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1.
HLA-A Locus is Associated With Sepsis and Septic Shock After Traumatic Injury.
Horn, DL, Mindrinos, M, Anderson, K, Krishnakumar, S, Wang, C, Li, M, Hollenbach, J, O'Keefe, GE
Annals of surgery. 2022;(1):203-207
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Abstract
OBJECTIVE Determine whether variation in the HLA region is associated with the development of post-traumatic sepsis and septic shock. BACKGROUND Sepsis-related deaths remain a major source of mortality after traumatic injury. Genetic characteristics may contribute to susceptibility to adverse outcomes including sepsis and septic shock. Recent advances in next-generation sequencing technology now allow comprehensive genotyping of the HLA region. METHODS White adult trauma patients requiring more than 2 days of mechanical ventilation underwent HLA genotyping, and were followed for the development of sepsis and septic shock. Odds ratios (OR) for the associations between our outcomes and HLA variants were estimated, a correction for multiple comparisons was applied, and significant variants were included in regression models adjusting for potential confounders. RESULTS A total of 1184 patients were included. Patients were severely injured (median injury severity score 33); 33% developed sepsis, 6% septic shock, and in-hospital mortality was 14%. An amino acid variant (156Q) within the HLA-A peptide-binding groove was associated with greater odds of sepsis [OR 1.50, (1.18-1.89)]. HLA-A∗02:01 was associated with lower odds of septic shock [OR 0.52, (0.32-0.82)]. These associations remained significant after adjusting for potential confounders. CONCLUSIONS This is the first study to apply next-generation sequencing techniques to evaluate associations between immunogenetic factors and post-traumatic sepsis and septic shock. Associations with class I HLA variants are novel as they implicate adaptive immunity in post-traumatic sepsis. These findings are a step towards developing a panel of genetic markers assessing risk of infection-related complications as we move towards more personalized medicine.
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Dietary Technologies to Optimize Healing from Injury-Induced Inflammation.
Sears, B, Perry, M, Saha, AK
Anti-inflammatory & anti-allergy agents in medicinal chemistry. 2021;(2):123-131
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Abstract
Inflammation is an acute adaptive response to injury. However, if the initial inflammatory response to an injury is not completely healed, it becomes chronic low-level inflammation that is strongly associated with many chronic disease states, including metabolic (obesity and diabetes), cardiovascular, auto-immune, and neurogenerative disorders as well as cancer. The healing process is far more complex than the initiation of inflammation. Within that complexity of healing is a sequence of events that are under profound dietary control and can be defined by specific blood markers. Those molecular events of the healing process that are under significant dietary control are termed as the Resolution Response. The purpose of this review is to describe the molecular components of the Resolution Response and how different dietary factors can either optimize or inhibit their actions. In particular, those dietary components that optimize the Resolution Response include a calorie-restricted, protein-adequate, moderate-carbohydrate, low-fat diet referred to as the Zone diet, omega-3 fatty acids, and polyphenols. The appropriate combination of these dietary interventions constitutes the foundation of Pro-Resolution Nutrition. The effect of these dietary components the actions of NF-κB, AMPK, eicosanoids, and resolvins are described in this review, as well as ranges of appropriate blood markers that indicate success in optimizing the Resolution Response by dietary interventions.
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The gut in trauma.
Patel, JJ, Rosenthal, MD, Miller, KR, Martindale, RG
Current opinion in critical care. 2016;(4):339-46
Abstract
PURPOSE OF REVIEW The purpose of this review is to describe established and emerging mechanisms of gut injury and dysfunction in trauma, describe emerging strategies to improve gut dysfunction, detail the effect of trauma on the gut microbiome, and describe the gut-brain connection in traumatic brain injury. RECENT FINDINGS Newer data suggest intraluminal contents, pancreatic enzymes, and hepatobiliary factors disrupt the intestinal mucosal layer. These mechanisms serve to perpetuate the inflammatory response leading to multiple organ dysfunction syndrome (MODS). To date, therapies to mitigate acute gut dysfunction have included enteral nutrition and immunonutrition; emerging therapies aimed to intestinal mucosal layer disruption, however, include protease inhibitors such as tranexamic acid, parenteral nutrition-supplemented bombesin, and hypothermia. Clinical trials to demonstrate benefit in humans are needed before widespread applications can be recommended. SUMMARY Despite resuscitation, gut dysfunction promotes distant organ injury. In addition, postresuscitation nosocomial and iatrogenic 'hits' exaggerate the immune response, contributing to MODS. This was a provocative concept, suggesting infectious and noninfectious causes of inflammation may trigger, heighten, and perpetuate an inflammatory response culminating in MODS and death. Emerging evidence suggests posttraumatic injury mechanisms, such as intestinal mucosal disruption and shifting of the gut microbiome to a pathobiome. In addition, traumatic brain injury activates the gut-brain axis and increases intestinal permeability.
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Nutritional therapy in critically ill and injured patients.
Latifi, R
The Surgical clinics of North America. 2011;(3):579-93
Abstract
Nutritional support of critically ill or injured patients has undergone significant advances in the last few decades. These advances are the direct result of the growing scientific progress and increased knowledge of the biology and biochemistry of key metabolic and nutrient changes induced by injury, sepsis, and other critical illnesses, both in adults and children. As this knowledge has increased, the science of nutritional support has become more disease based and disorder based. This article discusses protein and nitrogen metabolism in critically ill patients, immunomodulation, and the key nutrients involved in an immune-enhancing diet.
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Increasing plasma glutamine in postoperative patients fed an arginine-rich immune-enhancing diet--a pharmacokinetic randomized controlled study.
Loï, C, Zazzo, JF, Delpierre, E, Niddam, C, Neveux, N, Curis, E, Arnaud-Battandier, F, Cynober, L
Critical care medicine. 2009;(2):501-9
Abstract
OBJECTIVE Immune-enhancing diets (IEDs) rich in arginine (ARG) reduce morbi-mortality in trauma and surgical patients. Among the pharmaconutrients inducing these effects, ARG may be involved by generating active metabolites such as glutamine (GLN). However, the ability of an ARG-enriched diet to normalize GLN plasma levels in intensive care unit (ICU) patients has never been documented. To analyze plasma GLN and related amino acid (AA) kinetics in response to an ARG-enriched IED in ICU surgical patients. DESIGN This prospective, randomized, single-blind, comparative study was performed on 22 patients randomized to receive total enteral nutrition for 7 days with either an ARG-enriched IED or a standard formula (rendered isonitrogenous to the IED, S group, n = 11), providing 30 kcal/kg/day and 0.3 g N/kg/day. MEASUREMENTS Plasma AA concentrations were measured on day 5 after a 3-hour washout period (basal values = T0) and after 30, 60, 90, 120, 180, and 360 minutes of enteral nutrition. The primary end point was the variation in plasma GLN from T0 to T90. RESULTS Only the IED-fed patients showed an increase in plasma levels of GLN (differences [T90 - T0]: +40 +/- 6 vs. -35 +/- 18 micromol/L, mean +/- sem, p < 0.05, two-way analysis of variance), ARG (+35 +/- 5 vs.+1 +/- 4 micromol/L, p < 0.05), ornithine (+23 +/- 6 vs. -2 +/- 2 micromol/L, p < 0.05), and proline (+36 +/- 10 vs. -6 +/- 11 micromol/L, p < 0.05). CONCLUSION To our knowledge, this is the first reported pharmacokinetic study on an IED even though these products have been on the market for 20 years. Our main result is that administering an ARG-enriched IED causes a significant increase in plasma GLN probably from de novo GLN synthesis from ARG. This suggests that the ARG present in IED can serve to supply GLN to ICU patients, who are usually depleted in this conditionally essential AA during injury.
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Update on postinjury nutrition.
Todd, SR, Gonzalez, EA, Turner, K, Kozar, RA
Current opinion in critical care. 2008;(6):690-5
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Abstract
PURPOSE OF REVIEW Nutritional supplementation is paramount to the care of severely injured patients. Despite its widespread use in trauma, many areas of clinical nutrition remain controversial and not well defined. The benefit of early enteral nutrition in the care of injured patients has been well established, with further benefit derived by the administration of immune-enhancing formulas supplemented with glutamine, arginine, nucleotides, and omega-3-fatty acids. A new paradigm of pharmaconutrition has been developed that separates the administration of immunomodulatory nutrients from that of nutritional support. The optimal utilization and benefit of pharmaconutrients, however, remains unclear, as does the need for full caloric provision in the early postinjury phase. RECENT FINDINGS Nutrition studies with the greatest reduction in morbidity and mortality are those utilizing specific nutrients. The use of pharmaconutrients to modulate the inflammatory and immune response associated with critical illness seems to provide benefit to critically ill and injured patients. Additionally, studies at least suggest that trauma patients derive comparable if not additional benefit from hypocaloric feeding during the acute phase of injury. SUMMARY Building upon previous well performed studies in trauma patients, the current focus of nutritional investigations center on the use of pharmaconutrients to modulate the inflammatory response and the use of hypocaloric feeds. These practices will be reviewed and evidence presented for their use in critically ill and injured patients.
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Nutrition support in adult trauma patients.
Todd, SR, Kozar, RA, Moore, FA
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2006;(5):421-9
Abstract
Nutrition supplementation is paramount to the care of severely injured patients. Despite its widespread use in trauma patients, many areas of clinical practice remain controversial. The purpose of this paper is to critically review the literature studying the use of enteral vs parenteral nutrition (PN) and to provide the rationale for early enteral nutrition. Additional controversies confronting clinicians are reviewed, including the use of immune-enhancing agents and the optimal site for enteral nutrition delivery (gastric vs small intestinal). Evidence-based recommendations for clinical practice are presented when available.
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Posttraumatic inflammation is a complex response based on the pathological expression of the nervous, immune, and endocrine functional systems.
Aller, MA, Arias, JL, Nava, MP, Arias, J
Experimental biology and medicine (Maywood, N.J.). 2004;(2):170-81
Abstract
The successive phases that make up both the local and systemic posttraumatic acute inflammatory response could represent the expression of three concatenated pathological or "primitive" functional systems with trophic properties: the nervous, immune, and endocrine ones. The nervous functional system would play an important role in the phenomenon of ischemia-reperfusion, which would be represented by nutrition by diffusion that is either anaerobic (ischemia) or with defective use of oxygen (reperfusion) and, thus, with a limited energy requirement. The immune functional system would be represented by the infiltration of the tissues by inflammatory cells and bacteria, which would become mediators in providing nutrition to the injured tissues. Although the use of oxygen would still be defective, hypermetabolism and fever would occur. In these inflammatory response phases, the lymphatic is the most important circulation. The endocrine functional system would be the most specialized and would have high energy requirements because it would be represented by the blood capillary-mediated nutrition. Highly specialized epithelial cells would already possess a perfected oxidative metabolism. The successive expression of these three functional systems during embryonic development and also during the evolutionary development of our species could explain why the inflammatory response is a ubiquitous mechanism that is common to multiple diseases, because it is an integrator of the ontogeny and phylogeny.
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Honey: a potent agent for wound healing?
Lusby, PE, Coombes, A, Wilkinson, JM
Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society. 2002;(6):295-300
Abstract
Although honey has been used as a traditional remedy for burns and wounds, the potential for its inclusion in mainstream medical care is not well recognized. Many studies have demonstrated that honey has antibacterial activity in vitro, and a small number of clinical case studies have shown that application of honey to severely infected cutaneous wounds is capable of clearing infection from the wound and improving tissue healing. The physicochemical properties (eg, osmotic effects and pH) of honey also aid in its antibacterial actions. Research has also indicated that honey may possess antiinflammatory activity and stimulate immune responses within a wound. The overall effect is to reduce infection and to enhance wound healing in burns, ulcers, and other cutaneous wounds. It is also known that honeys derived from particular floral sources in Australia and New Zealand (Leptospermum spp) have enhanced antibacterial activity, and these honeys have been approved for marketing as therapeutic honeys (Medihoney and Active Manuka honey). This review outlines what is known about the medical properties of honey and indicates the potential for honey to be incorporated into the management of a large number of wound types.
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Catabolic response to stress and potential benefits of nutrition support.
Wray, CJ, Mammen, JM, Hasselgren, PO
Nutrition (Burbank, Los Angeles County, Calif.). 2002;(11-12):971-7
Abstract
The catabolic response to sepsis, severe injury, and burn is characterized by whole-body protein loss, mainly reflecting increased breakdown of muscle proteins, in particular myofibrillar proteins. Glucocorticoids and various proinflammatory cytokines are important regulators of muscle proteolysis in stressed patients. There is evidence that breakdown of proteins by the ubiquitin-proteasome pathway plays an important role in muscle cachexia, although other mechanisms may participate, such as calcium- and calpain-dependent release of myofilaments from the sarcomere. Three types of treatments have been used to reduce or prevent the catabolic response to injury and sepsis: 1). nutritional, 2). hormonal, and 3). pharmacologic. With regard to nutrition support, it is generally believed that enteral feeding is superior to parenteral feeding and that early feeding is better than late feeding. Although "immune-enhancing" enteral nutrition has been shown in several recent studies to improve outcome in critically ill patients, the specific effects of these treatments on the catabolic response in muscle are not known. In addition to nutrition support, various hormones, including insulin, growth hormone, and insulin-like growth factor-1, may blunt the catabolic response in patients with stress. Experimental studies have indicated that other treatments may become available in the future, including cytokine antibodies, calcium antagonists, and induction of heat shock response. Methods to prevent or reduce the catabolic response to stress are important considering the significant clinical consequences of muscle cachexia.