Dataset Information

Blast traumatic brain injury and serum inflammatory cytokines: a repeated measures case-control study among U.S. military service members.

ABSTRACT: BACKGROUND:There is a paucity of human data on exposure to blast traumatic brain injury (bTBI) and the corresponding systemic cytokine immune response at later time points (i.e., months, years) post-injury. METHODS:We conducted a repeated measures, case-control study, examining associations of serum levels of pro- and anti-inflammatory cytokines, measured both pre- and post-deployment with having mild and moderate/severe bTBI. Utilizing serum from the Department of Defense Serum Repository cytokines were measured via an ELISA-based array for 15 cytokines. We compared pre- vs. post-levels among mild cases, moderate/severe cases, and controls and carried out case-control comparisons, using paired t- tests and generalized linear models. RESULTS:The average time between bTBI and post-deployment/bTBI serum among cases was 315.8?days. From pre- to post-deployment/bTBI, levels of interleukin 8 (IL-8) were decreased among both mild cases (??=?-?83.43?pg/ml; s.e.?=?21.66) and moderate/severe cases (??=?-?107.67?pg/ml; s.e.?=?28.74?pg/ml), while levels increased among controls (??=?32.86?pg/ml; s.e.?=?30.29). The same pattern occurred for matrix metallopeptidase 3 (MMP3), with levels decreasing for moderate/severe cases (??=?-?3369.24?pg/ml; s.e.?=?1701.68) and increasing for controls (??=?1859.60?pg/ml; s.e.?=?1737.51) from pre- to post-deployment/bTBI. Evidence was also suggestive of case-control differences, from pre- to post-deployment/bTBI for interleukin 1 alpha (IL-1?), interleukin 4 (IL-4), and interleukin 6 (IL-6) among moderate/severe cases. CONCLUSION:The findings of this longitudinal study indicate that in the chronic phase of bTBI, levels of IL-8 and MMP3 may be substantially lower than pre-injury. These results need confirmation in other studies, potentially those that account for treatment differences, which was not possible in our study.

SUBMITTER: Rusiecki J

PROVIDER: S-EPMC6958571 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Blast traumatic brain injury and serum inflammatory cytokines: a repeated measures case-control study among U.S. military service members.

Rusiecki Jennifer J Levin Lynn I LI Wang Li L Byrne Celia C Krishnamurthy Jayasree J Chen Ligong L Galdzicki Zygmunt Z French Louis M LM

Journal of neuroinflammation 20200113 1

<h4>Background</h4>There is a paucity of human data on exposure to blast traumatic brain injury (bTBI) and the corresponding systemic cytokine immune response at later time points (i.e., months, years) post-injury.<h4>Methods</h4>We conducted a repeated measures, case-control study, examining associations of serum levels of pro- and anti-inflammatory cytokines, measured both pre- and post-deployment with having mild and moderate/severe bTBI. Utilizing serum from the Department of Defense Serum R ...[more]

PMID: 31931830

Similar Datasets

Project description:BackgroundThe underlying molecular mechanisms of PTSD are largely unknown. Distinct expression signatures for PTSD have been found, in particular for immune activation transcripts. DNA methylation may be significant in the pathophysiology of PTSD, since the process is intrinsically linked to gene expression. We evaluated temporal changes in DNA methylation in select promoter regions of immune system-related genes in U.S. military service members with a PTSD diagnosis, pre- and post-diagnosis, and in controls.MethodsCases (n?=?75) had a post-deployment diagnosis of PTSD in their medical record. Controls (n?=?75) were randomly selected service members with no PTSD diagnosis. DNA was extracted from pre- and post-deployment sera. DNA methylation (%5-mC) was quantified at specific CpG sites in promoter regions of insulin-like growth factor 2 (IGF2), long non-coding RNA transcript H19, interleukin-8 (IL8), IL16, and IL18 via pyrosequencing. We used multivariate analysis of variance and generalized linear models to calculate adjusted means (adjusted for age, gender, and race) to make temporal comparisons of %5-mC for cases (pre- to post-deployment) versus controls (pre- to post-deployment).ResultsThere were significant differences in the change of %5-mC pre- to post-deployment between cases and controls for H19 (cases: +0.57%, controls: -1.97%; p?=?0.04) and IL18 (cases: +1.39%, controls: -3.83%; p?=?0.01). For H19 the difference was driven by a significant reduction in %5-mC among controls; for IL18 the difference was driven by both a reduction in %5-mC among controls and an increase in %5-mC among cases. Stratified analyses revealed more pronounced differences in the adjusted means of pre-post H19 and IL18 methylation differences for cases versus controls among older service members, males, service members of white race, and those with shorter deployments (6-12?months).ConclusionIn the study of deployed personnel, those who did not develop PTSD had reduced %5-mC levels of H19 and IL18 after deployment, while those who did develop PTSD had increased levels of IL18. Additionally, pre-deployment the people who later became cases had lower levels of IL18 %5-mC compared with controls. These findings are preliminary and should be investigated in larger studies.

Project description:The purpose of this study was to analyze quantitative diffusion tensor imaging measures across the spectrum of traumatic brain injury severity and evaluate their trajectories in military service members. Participants were 96 U.S. military service members and veterans who had sustained a mild traumatic brain injury [including complicated mild traumatic brain injury (n = 16) and uncomplicated mild traumatic brain injury (n = 68)], moderate-severe traumatic brain injury (n = 12), and controls (with or without orthopaedic injury, n = 39). All participants had been scanned at least twice, with some receiving up to five scans. Both whole brain voxel-wise analysis and tract-of-interest analysis were applied to assess the group differences of diffusion tensor imaging metrics, and their trajectories between time points of scans and days since injury. Linear mixed modelling was applied to evaluate cross-sectional and longitudinal diffusion tensor imaging metrics changes within and between groups using both tract-of-interest and voxel-wise analyses. Participants with moderate to severe traumatic brain injury had larger white matter disruption both in superficial subcortical and deep white matter, mainly over the anterior part of cerebrum, than those with mild traumatic brain injury, both complicated and uncomplicated, and there was no evidence of recovery over the period of follow-ups in moderate-severe traumatic brain injury, but deterioration was possible. Participants with mild traumatic brain injury had white matter microstructural changes, mainly in deep central white matter over the posterior part of cerebrum, with more spatial involvement in complicated mild traumatic brain injury than in uncomplicated mild traumatic brain injury and possible brain repair through neuroplasticity, e.g. astrocytosis with glial processes and glial scaring. Our results did not replicate 'V-shaped' trajectories in diffusion tensor imaging metrics, which were revealed in a previous study assessing the sub-acute stage of brain injury in service members and veterans following military combat concussion. In addition, non-traumatic brain injury controls, though not demonstrating any evidence of sustaining a traumatic brain injury, might have transient white matter changes with recovery afterward. Our results suggest that white matter integrity following a remote traumatic brain injury may change as a result of different underlying mechanisms at the microstructural level, which can have a significant consequence on the long-term well beings of service members and veterans. In conclusion, longitudinal diffusion tensor imaging improves our understanding of the mechanisms of white matter microstructural changes across the spectrum of traumatic brain injury severity. The quantitative metrics can be useful as guidelines in monitoring the long-term recovery.

Project description:Blast-related traumatic brain injuries have been common in the Iraq and Afghanistan wars, but fundamental questions about the nature of these injuries remain unanswered.We tested the hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging (DTI), an advanced form of magnetic resonance imaging that is sensitive to axonal injury. The subjects were 63 U.S. military personnel who had a clinical diagnosis of mild, uncomplicated traumatic brain injury. They were evacuated from the field to the Landstuhl Regional Medical Center in Landstuhl, Germany, where they underwent DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mechanism of injury (e.g., being struck by a blunt object or injured in a fall or motor vehicle crash). Controls consisted of 21 military personnel who had blast exposure and other injuries but no clinical diagnosis of traumatic brain injury.Abnormalities revealed on DTI were consistent with traumatic axonal injury in many of the subjects with traumatic brain injury. None had detectable intracranial injury on computed tomography. As compared with DTI scans in controls, the scans in the subjects with traumatic brain injury showed marked abnormalities in the middle cerebellar peduncles (P<0.001), in cingulum bundles (P=0.002), and in the right orbitofrontal white matter (P=0.007). In 18 of the 63 subjects with traumatic brain injury, a significantly greater number of abnormalities were found on DTI than would be expected by chance (P<0.001). Follow-up DTI scans in 47 subjects with traumatic brain injury 6 to 12 months after enrollment showed persistent abnormalities that were consistent with evolving injuries.DTI findings in U.S. military personnel support the hypothesis that blast-related mild traumatic brain injury can involve axonal injury. However, the contribution of primary blast exposure as compared with that of other types of injury could not be determined directly, since none of the subjects with traumatic brain injury had isolated primary blast injury. Furthermore, many of these subjects did not have abnormalities on DTI. Thus, traumatic brain injury remains a clinical diagnosis. (Funded by the Congressionally Directed Medical Research Program and the National Institutes of Health; ClinicalTrials.gov number, NCT00785304.).

Project description:Background and objectivesAlthough polychlorinated biphenyls (PCBs) were banned decades ago, populations are continuously exposed to PCBs due to their persistence and bioaccumulation/biomagnification in the environment. Results from limited epidemiologic studies linking PCBs to thyroid cancer have been inconclusive. This study aimed to investigate the association between individual PCBs and PCB mixture and papillary thyroid cancer (PTC), the most common thyroid cancer histologic subtype.MethodsWe carried out a nested case-control study including 742 histologically confirmed PTC cases diagnosed in 2000-2013 and 742 individually matched controls among U.S. military service members. Pre-diagnostic serum samples that were collected on average nine years before PTC diagnosis were used to measure PCB congeners by gas chromatography isotope dilution high resolution mass spectrometry (GC/ID-HRMS). Conditional logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression were employed to estimate the association between single PCB congeners as well as their mixture and PTC.ResultsFour PCB congeners (PCB-74, PCB-99, PCB-105, PCB-118) had significant associations and dose-response relationships with increased risk of PTC in single congener models. When considering the effects from all measured PCBs and their potential interactions in the BKMR model, PCB-118 showed positive trends of association with PTC. Increased exposure to the PCB congeners as a mixturewas also associated with an increased risk of PTC in the WQS model, with the mixture dominated by PCB-118, followed by PCB-74 and PCB-99. One PCB congener, PCB-187, showed an inverse trend of association with PTC in the mixture analysis.DiscussionThis study suggests that exposure to certain PCBs as well as a mixture of PCBs were associated with an increased risk of PTC. The observed association was mainly driven by PCB-118, and to a lesser extent by PCB-74 and PCB-99. The findings warrant further investigation.

Project description:To detect cerebral microhemorrhages in military service members with chronic traumatic brain injury by using susceptibility-weighted magnetic resonance (MR) imaging. The longitudinal evolution of microhemorrhages was monitored in a subset of patients by using quantitative susceptibility mapping.The study was approved by the Walter Reed National Military Medical Center institutional review board and is compliant with HIPAA guidelines. All participants underwent two-dimensional conventional gradient-recalled-echo MR imaging and three-dimensional flow-compensated multiecho gradient-recalled-echo MR imaging (processed to generate susceptibility-weighted images and quantitative susceptibility maps), and a subset of patients underwent follow-up imaging. Microhemorrhages were identified by two radiologists independently. Comparisons of microhemorrhage number, size, and magnetic susceptibility derived from quantitative susceptibility maps between baseline and follow-up imaging examinations were performed by using the paired t test.Among the 603 patients, cerebral microhemorrhages were identified in 43 patients, with six excluded for further analysis owing to artifacts. Seventy-seven percent (451 of 585) of the microhemorrhages on susceptibility-weighted images had a more conspicuous appearance than on gradient-recalled-echo images. Thirteen of the 37 patients underwent follow-up imaging examinations. In these patients, a smaller number of microhemorrhages were identified at follow-up imaging compared with baseline on quantitative susceptibility maps (mean ± standard deviation, 9.8 microhemorrhages ± 12.8 vs 13.7 microhemorrhages ± 16.6; P = .019). Quantitative susceptibility mapping-derived quantitative measures of microhemorrhages also decreased over time: -0.85 mm(3) per day ± 1.59 for total volume (P = .039) and -0.10 parts per billion per day ± 0.14 for mean magnetic susceptibility (P = .016).The number of microhemorrhages and quantitative susceptibility mapping-derived quantitative measures of microhemorrhages all decreased over time, suggesting that hemosiderin products undergo continued, subtle evolution in the chronic stage.

Project description:Mortality and CKD risk have not been described in military casualties with post-traumatic AKI requiring RRT suffered in the Iraq and Afghanistan wars.This is a retrospective case series of post-traumatic AKI requiring RRT in 51 military health care beneficiaries (October 7, 2001-December 1, 2013), evacuated to the National Capital Region, documenting in-hospital mortality and subsequent CKD. Participants were identified using electronic medical and procedure records.Age at injury was 26±6 years; of the participants, 50 were men, 16% were black, 67% were white, and 88% of injuries were caused by blast or projectiles. Presumed AKI cause was acute tubular necrosis in 98%, with rhabdomyolysis in 72%. Sixty-day all-cause mortality was 22% (95% confidence interval [95% CI], 12% to 35%), significantly less than the 50% predicted historical mortality (P<0.001). The VA/NIH Acute Renal Failure Trial Network AKI integer score predicted 60-day mortality risk was 33% (range, 6%-96%) (n=49). Of these, nine died (mortality, 18%; 95% CI, 10% to 32%), with predicted risks significantly miscalibrated (P<0.001). The area under the receiver operator characteristic curve for the AKI integer score was 0.72 (95% CI, 0.56 to 0.88), not significantly different than the AKI integer score model cohort (P=0.27). Of the 40 survivors, one had ESRD caused by cortical necrosis. Of the remaining 39, median time to last follow-up serum creatinine was 1158 days (range, 99-3316 days), serum creatinine was 0.85±0.24 mg/dl, and eGFR was 118±23 ml/min per 1.73 m(2). No eGFR was <60 ml/min per 1.73 m(2), but it may be overestimated because of large/medium amputations in 54%. Twenty-five percent (n=36) had proteinuria; one was diagnosed with CKD stage 2.Despite severe injuries, participants had better in-hospital survival than predicted historically and by AKI integer score. No patient who recovered renal function had an eGFR<60 ml/min per 1.73 m(2) at last follow-up, but 23% had proteinuria, suggesting CKD burden.

Project description:As a result of armed conflict, head trauma from exposure to blasts is an increasing critical health issue, particularly among military service members. Whilst numerous studies examined the burden of blast-related brain injuries on service members', few systematic reviews have been published. This work provides a comprehensive summary of the evidence on blast-related mild traumatic brain injury (mTBI) burden in active U.S. military service members and inactive Veterans, describing characteristics and outcomes. Records published up to April 2017 were identified through a search of PubMed, Web of Science, Scopus, Ovid MEDLINE, and Cochrane Library. Records-based and original research reporting on U.S. military service members and Veterans with mild blast TBI were included. Data on subject characteristics, exposure, diagnostic criterion, and outcomes were extracted from included studies using a standardized extraction form and were presented narratively. Of the 2,290 references identified by the search, 106 studies with a total of 37,515 participants met inclusion criteria for blast-related mTBI. All but nine studies were based out of military or Veteran medical facilities. Unsurprisingly, men were over-represented (75-100%). The criteria used to define blast-related mTBI were consistent; however, the methodology used to ascertain whether individuals met those criteria for diagnosis were inconsistent. The diagnosis, most prevalent among the Army, heavily relied on self-reported histories. Commonly reported adverse outcomes included hearing disturbances and headaches. The most frequently associated comorbidities were post-traumatic stress disorder, depression, anxiety, sleep disorders, attention disorders, and cognitive disorders. The primary objective of this review was to provide a summary of descriptive data on blast-related mTBI in a U.S. military population. Low standardization of the methods for reaching diagnosis and problems in the study reporting emphasize the importance to collect high-quality data to fill knowledge gaps pertaining to blast-related mTBI.

Project description:OBJECTIVES:The study aimed tocompare recurring themes in the artistic expression of military service members (SMs) with post-traumatic stress disorder (PTSD), traumatic brain injury and psychological health (PH) conditions with measurable psychiatric diagnoses. Affective symptoms and struggles related to verbally expressing information can limit communication in individuals with symptoms of PTSD and deployment-related health conditions. Visual self-expression through art therapy is an alternative way for SMs with PTSD and other PH conditions to communicate their lived experiences. This study offers the first systematic examination of the associations between visual self-expression and standardised clinical self-report measures. DESIGN:Observational study of correlations between clinical symptoms of post-traumatic stress, depression and anxiety and visual themes in mask imagery. SETTING:The National Intrepid Center of Excellence at the Walter Reed National Military Medical Center, Bethesda, Maryland, USA. PARTICIPANTS:Active-duty military SMs (n=370) with a history of traumatic brain injury, post-traumatic stress symptoms and related PH conditions. INTERVENTION:The masks used for analysis were created by the SMs during art therapy sessions in week 1 of a 4-week integrative treatment programme. PRIMARY OUTCOMES:Associations between scores on the PTSD Checklist-Military, Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale on visual themes in depictions of aspects of individual identity (psychological injury, military symbols, military identity and visual metaphors). RESULTS:Visual and clinical data comparisons indicate that SMs who depicted psychological injury had higher scores for post-traumatic stress and depression. The depiction of military unit identity, nature metaphors, sociocultural metaphors, and cultural and historical characters was associated with lower post-traumatic stress, depression and anxiety scores. Colour-related symbolism and fragmented military symbols were associated with higher anxiety, depression and post-traumatic stress scores. CONCLUSIONS:Emergent patterns of resilience and risk embedded in the use of images created by the participants could provide valuable information for patients, clinicians and caregivers.

Dataset Information

Blast traumatic brain injury and serum inflammatory cytokines: a repeated measures case-control study among U.S. military service members.

Publications

Blast traumatic brain injury and serum inflammatory cytokines: a repeated measures case-control study among U.S. military service members.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets