Cílem práce je na ojedinělém případu pacienta po nadstandardní operaci šedého zákalu s preventivní primární zadní cirkulární kasulorexi (PCCC, z angl. posterior continuous curvilinear capsulorhexis) prezentovat možný vznik proliferativní sekundární katarakty. Vzhledem k negativnímu vlivu na zrakové funkce bylo rozhodnuto o ošetření Nd:YAG laserem, které bylo úspěšné s použitím minimální energie ale s porušením přední hyaloidní membrány. Kazuistika 65letý muž podstoupil na našem pracovišti v roce 2020 nekomplikovanou operaci šedého zákalu obou očí, oboustranně s primární PCCC s implantací tenzního kroužku a umělé nitrooční čočky do pouzdra. V únoru 2023 byl na doporučení spádového očního lékaře vyšetřen na naší ambulanci pro snížení zrakové ostrosti vpravo. Dominantní bylo rozmazané vidění. Diagnóza proliferativní formy sekundární katarakty byla potvrzena a zdokumentována pomocí fotografie předního segmentu v retroiluminaci a předněsegmentového OCT (Optovue, Avanti RTVue XR). Pacient byl indikován k Nd:YAG laserové disrupci proliferací v prostoru PCCC na pravém oku. Návrat zrakové ostrosti k původnímu stavu byl potvrzením správné diagnózy. V literárním přehledu a v diskuzi je shrnuta aktuální problematika sekundární katarakty a použití primární PCCC. Závěr: Sekundární katarakta je hlavní dlouhodobou komplikací moderní chirurgie katarakty. Jednou z možných řešení je preventivní provedení jednoduché PCCC, která může být provázená ojedinělým selháním.

The aim of the study is to present the possible development of proliferative secondary cataracts in the unique case of a patient having undergone premium cataract surgery with preventive primary posterior continuous curvilinear capsulorhexis (PCCC). Due to the negative effect on visual functions, it was decided to treat the patient with an Nd:YAG laser, which was successful with minimal energy but resulted in damage to the anterior hyaloid membrane. Case report In 2020, a 65-year-old man underwent uncomplicated cataract surgery in both eyes at our clinic bilaterally with primary PCCC with implantation of a tension ring and an artificial intraocular lens into the capsule. In February 2023, on the recommendation of the area ophthalmologist, he was examined at our outpatient clinic due to a decrease of visual acuity in the right eye. Blurred vision predominated. A diagnosis of proliferative form of secondary cataract was confirmed and documented using a photo of the anterior segment in retroillumination and anterior segment OCT (Optovue, Avanti RTVue XR). The patient was indicated for Nd:YAG laser disruption by proliferation in the PCCC space in the right eye. The return of visual acuity to its original state confirmed the correct diagnosis. The literature review and discussion summarize the current issue of secondary cataracts and the use of primary PCCC. Conclusion: Secondary cataract is the main long-term complication of modern cataract surgery. One of the possible solutions is the preventive implementation of a simple PCCC, which may be accompanied by isolated failure.

• MeSH
• Capsulorhexis * methods   adverse effects   MeSH
• Cataract Extraction methods   adverse effects   MeSH
• Lens Implantation, Intraocular MeSH
• Cataract etiology   MeSH
• Lasers, Solid-State therapeutic use   MeSH
• Humans MeSH
• Aged MeSH
• Capsule Opacification diagnosis   etiology   MeSH
• Visual Acuity MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH

INTRODUCTION: The immunosuppressive roles of galectin-3 (Gal-3) in carcinogenesis make this lectin an attractive target for pharmacological inhibition in immunotherapy. Although current clinical immunotherapies appear promising in the treatment of solid tumors, their efficacy is significantly weakened by the hostile immunosuppressive tumor microenvironment (TME). Gal-3, a prominent TME modulator, efficiently subverts the elimination of cancer, either directly by inducing apoptosis of immune cells or indirectly by binding essential effector molecules, such as interferon-gamma (IFNγ). METHODS: N-(2-Hydroxypropyl)methacrylamide (HPMA)-based glycopolymers bearing poly-N-acetyllactosamine-derived tetrasaccharide ligands of Gal-3 were designed, synthesized, and characterized using high-performance liquid chromatography, dynamic light scattering, UV-Vis spectrophotometry, gel permeation chromatography, nuclear magnetic resonance, high-resolution mass spectrometry and CCK-8 assay for evaluation of glycopolymer non-toxicity. Pro-immunogenic effects of purified glycopolymers were tested by apoptotic assay using flow cytometry, competitive ELISA, and in vitro cell-free INFγ-based assay. RESULTS: All tested glycopolymers completely inhibited Gal-3-induced apoptosis of monocytes/macrophages, of which the M1 subtype is responsible for eliminating cancer cells during immunotherapy. Moreover, the glycopolymers suppressed Gal-3-induced capture of glycosylated IFNγ by competitive inhibition to Gal-3 carbohydrate recognition domain (CRD), which enables further inherent biological activities of this effector, such as differentiation of monocytes into M1 macrophages and repolarization of M2-macrophages to the M1 state. CONCLUSION: The prepared glycopolymers are promising inhibitors of Gal-3 and may serve as important supportive anti-cancer nanosystems enabling the infiltration of proinflammatory macrophages and the reprogramming of unwanted M2 macrophages into the M1 subtype.

• MeSH
• Acrylamides chemistry   pharmacology   MeSH
• Apoptosis drug effects   MeSH
• Galectin 3 * antagonists & inhibitors   MeSH
• Galectins MeSH
• Interferon-gamma * metabolism   MeSH
• Blood Proteins MeSH
• Humans MeSH
• Macrophages drug effects   MeSH
• Monocytes * drug effects   MeSH
• Tumor Microenvironment drug effects   MeSH
• Polymers * chemistry   pharmacology   MeSH
• Antineoplastic Agents * pharmacology   chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

In electrospun scaffolds, coaxial electrospinning is gaining increased attention due to its potential for biocomponent encapsulation and controlled delivery. However, the encapsulation of biocomponents, such as liposomes, remains challenging because of their low stability in commonly used electrospinning solvents. This study, therefore, aims to develop a novel coaxial electrospinning formulation for crafting a liposome-encapsulated, rapid-release coaxial fiber. Liposomes demonstrated desirable stability in fish gelatin/phosphate-buffered saline (PBS) solutions, which remain liquid at room temperature and exhibit exceptional spinnability at concentrations exceeding 80 w/v% due to the reduction in surface tension. Fluorescent labelling examinations confirmed the successful encapsulation of liposomes within coaxial fibers electrospun from a 160 w/v% gelatin/PBS core and a 20 w/v% PCL/chloroform/N,N-dimethylformamide (DMF) shell. The gelatin/PBS core solution formed solid ends at the tips of the core-shell fiber post-spinning, while maintaining a liquid state within the shell, thereby enabling the encapsulation of liposomes within the PCL coaxial fiber. Upon exposure to medium, the solid ends dissolve, enabling the rapid release of liposomes. The successful development of this liposome-loaded electrospun coaxial fiber, using fish gelatin, highlights its potential for creating advanced liposome delivery systems.

• Publication type
• Journal Article MeSH

BACKGROUND AND PURPOSE: CNS embryonal tumor with pleomorphic adenoma gene-like 1 (PLAGL1)/pleomorphic adenoma gene-like 2 (PLAGL2) amplification (ET, PLAGL) is a newly identified, highly malignant pediatric tumor. Systematic MRI descriptions of ET, PLAGL are currently lacking. MATERIALS AND METHODS: MRI data from 19 treatment-naïve patients with confirmed ET, PLAGL were analyzed. Evaluation focused on anatomic involvement, tumor localization, MRI signal characteristics, DWI behavior, and the presence of necrosis and hemorrhage. Descriptive statistics (median, interquartile range, percentage) were assessed. RESULTS: Ten patients had PLAGL1 and nine had PLAGL2 amplifications. The solid components of the tumors were often multinodular with heterogeneous enhancement (mild to intermediate in 47% and intermediate to strong in 47% of cases). Nonsolid components included cysts in 47% and necrosis in 84% of the cases. The tumors showed heterogeneous T2WI hyper- and isointensity (74%), relatively little diffusion restriction (ADC values less than contralateral normal-appearing WM in 36% of cases with available DWI), and tendencies toward hemorrhage/calcification (42%). No reliable distinction was found between PLAGL1- and PLAGL2-amplified tumors or compared with other embryonal CNS tumors. CONCLUSIONS: The study contributes to understanding the imaging characteristics of ET, PLAGL. It underscores the need for collaboration in studying rare pediatric tumors and advocates the use of harmonized imaging protocols for better characterization.

• MeSH
• Gene Amplification MeSH
• Child MeSH
• DNA-Binding Proteins genetics   MeSH
• Neoplasms, Germ Cell and Embryonal diagnostic imaging   pathology   MeSH
• Infant MeSH
• Humans MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Adolescent MeSH
• Tumor Suppressor Proteins MeSH
• Central Nervous System Neoplasms diagnostic imaging   pathology   MeSH
• Brain Neoplasms diagnostic imaging   pathology   MeSH
• Child, Preschool MeSH
• Cell Cycle Proteins MeSH
• RNA-Binding Proteins MeSH
• Transcription Factors genetics   MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Health-related quality of life (HRQoL) is an important patient-reported outcome for all cancer patients, including adult patients with rare solid cancers. However, current knowledge of HRQoL in this population is limited, which hinders the delivery of personalized care. This review aimed to explore the heterogeneity of HRQoL among adult patients with a solid rare cancer across the ten European Reference Network for Rare Adult Solid Cancers (EURACAN) domains and to summarize the HRQoL measures used in clinical research. METHODS: A systematic literature search was conducted to identify all clinical studies assessing HRQoL in adult patients with a solid rare cancer. Four databases (MEDLINE, PubMed, PsycINFO, and Web of Science/Scopus) were searched (February 2023). RESULTS: The search yielded 18,704 articles, of which 1416 articles were fully screened and 463 were eligible for analysis. Of these, 397 studies used generic tools to assess HRQoL, while 270 used tumor-specific instruments. Three EURACAN domains (sarcoma, endocrine tumors, and thoracic tumors) primarily assessed HRQoL using generic questionnaires. Additionally, the rare gynecological tumor, rare male genitourinary, and sarcoma EURACAN domains lacked specific HRQoL measures. Brain, head and neck, and uveal melanoma EURACAN domains used tumor- or domain-specific questionnaires in more than half of the studies. CONCLUSIONS: This state-of-the-art literature review shows that HRQoL assessment is gradually becoming more prevalent in adult solid rare cancer research. A combination of generic, tumor-specific, and domain-specific questionnaires across various rare cancer domains has proven effective in capturing a broad range of HRQoL issues. However, many EURACAN domains still lack specific strategies for assessing HRQoL, which limits the ability to fully understand and address patients' experiences. Future research should prioritize developing comprehensive and robust HRQoL measurement strategies and tools to enable meaningful clinical research and to ensure that the patient voice is incorporated in their clinical care.

• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: The European Core Health Indicators (ECHI) are a set of 88 indicators that provide a compact overview of the extensive field of European public health and healthcare. The ECHI set adds value to European Union health information systems (HIS) for both Member States and EU-associated countries and the European Commission by providing a solid, comparable information base on national public health and healthcare trends and developments. The indicators allow for learning by comparison and the list supports the organisation of national health information systems. As the ECHI set was defined more than ten years ago, it is time to review its current needs and readiness for the future. METHODS: In this article, we reflect on the sustainability of the ECHI set and explore directions for improving future use, based on the activities in the Joint Action on Health Information (2018 - 2021). There, we looked into ECHI governance and reviewed the set's metadata, content and link with other indicator sets in the wider European health information landscape. CONCLUSIONS: We conclude that in order to remain relevant and keep up with technical and policy developments, the ECHI set needs maintenance and updates. This cannot be achieved in a non-systematic project-based manner; it requires sustainable funding, governance and formalised activities in a permanent structure. We call on the European Commission, Member States, research networks and individual users of the ECHI to take action in this.

• Publication type
• Journal Article MeSH

Changes in the protonation state of lyophilized proteins can impact structural integrity, chemical stability, and propensity to aggregate upon reconstitution. When a buffer is chosen, the freezing/drying process may result in dramatic changes in the protonation state of the protein due to ionization shift of the buffer. In order to determine whether protonation shifts are occurring, ionizable probes can be added to the formulation. Optical probes (dyes) have shown dramatic ionization changes in lyophilized products, but it is unclear whether the pH indicator is uniform throughout the matrix and whether the change in the pH indicator actually mirrors drug ionization changes. In solid-state NMR (SSNMR) spectroscopy, the chemical shift of the carbonyl carbon in carboxylic acids is very sensitive to the ionization state of the acid. Therefore, SSNMR can be used to measure ionization changes in a lyophilized matrix by employing a small quantity of an isotopically-labeled carboxylic acid species in the formulation. This paper compares the apparent pH of six trehalose-containing lyophilized buffer systems using SSNMR and UV-Vis diffuse reflectance spectroscopy (UVDRS). Both SSNMR and UVDRS results using two different ionization probes (butyric acid and bromocresol purple, respectively) showed little change in apparent acidity compared to the pre-lyophilized solution in a sodium citrate buffer, but a greater change was observed in potassium phosphate, sodium phosphate, and histidine buffers. While the trends between the two methods were similar, there were differences in the numerical values of equivalent pH (pHeq) observed between the two methods. The potential causes contributing to the differences are discussed.

• MeSH
• Phosphates * chemistry   MeSH
• Histidine * chemistry   MeSH
• Hydrogen-Ion Concentration MeSH
• Citric Acid chemistry   MeSH
• Freeze Drying * methods   MeSH
• Magnetic Resonance Spectroscopy * methods   MeSH
• Buffers MeSH
• Spectrophotometry, Ultraviolet methods   MeSH
• Trehalose * chemistry   MeSH
• Publication type
• Journal Article MeSH

BACKGROUND AND PURPOSE: To develop and test a decision tree for predicting contrast enhancement quality and shape using precontrast magnetic resonance imaging (MRI) sequences in a large adult-type diffuse glioma cohort. METHODS: Preoperative MRI scans (development/optimization/test sets: n = 31/38/303, male = 17/22/189, mean age = 52/59/56.7 years, high-grade glioma = 22/33/249) were retrospectively evaluated, including pre- and postcontrast T1-weighted, T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted imaging sequences. Enhancement prediction decision tree (EPDT) was developed using development and optimization sets, incorporating four imaging features: necrosis, diffusion restriction, T2 inhomogeneity, and nonenhancing tumor margins. EPDT accuracy was assessed on a test set by three raters of variable experience. True enhancement features (gold standard) were evaluated using pre- and postcontrast T1-weighted images. Statistical analysis used confusion matrices, Cohen's/Fleiss' kappa, and Kendall's W. Significance threshold was p < .05. RESULTS: Raters 1, 2, and 3 achieved overall accuracies of .86 (95% confidence interval [CI]: .81-.90), .89 (95% CI: .85-.92), and .92 (95% CI: .89-.95), respectively, in predicting enhancement quality (marked, mild, or no enhancement). Regarding shape, defined as the thickness of enhancing margin (solid, rim, or no enhancement), accuracies were .84 (95% CI: .79-.88), .88 (95% CI: .84-.92), and .89 (95% CI: .85-.92). Intrarater intergroup agreement comparing predicted and true enhancement features consistently reached substantial levels (≥.68 [95% CI: .61-.75]). Interrater comparison showed at least moderate agreement (group: ≥.42 [95% CI: .36-.48], pairwise: ≥.61 [95% CI: .50-.72]). Among the imaging features in the EPDT, necrosis assessment displayed the highest intra- and interrater consistency (≥.80 [95% CI: .73-.88]). CONCLUSION: The proposed EPDT has high accuracy in predicting enhancement patterns of gliomas irrespective of rater experience.

• MeSH
• Adult MeSH
• Gadolinium MeSH
• Glioma * diagnostic imaging   pathology   MeSH
• Contrast Media * MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Brain Neoplasms * diagnostic imaging   pathology   MeSH
• Reproducibility of Results MeSH
• Retrospective Studies MeSH
• Decision Trees MeSH
• Aged MeSH
• Sensitivity and Specificity MeSH
• Image Enhancement methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

T lymfocyty s chimerickým antigenním receptorem (CAR) představují nejmodernější technologii v cílené buněčné terapii onkologických onemocnění. Slibné klinické výsledky byly publikovány v léčbě hemato-onkologických malignit, avšak výsledky v léčbě solidních nádorů nejsou zatím tak povzbudivé. V navrhovaném projektu se budeme věnovat validaci protokolů pro výrobu CAR T-lymfocytů proti solidním nádorům v režimu správné laboratorní praxe. Zaměříme se hlavně na cílové antigeny GD2, PSMA a PSCA. Standardní operační protokoly a analytické certifikáty budou předány Státnímu ústavu pro kontrolu léčiv ke schválení. Na projektu budou spolupracovat tři špičková výzkumná pracoviště: (i) Mezinárodní centrum klinického výzkumu Fakultní nemocnice u sv. Anny v Brně, (ii) Centrum analýzy biomedicínského obrazu na Masarykově Univerzitě v Brně (MU-CBIA) a (iii) Ústav hematologie a krevní transfuze v Praze (ÚHKT). Naším hlavním cílem je zavést technologii výroby CAR T-lymfocytů pro cílenou buněčnou terapii solidních tumorů a tím umožnit přenos do klinické praxe.; Chimeric antigen receptor (CAR) T-cell is a cutting edge technology for targeted cell therapy of oncologic diseases. Promising clinical results were reported for hematological malignancies, but the results in solid tumors are not that encouranging yet. Here we propose to validate protocols for the production of CAR T-cells against solid tumor antigens under cGMP rules. We will focus mainly on target antigens GD2, PSMA, and PSCA. Standard operation protocols and analytical certificates will be presented to the State Institute for Drug Control for their approval. The consortium of three prominent research facilities will participate on this project: (i) International Clinical Research Center of St. Anne's University Hospital Brno (FNUSA-ICRC), (ii) Centre for Biomedical Image Analysis at Masaryk University Brno (MU-CBIA), and (iii) Institute of Hematology and Blood Transfusion in Prague (UHKT). Our main aim is to establish production of CAR T-cells for anti-solid tumor therapy which can be translated into clinical applications.

• Keywords
• advanced therapy medicinal products, solid tumors, T-lymfocyty, T-cells, solidní tumory, Chimerický antigenní receptor, Správná laboratorní praxe, Přípravky moderní terapie, Chimeric antigen receptor, Current Good Manufacturing Practice,

• NML Publication type
• závěrečné zprávy o řešení grantu AZV MZ ČR

Peritoneal carcinomatosis represents an advanced stage of tumors within the peritoneal cavity. Once considered an incurable terminal cancer metastasis, contemporary medicine is on the hunt for certain potentially curative options alongside the present day's palliative disease management. However, for most patients, peritoneal carcinomatosis continues to pose a fatal late-stage prognosis with a grim future outlook. Over the past two decades, non-coding RNAs have garnered significant attention due to their undeniable significance in regulating cellular processes across all levels. Disruption of the intricate regulation led by non-coding RNAs has been demonstrated to have a substantial impact on various human diseases, particularly in cancer, including solid tumors originating from the organs of the peritoneal cavity. This review aims to offer a comprehensive overview of the current state of knowledge in the under-researched field of peritoneal carcinomatosis, focusing specifically on the role of non-coding RNAs in the development of this condition and delineating potential avenues for future research.

• Publication type
• Journal Article MeSH
• Review MeSH