PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is a common, age-related cause of visual impairment. This systematic review synthesizes evidence from the literature on artificial intelligence (AI) models developed for the diagnosis and management of FECD. METHODS: We conducted a systematic literature search in MEDLINE, PubMed, Web of Science, and Scopus from January 1, 2000, to June 31, 2024. Full-text studies utilizing AI for various clinical contexts of FECD management were included. Data extraction covered model development, predicted outcomes, validation, and model performance metrics. We graded the included studies using the Quality Assessment of Diagnostic Accuracies Studies 2 tool. This review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. RESULTS: Nineteen studies were analyzed. Primary AI algorithms applied in FECD diagnosis and management included neural network architectures specialized for computer vision, utilized on confocal or specular microscopy images, or anterior segment optical coherence tomography images. AI was employed in diverse clinical contexts, such as assessing corneal endothelium and edema and predicting post-corneal transplantation graft detachment and survival. Despite many studies reporting promising model performance, a notable limitation was that only three studies performed external validation. Bias introduced by patient selection processes and experimental designs was evident in the included studies. CONCLUSIONS: Despite the potential of AI algorithms to enhance FECD diagnosis and prognostication, further work is required to evaluate their real-world applicability and clinical utility. TRANSLATIONAL RELEVANCE: This review offers critical insights for researchers, clinicians, and policymakers, aiding their understanding of existing AI research in FECD management and guiding future health service strategies.

• MeSH
• Fuchsova endoteliální dystrofie * diagnóza   terapie   MeSH
• lidé MeSH
• optická koherentní tomografie metody   MeSH
• umělá inteligence * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH

BACKGROUND: Interleukin 40 (IL-40) is a cytokine implicated in malignancies and rheumatic disorders. Its association with fibrotic mediators has been previously described. Since inflammation and fibrosis are hallmarks of systemic sclerosis (SSc), we aimed to analyze the role of IL-40 in SSc. METHODS: IL-40 levels were analyzed in the serum of 90 SSc patients and 75 healthy controls (HCs). IL-40 expression in dermal biopsies from 5 SSc patients and 5 HCs was assessed via immunohistochemistry. IL-40 was analyzed in 39 SSc patients with interstitial lung disease treated with cyclophosphamide (CPA) and in 24 SSc patients with active progressive disease treated with rituximab (RTX). SSc activity was assessed by the European Scleroderma Study Group (ESSG) index. The effect of recombinant IL-40 on peripheral blood mononuclear cells (PBMCs) from 10 SSc patients was determined in vitro. IL-40 was analyzed in 24 individuals at risk of developing SSc (VEDOSS), who were categorized as progressors (n = 11) and nonprogressors (n = 13). RESULTS: IL-40 expression was elevated in the skin of SSc patients compared to HCs, particularly in fibroblasts and immune infiltrates. Serum IL-40 was increased in SSc compared to HCs (p < 0.0001) and was associated with ESSG (r = 0.372, p = 0.0005) and gastrointestinal involvement (p < 0.05). IL-40 correlated with serum IL-8 (r = 0.270, p = 0.019) and TGF-β1 (r = 0.301, p = 0.024) levels. In the CPA and RTX cohort, no significant changes in the serum IL-40 were observed upon treatment. Baseline and changes in IL-40 levels were associated with changes in several clinical parameters. IL-40 was elevated in patients at risk of SSc compared to HCs (p = 0.0003). No significant changes were observed in progressors vs. nonprogressors; however, IL-40 was associated with capillaroscopy findings (p < 0.05). IL-40 induced the upregulation of IL-6 (p = 0.002), MCP-1 (p = 0.002) and IL-10 (p = 0.002) in PBMCs from SSc patients in vitro. CONCLUSIONS: IL-40 was upregulated in the skin and serum of SSc patients and was associated with disease activity, gastrointestinal involvement and fibrotic mediators. Our in vitro findings indicate that IL-40 might be involved in the immune response and fibrotic processes in SSc.

• MeSH
• dospělí MeSH
• fibróza MeSH
• gastrointestinální nemoci * krev   imunologie   MeSH
• imunohistochemie MeSH
• kůže patologie   metabolismus   MeSH
• leukocyty mononukleární metabolismus   účinky léků   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• systémová sklerodermie * krev   imunologie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Spatial navigation deficits are early symptoms of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for AD. This study investigated effects of APOE genotype on spatial navigation in biomarker-defined individuals with amnestic mild cognitive impairment (aMCI) and associations of AD biomarkers and atrophy of AD-related brain regions with spatial navigation. METHODS: 107 participants, cognitively normal older adults (CN, n = 48) and aMCI individuals stratified into AD aMCI (n = 28) and non-AD aMCI (n = 31) groups, underwent cognitive assessment, brain MRI, and spatial navigation assessment using the Virtual Supermarket Test with egocentric and allocentric tasks and a self-report questionnaire. Cerebrospinal fluid (CSF) biomarkers (amyloid-β1-42, phosphorylated tau181 and total tau) and amyloid PET imaging were assessed in aMCI participants. RESULTS: AD aMCI participants had the highest prevalence of APOE ε4 carriers and worst allocentric navigation. CSF levels of AD biomarkers and atrophy in AD-related brain regions were associated with worse allocentric navigation. Between-group differences in spatial navigation and associations with AD biomarkers and regional brain atrophy were not influenced by APOE genotype. Self-reported navigation ability was similar across groups and unrelated to spatial navigation performance. CONCLUSIONS: These findings suggest that allocentric navigation deficits in aMCI individuals are predominantly driven by AD pathology, independent of APOE genotype. This highlights the role of AD pathology as measured by biomarkers, rather than genetic status, as a major factor in navigational impairment in aMCI, and emphasizes the assessment of spatial navigation as a valuable tool for early detection of AD.

• MeSH
• Alzheimerova nemoc * genetika   mozkomíšní mok   diagnostické zobrazování   komplikace   patofyziologie   patologie   MeSH
• amyloidní beta-protein mozkomíšní mok   MeSH
• apolipoprotein E4 * genetika   MeSH
• apolipoproteiny E * genetika   MeSH
• atrofie MeSH
• biologické markery mozkomíšní mok   MeSH
• genotyp MeSH
• kognitivní dysfunkce * genetika   mozkomíšní mok   diagnostické zobrazování   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   diagnostické zobrazování   MeSH
• neuropsychologické testy MeSH
• peptidové fragmenty mozkomíšní mok   MeSH
• pozitronová emisní tomografie MeSH
• prostorová navigace * fyziologie   MeSH
• proteiny tau mozkomíšní mok   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The study focuses on the effects of fluvastatin on immunomarkers of the M1 and M2 macrophages and its direct role in macrophage (M0) polarization. Moreover, it investigates the dependency of immunomodulatory properties of fluvastatin on the mevalonate pathway. Macrophages (M0, M1, M2), differentiated from human blood monocytes, were treated with fluvastatin. Mevalonate and geranylgeranyl pyrophosphate intermediates were introduced to assess the mevalonate pathway dependence. The immunomarkers were evaluated with qPCR, ELISA, Griess assay, and flow cytometry. Fluvastatin significantly reduces the pro-inflammatory gene expression (NFκB, IL-1β, IL-6, iNOS) in M1 while enhancing the anti-inflammatory markers (Arg-1, TGFβ) in M2 macrophages. The production of the TNFα, IL-1β, and IL-6 cytokines is reduced in M1, and IL-10 production increased in M2 macrophages. Fluvastatin decreases the iNOS activity in M1 macrophages. The intermediates reverse the fluvastatin's effects on anti-inflammatory gene expression by M2 macrophages, cytokine production (by M1 and M2 macrophages), and iNOS activity (by M1 macrophages). Their impact on surface marker expression was somewhat limited. These findings demonstrate that fluvastatin exerts anti-inflammatory effects on polarized macrophages without affecting polarization per se and also highlight the dependency on the mevalonate pathway. This study deepens the understanding of statins' immunomodulatory mechanisms, suggesting potential applications in treating inflammatory diseases.

• MeSH
• antiflogistika * farmakologie   MeSH
• cytokiny metabolismus   MeSH
• fluvastatin * farmakologie   MeSH
• kyselina mevalonová * metabolismus   MeSH
• lidé MeSH
• makrofágy * účinky léků   metabolismus   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Prostate cancer (PCa) poses a significant global health threat, with high incidence and mortality rates. In 2022, the Council of the European Union (EU) updated its screening recommendations, prioritizing PCa screening. This signals a crucial step towards establishing new early detection programmes in EU member states. This study investigates the role of policy makers and governance in cancer screening to inform the development of PCa screening. We had a mixed-method study design. First, a rapid review was conducted on policy making and governance in EU-funded cancer screening initiatives. Second, a focus group discussion reviewed study concepts and methods. Third, a systematic literature review was performed and, fourth, a series of in-depth interviews with actors involved in PCa screening pilots was conducted. Data were analysed thematically and the findings are used to propose 10 recommendations for policy makers. The results of the rapid review and focus group discussion framed the study in the context of existing cancer screening programmes across the EU, and highlighted what already exists in terms of governance tools and methodology. The literature review and in-depth interviews presented key learnings from the literature and real-life settings. These findings are reported using a pre-existing conceptional framework for effective health system governance. The study underscores the critical importance of governance in effective cancer screening programmes. Ten recommendations are proposed, including: defining cancer screening governance, allocating budgets and defining common approaches and key performance indicators for evaluation, establishing methods to enhance citizen participation, and reinforcing network governance.

• MeSH
• časná detekce nádoru * metody   MeSH
• Evropská unie MeSH
• lidé MeSH
• nádory prostaty * diagnóza   MeSH
• plošný screening * organizace a řízení   MeSH
• správní úředníci * MeSH
• vytváření politiky * MeSH
• zdravotní politika * MeSH
• zjišťování skupinových postojů MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH

Improving the quality of the most basic health behavior among youth may contribute to short-term body composition management with long-term implications for noncommunicable disease regression. This investigation aimed to assess the impact of primary school physical activity (PA), dietary, or dual approach interventions on pupils' body weight (BW) and body mass index (BMI). A systematic review and meta-analysis was completed following a study protocol and a trial registration (PROSPERO: CRD4202347770) with the PRISMA approach. Publications in English or German were included with school-based randomized controlled trials on diet and/or PA. Pupils of primary schools (aged 5-10) with no major nutritional deficiency or unstable health condition were included. The Boolean search strategy revealed a total of 9479 articles, qualifying 39 studies with 20 462 pupils (including 10 211 girls and 10 251 boys) for quantitative synthesis. The interventions were mostly PA (n = 31), several were dietary (n = 6), and some were dual approach (n = 5). Random effects meta-analyses revealed PA intervention (n = 20) to have an effect size of +0.07 kg (95% CI: -0.01 to 0.15) and -0.12 kg/m2 (95% CI: -0.23 to -0.01). Low statistical heterogeneity was found for BW (I2 = 0%; P = 1.000) and BMI (I2 = 0%; P = .9688), respectively. The findings indicate a scarcity of top-quality scientific research performed on healthy diet for body weight management in primary schools. PA intervention for elementary school pupils provides support for a healthier body composition profile amidst the current world health crisis.

• MeSH
• cvičení * MeSH
• dieta * MeSH
• dítě MeSH
• index tělesné hmotnosti MeSH
• lidé MeSH
• podpora zdraví * metody   MeSH
• předškolní dítě MeSH
• randomizované kontrolované studie jako téma MeSH
• školní zdravotnické služby MeSH
• školy MeSH
• studenti * statistika a číselné údaje   MeSH
• tělesná hmotnost * MeSH
• veřejné zdravotnictví * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

IMPORTANCE: Progression independent of relapse activity (PIRA) is a significant contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (MS). Prior studies have used varying PIRA definitions, hampering the comparability of study results. OBJECTIVE: To compare various definitions of PIRA. DESIGN, SETTING, AND PARTICIPANTS: This cohort study involved a retrospective analysis of prospectively collected data from the MSBase registry from July 2004 to July 2023. The participants were patients with MS from 186 centers across 43 countries who had clinically definite relapsing-remitting MS, a complete minimal dataset, and 3 or more documented Expanded Disability Status Scale (EDSS) assessments. EXPOSURE: Three-hundred sixty definitions of PIRA as combinations of the following criteria: baseline disability (fixed baseline with re-baselining after PIRA, or plus re-baselining after relapses, or plus re-baselining after improvements), minimum confirmation period (6, 12, or 24 months), confirmation magnitude (EDSS score at/above worsening score or at/above threshold compared with baseline), freedom from relapse at EDSS score worsening (90 days prior, 90 days prior and 30 days after, 180 days prior and after, since previous EDSS assessment, or since baseline), and freedom from relapse at confirmation (30 days prior, 90 days prior, 30 days before and after, or between worsening and confirmation). MAIN OUTCOME AND MEASURE: For each definition, we quantified PIRA incidence and persistence (ie, absence of a 3-month confirmed EDSS improvement over ≥5 years). RESULTS: Among 87 239 patients with MS, 33 303 patients fulfilled the inclusion criteria; 24 152 (72.5%) were female and 9151 (27.5%) were male. At the first visits, the mean (SD) age was 36.4 (10.9) years; 28 052 patients (84.2%) had relapsing-remitting MS, and the median (IQR) EDSS score was 2.0 (1.0-3.0). Participants had a mean (SD) 15.1 (11.9) visits over 8.9 (5.2) years. PIRA incidence ranged from 0.141 to 0.658 events per decade and persistence from 0.753 to 0.919, depending on the definition. In particular, the baseline and confirmation period influenced PIRA detection. The following definition yielded balanced incidence and persistence: a significant disability worsening compared with a baseline (reset after each PIRA event, relapse, and EDSS score improvement), in absence of relapses since the last EDSS assessment, confirmed with EDSS scores (not preceded by relapses within 30 days) that remained above the worsening threshold for at least 12 months. CONCLUSION AND RELEVANCE: Incidence and persistence of PIRA are determined by the definition used. The proposed standardized definition aims to enhance comparability among studies.

• MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• posuzování pracovní neschopnosti MeSH
• progrese nemoci * MeSH
• recidiva MeSH
• registrace MeSH
• relabující-remitující roztroušená skleróza * diagnóza   patofyziologie   MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

OBJECTIVES: The phase 3 ProDERM study demonstrated intravenous immunoglobulin (IVIg) was safe and effective in patients with dermatomyositis (DM). This analysis assessed clinical and serological predictors of IVIg response in DM patients from ProDERM. METHODS: ProDERM was a prospective, randomized, placebo-controlled study of DM patients. For weeks 0-16, patients received 2.0 g/kg IVIg (Octagam, 10%) or placebo every 4 weeks. Eligible patients entered the open-label extension phase, where all received IVIg to week 40. Univariate and multivariate analyses examined associations between baseline variables and total improvement score (TIS), including myositis disease activity assessment tool (MDAAT; assessing different organ involvement), and myositis-specific and myositis-associated autoantibodies. RESULTS: Ninety-five patients were enrolled. Univariate analyses found no significant association between TIS at week 16 or 40 and age; sex; ethnicity; disease duration/activity; cutaneous, skeletal, gastrointestinal or muscle disease activity; or previous failed or concomitant medications. Multivariate analysis found patients with higher MDAAT cutaneous scores had a better chance of at least minimal TIS improvement. Higher MDAAT pulmonary scores were associated with a lower, but still considerable, chance of improvement. Patients with TIF1-γ antibodies had a better TIS response; however, after controlling for cutaneous disease activity, there was no significant association between antibody classification (including anti-TIF1-γ) and efficacy outcome. CONCLUSION: IVIg was effective in treating DM patients regardless of demographic features and autoantibody status (for most autoantibodies). Patients with higher cutaneous disease activity and/or anti-TIF1-γ responded best to IVIg, while pulmonary disease activity predicted a lower, but still effective, IVIg response, warranting further investigation. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02728752.

