TBI Group Research Articles

Transcranial electrical stimulation in post-traumatic stress disorder and brain injury: possibilities of tuning neuronal networks

Transcranial direct current stimulation (tDCS) in the treatment of post-traumatic stress disorder (PTSD) is used to strengthen the inhibitory control of amygdala activity. However, there are still limited meta-analytic studies examining different tDCS protocols on core PTSD symptoms and the relationship between stimulation parameters and effect size. The objective is to investigate the effectiveness of such an intervention, which is a complex combination of a psychotherapy program with tDCS in the treatment of patients with PTSD and mild traumatic brain injury (mTBI) by assessing their level of functioning. 329 veterans (PTSD (n=109), mTBI (n=112), PTSD + mTBI (n=108) were examined using WHODAS 2.0. Standardized treatment was provided as well as psy­chotherapeutic intervention - a combination of psychoeducation with motivational interviewing and acceptance and commitment therapy for PTSD and tDCS. Clinical targets of therapy in the PTSD group were symptoms of intrusion, avoidance, hyperactivation and protocol of tDCS was dorsolateral prefrontal cortex arousing stimulation. In PTSD + TBI group clinical targets were neurocognitive symptoms, intrusion symptoms, avoidance, hyperactivation and tDCT protocol was motor cortex-supraorbital area inhibitory stimulation. The targest for TBI group was neurocognitive symptoms and tDCS protocol was occipital region exciting stimulation. The long-term effectiveness and the impact on neuroplasticity processes allow considering transcranial direct current stimulation as a promising method of neurorehabilitation of patients with a combination of posttraumatic stress disorder and mild traumatic brain injury.

Superior Survival After Unrelated Allogeneic Stem Cell Transplantation With Low-Dose ATG Compared to Low-Dose TBI in Myeloablative Fludarabine/Busulfan-Based Regimen for MDS on Behalf of the Adult MDS Working Group of the JSTCT

The fludarabine/intravenous busulfan 12.8 mg/kg (FB4) regimen is an effective conditioning regimen in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome (MDS); however, limited data is available on the prognostic impact of FB4 with low-dose anti-thymoglobulin (ATG ≤ 5 mg/kg) or low-dose total body irradiation (TBI ≤ 4 Gy). Therefore, we retrospectively evaluated the outcomes in 280 adults with de novo MDS who underwent their first transplantation from an unrelated donor between 2009 and 2018. Median age was 61 years (range, 16 to 70 years). In the FB4 alone (FB4), FB4 plus ATG (FB4-ATG), and FB4 plus TBI (FB4-TBI) groups, 3-years overall survival (OS) rates were 39.9%, 64.8%, and 43.7%; 3-years nonrelapse mortality (NRM) were 32.1%, 22.1%, and 27.1%; and 3-years relapse incidences were 34.7%, 21.2%, and 28.9%, respectively. The multivariate analyses showed that FB4-ATG group significantly correlated with better OS (hazard Ratio [HR], 0.51; 95% confidence interval [CI], 0.27 to 0.95; P = .032) than FB4 group. FB4-ATG group tended to correlate with lower NRM (HR, 0.36; 95% CI, 0.13 to 1.06; P = .063) than FB4 group. In comparison with FB4-TBI group, FB4-ATG group showed better OS (HR 0.52, 95% CI 0.27 to 0.99, P = .049) and NRM (HR 0.034, 95% CI 0.11 to 0.92, P = .034). No significant differences were observed in OS and NRM between the FB4-TBI and FB4 groups. The present study demonstrated that the FB4 plus low-dose ATG regimen improved OS and NRM, but FB4 plus low-dose TBI regimen had no clear benefit over FB4 alone, in MDS patients who used unrelated donors.

