RESUMEN
BACKGROUND AND PURPOSE: The Intensive Blood Pressure Reduction In Acute Cerebral Haemorrhage Trial (INTERACT) study suggests that early intensive blood pressure (BP) lowering can attenuate hematoma growth at 24 hours after intracerebral hemorrhage. The present analyses aimed to determine the effects of treatment on hematoma and perihematomal edema over 72 hours. METHODS: INTERACT included 404 patients with CT-confirmed intracerebral hemorrhage, elevated systolic BP (150 to 220 mm Hg), and capacity to start BP-lowering treatment within 6 hours of intracerebral hemorrhage. Patients were randomly assigned to an intensive (target systolic BP 140 mmHg) or standard guideline-based management of BP (target systolic BP 180 mm Hg) using routine intravenous agents. Baseline and repeat CTs (24 and 72 hours) were performed using standardized techniques with digital images analyzed centrally. Outcomes were increases in hematoma and perihematomal edema volumes over 72 hours. RESULTS: Overall, 296 patients had all 3 CT scans available for the hematoma and 270 for the edema analyses. Mean systolic BP was 11.7 mm Hg lower in the intensive group than in the guideline group during 1 to 24 hours. Adjusted mean absolute increases in hematoma volumes (mL) at 24 and 72 hours were 2.40 and 0.15 in the guideline group compared with -0.74 and -2.31 in the intensive group, respectively, an overall difference of 2.80 (95% CI, 1.04 to 4.56; P=0.002). Adjusted mean absolute increases in edema volumes (mL) at 24 and 72 hours were 6.27 and 10.02 in the guideline group compared with 4.19 and 7.34 in the intensive group, respectively, for an overall difference of 2.38 (95% CI, -0.45 to 5.22; P=0.10). CONCLUSIONS: Early intensive BP-lowering treatment attenuated hematoma growth over 72 hours in intracerebral hemorrhage. There were no appreciable effects on perihematomal edema.
Asunto(s)
Antihipertensivos/administración & dosificación , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/patología , Hipertensión/tratamiento farmacológico , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Hemorragia Intracraneal Hipertensiva/patología , Enfermedad Aguda/terapia , Adulto , Anciano , Antihipertensivos/efectos adversos , Australia , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Edema Encefálico/etiología , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/efectos de los fármacos , Arterias Cerebrales/patología , China , Progresión de la Enfermedad , Esquema de Medicación , Diagnóstico Precoz , Servicios Médicos de Urgencia/métodos , Servicios Médicos de Urgencia/estadística & datos numéricos , Femenino , Humanos , Hipertensión/complicaciones , Hemorragia Intracraneal Hipertensiva/complicaciones , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Guías de Práctica Clínica como Asunto , República de Corea , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Purpose: Pre-operative botulinum toxin A (BTA) injection of the lateral obliques aims to facilitate the closure of large ventral hernia defects and decrease the risk of repair breakdown during the critical healing phase. The exact duration of post-operative BTA effect and top-up timing in cases at high risk of recurrence remains uncertain. This study was designed to assess the value of electromyography (EMG) in determining the appropriate time for BTA top-up. Methods: 56 patients underwent ventral hernia repair with pre-operative BTA infiltration of the lateral obliques. Eleven patients at high risk of recurrence considered suitable for BTA top-up were assessed post-operatively with both functional computed tomography (CT) and EMG. CT assessed segmental contractility of each muscle layer. Single-point EMG assessed the activity of individual muscle layers bilaterally in the anterior axillary line. Results: CT showed (i) variable contractility of anterior and posterior muscle segments prior to BTA injection; (ii) absent or incomplete muscle paralysis in over half of all segments; (iii) increased BTA effect on progress scans; and (iv) non-uniform pattern of change in BTA effect between the anterior and posterior muscle. EMG demonstrated modest voluntary activity in most muscle layers. Compared to standard of reference (CT), EMG showed moderate sensitivity (0.62), poor specificity (0.48), poor accuracy (0.57), and incorrect grading in 71% of true positive results. Conclusions: As BTA effect wanes, single-point EMG cannot reliably determine functional muscle status. A novel finding is that BTA-induced paralysis of the abdominal muscles may be remarkably non-uniform in degree, distribution and duration.
RESUMEN
BACKGROUND: There is much uncertainty about the effects of early lowering of elevated blood pressure (BP) after acute intracerebral haemorrhage (ICH). Our aim was to assess the safety and efficiency of this treatment, as a run-in phase to a larger trial. METHODS: Patients who had acute spontaneous ICH diagnosed by CT within 6 h of onset, elevated systolic BP (150-220 mm Hg), and no definite indication or contraindication to treatment were randomly assigned to early intensive lowering of BP (target systolic BP 140 mm Hg; n=203) or standard guideline-based management of BP (target systolic BP 180 mm Hg; n=201). The primary efficacy endpoint was proportional change in haematoma volume at 24 h; secondary efficacy outcomes included other measurements of haematoma volume. Safety and clinical outcomes were assessed for up to 90 days. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00226096. FINDINGS: Baseline characteristics of patients were similar between groups, but mean haematoma volumes were smaller in the guideline group (12.7 mL, SD 11.6) than in the intensive group (14.2 mL, SD 14.5). From randomisation to 1 h, mean systolic BP was 153 mm Hg in the intensive group and 167 mm Hg in the guideline group (difference 13.3 mm Hg, 95% CI 8.9-17.6 mm Hg; p<0.0001); from 1 h to 24 h, BP was 146 mm Hg in the intensive group and 157 mm Hg in the guideline group (10.8 mm Hg, 95% CI 7.7-13.9 mm Hg; p<0.0001). Mean proportional haematoma growth was 36.3% in the guideline group and 13.7% in the intensive group (difference 22.6%, 95% CI 0.6-44.5%; p=0.04) at 24 h. After adjustment for initial haematoma volume and time from onset to CT, median haematoma growth differed between the groups with p=0.06; the absolute difference in volume between groups was 1.7 mL (95% CI -0.5 to 3.9, p=0.13). Relative risk of haematoma growth >or=33% or >or=12.5 mL was 36% lower (95% CI 0-59%, p=0.05) in the intensive group than in the guideline group. The absolute risk reduction was 8% (95% CI -1.0 to 17%, p=0.05). Intensive BP-lowering treatment did not alter the risks of adverse events or secondary clinical outcomes at 90 days. INTERPRETATION: Early intensive BP-lowering treatment is clinically feasible, well tolerated, and seems to reduce haematoma growth in ICH. A large randomised trial is needed to define the effects on clinical outcomes across a broad range of patients with ICH. FUNDING: National Health and Medical Research Council of Australia.
Asunto(s)
Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/fisiopatología , Cuidados Críticos/métodos , Anciano , Análisis de Varianza , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Presión Sanguínea/fisiología , Monitoreo Ambulatorio de la Presión Arterial , Diuréticos/uso terapéutico , Esquema de Medicación , Femenino , Escala de Coma de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Conducta de Reducción del Riesgo , Método Simple Ciego , Factores de TiempoRESUMEN
The pilot phase of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT) showed that rapid blood pressure (BP) lowering can attenuate hematoma growth in acute intracerebral hemorrhage. We sought to define the systolic BP level associated with greatest attenuation of hematoma growth. INTERACT included 404 patients with computed tomographic-confirmed intracerebral hemorrhage, elevated systolic BP (150 to 220 mm Hg), and capacity to commence BP lowering treatment within 6 hours of onset. Computed tomography was done at baseline and at 24 hours using standardized techniques, with digital images analyzed centrally, blinded to clinical data. Associations of baseline and achieved on-treatment (mean during the first 24 hours) systolic BP levels with the primary outcome of increase in hematoma volume were explored. There were 346 patients with duplicate computed tomographic scans. There was no significant association between baseline systolic BP levels and either the absolute or proportional growth in hematoma volume (P trend=0.26 and 0.12, respectively). By contrast, achieved on-treatment systolic BP levels in the first 24 hours were clearly associated with both absolute and proportional hematoma growth (both P trend=0.03). Maximum reduction in hematoma growth occurred in the one third of participants with the lowest on-treatment systolic BP levels (median: 135 mm Hg). Intensive BP reduction to systolic levels between 130 and 140 mm Hg is likely to provide the maximum protection against hematoma growth after intracerebral hemorrhage.
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Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Hemorragia Cerebral/tratamiento farmacológico , Hematoma/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Hemorragia Cerebral/diagnóstico por imagen , Femenino , Hematoma/diagnóstico por imagen , Hematoma/prevención & control , Humanos , Hipertensión/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Selección de Paciente , Radiografía , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Separación Celular/métodos , Clonación Molecular/métodos , Inmunidad Celular/inmunología , Inmunoensayo/métodos , Microdisección/métodos , Proteínas del Tejido Nervioso/inmunología , Linfocitos T/inmunología , Linfocitos T/patología , Autoantígenos , Humanos , Proteínas del Tejido Nervioso/análisis , Proteínas del Tejido Nervioso/genética , Linfocitos T/clasificaciónRESUMEN
We surveyed the T cell receptor repertoire in three separate compartments (brain, cerebrospinal fluid, and blood) of two multiple sclerosis patients who initially had diagnostic brain biopsies to clarify their unusual clinical presentation but were subsequently confirmed to have typical multiple sclerosis. One of the brain biopsy specimens had been previously investigated by microdissection and single-cell PCR to determine the clonal composition of brain-infiltrating T cells at the single-cell level. Using complementarity-determining region 3 spectratyping, we identified several identical, expanded CD8+ (but not CD4+) T cell clones in all three compartments. Some of the expanded CD8+ T cells also occurred in sorted CD38+ blood cells, suggesting that they were activated. Strikingly, some of the brain-infiltrating CD8+ T cell clones persisted for >5 years in the cerebrospinal fluid and/or blood and may thus contribute to the progression of the disease.