Tomasz Dziedzic

Background: Animal studies suggest that post-stroke inflammatory responses are sexually dimorphic and may influence recovery. We examined whether men and women with acute ischemic stroke differ in ex vivo cytokine synthesis and whether such differences relate to functional outcome. Methods: We included 279 patients with acute ischemic stroke (mean age: 68.5 ± 12.8; 41.2% women). Blood samples collected on day 3 after stroke were stimulated with lipopolysaccharide (LPS). Ex vivo production of TNFα, IP-10, IL-1β, IL-6, IL-8, IL-10, and IL-12p70 was measured using enzyme-linked immunoassay or cytometric methods, and expression of LPS-induced cytokine and chemokine genes was assessed by RNA sequencing. Results: Greater stroke severity, lower monocyte counts, and the use of angiotensin receptor blockers were associated with decreased production of pro-inflammatory cytokines. Compared with females, males showed higher ex vivo synthesis of TNFα (mean: 2814.2 vs 2302.7 pg/mL, P = 0.003), IL-1β (1851.9 vs 1461.3 pg/mL, P = 0.002), IL-6 (14345.3 vs 11846.5 pg/mL, P = 0.004), IL-12 (7.1 vs 4.2 pg/mL, P = 0.002), and IP-10 (557.9 vs 435.1 pg/mL, P = 0.038), with correspondingly higher gene expression levels of TNFα, IL-1β, IL-6, and IL-12. In multivariable quantile regression models adjusted for cytokine-specific covariates, male sex remained significantly associated with higher levels of TNFα, IL-1β, and IL-6. Despite this sex-related difference in inflammatory response, three-month functional outcomes were similar in men and women. Conclusion: Males exhibited greater ex vivo pro-inflammatory cytokine production after ischemic stroke, but this sexual dimorphism did not translate into differences in functional recovery.

Stroke-associated pneumonia (SAP), which occurs in approximately 12%, is the most frequent infectious complication after acute stroke and a major contributor to morbidity and mortality. Despite its clinical importance, high-quality evidence to guide the diagnosis, prediction, prevention and treatment of SAP remains limited, underscoring the need for structured, consensus-based recommendations in stroke care. This guideline was developed following the standard methodology of the European Stroke Organisation (ESO): an interdisciplinary working group identified 15 clinically relevant questions, conducted systematic literature reviews and meta-analyses, appraised the quality of the available evidence and formulated evidence-based recommendations. Notably, only 3 of 15 questions were supported by predominantly low-quality evidence, and most guideline statements therefore rely on expert consensus rather than evidence-based recommendations. For clinical practice, standardised diagnostic criteria are recommended, while chest CT and plasma C-reactive protein may provide additional diagnostic value. Clinical prediction scores and biomarkers demonstrate moderate to good discriminative performance, However, their routine use will depend on the availability of effective preventive measures. Prevention strategies include positioning, early mobilisation and individualised nutritional approaches. Dysphagia screening and swallowing management are established components of post-stroke care for SAP prevention and are addressed in a separate ESO guideline. Adjunctive therapies are not part of standard care but may be considered in selected patients. Preventive antibiotic therapy is not recommended due to a lack of benefit on SAP incidence or clinical outcomes, whereas empirical antibiotic treatment should be initiated promptly after diagnosis and guided by local protocols targeting aspiration-associated pathogens. In addition, this guideline provides a framework for future randomised trials aimed at improving the evidence base for SAP management.

Objectives: Delirium is a common and serious post-stroke complication. Early reperfusion by ameliorating brain damage could potentially prevent delirium after ischemic stroke, but the impact of this therapy on delirium remains unclear. We aimed to explore the association between reperfusion therapy (RT) and post-stroke delirium. Methods: We retrospectively analyzed data from the PRospective Observational POLIsh Study on post-stroke delirium. Symptoms of delirium were examined during the first 7 days after admission and a diagnosis of delirium was made using Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. We used logistic regression to examine the association between RT and delirium. Results: We included 301 acute stroke patients (median age: 77; median NIHSS: 14; 55.1% female). In the whole group of patients, RT was associated with a lower odds of delirium (34.2% vs 44.8%; adjusted OR: 0.56, 95% CI: 0.32-0.96, p = 0.035). There was a significant interaction between RT and pre-stroke cognitive status. As a result, RT was associated with a lower odds of delirium in patients without premorbid cognitive decline (28.8% vs 48.2%; adjusted OR: 0.34, 95% CI: 0.17-0.66, p = 0.002) and a higher odds of delirium in patients with pre-stroke cognitive decline (72.7% vs 41.0%; adjusted OR: 3.55, 95% CI: 1.03-12.20, p = 0.040). Discussion: The association between RT and delirium is modified by pre-stroke cognitive status. In patients without cognitive decline, RT is associated with a lower likelihood of delirium. Delirium should be considered as a relevant outcome in future controlled trials.

Chemokines are vital in post-cerebral ischemia inflammatory reactions. We investigate the possible relationship between plasma chemokines and short-term and long-term outcomes after stroke. This study included 235 patients (median age, 72 years; 49.8% female) suffering from ischemic stroke, or transient ischemic attack admitted to the hospital within 24 h of onset. We evaluated chemokines CCL2, CCL5, CXCL8, CXCL9, and CXCL10 in plasma samples collected upon admission. Further, we assessed functional outcomes at 3- and 12-months, all-cause fatality over 5 years, and episodes of delirium within the first 7 days of admission. Multivariate analysis revealed an association between higher CXCL10 levels and an increased risk of poor functional outcomes at 3 months (OR: 3.02, 95%CI: 1.22–7.46, p = 0.016) and 12 months (OR: 2.32, 95%CI: 1.03–5.26, p = 0.043), as well as an increased death risk (HR: 1.79, 95%CI: 1.04–3.07, p = 0.036). High CXCL8 levels independently predicted poor functional outcomes at 12 months (OR: 2.69, 95%CI: 1.39–6.31, p = 0.005) and a higher 5-year case fatality rate (HR: 1.90, 95%CI: 1.23–2.93, p = 0.004). Elevated CXCL9 levels also predicted unfavourable functional outcomes at 12 months (OR: 2.45, 95%CI: 1.07–5.61, p = 0.034). In univariate analysis, increased levels of CXCL8, CXCL9, and CXCL10 showed an association with delirium, although this link was not evident in the multivariate analysis. Plasma CXCL8 and CXCL10 show potential as prognostic biomarkers for stroke outcomes and as therapeutic targets suitable for reverse translation.

Objectives: Apathy is a frequent neuropsychiatric syndrome after stroke. We determined whether pre‐morbid and early post‐stroke apathy predicts dementia 3 months after stroke.Methods: We included ischemic stroke patients without dementia who participated in the Prospective Observational Polish Study on post‐stroke delirium. We used the Neuropsychiatric Inventory and clinician‐reported version of Apathy Evaluation Scale to score apathy symptoms before stroke and on day 8 after stroke. Patients underwent neuropsychological examination 3 months after stroke.Results: Of 422 patients with ischemic stroke and without pre‐stroke dementia, 194 patients (mean age: 67.5 ± 12.3; 45.9% female) underwent neuropsychological examination. Dementia was diagnosed in 21.6% of them. Patients with dementia had higher apathy scores before stroke (mean: 0.9 ± 1.7 vs. 0.2 ± 0.9, p < 0.01) and on day 8 (mean: 37.2 ± 9.3 vs. 29.0 ± 9.6, p < 0.01). Depressive symptoms did not differ between groups. In multivariate analysis adjusted for age, diabetes mellitus, stroke severity and in‐hospital delirium, apathy symptoms before stroke and on day 8 after stroke predicted post‐stroke dementia (adjusted OR: 1.59, 95%CI: 1.13–2.26, p = 0.01 and OR: 1.06, 95%CI: 1.01–1.11, p = 0.03, respectively).Conclusions: Pre‐stroke and early post‐stroke apathy independently from age, stroke severity and delirium predicted dementia 3 months after stroke. Apathy might be useful in identifying at‐risk patients.

Prediction of post‐stroke depressive symptoms (DSs) is challenging in patients without a history of depression. Gene expression profiling in blood cells may facilitate the search for biomarkers. The use of an ex vivo stimulus to the blood helps to reveal differences in gene profiles by reducing variation in gene expression. We conducted a proof‐of‐concept study to determine the usefulness of gene expression profiling in lipopolysaccharide (LPS)‐stimulated blood for predicting post‐stroke DS. Out of 262 enrolled patients with ischemic stroke, we included 96 patients without a pre‐stroke history of depression and not taking any anti‐depressive medication before or during the first 3 months after stroke. We assessed DS at 3 months after stroke using the Patient Health Questionnaire‐9. We used RNA sequencing to determine the gene expression profile in LPS‐stimulated blood samples taken on day 3 after stroke. We constructed a risk prediction model using a principal component analysis combined with logistic regression. We diagnosed post‐stroke DS in 17.7% of patients. Expression of 510 genes differed between patients with and without DS. A model containing 6 genes (PKM, PRRC2C, NUP188, CHMP3, H2AC8, NOP10) displayed very good discriminatory properties (area under the curve: 0.95) with the sensitivity of 0.94 and specificity of 0.85. Our results suggest the potential utility of gene expression profiling in whole blood stimulated with LPS for predicting post‐stroke DS. This method could be useful for searching biomarkers of post‐stroke depression. image