Κινητική της πρωτεΐνης που δεσμεύει την Ηπαρίνη σε ασθενείς με πνευμονία που συνδέεται με τον μηχανικό αερισμό

Η πνευμονία που συνδέεται με τον μηχανικό αερισμό είναι η λοίμωξη με την μεγαλύτερη συχνότητα που απαντάται στους ασθενείς της Μονάδας Εντατικής Θεραπείας. Ως πνευμονία σχετιζόμενη με τον αναπνευστήρα ορίζεται η πνευμονία που εμφανίζεται 48 ώρες μετά τη διασωλήνωση. Είναι ευρέως γνωστό ότι υπάρχει ανάγκη για εύρεση βιοδεικτών σε ασθενείς με πνευμονία που συνδέεται με μηχανικό αερισμό. Στην παρούσα εργασία εισήχθησαν 30 ασθενείς με πνευμονία που συνδέεται με τον μηχανικό αερισμό και μελετήθηκε κατά πόσο η Πρωτεΐνη που συνδέεται με την Ηπαρίνη (HBP: Ηeparin Binding Protein) μπορεί να συμβάλλει πρόγνωση της θνητότητας των παραπάνω ασθενών και κατά πόσο τα αυξημένα επίπεδά της επάγουν την προφλεγμονώδη δραστικότητα των μονοκυττάρων.Pneumoniae which is associated with ventilator is an infection with the greatest frequency in intensive care patients. Ventilator aquired pneumonia (VAP) is pneumonia that develops 48 hours or longer after mechanical ventilation is given by means of endotracheal tube or tracheostomy. Biomarkers are another piece of the VAP diagnosis is that need more research effort. A total of 30 patients with VAP were prospectively enrolled in this study and the objective of this study was to investigate how can contribute to prevent the risk of mortality and how the elevated levels of measuring serum Heparin Binding Protein (HBP) can induce the release of proinflammatory activity of monocyte

Impact of comorbidities on the performance of interferon-gamma release assay in an elderly Greek population without overt immunodeficiency

Contains fulltext : 223590.pdf (Publisher’s version ) (Closed access

Association of Vitamin D with severity and outcome of COVID-19: Clinical and Experimental Evidence

Introduction: The role of vitamin in COVID-19 remains controversial. We investigated the association between endogenous vitamin D and the severity of COVID-19 as well as the mechanisms of action of vitamin D supplementation. Methods: 25(OH)D3 in serum was associated with disease severity and outcome in 190 COVID-19 patients. In a COVID-19 animal model using intravenous injection of plasma from patients with COVID-19 ARDS into C57/BL6 mice, mice were treated with 0.25μg human 1,25(OH)D3 or vehicle. Mice were sacrificed on day 4. Cytokines and myeloperoxidase (MPO) in tissues were measured. Changes in gene expression after vitamin D supplementation were measured. Results: Vitamin D deficiency and insufficiency were associated with increased severity and unfavourable outcome after 28 days. Vitamin D levels were negatively associated with biomarkers of COVID-19 severity. Vitamin D supplementation after challenge of mice with COVID-19 plasma led to reduced levels of TNFα, IL-6, IFNγand MPO in the lung, as well as down-regulation of pro-inflammatory pathways. Conclusion: Normal levels of endogenous Vitamin D are associated with reduced severity and risk of unfavourable outcome in COVID-19, possibly through attenuation of tissue-specific hyperinflammation

Calprotectin and Imbalances between Acute-Phase Mediators Are Associated with Critical Illness in COVID-19

The trajectory from moderate and severe COVID-19 into acute respiratory distress syndrome (ARDS) necessitating mechanical ventilation (MV) is a field of active research. We determined serum levels within 24 h of presentation of 20 different sets of mediators (calprotectin, pro- and anti-inflammatory cytokines, interferons) of patients with COVID-19 at different stages of severity (asymptomatic, moderate, severe and ARDS/MV). The primary endpoint was to define associations with critical illness, and the secondary endpoint was to identify the pathways associated with mortality. Results were validated in serial measurements of mediators among participants of the SAVE-MORE trial. Levels of the proinflammatory interleukin (IL)-8, IL-18, matrix metalloproteinase-9, platelet-derived growth factor (PDGF)-B and calprotectin (S100A8/A9) were significantly higher in patients with ARDS and MV. Levels of the anti-inflammatory IL-1ra and IL-33r were also increased; IL-38 was increased only in asymptomatic patients but significantly decreased in the more severe cases. Multivariate ordinal regression showed that pathways of IL-6, IL-33 and calprotectin were associated with significant probability for worse outcome. Calprotectin was serially increased from baseline among patients who progressed to ARDS and MV. Further research is needed to decipher the significance of these findings compared to other acute-phase reactants, such as C-reactive protein (CRP) or ferritin, for the prognosis and development of effective treatments

Macrophage activation-like syndrome: an immunological entity associated with rapid progression to death in sepsis

Abstract Background A subanalysis of a randomized clinical trial indicated sepsis survival benefit from interleukin (IL)-1 blockade in patients with features of the macrophage activation-like syndrome (MALS). This study aimed to investigate the frequency of MALS and to develop a biomarker of diagnosis and prognosis. Methods Patients with infections and systemic inflammatory response syndrome were assigned to one test cohort (n = 3417) and a validation cohort (n = 1704). MALS was diagnosed for patients scoring positive either for the hemophagocytic syndrome score and/or having both hepatobiliary dysfunction and disseminated intravascular coagulation. Logistic regression analysis was used to estimate the predictive value of MALS for 10-day mortality in both cohorts. Ferritin, sCD163, IL-6, IL-10, IL-18, interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) were measured in the blood the first 24 h; ferritin measurements were repeated in 747 patients on day 3. Results The frequency of MALS was 3.7% and 4.3% in the test and the validation cohort, respectively. In both cohorts, MALS was an independent risk factor for 10-day mortality. A ferritin level above 4420 ng/ml was accompanied by 66.7% and 66% mortality after 28 days, respectively. Ferritin levels above 4420 ng/ml were associated with an increase of IL-6, IL-18, INF-γ, and sCD163 and a decreased IL-10/TNF-α ratio, indicating predominance of pro-inflammatory phenomena. Any less than 15% decrease of ferritin on day 3 was associated with more than 90% sensitivity for unfavorable outcome after 10 days. This high mortality risk was also validated in an independent Swedish cohort (n = 109). Conclusions MALS is an independent life-threatening entity in sepsis. Ferritin measurements can provide early diagnosis of MALS and may allow for specific treatment

Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial

Introduction The anti-inflammatory effect of macrolides prompted the study of oral clarithromycin in moderate COVID-19. Methods An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end of treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection and as at least 50% decrease of the respiratory symptoms score without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells and safety were assessed. Results The primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%); this was 91.7% and 81.4% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of production of interferon-gamma and decrease of production of interleukin-6 by mononuclear cells; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported. Conclusions Early clarithromycin treatment provides most of the clinical improvement in moderate COVID-19