RESUMEN
BACKGROUND/OBJECTIVES: Meteorological factors seem to influence stroke incidence, however, the complex association between weather and stroke remains unclear. Possible explanations from the literature do not categorize into subdivisions of ischemic strokes, only have small patient numbers, or refer to a selection of isolated weather elements without investigating weather changes and more. METHOD: In this exploratory trial, almost 18,000 stroke cases from a single stroke center in Southern Germany were analyzed from 2006 to 2015 and classified into the main subgroups of strokes and subdivisions of ischemic stroke etiologies applying the Trial of Org 10172 in Acute Stroke Treatment classification. For each stroke event, the air mass classification was determined from a subset of 7 air mass categories. Relative excess morbidities were derived for the 7 different air mass categories, taking into account the day of the event and up to 2 and 5 days preceding the stroke event. RESULTS: Statistically significant findings (α ≤0.1) reveal that dry tropical air masses were associated with a lower/higher risk for hemorrhagic (HEM)/macroangiopathic strokes (MAS), respectively. Dry polar air masses were associated with a higher risk for intracerebral bleedings and lower risk for ischemic stroke subtypes. Moist air masses were associated with a reduced incidence of MAS. A strong temperature increase 5 days prior to the event was associated with a lower risk of HEM strokes. Temperature increases were associated with lower risks for MAS and cardio-embolic strokes. Significant temperature decreases were associated with a higher risk of MAS. CONCLUSIONS: Temperature effects were dependent on both air masses and temperature changes within 5 days prior to the event and were associated with statistically relevant changes in stroke incidence. Decisive factors such as etiology, age, sex, and risk factors were also taken into account.
Asunto(s)
Accidente Cerebrovascular/epidemiología , Tiempo (Meteorología) , Anciano , Femenino , Alemania/epidemiología , Humanos , Humedad , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Temperatura , Factores de TiempoRESUMEN
PURPOSE: Most cancer-related deaths worldwide are associated with lung cancer. Subtyping of non-small cell lung cancer (NSCLC) into adenocarcinoma (AC) and squamous cell carcinoma (SqCC) is of importance, as therapy regimes differ. However, conventional staining and immunohistochemistry have their limitations. Therefore, a spatial metabolomics approach was aimed to detect differences between subtypes and to discriminate tumor and stroma regions in tissues. METHODS: Fresh-frozen NSCLC tissues (n = 35) were analyzed by matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) of small molecules (< m/z 1000). Measured samples were subsequently stained and histopathologically examined. A differentiation of subtypes and a discrimination of tumor and stroma regions was performed by receiver operating characteristic analysis and machine learning algorithms. RESULTS: Histology-guided spatial metabolomics revealed differences between AC and SqCC and between NSCLC tumor and tumor microenvironment. A diagnostic ability of 0.95 was achieved for the discrimination of AC and SqCC. Metabolomic contrast to the tumor microenvironment was revealed with an area under the curve of 0.96 due to differences in phospholipid profile. Furthermore, the detection of NSCLC with rarely arising mutations of the isocitrate dehydrogenase (IDH) gene was demonstrated through 45 times enhanced oncometabolite levels. CONCLUSION: MALDI-MSI of small molecules can contribute to NSCLC subtyping. Measurements can be performed intraoperatively on a single tissue section to support currently available approaches. Moreover, the technique can be beneficial in screening of IDH-mutants for the characterization of these seldom cases promoting the development of treatment strategies.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/clasificación , Neoplasias Pulmonares/clasificación , Metabolómica/métodos , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Cohortes , Técnicas Citológicas/métodos , Femenino , Alemania , Humanos , Inmunohistoquímica/métodos , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
A lack of nitric oxide (NO) may be a possible factor in the pathogenesis of an acute decrease of cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). This study was conducted to investigate whether early therapy with an NO-donor can improve CBF and offer neuroprotection after experimental SAH in rats. Male Sprague-Dawley rats were subjected to SAH by the endovascular filament model and treated with 1.5µg/kg/min of intravenous sodium nitroprusside (SNP) or vehicle (n=10) starting 15min after induction of SAH until 180min thereafter. SNP caused a moderate decrease of arterial blood pressure and cerebral perfusion pressure. Conversely, CBF measured by laser-Doppler flowmetry increased significantly in SNP-treated animals. The rate of injured neurons in the hippocampal CA1-field was significantly reduced in SNP-treated animals (10.5±5%) compared to controls (14.2±7%), as well as the number of Caspase-3 positive neurons. Low-dose treatment with SNP can attenuate an early perfusion deficit after SAH and reduce neuronal damage in spite of a hypotensive side effect. This may reflect the reversal of an early NO-deficit. In the clinical setting, the moderate hypotensive effect may be welcome since SAH-patients frequently present with elevated blood pressure.