The transverse aortic constriction heart failure animal model: a systematic review and meta-analysis

The transverse aortic constriction (TAC) model is frequently used to study adverse cardiac remodeling upon pressure overload. We set out to define the most important characteristics that define the degree of cardiac remodeling in this model. A systematic review and meta-analyses were performed on studies using the TAC mouse/rat model and reporting echocardiographic outcome parameters. We included all animal studies in which a constriction around the transverse aorta and at least one of the predefined echocardiography or MRI outcome parameters were assessed. A total of 502 articles and > 3000 wild-type, untreated animals undergoing TAC were included in this study and referenced to a control group. The duration of aortic constriction correlated to the degree of adverse remodeling. However, the mouse data is strongly biased by the preferential use of male C57Bl/6 mice (66% of studies). Furthermore, mostly ketamine/xylazine anesthetics, 27G needle constriction, and silk sutures are used. Nonetheless, despite the homogeneity in experimental design, the model contained a substantial degree of heterogeneity in the functional outcome measures. When looking at study quality, only 12% reported randomization, 23% mentioned any sort of blinding, 25% adequately addressed the outcomes, and an amazingly low percentage (2%) showed sample size calculation. Meta-analyses did not detect specific study characteristics that explained the heterogeneity in the reported outcome measures, however this might be related to the strong bias towards the use of specific mouse lines, sex as well as age or to poor reporting of characteristics of study quality

Endovascular treatment of patients with stroke caused by anterior cerebral artery occlusions

Background: Occlusion of the anterior cerebral artery (ACA) is uncommon but may lead to significant disability. The benefit of endovascular treatment (EVT) for ACA occlusions remains uncertain. Methods: We included patients treated with EVT and compared patients with ACA occlusions with patients who had internal carotid artery (ICA) or proximal (M1/M2) middle cerebral artery (MCA) occlusions from the MR CLEAN Registry. Primary outcome was the modified Rankin Scale score (mRS). Secondary outcomes were functional independence (mRS 0–2), National Institutes of Health Stroke Scale (NIHSS) score, delta-NIHSS (baseline minus NIHSS score at 24–48 h), and successful recanalization (expanded thrombolysis in cerebral infarction (eTICI) score 2b-3). Safety outcomes were symptomatic intracranial hemorrhage (sICH), periprocedural complications, and mortality. Results: Of 5193 patients, 11 (0.2%) had primary ACA occlusions. Median NIHSS at baseline was lower in patients with ACA versus ICA/MCA occlusions (11, IQR 9–14; versus 15, IQR 11–19). Functional outcome did not differ from patients with ICA/MCA occlusions. Functional independence was 4/11 (36%) in patients with ACA versus 1949/4815 (41%) in ICA/MCA occlusions; median delta-NIHSS was − 1 (IQR − 7 to 2) and − 4 (IQR − 9 to 0), respectively. Successful recanalization was 4/9 (44%), versus 3083/4787 (64%) in ICA/MCA occlusions. Mortality was 3/11 (27%) versus 1263/4815 (26%). One patient with ACA occlusion had sICH; no other complications occurred. Conclusion: In this cohort ACA occlusions were uncommon. Functional outcome did not differ between patients with ACA occlusions and ICA/MCA occlusions. Prospective research is needed to determine feasibility, safety, and outcomes of EVT for ACA occlusions.</p

Impact of the lockdown on acute stroke treatments during the first surge of the COVID-19 outbreak in the Netherlands

INTRODUCTION: We investigated the impact of the Corona Virus Disease 2019 (COVID-19) pandemic and the resulting lockdown on reperfusion treatments and door-to-treatment times during the first surge in Dutch comprehensive stroke centers. Furthermore, we studied the association between COVID-19-status and treatment times. METHODS: We included all patients receiving reperfusion treatment in 17 Dutch stroke centers from May 11th, 2017, until May 11th, 2020. We collected baseline characteristics, National Institutes of Health Stroke Scale (NIHSS) at admission, onset-to-door time (ODT), door-to-needle time (DNT), door-to-groin time (DGT) and COVID-19-status at admission. Parameters during the lockdown (March 15th, 2020 until May 11th, 2020) were compared with those in the same period in 2019, and between groups stratified by COVID-19-status. We used nationwide data and extrapolated our findings to the increasing trend of EVT numbers since May 2017. RESULTS: A decline of 14% was seen in reperfusion treatments during lockdown, with a decline in both IVT and EVT delivery. DGT increased by 12 min (50 to 62 min, p-value of < 0.001). Furthermore, median NIHSS-scores were higher in COVID-19 - suspected or positive patients (7 to 11, p-value of 0.004), door-to-treatment times did not differ significantly when stratified for COVID-19-status. CONCLUSIONS: During the first surge of the COVID-19 pandemic, a decline in acute reperfusion treatments and a delay in DGT was seen, which indicates a target for attention. It also appeared that COVID-19-positive or -suspected patients had more severe neurologic symptoms, whereas their EVT-workflow was not affected. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12883-021-02539-4

Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11-13 November 2018

The purpose of the European Stroke Organisation-Karolinska Stroke Update Conference is to provide updates on recent stroke therapy research and to give an opportunity for the participants to discuss how these results may be implemented into clinical routine. The meeting started 22 years ago as Karolinska Stroke Update, but since 2014 it is a joint conference with European Stroke Organisation. Importantly, it provides a platform for discussion on the European Stroke Organisation guidelines process and on recommendations to the European Stroke Organisation guidelines committee on specific topics. By this, it adds a direct influence from stroke professionals otherwise not involved in committees and work groups on the guideline procedure. The discussions at the conference may also inspire new guidelines when motivated. The topics raised at the meeting are selected by the scientific programme committee mainly based on recent important scientific publications. This year's European Stroke Organisation-Karolinska Stroke Update Meeting was held in Stockholm on 11-13 November 2018. There were 11 scientific sessions discussed in the meeting including two short sessions. Each session except the short sessions produced a consensus statement (Full version with background, issues, conclusions and references are published as web-material and at and ) and recommendations which were prepared by a writing committee consisting of session chair(s), scientific secretary and speakers. These statements were presented to the 250 participants of the meeting. In the open meeting, general participants commented on the consensus statement and recommendations and the final document were adjusted based on the discussion from the general participants Recommendations (grade of evidence) were graded according to the 1998 Karolinska Stroke Update meeting with regard to the strength of evidence. Grade A Evidence: Strong support from randomised controlled trials and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials, recommendations based on small randomised and/or non-randomised controlled trials evidence.Peer reviewe

Vertebral artery stenosis in the Basilar Artery International Cooperation Study (BASICS) : prevalence and outcome

We assessed the prevalence of vertebral artery (VA) stenosis or occlusion and its influence on outcome in patients with acute basilar artery occlusion (BAO). We studied 141 patients with acute BAO enrolled in the Basilar Artery International Cooperation Study (BASICS) registry of whom baseline CT angiography (CTA) of the intracranial VAs was available. In 72 patients an additional CTA of the extracranial VAs was available. Adjusted risk ratios (aRRs) for death and poor outcome, defined as a modified Rankin Scale score ≥4, were calculated with Poisson regression in relation to VA occlusion, VA occlusion or stenosis ≥50 %, and bilateral VA occlusion. Sixty-six of 141 (47 %) patients had uni- or bilateral intracranial VA occlusion or stenosis ≥50 %. Of the 72 patients with intra- and extracranial CTA, 46 (64 %) had uni- or bilateral VA occlusion or stenosis ≥50 % and 9 (12 %) had bilateral VA occlusion. Overall, VA occlusion or stenosis ≥50 % was not associated with the risk of poor outcome. Patients with intra- and extracranial CTA and bilateral VA occlusion had a higher risk of poor outcome than patients without bilateral VA occlusion (aRR, 1.23; 95 % CI 1.02–1.50). The risk of death did not depend on the presence of unilateral or bilateral VA occlusion or stenosis ≥50 %. In conclusion, in patients with acute BAO, unilateral VA occlusion or stenosis ≥50 % is frequent, but not associated with an increased risk of poor outcome or death. Patients with BAO and bilateral VA occlusion have a slightly increased risk of poor outcome

The transverse aortic constriction heart failure animal model: a systematic review and meta-analysis

The transverse aortic constriction (TAC) model is frequently used to study adverse cardiac remodeling upon pressure overload. We set out to define the most important characteristics that define the degree of cardiac remodeling in this model. A systematic review and meta-analyses were performed on studies using the TAC mouse/rat model and reporting echocardiographic outcome parameters. We included all animal studies in which a constriction around the transverse aorta and at least one of the predefined echocardiography or MRI outcome parameters were assessed. A total of 502 articles and > 3000 wild-type, untreated animals undergoing TAC were included in this study and referenced to a control group. The duration of aortic constriction correlated to the degree of adverse remodeling. However, the mouse data is strongly biased by the preferential use of male C57Bl/6 mice (66% of studies). Furthermore, mostly ketamine/xylazine anesthetics, 27G needle constriction, and silk sutures are used. Nonetheless, despite the homogeneity in experimental design, the model contained a substantial degree of heterogeneity in the functional outcome measures. When looking at study quality, only 12% reported randomization, 23% mentioned any sort of blinding, 25% adequately addressed the outcomes, and an amazingly low percentage (2%) showed sample size calculation. Meta-analyses did not detect specific study characteristics that explained the heterogeneity in the reported outcome measures, however this might be related to the strong bias towards the use of specific mouse lines, sex as well as age or to poor reporting of characteristics of study quality

A study into methodology and application of quantification of tumour vasculature in rectal cancer.

