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Biomedical subjects

W John Boscardin

Publications and source records attributed to W John Boscardin.

At least 19 recordsLinked to original sources

Elevated serum soluble CD30 precedes the development of AIDS-associated non-Hodgkin's B cell lymphoma.

CD30, first described as the Ki antigen on malignant B cells in Hodgkin's lymphoma, is also expressed on normal activated B and T cells. It can be cleaved from the cell surface and detected in normal serum as soluble CD30 (sCD30), where it can be an indicator of levels of immune activation. In a cross-sectional study utilizing archived sera at a time point close to but preceding a diagnosis of acquired immunodeficiency syndrome (AIDS)-associated non-Hodgkin's B cell lymphoma, AIDS lymphoma subjects (n = 49) showed elevated mean levels of sCD30 compared to controls with AIDS but no malignancy (n = 44, p < 0.01), HIV-infected but relatively healthy (n = 47, p < 0.001), or HIV-seronegative controls (n = 44, p < 0.001). Serum sCD30 was significantly correlated to serum levels of the B cell cytokines interleukin-6 (IL-6), IL-10, and sCD23, but only among lymphoma subjects (p < or = 0.05). Correlations between sCD30 and other markers of immune system activation were seen among all HIV-infected subjects (sCD27, sCD44, CXCL13, p < 0.05). These observations suggest that sCD30, especially in combination with other immune system molecules, could be an important biomarker for an immune system environment conducive to B cell hyperactivation and the development of AIDS-associated B cell lymphoma.

Acquired Immunodeficiency Syndrome↗

Interferon-gamma decreases replication of primary R5 HIV-1 isolates in thymocytes.

As interferon-gamma (IFN-gamma) is produced at lower levels by neonatal than adult T cells, we determined whether IFN-gamma influences HIV-1 replication in thymocytes. IFN-gamma significantly decreased replication of R5 but not X4 viruses, and reduced depletion of CD3(hi)CD27 (mature) thymocytes, the preferential targets for R5 HIV-1. Thus infection and depletion of functionally mature thymocytes that can produce endogenous IFN-gamma may mutually contribute to HIV-1 replication in the thymus and to reduced T-cell output.

Cells, Cultured↗

Lack of decay of HIV-1 in gut-associated lymphoid tissue reservoirs in maximally suppressed individuals.

Although peripheral blood mononuclear cells (PBMCs) and lymph nodes represent a principal reservoir, the contribution of gut-associated lymphoid tissue (GALT) has not been evaluated. In 15 HIV-1-infected subjects with maximal suppression of HIV replication by highly active antiretroviral therapy, we quantified HIV-1 DNA and RNA in mucosal biopsy specimens, PBMCs, and plasma with ultrasensitive assays. We also calculated compartmental burdens of HIV-1 DNA-positive cells and characterized the temporal decay of these reservoirs in a period of 1 year (with projections to >50 years). HIV-1 RNA was detected in 20% of the subjects' mucosal biopsy specimens and in 80% of the PBMC samples. Mucosal HIV-1 DNA was detected in 80% of the subjects and in 100% of the PBMC samples. Calculated numbers of lymphoid cells containing "potentially replication-competent" HIV-1 DNA showed that the PBMC compartment contained approximately 70,000 such cells, and GALT contained approximately 160,000 cells. Rates of decay slopes for all 15 subjects in both compartments were not statistically significantly different when compared with each other or with zero slope. Our data indicate that GALT is a quantitatively important reservoir of potentially replicative cells containing HIV-1 DNA, harboring at least as many or more of such cells as the PBMC compartment. In well-suppressed patients on highly active antiretroviral therapy, the GALT compartment showed no clear pattern of HIV-1 decay, similar to that in the PBMCs.

DNA, Viral↗

Risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis.

CONTEXT: Estimation of mortality risk in patients hospitalized with acute decompensated heart failure (ADHF) may help clinicians guide care. OBJECTIVE: To develop a practical user-friendly bedside tool for risk stratification for patients hospitalized with ADHF. DESIGN, SETTING, AND PATIENTS: The Acute Decompensated Heart Failure National Registry (ADHERE) of patients hospitalized with a primary diagnosis of ADHF in 263 hospitals in the United States was queried with analysis of patient data to develop a risk stratification model. The first 33,046 hospitalizations (derivation cohort; October 2001-February 2003) were analyzed to develop the model and then the validity of the model was prospectively tested using data from 32,229 subsequent hospitalizations (validation cohort; March-July 2003). Patients had a mean age of 72.5 years and 52% were female. MAIN OUTCOME MEASURE: Variables predicting mortality in ADHF. RESULTS: When the derivation and validation cohorts are combined, 37,772 (58%) of 65,275 patient-records had coronary artery disease. Of a combined cohort consisting of 52,164 patient-records, 23,910 (46%) had preserved left ventricular systolic function. In-hospital mortality was similar in the derivation (4.2%) and validation (4.0%) cohorts. Recursive partitioning of the derivation cohort for 39 variables indicated that the best single predictor for mortality was high admission levels of blood urea nitrogen (> or =43 mg/dL [15.35 mmol/L]) followed by low admission systolic blood pressure (<115 mm Hg) and then by high levels of serum creatinine (> or =2.75 mg/dL [243.1 micromol/L]). A simple risk tree identified patient groups with mortality ranging from 2.1% to 21.9%. The odds ratio for mortality between patients identified as high and low risk was 12.9 (95% confidence interval, 10.4-15.9) and similar results were seen when this risk stratification was applied prospectively to the validation cohort. CONCLUSIONS: These results suggest that ADHF patients at low, intermediate, and high risk for in-hospital mortality can be easily identified using vital sign and laboratory data obtained on hospital admission. The ADHERE risk tree provides clinicians with a validated, practical bedside tool for mortality risk stratification.

Acute Disease↗

Serum levels of the homeostatic B cell chemokine, CXCL13, are elevated during HIV infection.

HIV infection is associated with B cell dysfunction, which includes B cell hyperactivation, hypergammaglobulinemia, impaired production of antibodies against specific antigens, and a loss of B cell memory. Because lymph node architecture is progressively destroyed during HIV infection, it is possible that normal B cell trafficking is impaired as well, which could be a cause or a result of these abnormalities. Because the homeostatic chemokine, CXCL13 (BLC, BCA-1), is a major regulator of B cell trafficking, we assessed circulating levels of this molecule in HIV infection. Serum levels of CXCL13 were seen to be progressively elevated in HIV disease. Serum levels of CXCL13 correlated strongly with those of the inflammation-associated chemokine, inducible protein-10 (IP-10), in subjects who had advanced HIV disease, and more moderately with levels of soluble CD30 (sCD30), sCD27, and sCD23. CXCL13 levels also correlated moderately with viral load and showed a significant decline after use of highly active antiretroviral treatment (HAART). Elevated levels of CXCL13 could cause impaired or altered trafficking of B cells during HIV infection and could contribute to the previously reported loss of CXCR5, the receptor for CXCL13, from the surface of circulating B cells in HIV infection.

Antiretroviral Therapy, Highly Active↗

Differences in cause-specific mortality between Latino and white adults.

BACKGROUND: Understanding differences in cause-specific mortality between Latinos and whites is important for targeting future public health interventions and research aimed at eliminating health disparities. OBJECTIVES: We sought to determine the contribution of specific causes of death to Latino-white differences in mortality. RESEARCH DESIGN: Using nationally representative data, we estimated cause-specific mortality risks, which were then used in a simulation model to estimate mortality events for a cohort of persons starting at age 25 and followed until death or age 75. SUBJECTS: Subjects were 507,820 Latino and white adults, age 25 or older, who participated in the 1986-1994 National Health Interview Surveys. MEASURES: Outcomes were years of potential life lost before age 75 from specific causes of death and age-specific mortality rate ratios for Latinos compared with whites. RESULTS: Latinos had higher mortality rates than whites before age 45 and similar mortality rates at older ages. Latino women lost 315 (95% confidence interval [CI], 229-2423) more years of potential life (per 1000 persons before the age of 75) than white women and Latino men lost 595 (95% CI, 513-1675) more years than white men. For both men and women, whites lost substantially more years of potential life than Latinos from lung cancer. Homicide, diabetes, HIV, and liver disease contributed most to the excess years of potential life lost among Latino men, and diabetes and HIV contributed most to the excess years of potential life lost among Latino women. CONCLUSIONS: To eliminate health disparities between Latinos and whites, future health policy and public health efforts should target diabetes, homicide, HIV, and liver disease among Latinos and lung cancer among whites.

Acquired Immunodeficiency Syndrome↗

Imputation and variable selection in linear regression models with missing covariates.

Across multiply imputed data sets, variable selection methods such as stepwise regression and other criterion-based strategies that include or exclude particular variables typically result in models with different selected predictors, thus presenting a problem for combining the results from separate complete-data analyses. Here, drawing on a Bayesian framework, we propose two alternative strategies to address the problem of choosing among linear regression models when there are missing covariates. One approach, which we call "impute, then select" (ITS) involves initially performing multiple imputation and then applying Bayesian variable selection to the multiply imputed data sets. A second strategy is to conduct Bayesian variable selection and missing data imputation simultaneously within one Gibbs sampling process, which we call "simultaneously impute and select" (SIAS). The methods are implemented and evaluated using the Bayesian procedure known as stochastic search variable selection for multivariate normal data sets, but both strategies offer general frameworks within which different Bayesian variable selection algorithms could be used for other types of data sets. A study of mental health services utilization among children in foster care programs is used to illustrate the techniques. Simulation studies show that both ITS and SIAS outperform complete-case analysis with stepwise variable selection and that SIAS slightly outperforms ITS.

Algorithms↗

Posttraumatic vasospasm: the epidemiology, severity, and time course of an underestimated phenomenon: a prospective study performed in 299 patients.

OBJECT: The purpose of this prospective study was to evaluate the cumulative incidence, duration, and time course of cerebral vasospasm after traumatic brain injury (TBI) in a cohort of 299 patients. METHODS: Transcranial Doppler (TCD) ultrasonography studies of blood flow velocity in the middle cerebral and basilar arteries (VMCA and VBA, respectively) were performed at regular intervals during the first 2 weeks posttrauma in association with 133Xe cerebral blood flow (CBF) measurements. According to current definitions of vasospasm, five different criteria were used to classify the patients: A (VMCA > 120 cm/second); B (VMCA > 120 cm/second and a Lindegaard ratio [LR] > 3); C (spasm index [SI] in the anterior circulation > 3.4); D (VBA > 90 cm/second); and E (SI in the posterior circulation > 2.5). Criteria C and E were considered to represent hemodynamically significant vasospasm. Mixed-effects spline models were used to analyze the data of multiple measurements with an inconsistent sampling rate. Overall 45.2% of the patients demonstrated at least one criterion for vasospasm. The patients in whom vasospasm developed were significantly younger and had lower Glasgow Coma Scale scores on admission. The normalized cumulative incidences were 36.9 and 36.2% for patients with Criteria A and B, respectively. Hemodynamically significant vasospasm in the anterior circulation (Criterion C) was found in 44.6% of the patients, whereas vasospasm in the BA-Criterion D or E-was found in only 19 and 22.5% of the patients, respectively. The most common day of onset for Criteria A, B, D, and E was postinjury Day 2. The highest risk of developing hemodynamically significant vasospasm in the anterior circulation was found on Day 3. The daily prevalence of vasospasm in patients in the intensive care unit was 30% from postinjury Day 2 to Day 13. Vasospasm resolved after a duration of 5 days in 50% of the patients with Criterion A or B and after a period of 3.5 days in 50% of those patients with Criterion D or E. Hemodynamically significant vasospasm in the anterior circulation resolved after 2.5 days in 50% of the patients. The time course of that vasospasm was primarily determined by a decrease in CBF. CONCLUSIONS: The incidence of vasospasm after TBI is similar to that following aneurysmal subarachnoid hemorrhage. Because vasospasm is a significant event in a high proportion of patients after severe head injury, close TCD and CBF monitoring is recommended for the treatment of such patients.

Adult↗

Non-Hodgkin's B cell lymphoma in persons with acquired immunodeficiency syndrome is associated with increased serum levels of IL10, or the IL10 promoter -592 C/C genotype.

Interleukin-10 (IL10) may contribute to the development of non-Hodgkin's B cell lymphoma, especially in the context of acquired immunodeficiency syndrome (AIDS), where lymphoma incidence is greatly increased. Utilizing specimens from the Multicenter AIDS Cohort Study (MACS) obtained prior to diagnosis of AIDS-associated lymphoma, detectable serum human IL10 was seen much more frequently in lymphoma cases (n = 61, 26%) compared to CD4-matched AIDS controls (5%, P = 0.004), or to HIV-infected (2%, P = 0.002) or HIV uninfected subjects (0%, P = 0.0003). In longitudinal studies, detectable IL10 occurred at times closest to but preceding lymphoma diagnosis (P = 0.01). In an independent genetic analysis of single-nucleotide polymorphisms within the promoter region of the IL10 gene in 1157 MACS subjects, a high IL10-expressing genotype (-592 C/C) was overrepresented among lymphoma subjects (P = 0.009), even when controlling for race (P = 0.006). These results suggest that elevated serum IL10 or the IL10 promoter -592 C/C genotype are associated with development of AIDS lymphoma.

Acquired Immunodeficiency Syndrome↗

Ethnic differences in birth weight by gestational age: at least a partial explanation for the Hispanic epidemiologic paradox?

OBJECTIVE: The purpose of this study was to evaluate ethnic differences in low birth weight and gestational age-dependent birth weight. STUDY DESIGN: A retrospective cohort study of 47,669 newborn infants was conducted with the use of the perinatal database of the Memorial Health Care System. Logistic regression was used to estimate the odds ratio for low birth weight by ethnic group, which took into account gestational age at delivery. Multiple linear regression models were then developed to predict ethnic differences in birth weight by gestational age. RESULTS: When compared with white women, the adjusted odds ratio for low birth weight in of Mexican origin women (1.16; 95% CI, 1.02-1.32) was substantially lower than that of African American women (2.21; 95% CI, 1.87-2.60). An analysis of birth weight by gestational age suggested that African American neonates were intrinsically smaller than Hispanic neonates (difference, 4.22%). CONCLUSION: At least some of the differences in low birth weight that are noted among ethnic minorities may be attributable to ethnic differences in birth weight by gestational age.

Black or African American↗

Energy dysfunction as a predictor of outcome after moderate or severe head injury: indices of oxygen, glucose, and lactate metabolism.

UNLABELLED: The purpose of this study was to determine if the relationship between abnormalities in glucose, lactate, and oxygen metabolism were predictive of neurologic outcome after moderate or severe head injury, relative to other known prognostic factors. Serial assessments of the cerebral metabolic rates for glucose, lactate, and oxygen were performed using a modified Kety-Schmidt method. In total, 31 normal control subjects were studied once, and 49 TBI patients (mean age 36+/-16 years, median GCS 7) were studied five times median per patient from postinjury days 0 to 9. Univariate and multivariate analyses were performed. Univariate analysis showed that the 6-month postinjury Glasgow Outcome Scale (GOS) was most strongly associated with the mean cerebral metabolic rate of oxygen (CMRO2) (P = 0.0001), mean arterial lactate level (P = 0.0001), mean arterial glucose (P = 0.0008), mean cerebral blood flow (CBF), (P = 0.002), postresuscitation GCS (P = 0.003), and pupillary status (P = 0.004). Brain lactate uptake was observed in 44% of all metabolic studies, and 76% of patients had at least one episode of brain lactate uptake. By dichotomized GOS, patients achieving a favorable outcome (GOS 4-5) were distinguished from those with an unfavorable outcome (GOS1-3) by having a higher CMRO2 (P = 0.003), a higher rate of abnormal brain lactate uptake relative to arterial lactate levels (P = 0.04), and lesser degrees of blood-brain barrier damage based on CT findings (P = 0.03). CONCLUSIONS: During the first 6 days after moderate or severe TBI, CMRO2 and arterial lactate levels are the strongest predictors of neurologic outcome. However, the frequent occurrence of abnormal brain lactate uptake despite only moderate elevations in arterial lactate levels in the favorable outcome patients suggests the brain's ability to use lactate as a fuel may be another key outcome predictor. Future studies are needed to determine to what degree nonglycolytic energy production from alternative fuels such as lactate occurs after TBI and whether alternative fuel administration is a viable therapy for TBI patients.

Adult↗

Contribution of major diseases to disparities in mortality.

BACKGROUND: Mortality from all causes is higher for persons with fewer years of education and for blacks, but it is unknown which diseases contribute most to these disparities. METHODS: We estimated cause-specific risks of death from data from the National Health Interview Survey conducted from 1986 through 1994 and from linked vital statistics. Using these risk estimates, we calculated potential years of life lost and potential gains in life expectancy related to specific causes, with stratification according to education level and race. RESULTS: Persons without a high-school education lost 12.8 potential life-years per person in the population, as compared with 3.6 for persons who graduated from high school (ratio, 3.5; P<0.001). Ischemic heart disease contributed most (11.7 percent) to the difference according to education in potential life-years lost (with all cardiovascular diseases accounting for 35.3 percent). All cancers accounted for 26.5 percent, including 7.7 percent due to lung cancer; other lung diseases and pneumonia contributed 10.1 percent of the total, whereas human immunodeficiency virus (HIV) disease accounted for none of the difference according to education. The pattern of disparities according to level of income was similar to that according to level of education. Blacks and whites lost 7.0 and 5.2 potential life-years per person, respectively, as a result of deaths from any cause (ratio, 1.35; P<0.001). Cardiovascular diseases accounted for one third of this disparity, in large part because of hypertension (15.0 percent); HIV disease (11.2 percent) contributed almost as much as ischemic heart disease (5.5 percent), stroke (2.8 percent), and cancer (3.4 percent) combined; trauma and diabetes mellitus accounted for 10.7 percent and 8.5 percent, respectively. CONCLUSIONS: Although many conditions contribute to socioeconomic and racial disparities in potential life-years lost, a few conditions account for most of these disparities - smoking-related diseases in the case of mortality among persons with fewer years of education, and hypertension, HIV, diabetes mellitus, and trauma in the case of mortality among black persons. These findings have important implications for targeting efforts to reduce existing disparities in mortality rates.

Black People↗

Immunologic profile of highly exposed yet HIV type 1-seronegative men.

The host immune factors that determine susceptibility to HIV-1 infection are poorly understood. We compared multiple immunologic parameters in three groups of HIV-1-seronegative men: 14 highly exposed (HR10), 7 previously reported possibly to have sustained transient infection (PTI), and a control group of 14 low risk blood bank donors (BB). Virus-specific cellular immune assays were performed for CD4(+) T helper cell responses, CD8(+) cytotoxic T lymphocyte activity, CD8(+) cell chemokine release, and CD8(+) cell-derived antiviral soluble factor activity. General immune parameters evaluated included CCR5 genotype and phenotype, interferon alpha production by PBMCs, leukocyte subset analysis, and detailed T lymphocyte phenotyping. Comparisons revealed no detectable group-specific differences in measures of virus-specific immunity. However, the HR10 group differed from the BB group in several general immune parameters, having higher absolute monocyte counts, higher absolute CD8(+) T cell counts and percentages, lower naive and higher terminal effector CD8(+) cells, and lower levels of CD28(+)CD8(+) cells. These changes were not associated with seropositivity for other chronic viral infections. The PTI men appeared to have normal levels of monocytes and slightly elevated levels of CD8(+) T cells (also with increased effector and decreased naive cells). Although we cannot entirely exclude the contribution of other chronic viral infections, these findings suggest that long-lived systemic cellular antiviral immunity as detected by our assays is not a common mechanism for resistance to infection, and that resistance may be multifactorial. General immune parameters reflected by CD8(+) T cell levels and activation, and monocyte concentrations may affect the risk of infection with HIV-1, and/or serve as markers of exposure.

Adult↗

Impact of cytokines on replication in the thymus of primary human immunodeficiency virus type 1 isolates from infants.

Early infection of the thymus with the human immunodeficiency virus (HIV) may explain the more rapid disease progression among children infected in utero than in children infected intrapartum. Therefore, we analyzed infection of thymocytes in vitro by HIV type 1 primary isolates, obtained at or near birth, from 10 children with different disease outcomes. HIV isolates able to replicate in the thymus and impact thymopoiesis were present in all infants, regardless of the timing of viral transmission and the rate of disease progression. Isolates from newborns utilized CCR5, CXCR4, or both chemokine receptors to enter thymocytes. Viral expression was observed in discrete thymocyte subsets postinfection with HIV isolates using CXCR4 (X4) and isolates using CCR5 (R5), despite the wider distribution of CXCR4 in the thymus. In contrast to previous findings, the X4 primary isolates were not more cytopathic for thymocytes than were the R5 isolates. The cytokines interleukin-2 (IL-2), IL-4, and IL-7 increased HIV replication in the thymus by inducing differentiation and expansion of mature CD27(+) thymocytes expressing CXCR4 or CCR5. IL-2 and IL-4 together increased expression of CXCR4 and CCR5 in this population, whereas IL-4 and IL-7 increased CXCR4 but not CCR5 expression. IL-2 plus IL-4 increased the viral production of all pediatric isolates, but IL-4 and IL-7 had a significantly higher impact on the replication of X4 isolates compared to R5 isolates. Our studies suggest that coreceptor use by HIV primary isolates is important but is not the sole determinant of HIV pathogenesis in the thymus.

Cell Differentiation↗

Progressive hemorrhage after head trauma: predictors and consequences of the evolving injury.

OBJECT: Progressive intracranial hemorrhage after head injury is often observed on serial computerized tomography (CT) scans but its significance is uncertain. In this study, patients in whom two CT scans were obtained within 24 hours of injury were analyzed to determine the incidence, risk factors, and clinical significance of progressive hemorrhagic injury (PHI). METHODS: The diagnosis of PHI was determined by comparing the first and second CT scans and was categorized as epidural hematoma (EDH), subdural hematoma (SDH), intraparenchymal contusion or hematoma (IPCH), or subarachnoid hemorrhage (SAH). Potential risk factors, the daily mean intracranial pressure (ICP), and cerebral perfusion pressure were analyzed. In a cohort of 142 patients (mean age 34 +/- 14 years; median Glasgow Coma Scale score of 8, range 3-15; male/female ratio 4.3: 1), the mean time from injury to first CT scan was 2 +/- 1.6 hours and between first and second CT scans was 6.9 +/- 3.6 hours. A PHI was found in 42.3% of patients overall and in 48.6% of patients who underwent scanning within 2 hours of injury. Of the 60 patients with PHI, 87% underwent their first CT scan within 2 hours of injury and in only one with PHI was the first CT scan obtained more than 6 hours postinjury. The likelihood of PHI for a given lesion was 51% for IPCH, 22% for EDH, 17% for SAH, and 11% for SDH. Of the 46 patients who underwent craniotomy for hematoma evacuation, 24% did so after the second CT scan because of findings of PHI. Logistic regression was used to identify male sex (p = 0.01), older age (p = 0.01), time from injury to first CT scan (p = 0.02), and initial partial thromboplastin time (PTT) (p = 0.02) as the best predictors of PHI. The percentage of patients with mean daily ICP greater than 20 mm Hg was higher in those with PHI compared with those without PHI. The 6-month postinjury outcome was similar in the two patient groups. CONCLUSIONS: Early progressive hemorrhage occurs in almost 50% of head-injured patients who undergo CT scanning within 2 hours of injury, it occurs most frequently in cerebral contusions, and it is associated with ICP elevations. Male sex, older age, time from injury to first CT scan, and PTT appear to be key determinants of PHI. Early repeated CT scanning is indicated in patients with nonsurgically treated hemorrhage revealed on the first CT scan.

Adolescent↗

Early and persistent impaired percent alpha variability on continuous electroencephalography monitoring as predictive of poor outcome after traumatic brain injury.

OBJECT: Early prediction of outcomes in patients after they suffer traumatic brain injury (TBI) is often nonspecific and based on initial imaging and clinical findings alone, without direct physiological testing. Improved outcome prediction is desirable for ethical, social, and financial reasons. The goal of this study was to determine the usefulness of continuous electroencephalography (EEG) monitoring in determining prognosis early after TBI, while the patient is in the intensive care unit. METHODS: The authors hypothesized that the reduced percentage of alpha variability (PAV) in continuous EEG tracings indicates a poor prognosis. Prospective continuous EEG monitoring was performed in 89 consecutive patients with moderate to severe TBI (Glasgow Coma Scale [GCS] Scores 3-12) from 0 to 10 days after injury. The PAV was calculated daily, and the time course and trends of the PAV were analyzed in comparison with the patient's Glasgow Outcome Scale (GOS) score at the time of discharge. In patients with GCS scores of 8 or lower, a PAV value of 0.1 or lower is highly predictive of a poor outcome or death (positive predictive value 86%). The determinant PAV value was obtained by Day 3 after injury. Persistent PAV values of 0.1 or lower over several days or worsening of the PAV to a value of 0.1 or lower indicated a high likelihood of poor outcome (GOS Scores 1 and 2). In comparison with the combination of traditional initial clinical indicators of outcome (GCS score, pupillary response to light, patient age, results of computerized tomography scanning, and early hypotension or hypoxemia), the early PAV value during the initial 3 days after injury independently improved prognostic ability (p < 0.01). CONCLUSIONS: Continuous EEG monitoring performed with particular attention paid to the PAV is a sensitive and specific method of prognosis that can indicate outcomes in patients with moderate to severe TBI within 3 days postinjury.

Adult↗

Efficacy of hyperventilation, blood pressure elevation, and metabolic suppression therapy in controlling intracranial pressure after head injury.

OBJECT: Hyperventilation therapy, blood pressure augmentation, and metabolic suppression therapy are often used to reduce intracranial pressure (ICP) and improve cerebral perfusion pressure (CPP) in intubated head-injured patients. In this study, as part of routine vasoreactivity testing, these three therapies were assessed in their effectiveness in reducing ICP. METHODS: Thirty-three patients with a mean age of 33 +/- 13 years and a median Glasgow Coma Scale (GCS) score of 7 underwent a total of 70 vasoreactivity testing sessions from postinjury Days 0 to 13. After an initial 133Xe cerebral blood flow (CBF) assessment, transcranial Doppler ultrasonography recordings of the middle cerebral arteries were obtained to assess blood flow velocity changes resulting from transient hyperventilation (57 studies in 27 patients), phenylephrine-induced hypertension (55 studies in 26 patients), and propofol-induced metabolic suppression (43 studies in 21 patients). Changes in ICP, mean arterial blood pressure (MABP), CPP, PaCO2, and jugular venous oxygen saturation (SjvO2) were recorded. With hyperventilation therapy, patients experienced a mean decrease in PaCO2 from 35 +/- 5 to 27 +/- 5 mm Hg and in ICP from 20 +/- 11 to 13 +/- 8 mm Hg (p < 0.001). In no patient who underwent hyperventilation therapy did SjvO2 fall below 55%. With induced hypertension, MABP in patients increased by 14 +/- 5 mm Hg and ICP increased from 16 +/- 9 to 19 +/- 9 mm Hg (p = 0.001). With the aid of metabolic suppression, MABP remained stable and ICP decreased from 20 +/- 10 to 16 +/- 11 mm Hg (p < 0.001). A decrease in ICP of more than 20% below the baseline value was observed in 77.2, 5.5, and 48.8% of hyperventilation, induced-hypertension, and metabolic suppression tests, respectively (p < 0.001 for all comparisons). Predictors of an effective reduction in ICP included a high PaCO2 for hyperventilation, a high study GCS score for induced hypertension, and a high PaCO2 and a high CBF for metabolic suppression. CONCLUSIONS: Of the three modalities tested to reduce ICP, hyperventilation therapy was the most consistently effective, metabolic suppression therapy was variably effective, and induced hypertension was generally ineffective and in some instances significantly raised ICP. The results of this study suggest that hyperventilation may be used more aggressively to control ICP in head-injured patients, provided it is performed in conjunction with monitoring of SjvO2.

Adult↗