OBJECTIVE: To evaluate the effectiveness and safety of sonolysis using a low intensity 2 MHz pulsed wave ultrasound beam during carotid endarterectomy. DESIGN: Multicentre, phase 3, double blind, randomised controlled trial. SETTING: 16 European centres. PARTICIPANTS: 1004 patients (mean age 68 years; 312 (31%) female) were enrolled in the study between 20 August 2015 and 14 October 2020 until the interim analysis was performed. INTERVENTIONS: Sonolysis (n=507) versus sham procedure (n=497). MAIN OUTCOME MEASURES: The primary endpoint was the composite incidence of ischaemic stroke, transient ischaemic attack, and death within 30 days. The incidence of new ischaemic lesions on follow-up brain magnetic resonance imaging was the main substudy endpoint, and incidence of intracranial bleeding was the main safety endpoint. RESULTS: The results favoured the sonolysis group for the primary endpoint (11 (2.2%) v 38 (7.6%); risk difference -5.5%, 95% confidence interval (CI) -8.3% to -2.8%; P<0.001), as well as in the substudy for magnetic resonance imaging detected new ischaemic lesions (20/236 (8.5%) v 39/224 (17.4%); risk difference -8.9%, -15% to -2.8%; P=0.004). Sensitivity analysis resulted in a risk ratio for sonolysis of 0.25 (95% CI 0.11 to 0.56) for ischaemic stroke and 0.23 (0.07 to 0.73) for transient ischaemic attack within 30 days. Sonolysis was found to be safe, and 94.4% of patients in the sonolysis group were free from serious adverse events 30 days after the procedure. CONCLUSION: Sonolysis was safe for patients undergoing carotid endarterectomy and resulted in a significant reduction in the composite incidence of ischaemic stroke, transient ischaemic attack, and death within 30 days. TRIAL REGISTRATION: Clinicaltrials.gov NCT02398734.

• MeSH
• dvojitá slepá metoda MeSH
• ischemická cévní mozková příhoda prevence a kontrola   epidemiologie   MeSH
• karotická endarterektomie * škodlivé účinky   metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• senioři MeSH
• stenóza arteria carotis chirurgie   MeSH
• tranzitorní ischemická ataka * prevence a kontrola   etiologie   MeSH
• ultrazvuková terapie metody   škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Glioblastoma is the commonest malignant brain tumor and has a very poor prognosis. Reduced expression of the MGMT gene (10q26.3), influenced primarily by the methylation of two differentially methylated regions (DMR1 and DMR2), is associated with a good response to temozolomide treatment. However, suitable methods for detecting the methylation of the MGMT gene promoter and setting appropriate cutoff values are debated. RESULTS: A cohort of 108 patients with histologically and genetically defined glioblastoma was retrospectively examined with methylation-specific Sanger sequencing (sSeq) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) methods. The DMR2 region was methylated in 29% of samples, whereas DMR1 was methylated in 12% of samples. Methylation detected with the MS-MLPA method using probes MGMT_215, MGMT_190, and MGMT_124 from the ME012-A1 kit (located in DMR1 and DMR2) correlated with the methylation of the corresponding CpG dinucleotides detected with sSeq (p = 0.005 for probe MGMT_215; p < 0.001 for probe MGMT_190; p = 0.016 for probe MGMT_124). The threshold for methylation detection with the MS-MLPA method was calculated with a ROC curve analysis and principal components analysis of the data obtained with the MS-MLPA and sSeq methods, yielding a weighted value of 0.362. Thus, methylation of the MGMT gene promoter was confirmed in 36% of samples. These patients had statistically significantly better overall survival (p = 0.003). CONCLUSIONS: Our results show that the threshold for methylation detection with the MS-MLPA method determined here is useful from a diagnostic perspective because it allows the stratification of patients who will benefit from specific treatment protocols, including temozolomide. Detailed analysis of the MGMT gene promoter enables the more-precise and personalized treatment of patients with glioblastoma.

• MeSH
• CpG ostrůvky genetika   MeSH
• DNA modifikační methylasy * genetika   MeSH
• dospělí MeSH
• enzymy opravy DNA * genetika   MeSH
• glioblastom * genetika   farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA * genetika   MeSH
• nádorové supresorové proteiny * genetika   MeSH
• nádory mozku * genetika   MeSH
• promotorové oblasti (genetika) * genetika   MeSH
• retrospektivní studie MeSH
• sekvenční analýza DNA metody   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• temozolomid terapeutické užití   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
• srovnávací studie MeSH
• validační studie MeSH

The histological grade is crucial for therapeutic management, and its reliable preoperative detection can significantly influence treatment approach. Lacking established risk factors, this study identifies preoperative predictors of high-grade skull base meningiomas and discusses the implications of non-invasive detection. A multicentric study was conducted on 552 patients with skull base meningiomas who underwent primary surgical resection between 2014 and 2019. Data were gathered from clinical, surgical and pathology records and radiological diagnostics. The predictive factors of higher WHO grade were analysed in univariate analysis and multivariate stepwise selection logistic regression analysis. Histological analysis revealed 511 grade 1 (92.6%) and 41 grade 2 (7.4%) meningiomas. A prognostic model predicting the probability of WHO grade 2 skull base meningioma (AUC 0.79; SE 0.04; 95% Wald Confidence Limits (0.71; 0.86)) based on meningioma diameter, presence of an arachnoid plane and cranial nerve palsy was built. Accurate preoperative detection of WHO grade in skull base meningiomas is essential for effective treatment planning. Our logistic regression model, based on diameter, cranial nerve palsy, and arachnoid plane, is tailored for detecting WHO grade 2 skull base meningiomas, even in outpatient settings.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• meningeální nádory * patologie   chirurgie   diagnostické zobrazování   MeSH
• meningeom * patologie   chirurgie   diagnostické zobrazování   MeSH
• mladý dospělý MeSH
• nádory baze lební * patologie   chirurgie   diagnostické zobrazování   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň nádoru * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý 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

BACKGROUND AND PURPOSE: Diffuse gliomas, a heterogeneous group of primary brain tumors, have traditionally been stratified by histology, but recent insights into their molecular features, especially the IDH mutation status, have fundamentally changed their classification and prognosis. Current diagnostic methods, still predominantly relying on invasive biopsy, necessitate the exploration of noninvasive imaging alternatives for glioma characterization. MATERIALS AND METHODS: In this prospective study, we investigated the utility of the spherical mean technique (SMT) in predicting the IDH status and histologic grade of adult-type diffuse gliomas. Patients with histologically confirmed adult-type diffuse glioma underwent a multiparametric MRI examination using a 3T system, which included a multishell diffusion sequence. Advanced diffusion parameters were obtained using SMT, diffusional kurtosis imaging, and ADC modeling. The diagnostic performance of studied parameters was evaluated by plotting receiver operating characteristic curves with associated area under curve, specificity, and sensitivity values. RESULTS: A total of 80 patients with a mean age of 48 (SD, 16) years were included in the study. SMT metrics, particularly microscopic fractional anisotropy (μFA), intraneurite voxel fraction, and μFA to the third power (μFA3), demonstrated strong diagnostic performance (all AUC = 0.905, 95% CI, 0.835-0.976; P < .001) in determining IDH status and compared favorably with diffusional kurtosis imaging and ADC models. These parameters also showed a strong predictive capability for tumor grade, with intraneurite voxel fraction and μFA achieving the highest diagnostic accuracy (AUC = 0.937, 95% CI, 0.880-0.993; P < .001). Control analyses on normal-appearing brain tissue confirmed the specificity of these metrics for tumor tissue. CONCLUSIONS: Our study highlights the potential of SMT for noninvasive characterization of adult-type diffuse gliomas, with a potential to predict IDH status and tumor grade more accurately than traditional ADC metrics. SMT offers a promising addition to the current diagnostic toolkit, enabling more precise preoperative assessments and contributing to personalized treatment planning.

• MeSH
• difuzní magnetická rezonance metody   MeSH
• dospělí MeSH
• gliom * diagnostické zobrazování   patologie   MeSH
• isocitrátdehydrogenasa * genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mutace MeSH
• nádory mozku * diagnostické zobrazování   patologie   MeSH
• prospektivní studie MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• stupeň nádoru MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Glioblastoma is the commonest primary malignant brain tumor, with a very poor prognosis and short overall survival. It is characterized by its high intra- and intertumoral heterogeneity, in terms of both the level of single-nucleotide variants, copy number alterations, and aneuploidy. Therefore, routine diagnosis can be challenging in some cases. We present a complicated case of glioblastoma, which was characterized with five cytogenomic methods: interphase fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, comparative genomic hybridization array and single-nucleotide polymorphism, targeted gene panel, and whole-genome sequencing. These cytogenomic methods revealed classical findings associated with glioblastoma, such as a lack of IDH and TERT mutations, gain of chromosome 7, and loss of chromosome 10. At least three pathological clones were identified, including one with whole-genome duplication, and one with loss of 1p and suspected loss of 19q. Deletion and mutation of the TP53 gene were detected with numerous breakends on 17p and 20q. Based on these findings, we recommend a combined approach to the diagnosis of glioblastoma involving the detection of copy number alterations, mutations, and aneuploidy. The choice of the best combination of methods is based on cost, time required, staff expertise, and laboratory equipment. This integrated strategy could contribute directly to tangible improvements in the diagnosis, prognosis, and prediction of the therapeutic responses of patients with brain tumors.

• MeSH
• glioblastom * genetika   patologie   diagnóza   MeSH
• hybridizace in situ fluorescenční metody   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery genetika   MeSH
• nádory mozku * genetika   patologie   diagnóza   MeSH
• prognóza MeSH
• srovnávací genomová hybridizace metody   MeSH
• variabilita počtu kopií segmentů DNA MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Cílem karotické endarterektomie je prevence ischemické cévní mozkové příhody, jedné z nejčastějších příčin trvalého postižení či úmrtí ve vyspělých zemích. Současná indikační doporučení jsou založena dominantně na hodnocení stupně stenózy způsobené aterosklerotickým plátem. Přestože je známo, že charakter plátu může souviset s jeho rizikem klinické symptomatologie, zatím není vyjádřen v současných doporučeních American Heart Association (AHA). Na vývoj a charakter plátu má nejspíše velký význam hemodynamika v karotickém řečišti. Cílem našeho projektu je popsat vztah mezi hemodynamickými parametry a charakterem karotického plátu. Správnost našich matematických kalkulací chceme potvrdit pomocí laboratorních modelů karotických stenóz. Vizí našeho projektu je získat nástroj, který by dokázal včas diferencovat rizikové pláty od těch méně rizikových a poskytl možnost časné intervence před rozvojem klinické symptomatologie a tím zefektivnil význam preventivních opatření, jakým je karotické endarterektomie.; The goal of carotid endarterectomy is prevention of ischemic stroke, one of the most common causes of morbidity or mortality in developed countries. The current indication criteria are primarily based on the grade of stenosis caused by the atherosclerotic plaque. Even though it is known that the character of atherosclerotic plaque may be associated with the risk of clinical symptoms, this parameter is not expressed in the recommendations of the American Heart Association (AHA). The development and the character or the plaque are probably influenced by the hemodynamics in the carotid arteries. The goal of our project is to describe the relationship between the hemodynamic parameters and the character of the plaque. The mathematical calculations will be verified with laboratory modelling. The vision of our project is to obtain a tool that would help in early differentiation between risky and less risky plaques and provide the possibility of early intervention before the onset of clinical symptomatology thus making the preventive measures, such as carotid endarterectomy, more effective.

• Klíčová slova
• Iktus;, Hemodynamika;, Stenóza karotidy;, Nestabilní aterosklarotický plát;, Stroke;, Hemodynamics;, Carotid stenosis;, Unstable atherosclerotic plaque;,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Extra­‐axiální nádory vycházejí z tkání zevně od pia mater (z arachnoidey, dury mater nebo kosti) a jsou anatomicky oddělené od parenchymu centrální nervové soustavy. Z patologického hlediska představují tyto nádory různorodou skupinu lézí s proměnlivými morfologickými, biologickými, genetickými a klinickými charakteristikami. Taktéž patří do širokého spektra histopatologických podskupin v současné 5. edici WHO klasifikace nádorů CNS. Tento článek poskytuje stručný přehled o spektru těchto nádorů, jejich genetice a úskalích v diferenciální diagnostice. Hlavní důraz je kladen na meningiomy, nádory kraniálních a paraspinálních nervů, ne­‐meningoteliální mezenchymální nádory, sekundární nádory mozkových plen a pseudotumory mozkových plen.

Extra-axial tumors originate from tissues outside the pia mater (arachnoid, dura mater, bone), distinct anatomically from the central nervous system parenchyma. Pathologically, these tumors comprise a diverse range of lesions with varying morphological, biological, genetic, and clinical characteristics. They are classified into numerous histopathological subgroups in the latest 5th edition of the WHO classification of CNS tumors. This article offers a concise overview of these tumors, exploring their genetic aspects and addressing key considerations in differential diagnosis. Emphasis is placed on meningiomas, cranial and paraspinal nerve tumors, non-meningothelial mesenchymal tumors, secondary meningeal tumors, and meningeal pseudotumors.

• MeSH
• cauda equina patologie   MeSH
• hemangioblastom genetika   patologie   MeSH
• hemangiopericytom genetika   patologie   MeSH
• lidé MeSH
• melanom patologie   MeSH
• meningeální nádory genetika   patologie   MeSH
• meningy patologie   MeSH
• nádorové biomarkery genetika   MeSH
• nádory centrálního nervového systému * genetika   patologie   MeSH
• neurilemom genetika   patologie   MeSH
• neuroendokrinní nádory genetika   patologie   MeSH
• neurofibrom genetika   patologie   MeSH
• sekundární malignity patologie   MeSH
• Check Tag
• lidé MeSH

Nádory hypofýzy jsou běžné intrakraniální tumory dospělé populace. Naprostá většina nádorů hypofýzy je představována pituitárními neuroendokrinními tumory (PitNETy, dříve adenomy), které lze klasifikovat v závislosti na linii diferenciace nádorových buněk, jež odráží buněčné populace normální hypofýzy. Příslušnost k různým subpopulacím je řízena jedním či více transkripčními faktory (Pit1, Tpit, SF1 a GATA3), které regulují mimo jiné též hormonální produkci v normálních i nádorových buňkách hypofýzy. Tento přehledový článek v krátkosti z perspektivy diagnostické patologie shrnuje novinky ve WHO klasifikaci PitNETů a dále se zabývá vzácnějšími lézemi hypofýzy, jmenovitě kraniofaryngiomy, pituicytomy a sekundárními nádory sellární oblasti.

Pituitary tumors are common intracranial tumors in adults. Pituitary neuroendocrine tumors (PitNETs, formerly adenomas) represent a vast majority of pituitary lesions. These tumors can be classified according to the lineage of differentiation in tumor cells that corresponds to cellular subpopulations of normal pituitary. These cell lineages are determined by one or more transcription factors (Pit1, Tpit, SF1 and GATA3) that also regulate hormonal production in both normal pituitary cells and their neoplastic counterparts. This review article summarizes briefly current approach in histopathological diagnosis of PitNETs according to the latest WHO classification. Furthermore, rarer entities, including pituictyomas and craniopharyngiomas are discussed, as well as secondary tumors of sellar region.

• MeSH
• histologické techniky MeSH
• kraniofaryngeom diagnóza   patologie   MeSH
• lidé MeSH
• nádory hypofýzy * diagnóza   patologie   MeSH
• neuroendokrinní nádory MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• kognice fyziologie   MeSH
• kognitivní dysfunkce psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• normotenzní hydrocefalus * chirurgie   diagnóza   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• srovnávací studie MeSH

BACKGROUND AND OBJECTIVES: Endovascular treatment of cerebral aneurysms has tremendously advanced over the past decades. Nevertheless, aneurysm residual and recurrence remain challenges after embolization. The objective of this study was to elucidate the portion of embolized aneurysms requiring open surgery and evaluate whether newer endovascular treatments have changed the need for open surgery after failed embolization. METHODS: All 15 cerebrovascular centers in Austria and the Czech Republic provided overall aneurysm treatment frequency data and retrospectively reviewed consecutive cerebral aneurysms treated with open surgical treatment after failure of embolization from 2000 to 2022. All endovascular modalities were included. RESULTS: On average, 1362 aneurysms were treated annually in the 2 countries. The incidence increased from 0.006% in 2005 to 0.008% in 2020 in the overall population. Open surgery after failed endovascular intervention was necessary in 128 aneurysms (0.8%), a proportion that remained constant over time. Subarachnoid hemorrhage was the initial presentation in 70.3% of aneurysms. The most common location was the anterior communicating artery region (40.6%), followed by the middle cerebral artery (25.0%). The median diameter was 6 mm (2-32). Initial endovascular treatment included coiling (107 aneurysms), balloon-assist (10), stent-assist (4), intrasaccular device (3), flow diversion (2), and others (2). Complete occlusion after initial embolization was recorded in 40.6%. Seventy-one percent of aneurysms were operated within 3 years after embolization. In 7%, the indication for surgery was (re-)rupture and, in 88.3%, reperfusion. Device removal was performed in 16.4%. Symptomatic intraoperative and postoperative complications occurred in 10.2%. Complete aneurysm occlusion after open surgery was achieved in 94%. CONCLUSION: Open surgery remains a rare indication for cerebral aneurysms after failed endovascular embolization even in the age of novel endovascular technology, such as flow diverters and intrasaccular devices. Regardless, it is mostly performed for ruptured aneurysms initially treated with primary coiling that are in the anterior circulation.

• MeSH
• dospělí MeSH
• endovaskulární výkony * metody   MeSH
• intrakraniální aneurysma * chirurgie   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrochirurgie metody   MeSH
• neurochirurgické výkony metody   MeSH
• neúspěšná terapie MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• terapeutická embolizace * metody   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
• multicentrická studie MeSH
• Geografické názvy
• Česká republika MeSH
• Rakousko MeSH