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1.
Cerebrovasc Dis ; 50(1): 100-107, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33279889

RESUMO

INTRODUCTION: We have demonstrated that asymptomatic cerebral small vessel disease (cSVD) measured by white matter hyperintensity volume is associated with reduced manipulative manual dexterity on the Grooved Peg Board Test (GPBT) in middle-aged healthy individuals with a family history of early coronary artery disease. In this current study, we aim to identify the association of subcortical white matter microstructural impairment measured by diffusion tensor imaging, manual dexterity measured by GPBT and circulating serums ceramide, another marker for white matter injury. We hypothesize that lower regional fractional anisotropy (rFA) is associated with worse performance on GPBT and elevated serum ceramides in the same study population. METHODS: rFA of 48 regions representing the subcortical white matters were analyzed in GeneSTAR participants in addition to serum ceramides and GPBT scores. Unadjusted univariable analyses with Bonferroni correction for multiple comparisons were completed using Spearman correlation for testing the associations between ceramides, rFA of subcortical white matter, and GPBT performance. Subsequently, sensitivity analyses were performed after excluding the participants that had any physical limitation that may influence their performance on GPBT. Finally, in the adjusted analysis using generalized estimating equation, linear regression models were performed for the areas that met significance threshold in the unadjusted analyses. RESULTS: 112 subjects (age [49 ± 11], 51% female, 39.3% African American) were included. Adjusted analyses for the significant correlations that met the Bonferroni correction threshold in the unadjusted univariable analyses identified significant negative associations between rFA of the right fornix (RF) and log-GPBT score (ß = -0.497, p = 0.037). In addition, rFA of RF negatively correlated with log serum ceramide levels (C18: ß = -0.03, p = 0.003, C20: ß = -0.0002, p = 0.004) and rFA of left genu of corpus callosum negatively correlated with log C18 level (ß = -0.0103, p = 0.027). CONCLUSIONS: These results demonstrate that subcortical microstructural white matter disruption is associated with elevated serum ceramides and reduced manual dexterity in a population with cSVD. These findings suggest that injury to white matter tracts undermines neural networks, with functional consequences in a middle-aged population with cardiovascular risk factors.


Assuntos
Ceramidas/sangue , Doenças de Pequenos Vasos Cerebrais/diagnóstico , Cognição , Imagem de Tensor de Difusão , Leucoencefalopatias/diagnóstico , Atividade Motora , Testes Neuropsicológicos , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Biomarcadores/sangue , Doenças de Pequenos Vasos Cerebrais/sangue , Doenças de Pequenos Vasos Cerebrais/fisiopatologia , Doenças de Pequenos Vasos Cerebrais/psicologia , Estudos Transversais , Feminino , Humanos , Leucoencefalopatias/sangue , Leucoencefalopatias/fisiopatologia , Leucoencefalopatias/psicologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Regulação para Cima , Substância Branca/fisiopatologia
2.
Stroke ; 51(1): 129-136, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31744426

RESUMO

Background and Purpose- Patients with active malignancy are at risk for intracerebral hemorrhage (ICH). We aimed to characterize perihematomal edema (PHE) and hematoma volumes after spontaneous nontraumatic ICH in patients with cancer without central nervous system involvement. Methods- Patients with active malignancy who developed ICH were retrospectively identified through automated searches of institutional databases. Control patients were identified with ICH and without active cancer. Demographic and cancer-specific data were obtained by chart review. Hematoma and PHE volumes were determined using semiautomated methodology. Univariate and multivariate linear regression models were created to assess which variables were associated with hematoma and PHE expansion. Results- Patients with cancer (N=80) and controls (N=136) had similar demographics (all P>0.20), although hypertension was more prevalent among controls (P=0.004). Most patients with cancer had received recent chemotherapy (n=45, 56%) and had recurrence of malignancy (n=43, 54%). Patients with cancer were thrombocytopenic (median platelet count 90 000 [interquartile range, 17 500-211 500]), and most had undergone blood product transfusion (n=41, 51%), predominantly platelets (n=38, 48%). Thirty-day mortality was 36% (n=29). Patients with cancer had significantly increased PHE volumes (23.67 versus 8.61 mL; P=1.88×10-9) and PHE-to-ICH volume ratios (2.26 versus 0.99; P=2.20×10-16). In multivariate analyses, variables associated with PHE growth among patients with cancer were ICH volume (ß=1.29 [95% CI, 1.58-1.30] P=1.30×10-5) and platelet transfusion (ß=15.67 [95% CI, 3.61-27.74] P=0.014). Variables associated with 30-day mortality were ICH volume (odds ratio, 1.06 [95% CI, 1.03-1.10] P=6.76×10-5), PHE volume (odds ratio, 1.07 [95% CI, 1.04-1.09] P=7.40×10-6), PHE growth (odds ratio, 1.05 [95% CI, 1.01-1.10] P=0.01), and platelet transfusion (odds ratio, 1.48 [95% CI, 1.22-1.79] P=0.0001). Conclusions- Patients with active cancer who develop ICH have increased PHE volumes. PHE growth was independent of thrombocytopenia but associated with blood product transfusion. Thirty-day mortality was associated with PHE and ICH volumes and blood product transfusion.


Assuntos
Edema Encefálico/patologia , Hemorragia Cerebral/patologia , Hematoma/patologia , Neoplasias/complicações , Idoso , Edema Encefálico/complicações , Hemorragia Cerebral/complicações , Edema/complicações , Edema/patologia , Feminino , Hematoma/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença
3.
Neurocrit Care ; 32(2): 407-418, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32034657

RESUMO

BACKGROUND: With increasing use of direct oral anticoagulants (DOACs) and availability of new reversal agents, the risk of traumatic intracranial hemorrhage (tICH) requires better understanding. We compared hemorrhage expansion rates, mortality, and morbidity following tICH in patients treated with vitamin k antagonists (VKA: warfarin) and DOACs (apixaban, rivaroxaban, dabigatran). METHODS: Retrospective chart review of patients from 2010 to 2017 was performed to identify patients with imaging diagnosis of acute traumatic intraparenchymal, subdural, subarachnoid, and epidural hemorrhage with preadmission use of DOACs or VKAs. We identified 39 patients on DOACs and 97 patients on VKAs. Demographic information, comorbidities, hemorrhage size, and expansion over time, as well as discharge disposition and Glasgow Outcome Scale (GOS) were collected. Primary outcome was development of new or enlargement of tICH within the first 48 h of initial CT imaging. RESULTS: Of 136 patients with mean (SD) age 78.7 (13.2) years, most common tICH subtype was subdural hematoma (N = 102/136; 75%), and most common mechanism was a fall (N = 130/136; 95.6%). Majority of patients in the DOAC group did not receive reversal agents (66.7%). Hemorrhage expansion or new hemorrhage occurred in 11.1% in DOAC group vs. 14.6% in VKA group (p = 0.77) at a median of 8 and 11 h from initial ED admission, respectively (p = 0.82). Patients in the DOAC group compared to VKA group had higher median discharge GOS (4 vs. 3 respectively, p = 0.03), higher percentage of patients with good outcome (GOS 4-5, 66.7% vs. 40.2% respectively, p = 0.005), and higher rate of discharge to home or rehabilitation (p = 0.04). CONCLUSIONS: We report anticoagulation-associated tICH outcomes predominantly due to fall-related subdural hematomas. Patients on DOACs had lower tICH expansion rates although not statistically significantly different from VKA-treated patients. DOAC-treated patients had favorable outcomes versus VKA group following tICH despite low use of reversal strategies. DOAC use may be a safer alternative to VKA in patients at risk of traumatic brain hemorrhage.


Assuntos
Anticoagulantes/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Hemorragia Intracraniana Traumática/fisiopatologia , Varfarina/efeitos adversos , Acidentes por Quedas , Idoso , Idoso de 80 Anos ou mais , Antifibrinolíticos/uso terapêutico , Antitrombinas/efeitos adversos , Fatores de Coagulação Sanguínea/uso terapêutico , Coagulantes/uso terapêutico , Dabigatrana/efeitos adversos , Progressão da Doença , Feminino , Escala de Resultado de Glasgow , Humanos , Hemorragia Intracraniana Traumática/induzido quimicamente , Hemorragia Intracraniana Traumática/terapia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Mortalidade , Procedimentos Neurocirúrgicos , Plasma , Transfusão de Plaquetas , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Piridonas/efeitos adversos , Estudos Retrospectivos , Rivaroxabana/efeitos adversos , Tiazóis/efeitos adversos , Vitamina K/uso terapêutico
4.
Neurocrit Care ; 31(1): 229, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31119686

RESUMO

The authors note that there is a discrepancy between the text of the paper and Table 2 regarding physician subspecialty certification requirements in neurocritical care for Level II centers.

5.
Stroke ; 49(8): 1812-1819, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30002152

RESUMO

Background and Purpose- White matter hyperintensities (WMH) on brain magnetic resonance imaging are typical signs of cerebral small vessel disease and may indicate various preclinical, age-related neurological disorders, such as stroke. Though WMH are highly heritable, known common variants explain a small proportion of the WMH variance. The contribution of low-frequency/rare coding variants to WMH burden has not been explored. Methods- In the discovery sample we recruited 20 719 stroke/dementia-free adults from 13 population-based cohort studies within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, among which 17 790 were of European ancestry and 2929 of African ancestry. We genotyped these participants at ≈250 000 mostly exonic variants with Illumina HumanExome BeadChip arrays. We performed ethnicity-specific linear regression on rank-normalized WMH in each study separately, which were then combined in meta-analyses to test for association with single variants and genes aggregating the effects of putatively functional low-frequency/rare variants. We then sought replication of the top findings in 1192 adults (European ancestry) with whole exome/genome sequencing data from 2 independent studies. Results- At 17q25, we confirmed the association of multiple common variants in TRIM65, FBF1, and ACOX1 ( P<6×10-7). We also identified a novel association with 2 low-frequency nonsynonymous variants in MRPL38 (lead, rs34136221; PEA=4.5×10-8) partially independent of known common signal ( PEA(conditional)=1.4×10-3). We further identified a locus at 2q33 containing common variants in NBEAL1, CARF, and WDR12 (lead, rs2351524; Pall=1.9×10-10). Although our novel findings were not replicated because of limited power and possible differences in study design, meta-analysis of the discovery and replication samples yielded stronger association for the 2 low-frequency MRPL38 variants ( Prs34136221=2.8×10-8). Conclusions- Both common and low-frequency/rare functional variants influence WMH. Larger replication and experimental follow-up are essential to confirm our findings and uncover the biological causal mechanisms of age-related WMH.


Assuntos
Encéfalo/diagnóstico por imagem , Exoma/genética , Variação Genética/genética , Imageamento por Ressonância Magnética/métodos , Proteínas Mitocondriais/genética , Substância Branca/diagnóstico por imagem , Estudos de Coortes , Humanos
6.
Neurocrit Care ; 29(2): 145-160, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30251072

RESUMO

Neurocritical care is a distinct subspecialty focusing on the optimal management of acutely ill patients with life-threatening neurologic and neurosurgical disease or with life-threatening neurologic manifestations of systemic disease. Care by expert healthcare providers to optimize neurologic recovery is necessary. Given the lack of an organizational framework and criteria for the development and maintenance of neurological critical care units (NCCUs), this document is put forth by the Neurocritical Care Society (NCS). Recommended organizational structure, personnel and processes necessary to develop a successful neurocritical care program are outlined. Methods: Under the direction of NCS Executive Leadership, a multidisciplinary writing group of NCS members was formed. After an iterative process, a framework was proposed and approved by members of the writing group. A draft was then written, which was reviewed by the NCS Quality Committee and NCS Guidelines Committee, members at large, and posted for public comment. Feedback was formally collated, reviewed and incorporated into the final document which was subsequently approved by the NCS Board of Directors.


Assuntos
Cuidados Críticos/normas , Doenças do Sistema Nervoso/terapia , Neurologia/normas , Recursos Humanos em Hospital/normas , Guias de Prática Clínica como Assunto/normas , Melhoria de Qualidade/normas , Sociedades Médicas/normas , Humanos
8.
Cerebrovasc Dis ; 37(4): 244-50, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24686322

RESUMO

BACKGROUND: African Americans (AAs) have a higher prevalence of extreme ischemic white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) than do European Americans (EAs) based on the Cardiovascular Health Study (CHS) score. Ischemic white matter disease, limited to the deep white matter, may be biologically distinct from disease in other regions and may reflect a previously observed trend toward an increased risk of subcortical lacunar infarcts in AAs. We hypothesized that extreme deep WMH volume (DWMV) or periventricular volume (PV) may also have a higher prevalence in AAs. Thus, we studied extreme CHS scores and extreme DWMV and PV in a healthy population enriched for cardiovascular disease risk factors. METHODS: We imaged the brains of 593 subjects who were first-degree relatives of probands with early onset coronary disease prior to 60 years of age. WMHs were manually delineated on 3-tesla cranial MRI by a trained radiology reader; the location and volume of lesions were characterized using automated software. DWMV and PV were measured directly with automated software, and the CHS score was determined by a neuroradiologist. Volumes were characterized as being in the upper 25% versus lower 75% of total lesion volume. Volumes in the upper versus the remaining quartiles were examined for AA versus EA race using multiple logistic regression (generalized estimating equations adjusted for family relatedness) and adjusted for major vascular disease risk factors including age ≥55 years versus <55, sex, current smoking, obesity, hypertension, diabetes and low-density lipoprotein >160 mg/dl. RESULTS: Participants were 58% women and 37% AAs, with a mean age of 51.5 ± 11.0 years (range, 29-74 years). AAs had significantly higher odds of having extreme DWMVs (odds ratio, OR, 1.8; 95% confidence interval, CI, 1.2-2.9; p = 0.0076) independently of age, sex, hypertension and all other risk factors. AAs also had significantly higher odds of having extreme CHS scores ≥3 (OR, 1.3; 95% CI, 1.1-3.6; p = 0.025). Extreme PV was not significantly associated with AA race (OR, 1.3; 95% CI, 0.81-2.1; p = 0.26). CONCLUSIONS: AAs from families with early-onset cardiovascular disease are more likely to have extreme DWMVs (a subclinical form of cerebrovascular disease) and an extreme CHS score, but not extreme PV, independently of age and other cardiovascular disease risk factors. These findings suggest that this AA population is at an increased risk for DWMV and may be at an increased risk for future subcortical stroke. Longitudinal studies are required to see if DWMV is predictive of symptomatic subcortical strokes in this population.


Assuntos
Transtornos Cerebrovasculares/patologia , Substância Branca/patologia , Adulto , Negro ou Afro-Americano , Fatores Etários , Idoso , Transtornos Cerebrovasculares/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , População Branca
9.
Res Sq ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38746210

RESUMO

Background: Females have greater brain volume and cerebral blood flow than males when controlling for intracranial volume and age. Brain volume decreases after menopause, suggesting a role of sex hormones. We studied the association of sex hormones with brain volume, white matter hyperintensity volumes and cerebral blood flow in people with Type 2 Diabetes and with overweight and obesity conditions that accelerate brain atrophy. Methods: We analyzed data from 215 participants with overweight or obesity and Type 2 Diabetes from the Look AHEAD Brain Magnetic Resonance Imaging ancillary study (mean age 68 years, 73% postmenopausal female). Estradiol and total testosterone levels were measured with electrochemoluminescence assays. The ratio of brain measurements to intracranial volume was analyzed to account for body size. We analyzed sex hormones as quantitative measures in males, whereas in females we grouped those with detectable vs. undetectable hormone levels (Estradiol <73 pmol/L [20 pg/mL]: 79%; Total Testosterone < 0.07 mmol/L [0.02 ng/mL]: 37% undetectable in females). Results: Females with detectable total testosterone levels had higher brain volume to intracranial volume ratio (median [25th, 75th percentile]: 0.85 [0.84, 0.86]) as compared to those with undetectable Total Testosterone levels (0.84 [0.83, 0.86]; rank sum p=0.04). This association was attenuated after age and body mass index adjustment (p=0.08). Neither white matter hyperintensity volumes or cerebral blood flow in females, nor any brain measures in males, were significantly associated with Estradiol or Total Testosterone. Conclusions: In postmenopausal females with Type 2 Diabetes with overweight and obesity, detectable levels of total testosterone were associated greater brain volume relative to intracranial volume, suggesting a protective role for testosterone in female brain health. Our findings are limited by a small sample size and low sensitivity of hormone assays. Our suggestive findings can be combined with future larger studies to assess clinically important differences. Trial Registration: NCT00017953.

10.
Acta Neurochir Suppl ; 115: 23-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22890638

RESUMO

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological disease. It has many sequelae, including vasospasm and delayed ischemic neurological deficits (DINDs). We explored the blood proteome in patients with aSAH using transcranial Doppler (TCD) velocity as a guide to patients who are at risk for symptomatic vasospasm and DIND. Blood was drawn on all days that patients were observed in the neurocritical care unit (NCCU) after aSAH. A team of neurologists and neurosurgeons identified patients with clinical evidence of vasospasm and DIND. Serum was fractionated using protein chips and surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF MS). We detected a pattern of protein expression associated with those at risk for elevated TCD velocities by day 8, compared with blood collected in the presymptomatic stage (days 1-3). We further analyzed serum using pooled samples from study entry to the time of elevated TCD velocities using a protein microarray that analyzed 500 human proteins thematically oriented toward inflammation. After identifying several candidates with elevated concentrations in the pooled samples, we then used reverse protein arrays to quantitate the concentration of potential candidate proteins in the individual samples. Proteins with significantly elevated concentrations included apolipoprotein-E, apolipoprotein-A, serum amyloid protein-4, and serum amyloid protein-P. Future studies in larger sample populations are needed to evaluate these biomarkers further as representative of biosystems involved in vasospasm and DIND or as potential biomarkers predictive of risk associated with disease.


Assuntos
Biomarcadores/sangue , Proteínas Sanguíneas/metabolismo , Isquemia Encefálica/sangue , Doenças do Sistema Nervoso/sangue , Vasoespasmo Intracraniano/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Isquemia Encefálica/etiologia , Circulação Cerebrovascular , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etiologia , Análise Serial de Proteínas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Fatores de Tempo , Ultrassonografia Doppler Transcraniana , Vasoespasmo Intracraniano/etiologia , Adulto Jovem
11.
Neurology ; 100(18): e1930-e1943, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36927883

RESUMO

BACKGROUND AND OBJECTIVES: Previous studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults. METHODS: We included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear DNA. Brain MRI markers included total brain, hippocampal, and white matter hyperintensity volumes. General cognitive function was derived from distinct cognitive domains. We performed cohort-specific association analyses of mtDNA CN with AD/ADRD endophenotypes assessed within ±5 years (i.e., cross-sectional analyses) or 5-20 years after blood draw (i.e., prospective analyses) adjusting for potential confounders. We further explored associations stratified by sex and age (<60 vs ≥60 years). Fixed-effects or sample size-weighted meta-analyses were performed to combine results. Finally, we performed mendelian randomization (MR) analyses to assess causality. RESULTS: We included up to 19,152 participants (mean age 59 years, 57% women). Higher mtDNA CN was cross-sectionally associated with better general cognitive function (ß = 0.04; 95% CI 0.02-0.06) independent of age, sex, batch effects, race/ethnicity, time between blood draw and cognitive evaluation, cohort-specific variables, and education. Additional adjustment for blood cell counts or cardiometabolic traits led to slightly attenuated results. We observed similar significant associations with cognition in prospective analyses, although of reduced magnitude. We found no significant associations between mtDNA CN and brain MRI measures in meta-analyses. MR analyses did not reveal a causal relation between mtDNA CN in blood and cognition. DISCUSSION: Higher mtDNA CN in blood is associated with better current and future general cognitive function in large and diverse communities across the United States. Although MR analyses did not support a causal role, additional research is needed to assess causality. Circulating mtDNA CN could serve nevertheless as a biomarker of current and future cognitive function in the community.


Assuntos
Doença de Alzheimer , DNA Mitocondrial , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Masculino , DNA Mitocondrial/genética , Variações do Número de Cópias de DNA , Estudos Prospectivos , Estudos Transversais , Imageamento por Ressonância Magnética , Cognição , Encéfalo
12.
Crit Care Med ; 40(2): 587-93, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21946655

RESUMO

OBJECTIVE: Acute lung injury and acute respiratory distress syndrome have been reported in a significant proportion of patients with critical neurologic illness. Our aim was to identify risk factors for acute lung injury/acute respiratory distress syndrome in this population. DESIGN: Prospective, observational study. SETTING: A 22-bed, adult neurosciences critical care unit at a tertiary care hospital. PATIENTS: Primary neurologic disorder, mechanical ventilation >48 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 192 patients were enrolled with a range of neurologic disorders. Among these, 68 (35%) were diagnosed with acute lung injury/acute respiratory distress syndrome. In a multivariate logistic regression analysis, independent risk factors for acute lung injury/acute respiratory distress syndrome were pneumonia (odds ratio [95% confidence interval] 3.12 [1.5-6.0], p = .002), circulatory shock (2.2 [1.07-4.57], p = .03), and absence of a gag or cough reflex (3.41 [1.34-8.68], p = .01). Neither neurologic diagnosis nor neurologic severity, assessed with the Glasgow Coma Scale, was significantly associated with the development of acute lung injury/acute respiratory distress syndrome. CONCLUSION: Acute lung injury/acute respiratory distress syndrome occurred in more than one third of mechanically ventilated neurosciences critical care unit patients. Loss of the cough or gag reflex is strongly predictive of acute lung injury/acute respiratory distress syndrome, while neurologic diagnosis and Glasgow Coma Scale are not. Lower brainstem dysfunction, a clinical marker of neurologic injury not captured by the Glasgow Coma Scale, is a risk factor for acute lung injury/acute respiratory distress syndrome and could inform decisions regarding airway protection and mechanical ventilation.


Assuntos
Lesão Pulmonar Aguda/epidemiologia , Encefalopatias/diagnóstico , Encefalopatias/epidemiologia , Mortalidade Hospitalar , Síndrome do Desconforto Respiratório/epidemiologia , Lesão Pulmonar Aguda/diagnóstico , Lesão Pulmonar Aguda/terapia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Encefalopatias/terapia , Estudos de Coortes , Comorbidade , Cuidados Críticos/métodos , Estado Terminal/mortalidade , Estado Terminal/terapia , Feminino , Humanos , Incidência , Unidades de Terapia Intensiva , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Prospectivos , Respiração Artificial , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/terapia , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Análise de Sobrevida , Adulto Jovem
14.
Neurocrit Care ; 16(1): 72-81, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21922343

RESUMO

BACKGROUND: Neurocritical care is a new subspecialty field in medicine that intersects with many of the neuroscience and critical care specialties, and continues to evolve in its scope of practice and practitioners. The objective of this study was to assess the perceived need for and roles of neurocritical care intensivists and neurointensive care units among physicians involved with intensive care and the neurosciences. METHODS: An online survey of physicians practicing critical care medicine, and neurology was performed during the 2008 Leapfrog initiative to formally recognize neurocritical care training. RESULTS: The survey closed in July 2009 and achieved a 13% response rate (980/7524 physicians surveyed). Survey respondents (mostly from North America) included 362 (41.4%) neurologists, 164 (18.8%) internists, 104 (11.9%) pediatric intensivists, 82 (9.4%) anesthesiologists, and 162 (18.5%) from other specialties. Over 70% of respondents reported that the availability of neurocritical care units staffed with neurointensivists would improve the quality of care of critically ill neurological/neurosurgical patients. Neurologists were reported as the most appropriate specialty for training in neurointensive care by 53.3%, and 57% of respondents responded positively that neurology residency programs should offer a separate training track for those interested in neurocritical care. CONCLUSION: Broad level of support exists among the survey respondents (mostly neurologists and intensivists) for the establishment of neurological critical care units. Since neurology remains the predominant career path from which to draw neurointensivists, there may be a role for more comprehensive neurointensive care training within neurology residencies or an alternative training track for interested residents.


Assuntos
Cuidados Críticos/normas , Doenças do Sistema Nervoso/terapia , Neurologia/educação , Neurociências/educação , Especialização/normas , Inquéritos Epidemiológicos , Humanos , Neurociências/normas , Recursos Humanos
15.
J Am Heart Assoc ; 11(11): e024606, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35621212

RESUMO

Background The periventricular white matter is more sensitive to the systemic hemodynamic alterations than the deep white matter because of differences in its vascular structure and systemic circulation relationship. We hypothesize that periventricular white matter hyperintensity (PVWMH) volume shows greater association than deep white matter hyperintensity (DWMH) volume with vascular properties (VPs) reflecting arterial stiffness and cardiovascular remodeling, indicators of the systemic circulation. Methods and Results A total of 426 participants (age, 59.0±6.1 years; 57.5% women; and 39.7% Black race) in the Genetic Study of Atherosclerosis Risk who were aged ≥50 years and had brain magnetic resonance imaging were studied. VPs included pulse pressure, hypertensive response to exercise, diastolic brachial artery diameter, diastolic common carotid artery diameter, common carotid artery distensibility coefficient, and left ventricular function. The relative associations of VPs with PVWMH and DWMH as multiple measures within the same individual were determined using multilevel linear models. We also determined if age modified the differences in VPs associations with PVWMH and DWMH. Our findings indicated that, within the same subject, PVWMH volume had greater association than DWMH volume with pulse pressure (P=0.002), hypertensive response to exercise (P=0.04), diastolic brachial artery diameter (P=0.012), and diastolic common carotid artery diameter (P=0.04), independent of age and cardiovascular risk factors. The differences of PVWMH versus DWMH associations with VPs did not differ at any age threshold. Conclusions We show, for the first time, that PVWMH has greater association than DWMH, independent of age, with vascular measurements of arterial stiffness and cardiovascular remodeling suggesting that changes in the systemic circulation affect the PVWMH and DWMH differently.


Assuntos
Leucoaraiose , Substância Branca , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
16.
Mol Neurobiol ; 58(12): 6684-6696, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34606050

RESUMO

Efforts to develop effective neuroprotective therapies for ischemic stroke have had little success to date. One promising approach to neuroprotection is ischemic postconditioning, which utilizes brief bouts of ischemia after acute ischemic stroke to elicit neuroprotection, although the mechanism is largely unknown. As the primary components of transient ischemia are local hypoxia and acidosis, and hypoxic postconditioning has had little success, it is possible that the acidosis component may be the primary driver. To address the evidence behind this, we performed a systematic review of preclinical studies focused on the neuroprotective role of transient acidosis after ischemia. Animal studies demonstrated that mild-to-moderate acidosis after ischemic events led to better functional neurologic outcomes with reduced infarct volumes, while severe acidosis often led to cerebral edema and worse functional outcomes. In vitro studies demonstrated that mild-to-moderate acidosis improves neuronal survival largely through two means: (1) inhibition of harmful superoxide formation in the excitotoxic pathway and (2) remodeling neuronal mitochondria to allow for efficient ATP production (i.e., oxidative phosphorylation), even in the absence of oxygen. Similar to the animal studies, acidotic postconditioning in humans would entail short cycles of carbon dioxide inhalation, which has already been demonstrated to be safe as part of a hypercapnic challenge when measuring cerebrovascular reactivity. Due to the preclinical efficacy of acidotic postconditioning, its relatively straightforward translation into humans, and the growing need for neuroprotective therapies, future preclinical studies should focus on filling the current knowledge gaps that are currently restricting the development of phase I/II clinical trials.