• MeSH
• autoprotilátky krev   imunologie   MeSH
• dermatomyozitida * farmakoterapie   imunologie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• imunologické faktory * terapeutické užití   MeSH
• intravenózní imunoglobuliny * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

OBJECTIVE: In patients with axial spondyloarthritis (axSpA) initiating secukinumab (SEC), we aimed to identify baseline (treatment start) predictors of achieving low disease activity (LDA) after 6 months, as measured by the Axial Spondyloarthritis Disease Activity Score using C-reactive protein (ASDAS-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), as well as treatment continuation after 12 months. METHODS: From 11 European registries, patients with axSpA who initiated SEC treatment in routine care, with available data on 6-month ASDAS-CRP and BASDAI assessments were included. Logistic regression analyses on multiply imputed baseline data were performed; potential baseline predictors included demographic, diagnosis, lifestyle, clinical, and patient-reported variables. RESULTS: In a pooled cohort of 1174 patients with axSpA, 5 of 19 potential assessed variables were mutually predictive for achieving LDA by ASDAS-CRP and BASDAI: higher physician global assessment score, noncurrent smoking, lack of prior exposure to biologic/targeted synthetic disease-modifying antirheumatic drugs, and lower Health Assessment Questionnaire scores and BASDAI scores. Moreover, radiographic axSpA and CRP ≤ 10 mg/L were associated with achieving ASDAS-CRP LDA, and HLA-B27 positivity and history of psoriasis with achieving BASDAI LDA, whereas earlier time of secukinumab initiation (2015-2017) was associated with treatment continuation. CONCLUSION: In this European real-world study of patients with axSpA initiating SEC, predictors of achieving LDA by ASDAS-CRP and BASDAI at 6 months and remaining on treatment at 12 months included both clinical, patient-reported, and lifestyle factors, underscoring the complex mechanisms of real-world drug effectiveness.

• MeSH
• antirevmatika * terapeutické užití   MeSH
• axiální spondyloartritida * farmakoterapie   MeSH
• C-reaktivní protein metabolismus   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• registrace MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: The manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is more complex than that of pulmonary infection, and neuropsychiatric symptoms play a role in this complexity. In this paper, we present the case of a 29-year-old schizophrenic patient who suffered from neuroleptic malignant syndrome (NMS) that developed during coronavirus disease 2019 (COVID-19) infection, with an emphasis on the possible connection between these two conditions. Additionally, we provide an overview of published NMS cases in patients with COVID-19 or after vaccination against SARS-CoV-2. CASE PRESENTATION: A 29-year-old patient treated for schizophrenia, treated with paliperidone palmitate (150 mg every four weeks) and cariprazine (6 mg daily), was admitted to the hospital for agitation and aggressivity; shortly after arrival at the hospital, laryngospasm and hypoxia occurred. The patient tested positive for SARS-CoV-2, and later, he developed pneumonia. During hospitalization, olanzapine (20 mg daily) was added to his regimen. However, due to continuing restlessness, haloperidol was administered (20 mg over the course of one day). A few days later, neuroleptic malignant syndrome occurred. He was treated with bromocriptine (15 mg daily) and clonazepam (2 mg daily) and recovered. CONCLUSIONS: As SARS-CoV-2 is known to interact with angiotensin-converting enzyme 2 and DOPA-decarboxylase is known to be coexpressed with this receptor, we hypothesized that COVID-19 infection might play a substantial role in the development of NMS.

• MeSH
• antipsychotika terapeutické užití   škodlivé účinky   MeSH
• COVID-19 * komplikace   virologie   MeSH
• dospělí MeSH
• lidé MeSH
• maligní neuroleptický syndrom * diagnóza   farmakoterapie   virologie   MeSH
• olanzapin terapeutické užití   MeSH
• SARS-CoV-2 * patogenita   MeSH
• schizofrenie * farmakoterapie   komplikace   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH