- MeSH
- alkoholická steatóza jater diagnóza etiologie komplikace terapie MeSH
- azathioprin aplikace a dávkování MeSH
- biologická terapie metody MeSH
- bulózní pemfigoid * farmakoterapie komplikace MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- komorbidita MeSH
- lidé středního věku MeSH
- lidé MeSH
- prednison aplikace a dávkování MeSH
- psoriatická artritida farmakoterapie komplikace MeSH
- psoriáza * farmakoterapie komplikace MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
T-lineage acute lymphoblastic leukemia (T-ALL) accounts for about 15% of pediatric and about 25% of adult ALL cases. Minimal/measurable residual disease (MRD) assessed by flow cytometry (FCM) is an important prognostic indicator for risk stratification. In order to assess the MRD a limited number of antibodies directed against the most discriminative antigens must be selected. We propose a pipeline for evaluating the influence of different markers for cell population classification in FCM data. We use linear support vector machine, fitted to each sample individually to avoid issues with patient and laboratory variations. The best separating hyperplane direction as well as the influence of omitting specific markers is considered. Ninety-one bone marrow samples of 43 pediatric T-ALL patients from five reference laboratories were analyzed by FCM regarding marker importance for blast cell identification using combinations of eight different markers. For all laboratories, CD48 and CD99 were among the top three markers with strongest contribution to the optimal hyperplane, measured by median separating hyperplane coefficient size for all samples per center and time point (diagnosis, Day 15, Day 33). Based on the available limited set tested (CD3, CD4, CD5, CD7, CD8, CD45, CD48, CD99), our findings prove that CD48 and CD99 are useful markers for MRD monitoring in T-ALL. The proposed pipeline can be applied for evaluation of other marker combinations in the future.
- MeSH
- akutní lymfatická leukemie * diagnóza MeSH
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- lymfoblastická leukemie-lymfom z prekurzorových T-buněk * diagnóza MeSH
- průtoková cytometrie MeSH
- reziduální nádor diagnóza MeSH
- T-lymfocyty MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- časná diagnóza MeSH
- lidé MeSH
- průzkumy a dotazníky MeSH
- psoriatická artritida * diagnóza terapie MeSH
- Check Tag
- lidé MeSH
Diagnostic criteria for juvenile myelomonocytic leukemia (JMML) are currently well defined, however in some patients diagnosis still remains a challenge. Flow cytometry is a well established tool for diagnosis and follow-up of hematological malignancies, nevertheless it is not routinely used for JMML diagnosis. Herewith, we characterized the CD34+ hematopoietic precursor cells collected from 31 children with JMML using a combination of standardized EuroFlow antibody panels to assess the ability to discriminate JMML cells from normal/reactive bone marrow cell as controls (n=29) or from cells of children with other hematological diseases mimicking JMML (n=9). CD34+ precursors in JMML showed markedly reduced B-cell and erythroid-committed precursors compared to controls, whereas monocytic and CD7+ lymphoid precursors were significantly expanded. Moreover, aberrant immunophenotypes were consistently present in CD34+ precursors in JMML, while they were virtually absent in controls. Multivariate logistic regression analysis showed that combined assessment of the number of CD34+CD7+ lymphoid precursors and CD34+ aberrant precursors or erythroid precursors had a great potential in discriminating JMMLs versus controls. Importantly our scoring model allowed highly efficient discrimination of truly JMML versus patients with JMML-like diseases. In conclusion, we show for the first time that CD34+ precursors from JMML patients display a unique immunophenotypic profile which might contribute to a fast and accurate diagnosis of JMML worldwide by applying an easy to standardize single eight-color antibody combination.
Bimekizumab je humanizovaná monoklonální protilátka, která se selektivně váže na cytokiny IL-17A, IL-17F a IL-17AF a blokuje jejich působení; inhibice IL-17A, IL-17F a IL-17AF se přitom jeví účinnější než inhibice samotného IL-17A. Bezpečnost a účinnost bimekizumabu u pacientů se středně těžkou až těžkou ložiskovou psoriázou byla hodnocena ve 4 klinických randomizovaných kontrolovaných studiích III. fáze (BE READY, BE SURE, BE VIVID a BE RADIANT), ve kterých byl prokázán rychlejší nástup účinku a vyšší účinnost bimekizumabu nejen v porovnání s placebem, ale i ve srovnání s jinými biologickými léky (adalimumab, ustekinumab, secukinumab). Bezpečnostní profil bimekizumabu byl příznivý, nejčastěji hlášenými nežádoucími účinky byly nasofaryngitida, orální kandidóza (jejíž výskyt byl vyšší v porovnání s léčbou jinými inhibitory IL-17) a infekce horních cest dýchacích. Vysokou účinnost a dobrou snášenlivost bimekizumabu potvrzuje také prezentovaná kazuistika.
Bimekizumab is a humanized monoclonal antibody that selectively binds and blocks the cytokines IL-17A, IL-17F and IL-17AF; inhibition of IL-17A, IL-17F and IL-17AF appears to be more effective than inhibition of IL-17A alone. The safety and efficacy of bimekizumab in patients with moderate-to-severe plaque psoriasis was evaluated in 4 phase III randomised controlled clinical trials (BE READY, BE SURE, BE VIVID and BE RADIANT), which demonstrated a faster onset of action and higher efficacy of bimekizumab not only compared to placebo but also compared to other biologics (adalimumab, ustekinumab, secukinumab). The safety profile of bimekizumab was also favourable, with nasopharyngitis, oral candidiasis (the incidence of which was higher compared to treatment with other IL-17 inhibitors) and upper respiratory tract infections being the most frequently observed adverse events. The high efficacy and good tolerability of bimekizumab is also confirmed by the presented case report.
Liquid chromatography-mass spectrometry (LC-MS) is the key technique for analyzing complex lipids in biological samples. Various LC-MS modes are used for lipid separation, including different stationary phases, mobile-phase solvents, and modifiers. Quality control in lipidomics analysis is crucial to ensuring the generated data's reliability, reproducibility, and accuracy. While several quality control measures are commonly discussed, the impact of organic solvent quality during LC-MS analysis is often overlooked. Additionally, the annotation of complex lipids remains prone to biases, leading to potential misidentifications and incomplete characterization of lipid species. In this study, we investigate how LC-MS-grade isopropanol from different vendors may influence the quality of the mobile phase used in LC-MS-based untargeted lipidomic profiling of biological samples. Furthermore, we report the occurrence of an unusual, yet highly abundant, ethylamine adduct [M+46.0651]+ that may form for specific lipid subclasses during LC-MS analysis in positive electrospray ionization mode when acetonitrile is part of the mobile phase, potentially leading to lipid misidentification. These findings emphasize the importance of considering solvent quality in LC-MS analysis and highlight challenges in lipid annotation.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Tumor necrosis factor-alpha (TNF-α) agonists revolutionized therapeutic algorithms in inflammatory bowel disease (IBD) management. However, approximately every third IBD patient does not respond to this therapy in the long term, which delays efficient control of the intestinal inflammation. METHODS: We analyzed the power of serum biomarkers to predict the failure of anti-TNF-α. We collected serum of 38 IBD patients at therapy prescription and 38 weeks later and analyzed them with relation to therapy response (no-, partial-, and full response). We used enzyme-linked immunosorbent assay to quantify 16 biomarkers related to gut barrier (intestinal fatty acid-binding protein, liver fatty acid-binding protein, trefoil factor 3, and interleukin (IL)-33), microbial translocation, immune system regulation (TNF-α, CD14, lipopolysaccharide-binding protein, mannan-binding lectin, IL-18, transforming growth factor-β1 (TGF-β1), osteoprotegerin (OPG), insulin-like growth factor 2 (IGF-2), endocrine-gland-derived vascular endothelial growth factor), and matrix metalloproteinase system (MMP-9, MMP-14, and tissue inhibitors of metalloproteinase-1). RESULTS: We found that future full-responders have different biomarker profiles than non-responders, while partial-responders cannot be distinguished from either group. When future non-responders were compared to responders, their baseline contained significantly more TGF-β1, less CD14, and increased level of MMP-9, and concentration of these factors could predict non-responders with high accuracy (AUC = 0.938). Interestingly, during the 38 weeks, levels of MMP-9 decreased in all patients, irrespective of the outcome, while OPG, IGF-2, and TGF-β1 were higher in non-responders compared to full-responders both at the beginning and the end of the treatment. CONCLUSIONS: The TGF-β1 and CD14 can distinguish non-responders from responders. The changes in biomarker dynamics during the therapy suggest that growth factors (such as OPG, IGF-2, and TGF-β) are not markedly influenced by the treatment and that anti-TNF-α therapy decreases MMP-9 without influencing the treatment outcome.
