ES2559104T3 - Método para predecir la evolución de un paciente que sufre de ictus - Google Patents
Método para predecir la evolución de un paciente que sufre de ictus Download PDFInfo
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- ES2559104T3 ES2559104T3 ES12704430.3T ES12704430T ES2559104T3 ES 2559104 T3 ES2559104 T3 ES 2559104T3 ES 12704430 T ES12704430 T ES 12704430T ES 2559104 T3 ES2559104 T3 ES 2559104T3
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- stroke
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- endostatin
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- 208000006011 Stroke Diseases 0.000 title abstract description 10
- 108010039471 Fas Ligand Protein Proteins 0.000 abstract description 7
- 102000015212 Fas Ligand Protein Human genes 0.000 abstract description 7
- 102100031162 Collagen alpha-1(XVIII) chain Human genes 0.000 abstract description 6
- 108010079505 Endostatins Proteins 0.000 abstract description 6
- 150000007523 nucleic acids Chemical class 0.000 abstract 2
- 102000039446 nucleic acids Human genes 0.000 abstract 2
- 108020004707 nucleic acids Proteins 0.000 abstract 2
- 239000012472 biological sample Substances 0.000 abstract 1
- 230000001419 dependent effect Effects 0.000 description 3
- 210000003657 middle cerebral artery Anatomy 0.000 description 3
- 230000002537 thrombolytic effect Effects 0.000 description 3
- 208000032382 Ischaemic stroke Diseases 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 101500026378 Homo sapiens Endostatin Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 108050006955 Tissue-type plasminogen activator Proteins 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 229960003318 alteplase Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 229940124301 concurrent medication Drugs 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 201000007309 middle cerebral artery infarction Diseases 0.000 description 1
- 230000037420 neurological improvement Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/475—Assays involving growth factors
- G01N2333/515—Angiogenesic factors; Angiogenin
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153 or CD154
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2871—Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/54—Determining the risk of relapse
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/56—Staging of a disease; Further complications associated with the disease
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Cell Biology (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
Método para predecir la evolución de un paciente que sufre de ictus, que comprende: a) evaluar en una muestra biológica obtenida de dicho paciente el nivel de endostatina y FasL, o de sus moléculas de ácido nucleico respectivas que las codifican; b) determinar si dichos niveles de endostatina y FasL juntos, o de sus moléculas de ácido nucleico respectivas que las codifican, están por encima o debajo de unos niveles de corte predeterminados; y c) predecir el resultado funcional del ictus en dicho paciente evaluando el resultado a la etapa b).
Description
Figura 3. Porcentaje de pacientes dependientes de ictus (calificación > de 2) dependientes del nivel de endostatina (igual o mayor de 184 ng/ml) y FasL igual o mayor de de 37,1 ng/ml.
Figura 4. Curvas ROC del modelo de variable clínica y del modelo de variable clínica + biomarcadores comparados con la línea de referencia.
En el alcance de la presente descripción, “variable clínica” significa los datos demográficos indicativos de ictus tal como la edad, el género, y la historia familiar del ictus, así como también la información clínica tal como la presencia de hipertensión, dislipidemia, diabetes, fibrilación atrial, enfermedad cardiaca, fumar, medicación, y la historia clínica pasada del ictus.
Los siguientes ejemplos se incluyen como soporte de la materia objeto reivindicado, en ningún caso limitando el alcance de la presente invención.
El estudio incluyó pacientes con ictus isquémico agudo (n = 61) que involucra el territorio de la Arteria Cerebral Media (MCA) admitida en el departamento de emergencias del Hospital Vall d´Hebron, Barcelona, España. Todos los pacientes recibieron terapia trombolítica en una dosis estándar de 0,9 mg/kg (10% de bolo y 90% de infusión continua durante 1h) dentro de las 3h desde el inicio de los síntomas. En la admisión, todos los pacientes tuvieron o se les hizo una exploración con una Tomografía Craneal Computarizada (CT) y una segunda exploración CT se repitió 24 a 48 horas después (o antes cuando ocurrió el deterioro neurológico rápido) para evaluar la presencia y el tipo de transformación hemorrágica (HT) que se definió de acuerdo con los criterios previamente publicados (Hacke et al., Thrombolysis with alteplase 3 to 4,5 hours after acute ischemic stroke. N Engl J Med. 2008; 359: 1317-29; Pessin 1990). Las mediciones Doppler Transcraneanas (TCD) se efectuaron por un neurólogo experimentado sin acceso a los resultados de laboratorio, con el uso de un dispositivo Multi-Dop X4 TCD (DWL Elektroniche System GmbH). Los exámenes TCD se efectuaron antes de iniciar el tratamiento, y al final de la infusión t-PA y en serie durante las primeras 24 h. Las oclusiones próximas y distantes MCA y los grados de recanalización de seguimiento fueron definidos como se describió previamente (Burgin et al, Transcranial doppler ultrasound criteria for recanalization after thrombolysis for middle cerebral artery stroke. Stoke 2000; 31: 1128-32).
Se obtuvo de cada paciente una historia detallada de los factores de riesgo vasculares, abuso de drogas, alcoholismo y medicación concomitante. Las Calificaciones de la Escala del Ictus del Instituto Nacional de Salud (NIHSS) se registraron para evaluar el nivel de conciencia y el estado neurológico en la admisión y durante las visitas de seguimiento (2,12, 24, 48h y a la descarga entre 3-7 días). La mejora neurológica se definió como una disminución en el NIHSS ≥ 4 puntos y el deterioro neurológico como muerte o incremento en el NIHSS ≥ 4 puntos a las 48h. El resultado funcional se definió mediante la escala Rankin modificada (mRS) tres meses después del ictus. Los pacientes fueron considerados dependientes cuando la calificación de la escala Rankin fue > de 2 puntos.
Las muestras de sangre venosa fueron extraídas de cada paciente en la admisión (línea base). El plasma fue extraído en tubos de EDTA, fue inmediatamente separado mediante centrifugación a 3000 rpm durante 15 minutos y almacenado a -80°C hasta el análisis. El nivel del plasma de la endostatina humana se determinó mediante ELISA comercialmente disponible (Quantikine, R& D Systems, MN, USA) y FasL a través de la tecnología SearchLight. Cada muestra de plasma se analizó dos veces y la media de dos valores fue dada en ng/ml. Los coeficientes intraensayo medios de la variación fueron de menos de 30% para ambos biomarcadores. La endostatina y los niveles de FasL fueron expresados como una media ± desviación estándar. El significado estadístico para las diferencias entre grupos se evaluó mediante la prueba Mann-Whitney. P < 0,05 se consideró estadísticamente significativo. Para estudiar las correlaciones entre las variables continuas, se utilizaron los coeficientes Spearman. Los niveles de endostatina y FasL no siguieron una distribución normal (Kolmogorov-Smirnov y gráfica P-P). Los niveles de endostatina y FasL (media ± desviación estándar) y su asociación con las características demográficas, variables clínicas y el perfil de factores de riesgo en pacientes con ictus dependiendo de las características demográficas se muestra en la Tabla 1.
7
Claims (1)
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imagen1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11382047 | 2011-02-22 | ||
| EP11382047A EP2492691A1 (en) | 2011-02-22 | 2011-02-22 | Method of predicting the evolution of a patient suffering of a neurovascular disease |
| PCT/EP2012/052876 WO2012113760A1 (en) | 2011-02-22 | 2012-02-20 | Method of predicting the evolution of a patient suffering of stroke |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2559104T3 true ES2559104T3 (es) | 2016-02-10 |
Family
ID=44279868
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12704430.3T Active ES2559104T3 (es) | 2011-02-22 | 2012-02-20 | Método para predecir la evolución de un paciente que sufre de ictus |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20140045198A1 (es) |
| EP (2) | EP2492691A1 (es) |
| CA (1) | CA2827461A1 (es) |
| ES (1) | ES2559104T3 (es) |
| WO (1) | WO2012113760A1 (es) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150302155A1 (en) * | 2014-04-16 | 2015-10-22 | Xerox Corporation | Methods and systems for predicting health condition of human subject |
| US9870449B2 (en) | 2015-02-24 | 2018-01-16 | Conduent Business Services, Llc | Methods and systems for predicting health condition of human subjects |
| WO2018183213A1 (en) | 2017-03-27 | 2018-10-04 | The Schepens Eye Research Institute, Inc. | Blood biomarkers and diagnostic methods for small vessel diseases |
| WO2018183216A1 (en) | 2017-03-27 | 2018-10-04 | The Schepens Eye Research Institute, Inc. | Notch3 agonist compositions and methods for treating small vessel diseases |
| WO2021009287A1 (en) * | 2019-07-16 | 2021-01-21 | Fundació Hospital Universitari Vall D'hebron - Institut De Recerca | Biomarkers for stroke prognosis |
| EP3940383A1 (en) * | 2020-07-16 | 2022-01-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the outcome of patients having acute ischemic stroke |
| CN113345581B (zh) * | 2021-05-14 | 2023-06-27 | 浙江工业大学 | 一种基于集成学习的脑卒中溶栓后出血概率预测方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003302340B8 (en) | 2002-12-24 | 2008-09-11 | Biosite Incorporated | Markers for differential diagnosis and methods of use thereof |
| CN104961831B (zh) | 2007-09-05 | 2020-06-23 | 江苏先声药业有限公司 | 一种修饰的重组人内皮抑素及其应用 |
| US20110123534A1 (en) * | 2007-12-12 | 2011-05-26 | Erasmus University Medical Center Rotterdam | Novel compounds for modulating neovascularisation and methods of treatment using these compounds |
| EP2166358A1 (en) | 2008-09-17 | 2010-03-24 | Fundacio Institut de Recerca de l'Hospital Universitari Vall d'Hebron | Differential diagnostic biomarkers of stroke mimicking conditions and methods of use thereof |
| JP2013509874A (ja) * | 2009-11-04 | 2013-03-21 | エラスムス ユニバーシティ メディカル センター ロッテルダム | 新脈管形成を調節する為の新規化合物及びこれらの化合物を使用する処置方法 |
-
2011
- 2011-02-22 EP EP11382047A patent/EP2492691A1/en not_active Withdrawn
-
2012
- 2012-02-20 CA CA2827461A patent/CA2827461A1/en not_active Abandoned
- 2012-02-20 US US14/001,006 patent/US20140045198A1/en not_active Abandoned
- 2012-02-20 EP EP12704430.3A patent/EP2678688B1/en not_active Not-in-force
- 2012-02-20 ES ES12704430.3T patent/ES2559104T3/es active Active
- 2012-02-20 WO PCT/EP2012/052876 patent/WO2012113760A1/en active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| CA2827461A1 (en) | 2012-08-30 |
| WO2012113760A1 (en) | 2012-08-30 |
| EP2678688B1 (en) | 2015-09-30 |
| EP2492691A1 (en) | 2012-08-29 |
| EP2678688A1 (en) | 2014-01-01 |
| US20140045198A1 (en) | 2014-02-13 |
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