Anti-TNF and anti-IL-12/IL-23 are commonly used therapies for immune-mediated inflammatory diseases (IMIDs), including inflammatory bowel disease (IBD). Although several studies have shown intact T cell responses following 2 to 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in biologics treated IMID patients, our group previously reported increased waning of T cell responses at 3-4 mos following the second vaccine dose in IMID patients compared to healthy controls, raising the possibility that a suboptimal initial T cell response could impact long term immunity. Here, to reduce patient heterogeneity, we focused only on IBD patients and further investigated T cell responses in vaccinated, untreated and biologics treated IBD patients compared to healthy controls. Following 1 vaccine dose, we observed a decreased frequency of Spike-reactive Th1 polarized cells and an increased frequency of Th2 cells in the IBD patients in general, relative to healthy controls. Additionally, IBD patients exhibited increased waning of Spike-specific cytokine T cell responses after 2 doses of vaccine. We also observed IBD-treatment specific effects. Spike-specific IL-2 secretion from anti-TNF or anti-IL-12/IL-23-treated patients' T cells was lower than from untreated patients following 1 dose of vaccine. However, single-cell RNA-sequencing of Spike-responsive T cells from anti-TNF and anti-IL-12/IL-23 treated IBD patients and healthy controls 2-4 wk after 2 or 3 vaccine doses revealed no major differences in T cell subsets, transcriptomes or TCR diversity. Thus, despite some evidence of impaired primary T cell responses, Spike-reactive T cells in patients treated with anti-TNF or anti-IL-12/IL-23 appear indistinguishable from healthy controls following a full vaccine course.

Comparative analysis of liver subpopulations of lymphocytes and cells of the system of mononuclear phagocytes on the material of autopsies in deaths from acute period of COVID-19, without its previous diseases and bacterial/mycotic superinfection, as well as from noninfection diseases in the distant future after the new coronavirus infection.

Study of morphological changes of the liver in 47 deaths from COVID-19, confirmed by a PCR test, and noninfection diseases within 40 to 300 days after a new coronavirus infection. The study did not include those who died with previous liver diseases and comorbid diseases accompanied by liver damage, and in the first two groups of observations - also with bacterial/mycotic superinfection, and after hepatotoxic therapy. 1 group consisted of 10 observations (average age - 75.2 years) with the exudative phase of diffuse alveolar damage (DAD), 2^nd group - 27 observations (average age - 71.7 years) with the proliferative or exudative-proliferative phases of DAD, 3d group - 10 observations (average age - 84.7 years), died from cardiovascular diseases in the period from 40 to 300 days after the transfer COVID-19. Imunohistochemical (IHC) reactions with antibodies to CD3, CD4, CD8, CD20, CD56 and CD68 were used with statistical analysis.

In portal tracts and perisinusoid spaces, the total number of CD3+, CD4+, CD8+, CD56+ and CD20+ lymphocytes and CD68+ cells are not higher in the acute period COVID-19, and in perisinusoid spaces are even less than in observations after a new coronavirus infection in patients died from cardiovascular diseases. The number of intraepithelial CD3+, CD4+, CD8+, CD56+ lymphocytes of the bile ducts of portal tracts was increased, which also infiltrate the walls of small vessels. Number of CD4+ lymphocytes in the stroma and liver parenchyma, ratio CD4+/CD8+ lymphocytes and proliferation of Kupfer cells are most increased in the exudative phase of DAD in COVID-19.

The study confirms that the morphological substrate COVID-19-associated liver damage may be ischemic hepatitis and COVID-19-associated cholangiopathy and microangiopathy give it a certain specificity. The revealed changes do not allow to exclude that the pathogenesis of liver damage can be also associated, including with other factors the direct action of SARS-CoV2 or immune disorders associated with COVID-19.

