BACKGROUND: The introduction of novel hormonal therapies represented by enzalutamide (ENZ) and abiraterone acetate (ABI) has reached a great progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The majority of mCRPC patients are elderly suffering from chronic co-morbidities requiring use of various concomitant medications. In the present study, we focused on impact of concomitant antihypertensive medication on the outcomes of mCRPC patients treated with ENZ or ABI. METHODS: In total, 300 patients were included and their clinical data were retrospectively analyzed. RESULTS: Angiotensin-converting enzyme inhibitors (ACEIs) represented the only concomitant medication significantly associated with survival. The median radiographic progression-free survival (rPFS) and overall survival (OS) for patients using ACEIs were 15.5 and 32.3 months compared to 10.7 and 24.0 months for those not using ACEIs (p = 0.0053 and p = 0.0238, respectively). Cox multivariable analysis revealed the use of ACEIs a significant predictive factor for both rPFS (HR = 0.704, p = 0.0364) and OS (HR = 0.592, p = 0.0185). CONCLUSION: The findings of this study suggest an association between the concomitant use of ACEIs and longer survival of mCRPC patients receiving ENZ or ABI therapy.

• MeSH
• abirateron * terapeutické užití   aplikace a dávkování   MeSH
• antihypertenziva * terapeutické užití   MeSH
• benzamidy * terapeutické užití   MeSH
• doba přežití bez progrese choroby MeSH
• fenylthiohydantoin * terapeutické užití   MeSH
• inhibitory ACE terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci * farmakoterapie   mortalita   patologie   MeSH
• nitrily * terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   škodlivé účinky   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• dospělí MeSH
• hysterektomie MeSH
• lidé MeSH
• nefrotomie MeSH
• peritonitida * diagnóza   terapie   MeSH
• roboticky asistované výkony MeSH
• ureter * chirurgie   patologie   zranění   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• kongresy jako téma MeSH
• urologie MeSH

V polovině minulého roku vyšlo již 5. vydání klasifikace nádorů urogenitálního traktu Světové zdravotnické organizace (WHO), tzv. modrá kniha. Nová WHO klasifikace přináší především změny v rámci kapitoly renálních tumorů, pouze menší změny se pak dotkly ostatních kapitol. Právě nová klasifikace renálních tumorů odráží velmi dynamický vývoj na poli renálních neoplazií z posledních let, který je z části i odrazem čím dál tím častějšího využití molekulární genetiky při diagnostice renálních tumorů. Nová klasifikace renálních tumorů upravuje některé tradiční jednotky a vymezuje a zařazuje též některé nově vzniklé entity. Toto sdělení si klade za cíl v krátkosti a přehledně nastínit a okomentovat nejvýznamnější změny v rámci klasifikace renálních neoplazií.

The 5th edition WHO (World Health Organization) classification of the urogenital tract tumors was published in the middle of last year (so-called blue book). The new WHO classification reflects very dynamic developments in the field of renal neoplasms (caused mainly by the more frequent implementation of molecular genetic testing into the routine diagnosis of kidney tumors), and the new WHO classification shows changes especially in the chapter on renal tumors. The new kidney tumor classification modifies some traditional entities and also redefines and includes some new kidney tumors. This review article aims to briefly outline and comment on the most significant changes in the WHO classification of renal neoplasia.

• MeSH
• lidé MeSH
• nádory ledvin * klasifikace   MeSH
• Světová zdravotnická organizace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Long-acting injectable formulations represent a rapidly emerging category of drug delivery systems that offer several advantages compared to orally administered medicines. Rather than having to frequently swallow tablets, the medication is administered to the patient by intramuscular or subcutaneous injection of a nanoparticle suspension that forms a local depot from which the drug is steadily released over a period of several weeks or months. The benefits of this approach include improved medication compliance, reduced fluctuations of drug plasma level, or the suppression of gastrointestinal tract irritation. The mechanism of drug release from injectable depot systems is complex, and there is a lack of models that would enable quantitative parametrisation of the process. In this work, an experimental and computational study of drug release from a long-acting injectable depot system is reported. A population balance model of prodrug dissolution from asuspension with specific particle size distribution has been coupled with the kinetics of prodrug hydrolysis to its parent drug and validated using in vitro experimental data obtained from an accelerated reactive dissolution test. Using the developed model, it is possible to predict the sensitivity of drug release profiles to the initial concentration and particle size distribution of the prodrug suspension, and subsequently simulate various drug dosing scenarios. Parametric analysis of the system has identified the boundaries of reaction- and dissolution-limited drug release regimes, and the conditions for the existence of a quasi-steady state. This knowledge is crucial for the rational design of drug formulations in terms of particle size distribution, concentration and intended duration of drug release.

• MeSH
• antipsychotika * MeSH
• injekce intramuskulární MeSH
• léky s prodlouženým účinkem MeSH
• lidé MeSH
• prekurzory léčiv * MeSH
• rozpustnost MeSH
• suspenze MeSH
• uvolňování léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND/AIM: Enzalutamide (ENZ) and abiraterone acetate with prednisone (AAP) represent novel hormonal therapies used in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The aim of the study was to assess the long-term outcome of mCRPC patients treated with ENZ or AAP in real-life clinical practice. PATIENTS AND METHODS: The outcomes of 337 mCRPC patients treated with ENZ or AAP were retrospectively analysed. RESULTS: Median radiographic progression-free (rPFS) and overall survival (OS) of patients treated in the first line (pre-chemotherapy) was 13.89 (95% CI=12.40-16.80) and 31.02 (95% CI=24.27-37.44) months vs. 10.97 (95% CI=8.97-14.82) and 26.57 (95% CI=15.97-33.92) months for those treated in the second line (post-chemotherapy). We found inferior survival for patients with synchronous metastases, high Gleason score (GS) and visceral metastases. CONCLUSION: The efficacy of both ENZ and AAP in mCRPC patients is herein confirmed. Synchronous metastases, high GS and visceral metastases were identified as significant adverse prognostic factors.

• MeSH
• abirateron * terapeutické užití   MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci * patologie   MeSH
• nitrily MeSH
• prednison terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• karcinom klasifikace   MeSH
• lidé MeSH
• nádory ledvin * klasifikace   MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH

• MeSH
• kongresy jako téma MeSH
• urologie * MeSH
• Publikační typ
• zprávy MeSH

PURPOSE: Fluid-bed coating processes make it possible to manufacture pharmaceutical products with tuneable properties. The choice of polymer type and coating thickness provides control over the drug release characteristics, and multi-layer pellet coatings can combine several active ingredients or achieve tailored drug release profiles. However, the fluid-bed coating is a parametrically sensitive process due to the simultaneous occurrence of polymer solution spraying and solvent evaporation. Designing a robust fluid-bed coating process requires the knowledge of thin film drying kinetics, which in turn critically depends on an accurate description of concentration-dependent solvent diffusion in the polymer. METHODS: This work presents a mathematical model of thin film drying as an enabling tool for fluid-bed process design. A custom-built benchtop drying cell able to record and evaluate the drying kinetics of a chosen polymeric excipient has been constructed, validated, and used for data collection. RESULTS: A semi-empirical mathematical model combining heat transfer, mass transfer, and film thickness evolution was formulated and used for estimating the solvent diffusion coefficient and solvent distribution in the polymer layer. The combined experimental and computational methodology was then used for analysing the drying kinetics of common polymeric excipients: poly(vinylpyrrolidone) and two grades of hydroxypropyl methylcellulose. CONCLUSIONS: The experimental setup together with the mathematical model represents a valuable tool for predictive modeling of pharmaceutical coating processes.

• MeSH
• deriváty hypromelózy MeSH
• kinetika MeSH
• polymery * MeSH
• pomocné látky * MeSH
• rozpouštědla MeSH
• Publikační typ
• časopisecké články MeSH