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Multiple sclerosis (MS) is a progressive neurodegenerative disease associated with increased infection rates, chronic inflammation, and premature death. Optimization of nutritional status via dietary supplementation may improve immune function in people suffering from MS and lead to decreased rates of infection. Fifteen individuals with a diagnosis of relapsing-remitting MS for an average of 12.4 years (SD =7.4; R = 2, 25) were enrolled in a one-year open-label clinical trial. Participants consumed a broad-spectrum dietary supplement regimen containing polysaccharides, phytochemicals, antioxidants, vitamins, and minerals three times per day. The occurrence of infections and a panel of cytokines, growth factors, and T- and B-cell subsets were assessed at baseline and 12 months. Seven female and 8 male participants with an average age of 51.3 years (SD =7.2; R = 38, 65) completed the study. At the end of the intervention, participants had fewer total infections (M = 7.9, SD =8.1 at baseline and M = 2.5, SD =4.3 at 12-month follow-up). At 12 months, IL-2, TNF-α, EGF, and CD95 + CD34+ significantly increased, while IL-1β significantly decreased. No major adverse effects were reported; only mild gastrointestinal intolerance was reported in four cases. A decreased occurrence of infection was observed in MS patients treated with 12 months of a polysaccharide-based multinutrient dietary supplement. Significant changes were also noted in several key biomarkers that would be physiologically favorable to the MS population. Thus, the results of this study suggest an immunomodulatory effect of the dietary supplement regimen studied.

Host defense peptides (HDPs) are crucial components of the body's first line of defense that protect organisms from infections and mediate immune responses. Defensins and cathelicidins are the two most important families of HDPs in mammals. In this review, we summarize the nutrients that are involved in inducible expression of endogenous defensins and cathelicidins. In addition, the mitogen-activated protein kinases (MAPK), nuclear factor kappa B (NF-κB) and histone deacetylase (HDAC) signaling pathways that play vital roles in the induction of defensin and cathelicidin expression are highlighted. Endogenous defensins and cathelicidins induced by nutrients may be potential alternatives to antibiotic treatments against infection and diseases. This review mainly focuses on the inducible expression and regulatory mechanisms of defensins and cathelicidins in multiple species by different nutrients and the potential applications of defensin- and cathelicidin-inducing nutrients., (Copyright © 2019. Published by Elsevier Inc.)

Currently, there is an increase in the resistance of microorganisms to the available arsenal of antimicrobial drugs, which makes it necessary to maintain and stimulate the body's own immune-protective properties. The main extraskeletal effect of vitamin D activity is associated with the homeostasis of the immune system. The role of vitamin D in reducing the risk of infection with infectious agents has been studied for a long time. Literature search on the effective use of vitamin D for immunoprophylaxis was carried out in Scopus, Web of Science, PubMed, clinicaltrials.gov databases over the past 10 years for related keywords: vitamin D, immunoprophylaxis. Vitamin D stimulates the synthesis of antimicrobial peptides, cathelicidins and defensins, which exhibit broad-spectrum activity against viruses, bacteria and fungal infections; reduces the concentration of pro-inflammatory cytokines; increases the concentration of anti-inflammatory cytokines. Vitamin D is also involved in cell differentiation, maturation and proliferation of immune cells. The article presents the literature review in order to justify additional intake of vitamin D in case of diagnosis of its deficiency and insufficiency for the purpose of immunoprophylaxis in children and adults, especially in risk groups (elderly age, pregnant women, patients with chronic diseases of respiratory, endocrine and urinary systems, gastrointestinal tract, and infectious diseases). Inclusion of vitamin D in the diet as a dietary supplement, as well as fortification of products with it, can be an effective measure to reduce the risk of both morbidity and mortality, especially during the period of quarantine measures., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)

In the present study, a new method for the synthesis of the open cell flexible polyurethane foams (PUFs) was developed by using starch powder and the modification of closed cell foam formulation. Starch is the second largest polymeric carbohydrate as a macromolecule on this planet with a large number of glucose units. Copper oxide nanoparticles (CuO NPs) were synthesized by thermal degradation method at different temperatures of 400, 600 and 800 °C as antimicrobial agents. The antimicrobial activity of CuO NPs and commercial CuO powder against the main causes of hospital infections were tested. CuO 600 was the most effective antimicrobial agent and enhanced polymer matrix tensile strength with starch powder as new polyurethane foams (PUFs) cell opener with high tensile strength. The effects of parameters on tensile strength were optimized using response surface methodology (RSM). CuO NPs and PUF had optimal conditions and were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). Foam synthesized at the optimal conditions had an open cell structure with high tensile strength and efficient antimicrobial activity that made them suitable to be used as an antimicrobial hospital mattress to control hospital infections., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The multicentre randomised controlled PEPaNIC trial showed that withholding parenteral nutrition (PN) during the first week of critical illness in children was clinically superior to providing early PN. This study describes the cost-effectiveness of this new nutritional strategy., Methods: Direct medical costs were calculated with use of a micro-costing approach. We compared the costs of late versus early initiation of PN (n = 673 versus n = 670 patients) in the Belgian and Dutch study populations from a hospital perspective, using Student's t test with bootstrapping. Main cost drivers were identified and the impact of new infections on the total costs was assessed., Results: Mean direct medical costs for patients receiving late PN (€26.680, IQR €10.090-28.830 per patient) were 21% lower (-€7.180, p = 0.007) than for patients receiving early PN (€33.860, IQR €11.080-34.720). Since late PN was more effective and less costly, this strategy was superior to early PN. The lower costs for PN only contributed 2.1% to the total cost reduction. The main cost driver was intensive care hospitalisation costs (-€4.120, p = 0.003). The patients who acquired a new infection (14%) were responsible for 41% of the total costs. Sensitivity analyses confirmed consistency across both healthcare systems., Conclusions: Late initiation of PN decreased the direct medical costs for hospitalisation in critically ill children, beyond the expected lower costs for withholding PN. Avoiding new infections by late initiation of PN yielded a large cost reduction. Hence, late initiation of PN was superior to early initiation of PN largely via its effect on new infections., Trial Registration: ClinicalTrials.gov, NCT01536275 . Registered on 16 February 2012.

In the past few years, increasing interest has been directed to bioactive peptides of animal and plant origin: in particular, researchers have focused their attention on their mechanisms of action and potential role in the prevention and treatment of cancer, cardiovascular and infective diseases. We have developed a search strategy to identify these studies in PubMed (January 1980 to May 2016); particularly those papers presenting comprehensive reviews or meta-analyses, plus in vitro and in vivo studies and clinical trials on those bioactive peptides that affect cardiovascular diseases, immunity or cancer, or have antioxidant, anti-inflammatory and antimicrobial effects. In this review we have mostly focused on evidence-based healthy properties of bioactive peptides from different sources. Bioactive peptides derived from fish, milk, meat and plants have demonstrated significant antihypertensive and lipid-lowering activity in clinical trials. Many bioactive peptides show selective cytotoxic activity against a wide range of cancer cell lines in vitro and in vivo, whereas others have immunomodulatory and antimicrobial effects. Furthermore, some peptides exert anti-inflammatory and antioxidant activity, which could aid in the prevention of chronic diseases. However, clinical evidence is at an early stage, and there is a need for solid pharmacokinetic data and for standardized extraction procedures. Further studies on animals and randomized clinical trials are required to confirm these effects, and enable these peptides to be used as preventive or therapeutic treatments., Linked Articles: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc., (© 2016 The British Pharmacological Society.)

Background/objectives: Intravenous (i.v.) glutamine supplementation of parenteral nutrition (PN) can improve clinical outcomes, reduce mortality and infection rates and shorten the length of hospital and/or intensive care unit (ICU) stays compared with standard PN. This study is a pharmacoeconomic analysis to determine whether i.v. glutamine supplementation of PN remains both a highly favourable and cost-effective option for Italian ICU patients., Subjects/methods: A previously published discrete event simulation model was updated by incorporating the most up-to-date and clinically relevant efficacy data (a clinically realistic subgroup analysis from a published meta-analysis), recent cost data from the Italian health-care system and the latest epidemiology data from a large Italian ICU database (covering 230 Italian ICUs and more than 77,000 patients). Sensitivity analyses were performed to test the robustness of the results., Results: Parenteral glutamine supplementation can significantly improve ICU efficiency in Italy, as the additional cost of supplemented treatment is more than completely offset by cost savings in hospital care. Supplementation was more cost-effective (cost-effectiveness ratio (CER)=[euro ]35,165 per patient discharged alive) than standard, non-supplemented PN (CER=[euro ]40,156 per patient discharged alive), and it resulted in mean cost savings of [euro ]4991 per patient discharged alive or [euro ]1047 per patient admitted to the hospital. Sensitivity analyses confirmed the robustness of these results., Conclusions: Alanyl-glutamine supplementation of PN is a clinically and economically attractive strategy for ICU patients in Italy and may be applicable to selected ICU patient populations in other countries.

The article describes the main principles of stepped diet therapy of acute intestinal infections in children developed on the basis of nutritive support staging, depending on patients' age, stage and severity of disease. Significance of functional food products for diet therapy tactics in patients with mild and moderately severe forms of infection is demonstrated.

Optimal functioning of the immune system is crucial to human health, and nutrition is one of the major exogenous factors modulating different aspects of immune function. Currently, no single marker is available to predict the effect of a dietary intervention on different aspects of immune function. To provide further guidance on the assessment and interpretation of the modulation of immune functions due to nutrition in the general population, International Life Sciences Institute Europe commissioned a group of experts from academia, government and the food industry to prepare a guidance document. A draft of this paper was refined at a workshop involving additional experts. First, the expert group defined criteria to evaluate the usefulness of immune function markers. Over seventy-five markers were scored within the context of three distinct immune system functions: defence against pathogens; avoidance or mitigation of allergy; control of low-grade (metabolic) inflammation. The most useful markers were subsequently classified depending on whether they by themselves signify clinical relevance and/or involvement of immune function. Next, five theoretical scenarios were drafted describing potential changes in the values of markers compared with a relevant reference range. Finally, all elements were combined, providing a framework to aid the design and interpretation of studies assessing the effects of nutrition on immune function. This stepwise approach offers a clear rationale for selecting markers for future trials and provides a framework for the interpretation of outcomes. A similar stepwise approach may also be useful to rationalise the selection and interpretation of markers for other physiological processes critical to the maintenance of health and well-being.

Objective: Pharmaconutrients have been shown in clinical and laboratory studies to modulate human and animal immune responses and thus to have potential benefits for the critically ill. However, reviews and meta-analyses continue to reflect controversy in the published research and a lack of agreement regarding these benefits. The objective of this study was to contribute to the resolution of such controversy by evaluating the effectiveness of immunonutrient-enriched diets in decreasing complications and mortality in patients with different critical illnesses., Methods: The present study is a meta-analysis of randomized clinical trials that evaluated the use of immunomodulating nutrients in critically ill adults. The PubMed and CINAHL datasets were searched., Results: Two hundred sixteen articles were initially found, but only 39 met the established inclusion criteria. In the general population, mortality did not show a statistically significant relative risk (RR) decrease (0.92, confidence interval [CI] 0.80-1.05); infection complications were decreased, with a general RR of 0.57 (CI 0.44-0.74) and an RR of 0.56 (CI 0.46-0.68) in surgical patients; and the sepsis incidence was decreased (RR 0.48, CI 0.27-0.83)., Conclusions: The administration of immunomodulating nutrient-enriched diets did not change the mortality of critically ill or surgical patients, but infection complications in critically ill patients, in particular the surgical population, were decreased. Explanatory clinical trials using isolated immunomodulating nutrients in different populations of critically ill patients followed by pragmatic trials based on clinical trial results should be considered in future research., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: To improve the clinical outcome, immunonutrition (IN) was usually used in the patients undergoing elective gastrointestinal caner surgery. However, its effectiveness remains uncertain., Methods: Randomized controlled trials (RCTs) published between 1995 and 2011 were identified and extracted by two reviewers independently from electronic databases, including PubMed, EMBASE, and Cochrane Library. The quality of included trials was assessed according to the handbook for Cochrane reviewer (V5.0.1). Statistical analysis was carried out with RevMan software., Results: Nineteen RCTs involving a total of 2331 patients were included in our meta-analysis. The results showed perioperative IN significantly reduced length of hospital stay (WMD, -2.62; 95% CI, -3.26 to -1.97; P < 0.01) and morbidity of postoperative infectious complication (RR, 0.44; 95% CI, 0.32 to 0.60; P < 0.01) compared with standard diet. Moreover, perioperative IN also significantly decreased morbidity of postoperative non-infectious complication in comparison with standard diet (RR, 0.72; 95% CI, 0.54 to 0.97; P = 0.03)., Conclusion: Perioperative IN is effective and safe to reduce postoperative infection, non-infection complication and length of hospital stay., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Vitamin D is being touted as an anti-infective agent and it has even been suggested that vitamin D supplementation could be effective against the H1N1 influenza virus. The claims are largely based on the ability of vitamin D to induce antibacterial peptides and evidence that the immune system produces active vitamin D (1,25(OH)(2)D(3)) in situ. While there are many examples of immune production of 1,25(OH)(2)D(3) in vitro, there is little in vivo evidence. In addition, it is not clear what role immune production of 1,25(OH)(2)D(3) has on the course of disease. Vitamin D and 1,25(OH)(2)D(3) inhibit T helper type 1 (Th1)/Th17-mediated immune responses and autoimmune diseases by acting on the innate and acquired immune system to inhibit the function of Th1 and Th17 cells. Th1 and Th17 cells are important in host resistance to many infections including tuberculosis (TB) caused by Mycobacterium tuberculosis. Paradoxically the innate immune system is induced to produce antibacterial peptides that are effective against TB in vitro. Data from several models of infection have so far not supported a role for vitamin D in affecting the course of disease. There is also very little evidence that vitamin D affects the course of human TB infection. Experiments have not been done in cells, mice or humans to evaluate the effect of vitamin D on influenza virus. At this time it would be premature to claim that vitamin D has an effect on TB, influenza or any other infection.

Prevention of infectious complications after major surgeries including those for cancer has been a major concern in the clinical field. To overcome this problem, probiotics and synbiotics (combination of probiotics and prebiotics have recently been introduced for post-operative treatment. Clinical application of synbiotics in severe cases, such as severe pediatric surgical cases, acute pancreatitis, liver transplantation, and biliary cancer, has been reported. The present article deals with the clinical effect of such synbiotic therapies for the patients under emergency medical care, and discusses the possible mechanism of action and prospect of synbiotic therapy.

Zinc is a nutritionally essential trace element, and thus zinc deficiency may severely affect human health. Many studies were published in which the effect of nutritional zinc supplementation on the incidence or severity of a certain disease was investigated. This review summarizes the main observations and aims to evaluate the use of nutritional zinc supplementation for prevention and treatment of human disease.

Proper nourishment is one of the basic elements in treatment patients suffering from acute pancreatitis and that's why it should be introduced in early phase of the disease. Patients suffering from light pancreatitis don't need dietary treatment because regular nourishment being.introduced a few days after the disease has developed itself. The proper supply of nourishing elements is crucial to patients with acute or chronic pancreatities. In this group of patient intravenous feeding or enteral nutrition methods are being used. They work as self sufficient and independent methods or they complete one another. The most recommended is the oligomeric diet with glutamine. Despite constant controversy over nourishment, early enternal nutrition is said to be better than intravenous feeding. Due to protection of intestinal barrier the enternal nutrition decrease the translocation of bacteria and endotoxin and as a result decrease the possibility of pancreaties parenchyma. The analysis of randomized clinical studies shows the improvement of clinical treatment and the improvement of prognosis in the group of patients using enternal nutrition. The number of complications and mortality rate has also decreased in this group. It allows also to shorten the hospitalization and cut the treatment costs. The patients, which do not tolerate internal nutrition or which cannot put up with intestinal entrance are to be fed with intravenous feeding. Presented above positive results of acute panctreatitis treatment, which were achieved after using internal nutrition, are the best basis for introducing this method in clinical practice.

Background and Aims: In many patients with dementia, the oral intake of fluids and nutrients becomes insufficient and a decision has to be made whether to start artificial nutrition or hydration (ANH). This study examines the incidence of ANH in nursing-home patients with dementia in The Netherlands, the methods of administration used, patient characteristics, and the characteristics of the ANH decision- making process., Methods: In June 2001, a postal questionnaire was sent to all nursing-home physicians (NHPs) (n=1054) in The Netherlands. The response rate was 77%., Results: Of the NHPs, 39% had started ANH during the 1-year study period, mostly by hypodermoclysis. As calculated from the total number of patients in The Netherlands, the incidence density for ANH in demented nursing-home patients was 3.4 per 100 patient-years. The most important considerations in taking this decision were the patient's physical condition, the expected result of rehydration, and the (presumed) wishes of the patient. Decisions to start hydration resembled decisions to start nutrition, but more frequently concerned incompetent patients with an intercurrent infectious disease., Conclusions: Compared with the USA literature, ANH is practised less in The Netherlands. This practice conforms to the prevailing treatment policy endorsed by the Dutch Association of Nursing-Home Physicians. In starting nutrition and/or hydration, an agreement about the (limited) duration of ANH is generally made, and the NHPs generally involve relatives and nurses in the decision-making process. Almost always, all parties involved agreed with decisions taken.

The article deals with the findings of the complex estimate of the new synbiotic product "Life Harmony" to treat acute intestinal infection among children. The authors show that application of this product, containing B. bifidum, B. longum and L. casei strains, in the diet therapy of the acute intestinal infections of "the watery" type among children contributes to the reduction of the duration of anorexia, flabbiness and diarrhea syndrome, as well as provides a complete recovery of the intestinal microflora balance.

The neutropenic diet is an intervention that excludes certain foods, especially fresh fruits and vegetables, from the diets of pediatric oncology patients to reduce infection rate. The purpose of this study was to demonstrate a safe and feasible methodology to evaluate the infection rate in pediatric cancer patients randomized to the neutropenic diet or to Food and Drug Administration (FDA)-approved food safety guidelines. Pediatric oncology patients receiving myelosuppressive chemotherapy were randomized to the neutropenic diet or to FDA food safety guidelines and followed through one chemotherapy cycle. The primary outcome was febrile neutropenia. Secondary outcomes were adherence and diet tolerability. Nineteen patients were enrolled. Four patients on each diet arm developed febrile neutropenia. The adherence rate was 94% for the neutropenic diet and 100% for the food safety guidelines. Although patients were able to tolerate both diets, there was more reported difficulty adhering to the neutropenic diet. Infection rates for children with cancer on the neutropenic diet were similar to those for patients following food safety guidelines. The results of this study suggest that a larger randomized trial to determine the effectiveness of food safety guidelines in minimizing the risk of food borne infection is safe and feasible in children with cancer.

Nutritional status has been indicated as a contributing factor to age-related dysregulation of the immune response. Vitamin E, a lipid-soluble antioxidant vitamin, is important for normal function of the immune cells. The elderly are at a greater risk for vitamin E intake that is lower than recommended levels. Vitamin E supplementation above currently recommended levels has been shown to improve immune functions in the aged including delayed-type hypersensitivity skin response and antibody production in response to vaccination, which was shown to be mediated through increased production of interleukin (IL)-2, leading to enhanced proliferation of T cells, and through reduced production of prostaglandin E(2), a T-cell suppressive factor, as a result of a decreased peroxynitrite formation. Vitamin E increased both cell-dividing and IL-producing capacities of naive T cells, but not memory T cells. The vitamin E-induced enhancement of immune functions in the aged was associated with significant improvement in resistance to influenza infection in aged mice and a reduced risk of acquiring upper respiratory infections in nursing home residents. Further studies are needed to determine the signaling mechanisms involved in the upregulation of naive T-cell function by vitamin E as well as the specific mechanisms involved in reduction of risk for upper respiratory infections.

Objective: Critical illness is associated with the generation of oxygen free radicals and low endogenous antioxidant capacity leading to a condition of oxidative stress. We investigated whether supplementing critically ill patients with antioxidants, trace elements, and vitamins improves their survival., Methods: We searched four bibliographic databases from 1980 to 2003 and included studies that were randomized, reported clinically important endpoints in critically ill patients, and compared various trace elements and vitamins to placebo., Results: Eleven articles met the inclusion criteria. When the results of all the trials were aggregated, overall antioxidants were associated with a significant reduction in mortality [Risk Ratio (RR) 0.65, 95% confidence intervals (CI) 0.44-0.97, p=0.03] but had no effect on infectious complications. Studies that utilized a single trace element were associated with a significant reduction in mortality [RR 0.52, 95% CI 0.27-0.98, p=0.04] whereas combined antioxidants had no effect. Studies using parenteral antioxidants were associated with a significant reduction in mortality [RR 0.56, 95% CI 0.34-0,92, p=0.02] whereas studies of enteral antioxidants were not. Selenium supplementation (alone and in combination with other antioxidants) may be associated with a reduction in mortality [RR 0.59, 95% CI 0.32-1.08, p=0.09] while nonselenium antioxidants had no effect on mortality., Conclusions: Trace elements and vitamins that support antioxidant function, particularly high-dose parenteral selenium either alone or in combination with other antioxidants, are safe and may be associated with a reduction in mortality in critically ill patients.

Immune-enhancing diets contain nutrients that have putative benefits, including arginine, (n-3) fats, glutamine, nucleotides, and structured lipids. Although under most circumstances the systemic inflammatory response is beneficial to the host, improving the eventual outcome of injury, infection, or inflammation, excessive proinflammation (leading to cardiac, hepatic, and mitochondrial dysfunction) or excessive counterinflammation (leading to immune depression) can worsen outcome. In critically ill septic patients, the synthesis of arginine can be exceeded by its catabolism to nitric oxide (NO) and urea, rendering arginine conditionally essential. In patients with sepsis, increased production of NO increases serum nitrite and nitrate levels, whereas levels in patients with trauma and trauma with sepsis are lower than in controls. In septic patients, supplemental arginine might further increase NO levels and be potentially harmful through excessive proinflammation. However, administration of increased amounts of arginine might improve immune function in surgical and trauma patients by increasing NO production in macrophages. When the diet provides at least 1 g of the (n-3) fatty acids eicosapentaenoic and docosahexaenoic acid combined, 2-series eicosanoids (prostaglandins, prostacyclins, thromboxanes) are replaced partially by 3-series eicosanoids, and 4-series leukotrienes are replaced partially by 5-series leukotrienes that are less proinflammatory. Thus, the effects of arginine and (n-3)-fat supplementation might be expected to be complementary-arginine might improve cytokine and NO production in patients with immunodepression, whereas (n-3) fats might be beneficial when there is excessive proinflammation, particularly when supplemental arginine is supplied, by reducing cytokine-induced eicosanoid production.

Immunonutrition contains nutritional elements which generally carry a positive effect on the immune system when given in large amounts. The main nutrients included in immunonutrition are: L-arginine, L-glutamine, nucleotides, and polyunsaturated fatty acids. Patients fed with immunonutrition had less infectious complications, were mechanically ventilated for shorter periods of time, and their hospitalization period was shorter. Mortality rates were generally not improved. In 2001, the U.S. Summit on Immune-Enhancing Enteral Therapy listed groups of patients who would benefit from immunonutrition. The article includes these recommendations. In conclusion, physicians should familiarize themselves with the issue of immunonutrition and consider using it in specific groups of hospital patients.

With advancing age there is a progressive decline in immune responses although this is not inevitable. The impairment in immunocompetence is noticeable as early as 35-40 years in many individuals. At the same time, some persons even in the 80s may show a vigorous immune system comparable with that of the young adult. Nutrient deficiencies are frequent in older populations. A variety of nutrients are affected: zinc, iron, beta-carotene, Vitamins B6, B12, C, D and E, ad folic acid. The causal interaction between nutritional deficiencies and impaired immunity has been known in children; a similar relationship has been postulated in the elderly. In the last 25 years, many studies employing different designs have examined the role of diet, nutritional status, and nutrient supplements in the immune responses of older individuals. Some nutrients, for example zinc and Vitamin E, have been shown to increase selected immune responses but have not been beneficial in terms of reduction in infectious morbidity. A growing consensus indicates that the use of a multinutrient containing optimum amounts of essential trace elements and vitamins is likely to result in enhanced immune responses and reduction in the occurrence of common infections. These findings have considerable fundamental, clinical and public health significance.

Older adults are at risk for malnutrition, which may contribute to their increased risk of infection. Nutritional supplementation strategies can reduce this risk and reverse some of the immune dysfunction associated with advanced age. This review discusses nutritional interventions that have been examined in clinical trials of older adults. The data support use of a daily multivitamin or trace-mineral supplement that includes zinc (elemental zinc, >20 mg/day) and selenium (100 microg/day), with additional vitamin E, to achieve a daily dosage of 200 mg/day. Specific syndromes may also be addressed by nutritional interventions (for example, cranberry juice consumption to reduce urinary tract infections) and may reduce antibiotic use in older adults, particularly those living in long-term care facilities. Drug-nutrient interactions are common in elderly individuals, and care providers should be aware of these interactions. Future research should evaluate important clinical end points rather than merely surrogate markers of immunity.

Objectives/hypothesis: Malnutrition is a significant risk factor for postoperative infections in patients undergoing oncologic surgery. This study was undertaken to determine if perioperative nutritional supplementation with an immune-enhancing formula is superior to standard formula in the prevention of postoperative infectious complications., Study Design: This was a prospective, randomized, double-blind trial comparing perioperative nutritional supplementation with Impact and standard nutritional formulas., Methods: Following stratification, 136 patients undergoing oncologic head and neck surgery were randomly assigned to one of four treatment groups: preoperative/postoperative Impact, postoperative Impact, preoperative/postoperative standard formula, and postoperative standard formula. Outcome measures included laboratory evaluations of nutritional status, infectious and wound healing complications, and duration of hospitalization. Statistical analysis was performed using chi2 or two-tailed Fisher Exact Tests, when appropriate., Results: Intent-to-treat (P = .02) and actual therapy (P = .04) analyses revealed a significant decrease in the incidence of postoperative infectious complications (all sites) in patients who received Impact. There was no significant difference in wound healing problems or duration of hospitalization. Postoperative measures of nutrition status demonstrated a higher serum albumin (P = .05) in patients who received Impact compared with standard formula., Conclusions: Compared with standard formula, perioperative nutritional supplementation with Impact significantly reduced the incidence of infectious complications. The length of hospitalization was significantly prolonged in patients with postoperative infections, suggesting potential cost savings with the use of immune-enhancing formulas such as Impact.

Nutritional support of the critically ill or postoperative pediatric patient continues to develop as a clinical science in the face of technologic, pharmacologic, and nutritional science advances. For ethical and logistical reasons, however, clinical trials of new technologies and interventions often are performed first in adult subjects, and the pediatric intensivist and nutritionist are thereby left to draw conclusions from this literature. This review summarizes recent developments in the clinical nutrition literature concerning the nutritional care of intensive care unit patients, emphasizing experience with pediatric patients when possible. The central role of estimating energy requirements in the intensive care unit, the development of enteral formulas with nutritional as well as possible immunologic properties, the use of anabolic hormones to attenuate the catabolic response to illness, the concept of "conditionally essential" amino acids, and the propensity to use the parenteral route of nutrition when the enteral route is still available are discussed. Future directions in nutritional support, including the development of nutritional pharmacotherapy, are also considered.

Advances in the understanding of the interrelationship between immunology and nutrition indicate that immune dysfunction in critically ill patients is linked with nutrient deficiency and abnormal acute-phase response to illness. Immune dysfunction requires special nutrition therapy and metabolic support; immunoregulation by nutrition manipulation may lead to specific immunotherapies for defined groups of patients. The success of dietary strategies must be measured not only by metabolic indexes but also by effects on immune function. The health profession must combat immune dysfunction and inflammation for the sick and frail patients under its care.

An increasingly large number of dietary components have been found to alter immune system function and, therefore, may be considered to have a pharmacologic effect (pharmacologic nutrition). Those dietary factors which have already been shown to influence outcome by producing a pharmacologic effect rather than correcting or preventing a simple deficiency include proteins (both type and amount), arginine, glutamine, omega-6 and omega-3 fatty acids, short-chain fatty acids, the metals iron and zinc, and the vitamins E, C, and A. Therapeutic outcome has already been influenced by dietary therapy (pharmacologic nutrition) in patients after burn injury or who have vascular diseases, and in experimental animals for the prevention of gut origin sepsis, the prevention and treatment of infection, prevention and development of secondary lesions in autoimmune diseases, augmentation of immunosuppression in transplantation, and in the treatment of cancer. Nutritional therapy using disease-specific formulations or supplements is an old idea now undergoing rapid evolution to increasing importance for successful therapeutic outcome.

This is a brief review of the observed hormonal alterations following trauma and sepsis. The major changes noted in the metabolic status of the stressed patient have been characterized by deranged carbohydrate metabolism, altered metabolic rate as measured by oxygen consumption and increased ureagenesis. Each of these phenomena are regulated to a large extent by the specific hormonal profile of the patient. Failure of insulin and growth hormone production have been associated with glucose intolerance, excessive urinary nitrogen loss and a fatal outcome. Glucagon, cortisol and catecholamines exhibit sustained elevation and have been associated with increased metabolic rate and excessive ureagenesis. These changes are usually self limited following trauma but will persist if the patient enters a septic phase. The use of specific nutritional support, namely hypertonic glucose versus a balanced fat emulsion system in the face of sepsis is considered.

Eighty-seven patients were entered into a randomized, prospective, double-blind, six-center study to evaluate the effect of amino acid loading and a formula that was branched chain enriched (50%) on nitrogen retention in metabolic stress. The patients had varying levels of metabolic stress (0-3) after major surgery, polytrauma, or surgical sepsis. The study was isocaloric and isonitrogenous and lasted for 7 days. The patients received either a standard amino acid formula (SAA) (Travasol) or a 50% branched chain enriched formula that was equimolar, leucine, isoleucine, and valine (MAA) (Travasol + Branchamin concentrate) at a dose of 1.0-2.0 g/kg/day in a fixed ratio with 114 glucose calories per gram of nitrogen administered. The nitrogen retention was proportionate to the nitrogen (and, therefore, caloric) load in both groups. The MAA group, however, had better nitrogen retention, reached nitrogen equilibrium at a lower dose of amino acids, and had less urinary nitrogen excretion per gram of nitrogen administered. Since the groups were isonitrogenous and the calorie to nitrogen ratios were fixed, it appears that nitrogen equilibrium in surgical stress is proportionate to the amino acid load over a range of 0.05-0.4 g/kg/day of nitrogen; and that MAA are more efficient at inducing nitrogen retention and a reduction in urea excretion. These effects on nitrogen retention were more significant at level 2 stress or greater. At these higher stress levels, a dose of 2 +/- 0.2 g/kg/day of MAA seemed most efficient in promoting nitrogen retention.

Protein malnutrition is one of the principal factors relating to morbidity and mortality during infection. Nutritional assessment is required to determine the severity of depletion and degree of hypermetabolism affecting this patient population. Simple anthropometric and 24-hr urine collections together with routine biochemical analyses can readily allow clinical assessment to occur. Optimal utilization of dietary intake is dependent on the degree of protein catabolism and energy expenditure in excess of the basal energy requirement. Urinary nitrogen excretion in 24-hr on a protein-free diet is especially valuable in aiding this assessment. This analysis together with urinary creatinine which provide important estimates of lean body mass and serial measures will allow estimates of the progression of malnutrition. In infected adults optimal protein intake to produce positive nitrogen balance is 1.5 to 2.0 g of protein/kg per day. This would appear to reflect the fact that 16% of the caloric expenditure comes from protein sources during injury. Since this value is approximately twice that seen during nonstress, the reutilization of body protein would appear to be decreased. Careful appreciation of the metabolic response during infection is necessary prior to consideration of the nutritional support plan. Knowledge regarding the phase of infection, severity of nutritional depletion, and degree of hypermetabolism will influence the attainable goals of nutritional support.

Previous studies showed that dopamine and norepinephrine levels in rat brain are reduced following stress and that rats fed supplemental tyrosine do not exhibit these reductions. We hypothesized that dietary supplementation with tyrosine would enhance resistance to acute hemorrhagic shock and sepsis by increasing substrate (tyrosine) availability for catecholamine synthesis. Rats were fed either a standard rat chow (6.8 g of tyrosine per kilogram of chow), which supports normal growth, fertility, and longevity, or the same chow supplemented with 10 g of tyrosine per kilogram of chow. Seven days later, the rats underwent cecal ligation and perforation while under intraperitoneal pentobarbital anesthesia. There was a significant increase in survival in the tyrosine-supplemented group. Similarly, in another experiment, tyrosine-supplemented rats were able to tolerate acute fulminant hemorrhagic shock better than were nonsupplemented control animals.

A series of eight septic patients was provided varying levels of beef fibrin protein hydrolysate by central vein in the presence of adequate calories for evaluation of nitrogen retention under septic conditions. The mean nitrogen intake to achieve nitrogen equilibrium was 240 mg/kg of body wt per day. This represents a 40% increase over that required to produce nitrogen equilibrium in normal adults. The mean caloric intake of these patients was 43.3 kcal/kg of body wt per day. The calorie to nitrogen ratio based on the above intake was calculated to be 180:1. In order to utilize effectively calorie to nitrogen ratios in the nutritional care of patients, it is suggested that ratios be standardized using daily total coloric expenditures. Correcting the mean measured resting calorie expenditures of these patients for minimal daily activity, a caloric to nitrogen ratio of 138:1 was obtained. The plasma amino acid ratios in these septic patients confirm the finding that valine and phenylalnine are limiting amino acids in a beef fibrin hydrolysate at infusion levels below 240 mg of N/kg of body wt per day. Analysis of the urinary excretion of total nitrogen, urea, and amino acids in two patients suggests that 30 to 50% of the infused peptides of a beef fibrin hydrolysate are lost in the urine in these septic patients.

Total parenteral nutrition has been used in the treatment of more than 100 children with gastrointestinal illnesses, including 90 under the age of 6 months. The incidence of complications has been reduced markedly as experience was acquired. Total parenteral nutrition has been especially valuable in patients with intractable diarrhea syndrome and it has been used successfully in the management of infants with overwhelming systemic infections.

Adequate nutritional support for the critically ill patient has evolved over the past 150 years from a time when starvation was accepted practice for patients with fever. Three to four thousand calories and other essential nutrients can now be safely provided each day to patients with infection or other critical illness. Nutrients may be provided in meals, administered by specialized enteral feedings, or infused intravenously. Nutrient mixtures with a high proportion of carbohydrate and protein appear the best dietary therapy to maintain body protein and support other organ systems and and cellular functions. New products and formulas offer the physician a wide variety of techniques for providing adequate nutrition to all patients with critical illness.