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

Therapeutic plasma exchange (PLEX) is an adjunctive treatment for patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and kidney involvement. Little is known about the effect of PLEX on early changes in kidney function. This post-hoc analysis of the PEXIVAS trial investigated the effects of PLEX on changes in kidney function within 12 months. PEXIVAS was a randomized controlled trial recruiting 691 patients with ANCA-associated glomerulonephritis, of whom 349 underwent PLEX and 342 received no-PLEX. The primary outcomes of this post hoc study of PEXIVAS were change in estimated glomerular filtration rate (eGFR) from baseline and recovery of kidney function (defined as eGFR increase of 15ml/min/1.73m2 or more). Baseline eGFR was 21.7 ± 20.3 and 20.6 ± 18.7 ml/min/1.73m2 in the PLEX and no-PLEX groups, respectively. Mean improvements in eGFR at weeks two, four, and eight after initiation of therapy were greater for the PLEX vs. the no-PLEX groups. The greatest significant difference in recovery of kidney function in the PLEX compared to the no-PLEX groups was at week four (relative risk (RR): 1.41; 95% confidence interval:1.09-1.82). Increased eGFR or recovery of kidney function at week four were significantly associated with lower risk for end-stage kidney disease at week 52 (RR: 0.96: 0.95-0.97, and RR: 0.29: 0.16-0.52; respectively). Neither changes in eGFR nor recovery of kidney function differed by reduced- compared to standard-dose glucocorticoid group. Overall, our study indicates that PLEX improves early kidney function in patients with ANCA-associated glomerulonephritis.

• Klíčová slova
• ANCA, end-stage kidney disease, glomerulonephritis, kidney function, plasma exchange, vasculitis,
• MeSH
• ANCA-asociované vaskulitidy * patofyziologie   terapie   farmakoterapie   komplikace   imunologie   diagnóza   MeSH
• dospělí MeSH
• glomerulonefritida * patofyziologie   imunologie   terapie   krev   MeSH
• glukokortikoidy * terapeutické užití   aplikace a dávkování   MeSH
• hodnoty glomerulární filtrace * MeSH
• ledviny * patofyziologie   účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• obnova funkce MeSH
• senioři MeSH
• výměna plazmy * 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
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• glukokortikoidy * 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

Patients with metastatic urothelial carcinoma (mUC) are typically elderly and often have other comorbidities that require the use of concomitant medications. In our study we evaluated the association of concomitant use of antibiotics (ATBs), proton pump inhibitors (PPIs), corticosteroids, statins, metformin and insulin with patient outcomes and we validated the prognostic role of a concomitant drug score in mUC patients treated with enfortumab vedotin (EV) monotherapy. Data from 436 patients enrolled in the ARON-2EV retrospective study were analyzed according to the concomitant medications used at baseline. Finally, the patients were stratified into three risk groups according to the concomitant drug score based on ATBs, corticosteroids and PPIs. Statistical analysis involved Fisher exact test, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. Inferior survival outcomes were observed in ATB users compared to non-users (OS: 7.3 months, 95%CI 5.0 - 12.3 vs 13.7 months, 95%CI 12.2 - 47.3, p = 0.001; PFS: 5.1 months 95%CI 3.3 - 17.7 vs 8.3 months, 95%CI 7.1 - 47.3, p = 0.001) and also in corticosteroid users compared to non-users (OS: 8.4 months, 95%CI 6.6 - 10.0 vs 14.2 months, 95%CI 12.7 - 47.3, p < 0.001; PFS: 6.0 months 95%CI 4.6 - 7.9 vs 8.9 months, 95%CI 7.2 - 47.3, p = 0.004). In the Cox multivariate analysis, the concomitant drug score was a significant factor predicting both OS (HR = 1.32 [95% CI 1.03 - 1.68], p = 0.026) and PFS (HR = 1.23 [95% CI 1.01 - 1.51], p = 0.044). Our findings suggest detrimental impact of concomitant use of ATBs and corticosteroids on survival outcomes and the prognostic utility of the concomitant drug score in previously treated mUC patients receiving EV.

• Klíčová slova
• ARON-2EV study, Antibiotics, Concomitant drug score, Concomitant medication, Corticosteroids, Enfortumab vedotin, NCT05290038, Urothelial cancer,
• MeSH
• antibakteriální látky terapeutické užití   MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• inhibitory protonové pumpy terapeutické užití   MeSH
• karcinom z přechodných buněk farmakoterapie   sekundární   patologie   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky * terapeutické užití   MeSH
• nádory močového měchýře farmakoterapie   patologie   mortalita   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• urologické nádory farmakoterapie   patologie   mortalita   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
• multicentrická studie MeSH
• Názvy látek
• antibakteriální látky MeSH
• enfortumab vedotin MeSH Prohlížeč
• hormony kůry nadledvin MeSH
• inhibitory protonové pumpy MeSH
• monoklonální protilátky * MeSH

Early life experiences have long-lasting effects on behaviour and physiology, influencing development of adaptive natural behaviours. Enriching farmed environments encourages expression of natural behaviours in captive fish, promoting positive animal welfare, important for conducting valid and reproducible research and informing better management practices. Using juvenile Atlantic Salmon (Salmo salar), we tested whether provision of environmental enrichment in early life improves welfare. Welfare indicators were measured comparing enriched to non-enriched tanks. Morphological (fin damage and body condition), physiological (plasma cortisol) and behavioural traits (activity, group cohesion, and neophobia) were recorded. Molecular expression of brain mRNA transcripts related to stress response, neuroplasticity and serotonergic system was analysed. Environmental enrichment did not affect morphological welfare indicators, activity, or cortisol. Enriched fish were more cohesive than non-enriched fish, less neophobic, with higher serotonergic turnover, suggesting enrichment mitigates against stress, promoting positive emotional states. Genes related to neuronal development and activity (bdnf and ndf1), cellular stress (hsp90 and hsp70), and serotonin synthesis (tph2) increased in enriched fish following stress, enhancing cognitive function. Our findings suggest early life environmental enrichment is advantageous for positive animal welfare by improving emotional states in captive environments, ensuring animals are free of negative experiences and able to access positive ones.

• Klíčová slova
• Cognitive abilities, Fish welfare, Neurogenesis, Social behaviour, Structural enrichment,
• MeSH
• chování zvířat * fyziologie   MeSH
• hydrokortison krev   metabolismus   MeSH
• pohoda zvířat * MeSH
• Salmo salar * fyziologie   genetika   růst a vývoj   MeSH
• vodní hospodářství * metody   MeSH
• životní prostředí MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hydrokortison MeSH

Indoor dust contains various endocrine-disrupting contaminants, yet the effect drivers of observed glucocorticoid activity are completely unknown. This study conducted an effect-directed analysis using orthogonal fractionation to identify effect drivers of glucocorticoid activity in indoor dust. After the detection of bioactivity using a human cell line stably transfected with a reporter gene, the sample underwent parallel HPLC fractionations with octadecyl, pentafluorophenyl, and aminopropyl columns to obtain orthogonal fractions. The bioassays were utilized to screen the fractions and guide efforts towards prioritization of the bioactive chemicals using targeted and non-targeted analysis with LC-HRMS. The glucocorticoid activity of the identified potential candidates was confirmed by their testing in the same bioassay. To assess their contribution to the detected mixture effects, we calculated their relative potencies. This approach led to the identification of two pharmaceuticals, clobetasol propionate and mometasone furoate, at concentrations ranging from ng to μg per gram of dust, which together accounted for up to 77% of the observed glucocorticoid activity. This is the first report documenting the effect drivers of glucocorticoid receptor agonism in indoor dust; however, together with previous studies of various environmental samples, it documents that in cases when glucocorticoid receptor-agonistic activity is detected, drugs should be considered as likely relevant contaminants. The discovery of potent drugs in household dust highlights concerns for individuals exposed within domestic environments and emphasizes the need to consider pharmaceuticals as relevant contributors to indoor contamination.

• Klíčová slova
• Effect-directed analysis, Endocrine disrupting compounds, Glucocorticoid activity, In vitro, Indoor dust, Orthogonal fractionation,
• MeSH
• chemická frakcionace MeSH
• endokrinní disruptory analýza   MeSH
• glukokortikoidy * analýza   MeSH
• klobetasol MeSH
• látky znečišťující vzduch analýza   MeSH
• lidé MeSH
• mometason furoát MeSH
• monitorování životního prostředí metody   MeSH
• prach * analýza   MeSH
• receptory glukokortikoidů metabolismus   MeSH
• znečištění vzduchu ve vnitřním prostředí * analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• endokrinní disruptory MeSH
• glukokortikoidy * MeSH
• klobetasol MeSH
• látky znečišťující vzduch MeSH
• mometason furoát MeSH
• prach * MeSH
• receptory glukokortikoidů MeSH

Estrogens in aquatic environments pose significant ecological and health risks due to their cumulative effects rather than individual impacts. This study investigates the voltammetric behavior of estrone (E1), 17β-estradiol (E2), estriol (E3), and 17α-ethinylestradiol (EE2), presenting a cost-effective and straightforward method for their simultaneous determination. Using differential pulse voltammetry (DPV) with a boron-doped diamond electrode, the method demonstrates high precision (deviations under 4%) and a linear dynamic range of 15.35-134.55 µmol·L-1. Integration of a vacuum evaporation step reduced detection limits to 10-8 mol·L-1, enabling effective analysis of real water samples. This optimized approach ensures practical applicability for monitoring total estrogen content in aquatic systems, providing an accessible and reliable alternative to conventional methods.

• Klíčová slova
• boron-doped diamond electrode, differential pulse voltammetry, estradiol, estriol, estrone, ethinylestradiol,
• MeSH
• chemické látky znečišťující vodu * analýza   MeSH
• elektrochemické techniky * metody   MeSH
• elektrody MeSH
• estradiol analýza   MeSH
• estriol analýza   MeSH
• estrogeny * analýza   MeSH
• estron analýza   MeSH
• ethinylestradiol analýza   MeSH
• limita detekce MeSH
• voda chemie   analýza   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chemické látky znečišťující vodu * MeSH
• estradiol MeSH
• estriol MeSH
• estrogeny * MeSH
• estron MeSH
• ethinylestradiol MeSH
• voda MeSH

A 70-year-old woman was examined with a 10-day history of photopsia and floaters in her left eye. Her best-corrected visual acuity was 20/25 in both eyes, with a normal intraocular pressure and some nuclear sclerosis. Spectral-domain optical coherence tomography revealed a separated posterior vitreous, with a rolled internal limiting membrane flap and inner retinal dimples in the left eye. Optical coherence tomography angiography demonstrated reduced vessel density in both the superficial and deep capillary plexuses of the left fundus. Sixteen months earlier, she had received a single intravitreal Dexamethasone implant injection, due to inferotemporal branch retinal vein occlusion-related macular edema. A diagnosis of internal limiting membrane tear following an uneventful posterior vitreous detachment was reached and no treatment was recommended.

• Klíčová slova
• Dexamethasone implant, inner retinal dimples, internal limiting membrane tear, intravitreal injection, macular edema, optical coherence tomography, posterior vitreous detachment, retinal vein occlusion,
• MeSH
• dexamethason * aplikace a dávkování   MeSH
• glukokortikoidy aplikace a dávkování   MeSH
• léky implantované * MeSH
• lidé MeSH
• makulární edém * farmakoterapie   diagnostické zobrazování   etiologie   MeSH
• okluze retinální žíly * komplikace   farmakoterapie   diagnóza   diagnostické zobrazování   MeSH
• optická koherentní tomografie MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• dexamethason * MeSH
• glukokortikoidy MeSH
• léky implantované * MeSH

The small airways, also referred to as the lung's silent zone, are closely associated with poor symptom control and more frequent asthma exacerbations. The oscillometry technique superimposes sound or airwaves onto normal tidal breathing and provides information on resistance and reactance, that is, obstacles to airflow occurring inside and outside of the bronchi. More recently, a management paradigm based on so-called "treatable traits" has been proposed to personalize and improve asthma care for individuals by proactively identifying and targeting modifiable pulmonary, extrapulmonary, and behavioral traits affecting asthma control. In this review article, we evaluate the literature on small airways dysfunction as a potential treatable trait in persistent asthma. In particular, we discuss whole- and intrabreath oscillometry and the impact of extrafine inhaled corticosteroids and systemic biologics on the peripheral airways.

• MeSH
• bronchiální astma * patofyziologie   farmakoterapie   diagnóza   MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• lidé MeSH
• oscilometrie * metody   MeSH
• plíce patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• hormony kůry nadledvin MeSH

OBJECTIVE: The aim of this study was to evaluate the outcomes of Ozurdex® (DEX) implant in patients with diabetic macular edema (DME) in real-world clinical practice, and to determine the correlation between known OCT biomarkers and the effect of treatment. MATERIAL AND METHODS: This retrospective study included 42 eyes of 33 patients (16 women, 17 men) treated with DEX at the Department of Ophthalmology, Faculty of Medicine and Dentistry of Palacký University and University Hospital Olomouc for DME indication between 2020 and 2023. Follow-up examinations were conducted at 1, 3, and 6 months after the first DEX application. The main assessed parameters were: best-corrected visual acuity (BCVA), intraocular pressure (IOP), central retinal thickness (CRT), OCT biomarkers. The results were subsequently statistically evaluated. RESULTS: At the first follow-up after DEX application, there was an average decrease in CRT of 186 ±146µm and a gain of 3 ±7 letters. Positive morphological and functional responses were observed in 39 eyes (92.9%) and 23 eyes (54.8%) respectively. The disorganization of retinal inner layers (DRIL) biomarker was initially present in 41 eyes (97.6%), with reduction or disappearance observed in 13 eyes (31%) post-application. Eyes with ellipsoid zone disruption (EZ disruption) had an average initial BCVA of 49.6 letters, compared to 57.8 letters in the group without this biomarker. The mean gain in BCVA was +8.7 letters in treatment-naive eyes and +2.1 letters in previously treated eyes. Chronic DME was less frequent in treatment-naive (n = 1, 14.3%) compared to previously treated eyes (n = 28, 84.8%). All these results were statistically significant (p < 0.05). An increase in IOP post-DEX application occurred in 9 patients (21.4%). CONCLUSION: Our results confirm DEX as a safe and effective treatment option for DME. Treatment-naive patients achieved better functional outcomes. We confirmed ellipsoid zone disruption (EZ disruption) as a negative biomarker. Additionally, we demonstrated the capacity of DEX to reduce disorganization of the retinal inner layers (DRIL).

• Klíčová slova
• OCT biomarkers, Ozurdex, dexamethasone, diabetic macular edema,
• MeSH
• dexamethason * aplikace a dávkování   MeSH
• diabetická retinopatie * farmakoterapie   MeSH
• glukokortikoidy aplikace a dávkování   MeSH
• injekce intravitreální * MeSH
• léky implantované * MeSH
• lidé středního věku MeSH
• lidé MeSH
• makulární edém * farmakoterapie   MeSH
• optická koherentní tomografie 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
• dexamethason * MeSH
• glukokortikoidy MeSH
• léky implantované * MeSH