Contains fulltext : 57501.pdf (publisher's version ) (Closed access)The application of new surgical techniques in combination with preoperative radiotherapy has minimised the risk of local recurrence in rectal cancer. However, distant metastasis is still a serious problem after seemingly curative resection in patients with rectal cancer. The present study aimed to evaluate the methodology for quantification and the characteristics of the tumour vasculature in relation to the development of metastasis in patients with rectal cancer. From a large multicentre trial, 88 patients were selected, ensuring a relatively high percentage of metastasis. This selection facilitates the study of tumour vasculature characteristics in relation to metastasis. Vessel number, perimeter and area were assessed at both the invasive front and intratumoural area. Hot-spot and random selections were performed simultaneously. The median of each vessel parameter in the study population was used to separate patients into a low- and high-vessel group. Differences in development of distant metastasis were studied between low- and high-vessel groups. The data of the present study show that only vascular perimeter randomly assessed at the invasive front was associated with distant metastasis. Patients with a high score had a lower distant metastasis rate than patients with a low score (37% and 62%, respectively). High-vessel perimeter was independent of tumor node metastasis staging, but was associated with an increased presence of immune cells, comprising T cells, mast cells, eosinophils and neutrophils. This methodological study on the biological relevance of various vessel characteristics showed that a large vascular endothelial surface, as reflected by a high perimeter, was the only vessel characteristic indicative of improved patient outcome. The underlying principle for this association may be the improved immune response

Prehospital transdermal glyceryl trinitrate in patients with presumed acute stroke (MR ASAP): an ambulance-based, multicentre, randomised, open-label, blinded endpoint, phase 3 trial

Background: Pooled analyses of previous randomised studies have suggested that very early treatment with glyceryl trinitrate (also known as nitroglycerin) improves functional outcome in patients with acute ischaemic stroke or intracerebral haemorrhage, but this finding was not confirmed in a more recent trial (RIGHT-2). We aimed to assess whether patients with presumed acute stroke benefit from glyceryl tr initrate started within 3 h after symptom onset. Methods: MR ASAP was a phase 3, randomised, open-label, blinded endpoint trial done at six ambulance services serving 18 hospitals in the Netherlands. Eligible participants (aged ≥18 years) had a probable diagnosis of acute stroke (as assessed by a paramedic), a face-arm-speech-time test score of 2 or 3, systolic blood pressure of at least 140 mm Hg, and could start treatment within 3 h of symptom onset. Participants were randomly assigned (1:1) by ambulance personnel, using a secure web-based electronic application with random block sizes stratified by ambulance service, to receive either transdermal glyceryl trinitrate 5 mg/day for 24 h plus standard care (glyceryl trinitrate group) or to standard care alone (control group) in the prehospital setting. Informed consent was deferred until after arrival at the hospital. The primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) at 90 days. Safety outcomes included death within 7 days, death within 90 days, and serious adverse events. Analyses were based on modified intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. We separately analysed the total population and the target population (ie, patients with intracerebral haemorrhage, ischaemic stroke, or transient ischaemic attack). The target sample size was 1400 patients. The trial is registered as ISRCTN99503308. Findings: On June 24, 2021, the MR ASAP trial was prematurely terminated on the advice of the data and safety monitoring board, with recruitment stopped because of safety concerns in patients with intracerebral haemorrhage. Between April 4, 2018, and Feb 12, 2021, 380 patients were randomly allocated to a study group. 325 provided informed consent or died before consent could be obtained, of whom 170 were assigned to the glyceryl trinitrate group and 155 to the control group. These patients were included in the total population. 201 patients (62%) had ischaemic stroke, 34 (10%) transient ischaemic attack, 56 (17%) intracerebral haemorrhage, and 34 (10%) a stroke-mimicking condition. In the total population (n=325), the median mRS score at 90 days was 2 (IQR 1–4) in both the glyceryl trinitrate and control groups (adjusted common OR 0·97 [95% CI 0·65–1·47]). In the target population (n=291), the 90-day mRS score was 2 (2–4) in the glyceryl trinitrate group and 3 (1–4) in the control group (0·92 [0·59–1·43]). In the total population, there were no differences between the two study groups with respect to death within 90 days (adjusted OR 1·07 [0·53–2·14]) or serious adverse events (unadjusted OR 1·23 [0·76–1·99]). In patients with intracerebral haemorrhage, 12 (34%) of 35 patients allocated to glyceryl trinitrate versus two (10%) of 21 allocated to the control group died within 7 days (adjusted OR 5·91 [0·78–44·81]); death within 90 days occurred in 16 (46%) of 35 in the glyceryl trinitrate group and 11 (55%) of 20 in the control group (adjusted OR 0·87 [0·18–4·17]). Interpretation: We found no sign of benefit of transdermal glyceryl trinitrate started within 3 h of symptom onset in the prehospital setting in patients with presumed acute stroke. The signal of potential early harm of glyceryl trinitrate in patients with intracerebral haemorrhage suggests that glyceryl trinitrate should be avoided in this setting. Funding: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation