The study aimed to assess prognostic significance of del(13q14), del(17p13), t(4;14)(p16;q32), and amp(1q21) in newly diagnosed myeloma patients treated mostly with thalidomide-based therapies. All genetic abnormalities except del(13q14) were independent prognostic factors associated with shortened progression-free survival (PFS) and overall survival (OS). Patients with no abnormalities, one abnormality, and ≥2 abnormalities had a median PFS of 41.8, 17.0, and 10.0 months, respectively; a median OS was not reached, 48.0 and 23.3 months, respectively. According to the presence of amp(1q21), t(4;14)(p16;q32), and del(17p13) and the International Staging System (ISS), we stratified patients into low-risk, intermediate-risk and high-risk groups. A median PFS was 52.9, 25.6, and 10.0 months, respectively; a median OS was not reached, 64.0 and 25.0 months, respectively. In conclusion, our study confirmed the prognostic value of cytogenetic changes and showed that prognostic models based on ISS and cytogenetic studies should include not only del(17p13) and t(4;14)(p16;q32), but also amp(1q21).

• MeSH
• analýza přežití MeSH
• chromozomální delece * MeSH
• duplikace chromozomů * MeSH
• hybridizace in situ fluorescenční MeSH
• incidence MeSH
• lidé MeSH
• lidské chromozomy, pár 1 MeSH
• lidské chromozomy, pár 14 MeSH
• lidské chromozomy, pár 17 MeSH
• lidské chromozomy, pár 4 MeSH
• mnohočetný myelom epidemiologie   genetika   mortalita   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• translokace genetická * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Polsko epidemiologie   MeSH

BACKGROUND: Biologics have greatly improved psoriasis management. However, primary and secondary non-response to treatment requires innovative strategies to optimize outcomes. OBJECTIVE: To describe the use of combined treatment of biologics with conventional systemic agents or phototherapy in daily clinical practice. METHODS: We collected data on frequency of use, demographics, treatment characteristics and drug survival of biologics combined with conventional systemic agents or phototherapy in five PSONET registries. RESULTS: Of 9922 biologic treatment cycles, 982 (9.9%) were identified as combination treatment. 72.9% of treatment cycles concerned concomitant use of methotrexate, 25.3% concerned concomitant UVB therapy, acitretin or cyclosporin and 1.8% concerned combined treatment with PUVA, fumaric acids or a second biologic. Substantial variation was detected in type and frequency of combination treatments prescribed across registries. Patients initiated on combined treatment had generally severe disease and were affected with psoriasis for many years. The extent to which patients had been priory treated with biologic monotherapy and the proportion of patients affected with psoriatic arthritis differed between registries. Survival rates for etanercept, adalimumab, infliximab and ustekinumab with methotrexate ranged between 43 and 92%, 28 and 83%, 65 and 87% and 53 and 77%, respectively, across registries after one year with no consistent superior survival for a particular biologic. Longest survival on a biologic combined with methotrexate, acitretin or cyclosporin was 103, 78 and 34 months, respectively. CONCLUSION: Methotrexate was the most commonly used concomitant treatment for patients on a biologic. Wide geographical variations in treatment selection and persistence of combination treatment exist. Data derived from ongoing studies may help to determine whether combined treatment is superior to biologic monotherapy.

• MeSH
• acitretin terapeutické užití   MeSH
• adalimumab terapeutické užití   MeSH
• biologické přípravky terapeutické užití   MeSH
• cyklosporin terapeutické užití   MeSH
• dermatologické látky terapeutické užití   MeSH
• etanercept terapeutické užití   MeSH
• fumaráty terapeutické užití   MeSH
• infliximab terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• kombinovaná farmakoterapie MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• methotrexát terapeutické užití   MeSH
• psoriáza terapie   MeSH
• PUVA terapie * MeSH
• registrace MeSH
• stupeň závažnosti nemoci MeSH
• ustekinumab terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Itálie MeSH
• Izrael MeSH
• Nizozemsko MeSH
• Rakousko MeSH

BACKGROUND: To evaluate the outcomes of first-line imatinib versus nilotinib treatment for chronic myeloid leukemia in the chronic phase (CML-CP) in real-world clinical practice. METHODS: A propensity score analysis was performed to eliminate imbalances between the treatment groups. In the analysis, 163 patients in the nilotinib group and 163 patients in the matched imatinib group were retrospectively evaluated. RESULTS: Nilotinib-treated patients achieved complete cytogenetic response (CCyR) and major molecular response more rapidly than imatinib-treated patients. However, there was no significant difference in 5-year overall survival (OS) or progression-free survival (PFS) between the two groups (OS: 94.3% vs. 90.5%, p = 0.602; PFS: 92.9% vs. 88.0%, p = 0.614). Nilotinib-treated patients had a higher failure-free survival (FFS) and event-free survival (EFS) than imatinib-treated patients (FFS: 71.7% vs. 54.3%, p = 0.040; EFS: 71.7% vs. 53.5%, p = 0.025). CONCLUSIONS: This retrospective analysis from clinical practice did not confirm any benefit of frontline nilotinib treatment for OS and PFS; however, it did demonstrate higher FFS and EFS in the nilotinib cohort.

• MeSH
• chronická myeloidní leukemie * farmakoterapie   mortalita   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• imatinib mesylát * terapeutické užití   škodlivé účinky   MeSH
• inhibitory proteinkinas terapeutické užití   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• protinádorové látky terapeutické užití   škodlivé účinky   MeSH
• pyrimidiny * terapeutické užití   škodlivé účinky   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• tendenční skóre 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

INTRODUCTION: The antifibrotic drug nintedanib is used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the effect of nintedanib on antifibrotic treatment outcome in real-world cohorts of Czech EMPIRE registry. PATIENTS/METHODS: Data of 611 Czech IPF subjects, 430 (70%) treated with nintedanib (NIN group), 181 (30%) with no-antifibrotic treatment (NAF group) were analysed. The influence of nintedanib on overall survival (OS), pulmonary function parameters as forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO), as well as GAP score (gender, age, physiology) and and CPI (composite physiological index) were investigated. RESULTS: During 2 year follow-up we observed that nintedanib treated patients had longer OS, compared to those treated with no-antifibrotic drugs (p < 0.00001). Nintedanib reduces risk of mortality over no-antifibrotic treatment by 55% (p < 0.001). We have observed no significant difference in the rate of FVC and DLCO decline between the NIN and NAF group. Changes within 24 months from baseline in CPI were not significant between the groups (NAF and NIN). CONCLUSION: Our real-practice study showed the benefit of nintedanib treatment on survival. There were no significant differences between NIN and NAF groups in changes from baseline in FVC %, DLCO % predicted and CPI.

• MeSH
• idiopatická plicní fibróza * farmakoterapie   MeSH
• lidé MeSH
• plíce MeSH
• registrace MeSH
• vitální kapacita MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

• MeSH
• biochemie metody   MeSH
• hmotnostní spektrometrie MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biochemie
• NLK Publikační typ
• učebnice vysokých škol

The objective of this retrospective study was to evaluate results from voriconazole therapeutic drug monitoring (TDM) in haematological patients in routine clinical practice. Between 2005 and 2010, 1228 blood samples were obtained from 264 haematological patients (median 3 samples/patient; range 1-27) receiving voriconazole for targeted/preemptive treatment of invasive aspergillosis (IA) (46.3% of samples), empirical therapy (12.9%) or prophylaxis (40.8%). A high-pressure liquid chromatography assay was used to analyse voriconazole concentrations. Clinical and laboratory data were analysed retrospectively. The median of the detected voriconazole plasma concentration was 1.00 μg ml(-1) (range <0.20-13.47 μg ml(-1)). Significant inter- and intra-patients variability of measured concentrations (81.9% and 50.5%) were identified. With the exception of omeprazole administration, there was no relevant relationship between measured voriconazole concentrations and drug dose, route administration, age, gender, CYP2C19*2 genotype, gastrointestinal tract abnormality, administration via nasogastric tube, serum creatinine, and liver enzymes. However, per patient analysis identified significant role of individual voriconazole dose and drug form change on measured plasma concentration. Measured voriconazole concentrations did not correlate with the treatment outcome of patients with IA. We only identified a limited number of adverse events related to voriconazole therapy; however, the median plasma concentration was not different from concentrations measured in samples without reported toxicity. Our retrospective study has suggested that routine monitoring of voriconazole plasma concentrations has probably only a limited role in daily haematological practice.

• MeSH
• antifungální látky aplikace a dávkování   škodlivé účinky   krev   MeSH
• aromatické hydroxylasy genetika   MeSH
• aspergilóza komplikace   farmakoterapie   genetika   MeSH
• dospělí MeSH
• jednonukleotidový polymorfismus MeSH
• krevní nemoci komplikace   farmakoterapie   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• monitorování léčiv * MeSH
• pyrimidiny aplikace a dávkování   škodlivé účinky   krev   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• triazoly aplikace a dávkování   škodlivé účinky   krev   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Data regarding real-life effectiveness of any treatment may improve clinical decision-making. The aim of this study was to evaluate real-life effectiveness of tyrosin-kinase inhibitors, bevacizumab and pemetrexed as first-line treatments in patients with advanced/metastatic non-small cell lung cancer (NSCLC). METHODS: We analyzed data of 2157 patients of the Czech TULUNG Registry of patients with advanced/metastatic NSCLC who received modern-era treatments between 2011 and 2018. Patients treated with gefitinib, erlotinib, afatinib, bevacizumab (+ maintenance), pemetrexed (+ maintenance) as first-line therapy were included in the study. A systematic literature search separately identified clinical trials suitable for calculation of comparator pooled OS and PFS for each regimen. For each subgroup, basic characteristics and survival data (Kaplan-Meier estimates) are shown. We propose the "index of real-life effectiveness" (IRE), a ratio of real-life OS/PFS and comparator pooled OS/PFS. Univariate and multivariate logistic regression identified factors were associated with longer OS (ie, IRE>1.1). RESULTS: Survival analysis showed median OS of 23 months for erlotinib, 29.3 months for afatinib, 19.6 months for gefitinib, 12.2 months for pemetrexed, 17.5 months for pemetrexed maintenance, 15.8 months for bevacizumab and 15.8 months for bevacizumab maintenance. Calculated IREs for OS for the regimens were: erlotinib 1.013, afatinib 1.184, gefitinib 0.736, pemetrexed 1.188, pemetrexed maintenance 1.294, bevacizumab 1.178, and bevacizumab maintenance 1.189. Multivariate regression analysis showed that these factors were associated with longer OS: lower PS for afatinib; lower PS, absence of adverse events and female sex for bevacizumab; and lower PS and female sex for pemetrexed. CONCLUSIONS: This study clearly demonstrated that real-life effectiveness of certain treatment regimens may strongly differ in various populations/health care systems, and comparison between TULUNG data and pooled survival data from trials showed higher real-life effectiveness for most of the studied first-line regimens. Lower ECOG PS, younger age, female sex and adverse events were associated with longer survival in most regimens. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Comparison between TULUNG data and pooled survival data from trials showed higher real-life effectiveness for most of the studied first-line regimens; for most regimens, lower ECOG PS, younger age, female sex and adverse events were associated with longer survival. WHAT THIS STUDY ADDS: Real-life effectiveness of certain treatment regimens may strongly differ in various populations/health care systems.

• MeSH
• analýza přežití MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory plic farmakoterapie   mortalita   patologie   MeSH
• nemalobuněčný karcinom plic farmakoterapie   mortalita   patologie   MeSH
• protokoly protinádorové kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• registrace MeSH
• staging nádorů MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

• Klíčová slova
• biologická léčba,
• MeSH
• biologická terapie metody   využití   MeSH
• dospělí MeSH
• financování organizované MeSH
• hodnocení léčiv MeSH
• interpretace statistických dat MeSH
• klinické zkoušky jako téma MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladý dospělý MeSH
• monoklonální protilátky terapeutické užití   MeSH
• revmatoidní artritida farmakoterapie   MeSH
• statistika jako téma MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

Current progress in the field of next-generation transcriptome sequencing have contributed significantly to the study of various malignancies including glioblastoma multiforme (GBM). Differential sequencing of transcriptomes of patients and non-tumor controls has a potential to reveal novel transcripts with significant role in GBM. One such candidate group of molecules are long non-coding RNAs (lncRNAs) which have been proved to be involved in processes such as carcinogenesis, epigenetic modifications and resistance to various therapeutic approaches. To maximize the value of transcriptome sequencing, a proper protocol for library preparation from tissue-derived RNA needs to be found which would produce high quality transcriptome sequencing data and increase the number of detected lncRNAs. It is important to mention that success of library preparation is determined by the quality of input RNA, which is in case of real-life tissue specimens very often altered in comparison to high quality RNA commonly used by manufacturers for development of library preparation chemistry. In the present study, we used GBM and non-tumor brain tissue specimens and compared three different commercial library preparation kits, namely NEXTflex Rapid Directional qRNA-Seq Kit (Bioo Scientific), SENSE Total RNA-Seq Library Prep Kit (Lexogen) and NEBNext Ultra II Directional RNA Library Prep Kit for Illumina (NEB). Libraries generated using SENSE kit were characterized by the most normal distribution of normalized average GC content, the least amount of over-represented sequences and the percentage of ribosomal RNA reads (0.3-1.5%) and highest numbers of uniquely mapped reads and reads aligning to coding regions. However, NEBNext kit performed better having relatively low duplication rates, even transcript coverage and the highest number of hits in Ensembl database for every biotype of our interest including lncRNAs. Our results indicate that out of three approaches the NEBNext library preparation kit was most suitable for the study of lncRNAs via transcriptome sequencing. This was further confirmed by highly consistent data reached in an independent validation on an expanded cohort.

• MeSH
• genová knihovna MeSH
• glioblastom genetika   MeSH
• lidé MeSH
• nádory mozku genetika   MeSH
• reagenční diagnostické soupravy MeSH
• regulace genové exprese u nádorů MeSH
• RNA dlouhá nekódující genetika   MeSH
• sekvenční analýza RNA MeSH
• stanovení celkové genové exprese metody   MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Východiska: Navzdory rozvoji protinádorové léčby karcinomu v posledních dekádách je kvalita života (quality of life – QoL) těchto pacientů špatná. Cílem této práce bylo zmapovat QoL nemocných s nádory plic v průběhu 1. linie moderní protinádorové terapie v ČR. Materiál a metody: Jedná se o prospektivní multicentrickou práci realizovanou na třech pneumoonkologických pracovištích ve Fakultních nemocnicích Brno, Olomouc a Plzeň. V období od dubna do srpna 2023 byli dotazováni nemocní s nádory plic začínající 1. linii protinádorové terapie o vyplnění dotazníku QoL EQRTC QoL-C30 v době 0, 6 a 12 týdnů. Výsledky: Soubor sestává z 50 pacientů, 60 % mužů, průměrný věk 66,9 roku, 76 % kuřáků, 22 % stadia III, 78 % stadia IV, 84 % nemalobuněčný karcinom plic, 16 % malobuněčný karcinom plic. Celkem 50 % nemocných bylo léčeno chemo/imunoterapií, 20 % imunoterapií, 24 % chemoterapií +/− radioterapií, 6 % tyrozinkinázovými inhibitory. Bylo patrno zlepšení QoL ve smyslu dušnosti, slabosti, deprese a strachu v průběhu léčby. V podskupině léčené chemo/imunoterapií bylo zaznamenáno také zlepšení celkové QoL. Pacienti dosahující kompletní či parciální odpovědi prokazovali zlepšení některých aspektů QoL. Z laboratorních parametrů byla s QoL spjata hladina albuminu. Závěr: QoL pacientů s nádory plic léčených 1. linií protinádorové terapie v české reálné praxi je uspokojivá.

Introduction: Despite of a progress in anticancer treatment in the last decades, quality of life (QoL) of these patients is still very poor. The aim of this study was to monitor QoL during the first line of modern era treatment in lung cancer patients in Czechia. Material and methods: It is a prospective multicenter study realized at three pneumo-oncology departments of University Hospitals in Brno, Olomouc and Pilsen. In the period of time from April to August 2023 we asked patients with non-small cell lung cancer starting the first line of anticancer treatment to fill the questionnaire of QoL “EQRTC QoL-C30” in the time 0 and 6 and 12 weeks. Results: We studied data from 50 patients, 60% men, the average age 66,9 years, 76% smokers, 22% in stage III, 78% in stage IV, 84% non-small cell lung cancer, 16% small cell lung cancer. A total of 50% patients were treated with chemoimmunotherapy, 20% by immunotherapy, 24% by chemotherapy +/− irradiation, and 6% by tyrosine kinase inhibitors. There was a significant improvement of QoL in the mean of dyspnoe, weakness, depression and fear during the treatment. In the subgroup analysis, patients treated with chemo/immunotherapy reached an improvement in total QoL. Subjects with complete/partial response to treatment reached improvement in some aspects of QoL. Out of laboratory parameters, albumin levels were associated with QoL. Conclusion: QoL of patients with lung cancer treated with first-line anticancer treatment in the Czech real-life practice is acceptable.