Thrombolysis in very elderly people: controlled comparison of SITS international stroke thrombolysis registry and virtual international stroke trials archive

<p>Objective To assess effect of age on response to alteplase in acute ischaemic stroke.</p> <p>Design Adjusted controlled comparison of outcomes between non-randomised patients who did or did not undergo thrombolysis. Analysis used Cochran-Mantel-Haenszel test and proportional odds logistic regression analysis.</p> <p>Setting Collaboration between International Stroke Thrombolysis Registry (SITS-ISTR) and Virtual International Stroke Trials Archive (VISTA).</p> <p>Participants 23 334 patients from SITS-ISTR (December 2002 to November 2009) who underwent thrombolysis and 6166 from VISTA neuroprotection trials (1998-2007) who did not undergo thrombolysis (as controls). Of the 29 500 patients (3472 aged >80 (“elderly,” mean 84.6), data on 272 patients were missing for baseline National Institutes of Health stroke severity score, leaving 29 228 patients for analysis adjusted for age and baseline severity.</p> <p>Main outcome measures Functional outcomes at 90 days measured by score on modified Rankin scale.</p> <p>Results Median severity at baseline was the same for patients who underwent thrombolysis and controls (median baseline stroke scale score: 12 for each group, P=0.14; n=29 228). The distribution of scores on the modified Rankin scale was better among all thrombolysis patients than controls (odds ratio 1.6, 95% confidence interval 1.5 to 1.7; Cochran-Mantel-Haenszel P<0.001). The association occurred independently among patients aged ≤80 (1.6, 1.5 to 1.7; P<0.001; n=25 789) and in those aged >80 (1.4, 1.3 to 1.6; P0.001; n=3439). Odds ratios were consistent across all 10 year age ranges above 30, and benefit was significant from age 41 to 90; dichotomised outcomes (score on modified Rankin scale 0-1 v 2-6; 0-2 v 3-6; and 6 (death) v rest) were consistent with the results of the ordinal analysis.</p> <p>Conclusions Outcome in patients with acute ischaemic stroke is significantly better in those who undergo thrombolysis compared with those who do not. Increasing age is associated with poorer outcome but the association between thrombolysis treatment and improved outcome is maintained in very elderly people. Age alone should not be a barrier to treatment.</p&gt

A proteomic approach to the myocardium of hypertensive-diabetic rats

Comunicaciones a congreso

Identification of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) as a possible biomarker of subclinical atherosclerosis

OBJECTIVES: Assessment of vascular risk in asymptomatic patients and the response to medical therapy is a major challenge for prevention of cardiovascular events. Our aim was to identify proteins differentially released by healthy versus atherosclerotic arterial walls, which could be found in plasma and serve as markers of atherosclerosis. METHODS AND RESULTS: We have analyzed supernatants obtained from cultured human carotid plaques and healthy arteries by surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry ProteinChip System. Surface-enhanced laser-desorption/ionization analysis unveiled an 18.4-kDa peak released in lower amount by carotid plaques than normal endarteries. This protein was identified as soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK). To confirm that sTWEAK was the protein of interest, Western blot and enzyme-linked immunosorbent assay were performed. Both techniques confirmed that sTWEAK levels were decreased in carotid plaque supernatants. Subsequent measurement of sTWEAK in plasma showed a reduced concentration in subjects with carotid stenosis (N=30) compared with healthy subjects matched by sex and age (N=28) (P<0.001). Furthermore, in a test population of 106 asymptomatic subjects, we showed that sTWEAK concentrations negatively correlated with the carotid intima-media thickness (r=-0.4; P<0.001), an index of subclinical atherosclerosis. CONCLUSIONS: These results suggest that sTWEAK could be a potential biomarker of atherosclerosis

The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies

Acessível em: www.ncbi.nlm.nih.gov/pmc/articles/PMC4423738/Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition

Solution of the Skyrme-Hartree-Fock-Bogolyubov equations in the Cartesian deformed harmonic-oscillator basis. (VII) HFODD (v2.49t): a new version of the program

We describe the new version (v2.49t) of the code HFODD which solves the nuclear Skyrme Hartree-Fock (HF) or Skyrme Hartree-Fock-Bogolyubov (HFB) problem by using the Cartesian deformed harmonic-oscillator basis. In the new version, we have implemented the following physics features: (i) the isospin mixing and projection, (ii) the finite temperature formalism for the HFB and HF+BCS methods, (iii) the Lipkin translational energy correction method, (iv) the calculation of the shell correction. A number of specific numerical methods have also been implemented in order to deal with large-scale multi-constraint calculations and hardware limitations: (i) the two-basis method for the HFB method, (ii) the Augmented Lagrangian Method (ALM) for multi-constraint calculations, (iii) the linear constraint method based on the approximation of the RPA matrix for multi-constraint calculations, (iv) an interface with the axial and parity-conserving Skyrme-HFB code HFBTHO, (v) the mixing of the HF or HFB matrix elements instead of the HF fields. Special care has been paid to using the code on massively parallel leadership class computers. For this purpose, the following features are now available with this version: (i) the Message Passing Interface (MPI) framework, (ii) scalable input data routines, (iii) multi-threading via OpenMP pragmas, (iv) parallel diagonalization of the HFB matrix in the simplex breaking case using the ScaLAPACK library. Finally, several little significant errors of the previous published version were corrected.Comment: Accepted for publication to Computer Physics Communications. Program files re-submitted to Comp. Phys. Comm. Program Library after correction of several minor bug

Safety and outcomes of routine endovascular thrombectomy in large artery occlusion recorded in the SITS Register: An observational study

[Background and objective] We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS–International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies.[Methods] We identified centres recording ≥10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014–2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST.[Results] Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44–47), 46.0% (42–50), 38% (35–41) and 37% (35–41), respectively; death was 19.2% (19–21), 15.3% (12.7–18.4), 29.2% (27–32) and 28.6% (27–31); and SICH was 3.6% (3–4), 4.4% (3.0–6.4), 5.8% (4.7–7.1) and not available.[Conclusion] Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies.SITS (Safe Implementation of Treatment in Stroke) is financed directly and indirectly by grants from Karolinska Institutet, Stockholm County Council, the Swedish Heart-Lung Foundation, the Swedish Order of St. John, Friends of Karolinska Institutet and private donors, as well as from an unrestricted sponsorship from Boehringer Ingelheim. SITS has previously received grants from the European Union Framework 7, the European Union Public Health Authority, Ferrer International and EVER Pharma. SITS is currently conducting studies supported by Boehringer Ingelheim and Biogen, as well as in collaboration with Karolinska Institutet, supported by Stryker, Covidien and Phenox. N Ahmed is supported by grants provided by the Stockholm County Council and the Swedish Heart-Lung Foundation. S Holmin is supported by grants provided by the Söderberg Foundations, the Stockholm County Council, the Erling Persson Foundation, VINNOVA and HMT. Irene Escudero-Martínez has received a grant from ‘Fundación Progreso y Salud, Junta de Andalucía’ (grant EF-0437-2018). RM has been supported by the project no. LQ1605 from the National Program of Sustainability II (MEYS CR). RH has been supported by the grants no. DRO–UHHK 00179906 from the Ministry of Health of the Czech Republic and no. PROGRES Q40 from Charles University, Czech Republic.Peer reviewe

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Enzimas antioxidantes en el infarto cerebral agudo

Background and purpose: Oxidative modification of DNA, protein and lipids by reactive oxygen peroxides plays an important role in acute cerebral infarction. The biological antioxidant defence system against oxidative stress is an integrated array of enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathion peroxidase (GPx). The purpose of this work was: 1. To investigate the evolution of SOD and CAT activities as possible markers of oxidative activity in patients with acute cerebral infarction. 2. To establish the relationship between the type of stroke and the activity of these two enzymes. 3. To analyze the relationship between the degree of neurological deficits of patients with stroke and SOD and CAT activities. Patients and methods: This is a prospective study comprising 45 patients with acute cerebral infarction (24 females and 21 males), aged from 48 to 96. The infarcts were classified in atherotrombotics and cardioembolics. SOD and CAT activities were measured on days 1, 3, 6 and 15. Results: Activities of SOD and CAT in patients on admission were lower than those of controls and showed a gradual increase over time. The activity mean of SOD was significantly higher in cardioembolic infarctions than in atherotrombotic infarctions (p 60, while CAT activity was higher. Conclusions: Our findings suggest that there is a progressive increase in SOD and CAT activity during ictus evolution, a different activity of SOD and CAT in cardioembolic and atherotrombotic infarctions, and that there is a relationship between activity of antioxidant enzymes and Mathew's score.Peer Reviewe

Tratamiento endovascular en el ictus isquémico agudo. Plan de Atención al Ictus en la Comunidad de Madrid

Resumen: Introducción: El tratamiento endovascular (trombólisis farmacológica intraarterial y trombectomía mecánica) en el ictus isquémico agudo se está implantando en la práctica clínica cotidiana, aunque continúa en desarrollo su investigación. En ausencia de datos suficientes que permitan fundamentar sólidamente las recomendaciones para su uso, es necesario elaborar protocolos de actuación basados en el conocimiento acumulado, así como monitorizar las actuaciones. Desarrollo: Tras revisión bibliográfica, en reuniones de trabajo de expertos para llegar a un consenso, se ha elaborado un protocolo de actuación que incluye indicaciones y contraindicaciones para la aplicación de tratamiento endovascular y recomendaciones referentes a la metodología de diagnóstico y selección de los pacientes, de los procedimientos de revascularización y manejo posterior, con el objetivo de incrementar las probabilidades de eficacia y beneficio del tratamiento y minimizar los riesgos de complicaciones y de recanalización fútil. En función del análisis de las necesidades asistenciales y los recursos disponibles se ha elaborado un sistema organizativo de colaboración interhospitalaria, para asegurar la accesibilidad al tratamiento garantizando el menor tiempo de respuesta y una relación coste/eficacia favorable. Incluye un registro prospectivo común con fines de monitorización para detectar oportunidades de mejora. Conclusiones: Para la implantación de técnicas endovasculares de tratamiento del ictus isquémico agudo es imprescindible la elaboración de protocolos de actuación basados en las evidencias disponibles y el establecimiento de sistemas adecuados de organización asistencial para garantizar el rigor y la eficacia de las actuaciones. Es necesario monitorizar los procedimientos con el fin de optimizar la metodología. Abstract: Introduction: Endovascular therapies (intra-arterial thrombolysis and mechanical thrombectomy) after acute ischaemic stroke are being implemented in the clinical setting even as they are still being researched. Since we lack sufficient data to establish accurate evidence-based recommendations for use of these treatments, we must develop clinical protocols based on current knowledge and carefully monitor all procedures. Development: After review of the literature and holding work sessions to reach a consensus among experts, we developed a clinical protocol including indications and contraindications for endovascular therapies use in acute ischaemic stroke. The protocol includes methodology recommendations for diagnosing and selecting patients, performing revascularisation procedures, and for subsequent patient management. Its objective is to increase the likelihood of efficacy and treatment benefit and minimise risk of complications and ineffective recanalisation. Based on an analysis of healthcare needs and available resources, a cooperative inter-hospital care system has been developed. This helps to ensure availability of endovascular therapies to all patients, a fast response time, and a good cost-to-efficacy ratio. It includes also a prospective register which serves to monitor procedures in order to identify any opportunities for improvement. Conclusions: Implementation of endovascular techniques for treating acute ischaemic stroke requires the elaboration of evidence-based clinical protocols and the establishment of appropriate cooperative healthcare networks guaranteeing both the availability and the quality of these actions. Such procedures must be monitored in order to improve methodology. Palabras clave: Ictus isquémico, Tratamiento endovascular, Neurointervencionismo, Trombectomía, Trombólisis, Activador tisular del plasminógeno recombinante, Keywords: Ischaemic stroke, Endovascular treatment, Neurointerventional surgery, Mechanical thrombectomy, Thrombolysis, rtP