A paradigm shift in clinical nutrition.

The current clinical nutrition paradigm is that decreased caloric intake, resulting in a caloric deficit, is central to the development disease-related malnutrition (DRM). In following with this paradigm, one should assume that nutrition interventions with artificially administered nutrition (food substitution paradigm) aimed at preventing a caloric deficit should result in the prevention and/or successful treatment of DRM. However, clear evidence demonstrates that the DRM observed in diverse illnesses is at least partially resistant to nutrition interventions aimed at preventing the development of a caloric deficit. Simply put, DRM cannot be prevented nor resolved through a nutrition intervention aimed solely on replacing what the person cannot or will not eat. It is time to stop oversimplifying nutrition therapy in clinical nutrition interventions as a food substitution issue, focusing instead on developing and testing innovative hypotheses aimed at a mechanistic understanding of how DRM develops. Through this effort, new paradigms should evolve. The aim of this opinion paper is to provide an overview of why we need a shift in the current paradigm.

Clinical Nutrition and Human Rights. An International Position Paper.

The International Working Group for Patients' Right to Nutritional Care presents its position paper regarding nutritional care as a human right intrinsically linked to the right to food and the right to health. All people should have access to food and evidence-based medical nutrition therapy including artificial nutrition and hydration. In this regard, the hospitalized malnourished ill should mandatorily have access to screening, diagnosis, nutritional assessment, with optimal and timely nutritional therapy in order to overcome malnutrition associated morbidity and mortality, while reducing the rates of disease-related malnutrition. This right does not imply there is an obligation to feed all patients at any stage of life and at any cost. On the contrary, this right implies, from an ethical point of view, that the best decision for the patient must be taken and this may include, under certain circumstances, the decision not to feed. Application of the human rights-based approach to the field of clinical nutrition will contribute to the construction of a moral, political, and legal focus to the concept of nutritional care. Moreover, it will be the cornerstone to the rationale of political and legal instruments in the field of clinical nutrition.

Clinical nutrition and human rights. An international position paper.

The International Working Group for Patients' Right to Nutritional Care presents its position paper regarding nutritional care as a human right intrinsically linked to the right to food and the right to health. All people should have access to food and evidence-based medical nutrition therapy including artificial nutrition and hydration. In this regard, the hospitalized malnourished ill should mandatorily have access to screening, diagnosis, nutritional assessment, with optimal and timely nutritional therapy in order to overcome malnutrition associated morbidity and mortality, while reducing the rates of disease-related malnutrition. This right does not imply there is an obligation to feed all patients at any stage of life and at any cost. On the contrary, this right implies, from an ethical point of view, that the best decision for the patient must be taken and this may include, under certain circumstances, the decision not to feed. Application of the human rights-based approach to the field of clinical nutrition will contribute to the construction of a moral, political and legal focus to the concept of nutritional care. Moreover, it will be the cornerstone to the rationale of political and legal instruments in the field of clinical nutrition.

Lessons Learned in Nutrition Therapy in Patients With Severe COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has reached worldwide, and until a vaccine is found, it will continue to cause significant morbidity and mortality. The clinical presentation of COVID-19 ranges from that of being asymptomatic to developing a fatal illness characterized by multiple organ involvement. Approximately 20% of the patients will require hospitalization; one-quarter of hospitalized patients will develop severe COVID-19 requiring admission to the intensive care unit, most frequently, with acute respiratory failure. An ongoing effort is being made to identify the patients that will develop severe COVID-19. Overall, patients present with 3 different phenotypes of nutrition risk: (1) the frail older patient, (2) the patient with severe ongoing chronic illness, and (3) the patient with severe and morbid obesity. These 3 phenotypes represent different nutrition risks and diverse nutrition interventions. This article explores the different potential approaches to nutrition intervention in patients with COVID-19, evaluating, in this process, the challenges faced in the implementation of guidelines written by different societies.

[Cartagena Declaration. The International Declaration on the Right to Nutritional Care and the Fight against Malnutrition]. / Declaración de Cartagena. Declaración Internacional sobre el Derecho al Cuidado Nutricional y la Lucha contra la Malnutrición.

INTRODUCTION: The need to promote the right to nutritional care, to fight against malnutrition and to advance in education and research in clinical nutrition has led all the FELANPE's societies to sign on May 3rd, during the 33rd Congress of the Colombian Clinical Nutrition Association (ACNC) in the city of Cartagena, the International Declaration on the Right to Nutritional Care and the Fight against Malnutrition, "Declaration of Cartagena". The Declaration provides a coherent framework of 13 principles which can serve as a guide for societies, schools and associations affiliated to FELANPE in the development of action plans. In addition, it will serve as an instrument to promote, through governments, the formulation of policies and legislation in the field of clinical nutrition. We believe that the general framework of principles proposed by the Declaration can contribute to raise awareness about the magnitude of this problem and to promote cooperation networks among Latin-American countries. Although this Declaration does not have a binding legal effect, it has an undeniable moral strength and it can provide practical guidance to States. An implementation program will allow developing a toolkit to transform principles into actions.

INTRODUCCIÓN: Frente a la necesidad de promover el derecho al cuidado nutricional, de luchar contra la malnutrición y de avanzar en temas de educación e investigación en nutrición clínica, las sociedades que constituyen la FELANPE firmaron la Declaración Internacional sobre el Derecho al Cuidado Nutricional y la Lucha contra la Malnutrición, "Declaración de Cartagena", el 3 de mayo del presente año en la ciudad de Cartagena, en el marco del 33º Congreso de la Asociación Colombiana de Nutrición Clínica. La Declaración proporciona un marco coherente de 13 principios, los cuales podrán servir de guía a las sociedades afiliadas a la FELANPE en el desarrollo de los planes de acción. Además, servirá como un instrumento para que promuevan, a través de los gobiernos, la formulación de políticas y legislaciones en el campo de la nutrición clínica. Consideramos que el marco general de principios propuesto por la Declaración puede contribuir a crear conciencia acerca de la magnitud de este problema y a forjar redes de cooperación entre los países de la región. Aunque esta Declaración no tiene un efecto jurídico vinculante (obligatorio), tiene una fuerza moral innegable y puede proporcionar orientación práctica a los estados. Un plan de implementación permitirá desarrollar la caja de herramientas necesaria para transformar los principios en acciones.

Arginine deficiency caused by myeloid cells: importance, identification and treatment.

Dietary arginine supplementation has been suggested as a means of improving T lymphocyte function and has found its greatest clinical utility in patients undergoing elective surgery. In other illnesses, arginine supplementation is controversial. Breakthroughs in understanding arginine metabolism have led to the identification of myeloid cells that express arginase 1, causing significant depletion of arginine - an essential amino acid for normal T lymphocyte function. Hence, myeloid cells expressing arginase 1 are also known as myeloid-derived suppressor cells. This chapter discusses the hypothesis that arginine replacement therapy may be necessary in arginine deficiency states.

Immunonutrition for patients undergoing elective surgery for gastrointestinal cancer: impact on hospital costs.

BACKGROUND: Oral or enteral dietary supplementation with arginine, omega 3 fatty acids and nucleotides (known as immunonutrition) significantly improve outcomes in patients undergoing elective surgery. The objective of the study was to determine the impact on hospital costs of immunonutrition formulas used in patients undergoing elective surgery for gastrointestinal cancer. METHODS: US hospital costs of stay with and without surgical infectious complications, and average cost per day in the hospital for patients undergoing elective surgery for gastrointestinal cancer were estimated using data from the Healthcare Cost and Utilization Project's 2008 Nationwide Inpatient Sample. These costs were then used to estimate the impact of perioperative immunonutrition on hospital costs using estimates of reduction in infectious complications or length of stay from a meta-analysis of clinical trials in patients undergoing elective surgery for gastrointestinal cancer. Sensitivity of the results to changes in baseline complication rates or length of stay was tested. RESULTS: From the meta-analysis estimates, use of immunonutrition resulted in savings per patient of $3,300 with costs based on reduction in infectious complication rates or $6,000 with costs based on length of hospital stay. Cost savings per patient were present for baseline complication rates above 3.5% or when baseline length of stay and infectious complication rates were reduced to reflect recent US data for those with upper and lower GI elective cancer surgery (range, $1,200 to $6,300). CONCLUSIONS: Use of immunonutrition for patients undergoing elective surgery for gastrointestinal cancer is an effective and cost-saving intervention.

Immunosupression and infection after major surgery: a nutritional deficiency.

T cell dysfunction significantly increases susceptibility to infections and organ failure after trauma or surgery (physical injury). This coincides with a persistent drop in arginine availability, a necessary amino acid for normal T cell function. Recent data led to the identification of a novel mechanism of T cell suppression caused by the depletion of arginine through the induction of arginase 1 (ARG1) in a specialized group of immature myeloid cells, now named myeloid-derived suppressor cells (MDSC). In addition to T cell dysfunction, arginine depletion leads to the decrease in nitric oxide (NO) production. Dietary therapy containing arginine at supraphysiologic concentrations along with other components such as omega-3 fat acids, antioxidants, nucleotides, and vitamin A is associated with improvement in T cell function, NO production, and a significant decrease in infection rates. The authors propose that a pathologic decrease in arginine availability is an identifiable nutrition deficiency syndrome that worsens outcomes if left untreated.

Arginine and immunity.

For many years, dietary arginine supplementation, often combined with other substances, has been used as a mechanism to boost the immune system. Considerable controversy, however, exists as to the benefits and indications of dietary arginine due in part to a poor understanding of the role played by this amino acid in maintaining immune function. Emerging knowledge promises to clear this controversy and allow for arginine's safe use. In myeloid cells, arginine is mainly metabolized either by inducible nitric oxide (NO) synthases (iNOS) or by arginase 1, enzymes that are stimulated by T helper 1 or 2 cytokines, respectively. Thus, activation of iNOS or arginase (or both) reflects the type of inflammatory response in a specific disease process. Myeloid suppressor cells (MSC) expressing arginase have been described in trauma (in both mice and humans), intra-abdominal sepsis, certain infections, and prominently, cancer. Myeloid cells expressing arginase have been shown to accumulate in patients with cancer. Arginase 1 expression is also detected in mononuclear cells after trauma or surgery. MSC efficiently deplete arginine and generate ornithine. Through arginine depletion, MSC may control NO production and regulate other arginine-dependent biological processes. Low circulating arginine has been documented in trauma and cancer, suggesting that MSC may exert a systemic effect and cause a state of arginine deficiency. Simultaneously, T lymphocytes depend on arginine for proliferation, zeta-chain peptide and T-cell receptor complex expression, and the development of memory. T-cells cocultured with MSC exhibit the molecular and functional effects associated with arginine deficiency. Not surprisingly, T-cell abnormalities, including decreased proliferation and loss of the zeta-chain, are observed in cancer and after trauma.

Citrulline can preserve proliferation and prevent the loss of CD3 zeta chain under conditions of low arginine.

BACKGROUND: Arginine depletion by the enzyme Arginase I, decreases expression of the TCR zeta chain preventing T-cell activation and causing T-cell dysfunction. We hypothesized that citrulline could substitute for arginine under conditions of increased arginase expression. Thus, the goal was to establish a possible mechanism of how citrulline could overcome arginine depletion caused by arginase. METHODS: Jurkat cells were cultured, with or without arginase, in media containing different amino-acid constituents: complete RPMI containing arginine (C-RPMI) (arginine), Arginine-Free-RPMI (Arg-Free RPMI) and Citrulline-containing RPMI (Cit RPMI). Incorporation of citrulline was measured via uptake of 3H-citrulline, whereas proliferation was measured via 3H-thymidine incorporation. zeta Chain was analyzed by 2-color flow cytometry. Argininosuccinate synthase (AS) and argininosuccinate lyase expression was detected using Northern blots, RT-PCR, and Western blots. RESULTS: Jurkat cells exhibited a significant decrease in proliferation and 5 chain expression when cultured in the presence of arginase or in the absence of arginine. With citrulline, zeta chain expression and proliferation were maintained in the absence of arginine or in the presence of the enzyme arginase. Jurkat cells, cultured in the absence of arginine, were associated with a 5-fold increase in citrulline uptake. The absence of arginine was also associated with increased expression of AS. CONCLUSIONS: T cells exhibit the molecular capability of increasing citrulline membrane transport and up-regulating AS expression, thus exhibiting the necessary mechanisms for converting citrulline into arginine and escaping the ill effects of arginine depletion. Therefore, citrulline has the potential to be a substitute for supplemental arginine in diseases associated with arginase-mediated T cell dysfunction.

Regulation of T cell receptor CD3zeta chain expression by L-arginine.

L-Arg plays a central role in the normal function of several organ systems including the immune system. L-Arg can be depleted by arginase I produced by macrophages and hepatocytes in several disease states such as trauma and sepsis and following liver transplantation. The decrease in L-Arg levels induces a profound decrease in T cell function through mechanisms that have remained unclear. The data presented here demonstrate that Jurkat T cells cultured in medium without L-Arg (L-Arg-free RPMI) have a rapid decrease in the expression of the T cell antigen receptor zeta chain (CD3zeta), the principal signal transduction element in this receptor, and a decrease in T cell proliferation. This phenomenon is completely reversed by the replenishment of L-Arg but not other amino acids. These changes are not caused by cell apoptosis; instead, the diminished expression of CD3zeta protein is paralleled by a decrease in CD3zeta mRNA. This change in CD3zeta mRNA expression is not caused by a decrease in the transcription rate but rather by a significantly shorter CD3zeta mRNA half-life. This mechanism is sensitive to cycloheximide. Therefore, the regulation of L-Arg concentration in the microenvironment could represent an important mechanism to modulate the expression of CD3zeta and the T cell receptor and consequently of T cell function.