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   MeSH
• dítě MeSH
• humanizované monoklonální protilátky * škodlivé účinky   terapeutické užití   MeSH
• kojenec MeSH
• kvalita života MeSH
• lidé MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• stupeň závažnosti nemoci * MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• 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
• dupilumab MeSH Prohlížeč
• humanizované monoklonální protilátky * MeSH

In this work, we present the synthesis and application of fluorescent rhodamine B hydrazide for the derivatization of simple oligosaccharides and complex glycans using a hydrazone formation chemistry approach. The labeling conditions and the experimental setup of CE/LIF were optimized by analyzing oligosaccharide standards. The CE/LIF separations were performed in polybrene-coated capillaries eliminating the need for the purification step after derivatization. The addition of methanol to the background electrolyte significantly increased the LIF detection sensitivity reaching the limits of detection in the attomole range. The resolution of carbohydrate samples was improved by using long (98 cm) capillaries and polymer additives (polybrene). The developed method was applied for CE/LIF and CE-MS analysis of N-linked glycans released from bovine ribonuclease B and the therapeutic monoclonal antibody of trastuzumab.

• Klíčová slova
• Capillary electrophoresis, Fluorescence, Glycan, Labeling, Mass spectrometry, Rhodamine B hydrazide,
• MeSH
• elektroforéza kapilární * metody   MeSH
• fluorescenční barviva * chemie   MeSH
• fluorescenční spektrometrie metody   MeSH
• hmotnostní spektrometrie metody   MeSH
• lasery MeSH
• oligosacharidy * chemie   analýza   MeSH
• polysacharidy * analýza   chemie   MeSH
• rhodaminy * chemie   MeSH
• skot MeSH
• trastuzumab chemie   analýza   MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fluorescenční barviva * MeSH
• oligosacharidy * MeSH
• polysacharidy * MeSH
• rhodamine B MeSH Prohlížeč
• rhodaminy * MeSH
• trastuzumab MeSH

Lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib in treatment of advanced renal cell carcinoma (aRCC) in the phase 3 CLEAR study. We report results of an exploratory post hoc analysis of tumor response data based on baseline metastatic characteristics of patients who received lenvatinib plus pembrolizumab versus sunitinib, at the final overall survival analysis time point of CLEAR (cutoff: July 31, 2022). Treatment-naïve adults with aRCC were randomized to: lenvatinib (20 mg PO QD in 21-day cycles) plus pembrolizumab (n = 355; 200 mg IV Q3W); lenvatinib plus everolimus (not reported here); or sunitinib (n = 357; 50 mg PO QD; 4 weeks on/2 weeks off). The most common (lenvatinib plus pembrolizumab; sunitinib, respectively) metastatic site was lung (71.0%; 63.9%), followed by lymph node (45.6%; 43.7%), bone (22.5%; 24.9%), and liver (17.7%; 19.6%). Across treatment arms, ≥65% had two or more metastatic organs/sites involved, >80% of patients had nontarget lesions, and ~45% had baseline sums of diameters of target lesions ≥60 mm. Lenvatinib plus pembrolizumab demonstrated greater progression-free survival, objective response rate, and duration of response versus sunitinib across evaluable subgroups regardless of site or size of baseline metastasis or number of metastatic sites at baseline. Overall survival generally trended to favor lenvatinib plus pembrolizumab versus sunitinib; and tumor shrinkage was greater across sites (lung, lymph node, liver, and bone) for patients in the lenvatinib-plus-pembrolizumab arm versus the sunitinib arm. These results further support lenvatinib plus pembrolizumab as a standard-of-care in patients with aRCC regardless of site or size of baseline metastasis or the number of metastatic sites.

• Klíčová slova
• lenvatinib, lenvatinib plus pembrolizumab, pembrolizumab, renal cell carcinoma,
• MeSH
• chinoliny * aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• fenylmočovinové sloučeniny * aplikace a dávkování   terapeutické užití   MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   terapeutické užití   MeSH
• karcinom z renálních buněk * farmakoterapie   patologie   mortalita   sekundární   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory ledvin * farmakoterapie   patologie   mortalita   MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sunitinib * aplikace a dávkování   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• chinoliny * MeSH
• fenylmočovinové sloučeniny * MeSH
• humanizované monoklonální protilátky * MeSH
• lenvatinib MeSH Prohlížeč
• pembrolizumab MeSH Prohlížeč
• sunitinib * MeSH

This article explores the use of expansion microscopy, a technique that enhances resolution in fluorescence microscopy, on the autotrophic protist Euglena gracilis A modified protocol was developed to preserve the cell structures during fixation. Using antibodies against key cytoskeletal and organelle markers, α-tubulin, β-ATPase, and Rubisco activase, the microtubular structures, mitochondria, and chloroplasts were visualised. The organisation of the cytoskeleton corresponded to the findings from electron microscopy while allowing for the visualisation of the flagellar pocket in its entirety and revealing previously unnoticed details. This study offered insights into the shape and development of mitochondria and chloroplasts under varying conditions, such as culture ages and light cycles. This work demonstrated that expansion microscopy is a robust tool for visualising cellular structures in E. gracilis, an organism whose internal structures cannot be stained using standard immunofluorescence because of its complex pellicle. This technique also serves as a complement to electron microscopy, facilitating tomographic reconstructions in a routine fashion.