Assuntos
Acidose/fisiopatologia , Isquemia Encefálica/fisiopatologia , Pós-Condicionamento Isquêmico/métodos , Neuroproteção/fisiologia , Animais , Modelos Animais de Doenças
17.
Neurocrit Care ; 13(1): 101-8, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20383610

RESUMO

BACKGROUND: The management of symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) can be often complicated by the presence of stunned myocardium and left ventricular failure. Vasopressors and inotropes are commonly used to optimize mean arterial pressure (MAP) and cerebral perfusion pressure (CPP). Intra-aortic balloon counterpulsation pump (IABP) may be indicated in the management of these patients. METHODS: We report the case of a 55-year-old patient who suffered an aSAH complicated by severe left ventricular failure, who subsequently developed symptomatic cerebral vasospasm. Left ventricular failure precluded traditional hemodynamic augmentation, and IABP was successfully used instead, which allowed for reinstitution of hypertensive hypervolemic therapy and prevented delayed cerebral ischemia. RESULTS: A review of the literature conducted on symptomatic cerebral vasospasm after aSAH and severe left ventricular failure revealed seven publications describing 14 patients with aSAH treated with an IABP during the period of vasospasm. CONCLUSIONS: Intra-aortic balloon counterpulsation pump (IABP) is used for hemodynamic support of patients in cardiogenic shock and its use in the setting of aSAH, cardiomyopathy, and cerebral vasospasm can be beneficial in preventing delayed ischemic deficits.


Assuntos
Cardiomiopatias/complicações , Balão Intra-Aórtico , Choque Cardiogênico/complicações , Choque Cardiogênico/terapia , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/complicações , Cardiomiopatias/etiologia , Angiografia Cerebral , Ecocardiografia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Ventrículos do Coração , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Miocárdio Atordoado/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Vasoespasmo Intracraniano/diagnóstico por imagem
19.
Cerebrovasc Dis ; 28(2): 124-30, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19506371

RESUMO

BACKGROUND: Monocyte chemoattractant protein 1 (MCP-1), acting in concert with its receptor chemokine receptor 2 (CCR2), promotes recruitment of macrophages into atherosclerotic plaque. We examined whether single nucleotide polymorphism (SNP) variants in the MCP-1 or CCR2 genes independently or in combination are associated with carotid artery atherosclerosis in an African American population at increased risk of vascular disease. METHODS: Four SNPs in MCP-1 and 1 in CCR2 were genotyped. Carotid artery duplex ultrasonography was used to identify the presence or absence of carotid plaque >1 mm. The study population included 325 apparently healthy 30- to 59-year-old black siblings of 185 probands with premature coronary artery disease (<60 years old). Associations between each independent SNP and the presence of carotid plaque were examined using multivariate logistic regression models adjusted for age, sex, educational level, diabetes, smoking, hypertension, obesity, low-density lipoprotein cholesterol and non-independence within families. Interactions between SNPs in the MCP-1 gene and the SNP in the CCR2 gene were examined by multivariate analysis. RESULTS: Siblings were 32% males, with a mean age of 46 +/- 7 years, and 77 (24%) demonstrated carotid plaque. In multivariate analyses, the CC genotype of MCP-1 SNP rs2857656 was independently associated with plaque (p = 0.05). Subjects who had both the MCP-1 CC genotype and were heterozygotic or homozygotic for the CCR2 V64I genotype (rs1799864; n = 12) had an even higher risk of carotid atherosclerosis (odds ratio 6.14, 95% confidence interval 1.82-20.73; p = 0.0037). CONCLUSION: The MCP-1 rs2857656 CC genotype is independently associated with carotid artery plaque in African American from families with premature coronary artery disease. The combination of the MCP-1 CC homozygous genotype and the homozygotic or heterozygote CCR2 V64I genotype is associated with a particularly high prevalence of carotid artery plaque.


Assuntos
Negro ou Afro-Americano/genética , Doenças das Artérias Carótidas/genética , Quimiocina CCL2/genética , Polimorfismo de Nucleotídeo Único , Receptores CCR2/genética , Adulto , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etnologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Ultrassonografia Doppler Dupla
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