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Younan SA, Ali D, Hawkins AT, Bradley JF, Hopkins MB, Geiger T, Jayaram J, Khan A. Association of perioperative immunonutrition with anastomotic leak among patients undergoing elective colorectal surgery within a robust enhanced recovery after surgery program. Surgery 2025; 181:109159. [PMID: 39904123 DOI: 10.1016/j.surg.2025.109159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 01/06/2025] [Accepted: 01/07/2025] [Indexed: 02/06/2025]
Abstract
BACKGROUND Immunonutrition supplementation has been shown to reduce the risk of surgical infectious complications; however, its effect on decreasing anastomotic leak rates, in the context of an otherwise robust Enhanced Recovery After Surgery (ERAS) program, remains unclear. This study aims to assess the association between perioperative immunonutrition supplementation and anastomotic leak in an elective Enhanced Recovery After Surgery colorectal surgical population. METHODS We performed a retrospective single-institution cohort study consisting of adult patients enrolled in an Enhanced Recovery After Surgery pathway and undergoing elective colorectal surgery from 2018 to 2023. Immunonutrition supplementation was defined as a 10-day perioperative supply of commercially available nutritional shakes. Relevant demographic covariates, preoperative characteristics, and operative methods were identified and analyzed. Multivariable logistic regression was performed to determine the association of immunonutrition with anastomotic leak. RESULTS A total of 708 patients were included in the study, of which n = 400 (56.5%) received perioperative immunonutrition. Patients who received immunonutrition were more likely to be older (median age 57.9 vs 55.7), male (52.7% vs 44.8%), have a higher body mass index (27.7 vs 26.3), and less likely to be current smokers (9.8% vs 16.2%). On adjusted analysis, there was no association between immunonutrition use and anastomotic leak (odds ratio = 0.96, 95% confidence interval = 0.45, 2.08), 30-day readmission (odds ratio = 0.97, 95% confidence interval = 0.60, 1.57), or length of stay (β = .40, 95% confidence interval = -0.06, 0.86) CONCLUSION: We did not observe an association between perioperative immunonutrition supplementation and postoperative anastomotic leak, suggesting that the role of immunonutrition within a comprehensive Enhanced Recovery After Surgery program for elective colorectal surgery may warrant further evaluation.
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Affiliation(s)
- Samuel A Younan
- Section of Colon & Rectal Surgery, Division of General Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Danish Ali
- Section of Colon & Rectal Surgery, Division of General Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Alexander T Hawkins
- Section of Colon & Rectal Surgery, Division of General Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Joel F Bradley
- Department of Surgery, Division of General Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - M Benjamin Hopkins
- Section of Colon & Rectal Surgery, Division of General Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Timothy Geiger
- Section of Colon & Rectal Surgery, Division of General Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Jennifer Jayaram
- Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN
| | - Aimal Khan
- Section of Colon & Rectal Surgery, Division of General Surgery, Vanderbilt University Medical Center, Nashville, TN.
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Velho TR, Pinto F, Ferreira R, Pereira RM, Duarte A, Harada M, Willmann K, Pedroso D, Paixão T, Guerra NC, Neves-Costa A, Santos I, Gouveia E Melo R, Brito D, Almeida AG, Nobre Â, Wang-Sattler R, Köcher T, Pedro LM, Pinto F, Moita LF. Role of major cardiovascular surgery-induced metabolic reprogramming in acute kidney injury in critical care. Intensive Care Med 2025; 51:259-271. [PMID: 39869158 DOI: 10.1007/s00134-024-07770-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 12/19/2024] [Indexed: 01/28/2025]
Abstract
PURPOSE Major cardiovascular surgery imposes high physiologic stress, often causing severe organ dysfunction and poor outcomes. The underlying mechanisms remain unclear. This study investigated metabolic changes induced by major cardiovascular surgery and the potential role of identified metabolic signatures in postoperative acute kidney injury (AKI). METHODS A prospective observational study included 53 patients undergoing major cardiovascular surgery in 3 groups: cardiac surgery with cardiopulmonary bypass (CPB n = 33), without CPB (n = 10), and major vascular surgery (n = 10). For each patient, peripheral blood samples were collected pre-surgery, and at 6 h and 24 h post-surgery. Untargeted metabolomics using mass spectrometry quantified 8668 metabolic features in serum samples. Linear mixed-effect models (adjusted for age, sex, and body mass index) and pathway analyses were performed. RESULTS In the cardiac surgery with CPB group, 772 features were significantly altered (P < 2.8E - 05) across the 3 time points. These features were enriched in five classes, all related to protein metabolism, with glycine and serine metabolism being the most represented. Cardiac surgery with CPB showed a distinct metabolic signature compared to other groups. Patients who developed postoperative AKI exhibited increased protein catabolism (including valine, leucine, and isoleucine degradation), disruptions in the citric acid cycle, and plasmatic accumulation of acylcarnitines. CONCLUSION Major cardiovascular surgery, particularly with CPB, induces significant changes in protein metabolism. Patients developing postoperative AKI exhibited specific metabolic signatures. These findings may be critical for designing interventions to minimize organ dysfunction, including AKI, and improve outcomes in major cardiovascular surgery.
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Affiliation(s)
- Tiago R Velho
- Cardiothoracic Surgery Department, Hospital de Santa Maria, Unidade Local de Saúde de Santa Maria, Lisbon, Portugal.
- Cardiothoracic Surgery Research Unit, Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
- Center for Disease Mechanisms Research, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
| | - Francisco Pinto
- Faculdade de Ciências da Universidade de Lisboa, Lisbon, Portugal
| | - Ricardo Ferreira
- Cardiothoracic Surgery Department, Hospital de Santa Maria, Unidade Local de Saúde de Santa Maria, Lisbon, Portugal
- Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Rafael Maniés Pereira
- Cardiothoracic Surgery Research Unit, Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
- Escola Superior de Saúde da Cruz Vermelha Portuguesa, Lisbon, Portugal
| | - António Duarte
- Vascular Surgery Department, Hospital de Santa Maria, Unidade Local de Saúde de Santa Maria, Lisbon, Portugal
| | - Makoto Harada
- Institute of Translational Genomics, Helmholtz Zentrum München - German Research Centre for Environmental Health, Neuherberg, Germany
| | - Katharina Willmann
- Center for Disease Mechanisms Research, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
- GIMM - Gulbenkian Institute for Molecular Medicine, Lisbon, Portugal
| | - Dora Pedroso
- Center for Disease Mechanisms Research, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
- GIMM - Gulbenkian Institute for Molecular Medicine, Lisbon, Portugal
| | - Tiago Paixão
- GIMM - Gulbenkian Institute for Molecular Medicine, Lisbon, Portugal
| | - Nuno Carvalho Guerra
- Cardiothoracic Surgery Department, Hospital de Santa Maria, Unidade Local de Saúde de Santa Maria, Lisbon, Portugal
| | - Ana Neves-Costa
- Center for Disease Mechanisms Research, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Isa Santos
- Center for Disease Mechanisms Research, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Ryan Gouveia E Melo
- Vascular Surgery Department, Hospital de Santa Maria, Unidade Local de Saúde de Santa Maria, Lisbon, Portugal
| | - Dulce Brito
- Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
- Department of Cardiology, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Ana G Almeida
- Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
- Department of Cardiology, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Ângelo Nobre
- Cardiothoracic Surgery Department, Hospital de Santa Maria, Unidade Local de Saúde de Santa Maria, Lisbon, Portugal
- Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Rui Wang-Sattler
- Institute of Translational Genomics, Helmholtz Zentrum München - German Research Centre for Environmental Health, Neuherberg, Germany
| | - Thomas Köcher
- Vienna BioCenter Core Facilities GmbH, Vienna, Austria
| | - Luís Mendes Pedro
- Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
- Vascular Surgery Department, Hospital de Santa Maria, Unidade Local de Saúde de Santa Maria, Lisbon, Portugal
| | - Fausto Pinto
- Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
- Department of Cardiology, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Luís Ferreira Moita
- Center for Disease Mechanisms Research, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
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Ham HJ, Kim J. Targeted nutritional strategies in postoperative care. Anesth Pain Med (Seoul) 2025; 20:34-45. [PMID: 39809503 PMCID: PMC11834873 DOI: 10.17085/apm.24067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Revised: 10/29/2024] [Accepted: 11/04/2024] [Indexed: 01/16/2025] Open
Abstract
Immunonutrition, which uses specific nutrients to modulate the immune response, has emerged as a vital adjunct to perioperative care. Surgery-induced stress triggers immune responses that can lead to complications, such as infections and delayed wound healing. Traditional nutritional support often overlooks the immunological needs of surgical patients. Immunonutrition addresses this oversight by providing key nutrients, such as arginine, omega-3 fatty acids, glutamine, nucleotides, and antioxidants (vitamins C and E) to enhance immune function and support tissue repair. This review examined the efficacy and safety of immunonutrition in surgical settings, guided by the recommendations of the American Society for Parenteral and Enteral Nutrition and the European Society for Clinical Nutrition and Metabolism. Both organizations recommend immunonutrition for high-risk or malnourished patients undergoing major surgery and support its use in reducing complications and improving recovery. The key nutrients in immunonutrition aim to improve immune cell function, reduce inflammation, and enhance wound healing. Clinical studies and meta-analyses have demonstrated that immunonutrition lowers the infection rate, shortens the length of hospital stay, and accelerates recovery. Challenges hindering the clinical application of immunonutrition include cost, logistics, and a lack of standardized and personalized protocols. Future studies should focus on biomarker-driven approaches, pharmacogenomics, and innovative nutrient formulations. Addressing these issues will help to integrate immunonutrition into clinical practice, ultimately improving surgical outcomes and patient recovery.
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Affiliation(s)
- Hye Jin Ham
- Department of Nutrition Care, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jeongmin Kim
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea
- Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea
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Aquilani R, Brugnatelli S, Maestri R, Iadarola P, Corallo S, Pagani A, Serra F, Bellini A, Buonocore D, Dossena M, Boschi F, Verri M. Chemotherapy-Induced Changes in Plasma Amino Acids and Lipid Oxidation of Resected Patients with Colorectal Cancer: A Background for Future Studies. Int J Mol Sci 2024; 25:5300. [PMID: 38791339 PMCID: PMC11121634 DOI: 10.3390/ijms25105300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Revised: 05/07/2024] [Accepted: 05/10/2024] [Indexed: 05/26/2024] Open
Abstract
Previous studies have documented that FOLFOX and XELOX therapies negatively impact the metabolism of skeletal muscle and extra-muscle districts. This pilot study tested whether three-month FOLFOX or XELOX therapy produced changes in plasma amino acid levels (PAAL) (an estimation of whole-body amino acid metabolism) and in plasma levels of malondialdehyde (MDA), a marker of lipid hyper oxidation. Fourteen ambulatory, resected patients with colorectal cancer scheduled to receive FOLFOX (n = 9) or XELOX (n = 5) therapy, after overnight fasting, underwent peripheral venous blood sampling, to determine PAAL and MDA before, during, and at the end of three-month therapy. Fifteen healthy matched subjects (controls) only underwent measures of PAAL at baseline. The results showed changes in 87.5% of plasma essential amino acids (EAAs) and 38.4% of non-EAAs in patients treated with FOLFOX or XELOX. These changes in EAAs occurred in two opposite directions: EAAs decreased with FOLFOX and increased or did not decrease with XELOX (interactions: from p = 0.034 to p = 0.003). Baseline plasma MDA levels in both FOLFOX and XELOX patients were above the normal range of values, and increased, albeit not significantly, during therapy. In conclusion, three-month FOLFOX or XELOX therapy affected plasma EAAs differently but not the baseline MDA levels, which were already high.
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Affiliation(s)
- Roberto Aquilani
- Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy; (R.A.); (P.I.); (A.B.); (D.B.); (M.D.)
| | - Silvia Brugnatelli
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (S.B.); (S.C.); (A.P.); (F.S.)
| | - Roberto Maestri
- Department of Biomedical Engineering of the Montescano Institute, Istituti Clinici Scientifici Maugeri IRCCS, 27040 Montescano, Italy;
| | - Paolo Iadarola
- Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy; (R.A.); (P.I.); (A.B.); (D.B.); (M.D.)
| | - Salvatore Corallo
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (S.B.); (S.C.); (A.P.); (F.S.)
| | - Anna Pagani
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (S.B.); (S.C.); (A.P.); (F.S.)
| | - Francesco Serra
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (S.B.); (S.C.); (A.P.); (F.S.)
| | - Anna Bellini
- Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy; (R.A.); (P.I.); (A.B.); (D.B.); (M.D.)
| | - Daniela Buonocore
- Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy; (R.A.); (P.I.); (A.B.); (D.B.); (M.D.)
| | - Maurizia Dossena
- Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy; (R.A.); (P.I.); (A.B.); (D.B.); (M.D.)
| | - Federica Boschi
- Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy;
| | - Manuela Verri
- Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy; (R.A.); (P.I.); (A.B.); (D.B.); (M.D.)
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Soh J, Raventhiran S, Lee JH, Lim ZX, Goh J, Kennedy BK, Maier AB. The effect of glycine administration on the characteristics of physiological systems in human adults: A systematic review. GeroScience 2024; 46:219-239. [PMID: 37851316 PMCID: PMC10828290 DOI: 10.1007/s11357-023-00970-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 10/04/2023] [Indexed: 10/19/2023] Open
Abstract
Functional decline of physiological systems during ageing leads to age-related diseases. Dietary glycine increases healthy lifespan in model organisms and might decrease inflammation in humans, suggesting its geroprotective potential. This review summarises the evidence of glycine administration on the characteristics of eleven physiological systems in adult humans. Databases were searched using key search terms: 'glycine', 'adult', 'supplementation'/ 'administration'/ 'ingestion'/ 'treatment'. Glycine was administered to healthy and diseased populations (18 and 34 studies) for up to 14 days and 4 months, respectively. The nervous system demonstrated the most positive effects, including improved psychiatric symptoms from longer-term glycine administration in psychiatric populations. While longer-term glycine administration improved sleep in healthy populations, these studies had small sample sizes with a high risk of bias. Larger and long-term studies with more robust study designs in healthy populations to examine the effects of glycine administration on preventing, delaying or reversing the ageing process are warranted.
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Affiliation(s)
- Janjira Soh
- Centre for Healthy Longevity, National University Health System (NUHS), Singapore, Singapore
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore
| | - Shivaanishaa Raventhiran
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore
| | - Jasinda H Lee
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore
| | - Zi Xiang Lim
- Centre for Healthy Longevity, National University Health System (NUHS), Singapore, Singapore
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore
| | - Jorming Goh
- Centre for Healthy Longevity, National University Health System (NUHS), Singapore, Singapore
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore
| | - Brian K Kennedy
- Centre for Healthy Longevity, National University Health System (NUHS), Singapore, Singapore
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore
| | - Andrea B Maier
- Centre for Healthy Longevity, National University Health System (NUHS), Singapore, Singapore.
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore.
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore.
- Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Van Der Boechorstsraat 7, Amsterdam, 1081 BT, The Netherlands.
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Ling ZN, Jiang YF, Ru JN, Lu JH, Ding B, Wu J. Amino acid metabolism in health and disease. Signal Transduct Target Ther 2023; 8:345. [PMID: 37699892 PMCID: PMC10497558 DOI: 10.1038/s41392-023-01569-3] [Citation(s) in RCA: 118] [Impact Index Per Article: 59.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 06/12/2023] [Accepted: 07/13/2023] [Indexed: 09/14/2023] Open
Abstract
Amino acids are the building blocks of protein synthesis. They are structural elements and energy sources of cells necessary for normal cell growth, differentiation and function. Amino acid metabolism disorders have been linked with a number of pathological conditions, including metabolic diseases, cardiovascular diseases, immune diseases, and cancer. In the case of tumors, alterations in amino acid metabolism can be used not only as clinical indicators of cancer progression but also as therapeutic strategies. Since the growth and development of tumors depend on the intake of foreign amino acids, more and more studies have targeted the metabolism of tumor-related amino acids to selectively kill tumor cells. Furthermore, immune-related studies have confirmed that amino acid metabolism regulates the function of effector T cells and regulatory T cells, affecting the function of immune cells. Therefore, studying amino acid metabolism associated with disease and identifying targets in amino acid metabolic pathways may be helpful for disease treatment. This article mainly focuses on the research of amino acid metabolism in tumor-oriented diseases, and reviews the research and clinical research progress of metabolic diseases, cardiovascular diseases and immune-related diseases related to amino acid metabolism, in order to provide theoretical basis for targeted therapy of amino acid metabolism.
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Affiliation(s)
- Zhe-Nan Ling
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, P.R. China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, P.R. China
- Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou, Zhejiang Province, P.R. China
- Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, P.R. China
| | - Yi-Fan Jiang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, P.R. China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, P.R. China
- Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou, Zhejiang Province, P.R. China
- Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, P.R. China
| | - Jun-Nan Ru
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, P.R. China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, P.R. China
- Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou, Zhejiang Province, P.R. China
- Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, P.R. China
| | - Jia-Hua Lu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, P.R. China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, P.R. China
- Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou, Zhejiang Province, P.R. China
- Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, P.R. China
| | - Bo Ding
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, P.R. China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, P.R. China
- Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou, Zhejiang Province, P.R. China
- Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, P.R. China
| | - Jian Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, P.R. China.
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, P.R. China.
- Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou, Zhejiang Province, P.R. China.
- Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, P.R. China.
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Okamoto Y, Sakaguchi T, Ikematsu Y, Kanai T, Hirayama K, Tamura H, Hayashi T, Nishiwaki Y, Konno H, Aoki K. Early enteral nutrition with arginine compensates for negative nitrogen balance in patients undergoing curative total gastrectomy. THE JOURNAL OF MEDICAL INVESTIGATION 2023; 70:325-333. [PMID: 37940515 DOI: 10.2152/jmi.70.325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2023]
Abstract
The effects of early enteral arginine-rich nutrition (EAN) were analyzed among patients undergoing curative-intent total gastrectomy for gastric cancer. There were 19 patients in this prospective study, all randomly assigned to either a parenteral nutrition (PN) group or an EAN group for the first seven days after surgery. The EAN group received 1.8-fold greater arginine (10.1 g/day) compared with the PN group, which was administered through an enteral tube inserted into the jejunal loop. Both groups were provided almost identical amounts of total amino acids (54 g/day), and the total energy was set at 65% of the total requirement (25 kcal/kg/day). No significant differences were observed between the two groups in postoperative complications, length of hospital stay, oral intake, nutritional status, or body weight. The serum arginine profile was similar in the two groups, as it decreased significantly on postoperative day (POD) 1, and gradually returned to preoperative levels by POD 7. The nitrogen balance remained negative until POD 7 in the PN group, but turned neutral at POD 7 in the EAN group. While we could not confirm body weight loss improvement, these results suggested that early arginine-rich enteral nutrition could improve the nitrogen balance after total gastrectomy. J. Med. Invest. 70 : 325-333, August, 2023.
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Affiliation(s)
- Yasuko Okamoto
- Faculty of Home Economics, Aichi Gakusen University, Okazaki, Aichi, Japan
- Clinical Nutritional Management, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan
| | | | - Yoshito Ikematsu
- Department of Gastroenterological Surgery, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan
| | - Toshikazu Kanai
- Department of Gastroenterological Surgery, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan
| | - Kazuhisa Hirayama
- Department of Gastroenterological Surgery, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan
- Surgery, Shizuoka City Shimizu Hospital, Shizuoka, Japan
| | - Hiroaki Tamura
- Department of Gastroenterological Surgery, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan
| | - Tadataka Hayashi
- Department of Gastroenterological Surgery, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan
| | - Yoshiro Nishiwaki
- Department of Gastroenterological Surgery, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan
| | - Hiroyuki Konno
- Department of Emergency Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Katsunori Aoki
- Department of Emergency Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
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Vanzant E, Frayman R, Hensley S, Rosenthal M. Should Anabolic Agents be Used for Resolving Catabolism in Post-ICU Recovery? CURRENT SURGERY REPORTS 2022. [DOI: 10.1007/s40137-022-00336-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
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Liu T, Wang X, Jia P, Liu C, Wei Y, Song Y, Li S, Liu L, Wang B, Shi H. Association between serum arginine levels and cancer risk: A community-based nested case-control study. Front Nutr 2022; 9:1069113. [PMID: 36466394 PMCID: PMC9712959 DOI: 10.3389/fnut.2022.1069113] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 11/02/2022] [Indexed: 01/10/2024] Open
Abstract
OBJECTIVE The effect of arginine on tumors appears to be bidirectional. The association of serum arginine with the risk of incident cancer remains uncovered at present. We aimed to investigate the prospective relationship of baseline serum arginine concentrations with the risk of incident cancer in hypertensive participants. MATERIALS AND METHODS A nested, case-control study with 1,389 incident cancer cases and 1,389 matched controls was conducted using data from the China H-Type Hypertension Registry Study (CHHRS). Conditional logistic regression analyses were performed to evaluate the association between serum arginine and the risk of the overall, digestive system, non-digestive system, and site-specific cancer. RESULTS Compared with matched controls, cancer patients had higher levels of arginine (21.41 μg/mL vs. 20.88 μg/mL, p < 0.05). When serum arginine concentrations were assessed as quartiles, compared with participants in the lowest arginine quartile, participants in the highest arginine quartile had a 32% (OR = 1.32, 95% CI: 1.03 to 1.71), and 68% (OR = 1.68, 95% CI: 1.09 to 2.59) increased risk of overall and digestive system cancer, respectively, in the adjusted models. In the site-specific analysis, each standard deviation (SD) increment of serum arginine was independently and positively associated with the risk of colorectal cancer (OR = 1.35, 95% CI: 1.01 to 1.82) in the adjusted analysis. CONCLUSION We found that hypertensive individuals with higher serum arginine levels exhibited a higher risk of overall, digestive system, and colorectal cancer.
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Affiliation(s)
- Tong Liu
- Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, China
| | - Xiaomeng Wang
- Department of Education, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
| | - Pingping Jia
- Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, China
| | - Chenan Liu
- Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, China
| | - Yaping Wei
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Food Sciences and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Yun Song
- Shenzhen Evergreen Medical Institute, Shenzhen, China
| | - Shuqun Li
- Shenzhen Evergreen Medical Institute, Shenzhen, China
| | - Lishun Liu
- Shenzhen Evergreen Medical Institute, Shenzhen, China
| | - Binyan Wang
- Shenzhen Evergreen Medical Institute, Shenzhen, China
| | - Hanping Shi
- Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, China
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10
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Xiao-Chai-Hu Decoction Ameliorates Poly (I:C)-Induced Viral Pneumonia through Inhibiting Inflammatory Response and Modulating Serum Metabolism. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:1240242. [PMID: 35865338 PMCID: PMC9296287 DOI: 10.1155/2022/1240242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/27/2022] [Accepted: 06/15/2022] [Indexed: 11/30/2022]
Abstract
Viral pneumonia is widespread, progresses rapidly, and has a high mortality rate. Developing safe and effective therapies to treat viral pneumonia can minimize risks to public health and alleviate pressures on the associated health systems. Xiao-Chai-Hu (XCH) decoction can be used in the treatment of viral pneumonia. However, the mechanisms of XCH on viral pneumonia remain unclear. In this study, poly (I:C) was used to establish a mouse model of viral pneumonia, and the therapeutic effects of XCH on viral pneumonia were assessed. Furthermore, we evaluated the effects of XCH on inflammatory response. Lastly, untargeted metabolomics were used to study the metabolic regulatory mechanisms of XCH on viral pneumonia model mice. Our results showed that XCH treatment decreased the wet/dry ratio in lung tissue, total protein concentration, and total cell count in bronchoalveolar lavage fluid (BALF). H&E staining indicated that XCH treatment alleviated the pathological changes in lung. Moreover, XCH treatment decreased the levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and lowered the ratio of CD86+/CD206+ macrophages and CD11b+LY6G+ neutrophils in BALF. XCH treatment also decreased the myeloperoxidase (MPO) and reduced the phosphorylations of PI3K, AKT, and NF-κB p65 in lung. Serum untargeted metabolomics analysis showed that XCH treatment could affect 18 metabolites in serum such as creatine, hydroxyproline, cortisone, hydrocortisone, corticosterone, hypotaurine, and taurine. These metabolites were associated with arginine and proline metabolism, steroid hormone biosynthesis, and taurine and hypotaurine metabolism processes. In conclusion, our study demonstrated that treatment with XCH can ameliorate viral pneumonia and reduce inflammatory response in viral pneumonia. The mechanism of action of XCH in the treatment of viral pneumonia may be associated with inhibiting the activation of PI3K/AKT/NF-κB signaling pathway in lung and regulating arginine and proline metabolism, steroid hormone biosynthesis, and taurine and hypotaurine metabolism in serum.
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11
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Bilal M, Ashraf S, Zhao X. Dietary Component-Induced Inflammation and Its Amelioration by Prebiotics, Probiotics, and Synbiotics. Front Nutr 2022; 9:931458. [PMID: 35938108 PMCID: PMC9354043 DOI: 10.3389/fnut.2022.931458] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/20/2022] [Indexed: 12/12/2022] Open
Abstract
A balanced diet with many dietary components maintains immune homeostasis directly by interacting with innate and adaptive immune components or indirectly through gut microbiota and their metabolites. Dietary components may inhibit pro-inflammatory mediators and promote anti-inflammatory functions or vice versa. Western diets with imbalanced dietary components skew the immune balance toward pro-inflammation and induce intestinal inflammation, consequently leading to many intestinal and systemic inflammatory diseases like ulcerative colitis, Crohn's disease, irritable bowel syndrome, cardiovascular problems, obesity, and diabetes. The dietary component-induced inflammation is usually chronic in nature and frequently caused or accompanied by alterations in gut microbiota. Therefore, microbiome-targeted therapies such as probiotics, prebiotics and synbiotics hold great potentials to amend immune dysregulation and gut dysbiosis, preventing and treating intestinal and systemic inflammatory diseases. Probiotics, prebiotics and synbioitcs are progressively being added to foods and beverages, with claims of health benefits. However, the underlining mechanisms of these interventions for preventing and treating dietary component-induced inflammation are still not very clear. In addition, possibly ineffective or negative consequences of some probiotics, prebiotics and synbiotics call for stringent testing and regulation. Here, we will first briefly review inflammation, in terms of its types and the relationship between different dietary components and immune responses. Then, we focus on current knowledge about the direct and indirect effects of probiotics, prebiotics and synbiotics on intestinal and systemic inflammation. Understanding how probiotics, prebiotics and synbiotics modulate the immune system and gut microbiota will improve our strategies for preventing and treating dietary component-induced intestinal inflammation and inflammatory diseases.
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12
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Hou X, Chen S, Zhang P, Guo D, Wang B. Targeted Arginine Metabolism Therapy: A Dilemma in Glioma Treatment. Front Oncol 2022; 12:938847. [PMID: 35898872 PMCID: PMC9313538 DOI: 10.3389/fonc.2022.938847] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Accepted: 06/20/2022] [Indexed: 11/29/2022] Open
Abstract
Efforts in the treatment of glioma which is the most common primary malignant tumor of the central nervous system, have not shown satisfactory results despite a comprehensive treatment model that combines various treatment methods, including immunotherapy. Cellular metabolism is a determinant of the viability and function of cancer cells as well as immune cells, and the interplay of immune regulation and metabolic reprogramming in tumors has become an active area of research in recent years. From the perspective of metabolism and immunity in the glioma microenvironment, we elaborated on arginine metabolic reprogramming in glioma cells, which leads to a decrease in arginine levels in the tumor microenvironment. Reduced arginine availability significantly inhibits the proliferation, activation, and function of T cells, thereby promoting the establishment of an immunosuppressive microenvironment. Therefore, replenishment of arginine levels to enhance the anti-tumor activity of T cells is a promising strategy for the treatment of glioma. However, due to the lack of expression of argininosuccinate synthase, gliomas are unable to synthesize arginine; thus, they are highly dependent on the availability of arginine in the extracellular environment. This metabolic weakness of glioma has been utilized by researchers to develop arginine deprivation therapy, which ‘starves’ tumor cells by consuming large amounts of arginine in circulation. Although it has shown good results, this treatment modality that targets arginine metabolism in glioma is controversial. Exploiting a suitable strategy that can not only enhance the antitumor immune response, but also “starve” tumor cells by regulating arginine metabolism to cure glioma will be promising.
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13
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Gill PA, Inniss S, Kumagai T, Rahman FZ, Smith AM. The Role of Diet and Gut Microbiota in Regulating Gastrointestinal and Inflammatory Disease. Front Immunol 2022; 13:866059. [PMID: 35450067 PMCID: PMC9016115 DOI: 10.3389/fimmu.2022.866059] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Accepted: 03/14/2022] [Indexed: 12/20/2022] Open
Abstract
Diet is an important lifestyle factor that is known to contribute in the development of human disease. It is well established that poor diet plays an active role in exacerbating metabolic diseases, such as obesity, diabetes and hypertension. Our understanding of how the immune system drives chronic inflammation and disease pathogenesis has evolved in recent years. However, the contribution of dietary factors to inflammatory conditions such as inflammatory bowel disease, multiple sclerosis and arthritis remain poorly defined. A western diet has been associated as pro-inflammatory, in contrast to traditional dietary patterns that are associated as being anti-inflammatory. This may be due to direct effects of nutrients on immune cell function. Diet may also affect the composition and function of gut microbiota, which consequently affects immunity. In animal models of inflammatory disease, diet may modulate inflammation in the gastrointestinal tract and in other peripheral sites. Despite limitations of animal models, there is now emerging evidence to show that anti-inflammatory effects of diet may translate to human gastrointestinal and inflammatory diseases. However, appropriately designed, larger clinical studies must be conducted to confirm the therapeutic benefit of dietary therapy.
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Affiliation(s)
- Paul A Gill
- Department of Microbial Diseases, UCL Eastman Dental Institute, University College London, London, United Kingdom
| | - Saskia Inniss
- Department of Microbial Diseases, UCL Eastman Dental Institute, University College London, London, United Kingdom
| | - Tomoko Kumagai
- Department of Microbial Diseases, UCL Eastman Dental Institute, University College London, London, United Kingdom
| | - Farooq Z Rahman
- Department of Microbial Diseases, UCL Eastman Dental Institute, University College London, London, United Kingdom.,Department of Gastroenterology, University College London Hospitals National Health Service (NHS) Foundation Trust, London, United Kingdom
| | - Andrew M Smith
- Department of Microbial Diseases, UCL Eastman Dental Institute, University College London, London, United Kingdom
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14
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Gupta A, Gupta E, Hilsden R, Hawel JD, Elnahas AI, Schlachta CM, Alkhamesi NA. Preoperative malnutrition in patients with colorectal cancer. Can J Surg 2021; 64:E621-E629. [PMID: 34824150 PMCID: PMC8628841 DOI: 10.1503/cjs.016820] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/12/2021] [Indexed: 01/04/2023] Open
Abstract
Preoperative malnutrition in patients with colorectal cancer is associated with several postoperative consequences and poorer prognosis. Currently, there is a lack of a universal screening tool to assess nutritional status, and intervention to treat preoperative malnutrition is often neglected. This review summarizes and compares preoperative screening and interventional tools to help providers optimize malnourished patients with colorectal cancer for surgery. We found that nutritional screenings, such as the Subjectibe Global Assessment, Patient-Generated Subjective Global Assessment, Prognostic Nutritional Index, Nutrition Risk Index, Malnutrition Universal Screening Tool, Nutrition Risk Screening 2002, Nutrition Risk Score, serum albumin, and prealbumin, have all effectively predicted postoperative outcome. Physicians should consider which of these tools best fits their needs based on the their mode of assessment, efficiency, and specified parameters. Additionally, preoperative nutritional support, such as trimodal prehabilitation, modified peripheral parenteral nutrition, and N-3 fatty acid and arginine supplementation, which have also benefited patients postoperatively, ought to be implemented appropriately according to their ease of execution. Given the high prevalence of preoperative malnutrition in patients undergoing surgery for colorectal cancer, it is essential that health care providers assess and treat this malnutrition to reduce postoperative complications and length of hospital stay, and to improve prognosis to augment a patient’s quality of care.
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Affiliation(s)
- Ashna Gupta
- From the Department of Surgery, Western University, London, Ont
| | - Eisha Gupta
- From the Department of Surgery, Western University, London, Ont
| | - Richard Hilsden
- From the Department of Surgery, Western University, London, Ont
| | - Jeffry D Hawel
- From the Department of Surgery, Western University, London, Ont
| | - Ahmad I Elnahas
- From the Department of Surgery, Western University, London, Ont
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15
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Martí I Líndez AA, Reith W. Arginine-dependent immune responses. Cell Mol Life Sci 2021; 78:5303-5324. [PMID: 34037806 PMCID: PMC8257534 DOI: 10.1007/s00018-021-03828-4] [Citation(s) in RCA: 160] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 03/23/2021] [Accepted: 03/29/2021] [Indexed: 02/07/2023]
Abstract
A growing body of evidence indicates that, over the course of evolution of the immune system, arginine has been selected as a node for the regulation of immune responses. An appropriate supply of arginine has long been associated with the improvement of immune responses. In addition to being a building block for protein synthesis, arginine serves as a substrate for distinct metabolic pathways that profoundly affect immune cell biology; especially macrophage, dendritic cell and T cell immunobiology. Arginine availability, synthesis, and catabolism are highly interrelated aspects of immune responses and their fine-tuning can dictate divergent pro-inflammatory or anti-inflammatory immune outcomes. Here, we review the organismal pathways of arginine metabolism in humans and rodents, as essential modulators of the availability of this semi-essential amino acid for immune cells. We subsequently review well-established and novel findings on the functional impact of arginine biosynthetic and catabolic pathways on the main immune cell lineages. Finally, as arginine has emerged as a molecule impacting on a plethora of immune functions, we integrate key notions on how the disruption or perversion of arginine metabolism is implicated in pathologies ranging from infectious diseases to autoimmunity and cancer.
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Affiliation(s)
| | - Walter Reith
- Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
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16
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Chronic Critical Illness and PICS Nutritional Strategies. J Clin Med 2021; 10:jcm10112294. [PMID: 34070395 PMCID: PMC8197535 DOI: 10.3390/jcm10112294] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 05/14/2021] [Accepted: 05/17/2021] [Indexed: 12/26/2022] Open
Abstract
The nutritional hallmark of chronic critical illness (CCI) after sepsis is persistent inflammation, immunosuppression, and catabolism syndrome (PICS), which results in global resistance to the anabolic effect of nutritional supplements. This ultimately leaves these patients in a downward phenotypic spiral characterized by cachexia with profound weakness, decreased capacity for rehabilitation, and immunosuppression with the propensity for sepsis recidivism. The persistent catabolism is driven by a pathologic low-grade inflammation with the inability to return to homeostasis and by ongoing increased energy expenditure. Better critical care support systems and advances in technology have led to increased intensive care unit (ICU) survival, but CCI due to PICS with poor long-term outcomes has emerged as a frequent phenotype among ICU sepsis survivors. Unfortunately, therapies to mitigate or reverse PICS-CCI are limited, and recent evidence supports that these patients fail to respond to early ICU evidence-based nutrition protocols. A lack of randomized controlled trials has limited strong recommendations for nutrition adjuncts in these patients. However, based on experience in other conditions characterized by a similar phenotype, immunonutrients aimed at counteracting inflammation, immunosuppression, and catabolism may be important for improving outcomes in PICS-CCI patients. This manuscript intends to review several immunonutrients as adjunctive therapies in treating PICS-CCI.
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17
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Yeh CL, Tanuseputero SA, Wu JM, Tseng YR, Yang PJ, Lee PC, Yeh SL, Lin MT. Intravenous Arginine Administration Benefits CD4 + T-Cell Homeostasis and Attenuates Liver Inflammation in Mice with Polymicrobial Sepsis. Nutrients 2020; 12:E1047. [PMID: 32290120 PMCID: PMC7231035 DOI: 10.3390/nu12041047] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 03/30/2020] [Accepted: 04/07/2020] [Indexed: 12/14/2022] Open
Abstract
This study investigated the effects of a single dose of arginine (Arg) administration at the beginning of sepsis on CD4+ T-cell regulation and liver inflammation in C57BL/6J mice. Mice were divided into normal control (NC), sham (SH), sepsis saline (SS), and sepsis Arg (SA) groups. An inducible nitric oxide (NO) synthase (iNOS) inhibitor was administered to additional sepsis groups to evaluate the role of NO during sepsis. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg (300 mg/kg body weight) via tail vein 1 h after CLP. Mice were euthanized at 12 and 24 h post-CLP. Blood, para-aortic lymph nodes, and liver tissues were collected for further measurement. The findings showed that sepsis resulted in decreases in blood and para-aortic lymph node CD4+ T-cell percentages, whereas percentages of interleukin (IL)-4- and IL-17-expressing CD4+ T cells were upregulated. Compared to the SS group, Arg administration resulted in maintained circulating and para-aortic lymph node CD4+ T cells, an increased Th1/Th2 ratio, and a reduced Th17/Treg ratio post-CLP. In addition, levels of plasma liver injury markers and expression of inflammatory genes in liver decreased. These results suggest that a single dose of Arg administered after CLP increased Arg availability, sustained CD4+ T-cell populations, elicited more-balanced Th1/Th2/Th17/Treg polarization in the circulation and the para-aortic lymph nodes, and attenuated liver inflammation in sepsis. The favorable effects of Arg were abrogated when an iNOS inhibitor was administered, which indicated that NO may be participated in regulating the homeostasis of Th/Treg cells and subsequent liver inflammation during sepsis.
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Affiliation(s)
- Chiu-Li Yeh
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; (C.-L.Y.); (S.A.T.); (Y.-R.T.); (S.-L.Y.)
- Nutrition Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan
- Research Center of Geriatric Nutrition, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan
| | - Sharon Angela Tanuseputero
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; (C.-L.Y.); (S.A.T.); (Y.-R.T.); (S.-L.Y.)
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10002, Taiwan; (J.-M.W.); (P.-J.Y.); (P.-C.L.)
| | - Jin-Ming Wu
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10002, Taiwan; (J.-M.W.); (P.-J.Y.); (P.-C.L.)
| | - Yi-Ru Tseng
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; (C.-L.Y.); (S.A.T.); (Y.-R.T.); (S.-L.Y.)
| | - Po-Jen Yang
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10002, Taiwan; (J.-M.W.); (P.-J.Y.); (P.-C.L.)
| | - Po-Chu Lee
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10002, Taiwan; (J.-M.W.); (P.-J.Y.); (P.-C.L.)
| | - Sung-Ling Yeh
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; (C.-L.Y.); (S.A.T.); (Y.-R.T.); (S.-L.Y.)
| | - Ming-Tsan Lin
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10002, Taiwan; (J.-M.W.); (P.-J.Y.); (P.-C.L.)
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18
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Chitapanarux I, Traisathit P, Chitapanarux T, Jiratrachu R, Chottaweesak P, Chakrabandhu S, Rasio W, Pisprasert V, Sripan P. Arginine, glutamine, and fish oil supplementation in cancer patients treated with concurrent chemoradiotherapy: A randomized control study. Curr Probl Cancer 2020; 44:100482. [DOI: 10.1016/j.currproblcancer.2019.05.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 05/15/2019] [Indexed: 11/17/2022]
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19
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Crossland MR, Salim AA, Capon RJ, Shine R. The Effects of Conspecific Alarm Cues on Larval Cane Toads (Rhinella marina). J Chem Ecol 2019; 45:838-848. [PMID: 31677136 DOI: 10.1007/s10886-019-01111-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 09/12/2019] [Accepted: 09/18/2019] [Indexed: 11/29/2022]
Abstract
Many aquatic organisms detect and avoid damage-released cues from conspecifics, but the chemical basis of such responses, and the effects of prolonged exposure to such cues, remain poorly understood. Injured tadpoles of the cane toad (Rhinella marina) produce chemical cues that induce avoidance by conspecific tadpoles; and chronic exposure to those cues decreases rates of tadpole survival and growth, and reduces body size at metamorphosis. Such effects suggest that we might be able to use the cane toads' alarm cue for biocontrol of invasive populations in Australia. In the present study, we examined behavioral and ecological effects of compounds that are present in cane toad tadpoles and thus, might trigger avoidance of crushed conspecifics. Four chemicals (L-Arg, L-Leu-L-Leu-OH, L-Leu-L-Ile-OH and suberic acid) induced behavioral avoidance in toad tadpoles at some (but not all) dosage levels, so we then exposed toad larvae to these chemicals over the entire period of larval development. Larval survival and size at metamorphosis were decreased by chronic exposure to crushed conspecifics (consistent with earlier studies), but not by exposure to any of the four chemicals. Indeed, L-Arg increased body size at metamorphosis. We conclude that the behavioral response to crushed conspecifics by cane toad tadpoles can be elicited by a variety of chemical cues, but that consistent exposure to these individual chemical cues does not affect tadpole viability or developmental trajectory. The optimal behavioral tactic of a tadpole may be to flee if it encounters even a single chemical cue likely to have come from an injured conspecific (indicative of predation risk), whereas the continuing presence of that single chemical (but no others) provides a less reliable signal of predation risk. Our data are consistent with results from studies on fish, that suggest a role for multiple chemicals in initiating alarm responses to damage-released cues.
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Affiliation(s)
- Michael R Crossland
- School of Life and Environmental Sciences A08, University of Sydney, Sydney, NSW, 2006, Australia
| | - Angela A Salim
- Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, 4072, Australia
| | - Robert J Capon
- Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, 4072, Australia
| | - Richard Shine
- School of Life and Environmental Sciences A08, University of Sydney, Sydney, NSW, 2006, Australia. .,Department of Biological Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
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20
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Ruiz-Tovar J, Blanca M, Garcia A, Gonzalez J, Gutierrez S, Paniagua A, Prieto MJ, Ramallo L, Llanos L, Duran M. Preoperative administration of Omega-3 fatty acids on postoperative pain and acute-phase reactants in patients undergoing Roux-en-Y gastric bypass: A randomized clinical trial. Clin Nutr 2019; 38:1588-1593. [DOI: 10.1016/j.clnu.2018.07.026] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 07/03/2018] [Accepted: 07/20/2018] [Indexed: 11/26/2022]
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21
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Karimian J, Hadi A, Salehi-Sahlabadi A, Kafeshani M. The Effect of Arginine Intake on Colorectal Cancer: a Systematic Review of Literatures. Clin Nutr Res 2019; 8:209-218. [PMID: 31384599 PMCID: PMC6675959 DOI: 10.7762/cnr.2019.8.3.209] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 06/14/2019] [Accepted: 07/01/2019] [Indexed: 12/31/2022] Open
Abstract
Colorectal cancer (CRC) is one of the major reasons of mortality in the worldwide. There is clear evidence that some amino acids such as arginine can improve CRC and its complications. Hence, in this systematic review we evaluated the association between arginine intake and CRC improvement. We searched the PubMed, Scopus, ISI Web of Science, Cochrane library, and Google Scholar databases by using proper keywords to find the relevant literatures, published to March 2019. Nine human studies of 523 screened articles were included in present systematic review. The majority of studies have found a positive association between consumption of arginine and CRC improvement. Increased inducible nitric oxide (NO) synthase expression and subsequently increasing the NO concentration in the tumor and/or serum, after arginine intake may be responsible for these protective effects. Also, arginine consumption may reduce cell proliferation in CRC and it can enhance immune function after remove the tumor. Although the benefits of arginine consumption in CRC patients were reported in previous trials, the finding need replication in well-designed studies before final conclusion.
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Affiliation(s)
- Jahangir Karimian
- Department of General Courses, School of Management and Medical Information Sciences, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
| | - Amir Hadi
- Halal Research Center of IRI, FDA, Tehran, Iran
| | - Ammar Salehi-Sahlabadi
- Student Research Committee, Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
| | - Marzieh Kafeshani
- School of Nutrition and Food Science, Food Security and Nutrition Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
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22
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Meesters DM, Wijnands KAP, Brink PRG, Poeze M. Malnutrition and Fracture Healing: Are Specific Deficiencies in Amino Acids Important in Nonunion Development? Nutrients 2018; 10:E1597. [PMID: 30384490 PMCID: PMC6266771 DOI: 10.3390/nu10111597] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 10/24/2018] [Accepted: 10/26/2018] [Indexed: 02/07/2023] Open
Abstract
With the increasing incidence of fractures now, and in the future, the absolute number of bone-healing complications such as nonunion development will also increase. Next to fracture-dependent factors such as large bone loss volumes and inadequate stabilization, the nutritional state of these patients is a major influential factor for the fracture repair process. In this review, we will focus on the influence of protein/amino acid malnutrition and its influence on fracture healing. Mainly, the arginine-citrulline-nitric oxide metabolism is of importance since it can affect fracture healing via several precursors of collagen formation, and through nitric oxide synthases it has influences on the bio-molecular inflammatory responses and the local capillary growth and circulation.
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Affiliation(s)
- Dennis M Meesters
- Department of Surgery, Maastricht University Medical Center, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
- NUTRIM School for Nutrition and Translational Research in Metabolism, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
| | - Karolina A P Wijnands
- Department of Surgery, Maastricht University Medical Center, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
- NUTRIM School for Nutrition and Translational Research in Metabolism, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
| | - Peter R G Brink
- Department of Surgery, Maastricht University Medical Center, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
| | - Martijn Poeze
- Department of Surgery, Maastricht University Medical Center, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
- NUTRIM School for Nutrition and Translational Research in Metabolism, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
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23
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Kanekiyo S, Takeda S, Iida M, Nishiyama M, Kitahara M, Shindo Y, Tokumitsu Y, Tomochika S, Tsunedomi R, Suzuki N, Abe T, Yoshino S, Hazama S, Ueno T, Nagano H. Efficacy of perioperative immunonutrition in esophageal cancer patients undergoing esophagectomy. Nutrition 2018; 59:96-102. [PMID: 30468936 DOI: 10.1016/j.nut.2018.08.006] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 07/19/2018] [Accepted: 08/03/2018] [Indexed: 12/30/2022]
Abstract
OBJECTIVE Malnutrition is common in patients with esophageal cancer, resulting in increased postoperative complications and mortality. Although preoperative immunonutrition can significantly reduce the incidence of postoperative infectious complications, its effect in patietns with esophageal cancer undergoing esophagectomy remains unclear. The aim of this study was to investigate the effects of perioperative immunonutritional support on the postoperative course and long-term survival of this group of patients. METHODS This prospective, randomized study enrolled 40 patients with thoracic esophageal carcinoma undergoing esophagectomy. The patients were divided into two groups and received either immunomodulating enteral nutrition (IMPACT group; IG) or standard enteral nutrition (Ensure group; EG) continuously for 7 d before and 7 d after surgery. Nutritional status, such as rapid turnover protein, postoperative intensive care unit (ICU) length of stay (LOS), postoperative hospital LOS, morbidity, and mortality were investigated prospectively. RESULTS There were no significant differences in patient demographic characteristics between the two groups. Levels of retinol-binding protein, as a rapid-turnover protein, were significantly higher on postoperative day (POD) -1, 7, and 14 in the IG compared with the EG group (P = 0.009, P = 0.004, and P = 0.024, respectively). The incidence of postoperative infectious complications and changes to therapeutic antibiotics were significantly lower in the IG group than in the EG group (P = 0.048 and P = 0.012, respectively). There was no significant difference in postoperative ICU or postoperative hospital LOS between the two groups. The 5-y progression-free survival rates in the IG and EG groups were 75% and 64%, respectively (P = 0.188), and the overall survival rates were 68% and 55%, respectively (P = 0.187). CONCLUSIONS Perioperative immunonutrition may improve early postoperative nutritional status and reduce postoperative infectious complications in patients with esophageal cancer undergoing esophagectomy.
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Affiliation(s)
- Shinsuke Kanekiyo
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Shigeru Takeda
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Michihisa Iida
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Mitsuo Nishiyama
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Masahiro Kitahara
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Yoshitaro Shindo
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Yukio Tokumitsu
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Shinobu Tomochika
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Ryoichi Tsunedomi
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Nobuaki Suzuki
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | | | | | - Shoichi Hazama
- Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University Faculty of Medicine, Ube, Japan
| | - Tomio Ueno
- Department of Digestive Surgery, Kawasaki Medical School, Kurashiki, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
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24
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Osland E, Memon B, Memon MA. Pharmaconutrition administration on outcomes of elective oncological surgery for gastrointestinal malignancies: is timing everything?-a review of published meta-analyses until the end of 2016. Transl Gastroenterol Hepatol 2018; 3:52. [PMID: 30225386 DOI: 10.21037/tgh.2018.07.12] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 07/30/2018] [Indexed: 01/01/2023] Open
Abstract
The last 25 years have seen an increasing number of publications attesting the benefits of pharmaconutrition in the management of patients undergoing elective oncological gastrointestinal surgery. A number of randomized controlled trials and meta-analyses suggest the use of pharmaconutrition in this group of patients produces superior outcomes to standard nutritional formulations in terms of postoperative infective complications, anastomotic breakdown and length of hospital stay. The use of pharmaconutrition products, therefore, has gained increasing acceptance for use in elective gastrointestinal oncological surgical populations and been incorporated into practice guidelines. However, there remains doubts as to the robustness of such data supporting these recommendation. This is because studies reporting improved outcomes with pharmaconutrition (I) frequently compare this intervention with non-equivalent control groups; (II) do not report on the actual nutritional provision received by study participants; (III) overlook the potential impact of industry funding on research conducted and (IV) do not adopt a multi-disciplinary approach to the research undertaken. For these reasons, a critical re-appraisal of the use and recommendations of pharmaconutrition in this group of patients is urgently warranted to resolve some of the above mentioned issues. The aim of this review was to analyse meta-analyses published until the end of 2016 in this area to highlight the strengths and weakness of the present research and prioritize certain areas which will benefit from future research.
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Affiliation(s)
- Emma Osland
- Department of Nutrition, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.,School of Human Movement and Nutrition Sciences, University of Queensland, Brisbane, Queensland, Australia
| | - Breda Memon
- Sunnybank Obesity Centre, McCullough Centre, Sunnybank, Queensland, Australia
| | - Muhammed Ashraf Memon
- Sunnybank Obesity Centre, McCullough Centre, Sunnybank, Queensland, Australia.,Mayne Medical School, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia.,School of Agricultural, Computational and Environmental Sciences, International Centre for Applied Climate Sciences and Centre for Health Sciences Research, University of Southern Queensland, Toowoomba, Queensland, Australia.,Faculty of Health and Social Science, Bolton University, Bolton, Lancashire, UK
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25
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Babajafari S, Hojhabrimanesh A, Sohrabi Z, Ayaz M, Noorafshan A, Akrami A. Comparing isolated soy protein with flaxseed oil vs isolated soy protein with corn oil and wheat flour with corn oil consumption on muscle catabolism, liver function, blood lipid, and sugar in burn patients: a randomized clinical trial. Trials 2018; 19:308. [PMID: 29866187 PMCID: PMC5987465 DOI: 10.1186/s13063-018-2693-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 05/17/2018] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND There is controversy regarding whether increasing isolated soy protein (ISP) with or without flaxseed oil (FO), as functional foods, would lead to reduce muscle catabolism and cachexia in burn patients. METHODS One hundred and eighty-eight patients were assessed for eligibility in this randomized controlled trial. Of these, seventy-three eligible patients (total burn surface area 20-50%) were randomly assigned to three groups, labeled as Control (wheat flour [WF] + corn oil [CO]), ISP + FO, and ISP + CO, to receive these nutrients for three weeks. Weight, body mass index (BMI), serum hepatic enzymes (alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase [ALP]), systemic inflammatory response syndrome (SIRS), 24-h urinary urea nitrogen excretion (UUN), serum creatinine, 24-h urinary creatinine (UUC) excretion, fasting blood sugar (FBS), triglyceride (TG), and cholesterol were measured. RESULTS Using analysis of covariance models in the intention-to-treat population (n = 73), we found that at three weeks, patients in the ISP groups had lost significantly less in weight and BMI compared to those in the control group (all P < 0.01). Nitrogen retention and serum creatinine (primary outcomes) increased significantly in the ISP groups compared with the control group. Even after controlling for potential covariates in ANCOVA models, changes in these indices were still statistically significant (P = 0.008 and P = 0.005 for nitrogen balance and serum creatinine, respectively). However, no such significant differences were found between the ISP groups. On the other hand, 24-h UUN, and UUC excretion, serum hepatic enzymes, FBS, TG, and cholesterol were not significant between the groups (P > 0.05). CONCLUSION ISP and FO compared to WF and CO reduced muscle catabolism and increased body weight in burn patients. TRIAL REGISTRATION Iranian Registry of Clinical Trials, IRCT2014051817740N1 . Registered on 27 June 2014.
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Affiliation(s)
- Siavash Babajafari
- Nutrition Research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Abdollah Hojhabrimanesh
- Nutrition Research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Sohrabi
- Nutrition Research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehdi Ayaz
- Burn Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Noorafshan
- Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Atefeh Akrami
- Nutrition Research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
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26
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Lewis S, Pugsley M, Schneider C, Rakita SS, Moudgill LJ. The Effect of Immunonutrition on Veterans Undergoing Major Surgery for Gastrointestinal Cancer. Fed Pract 2018; 35:S49-S56. [PMID: 30766401 PMCID: PMC6375420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
A randomized controlled trial found that providing immunonutrition supplementation before surgery reduced the rate of postoperative complications and the length of hospital stays.
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Affiliation(s)
- Sherri Lewis
- is a Dietetic Program Internship Director, is a Clinical Dietitian, is the Lead Surgical Service Physician Assistant, is Chief of Surgical Service, is Chief of Division of General Surgery, all at James A. Haley Veterans' Hospital in Tampa, Florida. Dr. Moudgill is an Assistant Professor, and Dr. Rakita is an Associate Professor in the Department of Surgery at University of South Florida
| | - Michelle Pugsley
- is a Dietetic Program Internship Director, is a Clinical Dietitian, is the Lead Surgical Service Physician Assistant, is Chief of Surgical Service, is Chief of Division of General Surgery, all at James A. Haley Veterans' Hospital in Tampa, Florida. Dr. Moudgill is an Assistant Professor, and Dr. Rakita is an Associate Professor in the Department of Surgery at University of South Florida
| | - Christopher Schneider
- is a Dietetic Program Internship Director, is a Clinical Dietitian, is the Lead Surgical Service Physician Assistant, is Chief of Surgical Service, is Chief of Division of General Surgery, all at James A. Haley Veterans' Hospital in Tampa, Florida. Dr. Moudgill is an Assistant Professor, and Dr. Rakita is an Associate Professor in the Department of Surgery at University of South Florida
| | - Steven S Rakita
- is a Dietetic Program Internship Director, is a Clinical Dietitian, is the Lead Surgical Service Physician Assistant, is Chief of Surgical Service, is Chief of Division of General Surgery, all at James A. Haley Veterans' Hospital in Tampa, Florida. Dr. Moudgill is an Assistant Professor, and Dr. Rakita is an Associate Professor in the Department of Surgery at University of South Florida
| | - Lisa J Moudgill
- is a Dietetic Program Internship Director, is a Clinical Dietitian, is the Lead Surgical Service Physician Assistant, is Chief of Surgical Service, is Chief of Division of General Surgery, all at James A. Haley Veterans' Hospital in Tampa, Florida. Dr. Moudgill is an Assistant Professor, and Dr. Rakita is an Associate Professor in the Department of Surgery at University of South Florida
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Rosenthal MD, Kamel AY, Rosenthal CM, Brakenridge S, Croft CA, Moore FA. Chronic Critical Illness: Application of What We Know. Nutr Clin Pract 2018; 33:39-45. [PMID: 29323761 DOI: 10.1002/ncp.10024] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Accepted: 11/08/2017] [Indexed: 12/16/2022] Open
Abstract
Over the last decade, chronic critical illness (CCI) has emerged as an epidemic in intensive care unit (ICU) survivors worldwide. Advances in ICU technology and implementation of evidence-based care bundles have significantly decreased early deaths and have allowed patients to survive previously lethal multiple organ failure (MOF). Many MOF survivors, however, experience a persistent dysregulated immune response that is causing an increasingly predominant clinical phenotype called the persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The elderly are especially vulnerable; thus, as the population ages the prevalence of this CCI/PICS clinical trajectory will undoubtedly grow. Unfortunately, there are no proven therapies to prevent PICS, and multimodality interventions will be required. The purpose of this review is to: (1) discuss CCI as it relates to PICS, (2) identify the burden on healthcare and poor outcomes of these patients, and (3) describe possible nutrition interventions for the CCI/PICS phenotype.
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Affiliation(s)
- Martin D Rosenthal
- Department of Surgery, Division of Acute Care Surgery and Center for Sepsis and Critical Illness Research, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Amir Y Kamel
- Department of Pharmacy, UF Health, University of Florida College of Pharmacy, Gainesville, Florida, USA
| | | | - Scott Brakenridge
- Department of Surgery, Division of Acute Care Surgery and Center for Sepsis and Critical Illness Research, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Chasen A Croft
- Department of Surgery, Division of Acute Care Surgery and Center for Sepsis and Critical Illness Research, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Frederick A Moore
- Department of Surgery, Division of Acute Care Surgery and Center for Sepsis and Critical Illness Research, University of Florida College of Medicine, Gainesville, Florida, USA
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28
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Probst P, Ohmann S, Klaiber U, Hüttner FJ, Billeter AT, Ulrich A, Büchler MW, Diener MK. Meta-analysis of immunonutrition in major abdominal surgery. Br J Surg 2017; 104:1594-1608. [DOI: 10.1002/bjs.10659] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Revised: 06/14/2017] [Accepted: 06/28/2017] [Indexed: 12/13/2022]
Abstract
Abstract
Background
The objective of this study was to evaluate the potential benefits of immunonutrition in major abdominal surgery with special regard to subgroups and influence of bias.
Methods
A systematic literature search from January 1985 to July 2015 was performed in MEDLINE, Embase and CENTRAL. Only RCTs investigating immunonutrition in major abdominal surgery were included. Outcomes evaluated were mortality, overall complications, infectious complications and length of hospital stay. The influence of different domains of bias was evaluated in sensitivity analyses. Evidence was rated according to the GRADE Working Group grading of evidence.
Results
A total of 83 RCTs with 7116 patients were included. Mortality was not altered by immunonutrition. Taking all trials into account, immunonutrition reduced overall complications (odds ratio (OR) 0·79, 95 per cent c.i. 0·66 to 0·94; P = 0·01), infectious complications (OR 0·58, 0·51 to 0·66; P < 0·001) and shortened hospital stay (mean difference –1·79 (95 per cent c.i. –2·39 to –1·19) days; P < 0·001) compared with control groups. However, these effects vanished after excluding trials at high and unclear risk of bias. Publication bias seemed to be present for infectious complications (P = 0·002). Non-industry-funded trials reported no positive effects for overall complications (OR 1·13, 0·88 to 1·46; P = 0·34), whereas those funded by industry reported large effects (OR 0·66, 0·48 to 0·91; P = 0·01).
Conclusion
Immunonutrition after major abdominal surgery did not seem to alter mortality (GRADE: high quality of evidence). Immunonutrition reduced overall complications, infectious complications and shortened hospital stay (GRADE: low to moderate). The existence of bias lowers confidence in the evidence (GRADE approach).
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Affiliation(s)
- P Probst
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Study Centre of the German Surgical Society, University of Heidelberg, Heidelberg, Germany
| | - S Ohmann
- Study Centre of the German Surgical Society, University of Heidelberg, Heidelberg, Germany
| | - U Klaiber
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Study Centre of the German Surgical Society, University of Heidelberg, Heidelberg, Germany
| | - F J Hüttner
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Study Centre of the German Surgical Society, University of Heidelberg, Heidelberg, Germany
| | - A T Billeter
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - A Ulrich
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - M W Büchler
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - M K Diener
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Study Centre of the German Surgical Society, University of Heidelberg, Heidelberg, Germany
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29
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Rosenthal MD, Rosenthal CM, Moore FA, Martindale RG. Persistent, Immunosuppression, Inflammation, Catabolism Syndrome and Diaphragmatic Dysfunction. CURRENT PULMONOLOGY REPORTS 2017. [DOI: 10.1007/s13665-017-0166-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Abstract
Clinicians in nearly all practice areas are confronted with the challenges associated with delayed and impaired wound healing. Although nutrition plays a critical role in the healing process, controversy exists regarding the optimal nutrition regimen. This article reviews literature related to nutrition interventions that facilitate wound healing. The limitations of the research that forms the scientific basis of many nutrition recommendations are also examined. The limited availability of rigorously performed clinical studies to develop evidence-based guidelines for nutrition support in wound care emphasizes the need for further research and underscores the importance of individualizing the nutrition care plan for each patient.
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Rosenthal MD, Carrott PW, Patel J, Kiraly L, Martindale RG. Parenteral or Enteral Arginine Supplementation Safety and Efficacy. J Nutr 2016; 146:2594S-2600S. [PMID: 27934650 DOI: 10.3945/jn.115.228544] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2015] [Revised: 02/01/2016] [Accepted: 10/04/2016] [Indexed: 01/01/2023] Open
Abstract
Arginine supplementation has the potential to improve the health of patients. Its use in hospitalized patients has been a controversial topic in the nutrition literature, especially concerning supplementation of septic patients. In this article, we review the relevant literature both for and against the use of arginine in critically ill, surgical, and hospitalized patients. The effect of critical illness on arginine metabolism is reviewed, as is its use in septic and critically ill patients. Although mounting evidence supports immunonutrition, there are only a few studies that suggest that this is safe in patients with severe sepsis. The use of arginine has been shown to benefit a variety of critically ill patients. It should be considered for inclusion in combinations of immunonutrients or commercial formulations for groups in whom its benefit has been reported consistently, such as those who have suffered trauma and those in acute surgical settings. The aims of this review are to discuss the role of arginine in health, the controversy surrounding arginine supplementation of septic patients, and the use of arginine in critically ill patients.
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Affiliation(s)
- Martin D Rosenthal
- Division of Acute Care Surgery, Department of Surgery, and.,Center for Sepsis and Critical Illness Research, University of Florida College of Medicine, Gainesville, FL
| | - Phillip W Carrott
- Section of Cardiothoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
| | - Jayshil Patel
- Division of Pulmonary Critical Care, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI; and
| | - Laszlo Kiraly
- Division of Gastrointestinal Surgery, Department of Surgery, Oregon Health and Science University, Portland, OR
| | - Robert G Martindale
- Division of Gastrointestinal Surgery, Department of Surgery, Oregon Health and Science University, Portland, OR
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32
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Albaugh VL, Pinzon-Guzman C, Barbul A. Arginine-Dual roles as an onconutrient and immunonutrient. J Surg Oncol 2016; 115:273-280. [PMID: 27861915 DOI: 10.1002/jso.24490] [Citation(s) in RCA: 89] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Accepted: 10/22/2016] [Indexed: 12/12/2022]
Abstract
Arginine is an important player in numerous biologic processes and studies have demonstrated its importance for cellular growth that becomes limiting in states of rapid turnover (e.g., malignancy). Thus, arginine deprivation therapy is being examined as an adjuvant cancer therapy, however, arginine is also necessary for immune destruction of malignant cells. Herein we review the data supporting arginine deprivation or supplementation in cancer treatment and the currently registered trials aimed at understanding these divergent strategies. J. Surg. Oncol. 2017;115:273-280. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Vance L Albaugh
- Division of General Surgery, Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Carolina Pinzon-Guzman
- Division of General Surgery, Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Adrian Barbul
- Division of General Surgery, Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee
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33
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Rosenthal MD, Brakenridge S, Rosenthal CM, Moore FA. Nutritional Support in the Setting of Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS). CURRENT SURGERY REPORTS 2016. [DOI: 10.1007/s40137-016-0152-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Hodges TR, Ferguson SD, Caruso HG, Kohanbash G, Zhou S, Cloughesy TF, Berger MS, Poste GH, Khasraw M, Ba S, Jiang T, Mikkelson T, Yung WKA, de Groot JF, Fine H, Cantley LC, Mellinghoff IK, Mitchell DA, Okada H, Heimberger AB. Prioritization schema for immunotherapy clinical trials in glioblastoma. Oncoimmunology 2016; 5:e1145332. [PMID: 27471611 DOI: 10.1080/2162402x.2016.1145332] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2015] [Revised: 01/12/2016] [Accepted: 01/16/2016] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Emerging immunotherapeutic strategies for the treatment of glioblastoma (GBM) such as dendritic cell (DC) vaccines, heat shock proteins, peptide vaccines, and adoptive T-cell therapeutics, to name a few, have transitioned from the bench to clinical trials. With upcoming strategies and developing therapeutics, it is challenging to critically evaluate the practical, clinical potential of individual approaches and to advise patients on the most promising clinical trials. METHODS The authors propose a system to prioritize such therapies in an organized and data-driven fashion. This schema is based on four categories of factors: antigenic target robustness, immune-activation and -effector responses, preclinical vetting, and early evidence of clinical response. Each of these categories is subdivided to focus on the most salient elements for developing a successful immunotherapeutic approach for GBM, and a numerical score is generated. RESULTS The Score Card reveals therapeutics that have the most robust data to support their use, provides a reference prioritization score, and can be applied in a reiterative fashion with emerging data. CONCLUSIONS The authors hope that this schema will give physicians an evidence-based and rational framework to make the best referral decisions to better guide and serve this patient population.
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Affiliation(s)
- Tiffany R Hodges
- Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center , Houston, TX, USA
| | - Sherise D Ferguson
- Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center , Houston, TX, USA
| | - Hillary G Caruso
- The Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center , Houston, TX, USA
| | - Gary Kohanbash
- Department of Neurosurgery, the University of California at San Francisco , San Francisco, USA
| | - Shouhao Zhou
- Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center , Houston, TX, USA
| | - Timothy F Cloughesy
- Department of Neuro-Oncology, the University of California at Los Angeles , Los Angeles, CA, USA
| | - Mitchel S Berger
- Department of Neurosurgery, the University of California at San Francisco , San Francisco, USA
| | | | | | - Sujuan Ba
- The National Foundation for Cancer Research, Bethesda, MD, USA, Asian Fund for Cancer Research , Hong Kong, People's Republic of China
| | - Tao Jiang
- Department of Neurosurgery, Tiantan Hospital, Capital Medical University , Beijing, China
| | - Tom Mikkelson
- Department of Neurosurgery, Henry Ford Health System , Detroit, MI, USA
| | - W K Alfred Yung
- Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center , Houston, TX, USA
| | - John F de Groot
- Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center , Houston, TX, USA
| | - Howard Fine
- Division of Neuro-Oncology, Weill Cornell Medical College , New York, NY, USA
| | - Lewis C Cantley
- Department of Systems Biology, Harvard Medical School , Boston, MA, USA
| | - Ingo K Mellinghoff
- Department of Neurology and Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center , New York, NY, USA
| | - Duane A Mitchell
- Department of Neurosurgery, University of Florida , Gainesville, FL, USA
| | - Hideho Okada
- Department of Neurosurgery, the University of California at San Francisco , San Francisco, USA
| | - Amy B Heimberger
- Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center , Houston, TX, USA
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YILDIZ SY, YAZICIOĞLU MB, TİRYAKİ Ç, ÇİFTÇİ A, BOYACIOĞLU Z, ÖZYILDIZ M, COŞKUN M, ŞUBAŞI Ö. The effect of enteral immunonutrition in upper gastrointestinalsurgery for cancer: a prospective study. Turk J Med Sci 2016; 46:393-400. [DOI: 10.3906/sag-1411-102] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2014] [Accepted: 07/06/2015] [Indexed: 11/03/2022] Open
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Huang HL, Chen WC, Hsu HP, Cho CY, Hung YH, Wang CY, Lai MD. Argininosuccinate lyase is a potential therapeutic target in breast cancer. Oncol Rep 2015; 34:3131-9. [PMID: 26397737 DOI: 10.3892/or.2015.4280] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2015] [Accepted: 07/23/2015] [Indexed: 11/06/2022] Open
Abstract
Arginine is a non-essential amino acid that modulates nitric oxide production and cancer homeostasis. In our previous study, we observed that blocking argininosuccinate lyase (ASL) attenuates tumor progression in liver cancer. However, the role of ASL in human breast cancer has been studied to a lesser degree. In the present study, we investigated the effect of targeting ASL in breast cancer. We found that ASL was induced by ER stress and was significantly upregulated in breast cancer tissues compared to that in the corresponding normal tissues. Downregulation of ASL inhibited the growth of breast cancer in vitro and in vivo. The level of cell cycle-related gene, cyclin A2, was reduced and was accompanied by a delay in G2/M transition. ASL shRNA-induced cell inhibition was rescued by exogenous cyclin A2. Furthermore, autophagy was observed in the cells expressing ASL shRNA, and inhibition of autophagy reduced cell growth, indicating that autophagy played a cell survival role in the ASL knockdown cells. Moreover, inhibition of ASL reduced NO content. Introduction of the NO donor partially restored the growth inhibition by ASL shRNA. Thus, the mechanism induced by ASL shRNA which occurred in human breast cancer may be attributed to a decrease in cyclin A2 and NO.
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Affiliation(s)
- Hau-Lun Huang
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan, R.O.C
| | - Wei-Ching Chen
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan, R.O.C
| | - Hui-Ping Hsu
- Department of Surgery, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan, R.O.C
| | - Chien-Yu Cho
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan, R.O.C
| | - Yu-Hsuan Hung
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan, R.O.C
| | - Chih-Yang Wang
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan, R.O.C
| | - Ming-Derg Lai
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan, R.O.C
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Ruiz-Tovar J, Zubiaga L, Diez M, Murcia A, Boix E, Muñoz JL, Llavero C. Preoperative Regular Diet of 900 kcal/day vs Balanced Energy High-Protein Formula vs Immunonutrition Formula: Effect on Preoperative Weight Loss and Postoperative Pain, Complications and Analytical Acute Phase Reactants After Laparoscopic Sleeve Gastrectomy. Obes Surg 2015; 26:1221-7. [DOI: 10.1007/s11695-015-1880-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Song GM, Tian X, Liang H, Yi LJ, Zhou JG, Zeng Z, Shuai T, Ou YX, Zhang L, Wang Y. Role of Enteral Immunonutrition in Patients Undergoing Surgery for Gastric Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Medicine (Baltimore) 2015; 94:e1311. [PMID: 26252314 PMCID: PMC4616579 DOI: 10.1097/md.0000000000001311] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Gastric cancer (GC) is one of the most common upper gastrointestinal malignancies. Surgical resection remains the mainstay of curative treatment for GC. Enteral immunonutrition (EIN) has been increasingly used to enhance host immunity and relieve inflammatory response of patients undergoing surgery for GC; however, conclusions across studies still remain unclear. We aimed to evaluate the effects of EIN for such patients.We searched some electronic databases including PubMed, EBSCO-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE to identify any latent studies which investigated the effects of EIN compared with standard EN on GC patients who undergoing surgery until the end of December 30, 2014. Relative risk (RR), mean difference (MD), or standard mean difference (SMD) with 95% confidence interval (CI) were calculated and we also assessed heterogeneity by using Cochrane Q and I statistic combined with corresponding P-value.We included 9 eligible studies which included 785 patients eventually. The meta-analysis results shown that EIN increased level of IgA (MD, 0.31; 95% CI, 0.12-0.51), IgG (MD, 1.5; 95% CI, 0.73-2.28), IgM (MD, 0.22; 95% CI, 0.06-0.39), CD4 (SMD, 0.81; 95% CI, 0.53-1.09), CD3 (SMD, 0.68; 95% CI, 0.21-1.15), CD4/CD8 ratio (MD, 0.56; 95% CI, 0.12-1.01), and NK cell (MD, 2.35; 95% CI, 0.66-4.05); decreased IL-6 (MD, -98.22; 95% CI, -156.16 to -40.28) and TNF-α (MD, -118.29; 95% CI, -162.00 to -74.58), but not improve remained outcomes of interest involving postoperative complications, length of hospitalization, serum total protein, and CD8. Descriptive analysis suggested that EIN also increased the concentration of IL-2 but not CRP. Impact on lymphocytes remains inconsistent.EIN is effective for enhancing host immunity and relieving the inflammatory response in GC patients undergoing gastrectomy, but clinical outcomes cannot be benefit from it. Heterogeneity caused by different compositions and timing of administration of EIN regimes and not enough sample size and number of eligible studies in most of sensitive analyses with subgroup analysis may impaired the power of our study, and thus some large-scale and well-designed studies are warranted to further establish effects.
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Affiliation(s)
- Guo-Min Song
- From the Department of Nursing, Tianjin Hospital, Tianjin, People's Republic of China (G-MS); Graduate College, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China (XT, L-JY, ZZ, TS, LZ); School of Nursing, Tianjin Medical University, Tianjin, People's Republic of China (HL); Department of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi, People's Republic of China (J-GZ); College of TCM, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China (Y-XO); and School of Nursing, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China (XT, L-JY, ZZ, TS, YW)
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Rosenthal MD, Vanzant EL, Martindale RG, Moore FA. Evolving paradigms in the nutritional support of critically ill surgical patients. Curr Probl Surg 2015; 52:147-82. [PMID: 25946621 DOI: 10.1067/j.cpsurg.2015.02.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Revised: 01/29/2015] [Accepted: 02/11/2015] [Indexed: 12/12/2022]
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Plank LD, Mathur S, Gane EJ, Peng SL, Gillanders LK, McIlroy K, Chavez CP, Calder PC, McCall JL. Perioperative immunonutrition in patients undergoing liver transplantation: a randomized double-blind trial. Hepatology 2015; 61:639-47. [PMID: 25212278 DOI: 10.1002/hep.27433] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2014] [Accepted: 09/07/2014] [Indexed: 12/15/2022]
Abstract
UNLABELLED Preliminary work suggested that perioperative immunonutrition (IMN) enriched in n-3 fatty acids, arginine, and nucleotides may improve preoperative nutritional status, enhance postoperative recovery, and reduce postoperative infectious complications in patients undergoing liver transplantation (LT). The current study examined these outcomes in a double-blind, randomized, controlled trial. Patients wait-listed for LT (n = 120) were randomized to either supplemental (0.6 L/d) oral IMN or an isocaloric control (CON). Enteral IMN or CON was resumed postoperatively and continued for at least 5 days. The change in total body protein (TBP) measured by neutron activation from study entry until immediately prior to LT was the primary endpoint and TBP measurements were repeated 10, 30, 90, 180, and 360 days after LT. Infectious complications were recorded for the first 30 postoperative days. Nineteen patients died or were delisted prior to LT. Fifty-two IMN and 49 CON patients received supplemental nutrition for a median (range) 56 (0-480) and 65 (0-348) days, respectively. Preoperative changes in TBP were not significant (IMN: 0.06 ± 0.15 [SEM]; CON: 0.12 ± 0.10 kg). Compared to baseline, a 0.7 ± 0.2 kg loss of TBP was seen in both groups at 30 days after LT (P < 0.0001) and, at 360 days, TBP had not increased significantly (IMN: 0.08 ± 0.19 kg; CON: 0.26 ± 0.23 kg). Infectious complications occurred in 31 (60%) IMN and 28 (57%) CON patients (P = 0.84). The median (range) postoperative hospital stay was 10 (5-105) days for IMN and 10 (6-27) days for CON patients (P = 0.68). CONCLUSION In patients undergoing LT, perioperative IMN did not provide significant benefits in terms of preoperative nutritional status or postoperative outcome.
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Affiliation(s)
- Lindsay D Plank
- Department of Surgery, University of Auckland, Auckland, New Zealand
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Synakiewicz A, Stachowicz-Stencel T, Adamkiewicz-Drozynska E. The role of arginine and the modified arginine deiminase enzyme ADI-PEG 20 in cancer therapy with special emphasis on Phase I/II clinical trials. Expert Opin Investig Drugs 2014; 23:1517-29. [DOI: 10.1517/13543784.2014.934808] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Fujiwara T, Kanazawa S, Ichibori R, Tanigawa T, Magome T, Shingaki K, Miyata S, Tohyama M, Hosokawa K. L-arginine stimulates fibroblast proliferation through the GPRC6A-ERK1/2 and PI3K/Akt pathway. PLoS One 2014; 9:e92168. [PMID: 24651445 PMCID: PMC3961283 DOI: 10.1371/journal.pone.0092168] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Accepted: 02/19/2014] [Indexed: 12/12/2022] Open
Abstract
l-Arginine is considered a conditionally essential amino acid and has been shown to enhance wound healing. However, the molecular mechanisms through which arginine stimulates cutaneous wound repair remain unknown. Here, we evaluated the effects of arginine supplementation on fibroblast proliferation, which is a key process required for new tissue formation. We also sought to elucidate the signaling pathways involved in mediating the effects of arginine on fibroblasts by evaluation of extracellular signal-related kinase (ERK) 1/2 activation, which is important for cell growth, survival, and differentiation. Our data demonstrated that addition of 6 mM arginine significantly enhanced fibroblast proliferation, while arginine deprivation increased apoptosis, as observed by enhanced DNA fragmentation. In vitro kinase assays demonstrated that arginine supplementation activated ERK1/2, Akt, PKA and its downstream target, cAMP response element binding protein (CREB). Moreover, knockdown of GPRC6A using siRNA blocked fibroblast proliferation and decreased phosphorylation of ERK1/2, Akt and CREB. The present experiments demonstrated a critical role for the GPRC6A-ERK1/2 and PI3K/Akt signaling pathway in arginine-mediated fibroblast survival. Our findings provide novel mechanistic insights into the positive effects of arginine on wound healing.
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Affiliation(s)
- Takashi Fujiwara
- Department of Plastic Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka, Japan
| | - Shigeyuki Kanazawa
- Department of Plastic Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka, Japan
- * E-mail:
| | - Ryoko Ichibori
- Department of Plastic Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka, Japan
| | - Tomoko Tanigawa
- Department of Plastic Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka, Japan
| | - Takuya Magome
- Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita-shi, Osaka, Japan
| | - Kenta Shingaki
- Department of Research & Development Noevir Co., Ltd. Higashiomi, Shiga, Japan
| | - Shingo Miyata
- Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osakasayama, Osaka, Japan
| | - Masaya Tohyama
- Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osakasayama, Osaka, Japan
| | - Ko Hosokawa
- Department of Plastic Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka, Japan
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Osland E, Hossain MB, Khan S, Memon MA. Effect of Timing of Pharmaconutrition (Immunonutrition) Administration on Outcomes of Elective Surgery for Gastrointestinal Malignancies. JPEN J Parenter Enteral Nutr 2014; 38:53-69. [DOI: 10.1177/0148607112474825] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Affiliation(s)
- Emma Osland
- Department of Nutrition, Royal Brisbane and Womens Hospital, Brisbane, Queensland, Australia
| | - Md Belal Hossain
- Department of Mathematics and Computing, Australian Centre for Sustainable Catchments, University of Southern Queensland, Toowoomba, Queensland, Australia
- Department of Statistics, Biostatistics and Informatics, University of Dhaka, Bangladesh
| | - Shahjahan Khan
- Department of Mathematics and Computing, Australian Centre for Sustainable Catchments, University of Southern Queensland, Toowoomba, Queensland, Australia
| | - Muhammed Ashraf Memon
- Sunnybank Obesity Centre, Sunnybank, Queensland, Australia
- Mayne Medical School, School of Medicine, University of Queensland, Brisbane, Queensland, Australia
- Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia
- Faculty of Health and Social Science, Bolton University, Bolton, Lancashire, UK
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Nagengast AK, Hurt RT, Downard CD, Smith JW, Garrison RN, Matheson PJ. Increased hepatic blood flow during enteral immune-enhancing diet gavage requires intact enterohepatic bile cycling. Nutrition 2013; 30:313-8. [PMID: 24355437 DOI: 10.1016/j.nut.2013.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2013] [Revised: 08/09/2013] [Accepted: 08/09/2013] [Indexed: 11/18/2022]
Abstract
OBJECTIVES Total hepatic blood flow (HBF) via the hepatic artery and portal vein is highly dependent on gastrointestinal perfusion. During postprandial hyperemia, intestinal blood flow depends on nutrient composition, gastrointestinal location, and time. Immune-enhancing diets (IEDs) containing n-3 polyunsaturated fatty acids (PUFAs) selectively augment blood flow in the ileum at 60-120 min via a bile-dependent mechanism. My colleagues and I hypothesized that liver blood flow would be similarly affected by IEDs containing n-3 PUFAs. METHODS Mean arterial blood pressure, heart rate, and effective HBF (galactose clearance) were measured in anesthetized male Sprague-Dawley rats after gastric gavage of either a control diet (CD, Boost, Novartis) or an IED (Impact, Nestle Nutrition), with or without bile-duct ligation (BDL), and with or without supplemental bile (bovine, dried, unfractionated). Significance was assessed by 2-way ANOVA for repeated measures with the Tukey-Kramer honestly significant difference test. RESULTS Compared with baseline levels, a CD increased HBF (peak at 40 min , *P < 0.05) whereas an IED increased HBF in two distinct peaks at 40 min (*P < 0.05) and 120 min (*P < 0.05), but BDL prevented both the early (CD and IED, †P < 0.05) and late peaks (IED, †P < 0.05). Bile supplementation in the CD + BDL or IED + BDL groups restored neither the CD peak nor the early or late IED peaks. CONCLUSIONS HBF during absorptive intestinal hyperemia is modulated by a mechanism that requires an intact enterohepatic circulation. The early peaks at 40 min (CD or IED) were prevented by BDL, even though fat absorption in the proximal gut occurs by bile-independent direct absorption. Bile supplementation with the diet (CD + BDL or IED + BDL) was insufficient to restore HBF hyperemia, which implies that a relationship exists between intestinal and hepatic blood flow that is not solely dependent on bile-mediated intestinal fat absorption and bile recirculation.
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Affiliation(s)
- Andrea K Nagengast
- Department of Surgery, University of Louisville, Louisville, Kentucky, USA
| | - Ryan T Hurt
- Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky, USA; Division of General Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Cynthia D Downard
- Department of Surgery, University of Louisville, Louisville, Kentucky, USA
| | - Jason W Smith
- Department of Surgery, University of Louisville, Louisville, Kentucky, USA; Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky, USA
| | - R Neal Garrison
- Department of Surgery, University of Louisville, Louisville, Kentucky, USA; Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky, USA; Louisville Robley Rex VA Medical Center, Louisville, Kentucky, USA
| | - Paul J Matheson
- Department of Surgery, University of Louisville, Louisville, Kentucky, USA; Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky, USA.
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Afifi I, Elazzazy S, Abdulrahman Y, Latifi R. Nutrition therapy for critically ill and injured patients. Eur J Trauma Emerg Surg 2013; 39:203-13. [PMID: 26815227 DOI: 10.1007/s00068-013-0272-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2012] [Accepted: 02/19/2013] [Indexed: 01/18/2023]
Abstract
BACKGROUND Nutrition support has undergone significant advances in recent decades, revolutionizing the care of critically ill and injured patients. However, providing adequate and optimal nutrition therapy for such patients is very challenging: it requires careful attention and an understanding of the biology of the individual patient's disease or injury process, including insight into the consequent changes in nutrients needed. OBJECTIVE The objective of this article is to review the current principles and practices of providing nutrition therapy for critically ill and injured patients. METHODS Review of the literature and evidence-based guidelines. RESULTS The evidence demonstrates the need to understand the biology of nutrition therapy for critically ill and injured patients, tailored to their individual disease or injury, age, and comorbidities. CONCLUSION Nutrition therapy for critically ill and injured patients has become an important part of their overall care. No longer should we consider nutrition for critically ill and injured patients just as "support" but, rather, as "therapy", because it is, indeed, a key therapeutic modality.
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Affiliation(s)
- I Afifi
- Trauma Section, Hamad General Hospital, Doha, Qatar
| | - S Elazzazy
- National Center of Cancer Care and Research, Doha, Qatar
| | | | - R Latifi
- Trauma Section, Hamad General Hospital, Doha, Qatar.
- Department of Surgery, University of Arizona, Tucson, AZ, USA.
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Turnock A, Calder PC, West AL, Izzard M, Morton RP, Plank LD. Perioperative immunonutrition in well-nourished patients undergoing surgery for head and neck cancer: evaluation of inflammatory and immunologic outcomes. Nutrients 2013; 5:1186-99. [PMID: 23571650 PMCID: PMC3705342 DOI: 10.3390/nu5041186] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Revised: 03/21/2013] [Accepted: 03/26/2013] [Indexed: 12/16/2022] Open
Abstract
Limited work is available on the benefits of nutritional support enriched with arginine and n-3 fatty acids in surgical patients with head and neck cancer, particularly if well-nourished. We conducted a pilot study in these patients to examine effects on inflammatory markers and clinical outcome. Patients scheduled for radical resection of the oral cavity were randomised to 5 day preoperative and 5 day postoperative Impact® (IMN, n = 4), or no preoperative supplementary nutrition and Isosource® postoperatively (STD, n = 4). Plasma fatty acids, C-reactive protein (CRP), tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were measured at baseline, day of surgery and on postoperative days (POD) 2, 4 and 10. Postoperative complications were recorded. The (eicosapentaenoic acid plus docosahexaenoic acid) to arachidonic acid ratio was significantly higher in IMN patients on POD 2, 4 and 10 (P < 0.01). While not statistically significant, CRP, TNF-α, and IL-6 concentrations were higher in the STD group on POD2 while IL-10 was lower. Median length of stay was 10 (range 10–43) days in the IMN group and 21.5 (7–24) days in the STD group. Five complications were seen in the STD group and two in the IMN group. The results support the need for a larger trial focusing on clinical outcome.
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Affiliation(s)
- Amy Turnock
- Department of Surgery, University of Auckland, Auckland 1142, New Zealand; E-Mail:
| | - Philip C. Calder
- Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; E-Mails: (P.C.C.); (A.L.W.)
| | - Annette L. West
- Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; E-Mails: (P.C.C.); (A.L.W.)
| | - Mark Izzard
- Department of Otorhinolaryngology, Auckland City Hospital, Auckland 1142, New Zealand; E-Mail:
| | - Randall P. Morton
- Department of Otolaryngology, Counties-Manukau District Health Board, Auckland 1640, New Zealand; E-Mail:
| | - Lindsay D. Plank
- Department of Surgery, University of Auckland, Auckland 1142, New Zealand; E-Mail:
- Author to whom correspondence should be addressed; E-Mail: ; Tel.: +64-9-923-6949; Fax: +64-9-377-9656
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Hurt RT, Garrison RN, Derhake BM, Matheson PJ. Fish oil increases blood flow in the ileum during chronic feeding in rats. Nutr Res 2012. [PMID: 23176794 DOI: 10.1016/j.nutres.2012.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Benefits of enteral feeding with immune-enhancing diets (IEDs) depend on route, timing, and composition. We hypothesized that chronic enteral feeding with certain individual immunonutrients would enhance gastrointestinal blood flow. Male rats were fed a standard enteral diet supplemented with immunonutrients for 5 days before study. Groups were (1) standard rat chow, (2) liquid control diet (CD) alone (CD), (3) CD + fish oil, (4) CD + L-arginine, and (5) CD + RNA fragments. Whole organ blood flow distribution was measured by colorimetric microsphere technique in antrum, small intestine (in thirds), colon, liver, spleen, pancreas, and kidneys. Chronic feeding for 5 days with CD + fish oil increased blood flow in the distal third of the small intestine compared with CD alone, whereas feeding with CD + L-arginine decreased blood flow in the small intestine (all segments) compared with CD alone. Acute gavage of CD + L-arginine or CD + fish oil increased blood flow in the proximal and middle third of the small intestine compared with CD alone. Control diet + RNA increased blood flow in the proximal small intestine compared with CD alone. These findings support prior acute feeding studies with CD, CD + individual immunonutrients, or IED. Our current data suggest that blood flow benefits associated with fish oil persist during chronic feeding in rats. Enhanced gastrointestinal perfusion might partially explain the benefits of early enteral feeding with IEDs not seen with regular enteral diets and parenteral immunonutrient delivery.
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Affiliation(s)
- Ryan T Hurt
- Department of Medicine, University of Louisville, Louisville, KY, USA.
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Walcott BP, Redjal N, Coumans JVCE. Infection following operations on the central nervous system: deconstructing the myth of the sterile field. Neurosurg Focus 2012; 33:E8. [DOI: 10.3171/2012.8.focus12245] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Neurosurgical patients are at a high risk for infectious sequelae following operations. For neurosurgery in particular, the risk of surgical site infection has a unique implication given the proximity of the CSF and the CNS. Patient factors contribute to some degree; for example, cancer and trauma are often associated with impaired nutritional status, known risk factors for infection. Additionally, care-based factors for infection must also be considered, such as the length of surgery, the administration of steroids, and tissue devascularization (such as a craniotomy bone flap). When postoperative infection does occur, attention is commonly focused on potential lapses in surgical “sterility.” Evidence suggests that the surgical field is not free of microorganisms. The authors propose a paradigm shift in the nomenclature of the surgical field from “sterile” to “clean.” Continued efforts aimed at optimizing immune capacity and host defenses to combat potential infection are warranted.
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Lye AD, Hayslip JW. Immunonutrition: does it have a role in improving recovery in patients receiving a stem cell transplant? Nutr Cancer 2012; 64:503-7. [PMID: 22519362 DOI: 10.1080/01635581.2012.675621] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
Numerous clinical trials have demonstrated that immunomodulating diets (IMDs) reduce treatment complications such as the risk of acquired infections, length of hospital stay, and wound complications in patients receiving planned surgery. These complications are possibly exacerbated by malnutrition at the time of surgery, resulting in decreased cell-mediated and humoral immune responses, which can be improved with the utilization of IMDs both prior to and following surgery. Although numerous randomized studies have investigated IMDs in the surgical setting, IMDs have not been well studied to evaluate whether their use improves outcomes for other patient groups with high incidence of malnutrition and acquired infections. Patients receiving stem cell transplantation following preparative myeloablative chemotherapy for treatment of a hematologic malignancy would be a prime example of another patient group who would share these characteristics. Given the proposed mechanism of action by which IMDs have aided recovery after surgery, it is reasonable to expect that IMDs may aid recovery after stem cell transplantation, and current preclinical and clinical data support the need for further clinical studies.
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Affiliation(s)
- Adam D Lye
- University of Kentucky Markey Cancer Center, Hematology and Blood & Marrow Transplantation, Lexington, Kentucky 40536, USA.
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50
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Matsumoto Y, Arai K, Momose H, Kuroyanagi Y. Development of a Wound Dressing Composed of a Hyaluronic Acid Sponge Containing Arginine. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2012; 20:993-1004. [DOI: 10.1163/156856209x444394] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Yasuhiro Matsumoto
- a R&D Center for Artificial Skin, School of Allied Health Sciences, Kitasato University, Kitasato 1-15-1, Sagamihara, Kanagawa 228-8555, Japan
| | - Kiwako Arai
- b R&D Center for Artificial Skin, School of Allied Health Sciences, Kitasato University, Kitasato 1-15-1, Sagamihara, Kanagawa 228-8555, Japan
| | - Hitomi Momose
- c R&D Center for Artificial Skin, School of Allied Health Sciences, Kitasato University, Kitasato 1-15-1, Sagamihara, Kanagawa 228-8555, Japan
| | - Yoshimitsu Kuroyanagi
- d R&D Center for Artificial Skin, School of Allied Health Sciences, Kitasato University, Kitasato 1-15-1, Sagamihara, Kanagawa 228-8555, Japan
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