• MeSH
• chloroplasty ultrastruktura   MeSH
• cytoskelet * ultrastruktura   MeSH
• Euglena gracilis * ultrastruktura   MeSH
• flagella ultrastruktura   MeSH
• fluorescenční mikroskopie * metody   MeSH
• mitochondrie ultrastruktura   MeSH
• mitóza MeSH
• protilátky chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• protilátky MeSH

This work focuses on profiling N-linked glycans by capillary electrophoresis coupled to mass spectrometry using a novel fluorescent and mass spectrometry (MS) active derivatization tag. The label is based on 2-phenylpyridine bearing tertiary amine and hydrazide functionalities. It provides efficient labeling via hydrazone formation chemistry, promising fluorescence properties, and ionization efficiency in the positive ion MS mode. Electrophoretic analysis in a neutral-coated capillary allowed baseline separation of maltooligosaccharides with limits of detection in nanomolar concentrations. The developed labeling method was successfully applied to the analyses of N-linked glycans released from several glycoproteins such as bovine ribonuclease B, human immunoglobulin G, or chicken albumin.

• Klíčová slova
• Capillary electrophoresis, Glycans, Labeling, Mass spectrometry, Oligosaccharides, Phenylpyridine,
• MeSH
• elektroforéza kapilární * metody   MeSH
• glykoproteiny analýza   chemie   MeSH
• hmotnostní spektrometrie * metody   MeSH
• imunoglobulin G chemie   analýza   MeSH
• kationty chemie   MeSH
• kur domácí MeSH
• lidé MeSH
• polysacharidy * analýza   chemie   MeSH
• pyridiny * chemie   MeSH
• ribonukleasy MeSH
• skot MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glykoproteiny MeSH
• imunoglobulin G MeSH
• kationty MeSH
• polysacharidy * MeSH
• pyridiny * MeSH
• ribonuclease B MeSH Prohlížeč
• ribonukleasy MeSH

AIMS: To investigate the efficacy and safety of intravitreal Dexamethasone implant (DEX-I) therapy in the treatment of diabetic macular edema (DME) refractory to intravitreal bevacizumab (IVB). MATERIAL AND METHODS: This retrospective and cross-sectional study included 37 eyes of 37 patients who received 3 loading doses of IVB injections for DME with no response and underwent DEX-I implant. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurements and central foveal thickness (CFT) measured by spectral domain optical coherence tomography (SD-OCT) were recorded and compared before DEX-I, at the first week, first, second, third and sixth months. Duration of DME, glycated hemoglobin (HbA1c) levels, DME types and lens status (phakic, pseudophakic) were also recorded. RESULTS: The mean age of the patients was 61.14 ±8.69 years (59.5% male, 40.5% female). 35.1% of the patients had cystoid macular edema, 64.9% had diffuse macular edema and 73 % were phakic and 27% were pseudophakic. BCVA, CFT and IOP values before DEX-I injection were 0.78 ±0.16 LogMAR, 493.73 ±107.6 µm and 13.05 ±2.59 mmHg, respectively. At 6 months after DEX-I, BCVA, CFT and IOP values were 0.64 ±0.11 LogMAR, 397.35 ±59.72 µm and 16.3 ±2.51 mmHg, respectively. In all follow-ups, there was a significant improvement in BCVA, a significant decrease in CFT and a significant increase in IOP compared to pre-injection. Ocular hypertension was observed in 0.8 % of patients and progression of cataract progression in 1% of patients after treatment. CONCLUSION: DEX-I therapy is an effective and safe treatment option for DME refractory to IVB treatment.

• Klíčová slova
• Dexamethasone implant, bevacizumab, cataract, diabetic macular edema, intraocular pressure,
• MeSH
• bevacizumab aplikace a dávkování   škodlivé účinky   MeSH
• dexamethason * aplikace a dávkování   škodlivé účinky   MeSH
• diabetická retinopatie * farmakoterapie   MeSH
• glukokortikoidy aplikace a dávkování   škodlivé účinky   MeSH
• injekce intravitreální * MeSH
• léky implantované * MeSH
• lidé středního věku MeSH
• lidé MeSH
• makulární edém * farmakoterapie   etiologie   diagnostické zobrazování   MeSH
• průřezové studie MeSH
• retrospektivní studie MeSH
• senioři MeSH
• zraková ostrost MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bevacizumab MeSH
• dexamethason * MeSH
• glukokortikoidy MeSH
• léky implantované * MeSH

OBJECTIVES: To compare the drug survival of etanercept to monoclonal tumour necrosis factor-α inhibitors in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. METHODS: Patients initiating first line biological therapy with tumour necrosis factor-α were propensity score matched and compared for drug survival with a Kaplan-Meier analysis. RESULTS: We matched 657 to 657 patients in rheumatoid arthritis, the median survival time on etanercept was 44.6 months vs. 36.8 months on monoclonal antibody tumour necrosis factor-α inhibitors, with a hazard ratio of 0.94, p = 0.416 We matched 187 to 356 patients in ankylosing spondylitis, the median survival time on etanercept was 75.1 compared to 68.0 months, hazard ratio of 0.78, p = 0.087 We matched 81 to 160 psoriatic arthritis patients, the median survival time on etanercept was 35.8. compared to 65.7 months, hazard ratio 1.61, p = 0.011. Patients treated with etanercept had significantly worse psoriasis scoring during follow up. CONCLUSIONS: We found comparable survival in rheumatoid arthritis and ankylosing spondylitis. In psoriatic arthritis, we found significantly shorter survival on etanercept, possibly due to worse response of skin and nail manifestations.

• MeSH
• adalimumab terapeutické užití   MeSH
• ankylózující spondylitida * farmakoterapie   mortalita   MeSH
• antirevmatika * terapeutické užití   MeSH
• dospělí MeSH
• etanercept * terapeutické užití   MeSH
• infliximab terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• psoriatická artritida * farmakoterapie   mortalita   MeSH
• registrace * MeSH
• revmatoidní artritida * farmakoterapie   mortalita   MeSH
• senioři MeSH
• tendenční skóre * MeSH
• TNF-alfa * antagonisté a inhibitory   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• adalimumab MeSH
• antirevmatika * MeSH
• etanercept * MeSH
• infliximab MeSH
• monoklonální protilátky MeSH
• TNF-alfa * MeSH

PURPOSE: This study evaluated the efficacy, safety, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of SB16 versus reference denosumab (DEN) up to 18 months in postmenopausal osteoporosis (PMO) patients, and assessed outcomes after switching from DEN to SB16 compared to those who continued with DEN or SB16. METHODS: 457 PMO patients were initially randomized, with 407 re-randomized at Month 12 to either continue DEN (DEN+DEN), switch to SB16 (DEN+SB16), or continue SB16 (SB16 + SB16) through Month 18. Efficacy was assessed by the percent change from baseline in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck. Safety, PD, PK, and immunogenicity were evaluated throughout the study period. RESULTS: Mean percent changes from baseline in lumbar spine, total hip, and femoral neck BMD at Month 18 were comparable across treatment groups, indicating comparable efficacy between SB16 and DEN. The mean percent change in lumbar spine BMD was 6.8 % (SB16 + SB16), 6.2 % (DEN+SB16), and 6.8 % (DEN+DEN). Total hip BMD increased by 4.4 %, 3.5 %, and 4.0 %, and femoral neck BMD by 3.4 %, 3.1 %, and 2.7 % for SB16 + SB16, DEN+SB16, and DEN+DEN, respectively. Safety profiles were similar among groups, with no new safety concerns identified after switching. Only one patient in the DEN+SB16 group developed non-neutralizing anti-drug antibodies by Month 18, indicating a low immunogenicity risk for SB16. CONCLUSION: Switching from DEN to SB16 demonstrated comparable efficacy, safety, PD, PK, and immunogenicity in PMO patients relative to those who continued DEN. SB16 was well tolerated over 18 months, demonstrating comparable outcomes to DEN.

• Klíčová slova
• Biosimilar, Bone mineral density, Clinical trials, Denosumab, Postmenopausal osteoporosis, SB16,
• MeSH
• bederní obratle účinky léků   MeSH
• denosumab * terapeutické užití   MeSH
• inhibitory kostní resorpce * terapeutické užití   MeSH
• kostní denzita * účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• postmenopauzální osteoporóza * farmakoterapie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• denosumab * MeSH
• inhibitory kostní resorpce * MeSH

