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Moderate and severe traumatic brain injury: epidemiologic, imaging and neuropathologic perspectives.

This article examines 3 contexts in which moderate or severe traumatic brain injury can be approached. The epidemiologic background of moderate and severe traumatic brain injury is presented, with particular attention paid to new findings from the study of a national hospital inpatient database. We review aspects of neuroimaging and how new imaging modalities can reveal fine detail about traumatic brain injury. Finally we examine the current state of neuropathologic evaluation of, and recent developments in, understanding of the neural disruptions that occur following traumatic brain injury, together with cellular reactions to these disruptions.

Brain↗

Assessment of executive function in patients with mild traumatic brain injury.

BACKGROUND: The nature of functional deficit after mild traumatic brain injury (TBI) defined by Glasgow Coma Score of 13-15 is not fully described. This study explored the sensitivity of several neuropsychological tests to identify sequelae of mild traumatic brain injury (TBI). METHODS: Eleven adult patients with mild TBI admitted to a Level 1 trauma center were studied. The battery of tests included the Wechsler Intelligence Scale for Children -Revised: Mazes Subtest, Trails A and B, the Boston Naming Test, The Multilingual Aphasia Examination: Controlled Oral Word Association Test, and the Paced Auditory Serial Addition Task. RESULTS: Control subjects performed significantly better than patients with mild TBI on Trails A and B, the Controlled Oral Word Association Test, and Paced Auditory Serial Addition Task (subtests 2-4). No significant differences in performances between patients and controls was found for the Wechsler Intelligence Scale for Children -Revised: Mazes Subtest, Boston Naming Test, and Paced Auditory Serial Addition Task Subtest 1. CONCLUSION: The results suggest that tests of specific frontal lobe executive functions are valuable in diagnosing and monitoring recovery from mild TBI.

Adult↗

Describing quality of life and psychosocial outcomes after traumatic brain injury.

OBJECTIVE: To describe the quality of life (QOL) and psychosocial outcomes of a sample of adults with traumatic brain injury in 50 community dwelling adults with traumatic brain injury and examine the associations among these variables. DESIGN: Cross-sectional. RESULTS: Mean QOL rating was low average. Standardized measures had acceptable internal reliability and normal distributions in this sample. Subjects had significantly lower QOL and social support, higher negative affect, and similar positive affect and spirituality compared with standardization and other nondisabled samples. They also had a significantly higher level of community integration than other traumatic brain injury samples. Regression analyses suggested that social support, community integration, and positive affect make a unique and significant contribution to the QOL variance with R of 0.492. The addition of spirituality reduced their respective unique variance, reducing positive affect to nonsignificant levels due to their high intercorrelation. CONCLUSIONS: Findings suggest that this sample experiences a wide range of QOL. Factors significantly associated with good QOL include community integration, positive affect, and social support; demographic variables had virtually no association with QOL. Evaluation of the sample's response to standardized scales not designed for a traumatic brain injury population support their use in similar QOL investigations.

Adult↗

[Serum S-100B protein and neuron-specific enolase after traumatic brain injury].

OBJECTIVE: The aim of this study was to investigate S-100B protein and NSE as a serum marker of brain cell damage after traumatic brain injury. MATERIAL AND METHODS: Forty-one patients with traumatic brain injury were included in this prospective study. Venous blood samples for S-100B protein and NSE were taken after admission and on the next day. Serum levels of S-100 protein and NSE were compared with Glasgow Coma Scale score, computed tomographic findings and outcome after 3 months. RESULTS: Serum S-100B protein and NSE were significantly correlated with Glasgow Coma Scale score and outcome after 3 months. The significant correlation was found between the initial S-100B and NSE (P < 0.001). In patients without parenchymal injuries on computed tomographic scan such as epidural hematoma and concussion, the elevation of S-100B protein and NSE was observed. The initial values of S-100B and NSE in acute subdural hematomas with unfavorable outcome were significantly higher than in those with favorable outcome. Secondary increase of serum markers was associated with the presence of secondary insult such as hypoxia or hypotension, and was found to have an unfavorable outcome. CONCLUSIONS: Serum concentration and kinetics of S-100B protein and NSE provide the clinical assessment of the primary brain damage and have a predictive value for outcome after traumatic brain injury.

Analysis of Variance↗

Outcome of prolonged coma following severe traumatic brain injury.

PRIMARY OBJECTIVE: To assess the outcome of severe traumatic brain injury 1 year after trauma. RESEARCH DESIGN: Prospective study conducted at the neurosurgical department of a university hospital. METHODS AND PROCEDURES: A total of 24 patients were included. Outcome was assessed by means of Glasgow outcome scale, Barthel index, Functional independence measure (FIM) and Disability rating scale (DRS). Need of care and job ability were also evaluated. EXPERIMENTAL INTERVENTIONS: Patients received multimodal early-onset stimulation and continuous inpatient and outpatient rehabilitation therapy. MAIN OUTCOMES AND RESULTS: Six patients died, three remained in a vegetative state, six were severely disabled, six were moderately disabled and three achieved a good recovery 1 year after injury. Mean Barthel index was 68.9, mean FIM was 88.3 and mean DRS 27.7. The majority of patients still were at least intermittently dependent on care. Most of the trauma survivors were unable to work. CONCLUSIONS: Despite intensive rehabilitation treatment, severe traumatic brain injury is still burdened with significant mortality and morbidity.

Adolescent↗

An appraisal of the impact of management guidelines in traumatic brain injury.

OBJECTIVE: To consider the evidence for the beneficial effects of the current management guidelines in traumatic brain injury, and to highlight the important issues. DATA SOURCES: Articles and published peer-review abstracts about the mechanisms and management of traumatic brain injury. SUMMARY OF REVIEW: Guidelines for the management of traumatic brain injury focus on the recognition, detection and prevention of secondary brain insults. Defence of cerebral perfusion pressure with optimisation of cerebral blood flow and substrate delivery, form the vanguard of these guidelines. The impact of guidelines per se on outcome is difficult to determine due to rapid changes in practice and a dearth of controlled evidence predating these guidelines. Technological developments in multimodal monitoring may identify trends in changing practice. However, there are still significant limitations in the accuracy of assessment of the underlying neuropathological processes. The impact of management strategies using current or novel therapies on these neuropathological processes is difficult to assess in randomised controlled trials due to small sample sizes and heterogeneous practice. Preliminary studies using continuous multimodal monitoring in accordance with current management guidelines have identified that episodes of sustained jugular venous desaturation were significantly reduced, indicating that potentially harmful episodes of cerebral oligaemia were prevented. Although the impact of these strategies on outcome was favourable, limitations in these studies do not allow firm outcome based assessments. However, these studies suggest that by defending cerebral perfusion pressure, potentially ischaemic or hypoxic cerebral insults may be prevented and may result in a reassessment of the indications and clinical utility of neuromonitoring. CONCLUSIONS: The impact of management guidelines in traumatic brain injury on patient outcome has been difficult to determine. However, there is a large body of uncontrolled evidence that suggests secondary global cerebral ischaemia-hypoxic insults are the major determinants in influencing outcome and that therapeutic interventions that maintain and defend cerebral perfusion pressures may improve outcome.

Journal Article↗

Use of injury severity variables in determining disability and community integration after traumatic brain injury.

BACKGROUND: Long-term outcome is important in managing traumatic brain injury (TBI), an epidemic in the United States. Many injury severity variables have been shown to predict major morbidity and mortality. Less is known about their relationship with specific long-term outcomes. METHODS: Glasgow Coma Scale, Revised Trauma Score, Injury Severity Score, and Trauma and Injury Severity Score, along with other demographic and premorbid values, were obtained for 378 consecutive patients hospitalized after TBI at a Level I trauma center between September 1997 and May 1998. Of this cohort, 120 patients were contacted for 1-year follow-up assessment with the Disability Rating Scale, Community Integration Questionnaire, and employment data. RESULTS: Univariate analyses showed these to be significant single predictors of 1-year outcome. Multivariate analyses revealed that the Revised Trauma Score and Glasgow Coma Scale had significant additive value in predicting injury variables Disability Rating Scale scores when combined with other demographic and premorbid variables studied. Predictive models of 1-year outcome were developed. CONCLUSION: Injury severity variables are significant single outcome predictors and, in combination with premorbid and demographic variables, help predict long-term disability and community integration for individuals hospitalized with TBI.

Adolescent↗

Interaction between anesthesia, gender, and functional outcome task following diffuse traumatic brain injury in rats.

A number of experimental and clinical studies have demonstrated that functional outcome following traumatic brain injury differs between males and females. Some studies report that females have a better outcome than males following trauma while others report the opposite. In experimental studies, some of the contradictory results may be due to the different experimental conditions, including type of anesthesia and the outcome measures employed. In the present study we have used three different anesthetic protocols and four different outcome measures to determine how these parameters interact and affect functional outcome following traumatic brain injury in male and female rats. Diffuse traumatic brain injury was induced in adult male and female animals using the impact-acceleration brain injury model. Mortality in female animals was no different than males when using halothane anesthesia, slightly better than males when using isoflurane anesthesia, but significantly worse than males under pentobarbital anesthesia. Female animals always performed better than males on rotarod tests of motor outcome, with this effect being unrelated to anesthetic effects. Conversely, in cognitive tests using the Barnes Maze, only isoflurane-anesthetized females performed better than their male counterparts. Similarly, in an open field activity task, females always performed better than males after trauma, with isoflurane-anesthetized females also performing significantly better than the halothane-anesthetized female group after injury. Our results suggest that female animals do better than males after diffuse traumatic brain injury, although this observation is dependent upon the type of anesthesia and the functional task employed. Isoflurane is particularly protective in females, pentobarbital is deleterious to female outcome, while halothane anesthesia has the least influence on gender-related outcome.

Anesthesia↗

The immunophilin ligand FK506 attenuates axonal injury in an impact-acceleration model of traumatic brain injury.

The immunophilin ligand, cyclosporin A (CsA), is effective in reducing the axonal damage associated with traumatic brain injury (TBI). Based upon extensive ultrastructural and immunohistochemical studies, the neuroprotection afforded by CsA appeared to be mediated via mitochondrial protection, specifically, the prevention of mitochondrial swelling and inhibition of mitochondrial permeability transition (MPT). However, the potential that CsA could also be neuroprotective via the immunophilin-mediated inhibition of the protein phosphatase, calcineurin (CN) has not been directly assessed. To address this issue, the current study assessed the ability of FK506, another immunophilin ligand that inhibits CN with no effect on MPT, to attenuate axonal damage in a rat impact-acceleration model of TBI. Traumatic axonal injury (TAI), detected via an antibody against beta-amyloid precursor protein (APP), a specific marker of axonal injury, was significantly reduced at 24 hr postinjury in Sprague-Dawley rats receiving intravenous FK506 (2 mg/kg; n = 5) 30 min prior to injury compared to vehicle controls (n = 3). While not rejecting the established efficacy of CsA in providing neuroprotection via its targeting of MPT, this study does underscore the potential importance of CN in the progressive pathobiology of TAI, suggesting that CN may constitute another important therapeutic target.

Acceleration↗

Weak, but complex pulsed magnetic fields may reduce depression following traumatic brain injury.

Many patients who display psychological depression following a traumatic brain injury do not respond completely to antidepressant drugs. We hypothesized that this type of depression is strongly correlated with subclinical, complex partial seizure-activity within the hippocampal-amygdaloid region that continues for months to years after apparent neurological and behavioral "recovery." Four depressed patients who had sustained traumatic brain injuries and who exhibited mild to moderate brain impairment according to standardized tests received 30 min. of weak (1 microT) burst-firing magnetic fields across the temporal lobes once per week for 5 weeks. There was a significant improvement of depression and reduction of phobias while physical symptoms and other complaints were not changed.

Adult↗

Somatosensory evoked fields in comatose survivors after severe traumatic brain injury.

OBJECTIVE: To evaluate the cortical function quantitatively in patients in the chronic phase of severe traumatic brain injury. METHODS: Thirteen patients with severe traumatic brain injury due to traffic accident followed by persistent consciousness disturbance and disability were studied. Somatosensory evoked magnetic fields (SEFs) for unilateral median nerve stimulation were measured using a whole-head magnetoencephalography system. The latency and electrical current dipole (ECD) moment for the N20m, P30m, N45m and P60m components were calculated and compared with those of 14 age-matched healthy adults. RESULTS: The peak latency of N20m was longer (P<0.05) and those of P30m and N45m were shorter (P<0.01) in the patients than in normal adults. The ECD moment of N20m and P30m was smaller and that of N45m and P60m was larger in the patients than in normal adults (P<0.01). CONCLUSIONS: These results can be explained by the hypothesis that diffuse brain injury induces decreased and delayed input of the somatosensory afferent and compensational amplification of the response in the primary somatosensory cortex. Middle-latency SEFs may be applicable as a cortical functional measure for patients with severe traumatic brain injury.

Adult↗

Neuroprotection and traumatic brain injury: theoretical option or realistic proposition.

PURPOSE OF REVIEW: Preclinical studies have shown that treatment to limit secondary cell damage can significantly improve outcome after traumatic brain injury. In contrast, neuroprotection trials in human traumatic brain injury have failed to convincingly demonstrate therapeutic benefit. Recent literature has begun to address this discrepancy between preclinical and clinical trials. RECENT FINDINGS: Perhaps the most important recent observations relate to the potential role of apoptosis in secondary brain injury. Because apoptosis peaks more than 24 h after injury, concepts about the therapeutic window for traumatic brain injury treatment have changed. Apoptosis and necrosis are in delicate balance and inhibition of one cell death pathway may enhance the other. This raises questions about the ultimate effectiveness of treatment strategies directed toward a single injury mechanism. In contrast to clinical head injury, which reflects a complex multi-factorial disorder, animal models are generally designed to address only a single injury component and are performed in genetically inbred animals of a single sex. Moreover, animal studies usually employ pretreatment or early posttreatment administration, examine moderate rather than severe injury, fail to examine brain drug levels or treatment optimization, and do not use an intent-to-treat methodology. SUMMARY: Recognition of these methodological differences between animal and human studies has led to new trial design proposals. For clinical studies, there should be better stratification of patients, a focus on moderate injury and earlier treatment, and larger sample sizes. Animal experiments should better parallel clinical studies and address therapeutic window and treatment optimization. Recognition of multiple cell death pathways should lead to new treatment strategies--including both combination drug treatment and drugs that affect multiple components of the secondary injury cascade.

Animals↗

Accuracy of world-wide-web death searches for persons with traumatic brain injury.

PRIMARY OBJECTIVE: Determine (1) the sensitivity of world-wide-web searches for deaths among persons with traumatic brain injuries and (2) factors associated with the likelihood of identifying deceased persons with traumatic brain injuries. RESEARCH DESIGN: Stratified case series. METHODS AND PROCEDURES: Sequential submission of 371 deceased persons with traumatic brain injuries to a world-wide-web site to determine inclusion in the Social Security Death Index (SSDI). MAIN OUTCOMES AND RESULTS: Almost 87% of deceased persons ages 50+ were found, 69.8% of persons ages 30-49 and 34.6% of persons younger than age 30. Other factors influencing the likelihood of finding deceased persons in the SSDI were male gender, white race, being married, knowing the Social Security number and survival of 1+ years post-injury. CONCLUSIONS: The SSDI provides useful information for mortality studies among persons with traumatic brain injuries, but does a poor job of identifying deaths among younger persons. Sole reliance on the SSDI may result in under-ascertainment of mortality.

Adolescent↗

Factors contributing to fatal outcome of traumatic brain injury: a pilot case control study.

OBJECTIVE: Patients with traumatic brain injury (TBI) have a high mortality and morbidity. This pilot study was undertaken to identify contributors to outcome in the early management of patients with TBI and to investigate the feasibility of a larger study. METHODS: Road trauma patients who died between January 1 and April 30, 2000 were selected from the Alfred Hospital's Intensive Care Traumatic Brain Injury database. These patients were matched with 2 survivors from the data base during the same period for age, injury severity score (ISS) and severity of brain injury using the head abbreviated injury score (head AIS). Patient injury scoring (using the revised trauma score, trauma and injury severity score and Glasgow coma score), arterial blood gas analysis, lactate concentration, inspired oxygen concentration, systolic and mean arterial blood pressure, intracranial pressure, intravenous fluid and blood transfusion volumes, body temperature, haemoglobin, white cell count, INR, APTT, temperature and plasma glucose, urea and creatinine concentrations were recorded for 48 hours from the time of injury. Time periods from the accident to key events (e.g. arrival of ambulance at accident scene, intubation, arrival at the emergency department, insertion of intracranial pressure monitor and primary surgery) were also recorded. RESULTS: Eighteen patients (6 deceased, 12 survivors) were identified. Despite matching, deceased patients had lower initial Glasgow Coma Scores (GCS) (3.6 vs. 7.4, P = 0.01) and lower revised trauma scores (4.41 vs. 5.75; P = 0.044) compared with survivors. There were no significant differences in other parameters. However, deceased patients tended to have longer times to treatment (P = NS) and experienced trauma at night more frequently, and survivors received almost double the volume of fluid resuscitation during the first 12 hours (19.7 +/- 19.1 vs. 11.8 +/- 2.7 mL/kg/hr, P = 0.513). CONCLUSIONS: Both initial GCS and severity of brain injury should be used to match TBI patients for injury severity in future studies. Lower initial GCS in deceased patients was likely due to greater severity of brain injury, although it is also possible that the lower GCS was due to decreased brain perfusion (perhaps reflecting inadequate resuscitation) in these patients. Volume of early fluid resuscitation, time to definitive therapy, and time of presentation to hospital may also be important determinants of patient outcome. A large case control outcome study is required to extend these observations.

Journal Article↗

Factors Associated With Accelerated Fracture Healing in Patients With Traumatic Brain Injury and Extremity Comminuted Fractures: A Retrospective Case-Control Study.

OBJECTIVE: Although traumatic brain injury (TBI) has been clinically associated with accelerated bone healing, the factors that determine which patients experience this phenomenon remain poorly defined, and previous findings are conflicting. This study aimed to investigate the clinical factors associated with accelerated fracture healing in patients with TBI combined with comminuted fractures of the limbs, so as to provide an evidence-based foundation for elucidating the clinical phenomenon of TBI-promoted fracture healing. METHODS: A retrospective case-control study design was employed. Patients between January 2020 and April 2024 with concurrent diagnoses of TBI and comminuted fractures were included. Based on radiographic findings and RUST/mRUST scores, patients were divided into an accelerated healing group (AHG) and a normal/delayed healing group (NDHG). Clinical data including demographics (age, sex, BMI), TBI characteristics (injury site, GCS score), admission laboratory indices (blood count, coagulation function, inflammatory markers), and fracture site/local soft tissue conditions, as well as functional outcomes assessed by the Short Musculoskeletal Function Assessment (SMFA) questionnaire at final follow-up were collected. Univariate analysis and multivariate logistic regression analysis were used to identify independent factors influencing accelerated fracture healing. Receiver operating characteristic (ROC) curves were plotted to evaluate their predictive value. RESULTS: A total of 119 patients were included, with 69 in the AHG and 50 in the NDHG. Significant differences were observed between the two groups in terms of age, BMI, GCS score, and platelet count (p&#x2009;<&#x2009;0.05). Univariate analysis showed that age, BMI, GCS score, red blood cell count, and platelet count were associated with accelerated fracture healing (p&#x2009;<&#x2009;0.20). Multivariate logistic regression analysis indicated that younger age (OR&#x2009;=&#x2009;0.875, 95% CI: 0.821-0.934) and lower GCS score (indicating more severe TBI; OR&#x2009;=&#x2009;0.490, 95% CI: 0.339-0.707) were independent predictors of accelerated fracture healing. ROC curve analysis showed that the area under the curve (AUC) for age and GCS score in predicting accelerated healing were 0.893 and 0.851, respectively. CONCLUSIONS: In patients with TBI combined with comminuted fractures, younger age and greater TBI severity (lower GCS score) are independent predictors of accelerated fracture healing. These findings assist clinicians in the early identification of patients with high healing potential to optimize treatment strategies, facilitate the early identification of high-risk patients, and provide clinical clues for further exploration of the molecular mechanisms underlying neurohumoral regulation of bone regeneration.

Humans↗

Interstitial brain adenosine and xanthine increase during jugular venous oxygen desaturations in humans after traumatic brain injury.

OBJECTIVE: Adenosine decreases the cerebral metabolic rate for oxygen and increases cerebral blood flow, and it may play an important role in cerebrometabolic and cerebrovascular responses to hypoperfusion after traumatic brain injury. Jugular venous oxygen saturation is monitored after traumatic brain injury to assess brain oxygen extraction, and desaturations may reflect secondary brain insults. We hypothesized that brain interstitial adenosine and related purine metabolites would be increased during jugular venous oxygen saturation desaturations (<50%) and determined associations between the purines, lactate, and glucose to assess the role of adenosine during secondary insults in humans. DESIGN: Study of critically ill adults with severe traumatic brain injury. SETTING: Adult neurointensive care unit. PATIENTS: We prospectively defined periods of normal saturation and desaturation in six patients after severe traumatic brain injury. INTERVENTIONS: During these periods, cerebral microdialysis samples of brain interstitial fluid were collected, and adenosine and purine metabolites were measured by high-pressure liquid chromatography. MEASUREMENTS AND MAIN RESULTS: Adenosine increased 3.1-fold and xanthine increased 2.5-fold during desaturation periods (both p <.05 vs. normal saturation period, signed rank). Adenosine, xanthine, hypoxanthine, and cyclic-adenosine monophosphate correlated with lactate over both study periods (r(2) =.32,.14,.31,.07, and.26, respectively, all p <.05, Pearson product moment correlation). CONCLUSION: The marked increases in interstitial brain adenosine that occur during jugular venous oxygen desaturations suggest that adenosine may play an important role during periods of secondary insults after traumatic brain injury. The correlation of these metabolites with lactate further suggests that adenosine is increased during periods of enhanced glycolytic metabolism.

Adenosine↗

Psychosocial adjustment after traumatic brain injury: what are the important variables?

BACKGROUND: The common legacy of severe degrees of traumatic brain injury is varying degrees and types of impairments, which impact significantly upon the individual's resumption of pre-morbid psychosocial roles. Yet there are few data to indicate the relative contribution of these and other non-injury related variables. METHODS: Seventy individuals with varying levels of disability after severe traumatic brain injury were examined neurologically and neuropsychologically, on average at 6 years post-trauma. A range of biographical, injury, impairment and psychological variables were examined with multiple regression analyses to identify those that contributed to successful psychosocial reintegration. RESULTS: Severity of injury and impairments, along with chronicity and level of self-esteem were significant predictors of psychosocial adjustment. Further analyses revealed that within the neuropsychological domain, the variable measuring behavioural regulation of abilities was the most significant. Examination of specific domains of psychosocial functioning (occupational activities, interpersonal relationships and independent living skills) revealed different patterns of significant predictor variables, in addition to indices of the severity of initial injury: neurophysical impairments and memory functioning predicted successful occupational activities; chronicity, cognitive speed and behavioural regulation predicted success in interpersonal relationships; and neurophysical impairments, behavioural regulation and memory functioning predicted independent living skills. CONCLUSIONS: These results reinforce the overriding importance of injury severity and neurological factors (both neurophysical as well as neuropsychological) in predicting psychosocial adjustment after traumatic brain injury. Support for the contribution of non-neurological factors was also found.

Adaptation, Psychological↗

Apoptosis-related gene bcl-2 in lung tissue after experimental traumatic brain injury in rats.

BACKGROUND: We have recently shown that experimental traumatic brain injury resulted in ultra structural damage in lung tissue. The main objective of the current study was to investigate in a rat model of brain injury whether expression of Bcl-2 gene and lipid peroxidation levels in the lung tissue after traumatic brain injury were affected by methylprednisolone sodium succinate (MPSS) treatment. METHODS: Fifty-six Wistar-Albino female rats weighing 180-220 g were used, which were allocated into seven groups. A weight-drop method was used to achieve head trauma. Real time quantitative PCR analyses for Bcl-2 gene expression and measurement of the levels of lipid peroxidation were carried out. All the data was analyzed by using SPSS 11.5 for Windows. RESULTS: Mean Bcl-2 expression in the methylprednisolone group was considerably higher compared to that of all the other groups (p<.05). Mean lipid peroxidation levels were significantly higher in the trauma group and notably lower in the methylprednisolone group (p<.01). CONCLUSIONS: The oxidative stress imposed on lung tissue, as seen by high levels of lipid peroxidation, after brain injury was significantly attenuated by MPSS treatment. MPSS treatment following brain injury also augmented putative anti-apoptotic Bcl-2 gene expression in lung tissue. Further studies are required to determine the full range and lower limits of effective MPSS dose. More importantly the optimal efficacy according to the timing of MPSS treatment after brain injury needs to be determined for impact on more diverse markers of cell inflammation, apoptosis and injury.

Analysis of Variance↗