novel mouse sNrp1 isoform from liver and provide evidence that this endogenous angiogenesis inhibitor may regulate VEGF or HGF bioavailability during normal physiological growth and development as well as during liver regeneration.

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Malnutrition is exceedingly common in cancer patients, with some of the highest rates seen in gastrointestinal (GI) malignancies. Malnutrition and cachexia in cancer patients is associated with worse quality of life, poor treatment tolerance, and increased morbidity and mortality. The importance of early recognition of malnutrition in cancer patients is key, and numerous screening tools have been validated to aid practitioners in this diagnosis. In this paper, we summarize the importance of identifying and managing malnutrition in GI cancer patients as well as its impact on clinical outcomes. We then focus on presenting our own novel quality improvement project that aims to expand access to dietitian services in a GI cancer clinic at a large safety‐net hospital system. Utilizing evidence‐based quality improvement methodologies including the Model for Improvement and Plan‐Do‐Study‐Act cycles, we increased the proportion of GI oncology patients seen by a dietitian from 5% to 20% from October 2018 to July 2019. In particular, we outline the challenges faced in the implementation process of a malnutrition screening tool built into the electronic medical record in an outpatient oncology clinic. We focus on the tool's ability to capture a greater number of patients with malnutrition and its clinical impact.

PURPOSE: Rates of malnutrition are high in patients with GI cancer, leading to poor outcomes. The aim of our project was to increase the rate of documented dietitian assessment in patients with GI cancer at Parkland Health and Hospital System from 5% to 25%. METHODS: Three PDSA cycles were conducted after identifying barriers to dietitian services. A registered dietitian was assigned to the GI oncology clinic during the first cycle, an adapted Malnutrition Screening Tool was implemented through the electronic medical record during the second cycle, and clinical staff training was performed during the third cycle. New patients with GI cancer seen by the registered dietitian had weight, Eastern Cooperative Oncology Group performance status, and serum albumin recorded at initial visit and 3-month follow-up. Paired t tests were performed. Emergency department visits and hospital admissions were also recorded during this time. RESULTS: Through these interventions, the percentage of patients with GI cancer with documented assessment by the registered dietitian increased from 5.1% in October 2018 prior to our interventions to 21.8% in July 2019 and has sustained in the 15%-20% range thereafter. From May to July 2019, there were 63 new patients with GI cancer seen by a registered dietitian. No significant difference was observed in average difference in weight and serum albumin level at initial visit and 3-month follow-up. CONCLUSION: A nutrition-focused quality improvement project led to a more than three-fold increase in the rate of documented dietitian assessment in patients with GI cancer.