PURPOSE: High-dose intravenous glucocorticoids are the standard first-line treatment in active, moderate to severe and severe thyroid eye disease (TED). We evaluate the usefulness of clinical activity score (CAS) and thyroid-stimulating immunoglobulin (TSI) as predictors and/or post-treatment markers of corticoresistance in patients with TED and the effect of rituximab in second-line treatment. METHODS: We enrolled 236 patients with an active TED into this retrospective single-tertiary-center cohort study. All patients were initially treated with high-dose systemic glucocorticoids. Rituximab was later administered to 29 of 42 corticoresistant patients. RESULTS: The CAS of the corticoresistant patients was significantly higher both before (p = 0.0001) and after (p = <0.0001) first-line treatment compared to the corticosensitive group. ROC analysis established the cut-point value as CAS ≥ 2.5 with a sensitivity of 96.3%, specificity of 57.5% and area under the curve of 82.8%. In 22 patients treated with rituximab, CAS gradually decreased to zero values without reactivation during extended follow-up. There was no difference in the TSI of corticosensitive and corticoresistant patients before or after first-line therapy. CONCLUSION: CAS ≥ 2, after first-line treatment, could be used as a corticoresistance marker. Corticoresistant patients should be subject to long-term follow-up for early detection of reactivation to reduce the delay to second-line treatment. Rituximab is a well-tolerated choice of second-line treatment and has a long-lasting effect on disease activity. Although TSI is a valuable biomarker of Graves' disease and TED activity, according to our results, TSI cannot be used as a marker of corticoresistance.

• Klíčová slova
• clinical activity score, corticoresistance, corticosensitivity, immunosuppressive treatment, rituximab, thyroid eye disease,
• MeSH
• dospělí MeSH
• glukokortikoidy terapeutické užití   MeSH
• Gravesova oftalmopatie * farmakoterapie   krev   MeSH
• imunoglobuliny stimulující tyreoideu krev   MeSH
• imunologické faktory terapeutické užití   MeSH
• léková rezistence * MeSH
• lidé středního věku MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rituximab * terapeutické užití   MeSH
• senioři 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
• Názvy látek
• glukokortikoidy MeSH
• imunoglobuliny stimulující tyreoideu MeSH
• imunologické faktory MeSH
• rituximab * MeSH

Our aim is to determine the number of leukocytes, T lymphocytes and B lymphocytes and the expression of activation markers CD200 and CD23 on B lymphocytes in atopic dermatitis (AD) patients (treated and not treated with dupilumab) during the pollen season. We examined 29 patients not treated with dupilumab, 24 patients treated with dupilumab and 40 healthy subjects as a control group. The count of T and B lymphocytes and their subsets were assessed by flow cytometry. The non-parametric Kruskal-Wallis one-factor analysis of variance with post hoc by Dunn's test with Bonferroni's modification was used for statistical processing. Although there was a significant improvement in skin findings in patients treated with dupilumab, the changes in immunological profile show a persistent altered immune response characterized by dysregulation and overactivation of B lymphocytes. Dupilumab therapy leads to normalization of relative T regulatory lymphocytes and total memory B lymphocytes and to decreased count of absolute CD8+ T lymphocytes. Why carry out this study?Studies investigating the immunological profile of atopic dermatitis (AD) patients during the pollen season are rare. There are no studies investigating the count of B lymphocytes (CD5+, CD22+ and CD73+ B lymphocytes) and the expression of activation markers CD23 and CD200 on B lymphocytes and on their subsets during pollen season in AD patients treated and non-treated with dupilumab therapy.What was learned from the study?In atopic dermatitis (AD) patients with and without dupilumab therapy, we confirmed the significantly higher count of absolute neutrophils, absolute monocytes, absolute eosinophils, absolute basophils, non-switched B lymphocytes, transitional B lymphocytes, CD23 memory, naive, non-switched, switched and total CD23 B lymphocytes, the relative count of CD200 memory and CD200 switched B lymphocytes.In dupilumab treated patients, we confirmed the significantly higher count of relative eosinophils, relative CD16+ eosinophils, relative CD200 non-switched B lymphocytes and lower count of absolute CD8+ T lymphocytes. Further studies should focus on investigating the effect of dupilumab on CD8+ T lymphocytes and their subpopulations.In patients without dupilumab therapy, we confirmed the significantly higher count of relative neutrophils, relative T regulatory lymphocytes and total memory B lymphocytes.The changes in the count of CD5+, CD22+ and CD73+ B lymphocytes were not observed during pollen season in both groups of AD patients.

• Klíčová slova
• B lymphocytes, Dupilumab, T lymphocytes, atopic dermatitis,
• MeSH
• atopická dermatitida * farmakoterapie   imunologie   MeSH
• B-lymfocyty imunologie   MeSH
• CD antigeny MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• pyl imunologie   MeSH
• receptory IgE MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigens, CD200 MeSH Prohlížeč
• CD antigeny MeSH
• dupilumab MeSH Prohlížeč
• humanizované monoklonální protilátky * MeSH
• receptory IgE MeSH