@misc{Gradek-Kwinta_Elżbieta_Predisposing_2023, author={Gradek-Kwinta, Elżbieta}, address={Kraków}, howpublished={online}, year={2023}, school={Rada Dyscypliny Nauki medyczne}, language={pol; eng}, abstract={The aim of the first study was to determine a profile of ex vivo released cytokines in patients with stroke-associated pneumonia (SAP) and to assess the clinical utility of individual cytokines and their combination as a biomarker of SAP. Two hundred seventy-nine patients with ischemic stroke were included into this study (median age: 69 years; 41.6% female). Blood samples were collected on the third day after the onset of stroke and stimulated ex vivo with lipopolysaccharide (LPS). LPS-induced cytokine concentrations (TNFα, IP-10, IL-1β, IL-6, IL-8, IL-10 and IL-12p70) were measured in supernatants. In addition, interleukin-6 (IL-6), a marker of systemic inflammation, was measured in plasma. During the first 5 days after stroke pneumonia occurred in 7.2% of patients. Patients with pneumonia were older, more often suffered from atrial fibrillation and ischemic heart disease, and had more severe neurological deficit on admission. Compared to patients without SAP, patients with SAP had lower ex vivo release of TNFα, IL-1β, IL-12, IP-10 and a higher level of circulating IL-6. The multimarker score composed of ex vivo synthesized IL-12, IP-10, and plasma IL-6 displayed very good discriminatory properties for SAP (area under curve [AUC]: 0.90) with sensitivity of 0.89 and specificity of 0.88. Discriminatory abilities of the multimarkers score was better than individual cytokines. Th}, abstract={e results of the study suggest the potential utility of ex vivo synthesized cytokines as a biomarker of SAP. The aim of the second study was to determine the clinical utility of lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) as risk markers of SAP. Three hundred thirty-one patients with ischemic stroke were included into study (median age: 71 years; 47.4% female). Blood samples were taken within 24 hours after stroke onset. SAP was diagnosed in 13% of patients. Patients with SAP had higher plasma levels of LBP (median: 19.4 vs 15.3 μg∕mL, P < 0.01) and sCD14 (median: 1.5 vs 1.4 μg∕mL, P = 0.04) compared to patients without SAP. In univariate logistic regression analysis, higher LBP and sCD14 levels were associated with an increased risk of SAP (OR: 1.09, 95%CI: 1.05 - 1.13, P<0.01 and OR: 2.76, 95%CI: 1.31 - 5.82, P<0.01, respectively). In multivariate analysis adjusted for age, National Institute of Health Stroke Scale (NIHSS) score, and atrial fibrillation, a higher level of LBP (OR: 1.09, 95%CI: 1.05-1.13, P<0.01), but not sCD14 (OR: 2.16, 0.94-4.97, P=0.07), was associated with SAP. The AUC for the clinical model of SAP that included age, NIHSS and atrial fibrillation was 0.80. Discriminatory ability of both LBP and sCD14 were inferior to the clinical model (AUC: 0.67 and 0.60, respectively). Moreover, addition of LBP (AUC: 0.84, P=0.11) or sCD14 (AUC:}, abstract={0.81, P=0.15) to the clinical model did not improve its discriminatory ability. Our results suggest that due to the limited predictive value, LBP and sCD14 could not be recommended as biomarkers of SAP for the clinical practice. The aim of the third study was to determine if there is any association between anticholinergic medication used before stroke and SAP. Prospectively collected data of 675 patients with acute stroke (mean age: 71.4±13.3; 53.1% women) were analyzed. The Anticholinergic Drug Scale (ADS) was used to assess anticholinergic exposure during a month preceding stroke onset. ADS is a well-established scale which correlates with serum anticholinergic activity. SAP was diagnosed in 14.7% of patients. The use of anticholinergic medication before stroke was associated with an elevated risk of SAP (OR: 2.56, 95% CI: 1.59-4.11, P<0.01) in univariate analysis. This association remained significant in multivariable analysis adjusted for age, stroke severity, atrial fibrillation, previous myocardial infarction and respiratory tract diseases (OR: 2.06, 95% CI: 1.01-4.22, P=0.04). The results of the study suggest that the use of anticholinergic medication before stroke is associated with an increased risk of SAP.}, title={Predisposing factors, diagnostic, and predictive markers of stroke-associated pneumonia}, type={Praca doktorska}, keywords={pneumonia, stroke, biomarker LBP sCD14, inflammation, anticholinergic drugs, cytokines}, }