The pressure reactivity index (PRx) is a parameter for the assessment of cerebrovascular autoregulation, but its calculation is affected by artifacts in the source biosignals-intracranial pressure (ICP) and arterial blood pressure. We sought to describe the most common short-duration artifacts and their effect on the PRx. A retrospective analysis of 935 h of multimodal monitoring data was conducted, and five types of artifacts, characterized by their shape, duration, and amplitude, were identified: rectangular, fast impulse, isoline drift, saw tooth, and constant ICP value. Subsequently, all types of artifacts were mathematically modeled and inserted into undisturbed segments of biosignals. Fast impulse, the most common artifact, did not alter the PRx index significantly when inserted into one or both signals. Artifacts present in one signal exceeded the threshold PRx in less than 5% of samples, except for isoline drift. Compared to that, the shortest rectangular artifact inserted into both signals changed PRx to a value above the set threshold in 55.4% of cases. Our analysis shows that the effect of individual artifacts on the PRx index is variable, depending on their occurrence in one or both signals, duration, and shape. This different effect suggests that potentially not all artifacts need to be removed.

• MeSH
• artefakty * MeSH
• arteriální tlak fyziologie   MeSH
• intrakraniální tlak fyziologie   MeSH
• lidé MeSH
• mozkový krevní oběh fyziologie   MeSH
• retrospektivní studie MeSH
• traumatické poranění mozku * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND/AIM: Gliomas are primary malignancies of the central nervous system (CNS). High-grade gliomas are associated with poor prognosis and modest survival rates despite intensive multimodal treatment strategies. Targeting gene fusions is an emerging therapeutic approach for gliomas that allows application of personalized medicine principles. The aim of this study was to identify detectable fusion oncogenes that could serve as predictors of currently available or newly developed targeted therapeutics in cross-sectional samples from glioma patients using next-generation sequencing (NGS). PATIENTS AND METHODS: A total of 637 patients with glial and glioneuronal tumours of the CNS who underwent tumour resection between 2017 and 2020 were enrolled. Detection of fusion transcripts in FFPE tumour tissue was performed by a TruSight Tumour 170 assay and two FusionPlex kits, Solid Tumour and Comprehensive Thyroid and Lung. RESULTS: Oncogene fusions were identified in 33 patients. The most common fusion was the KIAA1549-BRAF fusion, detected in 13 patients, followed by FGFR fusions (FGFR1-TACC1, FGFR2-CTNNA3, FGFR3-TACC3, FGFR3-CKAP5, FGFR3-AMBRA1), identified in 10 patients. Other oncogene fusions were also infrequently diagnosed, including MET fusions (SRPK2-MET and PTPRZ1-MET) in 2 patients, C11orf95-RELA fusions in 2 patients, EGFR-SEPT14 fusion in 2 patients, and individual cases of SRGAP3-BRAF, RAF1-TRIM2, EWSR1-PALGL1 and TERT-ALK fusions. CONCLUSION: The introduction of NGS techniques provides additional information about tumour molecular alterations that can aid the multimodal management of glioma patients. Patients with gliomas positive for particular targetable gene fusions may benefit from experimental therapeutics, enhancing their quality of life and prolonging survival rates.

• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• gliom * genetika   patologie   MeSH
• kvalita života MeSH
• lidé MeSH
• onkogenní fúze * MeSH
• onkogeny genetika   MeSH
• protein-serin-threoninkinasy MeSH
• proteiny asociované s mikrotubuly genetika   MeSH
• průřezové studie MeSH
• tyrosinfosfatasy receptorového typu, třída 5 genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Hypokinetic dysarthria (HD) is common in Parkinson's disease (PD). Our objective was to evaluate articulatory networks and their reorganization due to PD pathology in individuals without overt speech impairment using a multimodal MRI protocol and acoustic analysis of speech. METHODS: A total of 34 PD patients with no subjective HD complaints and 25 age-matched healthy controls (HC) underwent speech task recordings, structural MRI, and reading task-induced and resting-state fMRI. Grey matter probability maps, task-induced activations, and resting-state functional connectivity within the regions engaged in speech production (ROIs) were assessed and compared between groups. Correlation with acoustic parameters was also performed. RESULTS: PD patients as compared Tto HC displayed temporal decreases in speech loudness which were related to BOLD signal increases in the right-sided regions of the dorsal language pathway/articulatory network. Among those regions, activation of the right anterior cingulate was increased in PD as compared to HC. We also found bilateral posterior superior temporal gyrus (STG) GM loss in PD as compared to HC that was strongly associated with diadochokinetic (DDK) irregularity in the PD group. Task-induced activations of the left STG were increased in PD as compared to HC and were related to the DDK rate control. CONCLUSIONS: The results provide insight into the neural correlates of speech production control and distinct articulatory network reorganization in PD apparent already in patients without subjective speech impairment.

• MeSH
• akustika řeči * MeSH
• dysartrie * diagnóza   etiologie   patologie   patofyziologie   MeSH
• konektom * MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• multimodální zobrazování MeSH
• nervová síť * diagnostické zobrazování   patologie   patofyziologie   MeSH
• Parkinsonova nemoc * komplikace   diagnostické zobrazování   patologie   patofyziologie   MeSH
• šedá hmota * diagnostické zobrazování   patologie   patofyziologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spánkový lalok * diagnostické zobrazování   patologie   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Colorectal cancer (CRC) is a disease with constantly increasing incidence and high mortality. The treatment efficacy could be curtailed by drug resistance resulting from poor drug penetration into tumor tissue and the tumor-specific microenvironment, such as hypoxia and acidosis. Furthermore, CRC tumors can be exposed to different pH depending on the position in the intestinal tract. CRC tumors often share upregulation of the Akt signaling pathway. In this study, we investigated the role of external pH in control of cytotoxicity of perifosine, the Akt signaling pathway inhibitor, to CRC cells using 2D and 3D tumor models. In 3D settings, we employed an innovative strategy for simultaneous detection of spatial drug distribution and biological markers of proliferation/apoptosis using a combination of mass spectrometry imaging and immunohistochemistry. In 3D conditions, low and heterogeneous penetration of perifosine into the inner parts of the spheroids was observed. The depth of penetration depended on the treatment duration but not on the external pH. However, pH alteration in the tumor microenvironment affected the distribution of proliferation- and apoptosis-specific markers in the perifosine-treated spheroid. Accurate co-registration of perifosine distribution and biological response in the same spheroid section revealed dynamic changes in apoptotic and proliferative markers occurring not only in the perifosine-exposed cells, but also in the perifosine-free regions. Cytotoxicity of perifosine to both 2D and 3D cultures decreased in an acidic environment below pH 6.7. External pH affects cytotoxicity of the other Akt inhibitor, MK-2206, in a similar way. Our innovative approach for accurate determination of drug efficiency in 3D tumor tissue revealed that cytotoxicity of Akt inhibitors to CRC cells is strongly dependent on pH of the tumor microenvironment. Therefore, the effect of pH should be considered during the design and pre-clinical/clinical testing of the Akt-targeted cancer therapy.

• Publikační typ
• časopisecké články MeSH

• MeSH
• nádory radioterapie   MeSH
• nukleární lékařství metody   MeSH
• radioterapie metody   MeSH
• Publikační typ
• učebnice MeSH

• Konspekt
• Učební osnovy. Vyučovací předměty. Učebnice
• Lékařské vědy. Lékařství
• NLK Obory
• radiologie, nukleární medicína a zobrazovací metody
• onkologie
• NLK Publikační typ
• kolektivní monografie

Electroencephalography (EEG) signals recorded during simultaneous functional magnetic resonance imaging (fMRI) are contaminated by strong artifacts. Among these, the ballistocardiographic (BCG) artifact is the most challenging, due to its complex spatio-temporal dynamics associated with ongoing cardiac activity. The presence of BCG residuals in EEG data may hide true, or generate spurious correlations between EEG and fMRI time-courses. Here, we propose an adaptive Optimal Basis Set (aOBS) method for BCG artifact removal. Our method is adaptive, as it can estimate the delay between cardiac activity and BCG occurrence on a beat-to-beat basis. The effective creation of an optimal basis set by principal component analysis (PCA) is therefore ensured by a more accurate alignment of BCG occurrences. Furthermore, aOBS can automatically estimate which components produced by PCA are likely to be BCG artifact-related and therefore need to be removed. The aOBS performance was evaluated on high-density EEG data acquired with simultaneous fMRI in healthy subjects during visual stimulation. As aOBS enables effective reduction of BCG residuals while preserving brain signals, we suggest it may find wide application in simultaneous EEG-fMRI studies.

• MeSH
• artefakty * MeSH
• dospělí MeSH
• elektroencefalografie metody   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mladý dospělý MeSH
• multimodální zobrazování metody   MeSH
• počítačové zpracování obrazu metody   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

There have recently been considerable advances in our understanding of the neuronal mechanisms underlying multitasking, but the role of multimodal integration for this faculty has remained rather unclear. We examined this issue by comparing different modality combinations in a multitasking (stop-change) paradigm. In-depth neurophysiological analyses of event-related potentials (ERPs) were conducted to complement the obtained behavioral data. Specifically, we applied signal decomposition using second order blind identification (SOBI) to the multi-subject ERP data and source localization. We found that both general multimodal information integration and modality-specific aspects (potentially related to task difficulty) modulate behavioral performance and associated neurophysiological correlates. Simultaneous multimodal input generally increased early attentional processing of visual stimuli (i.e. P1 and N1 amplitudes) as well as measures of cognitive effort and conflict (i.e. central P3 amplitudes). Yet, tactile-visual input caused larger impairments in multitasking than audio-visual input. General aspects of multimodal information integration modulated the activity in the premotor cortex (BA 6) as well as different visual association areas concerned with the integration of visual information with input from other modalities (BA 19, BA 21, BA 37). On top of this, differences in the specific combination of modalities also affected performance and measures of conflict/effort originating in prefrontal regions (BA 6).

• MeSH
• akustická stimulace MeSH
• dospělí MeSH
• elektroencefalografie MeSH
• evokované potenciály fyziologie   MeSH
• lidé MeSH
• mapování mozku MeSH
• mladiství MeSH
• motorické korové centrum anatomie a histologie   diagnostické zobrazování   fyziologie   MeSH
• plnění a analýza úkolů MeSH
• pozornost fyziologie   MeSH
• prefrontální mozková kůra anatomie a histologie   diagnostické zobrazování   fyziologie   MeSH
• psychomotorický výkon fyziologie   MeSH
• rozpoznávání fyziologické * MeSH
• světelná stimulace MeSH
• zrakové korové centrum anatomie a histologie   diagnostické zobrazování   fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are found in 35-45 % of colorectal cancer (CRC) cases. Although the association between the RAS signaling and angiogenesis is well known, the negative predictive value of KRAS mutation has not been established in patients treated with bevacizumab. The aim of this study was to evaluate the association between specific KRAS mutation types and outcome of patients with metastatic CRC treated with bevacizumab. The study included 404 patients with metastatic CRC (mCRC) treated with bevacizumab. Clinical data obtained from the clinical registry CORECT were retrospectively analyzed. The shortest survival was observed in patients with tumors harboring G12V or G12A KRAS mutation (G12V/A). The median progression-free survival (PFS) and overall survival (OS) for patients with tumors harboring G12V/A KRAS mutation was 6.6 and 16.8 compared to 11.6 and 26.3 months for patients with tumors harboring other KRAS mutation type (p < 0.001 and p < 0.001), while the survival of patients harboring other KRAS mutation types was comparable to those with tumors harboring wild-type KRAS gene. In the Cox multivariable analysis, KRAS G12V/A mutation type remains a significant factor predicting both PFS (HR = 2.18, p < 0.001) and OS (HR = 2.58, p < 0.001). In conclusion, the results of the present study indicate that there is a significant difference in biological behavior between tumors harboring G12V/A and other KRAS mutations. Moreover, comparison of the survival of patients with tumors harboring G12V/A KRAS mutations with those harboring wild-type KRAS gene revealed that G12V/A KRAS mutations are prognostic biomarker for inferior PFS and OS in patients with mCRC treated with bevacizumab in univariate as well as multivariable analyses.

• MeSH
• alely * MeSH
• bevacizumab terapeutické užití   MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• kodon MeSH
• kolorektální nádory farmakoterapie   genetika   mortalita   patologie   MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• mutace * MeSH
• opakovaná terapie MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• ras proteiny genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Chronická lymfocytární leukemie (CLL) je onemocnění s mimořádně různorodým klinickým průběhem. Diagnostiku a léčbu je nutno individualizovat s přihlédnutím k věku, celkovému stavu, přidruženým chorobám a cílům léčby. V posledních letech přibyly zásadní poznatky týkající se posouzení prognózy i léčby (význam mutací genu TP53, nové monoklonální protilátky, inhibitory drah B-buněčného receptoru a další). Česká skupina pro CLL, sekce České hematologické společnosti ČLS JEP, proto vytvořila tato aktualizovaná doporučení k usnadnění rozhodnování o diagnostických a léčebných postupech v klinické praxi. Doporučení se zakládají na důkladné analýze současné literatury a vycházejí z principů medicíny založené na důkazech.

Chronic lymphocytic leukaemia (CLL) has a remarkably heterogeneous clinical course. The diagnostic procedures and therapeutic interventions need to be individually tailored according to patient age, comorbidities and therapeutic aims. There have been important developments in prognostication and therapy during recent years (e. g., significance of TP53 mutations, introduction of novel monoclonal antibodies and B-cell receptor signalling inhibitors). Therefore, the Czech CLL Study Group, the working group of the Czech Society of Haematology developed these updated guidelines to facilitate the decision-making process for diagnostic and therapeutic procedures in daily practice. The guidelines are based on a comprehensive analysis of current literature and follow the principles of evidence-based medicine.

• MeSH
• chronická lymfatická leukemie * diagnóza   terapie   MeSH
• hodnocení výsledků zdravotní péče metody   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• prognóza MeSH
• protinádorové látky terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie MeSH
• recidiva MeSH
• reziduální nádor diagnóza   MeSH
• stupeň závažnosti nemoci MeSH
• transplantace kmenových buněk MeSH
• výběr pacientů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• směrnice pro lékařskou praxi MeSH

Východiska: Kombinace moderní chemoterapie s cílenou anti-EGFR léčbou vede u senzitivních pacientů s metastatickým kolorektálním karcinomem k prodloužení života a zlepšení jeho kvality. U rezistentních pacientů může však přidání monoklonálních protilátek proti EGFR vést naopak ke zhoršení parametrů přežití. Z tohoto důvodu se identifikace senzitivních a rezistentních pacientů stala klíčovou záležitostí při iniciální rozvaze před zahájením cílené léčby metastatického kolorektálního karcinomu. Četné klinické studie vedly ke zjištění, že rezistence k anti-EGFR terapii je v naprosté většině případů spojena s trvalou aktivací signálních drah distálně od EGFR. Z mnoha studovaných faktorů (mutace onkogenů KRAS, NRAS, BRAF a PIK3CA, inaktivace nádorového supresoru PTEN a TP53, amplifikace EGFR a HER2, zvýšená hladina ligandů epiregulinu a amphiregulinu, mikroRNA miR-31-3p a miR-31-5p a další) se do rutinní klinické praxe dostaly pouze KRAS a NRAS. U ostatních faktorů je třeba dalších studií k verifikaci zjištěných závěrů. Na pokračující efektivitu anti-EGFR terapie mohou ukazovat i některé klinické parametry zjištěné až po zahájení cílené léčby, jako např. časná regrese nádoru, hloubka nádorové odpovědi či míra poklesu plazmatické hladiny hořčíku. Přesnost prediktivní dia­gnostiky lze zvýšit rovněž kombinací vyšetřovaných bio­markerů např. pomocí metod založených na sekvenování nové generace. Je však třeba varovat před nekritickým vyšetřováním řady molekulárních markerů, které může vést k problémům s interpretací získaných výsledků, především jejich klinické relevance. Cíl: Cílem tohoto přehledu je popsat současné možnosti predikce odpovědi na anti-EGFR terapii v kontextu EGFR signální dráhy a návaznosti na běžnou klinickou praxi.

Background: The combination of modern systemic chemotherapy and anti-EGFR monoclonal antibodies improves overall survival and quality of life for patients with metastatic colorecal cancer. By contrast, the addition of anti-EGFR therapy to the treatment regime of resistant patients may lead to worse progression-free survival and overall survival. Therefore, identifying sensitive and resistant patients prior to targeted therapy of metastatic colorecal cancer is a key point during the initial decision making process. Previous research shows that primary resistance to EGFR blockade is in most cases caused by constitutive activation of signaling pathways downstream of EGFR. Of all relevant factors (mutation of KRAS, NRAS, BRAF, and PIK3CA oncogenes, inactivation of tumor suppressors PTEN and TP53, amplification of EGFR and HER2, and expression of epiregulin and amphiregulin, mikroRNA miR-31-3p, and miR-31-5p), only evaluation of KRAS and NRAS mutations has entered routine clinical practice. The role of the other markers still needs to be validated. The ongoing benefit of anti-EGFR therapy could be indicated by specific clinical parameters measured after the initiation of targeted therapy, including early tumor shrinkage, the deepness of the response, or hypomagnesemia. The accuracy of predictive dia­gnostic tools could be also increased by examining a combination of predictive markers using next generation sequencing methods. However, unjustified investigation of many molecular markers should be resisted as this may complicate interpretation of the results, particularly in terms of their specific clinical relevance. Aim: The aim of this review is to describe current possibilities with respect to predicting responses to EGFR blockade in the context of the EGFR pathway, and the utilization of such results in routine clinical practice. Key words: colorectal cancer – cetuximab – panitumumab – EGFR – KRAS – BRAF The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 20. 3. 2016 Accepted: 19. 4. 2016

• MeSH
• analýza přežití MeSH
• erbB receptory * antagonisté a inhibitory   MeSH
• exantém MeSH
• exprese genu MeSH
• fosfatidylinositol-3-kinasy genetika   MeSH
• fosfohydroláza PTEN genetika   MeSH
• genetické testování * MeSH
• kolorektální nádory * genetika   terapie   MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• metastázy nádorů genetika   MeSH
• nádorové biomarkery MeSH
• nedostatek hořčíku MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie MeSH
• protoonkogenní proteiny B-raf genetika   MeSH
• ras proteiny * genetika   MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH