The relationship between the degree of malnutrition and changes in selected parameters of the immune response in critically ill patients.

Patients treated in intensive care units (ICUs) are at high risk of malnutrition and the resulting homeostasis, metabolic, histological and immunological disorders, especially leading to organ failure and increased susceptibility to infection. In 163 patients with malnutrition [mild in 33 (19.6%), moderate in 69 (42.9%), severe in 61 (37.4%)] treated in the ICU, changes in the concentration of selected proteins [interleukin (IL)-1Ra, tumor necrosis factor α (TNF-α), soluble tumour necrosis factor receptor-1 (sTNFR1), IL-6, IL-10, sTLR4, MyD88, A20, HSP70, HMGB1] were examined. In the whole group of malnourished patients, median values of sTNFR1, TNF-α, IL-6, TLR4, IL-1Ra were significantly increased, while the levels of MyD88 and A20 proteins were significantly reduced (in comparison to the well-nourished healthy group). Only the sTNFR1 protein showed a significant difference between mild, moderate and severe malnutrition, and increased concentrations as the severity of malnutrition increased (the correlation study found that as the degree of malnutrition increased, the sTNFR1 concentrations increased; p = 0.0000, R = 0.5442). It was observed that death was significantly more frequent in the group of patients who on the first day of hospitalization in the ICU scored 5 or more points on the NRS 2002 scale (p = 0.0004). In the patients who died significantly higher concentrations of sTNFR1, IL-6, IL-10, HSP70 were observed in comparison to the patients who survived. The present results are encouraging and indicate the desirability of undertaking multicentre clinical trials including monitoring of sTNFR1 in assessing the severity of malnutrition and immune disorders in the first hours after admission to the ICU, because it can be assumed that without early diagnosis of innate immunity disorders any attempts at their modulation may be ineffective.

Association between disease-related malnutrition and innate immunity gene expression in critically ill patients at intensive care unit admission.

The aim of the study was to analyse the relationship between nutritional disorders and the expression of innate antibacterial response genes in patients admitted to the intensive care unit (ICU). In 46 patients with severe malnutrition and life-threatening surgical complications, nutritional status tests were performed on the basis of the NRS 2002 (Nutritional Risk Screening) scale, cytokine, albumin, C-reactive protein concentrations, anthropometric tests, and body composition analysis. Concurrently, the expression of Toll-like receptor 2, NOD1, TRAF6, and HMGB1 genes was determined in peripheral blood leukocytes at the mRNA level using real-time polymerase chain reaction. It was found that both the nutritional status and the gene expression changed depending on the group of patients studied (including the group of survivors vs. non-survivors). Significant correlations were found between the results of routine tests used in the diagnostics of malnutrition (including NRS 2002, resistance, reactance, phase angle, excess of extracellular water) and the expression of the studied genes. Moreover, the expression of TRAF6 and HMGB1 genes correlated with the Acute Physiology and Chronic Health Evaluation II scale and the age of the patients. The results of the research suggest that the expression of innate antibacterial response genes may be a new diagnostic tool complementing the assessment of nutritional disorders in surgical patients admitted to the ICU. These tests may be helpful in providing more accurate diagnostics of the genetic effects of malnutrition and in the monitoring of patients for whom nutritional treatment is planned to support the functions of the immune system, thereby increasing the effectiveness of this type of treatment in the ICU.

Disorders of nutritional status in sepsis - facts and myths.

The problem of diagnosing nutritional status disorders in septic patients remains unresolved. This is associated with the necessity of the introduction of newer and newer methods of assessing nutritional status, often requiring precise and expensive equipment as well as employment of professionals in this field in hospital wards, primarily including intensive care units (ICU). Methods that have been applied thus far for assessing nutritional status, also used in severely ill septic patients, have little impact on improving treatment results. This is due to the high dynamics of changes in nutritional status in these patients, healing process variability in individual patients, and the "mismatch" of methods for assessing nutritional status in relation to the patient's clinical status. The diagnostic value of the traditional methods of assessing nutritional status, i.e. anthropometric analysis and selected laboratory tests, as markers of nutritional status disorders in septic patients, is still debatable. There is still no precise method that could become the "gold standard" allowing for early identification of malnutrition in these group of patients. Phase angle, bioelectrical impedance vector analysis (BIVA), and the "illness marker", obtained directly from the resistance, reactance, and impedance, can be used as prognostic or nutritional indices in severely ill septic patients, but the intensity of research on this subject needs to be increased. Detailed assessment of nutritional status should include tests of selected inflammation markers (including TLC, HMGB1, IL-6, IL-10, IL-1ra, sTNFRI).

Innate immunity gene expression changes in critically ill patients with sepsis and disease-related malnutrition.

The aim of this study was an attempt to determine whether the expression of genes involved in innate antibacterial response (TL R2, NOD 1, TRAF6, HMGB 1 and Hsp70) in peripheral blood leukocytes in critically ill patients, may undergo significant changes depending on the severity of the infection and the degree of malnutrition. The study was performed in a group of 128 patients with infections treated in the intensive care and surgical ward. In 103/80.5% of patients, infections had a severe course (sepsis, severe sepsis, septic shock, mechanical ventilation of the lungs). Clinical monitoring included diagnosis of severe infection (according to the criteria of the ACC P/SCC M), assessment of severity of the patient condition and risk of death (APACHE II and SAPS II), nutritional assessment (NRS 2002 and SGA scales) and the observation of the early results of treatment. Gene expression at the mRNA level was analyzed by real-time PCR. The results of the present study indicate that in critically ill patients treated in the IC U there are significant disturbances in the expression of genes associated with innate antimicrobial immunity, which may have a significant impact on the clinical outcome. The expression of these genes varies depending on the severity of the patient condition, severity of infection and nutritional status. Expression disorders of genes belonging to innate antimicrobial immunity should be diagnosed as early as possible, monitored during the treatment and taken into account during early therapeutic treatment (including early nutrition to support the functions of immune cells).