Altered amino acid profile in patients with SARS-CoV-2 infection.

Low plasma arginine bioavailability has been implicated in endothelial dysfunction and immune dysregulation. The role of arginine in COVID-19 is unknown, but could contribute to cellular damage if low. Our objective was to determine arginine bioavailability in adults and children with COVID-19 vs. healthy controls. We hypothesized that arginine bioavailability would be low in patients with COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We conducted a prospective observational study of three patient cohorts; arginine bioavailability was determined in asymptomatic healthy controls, adults hospitalized with COVID-19, and hospitalized children/adolescents <21 y old with COVID-19, MIS-C, or asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection identified on admission screen. Mean patient plasma amino acids were compared to controls using the Student's t test. Arginine-to-ornithine ratio, a biomarker of arginase activity, and global arginine bioavailability ratio (GABR, arginine/[ornithine+citrulline]) were assessed in all three groups. A total of 80 patients were included (28 controls, 32 adults with COVID-19, and 20 pediatric patients with COVID-19/MIS-C). Mean plasma arginine and arginine bioavailability ratios were lower among adult and pediatric patients with COVID-19/MIS-C compared to controls. There was no difference between arginine bioavailability in children with COVID-19 vs. MIS-C. Adults and children with COVID-19 and MIS-C in our cohort had low arginine bioavailability compared to healthy adult controls. This may contribute to immune dysregulation and endothelial dysfunction in COVID-19. Low arginine-to-ornithine ratio in patients with COVID-19 or MIS-C suggests an elevation of arginase activity. Further study is merited to explore the role of arginine dysregulation in COVID-19.

The central role of arginine catabolism in T-cell dysfunction and increased susceptibility to infection after physical injury.

OBJECTIVE: To explore the hypothesis that decreased arginine availability by myeloid-derived suppressor cells (MDSCs) is a cause of T-cell dysfunction after physical injury (PI). BACKGROUND: Arginine is an essential amino acid for normal T-cell function whose availability becomes limited after PI. MDSCs expressing arginase 1 are induced by PI. T-cell dysfunction after PI seems to increase the risk of infection but the mechanisms that cause it are unclear. METHODS: PI was created using a standard laparotomy model. Phenotypical and functional alterations in T cells were evaluated in vivo. MDSCs expressing arginase 1 were measured by flow cytometry. Infection after PI was created by intraperitoneal injection of Listeria monocytogenes. N-Hydroxy-Nor-L-arginine (Nor-NOHA) was used as an arginase inhibitor. The effect of arginine depletion on T-cell function and susceptibility to infection was assessed through adoptive transfer of MDSC or injection of arginase into noninjured mice. RESULTS: PI caused a decrease in intracellular arginine in T cells, loss of the T-cell receptor (TCR) CD3-ζ chain, inhibition of in vivo T-cell proliferation, memory, and cytotoxicity. PI exponentially increased bacterial growth and mortality to L. monocytogenes. T-cell dysfunction and increased infection were reversed by arginase inhibitor Nor-NOHA but were reproduced by adoptively transferring MDSC or injecting arginase 1 to noninjured mice. CONCLUSIONS: Arginine availability is decreased after PI coinciding with an induction of MDSC expressing arginase 1. Decreased arginine may inhibit T-cell function and increase susceptibility to infection after injury.

Analysis of factorial time-course microarrays with application to a clinical study of burn injury.

Time-course microarray experiments are capable of capturing dynamic gene expression profiles. It is important to study how these dynamic profiles depend on the multiple factors that characterize the experimental condition under which the time course is observed. Analytic methods are needed to simultaneously handle the time course and factorial structure in the data. We developed a method to evaluate factor effects by pooling information across the time course while accounting for multiple testing and nonnormality of the microarray data. The method effectively extracts gene-specific response features and models their dependency on the experimental factors. Both longitudinal and cross-sectional time-course data can be handled by our approach. The method was used to analyze the impact of age on the temporal gene response to burn injury in a large-scale clinical study. Our analysis reveals that 21% of the genes responsive to burn are age-specific, among which expressions of mitochondria and immunoglobulin genes are differentially perturbed in pediatric and adult patients by burn injury. These new findings in the body's response to burn injury between children and adults support further investigations of therapeutic options targeting specific age groups. The methodology proposed here has been implemented in R package "TANOVA" and submitted to the Comprehensive R Archive Network at http://www.r-project.org/. It is also available for download at http://gluegrant1.stanford.edu/TANOVA/.

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.

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.

Nutritional care is a human right: Translating principles to clinical practice.

We have previously advocated that nutritional care be raised to the level of a human right in a close relationship to two well recognized fundamental rights: the right to food and the right to health. This paper aims to analyze the implication of nutritional care as a human right for healthcare practitioners. We will focus on the impact of the Human Rights Basic Approach (HRBA) on health care professionals (HCPs), namely how they can translate HRBA into routine clinical practice. Ethics and human rights are guiding values for clinical nutrition practitioners. Together they ensure a patient-centered approach, where the needs and rights of the patients are of the most significant importance. Human rights are based on the powerful idea of equal dignity for all people while expressing a set of core values, including fairness, respect, equality, dignity, and autonomy (FREDA). Through the analysis of FREDA principles, we have provided the elements to understand human rights and how a HRBA can support clinicians in the decision-making process. Clinical practice guidelines in clinical nutrition should incorporate disease-specific ethical issues and the HRBA. The HRBA should contribute to build conditions for HCPs to provide optimal and timely nutritional care. Nutritional care must be exercised by HCPs with due respect for several fundamental ethical values: attentiveness, responsibility competence, responsiveness, and solidarity.

Nutritional care is a human right: Translating principles to clinical practice.

We have previously advocated that nutritional care be raised to the level of a human right, in close relationship to two well-recognized fundamental rights: the right to food and the right to health. This article aims to analyze the implication of nutritional care as a human right for healthcare practitioners. We will focus on the impact of the Human Rights Basic Approach (HRBA) on healthcare professionals (HCPs), namely how they can translate HRBA into routine clinical practice. Ethics and human rights are guiding values for clinical nutrition practitioners. Together they ensure a patient-centered approach, in which the needs and rights of the patients are of the most significant importance. Human rights are based on the powerful idea of equal dignity for all people while expressing a set of core values, including fairness, respect, equality, dignity, and autonomy (FREDA). Through the analysis of FREDA principles, we have provided the elements to understand human rights and how an HRBA can support clinicians in the decision-making process. Clinical practice guidelines in clinical nutrition should incorporate disease-specific ethical issues and the HRBA. The HRBA should contribute to building conditions for HCPs to provide optimal and timely nutritional care. Nutritional care must be exercised by HCPs with due respect for several fundamental ethical values: attentiveness, responsibility competence, responsiveness, and solidarity.

Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma.

Myeloid suppressor cells (MSCs) producing high levels of arginase I block T cell function by depleting l-arginine in cancer, chronic infections, and trauma patients. In cancer, MSCs infiltrating tumors and in circulation are an important mechanism for tumor evasion and impair the therapeutic potential of cancer immunotherapies. However, the mechanisms that induce arginase I in MSCs in cancer are unknown. Using the 3LL mouse lung carcinoma, we aimed to characterize these mechanisms. Arginase I expression was independent of T cell-produced cytokines. Instead, tumor-derived soluble factors resistant to proteases induced and maintained arginase I expression in MSCs. 3LL tumor cells constitutively express cyclooxygenase (COX)-1 and COX-2 and produce high levels of PGE2. Genetic and pharmacological inhibition of COX-2, but not COX-1, blocked arginase I induction in vitro and in vivo. Signaling through the PGE2 receptor E-prostanoid 4 expressed in MSCs induced arginase I. Furthermore, blocking arginase I expression using COX-2 inhibitors elicited a lymphocyte-mediated antitumor response. These results demonstrate a new pathway of prostaglandin-induced immune dysfunction and provide a novel mechanism that can help explain the cancer prevention effects of COX-2 inhibitors. Furthermore, an addition of arginase I represents a clinical approach to enhance the therapeutic potential of cancer immunotherapies.

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.

Transcriptome and Functions of Granulocytic Myeloid-Derived Suppressor Cells Determine their Association with Disease Severity of COVID-19.

COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19, that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of Granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1 + G-MDSC (Arg + G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg + G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.

Presence of antibody-dependent cellular cytotoxicity (ADCC) against SARS-CoV-2 in COVID-19 plasma.

BACKGROUND: Neutralizing-antibody (nAb) is the major focus of most ongoing COVID-19 vaccine trials. However, nAb response against SARS-CoV-2, when present, decays rapidly. Given the myriad roles of antibodies in immune responses, it is possible that antibodies could also mediate protection against SARS-CoV-2 via effector mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), which we sought to explore here. METHODS: Plasma of 3 uninfected controls and 20 subjects exposed to, or recovering from, SARS-CoV-2 infection were collected from U.S. and sub-Saharan Africa. Immunofluorescence assay was used to detect the presence of SARS-CoV-2 specific IgG antibodies in the plasma samples. SARS-CoV-2 specific neutralizing capability of these plasmas was assessed with SARS-CoV-2 spike pseudotyped virus. ADCC activity was assessed with a calcein release assay. RESULTS: SARS-CoV-2 specific IgG antibodies were detected in all COVID-19 subjects studied. All but three COVID-19 subjects contained nAb at high potency (>80% neutralization). Plasma from 19/20 of COVID-19 subjects also demonstrated strong ADCC activity against SARS-CoV-2 spike glycoprotein, including two individuals without nAb against SARS-CoV-2. CONCLUSION: Both neutralizing and non-neutralizing COVID-19 plasmas can mediate ADCC. Our findings argue that evaluation of potential vaccines against SARS-CoV-2 should include investigation of the magnitude and durability of ADCC, in addition to nAb.

Severe COVID-19 Is Characterized by an Impaired Type I Interferon Response and Elevated Levels of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells.

COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1+ G-MDSC (Arg+G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg+G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.

Stat 6-dependent induction of myeloid derived suppressor cells after physical injury regulates nitric oxide response to endotoxin.

OBJECTIVE: To delineate the role of T-helper 2 (Th2) cytokines in the induction of trauma induced myeloid suppressor cells (TIMSC) and the regulation of nitric oxide production. BACKGROUND: Trauma induces myeloid cells that express CD11b+/Gr1+ and arginase 1 and exhibit an immune suppressing activity. This article explores the mechanisms that induce TIMSC and the effects on nitric oxide production in response to endotoxin. METHODS: TIMSC were studied in response to Th2 cytokines and a subsequent challenge to endotoxin. The role of Th2 cytokines was studied in STAT6-/- mice. Accumulation of TIMSC in spleens was studied using flow cytometry and immunhistochemistry. Plasma was recovered to measure accumulation of nitric oxide metabolites. RESULTS: TIMSC accumulated in the spleen of injured mice and were particularly sensitive to IL-4 and IL-13 with large inductions of arginase activity. Significant blunting in both the accumulation of TIMSC in the spleen and induction of arginase 1 was observed in STAT6-/- mice after physical injury. Accumulation of nitric oxide metabolites to endotoxin was observed in STAT6-/- mice. CONCLUSION: This study shows that induction of CD11b+/Gr1+ cells after physical injury play an essential role in the regulation of nitric oxide production after a septic challenge. The accumulation and induction of arginase 1 in TIMSC is Th2 cytokine dependent. To our knowledge, the role of TIMSC in the regulation of nitric oxide is a novel finding. This observation adds to the possibility that TIMSC could play an important role in immunosuppression observed after physical injury.

Deferred primary anastomosis versus diversion in patients with severe secondary peritonitis managed with staged laparotomies.

BACKGROUND: There is inconclusive data on whether critically ill individuals with severe secondary peritonitis requiring multiple staged laparotomies may became eligible candidates for deferred primary anastomoses (DPA). We sought to compare a protocol for DPA against a protocol for diversion in severely ill critical patients with intra-abdominal sepsis. METHODS: A retrospective cohort study was performed examining 112 patients admitted through an ICU between 2002 and 2006, with diagnosis of secondary peritonitis and managed with staged laparotomies whom required small- or large-bowel segment resections. Patients were categorized and compared according to the surgical treatment necessitated to resolve the secondary peritonitis (DPA versus diversion). Outcome measures were days on mechanical ventilation, days required in ICU, days required in hospital, incidence of fistulas/leakages, acute respiratory distress syndrome (ARDS), and mortality. RESULTS: There were 34 patients subjected to DPA and 78 to diversion. Fistulas/leakages developed in three patients (8.8%) with DPA and four patients (5.1%) with diversion (p = 0.359). ARDS was present in 6 patients (17.6%) with DPA and 24 patients (30.8%) with diversion (p = 0.149). There were 30 patients (88.2%) with DPA and 65 patients (83.3%) with diversion discharged alive (p = 0.51). There were not statistical significant differences between groups among survivors regarding hospital length of stay, ICU length of stay, and days on mechanical ventilation. CONCLUSIONS: We did not find significant differences in morbidity or mortality when we compared DPA versus diversion surgical treatment. It is feasible to perform a primary anastomosis in critically ill patients with severe secondary peritonitis managed with staged laparotomies.

Nature of myeloid cells expressing arginase 1 in peripheral blood after trauma.

BACKGROUND: Myeloid cells that express arginase 1 are upregulated by different stimuli, including trauma, and are capable of depleting arginine from the surrounding environment. Through arginine depletion, myeloid cells are capable of regulating T-cell function. We have previously reported increased arginase 1 expression in the peripheral blood mononuclear cells (PBMCs) after injury. The nature of the cells expressing arginase in humans after trauma is unknown and is the focus of this article. METHODS: PBMCs were isolated using a Ficoll-Hypaque gradient. Arginase activity was measured by conversion of arginine to ornithine, and arginase 1 protein expression was measured by Western blot. The percent CD16 granulocytes and phenotypical analysis of the cells present in PBMCs were determined by flow cytometry. Magnetic microbeads were used for isolation and exclusion of specific cell subpopulations. RESULTS: Trauma patients exhibited a dramatic increase in arginase activity (p < 0.05) and an increased percentage of CD16 granulocytes in the PBMC layer (p < 0.05) compared with control volunteers. Increased arginase activity in the PBMC layer was due to the contamination of this layer by granulocytes, as their exclusion decreased arginase activity back to baseline (p < 0.05). Granulocytes isolated from the PBMC layer expressed increased CD11b (p < 0.05) and CD66b (p < 0.05), markers of granulocyte activation. Furthermore, these granulocytes were significantly more swollen and degranulated compared with noncontaminating granulocytes. CONCLUSION: In humans, increased arginase 1 expression after trauma observed in the PBMC layer seems to be exclusively the result of an increased number of activated granulocytes.

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.

Use of a nasal bridle prevents accidental nasoenteral feeding tube removal.

Reinserting feeding tubes that are accidentally removed exposes patients to risk and consumes hospital resources. We were interested to know if using a bridle to secure tubes would be more effective than tape at preventing accidental tube removal. This was a quality improvement project with a before-and-after design. Between May 2007 and August 2007, we prospectively followed 90 tubes (50 tape, 40 bridle). Tubes were followed up daily until accidental tube removal, ICU discharge, or planned tube removal. Our primary endpoint was accidental tube removal. We compared the 2 groups on the following: (1) proportion of tubes accidentally removed; (2) rate of accidental tube removal (per 100 tube-days); and (3) Kaplan-Meier survival analysis. Survival analysis data were right-censored at ICU discharge or planned tube removal. There were no significant differences between groups in any demographics. The proportion of tubes accidentally removed was 36% (18 of 50) in the tape group and 10% (4 of 40) in the bridle group; P<.05. The rate of accidental tube removal (per 100 tube-days) was 6.4 (18 in 281 tube-days) in the tape group and 1.6 (4 in 248 tube-days) in the bridle group; P<.05. Survival analysis showed a significant difference between the groups with a log-rank test for equality of survivor function of P<.05. Using a bridle to secure feeding tubes significantly reduces the proportion and rate of accidental tube removal and results in increased tube survival by Kaplan-Meier analysis.

[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.

Effect of calorically dense enteral nutrition formulas on outcome in critically ill trauma and surgical patients.

BACKGROUND: Surgical and trauma patients are traditionally provided with calorically dense dietary formulas to deliver high amounts of nutrients. The benefits of these formulas remain unproven and may be associated with significant side effects and even increased mortality. We studied outcomes on surgical and trauma patients receiving either a calorically dense dietary formula or a normocaloric dietary formula. METHODS: A retrospective analysis comparing outcomes in intensive care unit (ICU) surgical and trauma patients receiving either a calorically dense dietary formula or a normocaloric dietary formula was performed at the University of Pittsburgh Medical Center. RESULTS: One hundred seventeen patients met study criteria. Surgical and trauma patients were analyzed separately. Despite receiving different calorically dense diets, caloric intake was not significantly different in surgical patients receiving either diet. However, surgical patients receiving a normocaloric formula exhibited decreased length of stay (14.7 +/- 10.1 vs 25.0 +/- 11.3 days; p = .01), ventilator days (14.3 +/- 12.9 vs 21.3 +/- 10.5 days; p = .04), and average daily glucose levels (129.8 +/- 4.1 vs 157.9 +/- 13.6 mg/dL; p =.01), and were more likely to be directly discharged home compared with those receiving a calorically dense dietary formula. Trauma patients receiving a calorically dense dietary formula were on average 17 years younger (p = .01). However, trauma patients receiving a normocaloric formula exhibited decreased length of stay (15.3 +/- 1.6 vs 18.7 +/- 1.6 days; p = .02) and a greater likelihood of direct discharge home. CONCLUSIONS: The data generated suggest that what a patient is fed affects both short- and long-term outcomes. A prospective study should be designed to determine the ideal calories needed in surgical and trauma patients.