INTRODUCTION: Various analgesics are used to control intense headaches in patients following subarachnoid hemorrhage. In addition to pain control, it has been shown that some analgesics can affect various pathophysiological cascades. Therefore, we devised a study to assess whether the use of metamizole has a significant impact on the development of ischemic complications, hydrocephalus, and the overall outcome in patients following aneurysmal subarachnoid hemorrhage in the context of the other non-opioids and opioids effects. METHODS: In our retrospective, single-center cohort study, we enrolled 192 patients diagnosed with subarachnoid hemorrhage. We recorded their initial clinical status, comorbidities, and the daily dosage of analgesics over 14 days of hospitalization after the onset of subarachnoid hemorrhage. Using univariate and subsequent multivariate logistic regression analysis, we assessed the influence of various factors, including analgesics, on the development of delayed cerebral ischemia and hydrocephalus, as well as on 2-week and 6-month outcomes. RESULTS: Although the administration of non-opioids, in general, had no effect on the development of delayed cerebral ischemia or hydrocephalus, the use of metamizole as the main analgesic was associated with a significantly lower chance of poor outcome at both 2-weeks and 6-months, as well as the development of delayed cerebral ischemia. As opioids were indicated primarily for analgosedation in mechanically ventilated patients with poor clinical status, their usage was associated with a significantly higher chance of poor outcome, delayed cerebral ischemia, and hydrocephalus. CONCLUSION: Our results suggest that the prescription of metamizole may be associated with better outcomes and a lower chance of delayed cerebral ischemia development in patients after subarachnoid hemorrhage. Considering the retrospective nature of our study and the limited worldwide availability of metamizole due to its prohibition in some countries, our results do not demonstrate a clear benefit but rather justify the need for subsequent prospective studies.

• MeSH
• analgetika terapeutické užití   aplikace a dávkování   MeSH
• antiflogistika nesteroidní * terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• hydrocefalus etiologie   MeSH
• ischemie mozku farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metamizol * terapeutické užití   aplikace a dávkování   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• subarachnoidální krvácení * farmakoterapie   komplikace   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví 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

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

BACKGROUND: Asundexian (Bayer AG, Leverkusen, Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increasing bleeding. Asundexian's effect for secondary prevention of recurrent stroke is unknown. METHODS: In this randomised, double-blind, placebo-controlled, phase 2b dose-finding trial (PACIFIC-Stroke), patients with acute (within 48 h) non-cardioembolic ischaemic stroke were recruited from 196 hospitals in 23 countries. Patients were eligible if they were aged 45 years or older, to be treated with antiplatelet therapy, and able to have a baseline MRI (either before or within 72 h of randomisation). Eligible participants were randomly assigned (1:1:1:1), using an interactive web-based response system and stratified according to anticipated antiplatelet therapy (single vs dual), to once daily oral asundexian (BAY 2433334) 10 mg, 20 mg, or 50 mg, or placebo in addition to usual antiplatelet therapy, and were followed up during treatment for 26-52 weeks. Brain MRIs were obtained at study entry and at 26 weeks or as soon as possible after treatment discontinuation. The primary efficacy outcome was the dose-response effect on the composite of incident MRI-detected covert brain infarcts and recurrent symptomatic ischaemic stroke at or before 26 weeks after randomisation. The primary safety outcome was major or clinically relevant non-major bleeding as defined by International Society on Thrombosis and Haemostasis criteria. The efficacy outcome was assessed in all participants assigned to treatment, and the safety outcome was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04304508, and is now complete. FINDINGS: Between June 15, 2020, and July 22, 2021, 1880 patients were screened and 1808 participants were randomly assigned to asundexian 10 mg (n=455), 20 mg (n=450), or 50 mg (n=447), or placebo (n=456). Mean age was 67 years (SD 10) and 615 (34%) participants were women, 1193 (66%) were men, 1505 (83%) were White, and 268 (15%) were Asian. The mean time from index stroke to randomisation was 36 h (SD 10) and median baseline National Institutes of Health Stroke Scale score was 2·0 (IQR 1·0-4·0). 783 (43%) participants received dual antiplatelet treatment for a mean duration of 70·1 days (SD 113·4) after randomisation. At 26 weeks, the primary efficacy outcome was observed in 87 (19%) of 456 participants in the placebo group versus 86 (19%) of 455 in the asundexian 10 mg group (crude incidence ratio 0·99 [90% CI 0·79-1·24]), 99 (22%) of 450 in the asundexian 20 mg group (1·15 [0·93-1·43]), and 90 (20%) of 447 in the asundexian 50 mg group (1·06 [0·85-1·32]; t statistic -0·68; p=0·80). The primary safety outcome was observed in 11 (2%) of 452 participants in the placebo group versus 19 (4%) of 445 in the asundexian 10 mg group, 14 (3%) of 446 in the asundexian 20 mg group, and 19 (4%) of 443 in the asundexian 50 mg group (all asundexian doses pooled vs placebo hazard ratio 1·57 [90% CI 0·91-2·71]). INTERPRETATION: In this phase 2b trial, FXIa inhibition with asundexian did not reduce the composite of covert brain infarction or ischaemic stroke and did not increase the composite of major or clinically relevant non-major bleeding compared with placebo in patients with acute, non-cardioembolic ischaemic stroke. FUNDING: Bayer AG.

• MeSH
• antikoagulancia terapeutické užití   MeSH
• cévní mozková příhoda * farmakoterapie   prevence a kontrola   MeSH
• dvojitá slepá metoda MeSH
• faktor XIa MeSH
• inhibitory agregace trombocytů terapeutické užití   MeSH
• ischemická cévní mozková příhoda * MeSH
• ischemie mozku * farmakoterapie   prevence a kontrola   MeSH
• krvácení chemicky indukované   farmakoterapie   MeSH
• lidé MeSH
• senioři MeSH
• trombóza * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

INTRODUCTION: There are today two models of transporting patients with acute ischaemic stroke because of large artery occlusion (AIS-LVO): mothership (MS) and drip-and-ship (DS). Our aim was to evaluate our ongoing transport strategy (OT), which is an MS/DS hybrid. In our OT, the patient is transported directly to the CT of the Primary Stroke Centre (PSC), where intravenous thrombolysis (IVT) is administered. The patient then continues without delay to a Comprehensive Stroke Centre (CSC) with the same medical rescue team (MRT). The distance between our centres is 73 km. MATERIAL AND METHODS: We retrospectively analysed data of 100 consecutive AIS-LVO patients treated with mechanical thrombectomy (MT) between January 2017 and October 2019. OT, MS and DS groups were compared. 31 patients were transported as MS, 32 as DS, and 37 as OT. RESULTS: DS had significantly longer time to groin puncture (185 min) compared to OT and MS (p < 0.0001). OT shortened time almost to MS level (OT 124 min, MS 110 min, p = 0.002. Time to IVT administration (from MRT departure) differed statistically significantly in favour of OT (OT 27 min, MS 63 min, p < 0.0001). Logistical change in PSC had a significant effect on decreasing the door-to-needle time (DNT) median from 37 min to 11 min (p < 0.0001). DNT reduction also occurred in patients with AIS and without an indication for MT. CONCLUSIONS: OT is highly effective, significantly reducing the time to IVT administration, and combining all the benefits, while eliminating all the disadvantages, of DS and MS. The OT concept gives all indicated patients a chance for MT to be performed, and does not overload the performing centre.

• MeSH
• cévní mozková příhoda * farmakoterapie   etiologie   MeSH
• ischemická cévní mozková příhoda * MeSH
• ischemie mozku * farmakoterapie   MeSH
• lidé MeSH
• retrospektivní studie MeSH
• trombektomie škodlivé účinky   MeSH
• trombolytická terapie škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Intravenous thrombolysis (IVT) is a standard treatment for both anterior circulation ischaemic stroke (ACIS) and posterior circulation ischaemic stroke (PCIS). Our aim was to evaluate the predictors for a good clinical outcome and intracerebral haemorrhage (ICH) in patients undergoing posterior circulation IVT based on the initially performed CT or MR imaging. METHODS: The study cohort consisted of 1643 consecutive patients with acute ischaemic stroke (1440 ACIS, 203 PCIS cases) who underwent IVT. ICH was classified according to the European Cooperative Acute Stroke Study (ECASS) I protocol. Clinical outcome was assessed using the modified Rankin scale (mRS). Early ischaemic signs and pre-existing structural signs were assessed. RESULTS: Good clinical outcomes (mRS 0-1) were noted in 45.3% of patients with PCIS, with a mortality rate of 14.8%. ICH was noted in 8.3%, and a large haemorrhage was found in 2.4% of patients. Some early ischaemic signs and pre-existing structural signs on initial CT/MR imaging correlated significantly with the 90-day clinical outcome. CONCLUSIONS: Early ischaemic signs and pre-existing structural signs should be considered during the assessment of patients with PCIS eligible for IVT. Tissue hypoattenuation on initial CT scans correlates with an increased risk of death. Similarly to anterior circulation, atrophy on initial MRI may negatively predict good clinical outcome in posterior circulation.

• MeSH
• cévní mozková příhoda * diagnostické zobrazování   farmakoterapie   MeSH
• fibrinolytika terapeutické užití   MeSH
• ischemie mozku * diagnostické zobrazování   farmakoterapie   MeSH
• lidé MeSH
• neurozobrazování MeSH
• tkáňový aktivátor plazminogenu terapeutické užití   MeSH
• trombolytická terapie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition associated with the development of early brain injury (EBI) and delayed cerebral ischemia (DCI). Pharmacological treatment of vasospasm following aSAH currently mainly comprises nimodipine administration. In the past few years, many drugs that can potentially benefit cases of subarachnoid hemorrhage have become available. The objective of this review is to critically assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) following aSAH. A systematic literature review was conducted following PRISMA guidelines. The search was aimed at studies addressing aSAH and NSAIDs during the 2010 to 2019 period, and it yielded 13 articles. Following the application of search criteria, they were divided into two groups, one containing 6 clinical articles and the other containing 7 experimental articles on animal models of aSAH. Inflammatory cerebral changes after aneurysm rupture contribute to the development of EBI, DCI and cerebral vasospasm. It appears that NSAIDs (especially coxibs) are even more effective in reducing vasospasm than nimodipine. Other beneficial effects of NSAIDs include reduction in mortality, improved functional outcome and increased hypoaggregability. However, despite these positive effects, there is only one randomized, double-blind, placebo-controlled trial showing a tendency towards a better outcome with lower incidence of vasospasm or mortality in patients following aSAH.

• MeSH
• antiflogistika nesteroidní terapeutické užití   MeSH
• dvojitá slepá metoda MeSH
• intrakraniální vazospazmus farmakoterapie   etiologie   patofyziologie   MeSH
• ischemie mozku farmakoterapie   etiologie   patofyziologie   MeSH
• lidé MeSH
• nimodipin terapeutické užití   MeSH
• randomizované kontrolované studie jako téma metody   MeSH
• subarachnoidální krvácení komplikace   farmakoterapie   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH

OBJECTIVE: To investigate the association of blood pressure BP excursions, defined as greater than 185 SBP or greater than 105 DBP, with the probability of intracranial hemorrhage (ICH) and worse functional outcomes in patients with acute ischemic stroke (AIS) treated with tissue plasminogen activator (tPA). METHODS: We performed a post hoc analysis of the CLOTBUST-ER trial. Serial BP measurements were conducted using automated cuff recording according to the recommended BP protocol guidelines for tPA administration. The outcomes were prespecified efficacy and safety endpoints of CLOTBUST-ER. RESULTS: The mean number of serial BP recordings per patient was 37. Of the 674 patients, 227 (34%) had at least one BP excursion (>185/105 mmHg) during the first 24 h following tPA-bolus. The majority of BP excursions (46%) occurred within the first 75 min from tPA-bolus. Patients with at least one BP excursion in the first 24 h following tPA bolus had significantly lower rates of independent functional outcome at 90 days (31 vs. 40.1%, P = 0.028). The total number of BP excursions was associated with decreased odds of 24-h clinical recovery (OR = 0.88, 95% CI:0.80-0.96), 24-h neurological improvement (OR = 0.87, 95% CI: 0.81-0.94), 7-day functional improvement (common OR = 0.92, 95% CI: 0.87-0.97), 90-day functional improvement (common OR = 0.94, 95% CI: 0.88-0.98) and 90-day independent functional outcome (OR = 0.90, 95% CI: 0.82-0.98) in analyses adjusted for potential confounders. DBP excursions were independently associated with increased odds of any intracranial hemorrhage (OR = 1.26, 95% CI: 1.04-1.53). CONCLUSION: BP excursions above guideline thresholds during the first 24 h following tPA administration for AIS are common and are independently associated with adverse clinical outcomes.

• MeSH
• cévní mozková příhoda * farmakoterapie   MeSH
• fibrinolytika terapeutické užití   MeSH
• ischemická cévní mozková příhoda * MeSH
• ischemie mozku * farmakoterapie   MeSH
• krevní tlak * účinky léků   MeSH
• lidé MeSH
• tkáňový aktivátor plazminogenu farmakologie   terapeutické užití   MeSH
• trombolytická terapie * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND AND PURPOSE: Blood pressure (BP) variability has been associated with worse neurological outcomes in acute ischaemic stroke (AIS) patients receiving treatment with intravenous thrombolysis (IVT). However, no study to date has investigated whether pulse pressure (PP) variability may be a superior indicator of the total cardiovascular risk, as measured by clinical outcomes. METHODS: Pulse pressure variability was calculated from 24-h PP measurements following tissue plasminogen activator bolus in AIS patients enrolled in the Combined Lysis of Thrombus using Ultrasound and Systemic Tissue Plasminogen Activator for Emergent Revascularization (CLOTBUST-ER) trial. The outcomes of interest were the pre-specified efficacy and safety end-points of CLOTBUST-ER. All associations were adjusted for potential confounders in multivariable regression models. RESULTS: Data from 674 participants was analyzed. PP variability was identified as the BP parameter with the most parsimonious fit in multivariable models of all outcomes, and was independently associated (P < 0.001) with lower likelihood of both 24-h neurological improvement and 90-day independent functional outcome. PP variability was also independently related to increased odds of any intracranial bleeding (P = 0.011) and 90-day mortality (P < 0.001). Every 5-mmHg increase in the 24-h PP variability was independently associated with a 36% decrease in the likelihood of 90-day independent functional outcome (adjusted odds ratio 0.64, 95% confidence interval 0.52-0.80) and a 60% increase in the odds of 90-day mortality (adjusted odds ratio 1.60, 95% confidence interval 1.23-2.07). PP variability was not associated with symptomatic intracranial bleeding at either 24 or 36 h after IVT administration. CONCLUSIONS: Increased PP variability appears to be independently associated with adverse short-term and long-term functional outcomes of AIS patients treated with IVT.

• MeSH
• cévní mozková příhoda * farmakoterapie   MeSH
• fibrinolytika terapeutické užití   MeSH
• intravenózní podání MeSH
• ischemická cévní mozková příhoda * MeSH
• ischemie mozku * komplikace   farmakoterapie   MeSH
• krevní tlak MeSH
• lidé MeSH
• tkáňový aktivátor plazminogenu terapeutické užití   MeSH
• trombolytická terapie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The influence of cilostazol on learning and memory, and cyclin D1 expression in the cerebral cortex of rats with chronic cerebral ischemia were investigated. A chronic cerebral ischemia model was established using the permanent bilateral common carotid artery occlusion method (2VO), learning and memory capacity was detected using the Morris water maze, and expression changes in apoptosis regulating gene cyclin D1 were tested by RT-PCR. Results of the Morris water maze indicated that significant extensions were found in the escape latent period and swimming path of rats in the ischemia group (2VO group), learning and memory results in the cilostazol group was obviously superior compared to the 2VO group (P<0.05), and the expression of cyclin D1 was observed to increase in both the ischemia and cilostazol intervention groups at the 9th week of ischemia. A significant difference was observed, compared with the sham operation group (P<0.05), the expression level decreased in the ischemia group compared with the cilostazol group, and a significant difference was identified compared with the ischemia group (P<0.05). Cilostazol can reduce nerve function impairment and improve learning and memory functions by affecting changes in apoptosis regulating genes.

• MeSH
• bludiště - učení účinky léků   MeSH
• chronická nemoc MeSH
• cilostazol farmakologie   MeSH
• cyklin D1 biosyntéza   genetika   metabolismus   MeSH
• ischemie mozku farmakoterapie   genetika   metabolismus   patologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• mozková kůra účinky léků   metabolismus   MeSH
• neuroprotektivní látky farmakologie   MeSH
• paměť účinky léků   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH