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  1. Article ; Online: Chronic Use of Proton Pump Inhibitors Is Associated With an Increased Risk of Immune Checkpoint Inhibitor Colitis in Renal Cell Carcinoma.

    Yin, Jianyi / Elias, Roy / Peng, Lan / Levonyak, Nicholas / Asokan, Annapoorani / Christie, Alana / Kubiliun, Nisa / Brugarolas, James / Hammers, Hans J

    Clinical genitourinary cancer

    2022  Volume 20, Issue 3, Page(s) 260–269

    Abstract: Introduction: Immune checkpoint inhibitors (ICIs) have become a standard of care in metastatic renal cell carcinoma (mRCC) but are associated with immune-related adverse events (irAEs) including colitis. Growing evidence suggests proton pump inhibitors ( ...

    Abstract Introduction: Immune checkpoint inhibitors (ICIs) have become a standard of care in metastatic renal cell carcinoma (mRCC) but are associated with immune-related adverse events (irAEs) including colitis. Growing evidence suggests proton pump inhibitors (PPIs) increase the risk of inflammatory bowel disease (IBD). Given the pathophysiological overlap between IBD and ICI colitis, we sought to evaluate the relationship between PPI use and ICI colitis in mRCC patients.
    Patients and methods: We performed a retrospective study of adult patients who received ICI therapy for mRCC between 2015 and 2018 at University of Texas Southwestern Medical Center affiliated hospitals. Clinical characteristics, oncological outcomes, ICI colitis details, and PPI use details were collected by manual chart review. The diagnosis of ICI colitis was made via biopsy when available, or by clinical criteria (symptoms and response to immunosuppressive therapy) when biopsy specimens were unavailable or inconclusive. Univariable and multivariable logistic regression analyses were conducted to assess the potential contribution of PPIs to ICI colitis.
    Results: A total of 176 patients received ICI therapy for mRCC, of which 16 (9.1%) were diagnosed with ICI colitis. Patients with ICI colitis presented with elevated stool lactoferritin and calprotectin and a wide range of endoscopic and histologic findings. There were no significant differences between patients with and without ICI colitis in age, gender, medical comorbidities, RCC history, and overall survival. However, exposure to ipilimumab and PPI use were more frequently observed in patients with ICI colitis than those without. In univariable and multivariable logistic regression analyses, exposure to ipilimumab and chronic use of PPIs > 8 weeks were significantly associated with ICI colitis.
    Conclusion: In addition to ipilimumab use, chronic use of PPIs may be associated with ICI colitis in patients with mRCC.
    MeSH term(s) Adult ; Carcinoma, Renal Cell/drug therapy ; Colitis/chemically induced ; Colitis/drug therapy ; Humans ; Immune Checkpoint Inhibitors/adverse effects ; Inflammatory Bowel Diseases/drug therapy ; Ipilimumab/therapeutic use ; Kidney Neoplasms/drug therapy ; Proton Pump Inhibitors/adverse effects ; Retrospective Studies
    Chemical Substances Immune Checkpoint Inhibitors ; Ipilimumab ; Proton Pump Inhibitors
    Language English
    Publishing date 2022-02-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2225121-2
    ISSN 1938-0682 ; 1558-7673
    ISSN (online) 1938-0682
    ISSN 1558-7673
    DOI 10.1016/j.clgc.2022.01.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Importance of addressing malnutrition in cancer and implementation of a quality improvement project in a gastrointestinal cancer clinic

    Levonyak, Nicholas S. / Hodges, Mary P. / Haaf, Nicole / Brown, Timothy J. / Hardy, Shelli / Mhoon, Verca / Kainthla, Radhika / Beg, Muhammad Shaalan / Kazmi, Syed M.

    Nutrition in clinical practice. 2022 Feb., v. 37, no. 1

    2022  

    Abstract: 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 ... ...

    Abstract 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.
    Keywords cachexia ; dietitians ; gastrointestinal neoplasms ; gastrointestinal system ; hospitals ; malnutrition ; medical records ; models ; morbidity ; mortality ; nutrition ; quality of life
    Language English
    Dates of publication 2022-02
    Size p. 215-223.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 645074-x
    ISSN 1941-2452 ; 0884-5336
    ISSN (online) 1941-2452
    ISSN 0884-5336
    DOI 10.1002/ncp.10753
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Implementation of a Quality Improvement Project to Increase Access to Dietitian Services for Patients With Gastrointestinal Cancer in a Safety-Net Hospital System.

    Levonyak, Nicholas S / Hodges, Mary P / Haaf, Nicole / Mhoon, Verca / Lopez, Ricardo / Little Jones, Amy / Sanjeevaiah, Aravind / Kainthla, Radhika / Beg, Muhammad Shaalan / Kazmi, Syed M

    JCO oncology practice

    2021  Volume 17, Issue 7, Page(s) e1048–e1054

    Abstract: 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 ...

    Abstract 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
    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.
    MeSH term(s) Gastrointestinal Neoplasms/therapy ; Humans ; Malnutrition/diagnosis ; Malnutrition/therapy ; Nutritionists ; Quality Improvement ; Safety-net Providers
    Language English
    Publishing date 2021-04-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3028198-2
    ISSN 2688-1535 ; 2688-1527
    ISSN (online) 2688-1535
    ISSN 2688-1527
    DOI 10.1200/OP.20.01031
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Importance of addressing malnutrition in cancer and implementation of a quality improvement project in a gastrointestinal cancer clinic.

    Levonyak, Nicholas S / Hodges, Mary P / Haaf, Nicole / Brown, Timothy J / Hardy, Shelli / Mhoon, Verca / Kainthla, Radhika / Beg, Muhammad Shaalan / Kazmi, Syed M

    Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition

    2021  Volume 37, Issue 1, Page(s) 215–223

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Cachexia/diagnosis ; Cachexia/etiology ; Cachexia/therapy ; Gastrointestinal Neoplasms/complications ; Gastrointestinal Neoplasms/therapy ; Humans ; Malnutrition/diagnosis ; Malnutrition/epidemiology ; Malnutrition/etiology ; Nutrition Assessment ; Quality Improvement ; Quality of Life
    Language English
    Publishing date 2021-08-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645074-x
    ISSN 1941-2452 ; 0884-5336
    ISSN (online) 1941-2452
    ISSN 0884-5336
    DOI 10.1002/ncp.10753
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Inflammation and Lymphedema Are Exacerbated and Prolonged by Neuropilin 2 Deficiency.

    Mucka, Patrick / Levonyak, Nicholas / Geretti, Elena / Zwaans, Bernadette M M / Li, Xiaoran / Adini, Irit / Klagsbrun, Michael / Adam, Rosalyn M / Bielenberg, Diane R

    The American journal of pathology

    2016  Volume 186, Issue 11, Page(s) 2803–2812

    Abstract: 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 ...

    Abstract 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
    MeSH term(s) Animals ; Blood Vessels/physiopathology ; Capillary Permeability ; Female ; Humans ; Inflammation/genetics ; Inflammation/physiopathology ; Lymphatic Vessels/physiopathology ; Lymphedema/genetics ; Lymphedema/physiopathology ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred BALB C ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neuropilin-2/deficiency ; Neuropilin-2/genetics ; Neuropilin-2/metabolism ; Specific Pathogen-Free Organisms ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances Membrane Proteins ; Nerve Tissue Proteins ; Neuropilin-2 ; Sema3f protein, mouse ; Vascular Endothelial Growth Factor A ; vascular endothelial growth factor A, mouse
    Language English
    Publishing date 2016-10-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2943-9
    ISSN 1525-2191 ; 0002-9440
    ISSN (online) 1525-2191
    ISSN 0002-9440
    DOI 10.1016/j.ajpath.2016.07.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Regulation of soluble neuropilin 1, an endogenous angiogenesis inhibitor, in liver development and regeneration.

    Panigrahy, Dipak / Adini, Irit / Mamluk, Roni / Levonyak, Nicholas / Bruns, Christiane J / D'Amore, Patricia A / Klagsbrun, Michael / Bielenberg, Diane R

    Pathology

    2014  Volume 46, Issue 5, Page(s) 416–423

    Abstract: 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 ... ...

    Abstract 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 post-natal development and regeneration using northern blot, western blot, in situ hybridisation, 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 up-regulated 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.
    MeSH term(s) Animals ; Base Sequence ; Blotting, Northern ; Blotting, Western ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Liver/growth & development ; Liver/metabolism ; Liver Regeneration/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Molecular Sequence Data ; Neovascularization, Physiologic/physiology ; Neuropilin-1/biosynthesis ; Sequence Homology, Nucleic Acid ; Vascular Endothelial Growth Factor A/biosynthesis
    Chemical Substances Vascular Endothelial Growth Factor A ; vascular endothelial growth factor A, mouse ; Neuropilin-1 (144713-63-3)
    Language English
    Publishing date 2014-06-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 7085-3
    ISSN 1465-3931 ; 0031-3025
    ISSN (online) 1465-3931
    ISSN 0031-3025
    DOI 10.1097/PAT.0000000000000121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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