The aim of the study here was to evaluate the association between expression of CD23 molecule on B-lymphocytes and the level of specific IgE to molecular components of birch, Bermuda grass, hazel pollen, timothy, and rye grass in atopic dermatitis (AD) patients (with and without dupilumab therapy). A total of 46 patients suffering from AD were included: 26 without dupilumab treatment and 20 with dupilumab treatment. Serum levels of specific IgE were measured by the components resolved diagnostic assay ALEX2 Allergy Xplorer, the expression of CD23 molecule on B-lymphocytes was evaluated with flow cytometry. For the statistical analysis, the Spearman's rank correlation coefficient was used. In patients treated with dupilumab, the higher association was observed between the expression of CD23 on B-lymphocytes and specific IgE to molecular components Bet v 1, Cor a 1.0103, Cor a 1.0401, and Phl p 1. This study demonstrated that the relationship between CD23 expression on B-lymphocytes and specific IgE to pollen molecular components varies depending on whether the patient was treated with dupilumab and the type of molecular component involved.

What is already known about this topic?It is not yet known whether the expression of molecule CD23 on B lymphocytes is related to the level of allergen-specific IgE antibodies in AD patients. It is also not yet known what role dupilumab may have on this receptor.What does this article add to our knowledge?The study investigated the relationship between CD23 expression on B lymphocytes and specific IgE levels to various pollen molecular components in patients with atopic dermatitis (AD), both with and without dupilumab treatment.How does this study impact current management guidelines?The study provides insights into how dupilumab influences IgE interactions and allergic inflammation, potentially guiding more targeted treatments for AD patients.The findings suggest that dupilumab therapy may be more effective in AD patients sensitized to specific molecular components like Bet v 1, Cor a 1.0103, Cor a 1.0401, and Phl p 1, due to its role in reducing inflammatory responses.

• Klíčová slova
• Atopic dermatitis, B lymphocytes, CD23 molecule, dupilumab, molecular components, specific IgE,
• MeSH
• alergeny imunologie   MeSH
• atopická dermatitida * imunologie   farmakoterapie   MeSH
• B-lymfocyty * imunologie   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   MeSH
• imunoglobulin E * krev   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• pyl * imunologie   MeSH
• receptory IgE * metabolismus   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alergeny MeSH
• dupilumab MeSH Prohlížeč
• humanizované monoklonální protilátky * MeSH
• imunoglobulin E * MeSH
• receptory IgE * MeSH

In this multicentric real-world observational retrospective study, we evaluated the efficacy and safety of dupilumab for atopic dermatitis in children <6 years of age who underwent a minimum of 16 weeks of therapy. The analysis focused on EASI (Eczema Area and Severity Index), CDLQI (Children's Dermatology Life Quality Index), and Itch NRS (Numeric Rating Scale) changes from baseline to 4, 16, 24, 48, 72, and 96 weeks of follow-up (when available). Overall 24 children were included, with a mean age of 4.4 years. The baseline mean EASI among these patients was 26.7 (range 11.2-42.5). Since week 16 of therapy, all patients achieved and sustained at least 50% (EASI-50) atopic dermatitis improvement from baseline for the remainder of the follow-up period. At week 16, the mean EASI was 4.6 (0.8-13.1), EASI-75 reached 75% and EASI-90 38% of the patients. Within the initial 16 weeks of dupilumab treatment, 50% of patients experienced at least one adverse event, none of which were deemed severe. Conjunctivitis was among the most common adverse events (8.3%). In conclusion, dupilumab exhibited favorable tolerability, efficacy, and safety in children diagnosed with atopic dermatitis who were below the age of 6.

• Klíčová slova
• Atopic dermatitis, biologics, children, dupilumab, efficacy, safety,
• MeSH
• atopická dermatitida * farmakoterapie   diagnóza   MeSH
• dermatologické látky * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• humanizované monoklonální protilátky * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• kojenec MeSH
• kvalita života MeSH
• lidé MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Názvy látek
• dermatologické látky * MeSH
• dupilumab MeSH Prohlížeč
• humanizované monoklonální protilátky * MeSH

Monitoring patients with phenylketonuria (PKU) requires accurately measuring phenylalanine and tyrosine levels in a small volume of blood samples obtained by the dried blood spot (DBS) technique. The aim was to study selected parameters influencing the quantitative results. Phenylalanine and tyrosine were extracted from DBS samples with methanol, and 5 internal standard introduction techniques were tested. Phenylalanine and tyrosine levels were measured in 6-mm discs punched from DBS, pre-punched 9-mm discs containing the entire DBS sample, and liquid blood by HPLC-MS-MS. Levels in 6-mm discs punched from DBS measured by HPLC-MS/MS were compared with those measured by the HPLC-FLD. The analytical parameters of the method are satisfactory, linearity in the range of 25-1200 μmol/L (LOD, LOQ and LLOQ values 0.2 μmol/L, 0.5 μmol/L and 3.8 μmol/L for phenylalanine, 0.5 μmol/L, 1.5 μmol/L and 5.1 μmol/L for tyrosine), within-run precision 1.8 %-3.7 % for phenylalanine, 1.9 %-2.7 % for tyrosine, between-run precision 4.7 %-5.9 % for phenylalanine, 4.1 %-5.4 % for tyrosine, recovery 93.8 %-100.4 % for phenylalanine and 93.7 %-99.1 % for tyrosine. Good agreement was found between phenylalanine and tyrosine concentrations in 6-mm discs punched from DBS (R = 0.896, p < 0.001, and R = 0.907, p < 0.001, respectively), pre-punched 9-mm discs containing the entire DBS sample (R = 0.960, p < 0.001, and R = 0.950, p < 0.001, respectively) and liquid blood, as well as between phenylalanine and tyrosine concentrations obtained by HPLC-MS/MS and HPLC-FLD (R = 0.968, p < 0.001, and R = 0.984, p < 0.001, respectively). The presented method is suitable for monitoring patients with PKU.

• Klíčová slova
• Dried blood spot, Liquid chromatography with mass spectrometry and fluorescence detection, Parameters affecting quantitative results, Phenylalanine, Tyrosine,
• MeSH
• fenylalanin * krev   MeSH
• fenylketonurie * krev   diagnóza   MeSH
• lidé MeSH
• limita detekce MeSH
• reprodukovatelnost výsledků MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• test suché kapky krve * metody   MeSH
• tyrosin * krev   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fenylalanin * MeSH
• tyrosin * MeSH

BACKGROUND AND OBJECTIVES: N-acetyl-l-leucine (NALL) has been established to improve the neurologic manifestations of Niemann-Pick disease type C (NPC) after 12 weeks in a placebo-controlled trial. In the open-label extension phase (EP) follow-up, data were obtained after 12 and 18 months to evaluate the long-term effects of NALL for NPC. METHODS: This is an ongoing, multinational, multicenter EP. Patients with a genetic diagnosis of NPC aged 4 years or older who completed the placebo-controlled trial were eligible to continue in the EP and receive orally administered NALL 2-3 times per day in 3 tiers of weight-based dosing. The primary end point is the modified 5-domain NPC Clinical Severity Scale (NPC-CSS) (range 0-25 points; lower score representing better neurologic status); data from the EP cohort are compared with the expected annual trajectory of decline (i.e., disease progression) established in natural history studies. Analyses are also performed on exploratory end points, including the 15-domain and 4-domain NPC-CSSs and the Scale for Assessment and Rating of Ataxia (SARA). RESULTS: Fifty-three patients aged 5-67 years (45.3% female, 54.7% male) were enrolled in the EP. After 12 months, the mean (±SD) change from baseline on the 5-domain NPC-CSS was -0.27 (±2.42) with NALL vs +1.5 (±3.16) in the historical cohort (95% CI -3.05 to -0.48; p = 0.009), corresponding to a 118% reduction in annual disease progression. After 18 months, the mean (±SD) change was +0.05 (±2.95) with NALL vs +2.25 (±4.74) in the historical cohort (95% CI -4.06 to -0.35; p = 0.023). The 15-domain and 4-domain NPC-CSSs were consistent with the 5-domain NPC-CSS. The improvements in neurologic manifestations demonstrated in the placebo-controlled trial on the primary SARA end point were sustained over the long-term follow-up. NALL was well tolerated, and no treatment-related adverse events or serious reactions occurred. DISCUSSION: Treatment with NALL was associated with a significant reduction in NPC disease progression after 12 and 18 months, demonstrating a disease-modifying, neuroprotective effect. TRIAL REGISTRATION INFORMATION: The trial is registered with ClinicalTrials.gov (NCT05163288; registered December 6, 2021), EudraCT (2021-005356-10). The first patient was enrolled into the EP on March 8, 2023. The trial was funded by IntraBio Inc. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that NALL reduces disease progression in NPC.

• MeSH
• dítě MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• leucin * analogy a deriváty   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• neuroprotektivní látky * terapeutické užití   MeSH
• Niemannova-Pickova nemoc typu C * farmakoterapie   MeSH
• předškolní dítě MeSH
• progrese nemoci MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• acetylleucine MeSH Prohlížeč
• leucin * MeSH
• neuroprotektivní látky * MeSH

BACKGROUND: Liver glycogen storage disorders (GSDs) are rare inherited disorders of carbohydrate metabolism that are clinically characterized by hepatomegaly and fasting intolerance. This group of disorders comprises GSD Ia and Ib as well as the so-called ketotic GSDs including GSD III, VI, IX, XI and 0a. Although clinical practice guidelines exist for most GSD subtypes, diagnostics, treatment and monitoring differ significantly among metabolic centres. The aim of this study was to gain insight into current clinical practice for liver GSDs. METHODS: An international web-based survey was performed among health care professionals involved in the care of individuals with liver GSDs. RESULTS: Sixty-seven respondents from 28 different countries caring for approximately 2650 liver GSD patients completed the survey. While the diagnostic approach was generally consistent, significant differences among metabolic centres are still observed with respect to monitoring parameters and treatment approaches. Reasons for these differences are local availability of management tools and treatment options, the rarity of the different GSD subtypes, the experiences of health care professionals, and the existence of extreme phenotypes. CONCLUSION: The development of a standard set of outcomes for patients with liver GSDs is warranted as a reference for both daily care and the evaluation of safety and efficacy of future therapies. For various parameters that serve as valuable outcome measures, tools and target values should be better defined.

• Klíčová slova
• Diagnostics, Liver glycogen storage diseases, Management, Monitoring, Treatment,
• MeSH
• glykogenóza * terapie   diagnóza   MeSH
• játra metabolismus   patologie   MeSH
• lidé MeSH
• management nemoci MeSH
• nemoci jater * terapie   diagnóza   MeSH
• průzkumy a dotazníky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

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

The RFC4 gene has recently been linked to a multisystemic disorder Morimoto-Ryu-Malicdan neuromuscular syndrome, with myopathy being one of the key symptoms described in nine patients. We report the case of two brothers with a rapidly progressive congenital myopathy characterized by severe hypotonia and axial muscle weakness associated with previously unpublished biallelic variants in the RFC4 gene. Whole exome sequencing revealed biallelic variants NM_002916.5:c.1019_1020insCAAA and NM_002916.5:c.982_983insACT, corresponding to the protein-level changes p.(Gly341Lysfs*4) and p.(Thr328delinsAsnSer) in both brothers. This case expands the phenotypic spectrum of Morimoto-Ryu-Malicdan neuromuscular syndrome, highlighting severe early-onset axial muscle weakness, severe hypotonia, and preserved intellectual development. We also provide novel insights into the clinical progression and potential multidisciplinary interventions for patients with Morimoto-Ryu-Malicdan neuromuscular syndrome. Our findings highlight the importance of advanced genetic diagnostics and international collaboration in identifying rare neuromuscular diseases and improving the clinical management of affected patients.

• Klíčová slova
• Cerebellar atrophy, Hearing loss, Morimoto-Ryu-Malicdan neuromuscular syndrome, Multisystemic disorders, Myopathy, RFC4,
• MeSH
• dítě MeSH
• fenotyp MeSH
• lidé MeSH
• myotonia congenita * genetika   patofyziologie   MeSH
• předškolní dítě MeSH
• progrese nemoci MeSH
• sourozenci MeSH
• svalová hypotonie * genetika   patofyziologie   MeSH
• svalová slabost * genetika   patofyziologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Protein misfolding diseases, including α1-antitrypsin deficiency (AATD), pose substantial health challenges, with their cellular progression still poorly understood1-3. We use spatial proteomics by mass spectrometry and machine learning to map AATD in human liver tissue. Combining Deep Visual Proteomics (DVP) with single-cell analysis4,5, we probe intact patient biopsies to resolve molecular events during hepatocyte stress in pseudotime across fibrosis stages. We achieve proteome depth of up to 4,300 proteins from one-third of a single cell in formalin-fixed, paraffin-embedded tissue. This dataset reveals a potentially clinically actionable peroxisomal upregulation that precedes the canonical unfolded protein response. Our single-cell proteomics data show α1-antitrypsin accumulation is largely cell-intrinsic, with minimal stress propagation between hepatocytes. We integrated proteomic data with artificial intelligence-guided image-based phenotyping across several disease stages, revealing a late-stage hepatocyte phenotype characterized by globular protein aggregates and distinct proteomic signatures, notably including elevated TNFSF10 (also known as TRAIL) amounts. This phenotype may represent a critical disease progression stage. Our study offers new insights into AATD pathogenesis and introduces a powerful methodology for high-resolution, in situ proteomic analysis of complex tissues. This approach holds potential to unravel molecular mechanisms in various protein misfolding disorders, setting a new standard for understanding disease progression at the single-cell level in human tissue.

• MeSH
• alfa-1-antitrypsin metabolismus   MeSH
• analýza jednotlivých buněk MeSH
• deficit alfa1-antitrypsinu * patologie   metabolismus   genetika   MeSH
• fenotyp MeSH
• hepatocyty metabolismus   patologie   MeSH
• jaterní cirhóza patologie   metabolismus   MeSH
• játra patologie   metabolismus   MeSH
• lidé MeSH
• progrese nemoci MeSH
• proteom * analýza   metabolismus   MeSH
• proteomika * metody   MeSH
• signální dráha UPR MeSH
• strojové učení MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alfa-1-antitrypsin MeSH
• proteom * MeSH

Gout and hyperuricemia increase cardiovascular disease risk, highlighting the need for improved risk stratification. In this pilot study, we evaluated the Coronary Event Risk Test (CERT) in 94 hyperuricemic and 196 gout patients, and 53 controls. Plasma ceramides were determined by liquid chromatography-mass spectrometry. Elevated CERT scores (≥7) occurred in 11.7 % (2-fold increase) of hyperuricemic and 31.12 % (5.5-fold increase) of gout patients compared to controls. Additionally, both hyperuricemic and gout patients with increased CERT also exhibited higher levels of inflammation and atherogenic index of plasma, both of which were significantly associated with CERT. Incorporating CERT into routine care may enhance risk stratification and guide targeted interventions in this patient population.

• Klíčová slova
• Cardiovascular risk, Ceramides, Coronary event risk test, Gout, Hyperuricemia, Lipidomics,
• MeSH
• biologické markery krev   MeSH
• ceramidy * krev   MeSH
• chromatografie kapalinová MeSH
• dna (nemoc) * krev   diagnóza   komplikace   MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• hyperurikemie * krev   diagnóza   komplikace   MeSH
• kardiovaskulární nemoci * diagnóza   krev   etiologie   epidemiologie   MeSH
• kyselina močová * krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metody pro podporu rozhodování * MeSH
• pilotní projekty MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• ceramidy * MeSH
• kyselina močová * MeSH

Familial hypercholesterolemia (FH) is a relatively rare genetic disease associated with high serum cholesterol levels but also with abnormalities in blood coagulation. Novel pharmacotherapeutic approaches in FH including proprotein convertase subtilisin/kexin type 9 antibodies (PCSK9Ab) are very efficient in decreasing cholesterol levels but their impact on coagulation in FH is not yet established. Therefore, we hypothesized that these novel antidyslipidemic drugs can positively impact blood coagulation due to their more potent effect on cholesterol. A total of 15 healthy volunteers and all 15 available patients with severe FH treated at the University Hospital Hradec Králové were enrolled, coagulation was assessed by mechanic coagulometer, and the impact of four clinically used direct anticoagulants was analyzed ex vivo. FH patients were treated effectively as their total cholesterol was 4.11 ± 1.57 mM and LDL cholesterol was 2.44 ± 1.46 mM, which were even lower values than detected in our generally healthy controls. Twelve from the 15 FH patients were finally analyzed as 3 were treated with anticoagulants. Coagulation in FH patients was prolonged more extensively by dabigatran and rivaroxaban, when compared to healthy controls. Treatment with PCSK9Ab or lipid apheresis did not seem to have a significant effect on coagulation. The latter procedure however significantly decreased serum levels of one vitamin K form, MK4. Shorter coagulation time was associated with higher levels of LDL, non-HDL, and total cholesterol. Current treatment of FH seems to improve the effects of direct anticoagulants beyond known effects on LDL cholesterol levels.

• Klíčová slova
• Direct anticoagulants, Familial hypercholesterolemia, Proprotein convertase subtilisin/kexin type 9, Vitamin K,
• MeSH
• anticholesteremika terapeutické užití   MeSH
• antikoagulancia * terapeutické užití   farmakologie   MeSH
• cholesterol krev   MeSH
• dabigatran terapeutické užití   farmakologie   MeSH
• dospělí MeSH
• hemokoagulace * účinky léků   MeSH
• hyperlipoproteinemie typ II * krev   farmakoterapie   MeSH
• hypolipidemika * terapeutické užití   farmakologie   MeSH
• LDL-cholesterol krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• PCSK9 inhibitory MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 MeSH
• rivaroxaban terapeutické užití   farmakologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anticholesteremika MeSH
• antikoagulancia * MeSH
• cholesterol MeSH
• dabigatran MeSH
• hypolipidemika * MeSH
• LDL-cholesterol MeSH
• PCSK9 inhibitory MeSH
• PCSK9 protein, human MeSH Prohlížeč
• proproteinkonvertasa subtilisin/kexin typu 9 MeSH
• rivaroxaban MeSH