Olaparib treatment significantly improved objective response rate (primary end point) and progression-free survival versus nonplatinum chemotherapy in patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer in the open-label phase III SOLO3 trial (ClinicalTrials.gov identifier: NCT02282020). We report final overall survival (OS; prespecified secondary end point), post hoc OS analysis by number of previous chemotherapy lines, and exploratory BRCA reversion mutation analysis. Two hundred sixty-six patients were randomly assigned 2:1 to olaparib tablets (300 mg twice daily; n = 178) or physician's choice of single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan; n = 88). OS was similar with olaparib versus chemotherapy (hazard ratio [HR], 1.07 [95% CI, 0.76 to 1.49]; P = .71, median 34.9 and 32.9 months, respectively, full analysis set). OS with olaparib was favorable in patients with two previous chemotherapy lines (HR, 0.83 [olaparib v chemotherapy] [95% CI, 0.51 to 1.38]; median 37.9 v 28.8 months); however, a potential detrimental effect was seen in patients with at least three previous chemotherapy lines (HR, 1.33 [95% CI, 0.84 to 2.18]; median 29.9 v 39.4 months). BRCA reversion mutations might have contributed to this finding. No patient randomly assigned to olaparib with a BRCA reversion mutation detected at baseline (6 of 170 [3.5%]) achieved an objective tumor response.

• MeSH
• deoxycytidin analogy a deriváty   aplikace a dávkování   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• doxorubicin analogy a deriváty   aplikace a dávkování   MeSH
• ftalaziny * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• gemcitabin MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * farmakoterapie   MeSH
• nádory vaječníků * farmakoterapie   genetika   mortalita   patologie   MeSH
• paclitaxel aplikace a dávkování   MeSH
• PARP inhibitory * terapeutické užití   škodlivé účinky   MeSH
• piperaziny * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• polyethylenglykoly aplikace a dávkování   MeSH
• protein BRCA1 genetika   MeSH
• protein BRCA2 genetika   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• senioři MeSH
• topotekan aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m2/year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.

• MeSH
• alfa-galaktosidasa * aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• enzymová substituční terapie * metody   MeSH
• Fabryho nemoc * farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• polyethylenglykoly aplikace a dávkování   MeSH
• rekombinantní proteiny * aplikace a dávkování   terapeutické užití   MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• sfingolipidy krev   MeSH
• trihexosylceramidy krev   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

Spondyloartritidy jsou heterogenní skupina chronických zánětlivých onemocnění s pestrou škálou projevů, z nichž dominuje postižení axiálního skeletu, periferních kloubů, entezitida a daktylitida, časté jsou též projevy extraskeletální. Lze je dělit podle dominantního postižení na axiální či periferní spondyloartritidy, axiální pak dále podle radiograficky prokazatelných strukturálních změn na sakroiliakálních skloubeních na radiografickou a nonradiografickou formu. Základem léčby nadále zůstávají nesteroidní antirevmatika, významný pokrok však nastal zejména se zavedením biologické léčby, kterou je v současnosti dle mezinárodních doporučení možno nasadit již v druhé linii léčby. Jednou ze základních skupin biologických léčiv jsou inhibitory tumor nekrotizujícího faktoru a, jejichž zástupcem je i certolizumab pegol, humanizovaná monoklonální protilátka, která na rozdíl od ostatních zástupců této skupiny obsahuje pouze Fab fragment molekuly s dvěma navázanými molekulami polyethylenglykolu. Tato struktura minimalizuje transplacentární přestup, a proto je certolizumab pegol s výhodou užíván po celou dobu těhotenství u těhotných pacientek s revmatickým onemocněním. V následujícím textu demonstrujeme účinnost i bezpečnost užití certolizumab pegolu u dvou těhotných pacientek s axiální spondyloartritidou.

Spondyloarthritis is a heterogeneous group of chronic inflammatory diseases with various symptoms that mainly include the damage of axial skeleton, peripheral joints, enthesitis and dactylitis. Extraskeletal manifestations are often as well. Spondyloarthritis can be divided into two groups, axial and peripheral, depending on the dominant involvement. Axial type can be further divided into radiographic and non-radiographic type based on the radiographic evidence of structural damage of sacroiliac joints. Nonsteroidal anti-inflammatory drugs still remain the drug of the first choice, but it was the introduction of biological therapy that led to a significant treatment progress. According to the most recent international recommendations, biological therapy is approved as a second-line treatment of the disease. Tumor necrosis factor a inhibitors are one of the main groups of biologics that include certolizumab pegol, a humanized monoclonal antibody that consists of a single Fab fragment with no Fc portion compared to the other group agents. The Fab fragment is conjugated with two molecules of polyethylene glycol which minimizes the placental transfer. Therefore, certolizumab pegol is successfully used throughout pregnancy in pregnant women with rheumatic diseases. The following text demonstrates both the efficacy and safety of use of certolizumab pegol in two pregnant patients treating for axial spondyloarthritis.

Many photosensitive substances suitable for photodynamic therapy (PDT) have limited applications due to their insufficient solubility in polar solvents. Our research overcomes this challenge by means of nanotechnology in order to transform hydrophobic compounds into stable aqueous solutions, enabling them to use their full potential and unique properties in cancer therapy. In this study, the novel nano-composite cGQDs-PEG-curcumin was developed to overcome the insolubility of curcumin in water and its extraordinary efficacy in PDT was evaluated. Complex characterization was performed using high-resolution transmission electron microscopy (HR-TEM), FTIR, and UV-Vis spectroscopy. Further analysis involved fluorescence lifetime imaging (FLIM), and its cellular localization was mapped with confocal microscopy. In order to evaluate PDT effectiveness, cells treated with cGQDs-PEG-curcumin were irradiated with 5 J/cm2 of 414 nm light. After irradiation, cell viability assay, scanning electron microscopy (SEM), reactive oxygen species (ROS) detection, comet assay, and γH2AX-based DNA double-strand breaks (DSBs) detection were assessed and revealed a remarkable ability of the nano-composite to induce DNA damage after irradiation without ROS production. Our findings highlight the potential of cGQDs-PEG-curcumin as a cutting-edge PDT agent, capable of disrupting cell membrane and nucleolar integrity and impairing ribosomal synthesis, which is crucial for proliferating tumour cells.

• MeSH
• buněčné jadérko * účinky léků   metabolismus   MeSH
• dvouřetězcové zlomy DNA účinky léků   MeSH
• fotochemoterapie * metody   MeSH
• fotosenzibilizující látky * farmakologie   MeSH
• grafit * chemie   farmakologie   MeSH
• kurkumin * farmakologie   chemie   MeSH
• kvantové tečky * chemie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory * farmakoterapie   MeSH
• polyethylenglykoly * chemie   farmakologie   MeSH
• poškození DNA * účinky léků   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Exclusion of serum macroform presence is essential to avoid potential misdiagnosis. The aim of this study was to determine critical limits (CL) for enzymes (total and pancreatic amylase, AMY and pAMY; aminotransferases, AST and ALT; alkaline phosphatase, ALP; creatine kinase, CK; lipase, LIP; gamma-glutamyl transferase, GGT; lactate dehydrogenase, LDH) after polyethylene glycol (PEG) precipitation in children and adults. METHODS: A total of 126 sera of patients suspected for macroenzyme presence (adults or children) was matched by serum enzyme activity of controls and all these sera were precipitated by PEG. PEG-precipitable activity ( %PPA) and CLs of %PPA were calculated for adults, children, and controls. RESULTS: CLs of %PPA were substantially lower than common 60 % for ALP and CK in all subjects. Significant differences between adults and children were found for ALT and ALP (lower in children), and LIP and CK (higher in children). No meaningful correlation was found between initial enzyme activity and %PPA. CONCLUSIONS: Age specific CLs should be used for ALP, ALT, CK, and LIP. Generally accepted value of %PPA of 60 % may be used with caution for AMY, pAMY, AST, GGT, and LDH. A careful selection of CLs is needed for timely detection of macrocomplexes.

• MeSH
• chemická precipitace MeSH
• dítě MeSH
• dospělí MeSH
• enzymy * krev   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• polyethylenglykoly * chemie   MeSH
• předškolní dítě MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Celotělovápostmortem CTangiografie(PMCTA) představujevcelosvětovémměřítkuexperimentálnímetoduzávisloupředevšímnadostupnostiinterdisciplinární spolupráce, personálním a technickém vybavení a finančních možnostech pracoviště. Autoři prezentují technické poznámky k etablovaní PMCTA na pracovišti, které od roku 2015 rutinně provádělo nativní CT vyšetření. Aplikaci této diagnosticky i vědecko-výzkumně výtěžné metody do soudnělékařské praxe umožnila mezioborová spolupráce společně s institucionální podporou rozvoje nových diagnostických metod.

Whole-body post mortem CT angiography (PMCTA) is an innovative and experimental imaging technique that relies heavily on interdisciplinary collaboration, access to skilled personnel, advanced technical equipment and the financial possibilities of the workplace. Native CT examinations (PMCT) prior to autopsy are already a standard procedure in certain forensic departments in the Czech Republic (e.g., murders, suicides, deaths of children, traffic accidents etc.). Nonetheless, the progression of forensic sciences all over the world shows the necessity to integrate other advanced imaging modalities in routine forensic practice. Incorporating PMCTA into standard forensic workflows enhances the precision of forensic diagnostics, supplements traditional autopsy findings, and elevates the objectivity of forensic outputs. This paper presents technical notes on the development of PMCTA in forensic practice in a department that since 2015 until now has routinely performed native CT examinations. Institutional support was crucial in enabling the adoption of the imaging technique, which has so far been applied to more than thirty cases. The department is currently conducting a comparative study focused on the application of three different types of perfusion media – polyethylene glycol (PEG), saline, paraffin oil – and assessing the diagnostic efficacy of PMCTA relative to conventional autopsy. Based on our experience, PMCTA is suitable for all corpses except those with advanced post-mortem decomposition or extensive open injuries. The highest diagnostic yield is achieved in cases involving suspected gastrointestinal bleeding or vascular pathologies and lesions especially of large vessels (e.g., dissection/rupture of the aorta). The protocol for whole-body PMCTA can be adapted to meet the specific needs and conditions of individual forensic departments, providing a flexible yet robust framework for enhancing forensic medical investigations.

• MeSH
• CT angiografie metody   MeSH
• diagnostické zobrazování metody   MeSH
• lidé MeSH
• pitva * metody   MeSH
• počítačová rentgenová tomografie * metody   MeSH
• soudní lékařství metody   trendy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Pegylované růstové faktory granulopoézy, lipegfilgrastim a pegfilgrastim, mají zásadní roli ve snížení rizika febrilní neutropenie a těžké neutropenie po chemoterapii, a pomáhají tak udržet i její dávkovou intenzitu. Lipegfilgrastim, zavedený od roku 2014, zůstává doposud dostupný v originální molekule a bez biosimilárního ekvivalentu. Data observačních studií i z reálné praxe dokládají jeho účinnost a bezpečnost.

Pegylated granulocyte colony-stimulating factors, lipegfilgrastim and pegfilgrastim, play a crucial role in reducing the risk of febrile neutropenia and severe neutropenia after chemotherapy, and thus help maintain its dose intensity. Lipegfilgrastim, introduced in 2014, remains available as the original molecule and without its biosimilar equivalent. Data from observational studies and from real practice demonstrate its effectiveness and safety.

• Klíčová slova
• lipegfilgrastim,
• MeSH
• filgrastim farmakologie   terapeutické užití   MeSH
• lidé MeSH
• neutropenie * chemicky indukované   farmakoterapie   MeSH
• polyethylenglykoly farmakologie   terapeutické užití   MeSH
• pozorovací studie jako téma MeSH
• Check Tag
• lidé MeSH

The utilization of 3D printing- digital light processing (DLP) technique, for the direct fabrication of microneedles encounters the problem of drug solubility in printing resin, especially if it is predominantly composed of water. The possible solution how to ensure ideal belonging of drug and water-based printing resin is its pre-formulation in nanosuspension such as nanocrystals. This study investigates the feasibility of this approach on a resin containing nanocrystals of imiquimod (IMQ), an active used in (pre)cancerous skin conditions, well known for its problematic solubility and bioavailability. The resin blend of polyethylene glycol diacrylate and N-vinylpyrrolidone, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photoinitiator, was used, mixed with IMQ nanocrystals in water. The final microneedle-patches had 36 cylindrical microneedles arranged in a square grid, measuring approximately 600 μm in height and 500 μm in diameter. They contained 5wt% IMQ, which is equivalent to a commercially available cream. The homogeneity of IMQ distribution in the matrix was higher for nanocrystals compared to usual crystalline form. The release of IMQ from the patches was determined ex vivo in natural skin and revealed a 48% increase in efficacy for nanocrystal formulations compared to the crystalline form of IMQ.

• MeSH
• 3D tisk * MeSH
• aplikace kožní MeSH
• imichimod * chemie   aplikace a dávkování   MeSH
• jehly * MeSH
• kožní absorpce MeSH
• kůže metabolismus   MeSH
• lékové transportní systémy přístrojové vybavení   MeSH
• mikroinjekce přístrojové vybavení   MeSH
• nanočástice * chemie   aplikace a dávkování   MeSH
• polyethylenglykoly chemie   aplikace a dávkování   MeSH
• povidon chemie   MeSH
• rozpustnost * MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Skin represents the largest organ in the human body, functioning as a protective barrier against environmental factors while playing a critical role in thermoregulation. Acne vulgaris is recognized as the most common dermatological condition affecting adolescents, and if left untreated, it can result in lasting skin damage and associated psychosocial challenges. This study aims to develop innovative polymeric biomaterials that could effectively support the treatment of acne vulgaris. The synthesis of these biomaterials involves the use of polyethylene glycol 6000, sodium alginate, and the antioxidant protein glutathione (GHS) to create polymeric hydrogels. These hydrogels were generated via a UV-mediated crosslinking process. To enhance the functional properties of the hydrogels, zinc oxide microparticles (ZnO), synthesized through a wet precipitation method, were incorporated into the formulations. Characterization of the ZnO was performed using Fourier-Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), particle sizer analysis, and Scanning Electron Microscopy (SEM). Additionally, the bioactivity of the synthesized materials was evaluated through incubation in media simulating physiological body fluids. The cytotoxic effects of the biomaterials were assessed using an indirect test on mouse fibroblast (L929) cells, in accordance with ISO 10993-5 guidelines. The results of our research indicate that the developed biomaterials exhibit potential as a carrier for active substances, contributing positively to the treatment of acne vulgaris and potentially improving overall skin health.

• MeSH
• acne vulgaris farmakoterapie   MeSH
• algináty chemie   MeSH
• biokompatibilní materiály chemie   farmakologie   MeSH
• buněčné linie MeSH
• fibroblasty účinky léků   metabolismus   MeSH
• glutathion * metabolismus   MeSH
• hydrogely * chemie   MeSH
• kůže * účinky léků   metabolismus   MeSH
• lidé MeSH
• myši MeSH
• nosiče léků chemie   MeSH
• oxid zinečnatý * chemie   farmakologie   MeSH
• regenerace účinky léků   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Systematic review and meta-analysis on laboratory studies aimed to answer whether there is a difference in fracture resistance and fracture mode of structurally compromised teeth restored with direct composite restorations reinforced with short glass-fiber or bidirectional polyethylene fiber substructure, and between the two different fiber-reinforcement types. METHODS: An electronic literature search was conducted in Medline, Scopus, Web of Science, Lilacs, Google Scholar, Cochrane Library, and University Library databases. The last search was conducted on 16 November 2023. Only studies looking at Ribbond-reinforced restorations and/ or the use of EverX Posterior within restorations were included. Data were categorized and analyzed based on specific outcome measures including fracture resistance and fracture mode. Data from individual studies were divided into premolars and molars for each material category and then collated to compare the mean differences in fracture resistance between control groups (composite restorations) and intervention groups (fiber-reinforced composite restorations). RESULTS: From the initial 1266 articles identified, 23 laboratory-based studies were included for quantitative analysis. Twenty articles had an overall low risk of bias and 3 had an overall unclear risk of bias. The pooled estimate of the effect favored the intervention groups as having statistically significant higher fracture resistance when compared to control groups. CONCLUSIONS: Both fiber types improve fracture resistance and the fracture mode of structurally compromised teeth is equally efficient. Application technique deserves attention. Ribbond could be placed in a single layer at the cavity floor, whereas EverX Posterior should replace missing dentin in an anatomically shaped way.

• MeSH
• fraktury zubů * prevence a kontrola   MeSH
• lidé MeSH
• polyethyleny MeSH
• sklo chemie   MeSH
• složené pryskyřice * terapeutické užití   chemie   MeSH
• trvalá zubní náhrada * metody   MeSH
• zubní materiály chemie   MeSH
• zuby-sanace - selhání MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• systematický přehled MeSH