scholarly journals TACI και σήψη σε βαρέως πάσχοντες ασθενείς στη ΜΕΘ

2014 ◽  
Author(s):  
Μαρία Κομπότη
Keyword(s):  
Sofa Score ◽  
Hazard Ratio ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Odds Ratios ◽  
Toll Like Receptor 4 ◽  
Pcr Rflp

Σκοπός: ο προσδιορισμός των γενετικών πολυμορφισμών των μορίων TACI, BAFF και TLR4 και η διερεύνηση πιθανής συσχέτισής τους με την εμφάνιση σήψης και τη θνητότητα σε ασθενείς που εισάγονται στη ΜΕΘ. Ασθενείς-Μέθοδος: Προοπτική μελέτη παρακολούθησης όλων των ασθενών που εισήχθησαν στη Μονάδα Εντατικής Θεραπείας μέχρι την έκβαση (έξοδος, θάνατος). Για τη φυσική ανοσία μελετήθηκαν δύο πολυμορφισμοί του toll-like receptor 4 (ΤLR4-D299G και TLR4-T399I) και ένας πολυμορφισμός του C2 που προκαλεί ανεπάρκεια συμπληρώματος (C2del28bp). Για την επίκτητη ανοσία μελετήθηκαν δύο πολυμορφισμοί του BAFF-R (BAFF-R-H159Y και BAFF-R-P21R) και ένας του TACI (TACI-C104R). Η ανίχνευση των πολυμορφισμών έγινε με αλυσιδωτή αντίδραση πολυμεράσης και ανάλυση με ενδονουκλεάσες περιορισμού (PCR-RFLP). Αποτελέσματα: Στη μελέτη συμπεριελήφθησαν 215 ασθενείς (148 άνδρες και 67 γυναίκες). Η ηλικία (μέσος ± SD) ήταν 54,1±19,7 έτη, APACHE II score εισαγωγής στη ΜΕΘ 22,0±6,0 και SOFA score εισαγωγής στη ΜΕΘ 9,7±3,5. Σήψη στη ΜΕΘ βρέθηκε σε 108 ασθενείς (50,2%) και η θνητότητα στη ΜΕΘ ήταν 20,5% [95% διάστημα αξιοπιστίας 15,0–25,9]. Οι SNPs του TLR4 βρέθηκαν σε συζευγμένη κατάσταση. Οι φορείς κάποιου TLR4 SNP και οι φορείς του BAFFR-P21R συσχετίστηκαν ανεξάρτητα με χαμηλότερη πιθανότητα σήψης στη ΜΕΘ συγκριτικά με τους wild-type ομοζυγώτες [διορθωμένα odds ratios 0,32, 95%CI 0,12–0,86, p=0,024 για τον TLR4-T399I, 0,34, 95%CI 0,13–0,94, p=0,037 για τον TLR4-T399I and 0,44, 95%CI 0,20–0,97, p=0,044 για τον BAFFR-P21R]. Από την ανάλυση υποομάδων, φάνηκε ότι η συσχέτιση αυτή αφορούσε στους παθολογικούς ασθενείς και οριακά στους τραυματίες, ενώ στους χειρουργικούς ασθενείς δεν παρατηρήθηκε συσχέτιση. Η φορεία του TACI-C104R SNP είχε καλή προβλεπτική αξία μετά από διόρθωση ως προς συγχυτικούς παράγοντες [hazard ratio 5,01 (1,14–22,03, p=0,033). Ο BAFFR-H159Y SNP δεν συσχετίστηκε με την εμφάνιση σήψης και τη θνητότητα, ενώ ο πολυμορφισμός C2del28bp δεν ανευρέθηκε στο δείγμα της μελέτης.Συμπεράσματα: Η μελέτη μας έδειξε ότι σε βαρέως πάσχοντες ασθενείς ΜΕΘ, οι πολυμορφισμοί TLR4-D299G (rs4986790), TLR4-T399I (rs4986791) και TNFRSF13C/BAFFR-P21R (rs77874543) ασκούν προστατευτική επίδραση αναφορικά με την εμφάνιση σήψης, ενώ ο πολυμορφισμός TNFRSF13B/TACI-C104R (rs34557412) συσχετίζεται σημαντικά με αύξηση της θνητότητας στη ΜΕΘ. Ο πολυμορφισμός TNFRSF13C/BAFFR-H159Y (rs61756766) δεν συσχετίστηκε με την εμφάνιση σήψης ή τη θνητότητα στη ΜΕΘ. Διαπιστώθηκε ανισορροπία σύνδεσης για τους πολυμορφισμούς TLR4-D299G (rs4986790) και TLR4-T399I (rs4986791) και για τους πολυμορφισμούς TNFRSF13C/BAFFR-P21R (rs77874543) και TNFRSF13C/BAFFR-H159Y (rs61756766). Ο πολυμορφισμός C2-c.841_849+19del28 (rs9332736) δεν ανιχνεύτηκε στο δείγμα των ασθενών της μελέτης.

scholarly journals Toll-like Receptor 4 Signaling in Ventilator-induced Diaphragm Atrophy

2012 ◽  
Vol 117 (2) ◽  
pp. 329-338 ◽  
Author(s):  
Willem-Jan M. Schellekens ◽  
Hieronymus W. H. van Hees ◽  
Michiel Vaneker ◽  
Marianne Linkels ◽  
P. N. Richard Dekhuijzen ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Caspase 3 ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Toll Like Receptor 4 ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Diaphragm Atrophy ◽  
Deficient Mice

Background Mechanical ventilation induces diaphragm muscle atrophy, which plays a key role in difficult weaning from mechanical ventilation. The signaling pathways involved in ventilator-induced diaphragm atrophy are poorly understood. The current study investigated the role of Toll-like receptor 4 signaling in the development of ventilator-induced diaphragm atrophy. Methods Unventilated animals were selected for control: wild-type (n = 6) and Toll-like receptor 4 deficient mice (n = 6). Mechanical ventilation (8 h): wild-type (n = 8) and Toll-like receptor 4 deficient (n = 7) mice.Myosin heavy chain content, proinflammatory cytokines, proteolytic activity of the ubiquitin-proteasome pathway, caspase-3 activity, and autophagy were measured in the diaphragm. Results Mechanical ventilation reduced myosin content by approximately 50% in diaphragms of wild-type mice (P less than 0.05). In contrast, ventilation of Toll-like receptor 4 deficient mice did not significantly affect diaphragm myosin content. Likewise, mechanical ventilation significantly increased interleukin-6 and keratinocyte-derived chemokine in the diaphragm of wild-type mice, but not in ventilated Toll-like receptor 4 deficient mice. Mechanical ventilation increased diaphragmatic muscle atrophy factor box transcription in both wild-type and Toll-like receptor 4 deficient mice. Other components of the ubiquitin-proteasome pathway and caspase-3 activity were not affected by ventilation of either wild-type mice or Toll-like receptor 4 deficient mice. Mechanical ventilation induced autophagy in diaphragms of ventilated wild-type mice, but not Toll-like receptor 4 deficient mice. Conclusion Toll-like receptor 4 signaling plays an important role in the development of ventilator-induced diaphragm atrophy, most likely through increased expression of cytokines and activation of lysosomal autophagy.

scholarly journals Fr402 MELD-NA SCORE VERSUS SOFA SCORE AND APACHE II SCORE AS EARLY PREDICTORS OF MORTALITY IN COVID-19 PATIENTS WITH LIVER INVOLVEMENT

2021 ◽  
Vol 160 (6) ◽  
pp. S-312-S-313
Author(s):  
Sandra R. Gomez ◽  
Eric Lam ◽  
Luis Gonzalez Mosquera ◽  
Joshua Fogel ◽  
Paul Mustacchia
Keyword(s):  
Sofa Score ◽  
Apache Ii ◽  
Liver Involvement ◽  
Apache Ii Score ◽  
Predictors Of Mortality ◽  
Early Predictors

scholarly journals Serum Soluble Triggering Receptor Expressed on Myeloid Cells-1 and Procalcitonin Can Reflect Sepsis Severity and Predict Prognosis: A Prospective Cohort Study

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Zhenyu Li ◽  
Hongxia Wang ◽  
Jian Liu ◽  
Bing Chen ◽  
Guangping Li
Keyword(s):  
Sofa Score ◽  
Prognostic Significance ◽  
Elevated Serum ◽  
Myeloid Cells ◽  
Serum Levels ◽  
Clinical Severity ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Survival Group ◽  
Severity Scores

Objective. To investigate the prognostic significance of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), procalcitonin (PCT), N-terminal probrain natriuretic peptide (NT-pro-BNP), C-reactive protein (CRP), cytokines, and clinical severity scores in patients with sepsis.Methods. A total of 102 patients with sepsis were divided into survival group (n=60) and nonsurvival group (n=42) based on 28-day mortality. Serum levels of biomarkers and cytokines were measured on days 1, 3, and 5 after admission to an ICU, meanwhile the acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores were calculated.Results. Serum sTREM-1, PCT, and IL-6 levels of patients in the nonsurvival group were significantly higher than those in the survival group on day 1 (P<0.01). The area under a ROC curve for the prediction of 28 day mortality was 0.792 for PCT, 0.856 for sTREM-1, 0.953 for SOFA score, and 0.923 for APACHE II score. Multivariate logistic analysis showed that serum baseline sTREM-1 PCT levels and SOFA score were the independent predictors of 28-day mortality. Serum PCT, sTREM-1, and IL-6 levels showed a decrease trend over time in the survival group (P<0.05). Serum NT-pro-BNP levels showed the predictive utility from days 3 and 5 (P<0.05).Conclusion. In summary, elevated serum sTREM-1 and PCT levels provide superior prognostic accuracy to other biomarkers. Combination of serum sTREM-1 and PCT levels and SOFA score can offer the best powerful prognostic utility for sepsis mortality.

scholarly journals Risk factors for mortality in critically ill patients with COVID-19: a multicenter retrospective case-control study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jinghua Gao ◽  
Li Zhong ◽  
Ming Wu ◽  
Jingjing Ji ◽  
Zheying Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Organ Failure ◽  
Critically Ill ◽  
Sofa Score ◽  
Lymphocyte Count ◽  
Cox Regression ◽  
Survival Curve ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Hospital Death

Abstract Background Coronavirus disease 2019 (COVID-19) has spread around the world, until now, the number of positive and death cases is still increasing. Therefore, it remains important to identify risk factors for death in critically patients. Methods We collected demographic and clinical data on all severe inpatients with COVID-19. We used univariable and multivariable Cox regression methods to determine the independent risk factors related to likelihood of 28-day and 60-day survival, performing survival curve analysis. Results Of 325 patients enrolled in the study, Multi-factor Cox analysis showed increasing odds of in-hospital death associated with basic illness (hazard ratio [HR] 6.455, 95% Confidence Interval [CI] 1.658–25.139, P = 0.007), lymphopenia (HR 0.373, 95% CI 0.148–0.944, P = 0.037), higher Sequential Organ Failure Assessment (SOFA) score on admission (HR 1.171, 95% CI 1.013–1.354, P = 0.033) and being critically ill (HR 0.191, 95% CI 0.053–0.687, P = 0.011). Increasing 28-day and 60-day mortality, declining survival time and more serious inflammation and organ failure were associated with lymphocyte count < 0.8 × 109/L, SOFA score > 3, Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 7, PaO2/FiO2 < 200 mmHg, IL-6 > 120 pg/ml, and CRP > 52 mg/L. Conclusions Being critically ill and lymphocyte count, SOFA score, APACHE II score, PaO2/FiO2, IL-6, and CRP on admission were associated with poor prognosis in COVID-19 patients.

scholarly journals The Characteristics of Mortality Predictor Scoring for Sepsis Patients in Haji Adam Malik Hospital

2021 ◽  
Vol 8 (10) ◽  
pp. 339-344
Author(s):  
Abdul Halim Harahap ◽  
Franciscus Ginting ◽  
Lenni Evalena Sihotang
Keyword(s):  
Sofa Score ◽  
Scoring System ◽  
Scoring Systems ◽  
Developed Countries ◽  
Apache Ii ◽  
Apache Ii Score ◽  
P Value ◽  
Cross Sectional ◽  
Cross Sectional Design ◽  
Score Apache

Introduction: Sepsis is a leading cause of death in the Intensive Care Unit (ICU) in developed countries and its incidence is increasing. Many scoring systems are used to assess the severity of disease in patients admitted to the ICU. SOFA score to assess the degree of organ dysfunction in septic patients. The Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system is most often used for patients admitted to the ICU. CCI scoring system to assess the effect of comorbid disease in critically ill patients on mortality. The study aimed to describe the characteristics of the use of scoring to predict patients’ mortality admitted to Haji Adam Malik Hospital. Methods: This is an observational study with a cross-sectional design. A total of 299 study subjects met the inclusion criteria and exclusion criteria, three types of scoring, namely SOFA score, APACHE II score, and CCI score were used to assess the prognosis of septic patients. Data analysis was performed using SPSS. P-value <0.05 was considered statistically significant. Results: A total of 252 people (84.3%) of sepsis patients died. The mean age of the septic patients who died was 54.25 years. The SOFA score ranged from 0-24, the median SOFA score in deceased sepsis patients was 5.0. The APACHE II score ranged from 0-71, the median APACHE II score in deceased sepsis patients was 23.0. The CCI score ranged from 0-37, the median CCI score in deceased sepsis patients was 5.0. Conclusion: Higher scores are associated with an increased probability of death in septic patients. Keywords: Sepsis; mortality predictor; SOFA score; APACHE II score, CCI score.

scholarly journals Clinical Characteristics of Carbapenem-Resistant Klebsiella Pneumoniaee Infections In A Tertiary Hospital In China

2021 ◽  
Author(s):  
Zhiwen Cui ◽  
Lirui Wang ◽  
Wei Chang ◽  
Minghui Li ◽  
Yuexia Li ◽  
...  
Keyword(s):  
Survival Time ◽  
Sofa Score ◽  
Clinical Characteristics ◽  
Bloodstream Infections ◽  
Polymyxin B ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Drainage Fluid ◽  
Carbapenem Resistant ◽  
Antimicrobial Regimen

Abstract Background：The infections due to carbapenem-resistant Klebsiella pneumoniae (CR-KP) have become an important problem. The aim of the study is to evaluate the clinical characteristics of CR-KP.Methods: A retrospective cohort study has been made on all patients presenting with CR-KP infections. 615 patients with CR-KP humor infections diagnosed were identified. 135 patients who did not meet the requirements were excluded. Clinical characteristics, antimicrobial regimens, and outcomes of patients have been analyzed.Results: The CR-KP infections overall mortality was 37.3%, and bloodstream infections mortality was 66.2%. Survival analysis revealed that there were statistically significant differences between bloodstream infection and pulmonary and drainage fluid infection. Logistics regression analysis showed that hemopathy, age (>60 years), solid tumors, diabetes, septic shock, acute kidney injury and stroke were independent predictors associated with the 30-day mortality. Multivariate linear regression was performed in APACHE II score, SOFA score, lymphocyte absolute value (LYM) and survival time. Survival time was negatively correlated with APACHE II score and SOFA score, while positively correlated with LYM. Finally, we investigated different antimicrobial regimens for CR-KP infections. Chi-square test showed that antimicrobial regimen combined carbapenems, tigecycline with polymyxin B was superior the one combined carbapenems with polymyxin B. Ceftazidime avibactam-based antimicrobial regimens also had no advantage over other therapeutic regimens.Conclusions: Our study confirmed there is a high mortality rate in CR-KP infections, especially in the bloodstream infections. The outcome is greatly influenced by the patients’ clinical conditions. Antimicrobial regimen combined carbapenems, tigecycline with polymyxin B might be a better choice.

Monosodium urate crystal interleukin-1β release is dependent on Toll-like receptor 4 and transient receptor potential V1 activation

Rheumatology ◽  
2019 ◽  
Author(s):  
Mateus F. Rossato ◽  
Carin Hoffmeister ◽  
Gabriela Trevisan ◽  
Fabio Bezerra ◽  
Thiago M. Cunha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Synovial Fluid ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Acute Gout ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Toll Like Receptor 4 ◽  
Transient Receptor ◽  
Nitrite Nitrate

AbstractObjectiveThe present study aimed to elucidate the mechanisms involved in MSU-induced IL-1β release in a rodent animal model of acute gout arthritis.MethodsPainful (mechanical and thermal hypersensitivity, ongoing pain and arthritis score) and inflammatory (oedema, plasma extravasation, cell infiltration and IL-1β release) parameters were assessed several hours after intra-articular injection of MSU (100 µg/articulation) in wild-type or knockout mice for Toll-like receptor 4 (TLR4), inducible nitric oxide synthase (iNOS), transient receptor potential (TRP) V1 and the IL-1 receptor (IL-1R). Also, wild-type animals were treated with clodronate, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) (TLR4 antagonist), spleen tyrosine kinase (SYK) inhibitor (iSYK), aminoguanidine (AMG, an iNOS inhibitor) or SB366791 (TRPV1 antagonist). Nitrite/nitrate and IL-1β levels were measured on the synovial fluid of wild-type mice, 2 h after intra-articular MSU injections, or medium from macrophages stimulated for MSU (1000 μg) for 2 h.ResultsIntra-articular MSU injection caused robust nociception and severe inflammation from 2 up to 6 h after injection, which were prevented by the pre-treatment with clodronate, LPS-RS, iSYK, AMG and SB366791, or the genetic ablation of TLR4, iNOS, TRPV1 or IL-1R. MSU also increased nitrite/nitrate and IL-1β levels in the synovial fluid, which was prevented by clodronate, LPS-RS, iSYK and AMG, but not by SB366791. Similarly, MSU-stimulated peritoneal macrophages released nitric oxide, which was prevented by LPS-RS, iSYK and AMG, but not by SB366791, and released IL-1β, which was prevented by LPS-RS, iSYK, AMG and SB366791.ConclusionOur data indicate that MSU may activate TLR4, SYK, iNOS and TRPV1 to induce the release of IL-1β by macrophages, triggering nociception and inflammation during acute gout attack.

The phytosphingosine-CD300b interaction promotes zymosan-induced, nitric oxide–dependent neutrophil recruitment

2019 ◽  
Vol 12 (564) ◽  
pp. eaar5514 ◽  
Author(s):  
Mariko Takahashi ◽  
Kumi Izawa ◽  
Makoto Urai ◽  
Yoshinori Yamanishi ◽  
Akie Maehara ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Neutrophil Recruitment ◽  
No Production ◽  
Dependent Manner ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Neutrophil Accumulation ◽  
Toll Like Receptor 4 ◽  
Potential Ligand ◽  
Inflammatory Dendritic Cells

Zymosan is a glucan that is a component of the yeast cell wall. Here, we determined the mechanisms underlying the zymosan-induced accumulation of neutrophils in mice. Loss of the receptor CD300b reduced the number of neutrophils recruited to dorsal air pouches in response to zymosan, but not in response to lipopolysaccharide (LPS), a bacterial membrane component recognized by Toll-like receptor 4 (TLR4). An inhibitor of nitric oxide (NO) synthesis reduced the number of neutrophils in the zymosan-treated air pouches of wild-type mice to an amount comparable to that inCD300b−/−mice. Treatment with clodronate liposomes decreased the number of NO-producing, CD300b+inflammatory dendritic cells (DCs) in wild-type mice, thus decreasing NO production and neutrophil recruitment. Similarly, CD300b deficiency decreased the NO-dependent recruitment of neutrophils to zymosan-treated joint cavities, thus ameliorating subsequent arthritis. We identified phytosphingosine, a lipid component of zymosan, as a potential ligand of CD300b. Phytosphingosine stimulated NO production in inflammatory DCs and promoted neutrophil recruitment in a CD300b-dependent manner. Together, these results suggest that the phytosphingosine-CD300b interaction promotes zymosan-dependent neutrophil accumulation by inducing NO production by inflammatory DCs and that CD300b may contribute to antifungal immunity.

scholarly journals Differential Activation of Human and Mouse Toll-Like Receptor 4 by the Adjuvant Candidate LpxL1 of Neisseria meningitidis

2008 ◽  
Vol 76 (8) ◽  
pp. 3801-3807 ◽  
Author(s):  
Liana Steeghs ◽  
A. Marijke Keestra ◽  
Andries van Mourik ◽  
Heli Uronen-Hansson ◽  
Peter van der Ley ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Lipid A ◽  
Vaccine Development ◽  
Meningococcal Vaccine ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Toll Like Receptor 4 ◽  
Species Specific ◽  
Human And Mouse ◽  
Dc Maturation

ABSTRACT Neisseria meningitidis LpxL1 lipopolysaccharide (LPS) bearing penta-acylated lipid A is considered a promising adjuvant candidate for inclusion in future N. meningitidis vaccines, as it elicits a markedly reduced endotoxic response in human macrophages relative to that in wild-type (hexa-acylated) LPS, while it is an equally effective adjuvant in mice. As dendritic cells (DC) and Toll-like receptors (TLR) are regarded as central mediators in the initiation of an immune response, here we evaluated the ability of LpxL1 LPS to mature and to activate human DC and examined its TLR4-/MD-2-activating properties. Unexpectedly, purified LpxL1 LPS displayed minimal human DC-stimulating properties compared to wild-type LPS. Although whole bacteria induced DC maturation and activation irrespective of their type of LPS, the LpxL1 mutant failed to activate the human recombinant TLR4/MD-2 complex expressed in HeLa cells. Similarly, purified LpxL1 LPS was unable to activate human TLR4/MD-2 and it even acted as an antagonist of wild-type LPS. Both wild-type and LpxL1 LPSs activated the murine TLR4/MD-2 complex, consistent with their abilities to induce maturation and activation of murine DC. Assays with cells transfected with different combinations of human and murine TLR4 and MD-2 indicated that TLR4 was a more-major determinant of the LPS response than MD-2. The species-specific activation of the TLR4/MD-2 complex by LpxL1 LPS may have an impact on the use of LpxL1 LPS as an adjuvant and the use of murine immunization models in human meningococcal vaccine development.

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