BACKGROUND AND OBJECTIVE: Intracerebral hemorrhage (ICH) is a serious medical condition with high mortality. However, factors leading to long-term mortality after ICH are largely unclear. The aim of this community-based study is to assess predictors of long-term mortality after spontaneous ICH. METHODS: We identified all patients admitted with spontaneous ICH to hospitals with a certified stroke unit in Brno, the second largest city in the Czech Republic (CR), in 2011, the year of the Czech Population and Housing Census. We reviewed their medical records for risk factors, radiographic parameters, and measures of post-stroke neurological deficit [National Institutes of Health Stroke Scale (NIHSS)]. Using the dates of death from the Czech National Mortality Register, we calculated mortality at 30 days, six months, one year, and three years after the ICH. Multivariate analysis with forward stepwise logistic regression was performed to determine independent predictors of mortality (p < 0.05). RESULTS: In 2011, 1086 patients with stroke were admitted to the four stroke-certified hospitals in Brno, CR. Of these, 134 had spontaneous ICH, with complete data available in 93 of them entering the final analysis. The mortality at 30 days, 6 months, 1 year, and 3 years post-ICH was 34%, 47%, 51%, and 63%, respectively. The mortality was highest in the first few days post-event, with 50% of patients dying in 255 days and average survival being 884 ± 90 days. Both NIHSS and modified ICH (MICH) score showed to be strong and reliable predictors of short- as well as long-term mortality; the risk of death post-ICH increased with older age and size of ICH. Other risk factors contributing to higher, primarily shorter-term mortality included history of cardiac failure, myocardial infarction, or atrial fibrillation. CONCLUSIONS: In our community-based study, we found that severity of neurological deficit at admission (NIHSS), combined with age and size of ICH, well predicted short- as well as long-term mortality after spontaneous ICH. A history of cardiac failure, myocardial infarction, or atrial fibrillation at presentation were also predictors of mortality, underscoring the need for optimal cardiac management in patients with ICH.

• MeSH
• cerebrální krvácení * mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rizikové faktory 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
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

The safety and efficacy of intravenous thrombolysis (IVT) are well established in anterior circulation stroke (ACS) but are much less clear for posterior circulation stroke (PCS). The aim of this study was to evaluate the occurrence of parenchymal hematoma (PH) and 3-month clinical outcomes after IVT in PCS and ACS. In an observational, cohort multicenter study, we analyzed data from ischemic stroke patients treated with IVT prospectively collected in the SITS (Safe Implementation of Treatments in Stroke) registry in the Czech Republic between 2004 and 2018. Out of 10,211 patients, 1166 (11.4%) had PCS, and 9045 (88.6%) ACS. PH was less frequent in PCS versus ACS patients: 3.6 vs. 5.9%, odds ratio (OR) = 0.594 in the whole set, 4.4 vs. 7.8%, OR = 0.543 in those with large vessel occlusion (LVO), and 2.2 vs. 4.7%, OR = 0.463 in those without LVO. At 3 months, PCS patients compared with ACS patients achieved more frequently excellent clinical outcomes (modified Rankin scale [mRS] 0-1: 55.5 vs. 47.6%, OR = 1.371 in the whole set and 49.2 vs. 37.6%, OR = 1.307 in those with LVO), good clinical outcomes (mRS 0-2: 69.9 vs. 62.8%, OR = 1.377 in the whole set and 64.5 vs. 50.5%, OR = 1.279 in those with LVO), and had lower mortality (12.4 vs. 16.6%, OR = 0.716 in the whole set and 18.4 vs. 25.5%, OR = 0.723 in those with LVO) (p < 0.05 in all cases). In PCS versus ACS patients, an extensive analysis showed a lower risk of PH both in patients with and without LVO, more frequent excellent and good clinical outcomes, and lower mortality 3 months after IVT in patients with LVO.

• Publikační typ
• časopisecké články MeSH

The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which in aging and Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions of the involved tissues, the CSF abnormalities reported in these conditions are suggestive of ChP injury. Indeed, several studies document ChP damage in aging and AD, which nevertheless remains to be systematically characterized. We here report that the changes elicited in the CSF by AD are consistent with a perturbed aging process and accompanied by aberrant accumulation of inflammatory signals and metabolically active proteins in the ChP. Magnetic resonance imaging (MRI) imaging shows that these molecular aberrancies correspond to significant remodeling of ChP in AD, which correlates with aging and cognitive decline. Collectively, our preliminary post-mortem and in vivo findings reveal a repertoire of ChP pathologies indicative of its dysfunction and involvement in the pathogenesis of AD. HIGHLIGHTS: Cerebrospinal fluid changes associated with aging are perturbed in Alzheimer's disease Paradoxically, in Alzheimer's disease, the choroid plexus exhibits increased cytokine levels without evidence of inflammatory activation or infiltrates In Alzheimer's disease, increased choroid plexus volumes correlate with age and cognitive performance.

• MeSH
• Alzheimerova nemoc * patologie   MeSH
• lidé MeSH
• plexus chorioideus metabolismus   patologie   MeSH
• proteomika MeSH
• stárnutí MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND AND OBJECTIVE: Short- and long-term mortality following ischemic stroke (IS) and their predictors have not been defined in the Czech population, and studies on long-term mortality are largely missing for the populations of Central Europe. METHODS: Using the National Register of Hospitalized Patients and the Czech National Mortality Registry, we analyzed data on 1-month, 1-year, and 3-year all-cause mortality for patients admitted with IS to any of the 4 hospitals with a certified stroke unit in Brno, Czech Republic, in 2011. We reviewed discharge summaries and recorded potential factors impacting mortality after the index stroke event. Using univariate and multivariable analyses, we identified predictors of mortality at all 3 time points. RESULTS: In our multivariable model, statin use (odds ratio [OR] 0.095, p < 0.0001), age at stroke (OR 1.03, p = 0.0445), and admission National Institutes of Health Stroke Scale (NIHSS) score (OR 1.16, p < 0.0001) predicted 1-month mortality, while statin use (OR 0.43, p = 0.0004), history of cardiac failure (OR 2.17, p = 0.0137), age at stroke (OR 1.07, p < 0.0001), and admission NIHSS score (OR 1.14, p < 0.0001) predicted 1-year mortality. Statin use (OR 0.54, p = 0.0051), history of cardiac failure (OR 2.13, p = 0.0206), age at stroke (OR 1.07, p < 0.0001), and admission NIHSS score (OR 1.11, p < 0.0001) also predicted 3-year mortality. CONCLUSIONS: Our study is the first to report data on short- and long-term mortality rates and their predictors in patients hospitalized with IS in the Czech population. Our results indicate that mortality rates and predictors of mortality are consistent with those reported in studies from other populations throughout the world.

• MeSH
• cévní mozková příhoda * diagnóza   epidemiologie   terapie   MeSH
• ischemická cévní mozková příhoda * MeSH
• ischemie mozku * komplikace   diagnóza   terapie   MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• srdeční selhání * komplikace   MeSH
• statiny * MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Medical cannabis has recently been legalized in many countries, and it is currently prescribed with increasing frequency, particularly for treatment of chronic pain resistant to conventional therapy. The psychoactive substance delta-9-tetrahydro-cannabinol (THC) contained in cannabis may affect driving abilities. Therefore, the aims of this study (open-label, monocentric, nonrandomized) were to evaluate blood and saliva concentrations of THC after oral administration of medical cannabis and to assess the time needed for THC levels to decline below a value ensuring legal driving. The study involved 20 patients with documented chronic pain using long-term medical cannabis therapy. They were divided into two groups and treated with two different doses of cannabis in the form of gelatin capsules (62.5 mg or 125 mg). In all patients, the amount of THC was assessed in saliva and in blood at pre-defined time intervals before and after administration. THC levels in saliva were detected at zero in all subjects following administration of both doses at all-time intervals after administration. Assessment of THC levels in blood, however, showed positive findings in one subject 9 h after administration of the lower dose and in one patient who had been given a higher dose 7 h after administration. Our finding suggested that for an unaffected ability to drive, at least 9-10 h should elapse from the last cannabis use.

• MeSH
• agonisté kanabinoidních receptorů MeSH
• aplikace orální MeSH
• Cannabis * MeSH
• chronická bolest * MeSH
• lidé MeSH
• marihuana pro léčebné účely * MeSH
• sliny MeSH
• tetrahydrokanabinol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH

Background The benefit of intravenous thrombolysis is time dependent. It remains unclear, however, whether dramatic shortening of door-to-needle time (DNT) among different types of hospitals nationwide does not compromise safety and still improves outcome. Methods and Results Multifaceted intervention to shorten DNT was introduced at a national level, and prospectively collected data from a registry between 2004 and 2019 were analyzed. Generalized estimating equation was used to identify the association between DNT and outcomes independently from prespecified baseline variables. The primary outcome was modified Rankin score 0 to 1 at 3 months, and secondary outcomes were parenchymal hemorrhage/intracerebral hemorrhage (ICH), any ICH, and death. Of 31 316 patients treated with intravenous thrombolysis alone, 18 861 (60%) had available data: age 70±13 years, National Institutes of Health Stroke Scale at baseline (median, 8; interquartile range, 5-14), and 45% men. DNT groups 0 to 20 minutes, 21 to 40 minutes, 41 to 60 minutes, and >60 minutes had 3536 (19%), 5333 (28%), 4856 (26%), and 5136 (27%) patients. National median DNT dropped from 74 minutes in 2004 to 22 minutes in 2019. Shorter DNT had proportional benefit: it increased the odds of achieving modified Rankin score 0 to 1 and decreased the odds of parenchymal hemorrhage/ICH, any ICH, and mortality. Patients with DNT ≤20 minutes, 21 to 40 minutes, and 41 to 60 minutes as compared with DNT >60 minutes had adjusted odds ratios for modified Rankin score 0 to 1 of the following: 1.30 (95% CI, 1.12-1.51), 1.33 (95% CI, 1.15-1.54), and 1.15 (95% CI, 1.02-1.29), and for parenchymal hemorrhage/ICH: 0.57 (95% CI, 0.45-0.71), 0.76 (95% CI, 0.61-0.94), 0.83 (95% CI, 0.70-0.99), respectively. Conclusions Ultrashort initiation of thrombolysis is feasible, improves outcome, and makes treatments safer because of fewer intracerebral hemorrhages. Stroke management should be optimized to initiate thrombolysis as soon as possible optimally within 20 minutes from arrival to a hospital.

• MeSH
• cerebrální krvácení komplikace   MeSH
• cévní mozková příhoda * terapie   MeSH
• fibrinolytika škodlivé účinky   MeSH
• intravenózní podání MeSH
• ischemie mozku * komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tkáňový aktivátor plazminogenu MeSH
• trombolytická terapie škodlivé účinky   metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

(1) Background: Computer tomography (CT) is an imaging modality used in the pre-planning of radiofrequency catheter ablation (RFA) procedure in patients with cardiac arrhythmias. However, it is associated with a considerable ionizing radiation dose for patients. This study aims to develop and validate low-dose CT scanning protocols of the left atrium (LA) for RFA guidance. (2) Methods: 68 patients scheduled for RFA of atrial fibrillation were sequentially assigned to four groups of ECG-gated scanning protocols, based on the set tube current (TC): Group A (n = 20, TC = 33 mAs), Group B (n = 18, TC = 67 mAs), Group C (n = 10, TC = 135 mAs), and control Group D (n = 20, TC = 600 mAs). We used a 256-row multidetector CT with body weight-dependent tube voltage of 80 kVp (<70 kg), 100 kVp (70-90 kg), and 120 kVp (>90 kg). We evaluated scanning parameters including radiation dose, total scanning procedure time and signal-to-noise ratio (SNR). (3) Results: The average effective radiation dose (ED) was lower in Group A in comparison to Group B, C and D (0.83 (0.76-1.10), 1.55 (1.36-1.67), 2.91 (2.32-2.96) and 9.35 (8.00-10.04) mSv, p < 0.05). The total amount of contrast media was not significantly different between groups. The mean SNR was 6.5 (5.8-7.3), 7.1 (5.7-8.2), 10.8 (10.1-11.3), and 12.2 (9.9-15.7) for Group A, B, C and D, respectively. The comparisons of SNR in group A vs. B and C vs. D were without significant differences. (4) Conclusions: Optimized pre-ablation CT scanning protocols of the LA can reduce an average ED by 88.7%. Three dimensional (3D) models created with the lowest radiation protocol are useful for the integration of electro-anatomic-guided RFA procedures.

• Publikační typ
• časopisecké články MeSH

The selection of the best embryo for embryo transfer (ET) is one of the most important steps in IVF (in vitro fertilisation) treatment. Preimplantation genetic testing (PGT) is an invasive method that can greatly facilitate the decision about the best embryo. An alternative way to select the embryo with the greatest implantation potential is by cultivation in a time-lapse system, which can offer several predictive factors. Non-invasive time-lapse monitoring can be used to select quality embryos with high implantation potential under stable culture conditions. The embryo for ET can then be selected based on the determined morphokinetic parameters and morphological features, which according to our results predict a higher implantation potential. This study included a total of 1027 morphologically high-quality embryos (552 normal and 475 abnormal PGT-tested embryos) from 296 patients (01/2016-06/2021). All embryos were cultivated in a time-lapse incubator and PGT biopsy of trophectoderm cells on D5 or D6 was performed. Significant differences were found in the morphological parameters cc2, t5 and tSB and the occurrence of multinucleations in the stage of two-cell and four-cell embryos between the group of genetically normal embryos and abnormal embryos. At the same time, significant differences in the morphological parameters cc2, t5 and tSB and the occurrence of multinucleations in the two-cell and four-cell embryo stage were found between the group of genetically normal embryos that led to clinical pregnancy after ET and the group of abnormal embryos. From the morphokinetic data found in the PGT-A group of normal embryos leading to clinical pregnancy, time intervals were determined based on statistical analysis, which should predict embryos with high implantation potential. Out of a total of 218 euploid embryos, which were transferred into the uterus after thawing (single frozen embryo transfer), clinical pregnancy was confirmed in 119 embryos (54.6%). Our results show that according to the morphokinetic parameters (cc2, t5, tSB) and the occurrence of multinucleations during the first two cell divisions, the best euploid embryo for ET can be selected with high probability.

• Publikační typ
• časopisecké články MeSH

Canine non-infectious inflammatory meningoencephalomyelitis is termed meningoencephalomyelitis of unknown origin (MUO) and may affect dogs of every breed at any age. Treatment with immunosuppressive medication, the survival time based on MRI, and cerebrospinal fluid (CSF) findings has been widely reported; however, these studies only included a small number of patients, or they are summaries from the literature. Therefore, the aim of this study was to compare the clinical presentation, diagnostic findings, treatment protocol and long-term survival time in many dogs diagnosed with MUO in one clinic with previously published studies. One hundred eighty-two dogs met the inclusion criteria. Age, sex, duration of clinical signs before diagnosis, presence of neurological signs, MRI and CSF analysis were similar to those in previous reports. Our study revealed that dogs with a brainstem lesion have a 60% lower chance of death before 1 year than dogs with multifocal brain lesions. A total of 55.56% of treated dogs survived for more than 1 year, and 10.55% survived for more than 5 years since diagnosis. The median survival time for all dogs was 540 days. Our findings support glucocorticosteroid monotherapy as a viable treatment option for dogs with MUO.

• MeSH
• magnetická rezonanční tomografie veterinární   MeSH
• meningoencefalitida * diagnóza   farmakoterapie   veterinární   MeSH
• nemoci psů * diagnóza   farmakoterapie   MeSH
• psi MeSH
• zvířata MeSH
• Check Tag
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

Achondroplasia is the most prevalent genetic form of dwarfism in humans and is caused by activating mutations in FGFR3 tyrosine kinase. The clinical need for a safe and effective inhibitor of FGFR3 is unmet, leaving achondroplasia currently incurable. Here, we evaluated RBM-007, an RNA aptamer previously developed to neutralize the FGFR3 ligand FGF2, for its activity against FGFR3. In cultured rat chondrocytes or mouse embryonal tibia organ culture, RBM-007 rescued the proliferation arrest, degradation of cartilaginous extracellular matrix, premature senescence, and impaired hypertrophic differentiation induced by FGFR3 signaling. In cartilage xenografts derived from induced pluripotent stem cells from individuals with achondroplasia, RBM-007 rescued impaired chondrocyte differentiation and maturation. When delivered by subcutaneous injection, RBM-007 restored defective skeletal growth in a mouse model of achondroplasia. We thus demonstrate a ligand-trap concept of targeting the cartilage FGFR3 and delineate a potential therapeutic approach for achondroplasia and other FGFR3-related skeletal dysplasias.

• MeSH
• achondroplazie * farmakoterapie   genetika   MeSH
• aptamery nukleotidové * MeSH
• buněčná diferenciace MeSH
• chondrocyty MeSH
• krysa rodu rattus MeSH
• myši MeSH
• receptor fibroblastových růstových faktorů, typ 3 genetika   MeSH
• vývoj kostí MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH