CH-NES-011a_Cover.qxd:Layout 1 6/23/08 3:11 PM Page 2 ISSN 1815-7262 Science supporting better nutrition 2008 • Volume 4, Issue 2 In this issue The gut as an immune organ Clinical nutrition abstracts Highlights of Clinical Nutrition Week 2008 CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:12 PM Page 1 CLINICAL NUTRITION HIGHLIGHTS Science supporting better nutrition 2008 • Volume 4, Issue 2 Feature article 2 The gut as an immune organ Yoshifumi Sano, Joshua L Hermsen and Kenneth A Kudsk Clinical nutrition abstracts Cancer Cardiovascular disease Critical care nutrition Diabetes Gastrointestinal disorders Hepatic disease Nutrition support Pediatrics Highlights of Clinical Nutrition Week 8 8 9 9 12 12 13 13 16 18 10-14 February 2008 Conference calendar Sponsored as a service to the medical profession by the Nestlé Nutrition Institute. Editorial development by CMPMedica. The opinions expressed in this publication are not necessarily those of the editor, publisher or sponsor. Any liability or obligation for loss or damage howsoever arising is hereby disclaimed. Although great care has been taken in compiling and checking the information herein to ensure that it is accurate, the editor, publisher and sponsor shall not be responsible for the continued currency of the information or for any errors, omissions or inaccuracies in this publication. © 2008 Société des Produits Nestlé S.A. All rights reserved. No part of this publication may be reproduced by any process in any language without the written permission of the publisher. CMPMedica Pacific Ltd Unit 901-903, 9th Floor, AXA Centre, 151 Gloucester Road, Wan Chai, Hong Kong T +852 2559 5888 F +852 2559 6910 [email protected] www.cmpmedica.com 24 Feature article CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd { 6/23/08 3:12 PM Page 2 The gut as an immune organ Yoshifumi Sanob MD, PhD, Joshua L Hermsenb MD and Kenneth A Kudska,b MD a Veterans Administration Surgical Services, William S Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA b Department of Surgery, University of Wisconsin-Madison College of Medicine and Public Health, Madison, Wisconsin, USA Source of support: NIH grant R01 GM53439 Introduction } overall mucosal-associated lymphoid tissue (MALT). Because of, or more likely as a result of, this arrangement, all mucosal surfaces of Humans share the environment with huge numbers of micro- the body are immunologically linked. This can be demonstrated organisms. According to Whitman et al. 4–6 x 10 prokaryotic clinically, as immunization at one mucosal surface provides anti- cells exist on earth.1 All animals ingest food and water for energy, body against that antigen at other non-immunized mucosal sites.5 30 while living in contact with a significant bacterial burden in nearly Maintenance of mucosal immune integrity minimizes or every environment. Food is usually clean in industrialized cultures eliminates microbial invasion and infection. Since the gut contains but may not be in non-industrialized parts of the world. Regardless the largest collection of mucosal immune tissue/cells, the GALT, it of the food source and/or processing, the gut processes the food is not surprising that integrity of mucosal immunity depends upon and water in our daily life for digestion and absorption. The gut the type and route of nutrition. Clinically, trauma patients fed also functions as an immune organ to protect us from any ingested, parenterally (without any enteral stimulation) become more potentially pathogenic bacteria. susceptible to infectious complications than injured patients fed A single layer of epithelium lines the gut. Beneath this layer enterally.6-9 Current recommendations in critical care call for early lies a complex immunologic mucosal defense system, the mucosal enteral nutrition support as tolerated by the intestine.10 This review immune system. Mucosal immunity and mucosal immune system discusses some of the major mechanisms involved in providing components exist not only in the gut but also extend and interact innate and adaptive gut and mucosal immunity, and the influence with other mucosal/epithelial surfaces in extra-intestinal sites such of type and route of nutrition on this system. as the respiratory tract, the genitourinary tract, and the mammary and salivary glands. The gut is immunologically interconnected Innate mucosal immunity with these extra-intestinal sites but is considered the ‘command Intestinal innate mucosal immunity protects the host against CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 center’ and hub of mucosal immunity.2,3 2 The mucosal immune system consists of innate and adaptive potential microbial pathogen invasion. Features of the innate immune mechanisms. Innate mechanisms are ‘built in’ to the struc- immune system include physical barriers such as tight junctions ture and/or function of the gut and are not aimed specifically between epithelial cells, intraluminal secretions, gastric acid, against any individual pathogen. The adaptive arm of mucosal digestive enzymes, glycocalyx and mucus proteins, defensins, immunity generates immunoglobulin A (IgA) at mucosal surfaces. lysozyme, lactoferrin and physiomechanical barriers such as IgA provides antigen-specific, antibody-mediated immunity at peristalsis (Figure 1).11,12 mucosal body-environment interfaces through immune exclusion. The basic tubular structure of the gastrointestinal (GI) tract IgA binds to surfaces of potential pathogens, preventing their consists of epithelial cells, a connective tissue-derived lamina adherence to, and invasion through, the epithelial barrier. propria (LP) layer containing a large quantity of immunocytes, and In mice, at least 80% of total body immunoglobulin- a purely muscular layer enclosed in a thin serosal covering. A secreting cells are located in the small intestine. These simple columnar epithelium lines the tube from the stomach to immunoglobulin-producing plasma cells are programmed to rectum. This thin, single-cell thickness layer separates us from the produce predominately IgA. The plasma cells, co-localized T environment and works in conjunction with other complex, co- lymphocytes (CD4+ predominately) and other immune cells such as ordinated protective strategies. The mucosal epithelia adhere dendritic cells, constitute the gastrointestinal-associated lymphoid through cell-to-cell junctions primarily via tight junctions. Tight tissue (GALT). GALT comprises a significant portion of the body’s junctions maintain epithelial cell orientation as specific proteins 4 CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:12 PM Page 3 such as claudin and occludin cooperate to form these tight junctions between adjacent epithelial cells. These junctions act as an Figure 1. Schema of epithelial action against microbes in gut innate immunity innate paracellular barrier to microorganMicrobes ingested Stomach ions and solutes. Small intestine Large intestine 13 Mucus/glycocalyx Each part of the GI tract has specific defenses against bacteria. The stomach secretes gastric acid and digestive enzymes to kill most swallowed microorganisms. Gastric acid Bile Pancreatic juice α-defensins Lysozyme Group II A PLA2 Only a few organisms, extremophiles (such TLRs NODs as acidophiles), survive the strong acid pH Parietal cells (~2.0) in the stomach. Just distal to the 14 Papilla of Vater Paneth cells β-defensins Columnar epithelial cells Mucin Trefoil factor Feature article isms while controlling passive transport of Cathelicidins Goblet cells stomach, bacteriostatic bile and pancreatic Inflammatory or immune response juices also hinder bacterial colonization of the upper GI tract. 15 Digestion and absorption of nutri- , commensal microflora; , damaged microbe; PLA, phospholipase A; TLR, Toll-like receptor , ingested microbe; NOD, nucleotide-binding oligomerization domain; ents occurs in the jejunum and ileum. Its huge surface area of approximately 300 m2 is also covered by a covered by the dense overlying mucus, remains a generally sterile single-cell layer of epithelium. Because of its relative delicacy and environment.21 critical function, a more precise immunologic innate mechanism Certain bacteria protect the host. Commensal microflora, with which the host has a symbiotic relationship, are a constituent protects this region of the GI tract. Structurally, the intestinal epithelium forms villi and crypts of health. But how does the body sense which bacteria are that overlie stem cells capable of differentiating into epithelial commensal – and normal – and which are potential or overt cells. Two specialized intestinal epithelial cells, goblet and Paneth pathogens? Intestinal epithelial cells possess and rely upon several cells, play important roles in providing innate immunity. These cells kinds of sensors to make such determinations. Pattern recognition secrete nonspecific antimicrobial peptides and bacteriolytic receptors (PRRs), such as Toll-like receptors (TLRs) and enzymes. Accordingly, Paneth cells possess an abundance of cyto- nucleotide-binding oligomerization domain (NOD) proteins, detect plasmic secretory granules. Most of these antimicrobial molecules conserved microbial molecules called pathogen-associated are cationic to facilitate binding to anionic bacterial surface poly- molecular patterns (PAMPs). When stimulated by PAMPs, the mers. Paneth cells produce α-defensins, which damage microbial PRRs activate inflammatory or immune responses through cell membranes,11,18 lysozymes, which hydrolyzes peptidoglycans on cellular signaling systems such as nuclear factor, NFκB.22,23 16 17 bacterial cell walls, and group IIA phospholipase A2 (PLA2), which Through these different mechanisms innate immunity pres- disrupts cell integrity through rapidly degrading bacterial ents a standardized, stalwart defense against pathogenic disruption membrane phospholipids. Paneth cells are also found near collec- of homeostasis in the gut, one of our most vital and vulnerable tions of epithelial stem cells at the bottom of epithelial crypts. This organ systems. arrangement seems designed to let stem cells, which are critical for continued regeneration of the epithelium, specifically guard against Adaptive mucosal immunity bacterial attack and injury. Goblet cells produce mucus constituent Oral vaccination with oral polio vaccine proved the existence of surface provides protection by creating a significant physical barrier significant, active gut involvement in mucosal adaptive immune to invasion. Goblet cells also produce trefoil factor, which is responses. Observations that immunization induced production of involved in epithelial growth and repair. anti-polio secretory IgA in the feces by oral, but not parenteral, 20 The intestinal columnar epithelial cells themselves produce immunization highlighted a key gut function in generating an nonspecific antimicrobial weapons against pathogenic micro- immune response; ie, the gut ‘sees’, captures and initiates immune organisms that threaten the integrity of the intestinal epithelium. responses against luminal antigen.24 In the United States oral polio β-defensins are expressed by epithelial cells throughout the intes- vaccine is no longer used, not because it is ineffective, but because tine, while cathelicidins are produced by epithelial cells lining the the incidence of spontaneous polio from killed virus vaccination is colon. Both of these antimicrobial molecules provide bactericidal now lower than the risk of developing polio from mutation of live defenses by disrupting bacterial membrane integrity.11 As a result of oral virus vaccination. these multiple innate defense strategies, intestinal microflora Adaptive mucosal immune responses generate plasma cells remain in the intestinal lumen, while the direct epithelial surface, which produce secretory IgA for antigenic specific antibody- CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 proteins.19 The robust mucus layer that overlies the epithelial 3 CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM Page 4 specialized endothelium found within PPs. Cognate antigen Figure 2. Peyer’s patch presented to the naive lymphocytes by DCs or other antigenpresenting cells activates them against that antigen.25,35 Changes in cell surface adhesion molecules identifies them as activated lympho- Feature article cytes. Activated cells maintain L-selectin but upregulate α4β7 and lymphotoxin (LT) αβ expression.36-38 Most activated B cells switch immunoglobulin class and differentiate to IgA-producing cells; naive T cells mature into effector/memory T cells. During this time lymphotoxin β receptor (LTβR, the receptor activated by LTαβ ligands) expressed on DCs and stromal cells in the PPs stimulates more MAdCAM-1 expression to recruit more naive cells.39 LTβR mediated defenses at epithelial surfaces. Division of the mucosal signaling is involved in PP organization prenatally as well.40 In vivo immune system into inductive and effector sites is based upon the experiments which blockade LTβR function affirm its role in adap- function of the immune cell complement at specific locations. tive mucosal immune function.41 After activation in PPs, these Small intestinal Peyer’s patches (PPs) are the prototypical inductive lymphocytes migrate via efferent lymph channels, mesenteric lymph site and the LP under all mucosal surfaces serves as the effector site nodes (MLN) and the thoracic duct (TD) into the blood stream. (Figure 2). Maturation and further differentiation occurs between PPs and the 2,3,25 systemic circulation as evidenced by the increasing percentage of Inductive sites IgA-forming B cells at each site (PP < MLN < TD).42 Cells may Adaptive immune responses start at inductive sites such as PPs and remain in systemic circulation until called back to an effector site. isolated lymphoid follicles (ILFs) in the small intestine. PPs and 26 ILFs consist of a specialized follicle-associated epithelium (FAE) Effector sites including microvillus (M) cells, dendritic cells (DCs) within the Circulating sensitized lymphocytes home to LP effector sites subepithelial dome area and B lymphocyte follicles possessing through interactions between LTβR located on stromal cells in the germinal centers (Figure 3). PPs are a major inductive site for LP,38 endothelial-expressed MAdCAM-1 on the HEV, and a vari- mucosal immune responses and are formed independent of anti- ety of tissue-specific chemokines.43 These non-naive lymphocytes gen stimulation before birth. ILFs on the other hand, appear after are LTαβ+ which interacts strongly with stromal cells expressing birth, are dependent on antigenic stimulation and function similar LTβR. The α4β7 ligand interacts with MAdCAM-1 (Figure 4).34 to PPs to recognize antigen and initiate a mucosal immune The complete and exact mechanisms of homing to any mucosal site response. remain under active investigation; however, this process is multi- DCs underlying FAE take up luminal antigens, such as whole factorial and very site specific. In the gut, retinoic acid, a vitamin A pathogenic microorganisms or individual peptide antigens. The metabolite, enhances expression of α4β7 on T cells during activa- DCs take the antigen up through M cells or directly through tion and ‘imprints’ them to preferentially home back to the gut.44 dendrites projecting into the lumen. M cells possess several char- Following recruitment to effector sites, B cells terminally acteristics that enable them to effectively capture and transcytose differentiate into IgA-producing plasma cells, encouraged by the 27 antigen. A thinner mucus layer covers their apical surface because the FAE contains fewer Figure 3. Adaptive mucosal immunity: Inductive site goblet cells than non-FAE epithelial areas. M M cell cells are shorter than normal columnar epithelium and have smaller and irregular IEL microvilli, specific receptors against common DC CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 antigenic epitopes, and receptors for antigen 4 LTβR Antigen presentation opsonized by secretory IgA.20-23 M cells and the surrounding FAE capture and present antigen to the PPs, specific mechanisms to attract naive lymphocytes. 28-32 HEV Naive T/B α4β7++ T/B LTβR MAdCAM-1 α4β7+ L-selectin ++ Sensitized T/B PP L-selectin ++ LTαβ+ Naive lymphocytes bearing the ligands, Lselectin and α4β7, are recruited into the PP MLN through their interaction with the receptor mucosal addressin cellular adhesion molecule1 (MAdCAM-1) expressed on high endothelial venules (HEV).33,34 The HEV is a Effector sites Thoracic duct Blood stream DC, dendritic cell; HEV, high endothelial venule; IEL, intraepithelial lymphocyte; LTβR, lymphotoxin β receptor; MAdCAM-1, mucosal addressin cellular adhesion molecule-1; MLN, mesenteric lymph node, PP, Peyer’s patch CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM Figure 4. Adaptive mucosal immunity: Effector site Page 5 Figure 5. Cytokines in Th1 and Th2 subset Th1 Secretory IgA Cytokine Inflammatory plgR Th-cytokines Th2 Dimeric IgA B cells Cytokine Plasma cell βR -1 LT CAM d MA LTαβ+ Inflammatory TGF-β IL-4 IL-5 IL-6 IL-10 L-selectin ± Sensitized T/B X X X X IgA-plgR complex T cells α4β7++ Anti-inflammatory Feature article INF-γ TNF-α IL-1 IL-2 LT, lymphotoxin; LTβR, lymphotoxin β receptor; MAdCAM-1, mucosal addressin cellular adhesion molecule-1; plgR, polymeric immunoglobulin receptor X Anti-inflammatory X X X X X cytokine environment provided by Th2 lymphocytes.35,45,46 lower intestinal tract (Figure 6). This symbiotic population Cytokines drive secretory IgA production and provide an integral prevents overgrowth and invasion of pathogenic bacteria through component of adaptive mucosal immunity (Figure 5). mucosal surfaces. The total number of normal intestinal Transforming growth factor-β (TGFβ), along with interleukin-4, microflora in the human approximates 1014 organisms, with -5, -6, and -10 (IL-4, IL-5, IL-6, IL-10), belong to the family of T bacterial densities within the stomach/duodenum, jejunum/ileum helper type 2 (Th-2) cytokines which stimulate IgA production. T and large intestine of 101–103, 104–107 and 1011–1012 colony form- helper type 1 (Th-1) cytokines such as interferon-γ (IFNγ) counter- ing units/mL respectively.55 Most intestinal commensal microflora balance their action by inhibiting IgA production.46,47 The mutual are anaerobic due to low oxygen tension in the gut lumen. action of T and B cells, modulated largely by cytokine balance, Facultative anaerobes colonize the more proximal gut due to regulate production and transport of secretory IgA. slightly higher oxygen levels, while obligate anaerobes colonize the Dimeric IgA produced by plasma cells in the LP binds to the distal bowel.56,57 Although comprehensive culture and identifica- polymeric immunoglobulin receptor (pIgR) expressed on the baso- tion techniques for all commensal flora do not exist, the estimated lateral surface of epithelial cells.48,49 The IgA-pIgR complex is number of commensal bacterial species in humans is ≥500.58 endocytosed and transported from basal to apical within the The host mucosal immune system requires tolerance to these epithelial cell. After reaching the apical surface, the IgA-bound bacteria to co-exist, since the host recognizes intestinal microflora extracellular domains of the pIgR molecule (known as secretory as foreign microorganisms. The host possesses a system of toler- component), are cleaved as one unit from the pIgR protein and ance against intestinal commensal microflora to maintain the released into the lumen as secretory IgA. The presence of secretory ‘normal’ mucosal health status. TLRs are actively involved in sensing intestinal microflora enhancing both the stability and effectiveness of IgA as a pathogen but must be counterbalanced to not react against commensal neutralizer.50,51 Free secretory component is also released onto the species. Subtypes of TLRs include TLR2, which recognizes pepti- mucosal surface following transcytosis of ‘empty’ pIgR (pIgR not doglycan and lipotecoic acids, and TLR4, which is directed against bound to dimeric IgA). Free secretory component also neutralizes lipopolysaccharide. Both are expressed weakly in the intestine antigen through independent binding action directed against select where they are likely to encounter many commensal organisms antimicrobial peptide epitopes.52,53 Moreover, commensal and path- bearing such markers. TLR downregulating proteins like Toll- ogenic microorganisms upregulate expression of pIgR by means of interacting protein on epithelial cells act to balance TLR activity sensors of the innate immune system, such as TLRs.54 Therefore, and quiescence to maintain tolerogenic balance.22,59 Regulatory T synergism and cooperation between adaptive and innate mucosal cells under the direction of dendritic cells attenuate TLR signaling immune systems enables more robust and rapid protection.48 as well.60 Intestinal microflora health by supplying nutrients to intestinal epithelial cells. Besides the innate and adaptive mucosal immune strategies, the Commensal microflora ferment undigestable dietary fibers and presence of intestinal commensal microflora is a co-factor impact- starches in food in the lower intestine yielding fatty acid products. ing the gut as an immune organ. Commensal microflora inhabit These fatty acids stimulate blood flow and electrolyte uptake in the entire gut, with the largest burden of microorganisms in the the large intestine.61,62 Intestinal commensal microflora directly promote gut 55 CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 component protects secretory IgA from proteolytic degradation 5 CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM Page 6 into the PP, drops within hours of stopping enteral Figure 6. Commensal microflora of the digestive system stimulation due to drops in LTβR levels (which control MAdCAM-1 expression).66-68 As a result of reduced cell entry into the system, lymphocyte Feature article numbers drop quickly in the PP and LP,69 as well as in the lung. This effectively reduces the number of cells present to produce IgA by over 60%. Simultaneously, the remaining T cells decrease production of Th-2 cytokines such as IL-4 and IL-10, which are the key cytokine stimulators of IgA production.70 In addition, expression of intestinal pIgR, the principal protein in IgA transport from the LP to the gut lumen also decreases without enteral feeding.71 As a cumulative consequence of these changes associated with decreased enteral stimulation, levels of IgA drop at both intestinal and respiratory mucosal surfaces, rendering them susceptible to microbial invasion.70,72 The drops in mucosal IgA due to reduced Adapted from Simon GL, Gorbach SL. Intestinal flora in health and disease. Gastroenterology 1984;86:174-193. enteral stimulation has functional implications for animals. These mice become unable to effectively Although the gut remains sterile throughout fetal life, bacte- generate new mucosal immune responses to infectious challenges, rial population of the gut begins immediately after childbirth with particularly in the respiratory tract.73 They also cannot maintain initiation of oral intake. The type of diet, hygienic milieu and normal respiratory immunologic defenses against either bacteria medications affect this bacterial population process. Intestinal (in an model of pneumonia) or viral upper respiratory infection, commensal microflora contributes to establishment and develop- which would normally keep them immune from infection by these ment of the mucosal immune system. As stated earlier, PPs first organisms.74,75 However, if animals receive subsequent enteral appear during gestation but grow with exposure to luminal anti- feeding, these defenses return to normal, demonstrating that gens. Experiments in germ-free animals support this notion that PP immune ‘memory’ remains intact, just ineffective without enteral growth requires antigen exposure since these animals generate stimulation. In conjunction with reestablished immunity, re-feed- smaller PPs than normal. However, introduction of intestinal ing also restores MAdCAM-1 levels, and PP and LP lymphocyte microflora into germ-free mice restores normal mucosal immune populations.66,67,76 63 64 parameters.65 Moreover, ILFs, which function within the intestinal The reduction in mucosal IgA has potential clinical implica- epithelial layer like PPs, form only after birth, but not in germ-free tions. Several human studies have demonstrated a protective role of newborns.26 IgA in preventing pneumonia.77,78 Current work in trauma patients is underway to determine whether parenteral feeding impairs Enteral feeding and mucosal immunity airway IgA (similar to that seen in animal models) in efforts to CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 explain the increased incidence of infectious complications demon- 6 Although the gut is the largest immune organ in the body, the type strated in clinical trials.79 It is known that type and route of and route of nutrition alters mucosal immune ‘homeostasis’. nutrition affects commensal intestinal microflora as well. Results from prospective, randomized clinical trials in trauma Parenterally fed patients experience decreases in the number of patient populations support this observation. Severely injured fecal microflora compared with enterally fed patients.80 trauma patients fed via the gut incur significantly less infectious The active variable in these experimental situations is likely morbidity in the form of pneumonia and intra-abdominal abscess the absence of enteral stimulation and not the presence of than individuals fed exclusively parenterally.6-9 Investigative work parenteral nutrition. Mice die after 2–3 days of starvation but using animals exposed to varying types and routes of nutrition parenteral feeding maintains them by eliminating the variable of shows that these variables dramatically influence the mucosal protein/calorie malnutrition. Evidence suggests that as little as immune system and the host’s resistance to infections. 25%–50% of calories supplied via the gut (or as little as ¼ of Mice fed with only parenteral nutrition (PN) experience normal enteral stimulation) suffice to maintain at least some of the significant downregulation of multiple mucosal immune para- ‘enterally fed’ mucosal immune morphology.81 However, such a meters from inductive to effector sites. Levels of MAdCAM-1, the threshold or cutoff point for maintaining functional mucosal crucial ‘gatekeeper’ molecule which attracts naive lymphocytes immunity has not been determined. CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 Conclusions 3:13 PM Page 7 with decreased enteral stimulation indicates not only the GALT, but also the MALT is affected by type and route of nutrition. While the changes in adaptive mucosal immunity and virtue of its massive and nearly constant exposure to environ- commensal microflora induced by decreased enteral stimulation mental antigen at body/world interfaces, constitutes the largest have been explored, the relationship between changes in microflora secondary immune organ in the body. Under normal conditions it and mucosal immune status provides a fertile ground for investi- responds appropriately by producing large amounts (~3 g/day) of gation. Additionally the relationship between enteral stimulation protective antibody predominately in the form of IgA. Enteral stim- and innate mucosal immune measures remain relatively unstudied. ulation seems a key component of maintaining the health of the Finally, because of the known causal relationships between mucosal immune system. 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Trophic and cytoprotective nutrition for intestinal adaptation, mucosal repair, and barrier function. Annu Rev Nutr 2003;23:229-261. Gronlund MM, Lehtonen OP, Eerola E, Kero P. Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery. J Pediatr Gastroenterol Nutr 1999;28:19-25. Shanahan F. The host-microbe interface within the gut. Best Pract Res Clin Gastroenterol 2002;16:915-931. Umesaki Y, Okada Y, Matsumoto S, Imaoka A, Setoyama H. Segmented filamentous bacteria are indigenous intestinal bacteria that activate intraepithelial lymphocytes and induce MHC class II molecules and fucosyl asialo GM1 glycolipids on the small intestinal epithelial cells in the ex-germ-free mouse. Microbiol Immunol 1995;39:555-562. Ikeda S, Kudsk KA, Fukatsu K, et al. Enteral feeding preserves mucosal immunity despite in vivo MAdCAM-1 blockade of lymphocyte homing. Ann Surg 2003;237:677-685. Zarzaur BL, Fukatsu K, Johnson CJ, Eng E, Kudsk KA. A temporal study of dietinduced changes in Peyer patch MAdCAM-1 expression. Surg Forum 2001;52:194-196. Kang W, Gomez FE, Lan J, et al. Parenteral nutrition impairs gut-associated lymphoid tissue and mucosal immunity by reducing lymphotoxin Beta receptor expression. Ann Surg 2006;244:392-399. King BK, Li J, Kudsk KA. A temporal study of TPN-induced changes in gutassociated lymphoid tissue and mucosal immunity. Arch Surg 1997;132:13031309. Wu Y, Kudsk KA, DeWitt RC, Tolley EA, Li J. Route and type of nutrition influence IgA-mediating intestinal cytokines. Ann Surg 1999;229:662-667. Sano Y, Gomez FE, Kang W, et al. Intestinal polymeric immunoglobulin receptor is affected by type and route of nutrition. JPEN J Parenter Enteral Nutr 2007;31: 351-356. Renegar KB, Kudsk KA, Dewitt RC, Wu Y, King BK. Impairment of mucosal immunity by parenteral nutrition: depressed nasotracheal influenza-specific secretory IgA levels and transport in parenterally fed mice. Ann Surg 2001;233:134-138. Johnson CD, Kudsk KA, Fukatsu K, Renegar KB, Zarzaur BL. Route of nutrition influences generation of antibody-forming cells and initial defense to an active viral infection in the upper respiratory tract. Ann Surg 2003;237:565-573. King BK, Kudsk KA, Li J, Wu Y, Renegar KB. Route and type of nutrition influence mucosal immunity to bacterial pneumonia. Ann Surg 1999;229:272-278. Kudsk KA, Li J, Renegar KB. Loss of upper respiratory tract immunity with parenteral feeding. Ann Surg 1996;223:629-635. Janu P, Li J, Renegar KB, Kudsk KA. Recovery of gut-associated lymphoid tissue and upper respiratory tract immunity after parenteral nutrition. Ann Surg 1997;225:707-715. Kress HG, Scheidewig C, Schmidt H, Silber R. Reduced incidence of postoperative infection after intravenous administration of an immunoglobulin A- and immunoglobulin M-enriched preparation in anergic patients undergoing cardiac surgery. Crit Care Med 1999;27:1281-1287. Annane D, Clair B, Mathieu B, et al. Immunoglobulin A levels in bronchial samples during mechanical ventilation and onset of nosocomial pneumonia in critically ill patients. Am J Respir Crit Care Med 1996;153:1585-1590. Kudsk KA, Hermsen JL, Genton L, Faucher L, Gomez FE. Injury stimulates an innate respiratory immunoglobulin a immune response in humans. J Trauma 2008;64:316-323. Schneider SM, Le Gall P, Girard-Pipau F, et al. Total artificial nutrition is associated with major changes in the fecal flora. Eur J Nutr 2000;39:248-255. Wildhaber BE, Yang H, Spencer AU, Drongowski RA, Teitelbaum DH. Lack of enteral nutrition – effects on the intestinal immune system. J Surg Res 2005;123:8-16. CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 1. Whitman WB, Coleman DC, Wiebe WJ. Prokaryotes: the unseen majority. Proc Natl Acad Sci U S A 1998;95:6578-6583. 2. Kudsk KA. Current aspects of mucosal immunology and its influence by nutrition. Am J Surg 2002;183:390-398. 3. Jabbar A, Chang WK, Dryden GW, McClave SA. Gut immunology and the differential response to feeding and starvation. Nutr Clin Pract 2003;18:461-482. 4. van der Heijden PJ, Stok W, Bianchi AT. Contribution of immunoglobulin-secreting cells in the murine small intestine to the total 'background' immunoglobulin production. Immunology 1987;62:551-555. 5. Mestecky J, Lue C, Russell MW. Selective transport of IgA. Cellular and molecular aspects. Gastroenterol Clin North Am 1991;20:441-471. 6. Kudsk KA, Croce MA, Fabian TC, et al. Enteral versus parenteral feeding. Effects on septic morbidity after blunt and penetrating abdominal trauma. Ann Surg 1992;215:503-511. 7. Moore FA, Moore EE, Jones TN, McCroskey BL, Peterson VM. TEN versus TPN following major abdominal trauma – reduced septic morbidity. J Trauma 1989;29:916-922. 8. Moore EE, Jones TN. Benefits of immediate jejunostomy feeding after major abdominal trauma – a prospective, randomized study. J Trauma 1986;26: 874-881. 9. Moore FA, Feliciano DV, Andrassy RJ, et al. Early enteral feeding, compared with parenteral, reduces postoperative septic complications. The results of a metaanalysis. Ann Surg 1992;216:172-183. 10. Heyland DK, Dhaliwal R, Drover JW, et al. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr 2003;27:355-373. 11. Müller CA, Autenrieth IB, Peschel A. Innate defenses of the intestinal epithelial barrier. Cell Mol Life Sci 2005;62:1297-1307. 12. Tlaskalová-Hogenová H, Stepánková R, Hudcovic T, et al. Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett 2004;93:97-108. 13. Anderson JM. Molecular structure of tight junctions and their role in epithelial transport. News Physiol Sci 2001;16:126-130. 14. Fujiwara S. Extremophiles: developments of their special functions and potential resources. J Biosci Bioeng 2002;94:518-525. 15. Hofmann AF, Eckmann L. How bile acids confer gut mucosal protection against bacteria. Proc Natl Acad Sci U S A 2006;103:4333-4334. 16. Radtke F, Clevers H. Self-renewal and cancer of the gut: two sides of a coin. Science 2005;307:1904-1909. 17. Weidenmaier C, Kristian SA, Peschel A. Bacterial resistance to antimicrobial host defenses – an emerging target for novel antiinfective strategies? Curr Drug Targets 2003;4:643-649. 18. Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 2003;3:710-720. 19. Phillips TE. Both crypt and villus intestinal goblet cells secrete mucin in response to cholinergic stimulation. Am J Physiol 1992;262:G327-G331. 20. Kindon H, Pothoulakis C, Thim L, Lynch-Devaney K, Podolsky DK. Trefoil peptide protection of intestinal epithelial barrier function: cooperative interaction with mucin glycoprotein. Gastroenterology 1995;109:516-523. 21. Ouellette AJ. Paneth cell alpha-defensin synthesis and function. Curr Top Microbiol Immunol 2006;306:1-25. 22. Abreu MT, Fukata M, Arditi M. TLR signaling in the gut in health and disease. J Immunol 2005;174:4453-4460. 23. Mitchell JA, Paul-Clark MJ, Clarke GW, McMaster SK, Cartwright N. Critical role of toll-like receptors and nucleotide oligomerisation domain in the regulation of health and disease. J Endocrinol 2007;193:323-330. 24. Keller R, Dwyer JE, Oh W, D'Amodio M. Intestinal IgA neutralizing antibodies in newborn infants following poliovirus immunization. Pediatrics 1969;43:330-338. 25. Fagarasan S, Honjo T. Regulation of IgA synthesis at mucosal surfaces. Curr Opin Immunol 2004;16:277-283. 26. Hamada H, Hiroi T, Nishiyama Y, et al. Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J Immunol 2002;168:57-64. 27. Rescigno M, Urbano M, Valzasina B, et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2001;2:361-367. 28. Owen RL. Uptake and transport of intestinal macromolecules and microorganisms by M cells in Peyer's patches – a personal and historical perspective. Semin Immunol 1999;11:157-163. 7 CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM Page 8 CLINICAL NUTRITION ABSTRACTS CANCER Computational modeling of cancer cachexia Clinical nutrition abstracts Curr Opin Clin Nutr Metab Care 2008 May;11(3):214-221. Hall KD, Baracos VE. Laboratory of Biological Modeling, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. PURPOSE OF REVIEW: Measurements of whole-body energy expenditure, body composition and in vivo metabolic fluxes are required to quantitatively understand involuntary weight loss in cancer cachexia. Such studies are rare because cancer cachexia occurs near the end of life when invasive metabolic tests may be precluded. Thus, models of cancer-associated weight loss are an important tool for helping to understand this debilitating condition. RECENT FINDINGS: A computational model of human macronutrient metabolism was recently developed that simulates the normal metabolic adaptations to semi-starvation and re-feeding. Here, this model was used to integrate data on the metabolic changes in patients with cancer cachexia. The resulting computer simulations show how the known metabolic disturbances synergize with reduced energy intake to result in a progressive loss of body weight, fat mass and fat-free mass. The model was also used to simulate the effects of nutritional support and investigate inhibition of lipolysis versus proteolysis as potential therapeutic approaches for cancer cachexia. SUMMARY: Computational modeling is a new tool that can integrate clinical data on the metabolic changes in cancer cachexia and provide a conceptual framework to help understand involuntary weight loss and predict the effects of potential therapies. Nutritional support in multimodal therapy for cancer cachexia and metabolic change. Thus, alterations in both energy intake and components of energy expenditure may contribute to progressive weight loss. Increased resting energy expenditure related to the systemic inflammatory response is common and a sustained hypermetabolism over a long period of disease progression can make a large contribution to negative energy balance and wasting if not compensated for by an increase in energy intake. Hypermetabolism and diminished energy intake due to anorexia may thus constitute a vicious circle in the development of cancer cachexia. DISCUSSION: Though nutritional support alone can improve energy intake to a variable extent and for a variable period of time, it will not address the underlying catabolic metabolism and is thus likely to be of limited efficacy if attempts to attenuate the tumor-induced catabolic response are not carried out at the same time. Concomitant drug treatments for cancer cachexia may slow down the wasting process by reducing anorexia, attenuating the systemic inflammation, the skeletal muscle catabolism or stimulating the muscle protein anabolism. Thus, improved management of cancer cachexia may require a multimodal approach by a multidisciplinary team and is best commenced earlier rather than later. Early start of therapy also facilitates the use of oral nutritional supplementation, which is preferable to parenteral nutrition in the majority of cases. Once a patient is severely wasted it may be neither practical nor ethical to intervene with anything else than supportive care. CONCLUSION: An improvement in the condition of all patients with cachexia may not be possible, however, the goal must be to stabilize cachexia and prevent or delay further decline. There is currently no single or combined treatment strategy which is successful in all patients. However, strategies to counteract both hypermetabolism and reduced dietary intake have been demonstrated to be of importance for the survival, function and quality of life of cancer patients, and should be further explored in interventional studies. Support Care Cancer 2008 May;16(5):447-451. CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 Bosaeus I. Department of Clinical Nutrition, Sahlgrenska University Hospital, Göteborg, Sweden. 8 INTRODUCTION: Malnutrition has since long been known to be associated with adverse outcomes in cancer patients. The wasting in cancer cachexia involves loss of muscle and fat and reflects a catabolic metabolism induced by an abnormal host response to tumor presence and/or tumor factors. Patients with cancer cachexia frequently develop a chronic negative energy and protein balance driven by a combination of reduced food intake Refeeding syndrome in cancer patients Int J Clin Pract 2008 Mar;62(3):460-465. Marinella MA. Wright State University School of Medicine, Division of HematologyOncology, Dayton, Ohio, USA. BACKGROUND: Refeeding syndrome (RFS) is a common, yet underappreciated, constellation of electrolyte derangements that typically occurs in acutely ill, malnourished hospitalized patients who are administered glucose solutions or other forms of intravenous or enteral nutrition. DISCUSSION: The hallmark of RFS is The abstracts included in this section were selected from a search on clinical nutrition and related topics of the PubMed database of the United States National Library of Medicine. PubMed may be accessed via the National Library of Medicine Web site at www.nlm.nih.gov. CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 hypophosphatemia, but hypokalemia and hypomagnesemia are also common. Patients with various types of malignancies are at-risk for RFS, but very little exists in the oncologic literature about this disorder. CONCLUSIONS: As RFS can have many adverse metabolic, cardiovascular, hematologic and neurologic complications, practicing oncologists need to be aware of the pathophysiology, risk factors and clinical manifestations to promptly recognize this important, and potentially fatal, metabolic disorder. Clin J Oncol Nurs 2007 Dec;11(6):875-880. Cady J. The Radiation Oncology Department, The Virginia Mason Medical Center, Seattle, Washington, USA. Significant weight loss and resultant malnutrition in patients undergoing radiotherapy for head and neck carcinomas are recognized and preventable clinical concerns. Morbidity related to weight loss during treatment may include dehydration, hospitalization, compromised treatment efficacy and reduced quality of life, and may impact survival. Malnutrition effects on wound healing may prolong recovery following treatment and increase the risk of morbidity for those undergoing subsequent salvage surgery. Multiple interventions have been implemented to help ameliorate the impact of treatment on weight loss and nutritional status, including the use of percutaneous endoscopic gastrostomy (PEG) tubes. The value of prophylactic PEG tube placement at treatment initiation increasingly is being recognized, and evidence suggests that patients experience better outcomes. Criteria for patient selection have not been defined completely, and a great deal of variation in clinical practice exists, contributing to underuse of this supportive intervention. According to a literature review, patients who require therapeutic PEG tube placement in response to significant weight loss during treatment suffer greater morbidity than patients who receive PEG tubes prophylactically. Understanding patient-, tumor-, and treatment-related risk factors to systematically identify patients most likely to benefit from prophylactic PEG tube placement is an important aspect of nursing care. The nutritional and metabolic support of heart failure in the intensive care unit Curr Opin Clin Nutr Metab Care 2008 Mar;11(2):140-146. Meltzer JS, Moitra VK. Division of Critical Care Medicine, Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, USA. PURPOSE OF REVIEW: Heart failure and cardiovascular disease are common causes of morbidity and mortality, contributing to many ICU admissions. Nutritional deficiencies have been associated with the development and worsening of chronic heart failure. Nutritional and metabolic support may improve outcomes in critically ill patients with heart failure. This review analyzes the role of this support in the acute care setting of the ICU. RECENT FINDINGS: Cardiac cachexia is a complex pathophysiologic process. It is characterized by inflammation and anabolic-catabolic imbalance. Nutritional supplements containing selenium, vitamins and antioxidants may provide needed support to the failing myocardium. Evidence shows that there is utility in intensive insulin therapy in the critically ill. Finally, there is an emerging metabolic role for HMG-CoA reductase inhibition, or statin therapy, in the treatment of heart failure. SUMMARY: Shifting the metabolic milieu from catabolic to anabolic, reducing free radicals and quieting inflammation in addition to caloric supplementation may be the key to nutritional support in the heart failure patient. Tight glycemic control with intensive insulin therapy plays an expanding role in the care of the critically ill. Glucose-insulin-potassium therapy probably does not improve the condition of the patient with heart failure or acute myocardial infarction. CRITICAL CARE NUTRITION Early nutrition support in critical care: A European perspective Curr Opin Clin Nutr Metab Care 2008 Mar;11(2):156-159. Kreymann KG. Department of Intensive Care, University Medical Centre, HamburgEppendorf, Germany. PURPOSE OF REVIEW: Today, early nutrition support is considered standard care in most intensive care units. The recommended method is the enteral route, although there is only minor evidence for this. Often inadequate delivery of energy and a cumulative energy deficit are implied. The purpose of this paper is to evaluate the indication for early enteral nutrition or immunonutrition and to discuss the application of additional parenteral nutrition. RECENT FINDINGS: The indication for early enteral nutrition is also supported by guidelines for enteral nutrition recently published by the European Society for Clinical Nutrition and Metabolism. Some more recent results strengthen the indication for a special formula in acute respiratory distress syndrome and septic patients. A recent metaanalysis has shown that parenteral nutrition is superior to delayed enteral nutrition. Additional parenteral nutrition thus seems to be the way to avoid cumulative energy deficit associated with insufficient or no enteral nutrition. SUMMARY: Early enteral nutrition is recommended for critically ill patients, with special formulas indicated in specific subgroups of patients. If enteral nutrition is insufficient or fails, parenteral nutrition should be instituted, respecting the often reduced demand for exogenous substrates in critically ill patients. CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 CARDIOVASCULAR DISEASE Page 9 Clinical nutrition abstracts Nutritional support during radiotherapy for head and neck cancer: The role of prophylactic feeding tube placement 3:13 PM 9 CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM Fish oil in critical illness Curr Opin Clin Nutr Metab Care 2008 Mar;11(2):121-127. Clinical nutrition abstracts Mayer K, Seeger W. Department of Internal Medicine, Pulmonary and Critical Care Medicine, Justus Liebig University Giessen, Germany. PURPOSE OF REVIEW: The aim of this review is to discuss recent advances in the role of n-3 lipids derived from fish oil in clinical nutrition in an intensive care setting. RECENT FINDINGS: Fish oil supplies n-3 fatty acids which compete with arachidonic acid (n-6) for the conversion to lipid mediators, influence lipid-bound second-messenger generation and dependent cellular functions, and are a source for resolvins necessary for the resolution of inflammation. Enteral nutrition with n-3 fatty acids improved ventilation time in patients with acute lung injury and in one study reduced mortality in septic patients. Using a high-dose, short-term infusion of fish oil-based lipid emulsion, rapid immunologic changes and effects on the endotoxin-induced stress response may be achieved. Inclusion of n-3 fatty acids in parenteral nutrition improved immunologic parameters and length of stay in surgical patients. SUMMARY: Inclusion of fish oil in nutrition may influence the immune response and clinical outcomes by balancing the negative effects of n-6 fatty acids. Application as a part of enteral immunonutrition in surgical or acute respiratory distress syndrome patients and in lipid emulsions in surgical patients has beneficial effects. In septic patients, data on enteral use are highly controversial. Prospective data from randomized trials, however, are lacking. Treatment of mild malnutrition and reduction of morbidity in abdominal surgery: A trial on 153 patients [article in Italian] Clin Ter 2008 Jan-Feb;159(1):13-18. CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 Pronio A, Di Filippo A, Aguzzi D, Laviano A, Narilli P, Piroli S, Vestri A, Montesani C. Cattedra di Chirurgia Generale, Policlinico Umberto I, Università La Sapienza, Roma, Italy. 10 OBJECTIVES: Severe malnutrition (defined as weight loss more than 10% in a period of 6 months) is considered an important risk factor in major abdominal surgery, because of a higher post-operative mortality and morbidity. The aim of our study is to assess the role of mild malnutrition (weight loss low than 10% in a period of 6 months) as a risk factor in major abdominal surgery and to evaluate the efficacy of therapy in order to improve outcomes in terms of in-hospital mortality, length of hospital stay and post-operative complications. Moreover, we evaluated serum albuminemia and lymphocyte count, important nutritional indices, as predictive risk factors. MATERIALS AND METHODS: We performed a randomized prospective trial, and admitted in our institution 153 adult patients, 43 with mild malnutrition and 110 without. The malnourished patients were randomized in two groups: the first one received oral immunonutrition (Impact Oral) for 7–10 days before surgery (22 patients), the second one received no nutritional support. RESULTS: We observed a higher number of complications in the nontreated Page 10 malnourished patients (57%) versus both the treated malnourished patients (13.6%) and the normal group (19%) (p < 0.001). Increased morbidity was observed in patients with serum albuminemia <2.8 g/dL (69.2%) and with lymphocyte count <1.500 mm 3 (57%). CONCLUSIONS: Nutritional enriched support demonstrated efficacy in reducing morbidity and length of hospital stay. Pre-operative oral immuno-nutrition might be suggested and established in all the patients with mild malnutrition that will be operated on major abdominal surgery. Early enteral supplementation with key pharmaconutrients improves Sequential Organ Failure Assessment score in critically ill patients with sepsis: Outcome of a randomized, controlled, double-blind trial Crit Care Med 2008 Jan;36(1):131-144. Beale RJ, Sherry T, Lei K, Campbell-Stephen L, McCook J, Smith J, Venetz W, Alteheld B, Stehle P, Schneider H. Department of Adult Critical Care Medicine, Guy’s and St. Thomas’ Hospital, London, United Kingdom. OBJECTIVE: To assess the safety and efficacy of an early enteral pharmaconutrition supplement containing glutamine dipeptides, antioxidative vitamins and trace elements, and butyrate in critically ill, septic patients. DESIGN: A prospective, randomized, controlled, double-blind clinical trial. SETTING: Adult intensive care unit in a university hospital. PATIENTS: Fifty-five critically ill, septic patients requiring enteral feeding. INTERVENTIONS: Patients received either an enteral supplement (500 mL of Intestamin, Fresenius Kabi) containing conditionally essential nutrients or a control solution via the nasogastric route for up to 10 days. Inclusion occurred within 24 hours of intensive care unit admission. Additionally, patients received enteral feeding with an immunonutrition formula (experimental group) or standard formula (control group) initiated within 48 hours after enrollment. MEASUREMENTS AND MAIN RESULTS: Organ dysfunction was assessed by daily total Sequential Organ Failure Assessment (SOFA) score over the 10-day study period in both patient groups. Patients receiving the experimental supplement showed a significantly faster decline in the regression slopes of delta daily total SOFA score over time compared with control. The difference between the regression coefficients of the two slopes was significant irrespective of the level of analysis: intent to treat -0.32 vs -0.14, p < 0.0001; per protocol -0.34 vs -0.14, p < 0.0001; and completers (patients receiving ≥80% of the calculated caloric target over a period of 6 days), -0.26 vs -0.16, p = 0.0005. Vitamin C, as a marker of supplement absorption, increased from 10.6 (1.9–59.4) μmol/L (normal range 20–50 μmol/L) on day 1 to 58.7 (5.4–189.9) μmol/L by day 3 (p = 0.002) in the intervention group but remained below the normal range in the control group 17.0 (2.8–78.5) on day 1 and 14.3 (2.4–179.6) on day 3. Serum levels of glycine, serine, arginine, ornithine, vitamin E and beta-carotene all increased significantly with treatment in the CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 supplementation group. CONCLUSIONS: In medical patients with sepsis, early enteral pharmaconutrition with glutamine dipeptides, vitamin C and E, betacarotene, selenium, zinc and butyrate in combination with an immuno-nutrition formula results in significantly faster recovery of organ function compared with control. Brussels 2007 roundtable on metabolism in sepsis and multiple organ failure JPEN J Parenter Enteral Nutr 2008 Jan-Feb;32(1):1-5. Herndon DH, Wernerman J. Department of Surgery, Shriners Hospital for Children, Galveston, Texas, USA. Gastric motility function in critically ill patients tolerant versus intolerant to gastric nutrition JPEN J Parenter Enteral Nutr 2008 Jan-Feb;32(1):45-50. BACKGROUND: Administration of gastric enteral nutrition (EN) in the intensive care unit (ICU) is commonly impeded by high gastric residual volumes (GRV). This study evaluated gastric emptying in patients with limited GRV (tolerant group) vs volumes ≥150 mL (intolerant group) and whether prokinetic therapy improves gastric motility in intolerant patients. METHODS: To assess gastric motility, mechanically ventilated patients received acetaminophen 975 mg, and peak plasma concentration (Cmax), concentration at 60 minutes (C 60), time to Cmax (Tmax) and area under the concentration-time curve from 0 to 60 minutes (AUC 0-60 were determined. This evaluation was repeated in intolerant patients after 24 hours of either erythromycin 250 mg or metoclopramide 10 mg therapy, both administered intravenously every 6 hours. RESULTS: Ten tolerant and 20 intolerant patients were studied. Tolerant patients had significantly greater Cmax (14.12 ± 7.25 vs 9.28 ± 5.22 mg/L; p < 0.05), C60 (9.62 ± 4.65 vs 6.08 ± 4.00 mg/L; p < 0.001) and AUC0-60 (10.01 ± 5.97 vs 3.93 ± 2.84 mg/h/L; p < 0.01), and shortened Tmax (0.81 ± 0.61 vs 1.98 ± 1.26 hours; p < 0.001) compared with intolerant patients. After prokinetic therapy, Cmax (15.26 ± 8.85 mg/L), C60 (11.96 ± 5.99 mg/L) and AUC0-60 (10.90 ± 6.57 mg/h/L) increased and Tmax (1.07 ± 1.01 hours) decreased in the intolerant group to values similar to the tolerant group. CONCLUSIONS: ICU patients with elevated GRV during gastric EN have delayed gastric motility. Initiating prokinetic therapy accelerates gastric emptying to resemble that of ICU patients tolerating EN. Nutrition support in the critically ill: A physician survey JPEN J Parenter Enteral Nutr 2008 Mar-Apr;32(2):113-119. Behara AS, Peterson SJ, Chen Y, Butsch J, Lateef O, Komanduri S. Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA. BACKGROUND: Current clinical practice guidelines delineate optimal nutrition management in the intensive care unit (ICU) patient. In light of these existing data, the authors identify current physician perceptions of nutrition in critical illness, preferences relating to initiation of feeding and management practices specific to nutrition after initiation of feeding in the ICU patient. METHODS: The authors electronically distributed a 12question survey to attending physicians, fellows and residents who routinely admit patients to medical and surgical ICUs. RESULTS: On a scale ranging from 1 to 5 (1 = low, 5 = high), the attending physician’s mean rating for importance of nutrition in the ICU was 4.60, the rating for comfort level with the nutrition support at the authors’ institution was 3.70, and the rating for the physician’s own understanding of nutrition support in critically ill patients was 3.33. Attending physicians, fellows and residents reported waiting an average of 2.43, 1.79 and 2.63 days, respectively, before addressing nutrition status in an ICU patient. Fifty-two percent of attending physicians chose parenteral nutrition as the preferred route of nutrition support in a patient with necrotizing pancreatitis. If a patient experiences enteral feeding intolerance, physicians most commonly would stop tube feeds. There was no significant difference in responses to any of the survey questions between attending physicians, fellows and residents. CONCLUSIONS: This study demonstrates a substantial discordance in physician perceptions and practice patterns regarding initiation and management of nutrition in ICU patients, indicating an urgent need for nutrition-related education at all levels of training. CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 Landzinski J, Kiser TH, Fish DN, Wischmeyer PE, MacLaren R. Department of Pharmacy, Georgetown University Hospital, Washington, DC, USA. Page 11 Clinical nutrition abstracts At the 2007 International Symposium on Intensive Care and Emergency Medicine (ISICEM) in Brussels, a roundtable conference on "Metabolic Support in Sepsis and Multiple Organ Failure" was held. The roundtable was endorsed by the European Society of Intensive Care Medicine, the Society of Critical Care Medicine, the European Society for Clinical Nutrition and Metabolism, and the American Society for Parenteral and Enteral Nutrition. Metabolic support in intensive care has become an exciting topic in recent years, with improved understanding of the effects of compromised mitochondrial function, studies demonstrating outcome benefits of tight glucose control, new insights into the mechanisms behind insulin resistance, recognition of glutamine and antioxidants as key nutrients, and emerging knowledge concerning the interactions between metabolism and endocrinology. Together, these aspects have generated an increased interest in the importance of metabolism in intensive care medicine, reflected in the programs and abstracts at international congresses of the past few years. This roundtable’s participants each gave a presentation within their specific area of expertise, and each was followed by general discussion. Discussions became heated as new concepts and ideas were debated. New data will be discussed in this summary, which reveals metabolic and nutrition interventions that could lead to major improvements in clinically relevant outcomes. 3:13 PM 11 CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM Effect of calorically dense enteral nutrition formulas on outcome in critically ill trauma and surgical patients JPEN J Parenter Enteral Nutr 2008 Jan-Feb;32(1):6-11. Clinical nutrition abstracts Bryk J, Zenati M, Forsythe R, Peitzman A, Ochoa JB. University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. 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 = 0.01), ventilator days (14.3 ± 12.9 vs 21.3 ± 10.5 days; p = 0.04) and average daily glucose levels (129.8 ± 4.1 vs 157.9 ± 13.6 mg/dL; p = 0.01), 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 = 0.01). However, trauma patients receiving a normocaloric formula exhibited decreased length of stay (15.3 ± 1.6 vs 18.7 ± 1.6 days; p = 0.02) 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. CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 DIABETES 12 Effects of high-monounsaturated fatty acid enteral formula versus high-carbohydrate enteral formula on plasma glucose concentration and insulin secretion in healthy individuals and diabetic patients J Int Med Res 2008 Jan-Feb;36(1):137-146. Page 12 aged 20.8 ± 1.2 years and 12 diabetic patients with good glycemic control (glycosylated hemoglobulin <7%) aged 58.6 ± 7.7 years were randomly assigned to take highMUFA or high-carbohydrate formula after a 12-hour overnight fast. The patients switched to the other formula after 7 days. Postprandial plasma glucose and insulin response were significantly lower in all subjects after taking high-MUFA formula compared with high-carbohydrate formula. No differences were observed in free fatty acids, triglycerides and plasma glucagon between the two diet groups. In conclusion, a high-MUFA enteral formula suppresses postprandial hyperglycemia without exaggerated insulin secretion compared with a high-carbohydrate enteral diet in patients with type 2 diabetes and healthy subjects. GASTROINTESTINAL DISORDERS Nutritional support in acute pancreatitis Curr Opin Clin Nutr Metab Care 2008 May;11(3):261-266. Thomson A. Gastroenterology and Hepatology Unit, The Canberra Hospital and The Australian National University, Canberra, Australia. PURPOSE OF REVIEW: This review explores the role of enteral and parenteral nutrition in severe acute pancreatitis and discusses the potential benefits of glutamine, omega-3 fatty acids, arginine and selenium together with probiotics and prebiotics in these patients. In addition, the method of refeeding during the convalescent period is also examined. RECENT FINDINGS: A complex picture is emerging in which enteral nutritional support may be important early in the course of the disease with parenteral nutrition being used more as a backup and possibly only after the systemic inflammatory response has peaked. Nasogastric feeding, sometimes supplemented by parenteral nutrition, is as efficacious as nasojejunal feeding. An individualized approach, in which strategies of nutritional support are tailored to patient response, is gaining currency. Data regarding specialized formulae are mixed but the use of prebiotics is showing promise and is worthy of further exploration. In the convalescent period, preliminary data also indicate that the risk of pain developing is no greater if a light diet is instituted rather than clear fluids. SUMMARY: Nutritional support in acute pancreatitis remains challenging and controversial with a number of different and unexpected approaches, including the use of nasogastric feeding and dual enteral and parenteral nutrition support, being adopted in recent clinical trials. Yokoyama J, Someya Y, Yoshihara R, Ishii H. Division of Diabetes and Endocrinology, Department of Internal Medicine, Jikei Daisan University Hospital, Komae City, Tokyo, Japan. Covert assessment of concurrent and construct validity of a chart to characterize fecal output and diarrhea in patients receiving enteral nutrition We investigated the effects of high-monounsaturated fatty acid (MUFA) versus high-carbohydrate enteral formula on postprandial plasma glucose concentration and insulin response in Japanese patients with type 2 diabetes mellitus and healthy Japanese volunteers. Ten healthy volunteers Whelan K, Judd PA, Preedy VR, Taylor MA. Diet and Gastrointestinal Health, Nutritional Sciences Division, King’s College London, London, United Kingdom. JPEN J Parenter Enteral Nutr 2008 Mar-Apr;32(2):160-168. BACKGROUND: An accurate and convenient method for CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 HEPATIC DISEASE Malnutrition in end stage liver disease: Recommendations and nutritional support J Gastroenterol Hepatol 2008 Apr;23(4):527-533. Tsiaousi ET, Hatzitolios AI, Trygonis SK, Savopoulos CG. First Medical Propedeutic Department of the Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece. and Metabolism, simple bedside methods such as Subjective Global Assessment and anthropometric parameters are reliable in assessing the nutritional state of cirrhotic patients. Correcting the nutrient deficit of the affected patients is mandatory. Avoidance of alcohol and excess fat and ingestion of 4–6 meals/day containing carbohydrates and protein are the most common recommendations. In severe malnutrition, initiation of enteral feeding and/or use of special formulae such as branchedchain, amino acid-enriched nutrient mixtures are often recommended. Enteral nutrition improves nutritional status and liver function, reduces complications, prolongs survival and is therefore indicated. NUTRITION SUPPORT Early nutritional therapy: The role of enteral and parenteral routes Curr Opin Clin Nutr Metab Care 2008 May;11(3):255-260. de Aguilar-Nascimento JE, Kudsk KA. Department of Surgery, Federal University of Mato Grosso, Cuiaba, Brazil. PURPOSE OF REVIEW: Early nutrition is defined as the initiation of nutritional therapy within 48 hours of either hospital admission or surgery. However, optimal timing for initiation of nutritional therapy through either enteral or parenteral routes remains poorly defined with the existing data. We reviewed the recent literature investigating the role of early enteral and parenteral nutrition in critical illness and perioperative care. RECENT FINDINGS: Recent studies in both trauma/surgical and nonsurgical patients support the superiority of early enteral over early parenteral nutrition. However, late commencement of enteral feeding should be avoided if the gastrointestinal tract is functional. Both prolonged hypocaloric enteral feeding and hypercaloric parenteral nutrition should be avoided, although the precise caloric target remains controversial. SUMMARY: Early enteral nutrition remains the first option for the critically ill patient. However, there seems to be increased favor for combined enteralparenteral therapy in cases of sustained hypocaloric enteral nutrition. The key issue is when the dual regimen should be initiated. Although more study is required to determine the optimal timing to initiate a combined enteralparenteral approach, enteral nutrition should be initiated early and parenteral nutrition added if caloric-protein targets cannot be achieved after a few days. Role of enteral nutrition in the incidence of diarrhea among hospitalized adult patients Nutrition 2008 Apr 14; [Epub ahead of print]. Luft VC, Beghetto MG, de Mello ED, Polanczyk CA. Post-Graduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. OBJECTIVE: This study examined the risk of diarrhea as a result of providing enteral nutrition in the hospital setting, adjusting for other clinical and therapeutic factors. METHODS: Adults admitted to a general tertiary CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 Malnutrition has increasingly been acknowledged as an important prognostic factor which can influence the clinical outcome of patients suffering from end-stage liver disease (ESLD). Despite the fact that malnutrition is not included in the Child-Pugh classification, its presence should alert clinicians to the same extent as do other complications, such as ascites and hepatic encephalopathy. The pathophysiological mechanisms and the clinical conditions that drive cirrhotic patients to an ill-balanced metabolic state are multiple and they intertwine. Inadequate offer of nutrients, the hypermetabolic state in cirrhosis, the diminished synthetic capacity of the liver and the impaired absorption of nutrients are the main reasons that disrupt the metabolic balance in ESLD. Identifying patients that are approaching the state of malnutrition by simple and easily applied methods is necessary in order to provide nutritional support to those that need it most. According to the European Society for Clinical Nutrition Page 13 Clinical nutrition abstracts characterizing fecal output and a consistent threshold for classifying diarrhea in patients receiving enteral nutrition are required. The aim of this study is to covertly assess the construct and concurrent validity of a chart for characterizing fecal output and classifying diarrhea in patients receiving enteral nutrition. METHODS: The chart was used to monitor fecal output in patients receiving enteral nutrition for a total of 280 patient days. Nurses characterized 291 fecal samples, of which 84 underwent measurement of fecal water using lyophilization and 60 underwent Clostridium difficile enterotoxin analysis using enzyme-linked immunosorbent assay. Construct and concurrent validity was assessed covertly to measure the true performance of the chart in a real-life clinical and research context. RESULTS: Use of the chart demonstrated higher fecal frequency (p ≤ 0.04), heavier stools (p ≤ 0.167), more unformed stools (p ≤ 0.001), higher daily fecal scores (p ≤ 0.001) and higher incidence of diarrhea (p ≤ 0.002) on days when patients had severe hypoalbuminemia, were receiving antibiotics, or had a recent positive C difficile assay, demonstrating construct validity. The water content of samples assigned to hard and formed (62.0%), soft and formed (72.1%), loose and unformed (79.3%) and liquid (87.9%) categories was significantly different (p < 0.001), demonstrating concurrent validity. CONCLUSIONS: Under covert assessment, the chart demonstrated construct validity for characterizing fecal output, daily fecal score and diarrhea, together with concurrent validity for characterizing fecal consistency. Use of the chart in clinical practice and research will standardize the characterization of fecal output and classification of diarrhea in patients receiving enteral nutrition. 3:13 PM 13 Clinical nutrition abstracts CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM care university hospital, in clinical or surgical units, were enrolled in the study between June 2004 and May 2005 and prospectively followed during their hospital stay. For each patient treated with enteral nutrition (n = 302), a comparable nontreated patient from the same ward, (who also received antibiotics previously) and was similarly cared for by the same hospital staff was included in the study (n = 302), constituting a double-cohort study. All patients were seen three times per week, on alternating days, until the occurrence of diarrhea or hospital discharge. Cox’s regression analyses were applied for adjustments. RESULTS: The incidence of diarrhea was 18% for patients receiving enteral nutrition and 6% for nontreated patients (p < 0.01). In multivariate analyses, enteral nutrition was independently associated with diarrhea (hazard ratio 2.7, 95% confidence interval 1.6–4.7), even adjusting for age (hazard ratio 1.02, 95% confidence interval 1.00–1.03) and hospitalization during the summer months (hazard ratio 2.4, 95% confidence interval 1.5–3.9). Patients for whom strict adherence to delivery-set washing-and-changing procedures was observed (on >75% of days) presented a lower incidence of diarrhea (6.5% vs 20.3%, p = 0.02; and 5.9% vs 19.8%, p = 0.05, respectively). CONCLUSION: Providing enteral nutrition to the hospitalized elderly during the summer months is associated with a higher risk of diarrhea. Strategies aimed toward improvement in the quality of enteral nutrition practices should be evaluated to minimize this deleterious clinical outcome. Death resulting from overzealous total parenteral nutrition: The refeeding syndrome revisited Nutr Clin Pract 2008 Apr;23(2):166-171. CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 Miller SJ. University of Montana, Department of Pharmacy Practice, Missoula, Montana, USA. 14 Commentary is provided on the pivotal paper by Weinsier and Krumdieck from 1981 describing two patients who developed profound and fatal refeeding syndrome following initiation of aggressive total parenteral nutrition. This classic description was among the first to describe the overwhelming cardiovascular and pulmonary manifestations that can accompany parenteral refeeding with carbohydrate in chronically malnourished patients. The syndrome has also been described with oral and enteral nutrition. One of the hallmarks of the syndrome is hypophosphatemia. Since 1981, dosing schemes for addressing hypophosphatemia have been refined. Other manifestations of the syndrome include other electrolyte abnormalities such as hypokalemia and hypomagnesemia, hyperglycemia, fluid and sodium retention, and neurologic and hematologic complications. Case reports of refeeding syndrome continue to be published, particularly in the anorexia nervosa population. Stressed, critically ill patients may be at risk of refeeding following short periods of fasting; hypophosphatemia is commonly encountered in this situation. It behooves the current nutrition support practitioner to keep in mind the types of patients at risk of refeeding syndrome and to approach refeeding of such patients with caution and careful monitoring. Page 14 Diagnosis and treatment of simple acid-base disorders Nutr Clin Pract 2008 Apr;23(2):122-127. Ayers P, Warrington L. Mississippi Baptist Medical Center, Department of Pharmacy, Jackson, Mississippi, USA. The ability to diagnose and treat acid-base disorders is an important component in the practice of the nutrition support clinician. A complete understanding of the basic principles of metabolic and respiratory disorders allows the practitioner to formulate educated decisions regarding fluids, parenteral nutrition salts, and the management of electrolytes. This review will discuss the diagnosis and treatment of common metabolic and respiratory disorders encountered in nutrition support practice. Factors contributing to the development of hypophosphatemia when refeeding using parenteral nutrition Pharm World Sci 2008 Mar 30; [Epub ahead of print]. Marvin VA, Brown D, Portlock J, Livingstone C. Pharmacy Department, Royal Surrey County Hospital, Guildford, Surrey, United Kingdom. AIM: To identify individual attributes or risk factors which predispose to the development of refeeding hypophosphatemia in patients on parenteral nutrition (PN). SETTING: The Royal Surrey County Hospital (RSCH) a 530-bed, non-teaching Trust with a cancer center, medical and surgical inpatients and intensive care unit (ICU). Subjects were recruited prospectively from all adult inpatients referred for initiation of PN. METHOD: Seventy patients (cases) with refeeding hypophosphatemia were matched with controls who had not experienced a fall in phosphate levels when commenced on PN. Their nutritional requirements, nutrition intake and biochemical test results were compared and statistical analyses performed to show if any differences between cases and controls were due to chance. RESULTS: Independent risk factors for developing refeeding hypophosphatemia were: significant malnutrition measured as a Nutrition Risk Screening (NRS) score of three or more; less than 12 mmol total phosphate in the first day’s PN regimen; and an initial rate of infusion of PN of more than 70% of calculated requirements. In addition increasing amounts of nonlipid phosphate in the first day’s PN regimen were found to be protective. Hypomagnesemia prior to starting PN was nonsignificantly associated with refeeding hypophosphatemia. Other biochemical markers included in the study: albumin, calcium, C-reactive protein, glucose and urea, did not show an association. ICU, cancer and postoperative patients were not found to be more at risk. CONCLUSION: Patients with a high NRS score prior to commencing nutrition support may be more at risk than others of refeeding hypophosphatemia. The first 24 hour PN regimen should be run slowly providing less than 70% of calculated protein and calorie requirements but containing more than 12 mmol phosphate. CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 Glutamine: Role in critical illness and ongoing clinical trials Curr Opin Gastroenterol 2008 Mar;24(2):190-197. Wischmeyer PE. Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado, USA. Enteral feeding Curr Opin Gastroenterol 2008 Mar;24(2):184-189. DeLegge MH. Medical University of South Carolina, Charleston, South Carolina, USA. Multiple small clinical trials, observational studies and retrospective reviews must be analyzed to develop ‘best practice’ guidelines with enteral nutrition. Vitamin K-independent warfarin resistance after concurrent administration of warfarin and continuous enteral nutrition Pharmacotherapy 2008 Mar;28(3):308-313. Dickerson RN, Garmon WM, Kuhl DA, Minard G, Brown RO. Department of Clinical Pharmacy, University of Tennessee Center for the Health Sciences, Memphis, Tennessee, USA. STUDY OBJECTIVE: To assess the influence of withholding continuous enteral nutrition for 1 hour before and after warfarin administration compared with the coadministration of warfarin with continuous enteral nutrition on changes in international normalized ratios (INRs). DESIGN: Retrospective, crossover case series. SETTING: Intensive care units of a university-affiliated medical center. PATIENTS: Six adults who required nutritional support for at least the first 10 consecutive days of warfarin therapy; during that 10-day period, they had a period of at least 3 consecutive days during which the enteral feeding was withheld for 1 hour before and after warfarin administration, and had a period of at least 3 consecutive days when feedings were not withheld during warfarin administration. Patients with advanced liver disease and those who received therapies, during the observation period, that significantly alter warfarin metabolism were omitted from the study. MEASUREMENTS AND MAIN RESULTS: The change in INR during the 3-day observation period when feedings were withheld for 1 hour before and after warfarin administration was significantly different versus the change in INR during coadministration of warfarin with continuous feeding (mean ± SD 0.74 ± 0.66 vs -0.13 ± 0.81, p ≤ 0.05). This difference in INR response occurred despite the administration of similar dosages of warfarin (5.6 ± 2.1 vs 5.7 ± 2.1 mg/d, p > 0.05). Also noted was a clinically irrelevant, but statistically significant, difference in vitamin K intake between treatment periods (77 ± 36 µg/d when feedings were withheld vs 102 ± 28 µg/d when feedings were not withheld, p ≤ 0.05). CONCLUSION: Continuous enteral nutrition should be withheld for 1 hour before and after warfarin administration to prevent enteral nutrition-associated warfarin resistance. Estimating resting energy expenditure in patients requiring nutritional support: A survey of dietetic practice Eur J Clin Nutr 2008 Jan;62(1):150-153. Green AJ, Smith P, Whelan K. Department of Nutrition and Dietetics, St George’s Healthcare NHS Trust, London, United Kingdom. Estimation of resting energy expenditure (REE) involves predicting basal metabolic rate (BMR) plus adjustment for metabolic stress. The aim of this study was to investigate the methods used to estimate REE and to identify the CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 PURPOSE OF REVIEW: Enteral nutrition is a widely used therapy for nutritional treatment of patients with multiple pathologies. The present review selects important evidenced-based papers from 2006 and 2007 and critically reviews them for the reader. RECENT FINDINGS: Use of synbiotics and probiotics is gaining acceptance. Supplements such as glutamine may be important for wound healing. Enteral feeding in malnourished patients may result in rapid growth of gut mucosal protein. Antibiotics are important for reduction of postpercutaneous endoscopic gastrostomy infections. Early enteral nutrition in burn patients blunts the hypermetabolic response. Polymeric enteral formulations in vitro have a direct anti-inflammatory effect on enterocytes. Enteral nutrition, however, does not appear better than steroid use for induction of remission in Crohn’s disease. Longterm (12-week) infusion of immune-enhancing enteral formulas in a nonsurgical patient group is well tolerated and safe. Finally, large reviews of enteral nutrition and their efficacy for specific disease states continue to demonstrate the difficulty in interpreting multiple small clinical studies. SUMMARY: Enteral nutrition continues as a highly used medical therapy, usually as an adjuvant for other pharmacologic and supportive therapies. Page 15 Clinical nutrition abstracts PURPOSE OF REVIEW: This review will assess recent clinical and mechanistic data examining glutamine’s ability to reduce morbidity and mortality in critical illness. RECENT FINDINGS: Updated meta-analysis data reveal a significant benefit of glutamine supplementation on mortality, length of stay and infectious morbidity in critical illness. Recent data support glutamine’s use in critically ill patients requiring parenteral nutrition and new data reveal safety and efficacy in head-injured patients. Further, new findings on glutamine’s beneficial effect on insulin resistance in critical illness will be reviewed. Recent laboratory data have clarified a number of key mechanistic pathways by which glutamine may improve outcome in critical illness. SUMMARY: Severe glutamine deficiencies occur rapidly in critical illness. The magnitude of glutamine deficiency is correlated with ICU mortality. Further, meta-analysis reveals glutamine reduces morbidity and mortality in critical illness. It is likely that our new understanding of the molecular pathways by which glutamine acts will lead to insight on how best to utilize glutamine as a nutritional therapy. Presently, randomized, multicenter clinical trials utilizing glutamine as both nutritional replacement and pharmacologic intervention, independent of nutritional needs, are ongoing. 3:13 PM 15 Clinical nutrition abstracts CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM impact of the patient’s clinical condition and the dietitians’ work profile on the stress factor assigned. A random sample of 115 dietitians from the United Kingdom with an interest in nutritional support completed a postal questionnaire regarding the estimation of REE for 37 clinical conditions. The Schofield equation was used by the majority (99%) of dietitians to calculate BMR; however, the stress factors assigned varied considerably with coefficients of variation ranging from 18.5 (cancer with cachexia) to 133.9 (HIV). Dietitians specializing in gastroenterology assigned a higher stress factor to decompensated liver disease than those not specializing in gastroenterology (19.3 vs 10.7, p = 0.004). The results of this investigation strongly suggest that there is wide inconsistency in the assignment of stress factors within specific conditions and gives rise to concern over the potential consequences in terms of under- or overfeeding that may ensue. Enteral glutamine during active shock resuscitation is safe and enhances tolerance of enteral feeding JPEN J Parenter Enteral Nutr 2008 Jan-Feb;32(1):28-35. CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 McQuiggan M, Kozar R, Sailors RM, Ahn C, McKinley B, Moore F. Department of Surgery, University of Texas Medical School Houston, Houston, Texas, USA. 16 BACKGROUND: Feeding the hemodynamically unstable patient is increasingly practiced, yet few data exist on its safety. Because enteral glutamine is protective to the gut in experimental models of shock and improves clinical outcomes, it may benefit trauma patients undergoing shock resuscitation and improve tolerance if administered early. This pilot study aimed to evaluate gastrointestinal tolerance and safety of enteral feeding with glutamine, beginning during shock resuscitation in severely injured patients. METHODS: In a prospective randomized trial, 20 patients were randomly assigned to either an enteral glutamine group (n = 10) or a control group (n = 10). Patients with severe trauma meeting standardized shock resuscitation criteria received enteral glutamine 0.5 g/kg/d during the first 24 hours of resuscitation and 10 days thereafter. Immune-enhancing diet began on postinjury day 1, with a target of 25 kcal/kg/d. Control patients received isonitrogenous whey powder plus immune-enhancing diet. Tolerance (vomiting, nasogastric output, diarrhea and distention) was assessed throughout the study. RESULTS: Glutamine was well tolerated and no adverse events occurred. Treated patients had significantly fewer instances of high nasogastric output (5 vs 23; p = 0.010), abdominal distention (3 vs 12; p = 0.021), and total instances of intolerance (8 vs 42; p = 0.011). Intensive care unit (ICU) and hospital length of stay were comparable. Control patients required supplemental parenteral nutrition (PN) to meet goals at day 7. CONCLUSIONS: Enteral glutamine administered during active shock resuscitation and through the early postinjury period is safe and enhances gastrointestinal tolerance. A large clinical trial is warranted to determine if enteral glutamine administered to the hemodynamically unstable patient can reduce infectious morbidity and mortality. Page 16 Emergency high-loop jejunostomy as enteral nutrition access: A simple and safe method JPEN J Parenter Enteral Nutr 2008 Jan-Feb;32(1):94-97. Pacelli F, Rotondi F, Rosa F, Bossola M, Papa V, Tortorelli AP, Sollazzi L, Doglietto GB. Department of Surgical Sciences, Digestive Surgery Unit, Catholic University, School of Medicine, Rome, Italy. BACKGROUND: Emergency high-loop jejunostomies are seldom used for nutrition access in the clinical practice. METHODS: This paper describes the results of a simple and safe technique that uses emergency high-loop jejunostomy as an enteral feeding access. A feeding tube is inserted into the efferent loop of the jejunostomy and then subcutaneously tunneled. In this way, whenever it becomes necessary, the bag collecting fluids from the afferent loop can be changed without removing the tube, which remains permanently inserted into the efferent loop and secured to the skin in order to avoid displacements. RESULTS: Twenty-nine patients with high-loop jejunostomy were consecutively treated with the described technique during the period 2000–2006. The mean distance between the ligament of Treitz and tube was 38.3 ± 16.2 cm. After an induction period, all patients received full-strength enteral nutrition and were discharged after a mean of 25.1 ± 19.5 days of treatment. All patients were subsequently readmitted to our unit, and their ostomies were successfully closed. No major early and late complications were observed; particularly, no patient experienced local or systemic septic complications. CONCLUSION: From the analysis of our results, the described method for delivering enteral nutrition through an emergency high-loop ostomy proves easy to apply and clinically effective. Enteral nutrition can be started as soon as possible after operation through the efferent loop of the ostomy; the management of the jejunostomy is simple and safe, with no additional discomfort for the patients. PEDIATRICS Guidelines for the management of growth failure in childhood inflammatory bowel disease Inflamm Bowel Dis 2008 Feb 11; [Epub ahead of print]. Heuschkel R, Salvestrini C, Beattie RM, Hildebrand H, Walters T, Griffiths A. Royal Free Hampstead NHS Trust, Centre for Paediatric Gastroenterology, Hampstead, London, United Kingdom. Around 1 in 4 patients with inflammatory bowel disease (IBD) present in childhood, the majority around the time of their pubertal growth spurt. This presents challenges over and above those of managing IBD in adults, as this period is a time of dramatic psychological and physical transition for a child. Growth and nutrition are key priorities in the management of adolescents and young adults with IBD. Growth failure in IBD is characterized by delayed skeletal maturation and a delayed onset of puberty, and is best described in terms of height-for-age standard deviation score (Z score) or by variations in CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 Page 17 Long-term outcome, growth and digestive function in children 2 to 18 years after intestinal transplantation Gut 2008 Apr;57(4):455-461; [Epub 2007 Dec 13]. Lacaille F, Vass N, Sauvat F, Canioni D, Colomb V, Talbotec C, De Serre NP, Salomon J, Hugot JP, Cézard JP, Révillon Y, Ruemme FM, Goulet O. Pediatric Gastroenterology-Hepatology-Nutrition Unit, Necker-Enfants malades Hospital, Paris, France. OBJECTIVE: Small bowel (SB) transplantation (Tx), long considered a rescue therapy for patients with intestinal failure, is now a well recognized alternative treatment strategy to parental nutrition (PN). In this retrospective study, we analyzed graft functions in 31 children after SBTx with a follow-up of 2–18 years (median 7 years). PATIENTS: Twelve children had isolated SBTx, 19 had combined liver-SBTx and 17 received an additional colon graft. Growth, nutritional markers, stool balance studies, endoscopy and graft histology were recorded every 2–3 years post-Tx. RESULTS: All children were weaned from PN after Tx and 26 children remained PN-free. Enteral nutrition was required for 14/31 (45%) patients at 2 years post-Tx. All children had high dietary energy intakes. The degree of steatorrhoea was fairly constant, with fat and energy absorption rates of 84%–89%. Growth parameters revealed at transplantation a mean height Z-score of -1.17. After Tx, two thirds of children had normal growth, whereas in one third, Z-scores remained lower than -2, concomitant to a delayed puberty. Adult height was normal in 5/6. Endoscopy and histology analyses were normal in asymptomatic patients. Chronic rejection occurred only in noncompliant patients. Five intestinal grafts were removed 2.5–8 years post-Tx for acute or chronic rejection. CONCLUSIONS: This series indicates that long-term intestinal autonomy for up to 18 years is possible in the majority of patients after SBTx. Subnormal energy absorption and moderate steatorrhoea were often compensated for by hyperphagia, allowing normal growth and attainment of adult height. Long-term compliance is an important prerequisite for long-term graft function. Clinical nutrition abstracts Probiotics and other preventative strategies for necrotizing enterocolitis Semin Fetal Neonatal Med 2008 Feb;13(1):35-43; [Epub 2007 Oct 31]. Embleton ND, Yates R. Newcastle Neonatal Service, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom. Necrotizing enterocolitis (NEC) remains one of the commonest causes of death and significant morbidity in preterm infants after the first few postnatal days. NEC affects approximately 5%–10% of infants born at < or = 28 weeks; about a third will die. Although there do not appear to be any 'simple fixes', it is clear that there are many clinical strategies that affect NEC. There is controlled trial evidence for breast milk, fluid regimes, enteral antibiotics, immunonutrients and probiotic supplements. This paper will review the evidence relevant to current populations of preterm infants and determine which, if any, can be safely and effectively introduced into current clinical practice. CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 growth velocity over a period of 3–4 months. Growth failure is common at presentation in Crohn’s disease (CD), but less common in ulcerative colitis (UC). The etiology of growth failure is multifactorial. Principal determinants, however, include the inflammatory process per se, with proinflammatory cytokines (eg, IL1β, IL-6) being directly implicated. Furthermore, poor nutrition and the consequences of prolonged corticosteroid use also contribute to the significant reduction in final adult height of almost 1 in 5 children. Initially a prompt, where possible steroid-free, induction of remission is indicated. The ideal is then to sustain a relapse-free remission until growth is complete, which is often not until early adulthood. These goals can often be achieved with a combination of exclusive enteral nutrition (EEN) and early use of immunosuppressants. The advent of potent and efficacious biological agents considerably improves the range of growth-sparing interventions available to children around puberty, although well-timed surgery remains another highly effective means of achieving remission and significant catch-up growth. We carried out a systematic review of publications to identify the best available evidence for managing growth failure in children with IBD. Despite the paucity of high-quality publications, sufficient data were available in the literature to allow practical, evidence-based where possible, management guidelines to be formulated. Although there is clear evidence that exclusive enteral nutrition achieves mucosal healing, its effect on growth has only been assessed at 6 months. In contrast to corticosteroids, EEN has no negative effect on growth. Corticosteroids remain the key therapy responsible for medication-induced growth impairment, although the use of budesonide in selected patients may minimize the steroid effect on dividing growth plates. Immunosuppressants have become a mainstay of treatment in children with IBD, and are being used earlier in the disease course than ever before. However, there are currently no long-term data reporting better growth outcome if these agents are introduced very soon after diagnosis. In comparison, recent data from a large prospective trial of infliximab in children with moderate to severe CD suggested significant catch-up growth during the first year of regular infusions. The only other intervention that has documented clear catch-up growth has been surgical resection. Resection of localized CD, in otherwise treatment-resistant children, early in the disease process achieves clear catch-up growth within the next 6 months. There are no data available that growth hormone improves final adult height in children with CD. In conjunction with expert endocrinological support, pubertal delay, more common in boys, may be treated with parenteral testosterone if causing significant psychological problems. The optimal management of children and adolescents requires a multidisciplinary approach frequently available within the pediatric healthcare setting. Dedicated dietetic support, along with nurse-specialist, child psychologist, and with closely linked medical and surgical care will likely achieve the best possible start for children facing a lifetime of chronic gut disease. 3:13 PM 17 CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM Page 18 Highlights of Clinical Nutrition Week 10–14 February 2008 • Chicago, Illinois, USA Emerging interests and controversies in clinical nutrition and critical care – State of the art lecture: Where have we been and where are we going? Highlights of the Clinical Nutrition Week G Jensen State College, PA, USA changes in their bodies, taste and the manner in which they must eat can lead to embarrassment, social stigma and selfisolation, and contribute to a learned aversion to food and reduced food intake. Recent studies show a proactive approach can lessen side effects. Pre-treatment swallowing exercises improve post- After a period of decline in nutrition support teams that para- treatment swallowing and quality of life in H&N cancer lleled an emphasis on cost containment in health care, nutrition patients undergoing radiation or chemotherapy (Kulbersh BD, support is emerging as a key part of individual medical treatment et al. Laryngoscope 2006;116:883-886). Prophylactic percuta- plans for specific patient conditions and phenotypes. Identifying neous endoscopic gastrostomy (PEG) tube placement that and treating undernutrition continues to be a keystone in nutri- allows tube feedings to start earlier in patients with advanced tion support practice, due to the continued high prevalence of H&N cancer receiving chemoradiotherapy has been shown to undernutrition in hospital and acute care settings. However, the limit weight loss and results in few complications (Wiggenraad obesity epidemic has broad implications for nutrition support. RG, et al. Clin Otolaryngol 2007;32: 384-390). Considerable overlap exists among malnutrition While nutritional counseling and close follow-up helps syndromes. Sarcopenia and micronutrient deficiencies arise in to mitigate the nutritional compromise so often seen with both undernourished and overnourished patients, and demon- H&N cancer, cancer cachexia is a chronic systemic inflamma- strate that undernutrition and overnutrition can occur tory state that also requires anti-cachexia agents, such as simultaneously. Inflammation permeates cachexia, protein corticosteroids and megesterol acetate, to reverse its damaging energy malnutrition, sarcopenia, failure to thrive and obesity. effects. Future strategies may include nutraceuticals, omega-3 The lack of standardized definitions is confusing and may negatively impact therapeutic choices, pointing to the need for a fatty acids, inflammatory antagonists and other targeted treatments (Couch M, et al. Head Neck 2007;29:401-411). common nutrition language for malnutrition syndromes (Thomas DR. Clin Nutr 2007;26:389-399). A new international effort that builds on earlier attempts to define malnutrition terms is underway (Roubenoff R, et al. Am J Clin Nutr 1997;66: 192-196). Research priorities in nutrition support include further development and testing of screening and assessment tools, and CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 identification and validation of new laboratory indices for nutri- 18 Nestlé Nutrition Satellite Symposium – Setting up for success: Nutrition best practices for patients with impaired GI function S McClave (Louisville, KY, USA) R Martindale (Portland, OR, USA) J Lacy (Cincinnati, OH, USA) tion. Well-conceived nutrition intervention studies are needed Evidence supports the use of early enteral nutrition (EN) as that tie to clinically relevant outcome studies. Research is also primary therapy in severe acute pancreatitis (SAP), but its needed on nutritional modulation of inflammatory conditions success requires clinicians to be persistent in advancing the using specific nutrients and functional foods, and on the effect of feeding and to recognize symptoms of intolerance that would individualized interventions that are tailored to genetic poly- limit its use. In a patient with pancreatitis an APACHE II score morphisms. of ≥10 or ≥3 Ransom criteria suggests SAP. Enteral nutrition in SAP maintains gut integrity, sets the Nutrition challenges in head and neck cancer tone for systemic immunity, attenuates the stress response and JS Magnuson, JL Locher, CS RItchie Birmingham, AL, USA and results in fewer complications than parenteral nutrition disease severity, promotes faster resolution of the disease process (PN). More importantly, EN reduces mortality by 60%. Compared with other types of cancer, patients with head and An immune-modulating formula with arginine, fish oil neck (H&N) cancer report much lower quality of life and have and antioxidants is the formula of choice. Gastric feedings are a higher suicide rate. Alterations of self-identify related to well tolerated and should be started within 2 days to avoid CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM Page 19 delays due to ileus. Although gastric feedings carry a higher MAdCAM-1 expression in the PP, and are accompanied by risk for aspiration than small bowel feedings, the link to pneu- similar decreases in lymphocyte mass. IgA levels in the mucosa monia is tenuous. Placing the tube 40 cm below the ligament and the respiratory cell drop concomitant with decreases in of Treitz may improve tolerance. total intestinal levels of the IgA-stimulating cytokines IL-4 and Complicated cases of pancreatitis that require surgical IL-10. The system is highly dynamic and recovers following debridement for infected necrosis may need jejunal feedings introduction of enteral feedings (Zarzaur BL, et al. Shock and a more elemental formula. Postoperatively, attempts to 2001;15:411-420). feed patients by the enteral route should continue, but if intolerance persists PN is indicated. In the clinical setting, the absence of EN reduces the number of GALT cells in patients with colon cancer (Okamoto Patients with open abdomens can be fed enterally after K, et al. JPEN J Parenter Enteral Nutr 2005;29:56-58). The adequate resuscitation is achieved; however, clinicians must be lack of enteral feeding also impairs established mucosal immu- keenly aware of any signs of intolerance and should withhold nity and the immunologic response to new infectious challenges feedings if a patient shows any signs of distention, pain, low (King BK, et al. Ann Surg 1999;229:272-278. Johnson CD, et urine output or hemodynamic instability. al. Ann Surg 2003;237:565-573). Parenteral feeding may contribute to systemic inflammation and increase lung and liver permeability, leading to multiple organ dysfunction following arginine, and glutamine. Vitamins E and C and selenium are severe traumatic injuries (Fukatsu K, et al. Ann Surg also beneficial. At least 5–7 days of providing a minimum of 2001;233:660-668). 50% of estimated needs are required for immune-modulating formulas to show benefit. No data supports withholding jejunal feedings for Clearly there are immunologic benefits gained at the mucosal surface when nutrients are delivered via the GI tract that are not gained with parenteral feeding. surgery or holding patients with nothing by mouth (NPO) longer than 3 hours prior to surgery. However, if the patient Feeding the complex trauma patient develops pneumotosis postoperatively, enteral feedings should B Collier Nashville, TN, USA be stopped for 3–5 days to avoid nonocclusive bowel necrosis. Highlights of the Clinical Nutrition Week For severely injured trauma patients, data clearly support using immune-modulating formulas with fish oil, In complex trauma patients, the presence of persistent systemic Rhodes Research Lecture: Of mice and men . . . and a few hundred mice inflammatory response syndrome (SIRS), characterized by the KA Kudsk Madison, WI, USA quent immune system impairment. Compounding the systemic release of proinflammatory mediators, leads to increased catabolism, acute protein malnutrition and subseproblem, trauma patients who receive inadequate early nutrition can starve, accumulating large energy deficits that cannot Dr Kudsk hypothesizes that the route and type of nutrition be made up later on (Todd SR, et al. Nutr Clin Pract influence mucosal immunity when a lack of enteral stimulation 2006;21:421-429). creates a defect in mucosal immunity resulting in loss of IgA- The value of aggressive glucose control in the trauma mediated defenses in the respiratory tract and increased patient is unclear. Using an aggressive protocol to maintain susceptibility to pneumonia. tight glucose control in trauma patients resulted in no differ- The small intestine is the principal anatomic site for ence in outcomes (Collier B, et al. JPEN J Parenter Enteral immunologic sensitization. Sensitization of most B and T cells Nutr 2005;29:353-358). Although hyperglycemia is clearly for mucosal immunity occurs in the Peyer’s patches (PP), aided proinflammatory, the ideal goal for blood glucose in trauma by mucosal addressin cellular adhesion molecule-1 (MAdCAM- patients is unknown and an upper limit of 145 mg/dL may 1), a gateway molecule on the PP. Once sensitized, the cells move be ideal. During the resuscitative phase the focus should be on to the linings of the gastrointestinal (GI) tract, the mammary appropriate crystalloid and blood use for resuscitative efforts, tract of lactating females, the respiratory tract and the geni- early enteral feeds, glucose control, glutamine and early tourinary tract. antioxidants. In the early nutrition phase that begins on day 2, Experimental work has shown alterations in gut- trauma patients need hypocaloric feedings, immune-enhancing associated lymphoid tissue (GALT) impairs host defense. Lack diets, beta blockers and mitochondrial support. By day 7 the of enteral stimulation decreases T and B cells within PPs and the trauma patient enters the late anabolic phase of nutrition and intestinal lamina propria. These alterations occur with emphasis should be placed on reaching positive nitrogen decreases in the lymphotoxin-beta receptor (LTßR) signaling balance by giving adequate nutrition, oxandrolone and beta pathway (Kang W, et al. Ann Surg 2006;244:392-399) and in blockers. CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 out of the PP into the thoracic duct, where they are transported 19 CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM Feeding the hypotensive patient Highlights of the Clinical Nutrition Week R Kozar Houston, TX, USA Page 20 It remains unclear at what volume of gastric residual aspiration risk increases. In general feedings should not be held for residual volumes less than 250 mL, although a Feeding the hemodynamically unstable patient is gaining promotility agent should be considered for residual acceptance; yet the practice is not without danger. volumes persistently greater than 250 mL (McClave SA, et Nonocclusive bowel necrosis (NOBN) is a rare but serious al. Gastrointestinal Dis 2003;14:2-10). complication thought to be caused by metabolic stress when The inadvertent connection between an enteral the demand for oxygen during nutrient absorption exceeds feeding system and a non-enteral system, such as an supply. The resulting oxygen deprivation places further intravascular line or peritoneal dialysis catheter, often stress on the hypoperfused gut and leads to microvasular results in fatal complications when enteral formula acci- ischemia and necrosis. dentally infuses into intravenous lines or catheters. The Glucose and glutamine are metabolized by the gut and design of invasive access devices and human error contribute to energy production. Thus, unlike other nutri- contribute to enteral misconnections (Guenter P, et al. Jt ents, they abrogate metabolic stress in the hypoperfused gut, Comm J Qual Improv 2008;34:285-292). Solutions enhance gut blood flow and provide a protective effect, via involve staff and manufacturers, and include education activation of peroxisome proliferator-activated receptor and awareness, better purchasing strategies and design gamma (PPARγ), following mesenteric ischemia (Kozar RA, changes (Pratt N. Mater Manag Health Care 2006;15: et al. Gastroenterology 2002;123:810-816). 36-39). A recently published pilot study demonstrated that enteral glutamine supplementation during active shock resuscitation and throughout the early post-injury period is safe and enhances GI tolerance in severely injured patients (McQuiggan M, et al. JPEN J Parenter Enteral Nutr 2008;32:28-35). Glutamine supplementation was well Enteral feeding in the critically ill patient: Considerations in acute renal failure IF Btaiche Ann Arbor, MI, USA tolerated compared to protein supplementation and no Acute renal failure (ARF) is a highly catabolic state and adverse events occurred. Treated patients had significantly presents a specific and independent risk factor for poor fewer instances of GI intolerance. Intensive care unit and prognosis (Metnitz PG, et al. Crit Care Med 2002;30: hospital length of stay were comparable. The study was too 2051-2058. Cano N, et al. Clin Nutr 2006;25:295-310). small to evaluate differences in infectious morbidity or Similarly to end-stage renal disease, required treatment mortality. options compound nutrient losses. Although data is scarce, available studies indicate Safe practices for enteral nutrition: In search of evidence to support best practice enteral tube feeding (ETF) is the preferred route for nutri- MA Corkins (Indianapolis, IN, USA) S Brantley (Knoxville, TN, USA) J Boullata (Philadelphia, PA, USA) P Guenter (Silver Spring, MD, USA) shown to significantly improve outcomes in critically ill tional support in patients with ARF when oral feeding and nutritional supplements are inadequate. ETF was adult patients treated with chronic renal replacement therapy (CRRT), even after adjusting for predicted risk of CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 death (Scheinkestel CD, et al. Nutrition 2003;19:909- 20 This session highlighted ASPEN’s progress to date on devel- 916). Another study compared complications and oping evidence-based Safe Practices for Enteral Nutrition nutrient intake in ARF patients receiving tube feedings to with publication expected later this year. There is a lack of patients with normal renal function and found that all evidence to support commonly used methods to check groups received well above 90% of prescribed nutrition, enteral feeding tube placement, including auscultation, aspi- and except for high gastric residual volumes, there were ration and pH, and capnography. X-rays are the only no differences in GI or mechanical complications verified method to confirm placement; however, there are (Fiaccadori E. Kidney Int 2004;65:999-1008). concerns with the use of radiation in children. Direct jejunostomy placement requires significantly less intervention and is a better option than passing a jejunal feeding tube through the gastrostomy site (Raval MV, et al. J Pediatr Surg 2006;41:1679-1682). Feedings can begin Oral nutrition interventions in end-stage renal disease TA Ikizler Nashville, TN, USA within 48 hours in postoperative patients, even in those with Patients with end-stage renal disease (ESRD) frequently open abdominal wounds. have protein-energy malnutrition plus muscle wasting. CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM Page 21 Poor dietary intake, the hemodialysis (HD) process, 2007;17:341-347). A follow-up study is examining the chronic inflammation and insulin resistance have been effect of providing 10 g of ALA daily for 12 weeks. implicated as contributing factors (Ikizler TA. Am J Initial results show a favourable response with proba- Physiol ble effects on hypercoagulability and hyperfibrinolysis Endocrinol Metab 2002;282:E107-116). Intradialytic parenteral nutrition (IDPN) reverses the in subjects with defined inflammation. catabolic effects of dialysis, but it is costly and its use Given its low cost, good tolerance and absence of is restricted by Medicare and other payers (Pupim LB, side effects, additional studies using flaxseed powder et al. J Clin Invest 2002;110:483-492). are recommended. Nonetheless, patients with normal An initial study comparing IDPN and oral supple- or nearly normal inflammatory markers show no bene- mentation providing 60 g protein, 100 g carbohydrate fits from omega-3 fatty acid supplementation, even in and 40 g fat in malnourished ESRD patients showed those who are overweight or mildly obese, suggesting oral supplementation was as effective as IDPN in prophylactic use of omega-3 fatty acids is not indi- reversing HD-associated protein catabolism and main- cated for this population (Nelson TL, et al. Cytokine taining positive protein balance during HD. The 2007;38:101-106). anabolic effects of oral supplementation persisted beyond the HD period, providing an additional positive effect above and beyond what is observed with IDPN 3157). E Brett, J Mechanick New York City, NY, USA The French Intradialytic Nutrition Evaluation Enteral nutrition helps maintain tight glucose control Study (FINEs), a large, long-term study in malnour- during sepsis and should start as soon as the patient is ished patients with chronic renal failure (CRF), hemodynamically stable. Goals are ≤100% measured demonstrated that the route of administration of resting energy expenditure (MREE) during the shock nutritional supplementation has no significant effect and catabolic phases of sepsis, and 100%–130% on survival or the observed improvements in most MREE during the anabolic phase of critical illness nutritional markers. Nutritional supplementation (McClave SA, et al. JPEN J Parenter Enteral Nutr providing 1.2 g protein/kg/d and >30 kcal/kg/d 2003;27:16-20). improved nutritional markers (Cano NJ, et al. J Am Soc Hyperglycemia in hospitalized patients may be Nephrol 2007;18:2583-2591). Considering the finan- due to pre-existing type 1 or type 2 diabetes, or it may cial advantages, oral supplementation should be the result treatment of choice for all chronic renal disease Regardless of the cause, the adverse effects of acute patients requiring nutritional intervention. hyperglycemia, including impaired immune function, from stress or steroid-induced Highlights of the Clinical Nutrition Week (Pupim LB, et al. J Am Soc Nephrol 2006;17:3149- Managing diabetes in nutrition support patients diabetes. fluid and electrolyte imbalance, erythrocyte and Supplementation of flaxseed powder in morbid obesity platelet aggregation, endothelial dysfunction and J Faintuch Sao Paulo, Brazil (Cheung NW, et al. Diabetes Care 2005;28:2367- increased oxidative stress, result in worse outcomes 2371. Lin LY, et al. Am J Med Sci 2007;333:261-265). Morbid obesity is frequently associated with chronic Therefore, hyperglycemia is treated the same whether microinflammation, which carries potentially adverse or not there is an underlying diagnosis of diabetes. Compared to patients with diabetes who are inflammation usually improves after weight loss, even eating, those on tube feedings have higher peak minor elevations in C-reactive protein (CRP) have glucose loads and higher insulin requirements due to negative prognostic implications and predict mortality more rapid absorption of continuous low volume (Kushner I, et al. Am J Med 2006;166:e17-28). liquid formulas compared to solid food taken in bolus Flaxseed is the most abundant vegetable source feedings. However, enterally fed patients have a more of the omega-3 fatty acid alpha-linolenic acid (ALA) predictable caloric intake, making control of blood and is used in coronary disease. A 2-week study in glucose easier compared to patients who are eating. obese patients with elevated inflammatory markers Diabetes-specific formulas have been shown to showed that adding flaxseed powder to the diet to result in lower peak glucose, lower insulin requirements provide 5 g ALA a day alleviated inflammation. Levels and fewer complications than standard formulas in of CRP and serum amyloid A (SAA), another inflam- patients with diabetes. (Peters AL, et al. JPEN J matory marker, fell (Faintuch J, et al. Obes Surg Parenternteral Nutr 1992;16:69-74). CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 metabolic and cardiovascular consequences. Although 21 CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM Nestlé Nutrition Satellite Symposium – Clinical studies that have changed practice: Do you know them? Do you like them? Did you implement them? Highlights of the Clinical Nutrition Week RG Martindale (Portland, OR, USA) R Meier (Liestal, Switzerland) C Pichard (Geneva, Switzerland) Page 22 Selenium supplementation in the ICU – Have we found the magic bullet? A Shenkin Liverpool, England While good theoretical evidence exists that Se supplements improve the antioxidant state in critical illness, clinical trials have shown variable results. In patients with SIRS, Se supple- This session was designed to assist clinicians in analyzing the mentation significantly lowered mortality and reduced the quality of research when deciding whether to implement incidence of acute renal failure (Angstwurm MW, et al. Crit new findings into current practice. Presenters demonstrated Care Med 1999;27:1807-1813). A later meta-analysis of a systematic approach to evaluating clinical studies eleven studies showed Se supplementation may be associated considering the type of study, randomization, blinding of with a reduction in mortality in critically ill patients and investigators, percent of follow-up, intention to treat, concluded Se supplementation is safe (Heyland DK, et al. sample size for power analysis, patient demographics and Intensive Care Med 2005;31:327-337). More recently, a pilot primary endpoints vs ad hoc analysis. study to reduce deaths from oxidative stress (REDOX) showed In GI cancer strong evidence supports preemptively that higher doses of Se (300 μg given enterally plus 500 μg loading the cell with arginine, omega-3 fatty acids and RNA given parenterally) reduced oxidative stress and improved clin- prior to surgery, to reduce perioperative complications and ical outcomes. length of hospital stay (Gianotti L, et al. Gastroenterology Conversely, other studies have found no benefit, espe- 2002;122:1763-1770). Fourteen papers support the use of cially those using high loading doses. In a multicenter study of pre- or perioperative immune-modulating formulas. ICU patients with severe SIRS, higher doses of Se replacement In another surgical arena, a well-done study showed showed a strong but not statistically significant trend toward fish oil given perioperatively reduced the relative risk of reduced mortality (Angstwurm MW, et al. Crit Care Med postoperative atrial fibrillation after coronary artery bypass 2007;35:118-126). High loading doses of Se (4,000 μg) had no surgery by 54.4% and was associated with a shorter effect on mortality or adverse events and did not reduce oxida- hospital stay (Calò L, et al. J Am Coll Cardiol 2005;45: tive damages (Forceville X, et al. Crit Care 2007;11:R73. 1723-1728). Mishra V, et al. Clin Nutr 2007;26:41-50). Good evidence also exists for using synbiotics to Se supplementation is clearly beneficial in select patient improve outcomes in patients undergoing major abdominal populations. In burn patients Se supplementation to replace surgery. In another well-done study, EN using fiber- losses from the surface results in significantly decreased containing solutions plus Lactobacillus reduced the rate of bronchopneumonia infections and shortened hospital stays postoperative infections compared to parenteral nutrition (Berger MM, et al. Am J Clin Nutr 1998;68:365-371). (PN) or fiber-free EN (Rayes N, et al. Nutrition 2002;18: 609-615). Recent work challenges the practice of hypocaloric feedings and showed that energy deficits of more than 10,000 Kcal accumulating after only one week are associ- CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 ated with increased infection rate or impaired wound 22 Supplementation of vitamin C and vitamin E in the critically ill patient: Re-examining the evidence L-N Chan Seattle, WA, USA healing. The deficits are impossible to compensate for later Critically ill patients have low circulating concentrations of on and call for more aggressive measures to meet energy vitamins C and E, which could considerably compromise needs (Villet S, et al. Clin Nutr 2005;24:502-509). antioxidant defense. Seemingly, vitamin E and C supplementa- Supplemental PN combined with EN could be an tion would be beneficial, but most studies have been effective alternative to achieve energy targets when EN goals disappointing (Quasim T, et al. Clin Nutr 2003;22:459-462). are not met by day 4, but controversy surrounds its use in Chan postulates that failure of vitamin E and C supplementa- critical illness. A recent meta-analysis investigated the effect tion to show an expected dose-response may be due to the of trial quality on the overall conclusions reached when formulation, dose, route, and time and duration of vitamin comparing EN and PN. It showed that PN is not related to therapy. excess mortality and may even be associated with improved The optimal formulations and doses of vitamin C and E survival. (Simpson F, et al. Intensive Care Med 2005;31:12- required to produce a positive clinical outcome remain 23. Heidegger CP, et al. Intensive Care Med 2007;33: unknown. The many different available salt forms of vitamins 963-969). C and E could account for the variable responses seen with CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM Page 23 supplementation. In several studies, large doses of oral vitamin 2001;29:2075-2080. Garrel D, et al, Crit Care Med C (up to 10-fold increase) and oral and intravenous vitamin E 2003;31:2444-2449), reduce Gram-negative infections in (up to 15-fold increase) produced relatively small increases in patients with multiple trauma (Houdijk AP, et al. Lancet serum concentrations, suggesting cellular uptake of vitamins is 1998;352:772-776) and decrease nosocomial infections in limited (Nathens AB, et al. Ann Surg 2002;236:814-822. Long patients with SIRS (Conejero R, et al. Nutrition 2002;18:716- CL, et al. J Surg Res 2003;109: 144-148). 721). A combination of enteral and parenteral glutamine The route of administration affects the dose-response relationship. Very high levels of oral vitamin C produce only probably maximizes benefits in the critically ill patient by providing both a local and systemic effect. slightly elevated plasma concentrations, whereas intravenous administration of vitamin C produces substantially higher concentration levels. This suggests the intravenous route bypasses a tight oral control (Padayatty SJ, et al. Ann Intern Med 2004;140:533-537). A meta-analysis indicated parenteral Improving outcomes in critically ill patients: Glycemic control G Jensen State College, PA, USA antioxidants are associated with more favorable clinical Although Van den Berghe’s landmark study on the use of inten- outcomes than enteral antioxidants (Heyland DK, et al. sive insulin therapy (IIT) in cardiac surgery patients showed Intensive Care Med 2005;31:327-337). dramatic improvements in outcomes and has changed practice (Van den Berghe G, et al. N Eng J Med 2001;345:1359-1367), recent studies raise concern about the routine implementation weeks of supplementation were required to achieve a dose of IIT intervention. response relationship (Devaraj S, et al. Arterioscler Thromb A subsequent study by Van den Berghe in a medical ICU Vasc Biol 1997;17:2273-2279). On the other hand, more recent yielded confusing results; mortality was higher with IIT for studies on long-term supplementation of vitamin C and E found patients who stayed in the ICU less than 3 days and lower if significantly higher increases of vitamin concentrations in the they stayed longer than 3 days (Van den Berghe G, et al. New organs than in the serum, suggesting sequestering of vitamins to Engl J Med 2006;354:449-461). In a trauma population, protect the organs. This implies that serum or plasma concen- Collier et al found no differences in pneumonia, surgical infec- trations may not be a reliable marker for total body tion or mortality between patients who were managed with an concentration and calls into question the practice of long-term IIT protocol compared to the control group (Collier B, et al. supplementation to increase serum concentration (Mustacich JPEN J Parenter Enteral Nutr 2005;29:353-359). A more DJ, et al. Free Radic Biol Med 2007;43:610-618). recent study found IIT during cardiac surgery did not reduce Highlights of the Clinical Nutrition Week The time and duration of supplementation also influences the effectiveness of vitamin supplementation. In some studies perioperative death or morbidity compared with conventional Improving outcomes in critically ill patients: Glutamine supplementation intraoperative glucose management. The IIT group had an P van Leeuwen Amsterdam, The Netherlands Med 2007;146:233-243). increased incidence of death and stroke, suggesting a potential for harm with routine use of IIT (Gandhi GY, et al. Ann Intern A study comparing the effect on survival among patients with septic shock using IIT vs conventional insulin therapy and by closing the paracellular channels on the apical side, thereby crystalloids vs colloids for fluid resuscitation showed no signif- decreasing gut permeability (Kouznetsova L, et al. JPEN J icant difference in mortality or organ failure between groups. Parenter Enteral Nutr 1999;23:136-139. Le Bacquer O, et al. However, rates of severe hypoglycemia and serious adverse Am J Physiol Gastrointest Liver Physiol 2003;285:G128- events were higher in the IIT group than in the conventional- G136). Glutamine supports the gut-associated immune system therapy group, prompting researchers to stop the trial early. by serving as respiratory fuel for the small intestine and They concluded that IIT placed critically ill patients with sepsis substrate for the synthesis of glutathione (Manhart N, et al. at increased risk for serious adverse events related to hypo- Ann Surg 2001;234:92-97. Pithon-Curi TC, et al. Am J Physiol glycemia (Brunkhorst FM, et al. N Engl J Med 2008; Cell Physiol 2003;284:C1355-1361). Glutamine also stimu- 358:125-139). lates de novo synthesis of arginine, the precursor of nitric oxide, which regulates blood flow through the gut during stress. In the clinical setting, glutamine supplementation reduces The views expressed in this newsletter are of the presenters and participants, not Nestlé Nutrition. morbidity and mortality in critically ill patients, and low plasma levels significantly predict mortality. Glutamine supplementation has been shown to reduce Gram-negative bacteremia and death in burn patients (Wischmeyer PE, et al. Crit Care Med The next Clinical Nutrition Week will be held on 1–4 February 2009 in New Orleans, Louisiana, USA. Further information may be found at www.nutritionweek.org. CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 Experimental evidence shows glutamine maintains gut integrity 23 CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM Page 24 Conference Calendar 2008 August 2008 International Academy of Nutrition and Aging (IANA) 3rd International Meeting 1–2 August 2008 Albuquerque, New Mexico, USA Organizer: University of New Mexico, School of Medicine Clinical Nutrition Program, Aging Process Study Tel: +1 505 272 3942 Fax: +1 505 272 8604 E-mail: [email protected] Web site: www.serdi-fr.com/ABQ.htm 3rd World Congress of Pediatric Gastroenterology, Hepatology and Nutrition (WCPGHAN 3) 16–20 August 2008 Iguassu Falls, Brazil Conference calendar Organizer: LASPGHAN Tel: +55 41 3342 7175 Fax: +55 41 3342 7175 E-mail: [email protected] Web site: www.wcpghan2008.com September 2008 44 Annual Meeting of the European Association for the Study of Diabetes (EASD) 7–11 September 2008 Rome, Italy th Organizer: EASD Secretariat Tel: +49 211 758 46920 Fax: +49 211 758 46929 E-mail: [email protected] Web site: www.easd.org 21st European Society of Intensive Care Medicine (ESICM) Annual Congress 21–24 September 2008 Lisbon, Portugal Organizer: ESICM Congress Manager Tel: + 32 2 559 03 55 Fax: + 32 2 527 00 62 E-mail: [email protected] Web site: www.esicm.org 8th Advances in Pediatric Nutrition 22–24 September 2008 Baltimore, Maryland, USA Organizer: The Johns Hopkins University School of Medicine Tel: +1 410 502 9634 E-mail: [email protected] Web site: www.hopkinscme.net October 2008 ADA Food & Nutrition Conference & Expo (FNCE) 2008 25–28 October 2008 Chicago, Illinois, USA Organizer: American Dietetic Association Tel: +1 800/877 1600 4862 E-mail: [email protected] Web site: www.eatright.org/fnce November 2008 British Association for Parenteral and Enteral Nutrition (BAPEN) Conference 2008 4–5 November 2008 Harrogate, United Kingdom CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2 Organizer: 24 30th European Society for Clinical Nutrition and Metabolism (ESPEN) Congress 13–16 September 2008 Florence, Italy Organizer: MCI Suisse SA Tel: +41 22 33 99 580 Fax: +41 22 33 99 601 E-mail: [email protected] Web site: www.espen.org/npages/florence Sovereign Conference Tel: +44 1527 518 777 E-mail: [email protected] Web site: www.bapen.org.uk NASPGHAN-CDHNF Partnership: A Decade of Progress 13–15 November 2008 San Diego, California, USA Organizer: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Children’s Digestive Health and Nutrition Foundation Tel: +1 215 233 0808 E-mail: [email protected] Web site: www.naspghan.org CH-NES-011a(Ver7).qxd:CH-NES-011a_InsidePages.qxd 6/23/08 3:13 PM Page 25 CH-NES-011a_Cover.qxd:Layout 1 6/23/08 3:11 PM Page 1
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