Cognitive changes after treatment of ruptured anterior communicating artery (AComA) aneurysms have been recognized for decades. Whether such deficits occur after elective treatment of unruptured aneurysms remains uncertain. A systematic search in MEDLINE (via PubMed and via Ovid), Embase, Scopus, Web of Science, CENTRAL and PsycINFO was conducted from inception to 31 August 2025, in accordance with PRISMA guidelines. Duplicate records were removed prior to screening. Studies were eligible if they included adult patients undergoing elective treatment of at least 1 unruptured AComA aneurysm, reported pre- and post-treatment neurocognitive testing across at least one cognitive subdomain, and differentiated outcomes from other aneurysm locations. Critical appraisal was performed using the Newcastle-Ottawa Scale, and certainty of evidence was assessed using the GRADE framework. Eight studies comprising 95 patients were included. In most studies, patients underwent surgical clipping (n = 82), with a minority treated endovascularly (n = 13). In five out of eight studies, patients who underwent elective treatment of an AComA aneurysm had worse cognitive outcomes than patients with aneurysms at non-AComA locations. Neurocognitive deficits may be detected in a substantial proportion of patients undergoing elective treatment of unruptured AComA aneurysms when sensitive neuropsychological assessment is applied. However, the current evidence base is limited by small sample sizes, heterogeneity in neuropsychological assessment, and a predominance of surgically treated cases.

Lacunar strokes are caused by occlusion of small penetrating arteries. Although CT perfusion (CTP) is widely used in the acute settings, automated core/penumbra software often fails to detect lacunar perfusion abnormalities, so its diagnostic and prognostic roles remain unclear. This study aimed to assess the ability of CTP to detect perfusion asymmetries in patients with lacunar stroke and to determine whether such asymmetries are associated with clinical characteristics and functional outcomes.

We retrospectively analyzed 68 patients with lacunar stroke who underwent whole-brain CTP within 4.5 h from stroke onset or recognition. CTP maps (MTT, CBF, CBV, and summary) were visually assessed. Demographic, clinical and imaging data along with stroke metrics and outcomes measurements were collected. Statistical analyses explored CTP detection rate, the association between admission variables and the presence of CTP asymmetries and between these asymmetries and 3-month mRS (dichotomized as either mRS 0-1 or ≥ 2).

41.18% of patients exhibited CTP-detected asymmetries, with the MTT map showing the highest detection rate (39.71%). No demographic or clinical factors predicted CTP positivity. The presence of CTP asymmetries was associated with larger infarct volumes and was independently associated with lower odds of excellent functional recovery (3-month mRS 0-1) (OR 0.232; p = 0.012).

Qualitative assessment of individual CTP maps, and especially of MTT map, improves detection of lacunar strokes, particularly with whole-brain coverage. Asymmetries may reflect impaired microvascular perfusion and predict worse outcomes. Therefore, CTP is a valuable diagnostic and prognostic tool in lacunar stroke.

Myocardial infarction (MI) is a major global health concern influenced by diverse risk factors. Despite growing evidence of oral-systemic connections, current MI models largely exclude oral health indicators, reflecting the longstanding separation between dental and medical paradigms. This study introduces a multidomain, interpretable machine learning framework that integrates detailed periodontal and oral hygiene variables, marking one of the first efforts to quantitatively incorporate these features into MI incidence identification. A population-based case-control dataset comprising 1,355 individuals and heterogeneous variables was used to train and evaluate seven supervised classifiers via nested cross-validation. Among them, XGBoost achieved the best performance (AUC = 0.88 ± 0.01; F1 score = 0.74 ± 0.03) and was further probability-calibrated using isotonic regression, yielding a mean Brier score of 0.14 ± 0.01 and demonstrating well-aligned predicted probabilities. SHAP values confirmed the importance of conventional cardiovascular predictors, while several periodontal indicators such as mean clinical attachment loss, plaque index, and gingival bleeding emerged among the most influential features. Sex-stratified SHAP analysis revealed sex-specific patterns in the relative impact of oral features. Additionally, individual-level waterfall plots illustrated how oral inflammation may contribute independently or in combination with conventional factors to MI incidence identification. These findings support a systems-level view of periodontitis as a modifiable, biologically relevant factor in cardiovascular health and underscore the value of considering oral-health markers within screening and management frameworks.

Motor imagery-based brain-computer interface (MI-BCI) applications in stroke rehabilitation aim to match brain activity with real-time feedback, thereby establishing closed-loop neural pathways and providing a basis for evaluating patients' neuroplasticity changes. Thus, constructing EEG datasets under MI paradigms is crucial for optimizing MI-BCI systems and understanding the neural rehabilitation process. However, the current limitations of single MI paradigms and the lack of relevant EEG datasets may restrict the accurate interpretation and effective application in stroke rehabilitation. This study collected EEG data from 24 stroke patients during MI tasks, including a novel "sixth finger" MI and an affected-hand MI paradigm. The dataset comprehensively covers the complete longitudinal stages of stroke rehabilitation: pre-training, post-training, and follow-up periods. The data materials include: (1) raw EEG data, (2) preprocessed data, and (3) patient clinical information. Preliminary analysis using classical machine learning algorithms (CSP + SVM and CSP + LDA) demonstrated an average classification accuracy between the two MI paradigms maintained at approximately 85%~86%. We anticipate that this dataset will facilitate research on MI-BCI paradigms and neuroplasticity for stroke, and contribute to the development of high-efficiency MI-BCI systems in the field of stroke rehabilitation.

Recurrent stroke prevention is important for people who have suffered a stroke or transient ischaemic attack (TIA), as they are at increased risk of having another stroke. Nevertheless, treatment adherence is often low. Therefore, the StrokeCompass project was initiated to enhance medication adherence by empowering individuals who have had a stroke to take an active role in recurrent stroke prevention and medication management. In accordance with the UK Medical Research Council (MRC) guidelines, a complex intervention was developed that integrated evidence-based decision aids and a personalised, nurse-led coaching programme. The present stepped-wedge cluster-randomised controlled study addresses the second phase of the MRC framework by pilot testing the feasibility and acceptability of the intervention in a clinical setting.

A total of 452 patients with a recent ischaemic stroke or TIA will be recruited over a period of 16 months from seven stroke units across Germany. The study centres will be randomised and sequentially crossed over from the control phase to the intervention phase in three time periods (4, 8 and 12 months after initiation) until all clusters have been exposed to both conditions. The intervention comprises four core elements: first, a decision coaching programme, second, a physician consultation to discuss treatment targets, third, an adherence coaching programme, and fourth, a web-based patient decision aid. Furthermore, we developed a preparatory training programme for nurses and physicians. Feasibility outcomes (eg, recruitment strategies, participation, implementation and utilisation of intervention) will be analysed descriptively, while preliminary estimates of effectiveness, measured by changes in risk factor targets (eg, blood pressure and low-density lipoprotein cholesterol levels), will be analysed according to the intention-to-treat principle. Furthermore, an economic evaluation will be conducted focusing on the implementation costs. These findings could prove pivotal in the subsequent planning and rationale for a full-powered effectiveness study.

The study has received ethical approval from the Ethical Committee of the University of Lübeck (reference 2024-522). We will disseminate the findings in peer-reviewed journals, at conferences, and on relevant patient websites.

DRKS00036091.

Approximately 10%-20% of patients with Kawasaki disease (KD) are resistant to intravenous immunoglobulins (IVIG) and are at increased risk of developing coronary artery aneurysms (CAA). A potential therapeutic role of anakinra (ANK) in refractory KD has been suggested. The aim of this work is to systematically review and critically appraise the available clinical evidence on the use of ANK in the treatment of IVIG-resistant KD, focusing on treatment indications, timing, dosage, efficacy on fever, inflammation, CAA and safety.

A systematic literature search was conducted across PubMed, Embase, Web of Science, Cochrane Library, Emcare, Academic Search Premier and Google Scholar from inception to 9 October 2025, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Eligible studies included all study designs reporting outcomes of patients with KD treated with ANK.

Thirty-two publications (31 identified through database search and one by cross-referencing) describing 81 patients were included. Most reports were single cases or small series, with two early-phase clinical trials. Treatment with ANK was associated with resolution of fever and systemic inflammation in 94.9% of patients. Complete CAA resolution was reported in 32% and stabilisation/dimensional reduction in 56.3%. No serious safety concerns were identified. However, these findings derive from heterogeneous and low-quality evidence and should be interpreted with caution.

In IVIG-resistant KD, ANK was effective in controlling systemic inflammation, although more data are needed to assess its efficacy on coronary outcomes. While these findings are encouraging in supporting consideration of ANK for refractory KD, larger randomised clinical studies are warranted to define optimal ANK timing of introduction and dosing, and to evaluate its long-term efficacy on cardiac outcomes.

CRD420252129435.

The intrauterine environment may influence childhood immune-mediated disease risk. We investigated whether maternal prepregnancy body mass index (BMI), gestational weight gain (GWG) or hypertensive disorders during pregnancy (HDP) were associated with juvenile idiopathic arthritis (JIA) in children and whether genetic susceptibility modified associations.

We linked the Norwegian Mother, Father and Child Cohort Study (MoBa) to the Norwegian Patient Registry to identify children with JIA. Logistic regression estimated adjusted ORs (aORs) for associations with BMI, GWG and HDPs. Causal mediation analyses assessed whether hypertension mediated the GWG-JIA association. In a genotyped subsample, we tested interactions between exposures and a JIA Polygenic Risk Score (PRS).

Among 78 901 eligible children, 265 developed JIA (genotyped subsample: 192 JIA/44 053 non-JIA). By the end of follow-up, all children were ≥14 years old and 85% were ≥16 years old. Maternal prepregnancy BMI was not associated with JIA. Each 1 SD (~6 kg) increase in GWG was associated with modestly higher odds of JIA (aOR 1.12, 95% CI 1.00 to 1.26), particularly among women with prepregnancy obesity (aOR 1.40, 95% CI 1.10 to 1.77). Maternal hypertension and pre-eclampsia were associated with higher JIA risk (aOR 1.43, 95% CI 1.02 to 1.99 and aOR 1.61, 95% CI 1.10 to 2.37). Hypertension did not mediate the GWG-JIA association (p>0.05). Among children with lower PRS, maternal obesity was associated with a lower JIA risk (aOR 0.37, 95% CI 0.17 to 0.80).

Higher GWG and HDPs were independently associated with increased JIA risk. Genetic susceptibility may modify associations with maternal BMI, supporting a role for pregnancy health in JIA development.

Cardiovascular disease (CVD) is the leading cause of mortality globally and imposes a substantial disease burden. Addressing the social determinants of health (SDOH) presents a critical opportunity to reduce CVD-related mortality and disability. In Japan, CVD constitutes a major cause of death and necessitates long-term care, with current guidelines now incorporating SDOH related to CVD, indicative of a growing interest in these determinants. This review outlines the definition and conceptual frameworks of SDOH, along with its key domains: (1) Economic stability, (2) Education access and quality, (3) Social and community context, (4) Health care access and quality, and (5) Neighborhood and built environment. In addition to these established determinants, we discuss emerging SDOH such as climate change and digital health technologies, which may reshape cardiovascular risk and potentially widen existing disparities. We also summarize existing epidemiological findings and implications for intervention strategies, and outline future perspectives, including the implications of genetic testing and related ethical, legal, and social issues, as well as strategies aimed at reducing health disparities. Overall, advancing equitable cardiovascular health will require continued research, greater recognition of the role of SDOH, and efforts to address these determinants, including improving understanding of SDOH among health care professionals and the public and strengthening the evidence base for CVD and SDOH.