AZURE Dotaz Zobrazit nápovědu
INTRODUCTION: AZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year. METHODS: Patients were aged ≥ 51 years and had completed ≥ 1 year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [- 1 or + 2 weeks] for 3 months followed by IVT-AFL every 2 months [6-12 weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2 mg in either a T&E (minimum treatment interval of 8 weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n = 168), or a fixed dosing regimen (treatment every 8 weeks [± 3 days]; n = 168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (< 15-letter loss) at W52. RESULTS: The full analysis set comprised 332 patients (T&E: n = 165; fixed dosing: n = 167). Mean BCVA change (baseline to W52) was - 0.3 ± 7.5 vs. - 0.5 ± 8.4 letters (T&E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [- 1.51 to 1.96] letters; P < 0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was - 24 ± 55 (T&E) and - 33 ± 47 (fixed dosing) μm. Last treatment interval to W76 was ≥ 12 weeks for 37.0% of T&E patients. No new safety signals were identified. CONCLUSION: IVT-AFL T&E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52 weeks in patients with nAMD who have completed ≥ 1 year of treatment, while reducing treatment burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02540954.
- MeSH
- injekce intravitreální MeSH
- lidé středního věku MeSH
- lidé MeSH
- makulární degenerace * farmakoterapie MeSH
- receptory vaskulárního endoteliálního růstového faktoru * terapeutické užití MeSH
- rekombinantní fúzní proteiny * terapeutické užití MeSH
- senioři MeSH
- výsledek terapie MeSH
- zraková ostrost MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- hodnocení ekvivalence MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
Bisfosfonáty jsou látky dnes běžně používané k léčbě kostních metastáz a k prevenci ztráty kostní denzity v adjuvantní léčbě. Preklinické studie prokázaly přímý i nepřímý vliv bisfosfonátů na proliferaci nádorových buněk a metastazování. Klinické studie záhy ukázaly přínos adjuvantní léčby zoledronátem u postmenopauzálních pacientek s pozitivními estrogenovými receptory v parametru prodloužení přežívání bez známek nemoci. Ve studii ABCSG-12 přidání zoledronátu v intervalu 6 měsíců signifikantně zlepšilo přežívání bez známek nemoci u premenopauzálních pacientek léčených ovariální supresí. Podobné výsledky byly pozorovány u postmenopauzálních pacientek léčených inhibitorem aromatázy ve studii ZO-FAST a ve studii AZURE.
Bisphosphonates are commonly used in patients with breast cancer to reduce skeletal-related events in metastatic disease and to mitigate bone loss associated with adjuvant therapy. Preclinical studies have shown that bisphosphonates may directly inhibit breast cancer cell proliferation and metastasis. Subsequently, trials of zoledronic acid have demonstrated prolonged disease-free survival in postmenopausal or otherwise estrogen-depleted women with early breast cancer. In the ABCSG-12 trial, the addition of twice-yearly zoledronic acid (4 mg IV) to adjuvant endocrine therapy improved disease-free survival in premenopausal women undergoing ovarian suppression. Similar results were observed in postmenopausal women receiving aromatase inhibitors in the ZO-FAST trial, and in women who were at least 5 years past menopause in the AZURE trial.
- Klíčová slova
- zoledronát, AZURE, ZO-FAST, ABCSG-12,
- MeSH
- adjuvantní chemoterapie MeSH
- bisfosfonáty * farmakologie terapeutické užití MeSH
- imidazoly * farmakologie terapeutické užití MeSH
- inhibitory kostní resorpce terapeutické užití MeSH
- klinické zkoušky, fáze III jako téma MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- metastázy nádorů farmakoterapie prevence a kontrola MeSH
- nádory kostí prevence a kontrola sekundární MeSH
- nádory prsu * farmakoterapie MeSH
- postmenopauza MeSH
- premenopauza MeSH
- přežití po terapii bez příznaků nemoci MeSH
- Check Tag
- lidé MeSH
Biodegradation potential of Dichomitus squalens in biofilm cultures and rotating biological contactor (RBC) was investigated. The fungus formed thick biofilms on inert and lignocellulosic supports and exhibited stable activities of laccase and manganese peroxidase to reach 40-62 and 25-32% decolorization of anthraquinone Remazol Brilliant Blue R and heterocyclic phthalocyanine dyes, respectively. The decolorization ceased when glucose concentration dropped to 1 mmol l(-1). In RBC reactor, respective decolorizations of Remazol Brilliant Blue R and heterocyclic Methylene Blue and Azure B dyes (50 mg l(-1)) attained 99%, 93%, and 59% within 7, 40 and 200 h. The fungus exhibited tolerance to coliform and non-coliform bacteria on rich organic media, the inhibition occurred only on media containing tryptone and NaCl. The degradation efficiency in RBC reactor, capability to decolorize a wide range of dye structures and tolerance to bacterial stress make D. squalens an organism applicable to remediation of textile wastewaters.
- MeSH
- barva MeSH
- barvicí látky izolace a purifikace metabolismus MeSH
- Basidiomycota metabolismus MeSH
- biodegradace MeSH
- bioreaktory mikrobiologie MeSH
- chemické látky znečišťující vodu izolace a purifikace metabolismus MeSH
- čištění vody metody MeSH
- naftalensulfonany izolace a purifikace metabolismus MeSH
- rotace MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- erytrocyty imunologie MeSH
- homologní transplantace MeSH
- imunosupresiva farmakologie MeSH
- lidé MeSH
- myši MeSH
- protilátky analýza MeSH
- radiační účinky MeSH
- sérový albumin hovězí MeSH
- transplantace kůže MeSH
- triaziny farmakologie MeSH
- tvorba protilátek účinky záření účinky záření MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
The ingestion of chromogenic or fluorescent substrates for protease detection enables the visualization of digestive processes in mites in vivo due to their transparent bodies. The substrates for protease detection were offered to Lepidoglyphus destructor, and the resulting signals were observed in specimens under a compound microscope. The protease activity was successfully localized using chromogenic substrates (azoalbumin, AAPpNA, SAAPFpNA, elastin-orcein, SA(3) pNA, ZRRpNA, ArgpNA, and MAAPMpNA) and fluorescent substrates (casein-fluorescein, albumin-fluorescein, AAPAMC, BAAMC, ZRRAMC, ArgAMC, and AGPPPAMC). No activity was detected using the keratin azure and BApNA substrates. In the mesodeum, trypsin-like activity generated by hydrolysis of the BApNA substrate was not observed, but the BAAMC substrate allowed the visualization of trypsin-like activity in food boli in the posterior mesodeum. The results indicate that cathepsins B, D, and G and cathepsin H or aminopeptidase-like activities are present in the midgut of L. destructor. Among these activities, cathepsin D-like activity was identified for the first time in the gut of L. destructor. All proteases mentioned are produced in the mesodeal lumen and form the food bolus together with ingested food, afterward passing through the gut to be defecated. The method used enables the visualization of protease activities in the gut of transparent animals.
