BACKGROUND： Numerous studies have shown that tumor necrosis factor α （TNF-α） is closely correlated with spinal cord injury （SCI）, but the mechanisms of TNF-α and therapeutic treatments for SCI are still poorly...BACKGROUND： Numerous studies have shown that tumor necrosis factor α （TNF-α） is closely correlated with spinal cord injury （SCI）, but the mechanisms of TNF-α and therapeutic treatments for SCI are still poorly understood. OBJECTIVE： To determine the role of TNF-α in the pathogenesis of SCI. DESIGN, TIME AND SETTING： An in vivo experiment based on genetically engineered animals was performed at the Medical University of South Carolina, Charleston, South Carolina, USA, between June 2007 and October 2008. MATERIALS： TNF-α transgenic rats （Xenogen Biosciences in Cranbury, New Jersey, USA） were utilized in this study. METHODS： TNF-α transgenic （tg） and wild-type （WT） rats underwent a complete single-level laminectomy at the 10^th thoracic vertebra （T10）. MAIN OUTCOME MEASURES： Motor function of rat hindlimb was assessed using the Basso, Beattie, and Bresnahan hindlimb locomotor rating scale. Histological evaluation of spinal cord tissue loss was conducted. Immunohistochemistry for astrocytes, microglia/macrophages, and TNF receptors （TNFRs） was performed on spinal cord tissue sections. TNF-α mRNA expression was detected by real-time polymerase chain reaction. The concentrations of nerve growth factor （NGF） and brain-derived neurotrophic factor （BDNF） in the supernatant were determined using an enzyme-linked immunosorbent assay kit for rat NGF or BDNF, respectively. The rats were injected subcutaneously with etanercept to verify that TNF-α was the direct effect of the modulation of behavioral and neurodegenerative outcomes in the TNF-α tg rats. RESULTS： TNF-α tg rats showed higher expression of TNF-α mRNA in the spinal cord prior to SCI. TNF-α tg rats showed worse motor deficits than WT rats in the acute period （〈 3 days） after SCI （P 〈 0.01）, while in the chronic period, TNF-α tg rats exhibited persistent elevated baseline levels of TNF-α mRNA and improved recovery in motor function and tissue healing compared to WT rats （P 〈 0.01 ）. Following SCI, the number of microglia/macrophages in TNF-α tg rat was always greater than in WT rat （P 〈 0.01）. There were no significant differences in NGF and BDNF levels in the supernatant of spinal cord homogenates. TNFR1 expression was significantly greater in the TNF-α tg rats compared to the WT rats （P 〈 0.01）. However, TNFR2 expression did not reveal a significant increase in the TNF-α tg rats compared to the WT rats. Finally, treatment with etanercept reduced injury acutely, but exacerbated the injury chronically. CONCLUSION： Overexpression of TNF-α is deleterious in the acute phase, but beneficial in the chronic phase in the response to SCI. The role of TNF-α post-injury may depend on TNF-α expression in the spinal cord and its differential binding to TNFRI. Our observations may have clinical relevance that antagonists or inhibitors of TNF-α could be administered within the early time window post-injury, and appropriate amounts of TNF-α could be administered during the chronic stage, in order to improve the final neurological recovery in patients with SCI.展开更多
Background and Purpose -The presence of computed tomography dense signs in acute ischemic stroke indicates thrombosis. We sought to ascertain whether reversibility of these signs provides additional prognostic informa...Background and Purpose -The presence of computed tomography dense signs in acute ischemic stroke indicates thrombosis. We sought to ascertain whether reversibility of these signs provides additional prognostic information. Methods -Baseline and follow-up imaging was obtained from 18 patients who had received intra venous abciximab and heparin as part of an ongoing safety study in acute ischemic stroke. Presence of signs and their reversal were assessed and correlated with mortality and 90-day outcome. Results -Fourteen of the 18 patients had dense dot signs in the middle cerebral or dense signals in the basilar artery on baseline computed tomography. The signs reversed in 7 (group 1) and persisted in 7 (group 2). Mean baseline National Institutes of Health Stroke Scale did not differ. All 7 in group 1 were alive at 90 days, with 3 of 7 alive in group 2. Ninety- day modified Rankin Scale was lower in group 1 (1.9±1.57) compared with group 2 (4.6±1.9; P=0.01). Conclusions -The reversal of dense signs predicts a much better outcome than its persistence. These signs should receive additional attent ion for both their diagnostic and prognostic importance.展开更多
Ischemic stroke subtype distribution was compared between Mexican Americans (MAs) and non Hispanic whites (NHWs) in a community based stroke surveillance study in Nueces County,TX. Therewas no difference in the distri...Ischemic stroke subtype distribution was compared between Mexican Americans (MAs) and non Hispanic whites (NHWs) in a community based stroke surveillance study in Nueces County,TX. Therewas no difference in the distribution of stroke subtype by ethnicity (p = 0.19). There was a similar proportion of small vessel and large artery strokes between the two ethnic groups (p = 0.32). Differences in stroke rates among MAs and NHWs are not explained by the distribution of ischemic stroke subtypes.展开更多
The treatment approach for patients with internal carotid artery stenosis is receiving increased scrutiny.Major advances in optimal medical therapy have been associated with a declining stroke rate for symptomatic and...The treatment approach for patients with internal carotid artery stenosis is receiving increased scrutiny.Major advances in optimal medical therapy have been associated with a declining stroke rate for symptomatic and asymptomatic patients with carotid stenosis.Customising treatment according to gender is worthy of consideration,since earlier clinical trials showed reduced benefit with carotid endarterectomy in women compared to men.In this review,clinical trial results in women are summarised,studies pertaining to carotid plaque imaging in men and women are discussed and new clinical trials are identified.Finally,the rationale for a women’s carotid trial is provided.展开更多
Objective The concept of the‘self-fulfilling prophecy’is well established in intracerebral haemorrhage(ICH).The ability to improve prognostication and prediction of long-term outcomes during the first days of hospit...Objective The concept of the‘self-fulfilling prophecy’is well established in intracerebral haemorrhage(ICH).The ability to improve prognostication and prediction of long-term outcomes during the first days of hospitalisation is important in guiding conversations around goals of care.We previously demonstrated that incorporating delayed imaging into various prognostication scores for ICH improves the predictive accuracy of 90-day mortality.However,delayed prognostication scores have not been used to predict long-term functional outcomes beyond 90 days.Design,setting and participants We analysed data from the ICH Deferoxamine trial to see if delaying the use of prognostication scores to 96 hours after ICH onset will improve performance to predict outcomes at 180 days.276 patients were included.Interventions and measurements We calculated the original ICH score(oICH),modified-ICH score(MICH),max-ICH score and the FUNC score on presentation(baseline),and on day 4(delayed).Outcomes assessed were mortality and poor functional outcome in survivors(defined as modified Rankin Scale of 4-5)at 180 days.We generated receiver operating characteristic curves,and measured the area under the curve values(AUC)for mortality and functional outcome.We compared baseline and delayed AUCs with non-parametric methods.Results At 180 days,21 of 276(7.6%)died.Out of the survivors,54 of 255 had poor functional outcome(21.2%).The oICH,MICH and max-ICH performed significantly better at predicting 180-day mortality when calculated 4 days later compared with their baseline equivalents((0.74 vs 0.83,p=0.005),(0.73 vs 0.80,p=0.036),(0.74 vs 0.83,p=0.008),respectively).The delayed calculation of these scores did not significantly improve our accuracy for predicting poor functional outcomes.Conclusion Delaying the calculation of prognostication scores in acute ICH until day 4 improved prediction of 6-month mortality but not functional outcomes.Trial registration number ClinicalTrials.gov Registry(NCT02175225).展开更多
Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ...Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.Methods We conducted a cross-sectional,retrospective,observational study across 6 continents,37 countries and 140 comprehensive stroke centres.Patients with the diagnosis of SAH,aneurysmal SAH,ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases,10th Revision,codes.The 3-month cumulative volume,monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before(1 year and immediately before)and during the pandemic,defined as 1 March-31 May 2020.The prior 1-year control period(1 March-31 May 2019)was obtained to account for seasonal variation.Findings There was a significant decline in SAH hospitalisations,with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic,representing a relative decline of 22.5%(95%CI−24.3%to−20.7%,p<0.0001).Embolisation of ruptured aneurysms declined with 1170-1035 procedures,respectively,representing an 11.5%(95%CI−13.5%to−9.8%,p=0.002)relative drop.Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations,a 24.9%relative decline(95%CI−28.0%to−22.1%,p<0.0001).A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1%(95%CI 32.3%to 50.6%,p=0.008)despite a decrease in SAH admissions in this tertile.Interpretation There was a relative decrease in the volume of SAH hospitalisations,aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic.These findings in SAH are consistent with a decrease in other emergencies,such as stroke and myocardial infarction.展开更多
基金the ES016774-01A1VA Merit Award and National Science Foundation EPSCoR grant, No. EPS-0132573+1 种基金EPS-0447660 (MSK)NS050452-05 (JJH)
文摘BACKGROUND： Numerous studies have shown that tumor necrosis factor α （TNF-α） is closely correlated with spinal cord injury （SCI）, but the mechanisms of TNF-α and therapeutic treatments for SCI are still poorly understood. OBJECTIVE： To determine the role of TNF-α in the pathogenesis of SCI. DESIGN, TIME AND SETTING： An in vivo experiment based on genetically engineered animals was performed at the Medical University of South Carolina, Charleston, South Carolina, USA, between June 2007 and October 2008. MATERIALS： TNF-α transgenic rats （Xenogen Biosciences in Cranbury, New Jersey, USA） were utilized in this study. METHODS： TNF-α transgenic （tg） and wild-type （WT） rats underwent a complete single-level laminectomy at the 10^th thoracic vertebra （T10）. MAIN OUTCOME MEASURES： Motor function of rat hindlimb was assessed using the Basso, Beattie, and Bresnahan hindlimb locomotor rating scale. Histological evaluation of spinal cord tissue loss was conducted. Immunohistochemistry for astrocytes, microglia/macrophages, and TNF receptors （TNFRs） was performed on spinal cord tissue sections. TNF-α mRNA expression was detected by real-time polymerase chain reaction. The concentrations of nerve growth factor （NGF） and brain-derived neurotrophic factor （BDNF） in the supernatant were determined using an enzyme-linked immunosorbent assay kit for rat NGF or BDNF, respectively. The rats were injected subcutaneously with etanercept to verify that TNF-α was the direct effect of the modulation of behavioral and neurodegenerative outcomes in the TNF-α tg rats. RESULTS： TNF-α tg rats showed higher expression of TNF-α mRNA in the spinal cord prior to SCI. TNF-α tg rats showed worse motor deficits than WT rats in the acute period （〈 3 days） after SCI （P 〈 0.01）, while in the chronic period, TNF-α tg rats exhibited persistent elevated baseline levels of TNF-α mRNA and improved recovery in motor function and tissue healing compared to WT rats （P 〈 0.01 ）. Following SCI, the number of microglia/macrophages in TNF-α tg rat was always greater than in WT rat （P 〈 0.01）. There were no significant differences in NGF and BDNF levels in the supernatant of spinal cord homogenates. TNFR1 expression was significantly greater in the TNF-α tg rats compared to the WT rats （P 〈 0.01）. However, TNFR2 expression did not reveal a significant increase in the TNF-α tg rats compared to the WT rats. Finally, treatment with etanercept reduced injury acutely, but exacerbated the injury chronically. CONCLUSION： Overexpression of TNF-α is deleterious in the acute phase, but beneficial in the chronic phase in the response to SCI. The role of TNF-α post-injury may depend on TNF-α expression in the spinal cord and its differential binding to TNFRI. Our observations may have clinical relevance that antagonists or inhibitors of TNF-α could be administered within the early time window post-injury, and appropriate amounts of TNF-α could be administered during the chronic stage, in order to improve the final neurological recovery in patients with SCI.
文摘Background and Purpose -The presence of computed tomography dense signs in acute ischemic stroke indicates thrombosis. We sought to ascertain whether reversibility of these signs provides additional prognostic information. Methods -Baseline and follow-up imaging was obtained from 18 patients who had received intra venous abciximab and heparin as part of an ongoing safety study in acute ischemic stroke. Presence of signs and their reversal were assessed and correlated with mortality and 90-day outcome. Results -Fourteen of the 18 patients had dense dot signs in the middle cerebral or dense signals in the basilar artery on baseline computed tomography. The signs reversed in 7 (group 1) and persisted in 7 (group 2). Mean baseline National Institutes of Health Stroke Scale did not differ. All 7 in group 1 were alive at 90 days, with 3 of 7 alive in group 2. Ninety- day modified Rankin Scale was lower in group 1 (1.9±1.57) compared with group 2 (4.6±1.9; P=0.01). Conclusions -The reversal of dense signs predicts a much better outcome than its persistence. These signs should receive additional attent ion for both their diagnostic and prognostic importance.
文摘Ischemic stroke subtype distribution was compared between Mexican Americans (MAs) and non Hispanic whites (NHWs) in a community based stroke surveillance study in Nueces County,TX. Therewas no difference in the distribution of stroke subtype by ethnicity (p = 0.19). There was a similar proportion of small vessel and large artery strokes between the two ethnic groups (p = 0.32). Differences in stroke rates among MAs and NHWs are not explained by the distribution of ischemic stroke subtypes.
文摘The treatment approach for patients with internal carotid artery stenosis is receiving increased scrutiny.Major advances in optimal medical therapy have been associated with a declining stroke rate for symptomatic and asymptomatic patients with carotid stenosis.Customising treatment according to gender is worthy of consideration,since earlier clinical trials showed reduced benefit with carotid endarterectomy in women compared to men.In this review,clinical trial results in women are summarised,studies pertaining to carotid plaque imaging in men and women are discussed and new clinical trials are identified.Finally,the rationale for a women’s carotid trial is provided.
文摘Objective The concept of the‘self-fulfilling prophecy’is well established in intracerebral haemorrhage(ICH).The ability to improve prognostication and prediction of long-term outcomes during the first days of hospitalisation is important in guiding conversations around goals of care.We previously demonstrated that incorporating delayed imaging into various prognostication scores for ICH improves the predictive accuracy of 90-day mortality.However,delayed prognostication scores have not been used to predict long-term functional outcomes beyond 90 days.Design,setting and participants We analysed data from the ICH Deferoxamine trial to see if delaying the use of prognostication scores to 96 hours after ICH onset will improve performance to predict outcomes at 180 days.276 patients were included.Interventions and measurements We calculated the original ICH score(oICH),modified-ICH score(MICH),max-ICH score and the FUNC score on presentation(baseline),and on day 4(delayed).Outcomes assessed were mortality and poor functional outcome in survivors(defined as modified Rankin Scale of 4-5)at 180 days.We generated receiver operating characteristic curves,and measured the area under the curve values(AUC)for mortality and functional outcome.We compared baseline and delayed AUCs with non-parametric methods.Results At 180 days,21 of 276(7.6%)died.Out of the survivors,54 of 255 had poor functional outcome(21.2%).The oICH,MICH and max-ICH performed significantly better at predicting 180-day mortality when calculated 4 days later compared with their baseline equivalents((0.74 vs 0.83,p=0.005),(0.73 vs 0.80,p=0.036),(0.74 vs 0.83,p=0.008),respectively).The delayed calculation of these scores did not significantly improve our accuracy for predicting poor functional outcomes.Conclusion Delaying the calculation of prognostication scores in acute ICH until day 4 improved prediction of 6-month mortality but not functional outcomes.Trial registration number ClinicalTrials.gov Registry(NCT02175225).
文摘Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.Methods We conducted a cross-sectional,retrospective,observational study across 6 continents,37 countries and 140 comprehensive stroke centres.Patients with the diagnosis of SAH,aneurysmal SAH,ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases,10th Revision,codes.The 3-month cumulative volume,monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before(1 year and immediately before)and during the pandemic,defined as 1 March-31 May 2020.The prior 1-year control period(1 March-31 May 2019)was obtained to account for seasonal variation.Findings There was a significant decline in SAH hospitalisations,with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic,representing a relative decline of 22.5%(95%CI−24.3%to−20.7%,p<0.0001).Embolisation of ruptured aneurysms declined with 1170-1035 procedures,respectively,representing an 11.5%(95%CI−13.5%to−9.8%,p=0.002)relative drop.Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations,a 24.9%relative decline(95%CI−28.0%to−22.1%,p<0.0001).A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1%(95%CI 32.3%to 50.6%,p=0.008)despite a decrease in SAH admissions in this tertile.Interpretation There was a relative decrease in the volume of SAH hospitalisations,aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic.These findings in SAH are consistent with a decrease in other emergencies,such as stroke and myocardial infarction.
