The Direct Referral to Endovascular Center criteria: a proposal for pre-hospital evaluation of acute stroke in the Madrid Stroke Network.

BACKGROUND AND PURPOSE: For patients with acute ischaemic stroke due to large-vessel occlusion, it has recently been shown that mechanical thrombectomy (MT) with stent retrievers is better than medical treatment alone. However, few hospitals can provide MT 24 h/day 365 days/year, and it remains unclear whether selected patients with acute stroke should be directly transferred to the nearest MT-providing hospital to prevent treatment delays. Clinical scales such as Rapid Arterial Occlusion Evaluation (RACE) have been developed to predict large-vessel occlusion at a pre-hospital level, but their predictive value for MT is low. We propose new criteria to identify patients eligible for MT, with higher accuracy. METHODS: The Direct Referral to Endovascular Center criteria were defined based on a retrospective cohort of 317 patients admitted to a stroke center. The association of age, sex, RACE scale score and blood pressure with the likelihood of receiving MT were analyzed. Cut-off points with the highest association were thereafter evaluated in a prospective cohort of 153 patients from nine stroke units comprising the Madrid Stroke Network. RESULTS: Patients with a RACE scale score ≥ 5, systolic blood pressure <190 mmHg and age <81 years showed a significantly higher probability of undergoing MT (odds ratio, 33.38; 95% confidence interval, 12-92.9). This outcome was confirmed in the prospective cohort, with 68% sensitivity, 84% specificity, 42% positive and 94% negative predictive values for MT, ruling out 83% of hemorrhagic strokes. CONCLUSIONS: The Direct Referral to Endovascular Center criteria could be useful for identifying patients suitable for MT.

Use of healthcare resources and costs of acute cardioembolic stroke management in the Region of Madrid: The CODICE Study.

INTRODUCTION: Stroke is the main cause of admission to Neurology departments and cardioembolic stroke (CS) is one of the most common subtypes of stroke. METHODS: A multicentre prospective observational study was performed in 5 Neurology departments in public hospitals in the Region of Madrid (Spain). The objective was to estimate the use of healthcare resources and costs of acute CS management. Patients with acute CS at<48h from onset were recruited. Patients' socio-demographic, clinical, and healthcare resource use data were collected during hospitalisation and at discharge up to 30 days after admission, including data for rehabilitation treatment after discharge. RESULTS: During an 8-month recruitment period, 128 patients were recruited: mean age, 75.3±11.25; 46.9% women; mortality rate, 4.7%. All patients met the CS diagnostic criteria established by GEENCV-SEN, based on medical history or diagnostic tests. Fifty per cent of the patients had a history of atrial fibrillation and 18.8% presented other major cardioembolic sources. Non-valvular atrial fibrillation was the most frequent cause of CS (33.6%). Data for healthcare resource use, given a mean total hospital stay of 10.3±9.3 days, are as follows: rehabilitation therapy during hospital stay (46.9%, mean 4.5 days) and after discharge (56.3%, mean 26.8 days), complications (32%), specific interventions (19.5%), and laboratory and diagnostic tests (100%). Head CT (98.4%), duplex ultrasound of supra-aortic trunks (87.5%), and electrocardiogram (85.9%) were the most frequently performed diagnostic procedures. Average total cost per patient during acute-phase management and rehabilitation was €13,139. Hospital stay (45.0%) and rehabilitation at discharge (29.2%) accounted for the largest part of resources used. CONCLUSIONS: Acute CS management in the Region of Madrid resulted consumes large amounts of resources (€13,139), mainly due to hospital stays and rehabilitation.

KRAS p.G12C mutation occurs in 1% of EGFR-mutated advanced non-small-cell lung cancer patients progressing on a first-line treatment with a tyrosine kinase inhibitor.

BACKGROUND: KRAS is mutated in ∼30% of non-small-cell lung cancer (NSCLC) but it has also been identified as one of the mechanisms underlying resistance to tyrosine kinase inhibitors (TKIs) in EGFR-positive NSCLC patients. Novel KRAS inhibitors targeting KRAS p.G12C mutation have been developed recently with promising results. The proportion of EGFR-positive NSCLC tumours harbouring the KRAS p.G12C mutation upon disease progression is completely unexplored. MATERIALS AND METHODS: Plasma samples from 512 EGFR-positive advanced NSCLC patients progressing on a first first-line treatment with a TKI were collected. The presence of KRAS p.G12C mutation was assessed by digital PCR. RESULTS: Overall, KRAS p.G12C mutation was detected in 1.17% of the samples (n = 6). In two of these cases, we could confirm that the KRAS p.G12C mutation was not present in the pre-treatment plasma samples, supporting its role as an acquired resistance mutation. According to our data, KRASG12C patients showed similar clinicopathological characteristics to those of the rest of the study cohort and no statistically significant associations between any clinical features and the presence of the mutation were found. However, two out of six KRASG12C tumours harboured less common EGFR driver mutations (p.G719X/p.L861Q). All KRASG12C patients tested negative for the presence of p.T790M resistance mutation. CONCLUSIONS: The KRAS p.G12C mutation is detected in 1% of EGFR-positive NSCLC patients who progress on a first line with a TKI. All KRASG12C patients were negative for the presence of the p.T790M mutation and they did not show any distinctive clinical feature.

The beneficial effect of statins treatment by stroke subtype.

BACKGROUND AND PURPOSE: Statins have shown some protective effect after ischaemic stroke in observational studies. However, this effect has never been assessed by etiological subtypes. METHODS: Observational study using data from the Stroke Unit Data Bank from consecutive patients with cerebral infarction. Variables analyzed: demographic data, cardiovascular risk factors, treatment with statins at stroke onset, stroke severity, stroke subtype, in-hospital complications, length of stay, and functional status at discharge (modified Rankin Scale). RESULTS: A total of 2742 patients were included, 1539 were men. Mean age was 69.17 years (SD 12.19). Of these, 281 patients (10.2%) were receiving statins when admitted. The logistic regression analyses showed that previous treatment with statins was an independent predictor for better outcome at discharge among all strokes (OR, 2.08; 95% CI, 1.39 to 3.1) as well as for the atherothrombotic (OR, 2.79; 95% CI, 1.33 to 5.84) and lacunar strokes (OR, 2.28; 95% CI, 1.15 to 4.52) after adjustment for demographic data, risk factors, previous treatments, stroke subtypes, stroke severity, in-hospital complications and length of stay. This benefit was not observed either in cardioembolic or in other etiology strokes. CONCLUSIONS: Previous treatment with statins is an independent factor associated with good outcomes in patients with ischaemic stroke. Atherothrombotic and small vessel strokes show the greatest benefit.

Treatment with angiotensin receptor blockers before stroke could exert a favourable effect in acute cerebral infarction.

INTRODUCTION: Evidence from experimental and clinical studies is accumulating about the possible cerebral protective properties of antihypertensive drugs, mainly angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEI). Our aim was to analyse the impact of prestroke use of antihypertensive drugs on stroke severity and outcome. METHODS: We analysed 1968 consecutive patients with first-ever acute cerebral infarction admitted to an acute stroke unit. Stroke severity was evaluated using the Canadian Neurological Scale and the modified Rankin Score (mRS) was used to evaluate the outcome at discharge. RESULTS: Previous diagnosis of arterial hypertension was reported in 1212 patients and 73% were on antihypertensive treatment. No significant differences in stroke severity were found between patients with or without previous arterial hypertension, either in patients with or without antihypertensive treatment. Patients taking antihypertensive drugs at stroke onset had lower rates of poor outcome than those not on antihypertensive treatment (47 vs. 53%; P = 0.047) and those taking ARB had better outcomes than those without ARB (mRS

[Migraine as predictive factor of the presence of atrial septum aneurysm in patients with stroke and patent foramen ovale]. / Migraña como factor predictor de la presencia de aneurisma del septo auricular en pacientes con ictus y foramen oval permeable.

INTRODUCTION: Ischemic stroke in young patients is associated in up to 30% of cases to a patent foramen ovale (PFO) with or without atrial septum aneurism (ASA). Besides, a frequent association between migraine and PFO has been described, but few studies have addressed the possible association between ASA and migraine in stroke patients. METHODS: Observational study with inclusion of consecutive ischemic stroke patients in a Stroke Unit Data Bank of the Department of Neurology of a university hospital admitted between January 1994 and December 2005. Those patients who underwent transesophageal echocardiography (TEE) were selected and classified in two groups regarding the history of previous migraine. Logistic regression analysis models were developed to assess the risk of the combination of PFO and ASA in patients with migraine. RESULTS: 631 stroke patients with TEE were included. PFO was present in 61 patients (9.7%), isolated ASA in 34 (5.4%) and both abnormalities in 22 (3.49%). Patients with migraine and PFO had higher frequency of ASA than those with PFO and no migraine (75 vs 30.2%), and the relative risk to carry double interatrial septal abnormalities was 2.5 (95% confidence interval: 1.4-4.4). In the subgroup of patients under 55 years old, migraine history was associated to a nine-folder relative risk of carrying this combination, independently of age or gender. CONCLUSIONS: In patients with ischemic stroke and PFO the probability of having ASA could be higher in migrainous. This finding could have diagnostic implications, suggesting the convenience to seek for this association in these patients.

[Influence of previous diagnosis of diabetes mellitus in the stroke severity and in-hospital outcome in acute cerebral infarction]. / Influencia del antecedente de diabetes mellitus en la gravedad y evolución intrahospitalaria de un infarto cerebral.

INTRODUCTION: To analyze if previous diagnosis of diabetes influences stroke severity and in-hospital outcome in acute cerebral infarction (CI) patients. METHODS: Observational study between 1998-2004 with inclusion of consecutive patients with CI. Risk factors, stroke subtype, severity on admission (Canadian Stroke Scale [CSS]), in-hospital complications, mortality, length of stay and stroke outcome (modified Rankin Scale [mRS]) in CI patients with and without previous diagnosis of diabetes were compared. RESULTS: A total of 2,213 consecutive acute stroke patients; 661 with previous history of diabetes (29,9%) were included. These patients were older, had more rate of hypertension, dyslipidemia, coronary arterial disease, peripheral vascular disease and previous stroke than non-diabetic patients. Atherotrombotic and lacunar infarction were more frequent in diabetic patients. They also had more in-hospital complications as urinary tract infection (4.7 % vs 2.6 %; p < 0.05), multiple organ dysfunction syndrome (3.3% vs 1.8%; p<0.05), deteriorating stroke (6.1 % vs 3.4 %; p < 0.01), recurrent stroke (3.3% vs 1.7%; p<0.05) and increase of infarction volume (2.6 % vs 1.1%; p<0.05), with no differences in stroke severity at admission, mortality, length of in-hospital stay and stroke outcome. Previous history of diabetes was independently associated with in-hospital complications (OR: 1.377; CI 95%: 1.053-1.799). CONCLUSIONS: Previous diagnosis of diabetes is not associated by itself to higher stroke severity on admission although a greater risk of in-hospital complications is found.

Action on vascular risk factors: importance of blood pressure and lipid lowering in stroke secondary prevention.

