Patient Safety Events during Critical Care Transport.

OBJECTIVE: Patient safety events (PSEs) occurring during interfacility transport have not been studied comprehensively in critical care transport (CCT) teams in the United States. The purpose of this research was to investigate the type and frequency of PSEs during CCT between hospitals; to explore the impact of patient stability, vulnerability, complexity, predictability, and resiliency; and to examine if the nurse factors of licensure or experience and transport factors of duration or mode of transport influence the frequency of PSEs. The study was conducted at a large hospital-based quaternary health care system in the Midwestern United States. METHODS: This was a retrospective, descriptive correlational study using chart review. The study selected 50 sequential qualifying cases with PSEs and randomly selected control cases reviewed at a single site over a 5-month period. RESULTS: The rate of PSEs was 27.7 events per 1,000 patient contacts. Of 9 reported adverse event types, new or recurrent hypoxia had the greatest frequency. Hypoxia, when present at the time of initial CCT contact, was associated with the PSE occurrence (P = .046). Duration of transport was a significant predictor of PSEs (P = .025). CONCLUSION: Pretransport hypoxia and duration of transport are independent predictors for intratransport PSEs, particularly intratransport hypoxia.

Support for nursing science.

BACKGROUND: The mission of the Department of Health and Human Services is to enhance the health and well-being of the American people. It does this by providing oversight for more than 1,000 grant programs across 26 federal agencies at an annual cost of approximately $500 billion. The National Institute of Nursing Research (NINR) at the National Institutes of Health (NIH) is one institute originated to support health care research from a nursing perspective. However, funding of nursing research from federal agencies has remained relatively flat for more than a decade, despite increases in total NIH funding. PURPOSE: The purpose of this report is to describe the types of funding support provided by federal government agencies (including the NIH) to schools of nursing. METHOD: The NIH's Research Portfolio Online Reporting Tool, Expenditures and Results system from 1988 to 2014 was accessed to collect information on the grant recipient institutions as well as the source, number, type, and dollar amounts of grants. DISCUSSION: The funding level and its implications for the future of nursing science are considered.

Utilization of Shock Team and Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) in the Management of Cardiogenic Shock in Northern Ontario.

Background: Despite advancements in critical care and coronary revascularization, cardiogenic shock (CS) outcomes remain poor. Implementing a shock team and use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) have been associated with improved CS outcomes, but its feasibility in remote and rural areas remains unknown. Methods: This retrospective study included patients with CS who required mechanical circulatory support (MCS) at Health Sciences North, Sudbury, Ontario. The analysis aimed to accomplish 2 objectives: first, to review the outcomes associated with use of Impella (Abiomed, Danvers, MA) and, second, to assess the feasibility of establishing a shock team to facilitate the local implementation of VA-ECMO. The primary endpoint was in-hospital mortality. Results: The outcomes of 15 patients with CS who received Impella between 2015 and 2021 were reviewed. Their average age was 65 years (standard deviation [SD]: 13), and 8 patients (53%) were female. CS was ischemic in 12 patients (80%). Transfemoral Impella CP (cardiac power) was the most frequently used (93%). Thirteen patients (87%) died during the index hospital stay post-Impella because of progressive circulatory failure. The shock team was established following consultations with several Canadian MCS centres, leading to the development of a protocol to guide use of MCS. There have been 4 cases in which percutaneous VA-ECMO using Cardiohelp (Getinge/Maquet, Wayne, NJ) has been used; 3 (75%) survived beyond the index hospitalization. Conclusions: This analysis demonstrated the feasibility of implementing a shock team in remote Northern Ontario, enabling the use of VA-ECMO with success in a centre with a sizeable rural catchment area. This initiative helps address the gap in cardiac care outcomes between rural and urban areas in Ontario.

Introduction: En dépit des avancées des soins aux patients en phase critique et de la revascularisation coronarienne, les résultats du choc cardiogénique (CC) semblent mauvais. La mise en place d'une équipe de choc et l'utilisation de l'oxygénation extracorporelle (ECMO, de l'anglais extracorporeal membrane oxygenation) par voie veino-artérielle (VA) (VA-ECMO) ont été associées à de meilleurs résultats du CC, mais on ignore sa faisabilité dans les régions éloignées et rurales. Méthodes: La présente étude rétrospective portait sur des patients en CC qui ont eu besoin d'une assistance circulatoire mécanique (ACM) à Horizon Santé-Nord, à Sudbury, en Ontario. L'analyse visait 2 objectifs : le premier objectif était de passer en revue les résultats associés à l'utilisation de Impella (Abiomed, Danvers, MA) et, le deuxième était d'évaluer la faisabilité de la mise en place d'une équipe de choc pour faciliter la mise en œuvre locale de la VA-ECMO. Le principal critère d'évaluation était la mortalité intrahospitalière. Résultats: Nous avons passé en revue les résultats cliniques de 15 patients ayant subi un CC qui avaient reçu une Impella entre 2015 et 2021. L'âge moyen était de 65 ans (écart type [ET] : 13), et 8 patients (53 %) étaient des femmes. Le CC était d'origine ischémique chez 12 patients (80 %). L'Impella CP (cardiac power, soit la pompe cardiaque) par voie transfémorale était la plus fréquemment utilisée (93 %). Treize patients (87 %) sont morts durant le séjour de référence à l'hôpital après l'utilisation de l'Impella en raison d'insuffisance circulatoire progressive. La mise en place de l'équipe de choc à la suite des consultations dans plusieurs centres canadiens d'ACM a mené à l'élaboration d'un protocole d'utilisation de l'ACM. Il y a eu 4 cas chez lesquels la VA-ECMO par voie percutanée à l'aide de Cardiohelp (Getinge/Maquet, Wayne, New Jersey, É.-U.) a été utilisée ; 3 (75 %) ont survécu après l'hospitalisation de référence. Conclusions: Cette analyse a démontré la faisabilité de la mise en place d'une équipe de choc dans les régions éloignées du nord de l'Ontario, qui a permis d'utiliser efficacement la VA-ECMO dans un centre d'une circonscription hospitalière rurale non négligeable. Cette initiative aide à remédier à l'écart des résultats en soins cardiaques entre les régions rurales et urbaines de l'Ontario.

Efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist for vasomotor symptoms: a dose-finding clinical trial (SWITCH-1).

OBJECTIVE: Neurokinin (NK)-3 and NK-1 receptors have been implicated in the etiology of vasomotor symptoms (VMS) and sleep disturbances associated with menopause. This phase 2b, adaptive, dose-range finding study aimed to assess the efficacy and safety of multiple doses of elinzanetant (NT-814), a selective NK-1,3 receptor antagonist, in women experiencing VMS associated with menopause, and investigate the impact of elinzanetant on sleep and quality of life. METHODS: Postmenopausal women aged 40 to 65 years who experienced seven or more moderate-to-severe VMS per day were randomized to receive elinzanetant 40, 80, 120, or 160 mg or placebo once daily using an adaptive design algorithm. Coprimary endpoints were reduction in mean frequency and severity of moderate-to-severe VMS at weeks 4 and 12. Secondary endpoints included patient-reported assessments of sleep and quality of life. RESULTS: Elinzanetant 120 mg and 160 mg achieved reductions in VMS frequency versus placebo from week 1 throughout 12 weeks of treatment. Least square mean reductions were statistically significant versus placebo at both primary endpoint time points for elinzanetant 120 mg (week 4: -3.93 [SE, 1.02], P < 0.001; week 12: -2.95 [1.15], P = 0.01) and at week 4 for elinzanetant 160 mg (-2.63 [1.03]; P = 0.01). Both doses also led to clinically meaningful improvements in measures of sleep and quality of life. All doses of elinzanetant were well tolerated. CONCLUSIONS: Elinzanetant is an effective and well-tolerated nonhormone treatment option for postmenopausal women with VMS and associated sleep disturbance. Elinzanetant also improves quality of life in women with VMS.

Cerebrospinal fluid ferritin level, a sensitive diagnostic test in late-presenting subarachnoid hemorrhage.

The workup of patients with suspected subarachnoid hemorrhage (SAH) presenting late is complicated by a loss of diagnostic sensitivity of computed tomography (CT) brain imaging and cerebrospinal fluid (CSF) bilirubin levels. In this prospective longitudinal study of CSF ferritin levels in SAH, serial CSF samples from 14 patients with aneurysmal SAH requiring extraventricular drainage (EVD) were collected. The control group comprised 44 patients presenting with headache suspicious of SAH. Nine patients underwent a traumatic spinal tap. CSF ferritin levels were significantly higher in the patients with SAH compared with controls (P < .0001). The upper reference range of CSF ferritin is 12 ng/mL, and there was no significant difference between the traumatic and normal spinal taps (mean, 9.0 ng/mL vs 3.9 ng/mL; P = .59). CSF ferritin levels increased after SAH, from an average of 65 ng/mL on day 1 to 1750 ng/mL on day 11 (P < .01). Both the Fisher and Columbia CT scores were significantly correlated with CSF ferritin level. The increase in CSF ferritin level after SAH and possibly may provide additional diagnostic information in patients with suspected SAH who present late to the clinic.

Elinzanetant (NT-814), a Neurokinin 1,3 Receptor Antagonist, Reduces Estradiol and Progesterone in Healthy Women.

CONTEXT: The ideal therapy for endometriosis (EM) and uterine fibroids (UFs) would suppress estrogenic drive to the endometrium and myometrium, while minimizing vasomotor symptoms and bone loss associated with current treatments. An integrated neurokinin-kisspeptin system involving substance P and neurokinin B acting at the neurokinin (NK) receptors 1 and 3, respectively, modulates reproductive hormone secretion and represents a therapeutic target. OBJECTIVE: This work aimed to assess the effects of the novel NK1,3 antagonist elinzanetant on reproductive hormone levels in healthy women. METHODS: A randomized, single-blinded, placebo-controlled study was conducted in 33 women who attended for 2 consecutive menstrual cycles. In each cycle blood samples were taken on days 3 or 4, 9 or 10, 15 or 16, and 21 or 22 to measure serum reproductive hormones. In cycle 2, women were randomly assigned to receive once-daily oral elinzanetant 40, 80, 120 mg, or placebo (N = 8 or 9 per group). RESULTS: Elinzanetant dose-dependently lowered serum luteinizing hormone, estradiol (120 mg median change across cycle: -141.4 pmol/L, P = .038), and luteal-phase progesterone (120 mg change from baseline on day 21 or 22: -19.400 nmol/L, P = .046). Elinzanetant 120 mg prolonged the cycle length by median of 7.0 days (P = .023). Elinzanetant reduced the proportion of women with a luteal-phase serum progesterone concentration greater than 30 nmol/L (a concentration consistent with ovulation) in a dose-related manner in cycle 2 (P = .002). Treatment did not produce vasomotor symptoms. CONCLUSION: NK1,3 receptor antagonism with elinzanetant dose-dependently suppressed the reproductive axis in healthy women, with the 120-mg dose lowering estradiol to potentially ideal levels for UFs and EM. As such, elinzanetant may represent a novel therapy to manipulate reproductive hormone levels in women with hormone-driven disorders.

Effects of NT-814, a dual neurokinin 1 and 3 receptor antagonist, on vasomotor symptoms in postmenopausal women: a placebo-controlled, randomized trial.

OBJECTIVES: To evaluate the safety, pharmacokinetics, and preliminary efficacy of NT-814, a dual neurokinin 1,3 antagonist, in postmenopausal women with vasomotor symptoms (hot flashes). METHODS: We completed a double-blind, randomized, placebo-controlled trial in three US clinical research units in 76 postmenopausal women with moderate/severe hot flashes. Participants were randomized to 14 days of once-daily NT-814 or placebo within each of four sequential dose cohorts; 50, 100, 150, and 300 mg. Participants completed diaries of hot flash frequency and severity and waking due to night sweats before (baseline) and during treatment. RESULTS: All prespecified efficacy parameters (24-h hot flash frequency and severity, frequency of waking due to night sweats) decreased in all groups (including placebo). Mean reduction from baseline at week 2 in moderate/severe hot flash frequency was 37% in the placebo group and, respectively, 24% (P = 0.048 vs placebo), 59% (P = 0.155), 84% (P < 0.001) and 66% (P = 0.022) in the 50 mg, 100 mg, 150 mg, and 300 mg NT-814 groups; in waking due to night sweats reduction was 20% (P = 0.059), 55% (P = 0.135), 81% (P < 0.001), and 63% (P = 0.031) in the NT-814 groups and 32% in the placebo group. The improvement with NT-814 ≥150 mg was also evident in the first week of treatment. The most common treatment-related adverse events were mild somnolence and headache, more frequently in the 300 mg group. Safety monitoring identified no concerns. CONCLUSIONS: Once-daily NT-814 (≥150 mg/d) resulted in a rapid, marked improvement in hot flashes and waking due to night sweats. No safety concerns were identified. Doses up to 300 mg were well tolerated.

Genetic Variation Near chrXq22-q23 Is Linked to Emotional Functioning in Cystic Fibrosis.

INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive disease that affects many organ systems, most notably the pulmonary and gastrointestinal systems. Through genome-wide association studies, multiple genetic regions modifying CF-related pulmonary and gastrointestinal symptoms have been identified, but translation of these findings to clinical benefit remains elusive. Symptom variation in CF patients has been associated with changes in health-related quality of life (HRQOL), but the relationship between CF symptom-modifying genetic loci and HRQOL has not been explored. The purpose of this study was to determine whether two previously identified genetic modifiers of CF-related pathology also modify the subscales of HRQOL. METHODS: HRQOL and genotype data were obtained and analyzed. Linear regressions were used to examine the amount of variance in HRQOL subscales that could be explained by genotype for each modifier locus. RESULTS: A significant regression equation was found between genotype for rs5952223, a variant near chrXq22-q23, and emotional functioning in a sample of 129 CF patients. DISCUSSION: These data suggest that genotype for this single-nucleotide polymorphism is associated with emotional functioning in CF patients and highlight this genetic region as a potential therapeutic target, irrespective of CF transmembrane conductance regulator genotype.

Cerebrospinal fluid apolipoprotein E, calcium and cerebral vasospasm after subarachnoid hemorrhage.

Intracellular calcium (Ca++) regulation of cerebral vessels is impaired after subarachnoid hemorrhage (SAH), making secondary pathways, such as that involving apolipoprotein E, potentially more influential. To evaluate cerebrospinal fluid (CSF) apolipoprotein E and Ca++ levels as biomarkers of cerebral vasospasm, we examined changes in levels over time and apolipoprotein E (APOE) epsilon4 allele presence after SAH in individuals with and without vasospasm. We hypothesized that individuals with low apolipoprotein E levels, increased Ca++ levels and/or at least one copy of the APOE epsilon4 allele would have vasospasm. Daily samples from 50 participants, aged 18-75, with SAH were used to quantify apolipoprotein E and Ca++ levels. Vasospasm was verified using cerebral angiogram and/or elevated transcranial Dopplers in combination with clinical neurologic deterioration. Overall apolipoprotein E levels were higher in individuals with the APOE epsilon4 allele (p = .02) or angiographic vasospasm (p = .01), but there were no differences between individuals with and without symptomatic vasospasm. There were no significant changes in apolipoprotein E levels over time. Individuals with the epsilon4 allele had lower Ca++ levels (p = .02) with trends suggesting a different pattern of change over time (p = .07). CSF Ca++ levels were lower in individuals with symptomatic vasospasm (p < .01). Change in apolipoprotein E and Ca++ levels (p = .006) correlated over time regardless of genotype or vasospasm status. These findings suggest that apolipoprotein E and Ca++ may be interacting after SAH, but this interaction does not appear to influence vasospasm.

Apolipoprotein E4 allele presence and functional outcome after severe traumatic brain injury.

Presence of the apolipoprotein E (APOE) 4 allele has been associated with increased incidence and faster progression of neurodegenerative diseases, poorer recovery from neurologic insult, and decreased cognitive function in the well-elderly. The specific association between APOE genotype and recovery from severe traumatic brain injury (TBI) is conflicting with many groups finding the APOE 4 allele to be associated with poorer outcome while others have found no association. The purpose of this study was to investigate the association between APOE 4 allele presence and recovery during the two years after injury from severe TBI in light of other potential covariates, such as age, race, gender, hypotension or hypoxia before hospital admission and severity of injury. APOE genotype was determined for 123 subjects with severe TBI. Glasgow outcome score (GOS) and mortality were collected at 3, 6, 12, and 24 months after injury. Results showed individuals improved over the two year period following injury and those with the 4 allele had a slower recovery rate than those without the APOE 4 allele over the two year period. We did not however find significant differences in GOS at individual time points when controlling for other covariates. Our findings suggest that APOE 4 allele presence influences recovery rate from severe TBI independent of other covariates. The findings of this study are unique in that they address not only the relationship between APOE 4 allele presence and outcome from severe TBI, but also describe differences in trajectory of recovery by APOE 4 allele presence.

Sex and genetic associations with cerebrospinal fluid dopamine and metabolite production after severe traumatic brain injury.

OBJECT: Dopamine (DA) pathways have been implicated in cognitive deficits after traumatic brain injury (TBI). Both sex and the dopamine transporter (DAT) 3' variable number of tandem repeat polymorphism have been associated with differences in DAT protein density, and DAT protein affects both presynaptic DA release, through reverse transport, and DA reuptake. Catecholamines and associated metabolites are subject to autooxidation, resulting in the formation of reactive oxygen species that may contribute to subsequent oxidative injury. The purpose of this study was to determine associations between factors that affect DAT expression and cerebrospinal fluid (CSF) DA and metabolite levels after severe TBI. METHODS: Sixty-three patients with severe TBI (Glasgow Coma Scale score < or = 8) were evaluated. The patients' genotypes were obtained using previously banked samples of CSF, and serial CSF samples (416 samples) were used to evaluate DA and metabolite levels. High-performance liquid chromatography was used to determine CSF levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) during the first 5 days after injury. Mixed-effects multivariate regression modeling revealed that patients with the DAT 10/10 genotype had higher CSF DA levels than patients with either the DAT 9/9 or DAT 9/10 genotypes (p = 0.009). Females with the DAT 10/10 genotype had higher CSF DA levels than females with the DAT 9/9 or DAT 9/10 genotypes, and sex was associated with higher DOPAC levels (p = 0.004). Inotrope administration also contributed to higher DA levels (p = 0.002). CONCLUSIONS: In addition to systemic administration of DA, inherent factors such as sex and DAT genotype affect post-TBI CSF DA and DA metabolite levels, a phenomenon that may modulate susceptibility to DA-mediated oxidative injury.

Early identification of secondary brain damage in subarachnoid hemorrhage: a role for glial fibrillary acidic protein.

Secondary ischaemic deficit adversely affects outcome in patients with subarachnoid hemorrhage (SAH). Astrocytes are vulnerable to ischemia, releasing glial fibrillary acidic protein (GFAP) when challenged. In this study, we followed nine patients with SAH who underwent extra-ventricular drainage for the management of secondary hydrocephalus. Cerebrospinal fluid (CSF) was collected daily for up to 14 days. CSF GFAP was quantified using a standard ELISA. In the patients, we found that the CSF GFAP values were pathologically elevated in 83/89 (93%) of the CSF samples. The levels were highest on day 1 (median = 47.64 ng/mL) and decreased to 11.19 ng/mL on day 3, leveling out at approximately 1 ng/mL after 10 days. In non-survivors, a secondary rise of GFAP levels became significant during the high-risk period for vasospasm, with median levels of 21.76 ng/mL compared to 2.62 ng/mL in the survivors (p = 0.037) on day 6. This study suggests that CSF GFAP levels are of prognostic value in SAH. Additionally, the difference in the slope of GFAP levels between survivors (rapid wash-out) and non-survivors (secondary peaks) may allow difierentiation between primary brain injury from secondary brain damage due to delayed cerebral ischaemia.

Magnesium infusion for vasospasm prophylaxis after subarachnoid hemorrhage.

OBJECT: Despite the application of current standard therapies, vasospasm continues to result in death or major disability in patients treated for ruptured aneurysms. The authors investigated the effectiveness of continous MgSO4 infusion for vasospasm prophylaxis. METHODS: Seventy-six adults (mean age 54.6 years; 71% women; 92% Caucasian) were included in this comparative matched-cohort study of patients with aneurysmal subarachnoid hemorrhage on the basis of computed tomography (CT) findings. Thirty-eight patients who received continuous MgSO4 infusion were matched for age, race, sex, treatment option, Fisher grade, and Hunt and Hess grade to 38 historical control individuals who did not receive MgSO4infusion. Twelve grams of MgSO4 in 500 ml normal saline was given intravenously daily for 12 days if the patient presented within 48 hours of aneurysm rupture. Vasospasm was diagnosed on the basis of digital substraction angiography, CT angiography, and transcranial Doppler ultrasonography, and evidence of neurological deterioration. Symptomatic vasospasm was present at a significantly lower frequency in patients who received MgSO4 infusion (18%) compared with patients who did not receive MgSO4 (42%) (p = 0.025). There was no significant difference in mortality rate at discharge (p = 0.328). A trend toward improved outcome as measured by the modifed Rankin Scale (p = 0.084), but not the Glasgow Outcome Scale (p = 1.0), was seen in the MgSO4 treated group. CONCLUSIONS: Analysis of the results suggests that MgSO4 infusion may have a role in cerebral vasospasm prophylaxis if therapy is initiated within 48 hours of aneurysm rupture.

Identification and quantification of the hydroxyeicosatetraenoic acids, 20-HETE and 12-HETE, in the cerebrospinal fluid after subarachnoid hemorrhage.

PURPOSE: The monohydroxylated metabolite of arachidonic acid, 20-hydroxyeicosatetraenoic acid (20-HETE), is a potent vasoconstrictor of cerebral microvessels. 20-HETE formation is substantially elevated in the cerebral spinal fluid (CSF) in the rat subarachnoid hemorrhage (SAH) model. The presence of 20-HETE in human CSF has not been demonstrated. Therefore, it was the purpose of this study to determine if HETE metabolites are present in human CSF after SAH. METHODS: CSF samples were collected daily from four SAH patients over 15 days. HETE metabolites were separated by HPLC with identification by ion-trap MS/MS and quantification via single quadrupole MS operating in negative single ion monitoring mode. RESULTS: Two major metabolites were identified as 12-HETE and 20-HETE. 20-HETE maximal concentrations were 2.9 and 0.7 ng/ml at approximately 70 h in the two patients with symptomatic cerebral vasospasm (SV) after SAH. Concentrations of 12-HETE in these patients peaked at 21.9 ng/ml and 2.8 ng/ml. Concentrations of 20-HETE and 12-HETE were non-detectible in the majority of the samples obtained from two matched SAH patients without SV. CONCLUSIONS: This study is the first to demonstrate that 20-HETE and 12-HETE are present in the CSF of SAH patients at physiologically relevant concentrations. Based on this information future prospective studies will allow for the delineation of the role of these metabolites in the pathogenesis of SAH.

A comparison of gastric and rectal CO2 in cardiac surgery patients.

Critical care nurses assess and treat clinical conditions associated with inadequate oxygenation. Changes in regional organ (gut) blood flow are believed to occur in response to a decrease in oxygenation. Although the stomach is a widely accepted monitoring site, there are multiple methodological and measurement issues associated with the gastric environment that limit the accuracy of P CO2 detection. The rectum may provide nurses with an alternative site for monitoring changes in P CO2 without the limitations associated with gastric monitoring. This pilot study used a repeated measures design to examine changes in gastric and rectal P CO2 during elective coronary artery bypass grafting with cardiopulmonary bypass (CPB) and in the immediate 4-hr postoperative period in 26 subjects. The systemic indicators explained little variation in the regional indicators during protocol. A comparison of rectal and gastric P CO2 revealed no statistically significant differences in the direction or magnitude of change over any phase of cardiac surgery (baseline, CPB, post-CPB). A reduction in both rectal and gastric P CO2 occurred during CPB, and both values trended upward during the post-CPB phase. However, poor correlation and agreement was found between the measures of P CO2 at the two sites. Although clinically important, the cause is unclear. Possible explanations include variation in CO2 production between the gastric and rectal site, differences in sensitivity of the two monitoring instruments, or the absence of hemodynamic complications, which limited the extent of change in P CO2. Further investigation using patients with more profound changes in oxygenation are needed to identify response patterns and possible mechanisms.

Decreased cerebrospinal fluid apolipoprotein E after subarachnoid hemorrhage: correlation with injury severity and clinical outcome.

BACKGROUND AND PURPOSE: The apolipoprotein E (APOE) epsilon4 allele has been associated with unfavorable outcome after subarachnoid hemorrhage (SAH), suggesting that apoE plays an important role in the response of the brain to SAH. We determined the concentration of apoE in the cerebrospinal fluid (CSF) of patients with SAH and a control group to test the hypothesis that alterations in CSF apoE reflect the response of the brain to SAH and are correlated with the severity of injury and outcome. METHODS: ApoE and S100B (a marker of brain injury) were measured by ELISA in CSF from a non-brain-injured control group and patients with SAH. The severity of SAH was determined from the Glasgow Coma Scale, and the clinical outcome was determined from the Glasgow Outcome Scale. RESULTS: In contrast to increased CSF concentration of S100B, CSF apoE concentration was significantly lower in patients after SAH than in control subjects (Mann-Whitney test, P<0.0001). SAH patients with more severe injury and less favorable outcome had lower CSF apoE concentration than did patients with milder injury and better clinical outcome (Fisher exact test, P=0.02). CONCLUSIONS: The concentration of apoE in the CSF decreases after SAH, despite the likely leakage of plasma apoE into the CSF. We speculate that apoE is retained within the parenchyma of the central nervous system in response to injury, where, in view of previous data, it may have a protective role.

Temporal alterations in cerebrospinal fluid amyloid beta-protein and apolipoprotein E after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The mechanism underlying the association between possession of the APOEepsilon4 allele and less favorable outcome after subarachnoid hemorrhage (SAH) remains to be determined. After SAH the level of apolipoprotein E (apoE) in the cerebrospinal fluid (CSF) is decreased, and lower levels are associated with more severe injury and less favorable outcome. This study examined serial CSF samples to determine the time course for the decrease in CSF apoE and the relationship between CSF apoE and amyloid beta-protein (Abeta), testing the hypothesis that apoE-Abeta interactions occur in vivo after SAH. METHODS: Enzyme-linked immunosorbent assay was used to assay apoE, Abeta1-40, and Abeta1-42 in serial ventricular CSF samples from 19 patients with SAH and 13 controls. CSF S100B and tau were assayed as surrogate markers of brain injury. RESULTS: There was a sustained decrease in CSF apoE (P<0.001) and Abeta (P<0.001) after SAH in contrast to the observed elevation in CSF S100B (P<0.001) and tau (P<0.001) concentration. There was significant correlation between CSF Abeta concentration and clinical outcome (r=0.65, P<0.01), and the decrease in CSF Abeta concentration correlated significantly with that of apoE (r=0.85, P<0.0001). CONCLUSIONS: After SAH both apoE and Abeta levels decrease in the CSF, supporting the concept that interactions between these proteins occur in vivo. The possibility that apoE and Abeta influence outcome after SAH warrants further investigation.

The effects of admission alcohol level on cerebral blood flow and outcomes after severe traumatic brain injury.

This study examined the relationship between admission serum alcohol level (ETOH) and cerebral blood flow (CBF) and outcomes in the adult traumatic brain injured (TBI) population. We hypothesized that individuals with ETOH > 100 mg/dL will have decreased blood flow on admission and poorer outcomes. Eighty subjects, age 16-65, with severe TBI (Glasgow Coma Score [GCS] 100 mg/dL at the time of admission after a TBI were associated with a decrease in global CBF. Elevated serum ETOH level at time of injury did not, however, impact outcomes.

Cerebrospinal fluid apolipoprotein E concentration decreases after traumatic brain injury.

The APOE epsilon4 allele has been associated with unfavorable outcome after several types of acute brain injury, yet the biological mechanisms underlying this observation are poorly understood. Postmortem and experimental brain injury studies suggest the presence of increased amounts of apolipoprotein E (apoE) within the neuropil after acute brain injury. We assayed the concentration of apolipoprotein E in the cerebrospinal fluid (CSF) of non-injured controls and patients with traumatic brain injury (TBI) to determine whether differences exist, and if these differences correlate with injury severity and clinical outcome. CSF apoE and S100B, a marker of injury severity, were measured by enzyme linked immunosorbant assay. CSF was sampled from 27 traumatic brain injury patients (mean age 32, median 25, range 16-65 years) within 3 days of injury, and 28 controls (mean age 40, median 37, range 19-73 years). The TBI patients all had a Glasgow Coma Score (GCS) of less than eight (i.e., severe head injury). Clinical outcome was determined using the Glasgow Outcome Score (GOS). The average concentration of apoE in the CSF of controls was 12.4 mg/L (95% CI: 10.5-14.3 mg/L) and in TBI patients was 3.7 mg/L (95% CI: 2.1-4.1 mg/L; Mann-Whitney: p < 0.0001). In contrast, the concentration of S100B in the CSF of TBI patients was significantly higher than that of controls (Mann-Whitney: p < 0.0001). We speculate that apoE is retained within the parenchyma of the central nervous system in response to injury where in view of previous data, it may have a protective role.

Alterations in cerebrospinal fluid apolipoprotein E and amyloid beta-protein after traumatic brain injury.

There is evidence that apolipoprotein E (apoE) and amyloid beta-protein (Abeta), which are implicated in the pathology of chronic neurodegenerative disorders, are involved in the response of the brain to acute injury; however, human in vivo evidence is sparse. We conducted a prospective observational study to determine the magnitude and time-course of alterations in cerebrospinal fluid (CSF) apoE and Abeta concentrations after traumatic brain injury (TBI), and the relationship of these changes to severity of injury and clinical outcome. Enzyme linked immunosorbant assay (ELISA) was used to assay apoE, Abeta(1-40) and Abeta(1-42) in serial CSF samples from 13 patients with TBI and 13 controls. CSF S100B and tau were assayed as surrogate markers of brain injury. There was a significant decrease in CSF apoE (p < 0.001) and Abeta (p< 0.001) after TBI contrasting the observed elevation in CSF S100B (p < 0.001) and tau (p < 0.001) concentration. There was significant correlation (r = 0.67, p = 0.01) between injury severity and the decrease in Abeta(1-40) concentration after TBI. In vivo, changes in apoE and Abeta concentration occur after TBI and may be important in the response of the human brain to injury.