Spontánní intracerebrální hemoragie (SICH) jsou spojeny s řadou rizikových faktorů, které můžeme rozdělit na faktory ovlivnitelné a neovlivnitelné. Jejich nejvýznamnějším rizikovým faktorem je arteriální hypertenze. Péče o pacienty se SICH musí být komplexní a multidisciplinární. V akutní fázi se stává imperativem snaha o co nejrychlejší korekci arteriální hypertenze a zvrácení účinku antikoagulační terapie. Do budoucna lze recentně očekávat dosažení lepšího výsledného klinického stavu u vybraných pacientů se supratentoriální (především lobární) SICH operovaných do 24 h s využitím minimálně invazivní parafascikulární chirurgie.

Spontaneous intracerebral hemorrhages (SICH) are associated with a number of risk factors, which can be divided into controllable and uncontrollable factors. Their most important risk factor is arterial hypertension. The care for patients with SICH must be complex and multidisciplinary. In the acute phase, it becomes imperative to try to correct arterial hypertension and reverse the effect of anticoagulant therapy as quickly as possible. In the future, a better clinical outcome can recently be expected in selected patients with supratentorial (mainly lobar) SICH operated on within 24 h using minimally invasive parafascicular surgery.

• Klíčová slova
• spontánní intracerebrální hemoragie,
• MeSH
• antikoagulancia škodlivé účinky   terapeutické užití   MeSH
• cévní mozková příhoda diagnóza   etiologie   farmakoterapie   klasifikace   MeSH
• hypertenze diagnóza   klasifikace   komplikace   MeSH
• intrakraniální krvácení * diagnóza   farmakoterapie   prevence a kontrola   MeSH
• lidé MeSH
• management nemoci MeSH
• miniinvazivní chirurgické výkony klasifikace   metody   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Hypertenze, tedy zvýšení krevního tlaku nad 140/90 mm Hg, je spojena s poškozením řady orgánů. Mezi cílové orgány hypertenze patří i mozek. Klinické projevy zahrnují hypertenzní encefalopatii, syndrom reverzibilní encefalopatie v zadním povodí a cévní mozkové příhody. Chronická hypertenze se podílí na strukturálních a funkční změnách mozkové tkáně, které mohou vyústit v klinicky manifestní postižení kognitivních funkcí a rozvoj demence. Patofyziologický podklad hypertenzí navozeného postižení mozku je komplexní. Časný záchyt hypertenze a její adekvátní léčba jsou klíčové pro snižování rizika vzniku neurologických komplikací.

Hypertension, defined as an increase in blood pressure above 140/90 mmHg, is associa­ted with damage to a number of organs, including the brain. Clinical manifestations include hypertensive encephalopathy, posterior reversible encephalopathy syndrome, and cerebrovascular accidents. Chronic hypertension contributes to structural and functional changes in brain tissue, which can lead to clinically manifest impairment of cognitive functions and the development of dementia. The pathophysiological basis of brain damage induced by hypertension is complex. Early detection of hypertension and its adequate treatment are crucial for reducing the risk of neurological complications.

• MeSH
• antihypertenziva farmakologie   terapeutické užití   MeSH
• cévní mozková příhoda etiologie   farmakoterapie   prevence a kontrola   MeSH
• eklampsie MeSH
• epilepsie etiologie   MeSH
• homeostáza fyziologie   MeSH
• hypertenze * komplikace   patofyziologie   MeSH
• hypertenzní encefalopatie etiologie   MeSH
• kognitivní poruchy etiologie   MeSH
• lidé MeSH
• nemoci mozku * etiologie   MeSH
• syndrom zadní leukoencefalopatie etiologie   MeSH
• Check Tag
• lidé MeSH

• Klíčová slova
• semaglutid,
• MeSH
• cévní mozková příhoda * diagnóza   epidemiologie   farmakoterapie   prevence a kontrola   MeSH
• diabetes mellitus 2. typu farmakoterapie   komplikace   MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• receptor pro glukagonu podobný peptid 1 * agonisté   klasifikace   terapeutické užití   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH

Intravenous thrombolysis with a recombinant tissue plasminogen activator (rt-PA) is the first-line treatment of acute ischemic stroke. However, successful recanalization is relatively low and the underlying processes are not completely understood. The goal was to provide insights into clinically important factors potentially limiting rt-PA efficacy such as clot size, rt-PA concentration, clot age and also rt-PA in combination with heparin anticoagulant. We established a static in vitro thrombolytic model based on red blood cell (RBC) dominant clots prepared using spontaneous clotting from the blood of healthy donors. Thrombolysis was determined by clot mass loss and by RBC release. The rt-PA became increasingly less efficient for clots larger than 50 μl at a clinically relevant concentration of 1.3 mg/l. A tenfold decrease or increase in concentration induced only a 2-fold decrease or increase in clot degradation. Clot age did not affect rt-PA-induced thrombolysis but 2-hours-old clots were degraded more readily due to higher activity of spontaneous thrombolysis, as compared to 5-hours-old clots. Finally, heparin (50 and 100 IU/ml) did not influence the rt-PA-induced thrombolysis. Our study provided in vitro evidence for a clot size threshold: clots larger than 50 μl are hard to degrade by rt-PA. Increasing rt-PA concentration provided limited thrombolytic efficacy improvement, whereas heparin addition had no effect. However, the higher susceptibility of younger clots to thrombolysis may prompt a shortened time from the onset of stroke to rt-PA treatment.

• MeSH
• cévní mozková příhoda farmakoterapie   MeSH
• erytrocyty účinky léků   metabolismus   MeSH
• fibrinolytika terapeutické užití   MeSH
• hemokoagulace účinky léků   MeSH
• heparin * terapeutické užití   MeSH
• ischemická cévní mozková příhoda * farmakoterapie   MeSH
• lidé MeSH
• rekombinantní proteiny * terapeutické užití   MeSH
• tkáňový aktivátor plazminogenu * terapeutické užití   MeSH
• trombolytická terapie * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: We analysed outcomes of patients who received off-label repeated thrombolysis with recombinant tissue plasminogen activator for ischemic stroke recurrence within 10 days (ultraearly repeated thrombolysis, UERT). METHOD: We identified patients receiving UERT from the prospective telestroke network of South-East Bavaria (TEMPiS) registry and by database search (Pubmed, Google scholar). Corresponding authors were contacted for further details. Baseline demographic data and clinical, laboratory, and imaging findings were analysed in a multicentric case study. RESULTS: Sixteen patients receiving UERT were identified. The median time between first and second thrombolysis was 3.5 days. In patients with available data, second thrombolysis achieved an early clinical improvement (NIHSS reduction ≥4 points) in 12 of 14 (85.7%) and a favourable outcome (mRS 0-2 after 3 months) in 11 of 16 (68.8%) patients. Intracerebral haemorrhage (ICH) occurred in 4 patients (25.0%) with one fatal large parenchymatous haemorrhage (6.3%). Neither allergic reactions nor other immunoreactive events were observed. CONCLUSIONS: In our analysis UERT led to early clinical improvement and a favourable clinical outcome in a high percentage of patients with ICH rates comparable to prior publications. UERT might be considered in patients with early recurrent stroke under careful risk-benefit assessment.

• MeSH
• cerebrální krvácení etiologie   MeSH
• cévní mozková příhoda * diagnostické zobrazování   farmakoterapie   MeSH
• fibrinolytika terapeutické užití   MeSH
• ischemická cévní mozková příhoda * farmakoterapie   MeSH
• ischemie mozku * diagnostické zobrazování   farmakoterapie   MeSH
• lidé MeSH
• prospektivní studie MeSH
• tkáňový aktivátor plazminogenu terapeutické užití   MeSH
• trombolytická terapie metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

Despite advances in acute care, ischemic stroke remains a major cause of long-term disability. Approaches targeting both neuronal and glial responses are needed to enhance recovery and improve long-term outcome. The complement C3a receptor (C3aR) is a regulator of inflammation with roles in neurodevelopment, neural plasticity, and neurodegeneration. Using mice lacking C3aR (C3aR-/-) and mice overexpressing C3a in the brain, we uncovered 2 opposing effects of C3aR signaling on functional recovery after ischemic stroke: inhibition in the acute phase and facilitation in the later phase. Peri-infarct astrocyte reactivity was increased and density of microglia reduced in C3aR-/- mice; C3a overexpression led to the opposite effects. Pharmacological treatment of wild-type mice with intranasal C3a starting 7 days after stroke accelerated recovery of motor function and attenuated astrocyte reactivity without enhancing microgliosis. C3a treatment stimulated global white matter reorganization, increased peri-infarct structural connectivity, and upregulated Igf1 and Thbs4 in the peri-infarct cortex. Thus, C3a treatment from day 7 after stroke exerts positive effects on astrocytes and neuronal connectivity while avoiding the deleterious consequences of C3aR signaling during the acute phase. Intranasal administration of C3aR agonists within a convenient time window holds translational promise to improve outcome after ischemic stroke.

• MeSH
• astrocyty MeSH
• cévní mozková příhoda * farmakoterapie   genetika   MeSH
• infarkt MeSH
• ischemická cévní mozková příhoda * MeSH
• komplement C3a genetika   MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Statins have an important role in stroke prevention, especially in high-risk populations and may also affect the initial stroke severity and outcomes in patients taking them before an ischemic stroke. AIMS: Our aim was to evaluate the association of statin pre-treatment with the severity in acute ischemic stroke (AIS). METHODS: We analyzed AIS patients received intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT) and recorded in the SITS International Thrombolysis and Thrombectomy Registry from 2011 to 2017. We identified patients with statin information at baseline. The primary outcome was baseline National Institutes of Health Stroke Scale (NIHSS) score. Secondary outcomes were NIHSS score at 24 h, symptomatic intracerebral hemorrhage (SICH) and functional outcome at 90 days after acute intervention. Multivariable linear and logistic regression and propensity score matching (PSM) was used to quantify the effect of statin pre-treatment. RESULTS: Of 93,849 patients, 23,651 (25.2%) were treated with statins prior the AIS. Statin pre-treatment group was older and had higher comorbidity. Median NIHSS at baseline was similar between groups. In the adjusted and PSM analysis, statin pre-treatment was inversely associated with baseline NIHSS (odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.6-0.99 and OR for PSM 0.73, 95% CI = 0.54-0.99, p = 0.004) and independently associated with mild stroke defined as NIHSS ⩽8 in adjusted and PSM analysis (OR = 1.21, 95% CI = 1.1-1.34, p < 0.001 and OR for PSM 1.17, 95% CI = 1.05-1.31, p = 0.007). Regarding secondary outcomes, there were no differences in functional outcomes, death nor SICH rates between groups. CONCLUSION: Prior treatment with statins was associated with lower NIHSS at baseline. However, this association did not translate into any difference regarding functional outcome at 90 days. No association was found regarding SICH. These findings indicate the need of further studies to assess the effect on statin pre-treatment on initial stroke severity.

• MeSH
• cerebrální krvácení komplikace   MeSH
• cévní mozková příhoda * farmakoterapie   komplikace   MeSH
• endovaskulární výkony * MeSH
• ischemická cévní mozková příhoda * farmakoterapie   MeSH
• ischemie mozku * farmakoterapie   komplikace   MeSH
• lidé MeSH
• statiny * terapeutické užití   škodlivé účinky   MeSH
• trombolytická terapie škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

Společným nedostatkem dosud užívaných antikoagulancií inhibitorů trombinu, inhibitorů faktoru Xa či antivitaminů K je zvýšené riziko klinicky významného krvácení. To se napříč lékovými skupinami, napříč indikacemi pohybuje mezi 1 a 3 % ročně. Nepřekvapuje tedy snaha o snížení rizika krvácení při zachování antitrombotického účinku. V posledních letech se objevuje výrazný pokrok v oblasti inhibitorů vnitřní cesty koagulační kaskády. Tato strategie je slibná, neboť k nejčastějším indikacím antikoagulancií patří aktivace hemostázy kontaktem (navozená např. polyfosfáty na povrchu aktivovaných trombocytů či kontaktem s umělým povrchem) či reparačně zánětlivými pochody (zejm. vlákny extracelulárně uvolněné deoxyribonukleové kyseliny [DNA] z neutrofilních leukocytů [neutrofilní extracelulární pasti, neutrophil extracellular trap, NET] či řadou cytokinů). Podmínkou aktivace této vnitřní cesty koagulace je stagnace krve umožňující dosažení účinné lokální koncentrace enzymů koagulační kaskády. Těmto podmínkám odpovídají dvě nejčastější indikace antikoagulační léčby fibrilace síní či tromboembolická nemoc. Zachování aktivní vnější cesty koagulace pak umožní účinnou hemostázu při poškození cévní stěny. V inhibici této vnitřní cesty koagulace je v pokročilé fázi klinického hodnocení řada inhibitorů faktoru XI/XIa na bázi klasických malomolekulárních léčiv (např. asundexian, milvexian), monoklonálních protilátek (např. abelacimab, osocimab) či oligonukleotidů inhibujících syntézu faktoru XI (např. fesomersen). Klinické hodnocení probíhá v rámci profylaxe tromboembolické nemoci, v rámci prevence tromboembolických příhod při fibrilaci síní či v indikaci sekundární prevence po infarktu myokardu či cévní mozkové příhodě.

A common deficiency of the anticoagulants used so far thrombin inhibitors, factor Xa inhibitors or anti-vitamins K is an increased risk of clinically significant bleeding. This varies between 1 and 3% per year across drug groups, across indications. It is therefore not surprising that efforts are being made to reduce the risk of bleeding while maintaining antithrombotic effect. In recent years, there have been significant advances in the field of inhibitors of the intrinsic coagulation cascade. This strategy is promising as the most common indications for anticoagulants include activation of haemostasis by contact (e.g. induced by polyphosphates on the surface of activated platelets or by contact with an artificial surface) or reparative-inflammatory processes (in particular, by filaments of extracellularly released deoxyribonucleic acid [DNA] from neutrophil leukocytes [neutrophil extracellular trap, NET] or by a number of cytokines). A prerequisite for activation of this intrinsic pathway of coagulation is blood stagnation allowing an effective local concentration of the enzymes of the coagulation cascade to be achieved. The two most common indications for anticoagulation therapy, atrial fibrillation or thromboembolic disease, correspond to these conditions. Preservation of an active extrinsic pathway of coagulation then allows effective haemostasis in the presence of vascular wall damage. To inhibit this intrinsic pathway of coagulation, a number of factor XI/XIa inhibitors based on classical small molecule drugs (e.g. asundexian, milvexian), monoclonal antibodies (e.g. abelacimab, osocimab) or oligonucleotides inhibiting factor XI synthesis (e.g. fesomersen) are in advanced clinical trials. Clinical trials are underway for the prophylaxis of thromboembolic disease, for the prevention of thromboembolic events in atrial fibrillation or for the indication of secondary prevention after myocardial infarction or stroke.

• MeSH
• antikoagulancia * farmakologie   škodlivé účinky   terapeutické užití   MeSH
• cévní mozková příhoda farmakoterapie   prevence a kontrola   MeSH
• fibrilace síní farmakoterapie   komplikace   MeSH
• inhibitory faktoru Xa farmakologie   terapeutické užití   MeSH
• lidé MeSH
• trombóza farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Direct oral anticoagulants (DOACs) are increasingly used and are an important cornerstone in antithrombotic therapy. Adverse drug reactions (ADRs) such as bleedings have only partially been investigated during clinical trials. The primary goal was to analyse pharmacovigilance data based on spontaneous reports of gastrointestinal (GI) bleedings with DOACs reported to EudraVigilance. A second goal was to compare GI safety profiles between DOACs based on these signals. All DOAC related GI bleedings mentioned in individual case safety reports (ICSRs) from 2012 till 2017 in the European Economic Area were classified in four GI categories based on the reported site of occurrence of the haemorrhage. Age group and gender of the patient, seriousness and ADR outcome, and the reporter's qualification were assessed per category and per DOAC. Disproportionality analyses were performed to evaluate whether or not the reported ADRs were more prevalent with a given DOAC. ICSRs were bleeding-related in about half of the cases (n = 28,992/53,471). Of these bleedings, >25% was GI-related. Most patients experiencing GI bleedings were between 65 and 85 years old, with no obvious differences between men and women. Stomach, ulcer-related duodenal, and rectal bleedings were the most reported GI bleedings with a fatal outcome in 5.8%, 7.5%, and 9.8% of the cases for rivaroxaban, apixaban, and dabigatran, respectively. The disproportionality data suggest that dabigatran is more frequently involved in GI bleeding events than the other DOACs. DOACs were significantly associated with GI bleedings. Although the data should be interpreted with caution, it seems that dabigatran was associated more often than other DOACs with GI bleedings based on the analysis of spontaneous pharmacovigilance reports.

• MeSH
• antikoagulancia škodlivé účinky   MeSH
• aplikace orální MeSH
• cévní mozková příhoda * farmakoterapie   MeSH
• dabigatran škodlivé účinky   MeSH
• fibrilace síní * farmakoterapie   MeSH
• gastrointestinální krvácení chemicky indukované   epidemiologie   farmakoterapie   MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rivaroxaban škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

IMPORTANCE: Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety. OBJECTIVE: To determine whether excluding aspirin as part of the antithrombotic regimen with a fully magnetically levitated LVAD is safe and decreases bleeding. DESIGN, SETTING, AND PARTICIPANTS: This international, randomized, double-blind, placebo-controlled study of aspirin (100 mg/d) vs placebo with VKA therapy in patients with advanced heart failure with an LVAD was conducted across 51 centers with expertise in treating patients with advanced heart failure across 9 countries. The randomized population included 628 patients with advanced heart failure implanted with a fully magnetically levitated LVAD (314 in the placebo group and 314 in the aspirin group), of whom 296 patients in the placebo group and 293 in the aspirin group were in the primary analysis population, which informed the primary end point analysis. The study enrolled patients from July 2020 to September 2022; median follow-up was 14 months. INTERVENTION: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg/d) or placebo in addition to an antithrombotic regimen. MAIN OUTCOMES AND MEASURES: The composite primary end point, assessed for noninferiority (-10% margin) of placebo, was survival free of a major nonsurgical (>14 days after implant) hemocompatibility-related adverse events (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months. The principal secondary end point was nonsurgical bleeding events. RESULTS: Of the 589 analyzed patients, 77% were men; one-third were Black and 61% were White. More patients were alive and free of hemocompatibility events at 12 months in the placebo group (74%) vs those taking aspirin (68%). Noninferiority of placebo was demonstrated (absolute between-group difference, 6.0% improvement in event-free survival with placebo [lower 1-sided 97.5% CI, -1.6%]; P < .001). Aspirin avoidance was associated with reduced nonsurgical bleeding events (relative risk, 0.66 [95% confidence limit, 0.51-0.85]; P = .002) with no increase in stroke or other thromboembolic events, a finding consistent among diverse subgroups of patient characteristics. CONCLUSIONS AND RELEVANCE: In patients with advanced heart failure treated with a fully magnetically levitated LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes VKA, is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069156.

• MeSH
• Aspirin škodlivé účinky   MeSH
• cévní mozková příhoda * etiologie   prevence a kontrola   farmakoterapie   MeSH
• dvojitá slepá metoda MeSH
• fibrinolytika škodlivé účinky   MeSH
• inhibitory agregace trombocytů škodlivé účinky   MeSH
• krvácení etiologie   MeSH
• lidé MeSH
• podpůrné srdeční systémy * škodlivé účinky   MeSH
• srdeční selhání * patofyziologie   MeSH
• tromboembolie * etiologie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH
• práce podpořená grantem MeSH