INTRODUCTION: Secondary stroke prevention comprises a broad spectrum of therapeutic actions that includes the appropriate management of risk factors and the action on blood pressure and serum lipids that are of great importance to decrease stroke recurrences. METHODS: We conducted a review of the published studies analyzing the relevance of the treatment of blood pressure and serum lipids, with special attention to recent findings of clinical trials and current guidelines on stroke secondary prevention. RESULTS: The relationship between blood pressure and stroke has been widely demonstrated; however, the role of serum lipids has been discussed for a long time. Recent results from epidemiological studies and clinical trials have demonstrated its role as modifiable risk factor for stroke. Blood pressure and lipid lowering are associated with significant reductions in recurrent strokes as well as in other vascular events in transient ischemic attack (TIA) or stroke patients. The PROGRESS and MOSES trials suggest that diuretics, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers could confer additional benefits in stroke patients, and the SPARCL study did so for statins. These drugs are not only efficacious in the reduction of stroke recurrences, but also in other cardiovascular events. CONCLUSIONS: Blood pressure and serum lipids are two important and modifiable vascular risk factors that should be taken into consideration when planning secondary stroke prevention measures. This approach should include hypotensive drugs (mainly the combination of diuretics and ACE inhibitors) with the objective to maintain normal blood pressure, avoiding levels >130/80 mm Hg in all stroke patients, and statins (atorvastatin 80 mg) in patients with noncardioembolic TIA or stroke.

Systemic reperfusion therapy in acute ischemic stroke.

INTRODUCTION: Experimental and clinical studies indicate that early reperfusion of occluded brain-supplying arteries reduces the size of injury and improves outcome. Recombinant tissue plasminogen activator (t-PA) is the only drug approved for systemic reperfusion in acute ischemic stroke. However, the use of intravenous t-PA is currently limited by its narrow therapeutic window. METHODS: We reviewed the approaches to extending systemic reperfusion in cerebral ischemia currently under investigation in human clinical studies. RESULTS: Strategies to expand the systemic reperfusion include: a better use of conventional t-PA; to extend the intravenous rt-PA window to 270 min; new fibrinolytic agents (tenecteplase, microplasmin, desmoteplase, V10153); combination of lytics and antithrombotics (t-PA + tirofibran, t-PA + abciximab, reteplase + abciximab, t-PA + eptifibatide and t-PA + eptifibatide + aspirin + tinzaparin); combination of lytics and neuroprotectans; externally applied ultrasound to enhance enzymatic fibrinolysis, and improving patient selection with multimodal imaging. CONCLUSION: There is considerable opportunity to explore safe strategies to expand systemic reperfusion therapy which could further benefit stroke outcome.

Consistency of the benefits of stroke units over years of operation: an 8-year effectiveness analysis.

BACKGROUND: The efficacy of stroke units (SU) has been amply demonstrated in randomised trials. However, no long-term studies analysed their effectiveness in daily practice over several years of operation. METHODS: Observational study from the stroke data bank of our neurology ward that includes consecutive stroke patients hospitalised since the SU was established in 1995 until the year 2002 (8 years). Clinical effectiveness was analysed in terms of mortality on day 7, in-hospital mortality, functional state at discharge, length of stay, in-hospital complications and long-term hospitalisation rates on a yearly basis using for comparisons chi2 or Student t tests between the first and last 4 years of SU operation. Case-mix adjustments for baseline imbalances and stepwise multivariate logistic regression were also performed for comparative purposes. RESULTS: 3,986 consecutive in-patients were included. No significant differences in the proportion of independent patients at discharge (73.9 vs. 74.5%; n.s.), length of stay (11.2 vs. 11.3 days; n.s.), in-hospital complications (25.0 vs. 25.9%; n.s.) or long-stay hospitalisation (6.3 vs. 6.4%; n.s.) were found comparing the first and last 4 years of SU operation. No significant differences in in-hospital mortality were found after adjustment by case-mix and length of stay. CONCLUSIONS: SU effectiveness, in terms of length of stay, death or dependence and long-term hospitalisation, is sustained over the period of operation.

Plan de Cuidados Urológicos al paciente lesionado medular espinal con vejiga neurógena / No disponible

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