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Effects of different lipid emulsions on serum adipokines, inflammatory markers and mortality in critically ill patients with sepsis: A prospective observational cohort study.
Ulusoy, H, Kangalgil, M, Küçük, AO, Özdemir, A, Karahan, SC, Yaman, SÖ, Yavuz, HB, Ok, Ü
Clinical nutrition (Edinburgh, Scotland). 2021;(7):4569-4578
Abstract
BACKGROUND & AIMS Intravenous lipid emulsions in parenteral nutrition may cause different metabolic responses and immune effects in critically ill patients with sepsis. The aim of this study is to investigate the effects of different lipid emulsions on changes in concentrations of adipokine and cytokine and their relationship with mortality in patients. METHODS Patients enrolled in this prospective, single-center, observational cohort study, were estimated to require more than ten days of parenteral nutrition. They were treated with soybean oil-based or olive oil-based parenteral lipid emulsions. Adipokine and cytokine concentrations of septic patients were determined at enrollment and ten days after, in accordance with the diagnostic criteria of SEPSIS-3. The concentrations levels were measured in an enzyme-linked immunosorbent assay. Mortality was analyzed using the Kaplan-Meier method and Cox regressions. RESULTS Over a 25-month period, 145 patients were assessed for eligibility and consequently, 40 patients were analyzed. On admission, both groups had comparable physiological scores, comorbidities, malnutrition risk, anthropometric measurements, metabolic/hematologic biomarkers and concentrations of adipokines and cytokines (p > .05). Serum leptin, resistin, and cytokines (IL-6, IL-10, IL-1β and TNF-α) decreased significantly in the entire cohort over ten days following sepsis (p < .05). Serum resistin decreased in both olive oil-based and soybean oil-based lipid emulsions groups. Serum adiponectin only decreased in soybean oil-based lipid emulsions group (p < .05). There was association between survival and percentage changes in adiponectin, resistin and visfatin concentrations (log rank test: p < .05). CONCLUSION Adipokine and cytokine responses are affected by medical nutritional therapy in the sepsis process and adipokines may represent functional prognostic biomarkers in critically ill patients with sepsis.
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Altering Routine Intensive Care Unit Practices to Support Commensalism.
Hamilton, LA, Behal, ML
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2020;(3):433-441
Abstract
The gastrointestinal (GI) tract consists of trillions of organisms that support multiple functions in the body, from immunity, digestion, and absorption to drug metabolism. These microbes form an overall collection of microorganisms that form the body's microbiome. In critical illness, many of these functions are aberrant, and the microbiome is altered, leading to untoward effects. Some of the most common medications received by patients include antibiotics and proton pump inhibitors, which affect particular changes in the microbiome. In addition, patients receiving prolonged enteral and parenteral nutrition experience changes in the microbiological composition and diversity of their GI tracts. Research is ongoing to characterize the crosstalk between the microbiome and immune function as targets for drug and nutrition therapy.
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The rationale for Low-Molecular Weight Heparin (LMWH) use in SARS-CoV-2 infection.
Di Perri, G
Le infezioni in medicina. 2020;(suppl 1):52-56
Abstract
In spite of many ongoing attempts to repurpose existing antivirals, no drugs have emerged yet with the desirable activity against SARS-CoV-2. Hydroxychloroquine, lopinavir/ritonavir, remdesivir, umifenovir, favipiravir, ribavirin and beta-interferon-1 gave rise to variable but still inconsistent proof of clinical efficacy in the treatment of COVID-19. Pathogenetic studies have shown significant differences between commonly defined viral pneumonia and COVID-19 pulmonary disease. In severe forms, immune/inflammatory alterations reminiscent of disease forms like Macrophage Activation Syndrome (MAS) have been described, and therapeutic options other than anti-infective have been proposed and implemented, such as anti-inflammatory and anticoagulative agents. The thrombotic phenomena described in the pulmonary vascular bed of patients with severe COVID-19 suggest the administration of low-molecular weight heparin (LMWH) as standard measure in hospitalized patients with COVID-19.
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Critical care management of adults with community-acquired severe respiratory viral infection.
Arabi, YM, Fowler, R, Hayden, FG
Intensive care medicine. 2020;(2):315-328
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Abstract
With the expanding use of molecular assays, viral pathogens are increasingly recognized among critically ill adult patients with community-acquired severe respiratory illness; studies have detected respiratory viral infections (RVIs) in 17-53% of such patients. In addition, novel pathogens including zoonotic coronaviruses like the agents causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019 nCoV) are still being identified. Patients with severe RVIs requiring ICU care present typically with hypoxemic respiratory failure. Oseltamivir is the most widely used neuraminidase inhibitor for treatment of influenza; data suggest that early use is associated with reduced mortality in critically ill patients with influenza. At present, there are no antiviral therapies of proven efficacy for other severe RVIs. Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti-influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs. Evidence-based supportive care is the mainstay for management of severe respiratory viral infection. Non-invasive ventilation in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is associated with a high likelihood of transition to invasive ventilation. Limited existing knowledge highlights the need for data regarding supportive care and adjunctive pharmacologic therapy that is specific for critically ill patients with severe RVI. There is a need for more pragmatic and efficient designs to test different therapeutics both individually and in combination.
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Fat mass affects nutritional status of ICU COVID-19 patients.
De Lorenzo, A, Tarsitano, MG, Falcone, C, Di Renzo, L, Romano, L, Macheda, S, Ferrarelli, A, Labate, D, Tescione, M, Bilotta, F, et al
Journal of translational medicine. 2020;(1):299
Abstract
BACKGROUND Obesity and steatosis are associated with COVID-19 severe pneumonia. Elevated levels of pro-inflammatory cytokines and reduced immune response are typical of these patients. In particular, adipose tissue is the organ playing the crucial role. So, it is necessary to evaluate fat mass and not simpler body mass index (BMI), because BMI leaves a portion of the obese population unrecognized. The aim is to evaluate the relationship between Percentage of Fat Mass (FM%) and immune-inflammatory response, after 10 days in Intensive Care Unit (ICU). METHODS Prospective observational study of 22 adult patients, affected by COVID-19 pneumonia and admitted to the ICU and classified in two sets: (10) lean and (12) obese, according to FM% and age (De Lorenzo classification). Patients were analyzed at admission in ICU and at 10th day. RESULTS Obese have steatosis, impaired hepatic function, compromise immune response and higher inflammation. In addition, they have a reduced prognostic nutritional index (PNI), nutritional survival index for ICU patients. CONCLUSION This is the first study evaluating FM% in COVID-19 patient. We underlined obese characteristic with likely poorly prognosis and an important misclassification of obesity. A not negligible number of patients with normal BMI could actually have an excess of adipose tissue and therefore have an unfavorable outcome such as an obese. Is fundamental personalized patients nutrition basing on disease phases.
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Gastrointestinal Manifestations of COVID-19: Impact on Nutrition Practices.
Aguila, EJT, Cua, IHY, Fontanilla, JAC, Yabut, VLM, Causing, MFP
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2020;(5):800-805
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Although Coronavirus disease 2019 (COVID-19) is primarily a respiratory disease, growing evidence shows that it can affect the digestive system and present with gastrointestinal (GI) symptoms. Various nutrition societies have recently published their guidelines in context of the pandemic, and several points emphasize the impact of these GI manifestations on nutrition therapy. In patients with COVID-19, the normal intestinal mucosa can be disrupted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and this could result in GI symptoms and a compromise in nutrient absorption. Optimization of oral diet is still recommended. However, given the GI effects of COVID-19, a fraction of infected patients have poor appetite and would not be able to meet their nutrition goals with oral diet alone. For this at-risk group, which includes those who are critically ill, enteral nutrition is the preferred route to promote gut integrity and immune function. In carrying this out, nutrition support practices have been revised in such ways to mitigate viral transmission and adapt to the pandemic. All measures in the GI and nutrition care of patients are clustered to limit exposure of healthcare workers. Among patients admitted to intensive care units, a significant barrier is GI intolerance, and it appears to be exacerbated by significant GI involvement specific to the SARS-CoV-2 infection. Nevertheless, several countermeasures can be used to ease side effects. At the end of the spectrum in which intolerance persists, the threshold for switching to parenteral nutrition may need to be lowered.
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Role of heat shock protein and cytokine expression as markers of clinical outcomes with glutamine-supplemented parenteral nutrition in surgical ICU patients.
Wischmeyer, PE, Mintz-Cole, RA, Baird, CH, Easley, KA, May, AK, Sax, HC, Kudsk, KA, Hao, L, Tran, PH, Jones, DP, et al
Clinical nutrition (Edinburgh, Scotland). 2020;(2):563-573
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BACKGROUND Nutrients, such as glutamine (GLN), have been shown to effect levels of a family of protective proteins termed heat shock proteins (HSPs) in experimental and clinical critical illness. HSPs are believed to serve as extracellular inflammatory messengers and intracellular cytoprotective molecules. Extracellular HSP70 (eHSP70) has been termed a chaperokine due to ability to modulate the immune response. Altered levels of eHSP70 are associated with various disease states. Larger clinical trial data on GLN effect on eHSP expression and eHSP70's association with inflammatory mediators and clinical outcomes in critical illness are limited. OBJECTIVE Explore effect of longitudinal change in serum eHSP70, eHSP27 and inflammatory cytokine levels on clinical outcomes such as pneumonia and mortality in adult surgical intensive care unit (SICU) patients. Further, evaluate effect of parenteral nutrition (PN) supplemented with GLN (GLN-PN) versus GLN-free, standard PN (STD-PN) on serum eHSP70 and eHSP27 concentrations. METHODS Secondary observational analysis of a multicenter clinical trial in 150 adults after cardiac, vascular, or gastrointestinal surgery requiring PN support and SICU care conducted at five academic medical centers. Patients received isocaloric, isonitrogenous PN, with or without GLN dipeptide. Serum eHSP70 and eHSP27, interleukin-6 (IL-6), and 8 (IL-8) concentrations were analyzed in patient serum at baseline (prior to study PN) and over 28 days of follow up. RESULTS eHSP70 declined over time in survivors during 28 days follow-up, but non-survivors had significantly higher eHSP70 concentrations compared to survivors. In patients developing pneumonia, eHSP70, eHSP27, IL-8, and IL-6 were significantly elevated. Adjusted relative risk for hospital mortality was reduced 75% (RR = 0.25, p = 0.001) for SICU patients with a faster decline in eHSP70. The area under the receiver operating characteristic curve was 0.85 (95% CI: 0.76 to 0.94) for the final model suggesting excellent discrimination between SICU survivors and non-survivors. GLN-PN did not alter eHSP70 or eHSP27 serum concentrations over time compared to STD-PN. CONCLUSION Our results suggest that serum HSP70 concentration may be an important marker for severity of illness and likelihood of recovery in the SICU. GLN-supplemented-PN did not increase eHSP70.
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Medical treatment for botulism.
Chalk, CH, Benstead, TJ, Pound, JD, Keezer, MR
The Cochrane database of systematic reviews. 2019;(4):CD008123
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BACKGROUND Botulism is an acute paralytic illness caused by a neurotoxin produced by Clostridium botulinum. Supportive care, including intensive care, is key, but the role of other medical treatments is unclear. This is an update of a review first published in 2011. OBJECTIVES To assess the effects of medical treatments on mortality, duration of hospitalization, mechanical ventilation, tube or parenteral feeding, and risk of adverse events in botulism. SEARCH METHODS We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase on 23 January 2018. We reviewed bibliographies and contacted authors and experts. We searched two clinical trials registers, WHO ICTRP and clinicaltrials.gov, on 21 February 2019. SELECTION CRITERIA Randomized controlled trials (RCTs) and quasi-RCTs examining the medical treatment of any of the four major types of botulism (infant intestinal botulism, food-borne botulism, wound botulism, and adult intestinal toxemia). Potential medical treatments included equine serum trivalent botulism antitoxin, human-derived botulinum immune globulin intravenous (BIG-IV), plasma exchange, 3,4-diaminopyridine, and guanidine. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology.Our primary outcome was in-hospital death from any cause occurring within four weeks from randomization or the beginning of treatment. Secondary outcomes were death from any cause occurring within 12 weeks, duration of hospitalization, duration of mechanical ventilation, duration of tube or parenteral feeding, and proportion of participants with adverse events or complications of treatment. MAIN RESULTS A single RCT met the inclusion criteria. Our 2018 search update identified no additional trials. The included trial evaluated BIG-IV for the treatment of infant botulism and included 59 treatment participants and 63 control participants. The control group received a control immune globulin that did not have an effect on botulinum toxin. Participants were followed during the length of their hospitalization to measure the outcomes of interest. There was some violation of intention-to-treat principles, and possibly some between-treatment group imbalances among participants admitted to the intensive care unit and mechanically ventilated, but otherwise the risk of bias was low. There were no deaths in either group, making any treatment effect on mortality inestimable. There was a benefit in the treatment group on mean duration of hospitalization (BIG-IV: 2.60 weeks, 95% confidence interval (CI) 1.95 to 3.25; control: 5.70 weeks, 95% CI 4.40 to 7.00; mean difference (MD) -3.10 weeks, 95% CI -4.52 to -1.68; moderate-certainty evidence); mechanical ventilation (BIG-IV: 1.80 weeks, 95% CI 1.20 to 2.40; control: 4.40 weeks, 95% CI 3.00 to 5.80; MD -2.60 weeks, 95% CI -4.06 to -1.14; low-certainty evidence); and tube or parenteral feeding (BIG-IV: 3.60 weeks, 95% CI 1.70 to 5.50; control: 10.00 weeks, 95% CI 6.85 to 13.15; MD -6.40 weeks, 95% CI -10.00 to -2.80; moderate-certainty evidence), but not on proportion of participants with adverse events or complications (BIG-IV: 63.08%; control: 68.75%; risk ratio 0.92, 95% CI 0.72 to 1.18; absolute risk reduction 0.06, 95% CI 0.22 to -0.11; moderate-certainty evidence). AUTHORS' CONCLUSIONS We found low- and moderate-certainty evidence supporting the use of BIG-IV in infant intestinal botulism. A single RCT demonstrated that BIG-IV probably decreases the duration of hospitalization; may decrease the duration of mechanical ventilation; and probably decreases the duration of tube or parenteral feeding. Adverse events were probably no more frequent with immune globulin than with placebo. Our search did not reveal any evidence examining the use of other medical treatments including serum trivalent botulism antitoxin.
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Glucose homeostasis, nutrition and infections during critical illness.
Ingels, C, Vanhorebeek, I, Van den Berghe, G
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2018;(1):10-15
Abstract
Critical illness is a complex life-threatening disease characterized by profound endocrine and metabolic alterations and by a dysregulated immune response, together contributing to the susceptibility for nosocomial infections and sepsis. Hitherto, two metabolic strategies have been shown to reduce nosocomial infections in the critically ill, namely tight blood glucose control and early macronutrient restriction. Hyperglycaemia, as part of the endocrine-metabolic responses to stress, is present in virtually all critically ill patients and is associated with poor outcome. Maintaining normoglycaemia with intensive insulin therapy has been shown to reduce morbidity and mortality, by prevention of vital organ dysfunction and prevention of new severe infections. The favourable effects of this intervention were attributed to the avoidance of glucose toxicity and mitochondrial damage in cells of vital organs and in immune cells. Hyperglycaemia was shown to impair macrophage phagocytosis and oxidative burst capacity, which could be restored by targeting normoglycaemia. An anti-inflammatory effect of insulin may have contributed to prevention of collateral damage to host tissues. Not using parenteral nutrition during the first week in intensive care units, and so accepting a large macronutrient deficit, also resulted in fewer secondary infections, less weakness and accelerated recovery. This was at least partially explained by a suppressive effect of early parenteral nutrition on autophagic processes, which may have jeopardized crucial antimicrobial defences and cell damage removal. The beneficial impact of these two metabolic strategies has opened a new field of research that will allow us to improve the understanding of the determinants of nosocomial infections, sepsis and organ failure in the critically ill.
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Hypermetabolism and Nutritional Support in Sepsis.
Alverdy, JC
Surgical infections. 2018;(2):163-167
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BACKGROUND Surgical metabolism has been a founding field of investigation in surgery without which the boundaries of critical care, trauma, and surgical oncology could not have advanced. Traditionally, understanding the shifts in electrolytes, carbohydrates, fats, and amino acids that could explain the rapidly evolving proteolysis after catabolic stress and tumor growth has been a major focus of research that led to our current approach to maintaining homeostasis over the course of major surgical intervention and injury. METHOD Review of the English-language literature. RESULTS With the emerging field of inflammation and the discovery of cytokines and chemokines, surgical metabolism has taken a second seat in the surgical research arena. Yet central to all patient management after injury is an understanding of how catabolic stress erodes vital organ function and how current approaches can support metabolism through the most physiologically stressful perturbations known to man, for which there is no evolutionary precedent. Although it is well accepted that unabated proteolysis is not a sustainable physiologic state, in the era of modern medicine, precisely how to manipulate the body nutritionally to drive a recovery-directed immune response remains highly debated. This review incorporates multiple lines of inquiry in surgical metabolism, with a particular focus on sepsis. CONCLUSION The changing landscape of previous paradigms in the field is discussed. Finally, how next-generation technology might spark renewed interest in this field among surgical investigators is considered.