► Cytokines have been widely assessed as potential biomarkers in sepsis. ► None has sufficient specificity or sensitivity to be employed in clinical practice. ► A combined cytokine score was ...evaluated to predict mortality in severe sepsis. ► The combined score predicted better mortality than individual interleukins. ► Combined scores could improve the prognostic render of cytokines in severe sepsis.
Identification of patients at increased risk of death is dramatically important in severe sepsis. Cytokines have been widely assessed as potential biomarkers in this disease, but none of the cytokines studied has evidenced a sufficient specificity or sensitivity to be routinely employed in clinical practice. In this pilot study, we profiled 17 immune mediators in the plasma of 29 consecutively recruited patients with severe sepsis or septic shock, during the first 24h following admission to the ICU, by using a Bio-Plex Human Cytokine 17-Plex Panel (Bio-Rad). Patients were 66.1year old in average. Twelve patients of our cohort died during hospitalization at the ICU, eight of them in the first 72h due to multiorganic dysfunction syndrom (MODS). Levels in plasma of three pro-inflammatory mediators (IL-6, IL-8, MCP-1) and of an immunosuppressive one (IL-10) were higher in those patients with fatal outcome. We developed a combined score with those cytokines showing to better predict mortality in our cohort based on the results of Cox regression analysis. This way, IL-6, IL-8 and IL-10 were included in the score. Patients were split into two groups based on the percentile 75 (P75) of the plasma levels of these three interleukins. Those patients showing at least one interleukin value higher than P75 were given the value “1”. Those patients showing IL-6, IL-8, IL-10 levels below P75 were given the value “0”. Hazard ratios for mortality at day 3 and day 28th obtained with the combined score were 2–3-fold higher than those obtained with the individual interleukins values. In conclusion, we have described a combined cytokine score associated with a worse outcome in patients with sepsis, which may represent a new avenue to be explored for guiding treatment decisions in this disease.
A female patient in her 30s presented to the emergency department with a 10-day history of fever, weakness and diaphoresis. Subsequent investigations revealed a diagnosis of haemophagocytic syndrome, ...secondary to disseminated non-tuberculous mycobacterial infection affecting the bone marrow, lungs, lymph nodes and skin. The bone marrow culture confirmed the presence of
infection. The patient's haemophagocytic syndrome was managed using the HLH-2004 chemoimmunotherapy, and
infection was treated with a combination of clarithromycin, ethambutol, rifampicin, ciprofloxacin and amikacin. Throughout her hospitalisation, the patient faced several serious complications arising from both the medications and the prolonged hospital stay (lasting 12 months). However, these complications were promptly identified and effectively managed through a multidisciplinary and comprehensive approach. This approach was crucial in achieving a favourable patient outcome and successful recovery.
The interaction between influenza virus and the host response to infection clearly plays an important role in determining the outcome of infection. While much is known on the participation of ...inflammation on the pathogenesis of severe A (H1N1) pandemic 09-influenza virus, its role in the course of non-fatal pneumonia has not been fully addressed.
A systems biology approach was used to define gene expression profiles, histology and viral dynamics in the lungs of healthy immune-competent mice with pneumonia caused by a human influenza A (H1N1) pdm09 virus, which successfully resolved the infection.
Viral infection activated a marked pro-inflammatory response at the lung level paralleling the emergence of histological changes. Cellular immune response and cytokine signaling were the two signaling pathway categories more representative of our analysis. This transcriptome response was associated to viral clearance, and its resolution was accompanied by resolution of histopathology.
These findings suggest a dual role of pulmonary inflammation in viral clearance and development of pneumonia during non-fatal infection caused by the 2009 pandemic influenza virus. Understanding the dynamics of the host's transcriptomic and virological changes over the course of the infection caused by A (H1N1) pdm09 virus may help identifying the immune response profiles associated with an effective response against influenza virus.
Abstract Purpose Critical illness results in derangements of all components of the immune response. Nonetheless, most of the efforts evaluating immune status in critically ill patients have been done ...in the field of sepsis. Here we have evaluated the immunity status at intensive care unit (ICU) admission in a cohort of nonseptic critically ill patients and its influence on their outcome. Material and methods Ninety patients 18 years and older admitted to our ICU were studied for levels of immunoglobulin (Ig) G, IgM, IgA, CD3+ CD4+ T cells, CD3+ CD8+ T cells, B cells, natural killer (NK) cells, and C3 and C4 complement factors in peripheral blood in the next 24 hours after admission to the ICU. Patients with infection, sepsis, immunodeficiency, or concomitant immunosuppressive therapy were excluded. Results Levels of IgM, CD3+ T cells, CD4+ T cells, CD8+ T cells, and B lymphocytes correlated inversely with age. In turn, levels of CD3+ T cells, CD4+ T cells, CD8+ T cells, and C3 factor of the complement system correlated inversely with Acute Physiology and Chronic Health Evaluation II score. Multivariate Cox regression analysis censored at 28 days evidenced that levels of IgM played a protective role, whereas levels of NK cells behaved as a risk factor for mortality. Kaplan-Meier curves showed a cutoff of 58 mg/dL for IgM and 140 cells/mm3 for NK cells. Conclusions In conclusion, our results demonstrate that IgM plays a protective role in critically ill patients with no sepsis, whereas NK cell counts seem to play a deleterious one. Aging and severity at admission affect levels of key factors of the immune system in the blood of these patients.
Current methods for the hardening step of functional coatings over different materials imply the use of high temperatures, high energy consumption or long periods of time, which have repercussions on ...the speed and cost of the product. We report here a simple and low-cost methodology for the functionalization of low-cost stainless steel, which is modular, depending on the functionality pursued: a levelling layer for smoothing the surface of the material, an "easy to clean" property, or both of them. This research is based on sol-gel coatings cured under UV light without requiring high thermal hardening processes, making it applicable to plastics and other sensible materials and possessing high chemical and thermal stability. The film ensures lower processing costs and higher rates of hardening if adequate medium-pressure lamps are employed. This formulation is also well-defined for scaling up the process, so it is possible to perform a continuous coating in large areas by employing mild processing conditions (low temperature, atmospheric pressure). In addition, the sol-gel solution was fully characterized and studied in order to guarantee a long service life before deposition, with a focus on industrial applications in the domestic sector.
Severe status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity ...of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank:
= 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064-8.665),
< 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540-50.878),
= 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.
Host immunity should play a principal role in determining both the outcome and recovery of patients with sepsis that originated from a microbial infection. Quantification of the levels of key ...elements of the immune response could have a prognostic value in this disease.
In an attempt to evaluate the quantitative changes in the status of immunocompetence in severe sepsis over time and its potential influence on clinical outcome, we monitored the evolution of immunoglobulins (Igs) (IgG, IgA and IgM), complement factors (C3 and C4) and lymphocyte subsets (CD4+ T cells, CD8+ T cells, B cells (CD19+) and natural killer (NK) cells (CD3-CD16+CD56+)) in the blood of 50 patients with severe sepsis or septic shock at day 1, day 3 and day 10 following admission to the ICU.
Twenty-one patients died, ten of whom died within the 72 hours following admission to the ICU. The most frequent cause of death (n = 12) was multiorgan dysfunction syndrome. At day 1, survivors showed significantly higher levels of IgG and C4 than those who ultimately died. On the contrary, NK cell levels were significantly higher in the patients who died. Survivors exhibited a progressive increase from day 1 to day 10 on most of the immunological parameters evaluated (IgG, IgA, IgM, C3, CD4+, CD8+ T cells and NK cells). Multivariate Cox regression analysis, including age, sex, APACHE II score, severe sepsis or septic shock status and each one of the immunological parameters showed that NK cell counts at day 1 were independently associated with increased risk of death at 28 days (hazard ratio = 3.34, 95% CI = 1.29 to 8.64; P = 0.013). Analysis of survival curves provided evidence that levels of NK cells at day 1 (> 83 cells/mm³) were associated with early mortality.
Our results demonstrate the prognostic role of NK cells in severe sepsis and provide evidence for a direct association of early counts of these cells in blood with mortality.
The aim of this study was to investigate the relationship between the CD14 rs2569190 polymorphism and death related to septic shock in white European patients who underwent major cardiac or abdominal ...surgery. We carried out a retrospective study in 205 septic shock patients. The septic shock diagnosis was established by international consensus definitions. The outcome variable was the death within 28, 60 and 90 days after septic shock diagnosis. The CD14 rs2569190 polymorphism was analyzed by Agena Bioscience's MassARRAY platform. For the genetic association analysis with survival was selected a recessive inheritance model (GG vs. AA/AG). One hundred thirteen out of 205 patients (55.1%) died with a survival median of 39 days (95%CI = 30.6; 47.4). Patients with rs2569190 GG genotype had shorter survival probability than rs2569190 AA/AG genotype at 60 days (62.3% vs 50%; p = 0.035), and 90 days (62.3% vs 52.6%; p = 0.046). The rs2569190 GG genotype was associated with increased risk of septic shock-related death in the first 60 days (adjusted hazard ratio (aHR) = 1.67; p = 0.016) and 90 days (aHR = 1.64; p = 0.020) compared to rs2569190 AA/AG genotype. In conclusion, the presence of CD14 rs2569190 GG genotype was associated with death in shock septic patients who underwent major surgery. Further studies with bigger sample size are required to verify this relationship.
IL‐1B rs16944 polymorphism is related to septic shock and death Jiménez‐Sousa, María Ángeles; Medrano, Luz M.; Liu, Pilar ...
European journal of clinical investigation,
January 2017, 2017-Jan, 2017-01-00, 20170101, Letnik:
47, Številka:
1
Journal Article
Recenzirano
Background
IL‐1β is a primary mediator of systemic inflammatory response syndrome (SIRS) and it may lead to shock septic. Our aim was to analyse whether IL‐1B rs16944 polymorphism is associated with ...the onset of septic shock and death after major surgery.
Materials and methods
We performed a case–control study on 467 patients who underwent major cardiac or abdominal surgery. Of them, 205 patients developed septic shock (cases, SS group) and 262 patients developed SIRS (controls, SIRS group). The primary outcome variables were the development of septic shock and death within 90 days after diagnosis of septic shock. The IL‐1B rs16944 polymorphism was genotyped by Sequenom's MassARRAY platform. The association analysis was performed under a recessive genetic model (AA vs. GG/GC).
Results
The frequency of septic shock was higher in patients with IL‐1B rs16944 AA genotype than in patients with IL‐1B rs16944 GG/AG genotype when all patients were taken into account (63·6% vs. 41·8%; P = 0·006), cardiac surgery (52·2% vs. 33·3%; P = 0·072) and abdominal surgery (76·2% vs. 50·2%; P = 0·023). However, the IL‐1B rs16944 AA genotype was only associated with higher likelihood of septic shock in the analysis of all population adjusted odds ratio (aOR) = 2·26 (95%CI = 1·03; 4·97; P = 0·042, but not when it was stratified by cardiac surgery (P = 0·175) or abdominal surgery (P = 0·467). Similarly, IL‐1B rs16944 AA genotype was also associated with higher likelihood of septic shock‐related death in all population aOR = 2·67 (95%CI = 1·07; 4·97); P = 0·035.
Conclusions
IL‐1B rs16944 AA genotype seems to be related to the onset of septic shock and death in patients who underwent major surgery.
The role of systemic immunity in the pathogenesis of cirrhosis is not fully understood. Analysis of transcriptomic profiles in blood is an easy approach to obtain a wide picture of immune response at ...the systemic level. We studied gene expression profiles in blood from thirty cirrhotic patients and compared them against those of eight healthy volunteers. Most of our patients were male n = 21, 70% in their middle ages 57.4 ± 6.8 yr. Alcohol abuse was the most frequent cause of cirrhosis (n = 22, 73%). Eleven patients had hepatocellular carcinoma (36.7%). Eight patients suffered from hepatitis C virus infection (26.7%). We found a signature constituted by 3402 genes which were differentially expressed in patients compared to controls (2802 over-expressed and 600 under-expressed). Evaluation of this signature evidenced the existence of an active pro-fibrotic transcriptomic program in the cirrhotic patients, involving the extra-cellular matrix (ECM)-receptor interaction & TGF-beta signaling pathways along with the Cell adhesion molecules pathway. This program coexists with alterations in pathways participating in Glycine, serine and threonine metabolism, Phenylalanine metabolism, Tyrosine metabolism, ABC transporters, Purine metabolism, Arachidonic acid metabolism. In consequence, our results evidence the co-existence in blood of a genomic program mediating pro-fibrotic mechanisms and metabolic alterations in advanced cirrhosis. Monitoring expression levels of the genes involved in these programs could be of interest for predicting / monitoring cirrhosis evolution. These genes could constitute therapeutic targets in this disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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