ASA-score is associated with 90-day mortality after complicated mild traumatic brain injury – a retrospective cohort study

PurposeThis study explores the association of the American Society of Anesthesiologists (ASA) score with 90-day mortality in complicated mild traumatic brain injury (mTBI) patients, and in trauma patients without a TBI.MethodsThis retrospective study was conducted using a cohort of trauma patients treated at a level III trauma center in Stockholm, Sweden from January to December 2019. The primary endpoint was 90-day mortality. The population was identified using the Swedish Trauma registry. The Trauma and Injury Severity Score (TRISS) was used to estimate the likelihood of survival. Trauma patients without TBI (NTBI) were used for comparison. Data analysis was conducted using R software, and statistical analysis included univariate and multivariate logistic regression.ResultsA total of 244 TBI patients and 579 NTBI patients were included, with a 90-day mortality of 8.2% (n = 20) and 5.4% (n = 21), respectively. Deceased patients in both cohorts were generally older, with greater comorbidities and higher injury severity. Complicated mTBI constituted 97.5% of the TBI group. Age and an ASA score of 3 or higher were independently associated with increased mortality risk in the TBI group, with odds ratios of 1.04 (95% 1.00–1.09) and 3.44 (95% CI 1.10–13.41), respectively. Among NTBI patients, only age remained a significant mortality predictor. TRISS demonstrated limited predictive utility across both cohorts, yet a significant discrepancy was observed between the outcome groups within the NTBI cohort.ConclusionThis retrospective cohort study highlights a significant association between ASA score and 90-day mortality in elderly patients with complicated mTBI, something that could not be observed in comparative NTBI cohort. These findings suggest the benefit of incorporating ASA score into prognostic models to enhance the accuracy of outcome prediction models in these populations, though further research is warranted.

Evaluating the therapeutic effect of LIPUS in the early stage of traumatic brain injury using FA and T2* in rats.

To evaluate the protective effect of LIPUS at the early stage of brain trauma in rats, 45 rats were randomly divided into 3 groups: sham (n = 15), TBI (n = 15) and LIPUS treatment groups (n = 15). Ipsilateral and contralateral cortical and thalamic parameters obtained by diffusion tensor imaging (DTI) and fast low-angle shot magnetic resonance imaging (FLASH-MRI) were measured at different times after trauma. For fractional anisotropy (FA) and T2* values, two-way repeated measures ANOVA with Tukey's post hoc was used for intergroup comparisons. With observation time prolonged, the FA values of the ipsilateral cortex in the TBI group gradually increased and were significantly higher than those in the LIPUS treatment group on Day 7 (adjusted P = 0.0067). FA values in the contralateral cortex decreased at this time and were significantly lower than those in the LIPUS treatment group (adjusted P = 0.0192). Meanwhile, compared with LIPUS group, FA values were significantly higher in the injured thalamus (adjusted P = 0.0025). Combined with correlation analysis, FA values were positively correlated with neuronal damage (P = 0.0148, r2 = 0.895). At 7 days after trauma, T2* values in the ipsilateral cortex of the TBI group were significantly lower. After analysis of ferritin content and correlation, we found that T2* values were negatively correlated with ferritin (P = 0.0259, r2 = -0.849). By measuring post-traumatic changes in FA and T2* values, it is possible to demonstrate a neuronal protective effect of LIPUS in the early phase of TBI rats and promote brain rehabilitation.

The 20-item dysexecutive questionnaire after severe traumatic brain injury: Distribution of the total score and its significance

ABSTRACT The Dysexecutive questionnaire (DEX), a 20-item ecological measure used by patients (DEX-S) or significant others (DEX-SO) to assess dysexecutive syndrome, often complements performance-based executive functions (EF) tests. Previous studies highlighted its internal consistency, score variability across samples, weak DEX-S correlations with EF tests, but strong associations with self-assessments of anxiety/depression. This study examined DEX-S and DEX-SO scores from the PariS-TBI study, analyzing data from 76 severe TBI participants and 40 proxies assessed 8-years postinjury compared to matched healthy controls. DEX scores in the control group followed a normal distribution, but severe TBI participants reported significantly higher percentages of very low DEX scores and significantly higher percentages of extremely high scores in both self-reports and proxy-reports. Strong correlations were found between DEX-S and self-reported anxiety/depression (rho = 0.65, p < 0.001). These findings suggest a possible lack of self-awareness in some TBI participants, a probable tendency of some TBI-proxies to underestimate EF difficulties, and the presence of EF difficulties in the TBI group compared to controls. The tendency among some TBI participants and proxies to respond to the DEX questions based on their positive or negative valence (presence of a “valence bias”), rather than specific content, potentially elucidates our results and prior published DEX findings. Trial registration ClinicalTrials.gov identifier: NCT01437683..

Post-discharge 6-Month Functional Recovery of Traumatic Brain Injury Survivors with Unfavorable Functional Status at Discharge: A Registry-Based Cohort Study

BackgroundTraumatic Brain Injury (TBI) is a major cause of physical disabilities worldwide. Herein, we aimed to investigate the factors contributing to post-discharge recovery in patients who were discharged with an unfavorable outcome. MethodsWe collected data on the characteristics of patients, with a focus on those who survived TBI but had an unfavorable outcome at discharge as measured by Glasgow Outcome Scale Extended; GOSE categories two, three, and four. Post-discharge recovery was defined as achieving a favorable functional status at six months (GOSE of five or more) with a minimum two-point increase in GOSE. ResultsOf 4011 TBI patients in our registry, 797 had an unfavorable discharge functional status. In severe TBI, 51% achieved recovery, while in mild to moderate TBI, 57% achieved recovery after six months. Older patients and those with shorter intensive care unit length of stay were more likely to experience post-discharge recovery in both mild to moderate and severe TBI groups. The presence of base of skull fracture was also associated with post-discharge recovery in severe TBI patients. Lastly, we showed that, after adjustment for potential confounders, GOSE at discharge is associated with post-discharge recovery in both mild to moderate and severe TBI patients. ConclusionThis study found that the majority of the patients who were discharged with an unfavorable functional status were able to achieve a favorable outcome within six months. The novel post-discharge recovery in TBI patients might be a useful toll for illuminating the factors associated with a significant improvement after discharge.

Cerebral Gray Matter May Not Explain Sleep Slow-Wave Characteristics after Severe Brain Injury.

Sleep slow waves are the hallmark of deeper non-rapid eye movement sleep. It is generally assumed that gray matter properties predict slow-wave density, morphology, and spectral power in healthy adults. Here, we tested the association between gray matter volume (GMV) and slow-wave characteristics in 27 patients with moderate-to-severe traumatic brain injury (TBI, 32.0 ± 12.2 years old, eight women) and compared that with 32 healthy controls (29.2 ± 11.5 years old, nine women). Participants underwent overnight polysomnography and cerebral MRI with a 3 Tesla scanner. A whole-brain voxel-wise analysis was performed to compare GMV between groups. Slow-wave density, morphology, and spectral power (0.4-6 Hz) were computed, and GMV was extracted from the thalamus, cingulate, insula, precuneus, and orbitofrontal cortex to test the relationship between slow waves and gray matter in regions implicated in the generation and/or propagation of slow waves. Compared with controls, TBI patients had significantly lower frontal and temporal GMV and exhibited a subtle decrease in slow-wave frequency. Moreover, higher GMV in the orbitofrontal cortex, insula, cingulate cortex, and precuneus was associated with higher slow-wave frequency and slope, but only in healthy controls. Higher orbitofrontal GMV was also associated with higher slow-wave density in healthy participants. While we observed the expected associations between GMV and slow-wave characteristics in healthy controls, no such associations were observed in the TBI group despite lower GMV. This finding challenges the presumed role of GMV in slow-wave generation and morphology.

Serum metabolism alteration behind different etiology, diagnosis, and prognosis of disorders of consciousness

BackgroundPatients with disorders of consciousness (DoC) exhibit varied revival outcomes based on different etiologies and diagnoses, the mechanisms of which remain largely unknown. The fluctuating clinical presentations in DoC pose challenges in accurately assessing consciousness levels and prognoses, often leading to misdiagnoses. There is an urgent need for a deeper understanding of the physiological changes in DoC and the development of objective diagnostic and prognostic biomarkers to improve treatment guidance.MethodsTo explore biomarkers and understand the biological processes, we conducted a comprehensive untargeted metabolomic analysis on serum samples from 48 patients with DoC. Patients were categorized based on etiology (TBI vs. non-TBI), CRS-R scores, and prognosis. Advanced analytical techniques, including PCA and OPLS-DA models, were employed to identify differential metabolites.ResultsOur analysis revealed a distinct separation in metabolomic profiles among the different groups. The primary differential metabolites distinguishing patients with varying etiologies were predominantly phospholipids, with a notable decrease in glycerophospholipids observed in the TBI group. Patients with higher CRS-R scores exhibited a pattern of impaired carbohydrate metabolism coupled with enhanced lipid metabolism. Notably, serum concentrations of both LysoPE and PE were reduced in patients with improved outcomes, suggesting their potential as prognostic biomarkers.ConclusionsOur study underscores the critical role of phospholipid metabolism in the brain’s metabolic alterations in patients with DoC. It identifies key biomarkers for diagnosis and prognosis, offering insights that could lead to novel therapeutic targets. These findings highlight the value of metabolomic profiling in understanding and potentially treating DoC.

Mental and Physical Health Comorbidities in Traumatic Brain Injury: A Non-TBI Controls Comparison

ObjectiveTo examine whether aging with a TBI was associated with a greater burden of health-related comorbidities compared with a non-TBI control cohort and examine the associations between comorbidity burden, emotional outcomes, and health-related quality of life (HRQoL) after TBI across ages. DesignCross-sectional. SettingResearch center or telephone. ParticipantsThe study included 559 participants (NTBI=291, NControls=268). Participants with TBI were recruited during inpatient rehabilitation and had sustained a moderate-severe TBI 1-33 years previously. Non-TBI controls were a convenience sample recruited through advertisements in the community. InterventionsNot applicable. Main Outcome MeasuresThe number of cardiovascular, general physical health, and mental health comorbidities was compared between cohorts and age strata using Poisson regression. The relationships between comorbidities, age, emotional outcomes (Generalized Anxiety Disorder Scale-7, Patient Health Questionnaire-9), and HRQoL (PROMIS Global Health Measure) were examined with linear regression. Distinct subgroups of comorbidities were identified using latent class analysis. Associations between comorbidity classes with demographic and outcome variables were evaluated using multinomial logistic and linear regressions, respectively. ResultsTBI participants had a significantly higher comorbidity burden than controls, primarily driven by elevated rates of mental health disorders (RR=2.71, 95% confidence interval [1.37, 5.35]). Cardiovascular and physical health comorbidities were not elevated in the TBI group compared with controls. Both cohorts had 3 similar comorbidity subgroups, suggesting consistent patterns of co-occurring health conditions regardless of TBI exposure. Physical and mental health comorbidities were associated with elevated depression and anxiety symptoms and diminished HRQoL after TBI compared with controls. ConclusionTBI was associated with greater mental, but not physical, health comorbidities in the decades after injury. However, physical and mental health comorbidities significantly affected emotional and HRQoL status after TBI, underscoring a greater need for long-term support for individuals with TBI coping with both physical and mental health comorbidities.

Ghrelin ameliorates neuronal damage, oxidative stress, inflammatory parameters, and GFAP expression in traumatic brain injury

ABSTRACT Objective This study investigated the effects of ghrelin on oxidative stress, working memory, inflammatory parameters, and neuron degeneration. Methods TBI was produced with the weight-drop technique. Rats in the G+TBI and TBI+G groups received ghrelin for 7 or 2 days, respectively. The control group received saline. On the 8th day of the study, the brain and blood tissue were taken under anesthesia. Results A significant increase in brain GSH-PX, MDA, IL-1β, TGF-β1, and IL-8 levels and a significant decrease in CAT levels were found in the TBI group compared to the control. Serum MDA, GSH, IL-1β, and IL-8 levels were increased with TBI. Ghrelin treatment after TBI significantly increased the serum GSH, CAT, GSH-PX, and brain GSH and CAT levels, while it significantly decreased the serum MDA, IL-1β, and brain MDA, TGF-β1, and IL-8 levels. Histological evaluations revealed that ghrelin treatment led to a reduction in inflammation, while also significantly ameliorating TBI-induced neuron damage and vascular injuries. Immunohistochemistry staining showed that GFAP staining intensity was significantly increased in the cortex and hippocampus in TBI, and GFAP immunoreactivity was decreased with ghrelin treatment. Conclusion The results from this study suggested that ghrelin may have curative effects on TBI.

Rosiglitazone regulates astrocyte polarization and neuroinflammation in a PPAR-γ dependent manner after experimental traumatic brain injury

BackgroundTraumatic brain injury (TBI) is a leading cause of high mortality and disability worldwide. Overactivation of astrocytes and overexpression of inflammatory responses in the injured brain are characteristic pathological features of TBI. Rosiglitazone (ROS) is a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist known for its anti-inflammatory activity. However, the relationship between the inflammatory response involved in ROS treatment and astrocyte A1 polarization remains unclear. ObjectiveThis study aimed to investigate whether ROS treatment improves dysfunction and astrocyte A1 polarization induced after TBI and to elucidate the underlying mechanisms of these functions. MethodsSD rats were randomly divided into sham operation group, TBI group, TBI+ROS group, and TBI+ PPAR-γ antagonist group (GW9662 + TBI). The rat TBI injury model was prepared by the CCI method; brain water content test and wire grip test scores suggested the prognosis; FJB staining showed the changes of ROS on the morphology and number of neurons in the peripheral area of cortical injury; ELISA, immunofluorescence staining, and western blotting analysis revealed the effects of ROS on inflammatory response and astrocyte activation with the degree of A1 polarization after TBI. ResultsBrain water content, inflammatory factor expression, and astrocyte activation in the TBI group were higher than those in the sham-operated group (P < 0.05); compared with the TBI group, the expression of the above indexes in the ROS group was significantly lower (P < 0.05). Compared with the TBI group, PPAR-γ content was significantly higher and C3 content was considerably lower in the ROS group (P < 0.05); compared with the TBI group, PPAR-γ content was significantly lower and C3 content was substantially higher in the inhibitor group (P < 0.05). ConclusionROS can exert neuroprotective effects by inhibiting astrocyte A1 polarization through the PPAR-γ pathway based on the reduction of inflammatory factors and astrocyte activation in the brain after TBI.

The paradigm of total body irradiation in acute lymphoblastic leukaemia: Therapeutic effectiveness versus the challenges of toxicity

IntroductionTotal body irradiation (TBI) is part of the myeloablative conditioning for hematopoietic stem cell transplantation (HSCT) in malignant hematologic disorders. This therapy has recently shown improved survival in acute lymphoblastic leukemia (ALL) compared to chemotherapy-based regimens. However, side effects are a significant limitation, especially in the pediatric population. Patients and methodsWe retrospectively analyzed the survival of patients with ALL who underwent an HSCT at a tertiary hospital between 1996 and 2009 (N = 69 HSCT in 57 patients). We differentiated a cohort that received TBI (N = 44) from another that did not (N = 25). Subsequently, we interviewed the survivors from the TBI group with a minimum of 10 years of follow-up (N = 18), asking about the presence of side effects. ResultsThe overall survival (OS) at 2 and 5 years was 79.1% and 65.2% respectively for the TBI group and 66.2% and 55.8% for the non-TBI group, although this difference was not significant (P=.31). The event-free survival (EFS) at 2 and 5 years was 77.3% and 63.6% respectively for the TBI group and 56% and 32% for the non-TBI group (P=.02). The probability of relapse (PR) at 2 years for those who received TBI was 10% compared to 28.6% for those who did not receive TBI (P=.005). Survivors who received TBI developed secondary neoplasms (39%), dyslipidemia (67%), cognitive impairments affecting memory (44%), recurrent respiratory infections (39%), thyroid abnormalities (45%), premature ovarian failure (89%), cataracts (22%), and psychological problems (44%). However, the quality of life, as self-assessed by the patients, was considered good for 83% of the participants.. ConclusionsPatients who received TBI had significantly higher EFS and lower PR. However, adverse effects are frequent and significant, although they do not subjectively affect quality of life.

Traumatic brain injury is common and undertreated in the orthopaedic trauma population

IntroductionTraumatic brain injuries (TBIs) can be difficult to diagnose and are often marginalized when compared to more obvious physical injuries. Despite this, recognition and early treatment can lead to improved outcomes. Even mild TBIs have the potential to cause significant long-term consequences for patients, which may affect their physical recovery from orthopaedic injuries. The objective of this study was to examine the incidence and treatment of TBI within the orthopaedic trauma population. MethodsInclusion criteria were all patients presenting after an acute trauma with an orthopaedic surgery consult over a continuous 3 month timeframe (n = 187). A retrospective review was completed at an academic tertiary referral trauma center. The primary outcome was the rate of TBI. Secondary outcomes included rate of TBI listed as a discharge diagnosis and rate of follow up plan. Several secondary variables were noted and their associations with TBI evaluated. Results27 % of the 187 patients had an acute TBI. 61 % of TBI patients had the diagnosis listed in their discharge summary. 6 % had a follow up plan. The positive TBI group was associated with more high energy injuries (p = 0.032), average limbs involved (p = 0.007), upper extremity injury (p < 0.001), bilateral lower extremity injury (p = 0.004), and Injury Severity Score (p < 0.001). 82 % of patients with an acute TBI had an occupational therapy consult and 39 % had a neurosurgery consult. 24 % of patients with a TBI were admitted to the orthopaedic primary service. ConclusionsPatients presenting after an acute trauma with orthopaedic injuries have high rates of TBI, but low rates of diagnosis and treatment. This lack of diagnosis and treatment can negatively impact recovery from orthopaedic injuries. Orthopaedic providers should be aware of the diagnostic criteria and initial treatment steps for TBI to ensure prompt and effective treatment, which has been shown to improve outcomes.

Incidence, and factors associated with moderate/severe pediatric traumatic brain injury in children aged 5–15 years in western, Mexico

ObjectiveThe study objectives were to estimate the standardized incidence and evaluate factors associated with moderate/severe pediatric traumatic brain injury (p-TBI) in children aged 5–15 years in Western, Mexico. MethodsThe study was cross-sectional in design. We estimated the standardized incidence of moderate/severe p-TBI using the direct methods of the World Health Organization (WHO) standard populations. We utilized the Glasgow Coma Scale (GCS) to identify moderate/severe p-TBI patients (GCS ≤ 13). Logistic regression analysis was applied to evaluate variables associated with moderate/severe p-TBI. ResultsThe standardized incidence of patients diagnosed with moderate/severe p-TBI was 31.0/100,000 person-years (95 % CI 28.7–33.4). According to age, the moderate/severe TBI group was included. A total of 254 (38.5 %) patients were aged 5–9 years, 343 (52.0 %) were aged 10–14 years, and 62 (9.5 %) were aged 15 years. Factors associated with moderate/severe TBI in the crude analysis were male sex (OR 5.50, 95 % CI 4.16–7.39, p < 0.001), primary school (OR 2.15, 95 % CI 1.62–2.84, p < 0.001), and falls (OR 1.34, 95 % CI 1.02–1.77, p = 0.035). Factors associated with moderate/severe p-TBI in the adjusted analysis were male sex (OR 6.12, 95 % CI 4.53–8.29, p < 0.001), primary school (OR 3.25, 95 % CI 2.31–4.55, p < 0.001), and falls (OR 1.78, 95 % CI 1.28–2.47, p < 0.001). ConclusionThe incidence of moderate/severe p-TBI in children aged 5–15 years in western Mexico in this study was higher than that in other studies. One of the biggest factors associated with moderate/severe p-TBI was male sex, specifically those with lower education levels and those who were prone to falls.

Concomitant severe traumatic brain injury is not associated with increased red blood cell transfusion volumes in patients with pelvic fractures: A retrospective observational study

IntroductionTraumatic brain injury (TBI)-associated coagulopathy significantly influences survival outcomes in patients with multiple injuries. Severe TBI can potentially affect systemic hemostasis due to coagulopathy; however, there is limited evidence regarding whether the risk of hemorrhage increases in patients with pelvic fractures complicated with TBI. Therefore, through multivariable analysis, we aimed to examine the association between severe TBI and increased blood transfusion requirements in patients with pelvic fractures. Materials and methodsThis retrospective observational study was conducted at a tertiary care facility in Japan. Patients aged 16 years or older with pelvic fractures who were admitted to our intensive care unit between April 2014 and December 2021 were included in the analysis. The patients were categorized into no to mild and severe TBI groups according to whether the Head Abbreviated Injury Scale (AIS) score was 3 or higher. The primary outcome was the number of red blood cell (RBC) units transfused within 24 h after arrival at the hospital. The primary outcome was analyzed using univariable and multivariable linear regression analyses. The covariates used for the multivariable linear regression analysis were age, sex, antithrombotic therapy, mechanism of injury, Pelvic AIS score, and extravasation on contrast-enhanced computed tomography on admission. ResultsWe identified 315 eligible patients (221 and 94 in the no to mild and severe TBI groups, respectively). In the univariable analysis, the RBC transfusion volume within 24 h after arrival was significantly higher in the severe TBI group than in the no to mild TBI group (2.53-unit increase; 95 % confidence interval [CI]: 0.46–4.61). However, in the multivariable analysis, no statistically significant association was detected between severe TBI and the RBC transfusion volume within 24 h after arrival at the hospital (0.87-unit increase; 95 % CI: −1.11–2.85). ConclusionsConcomitant severe TBI was not associated with increased RBC transfusion volumes in patients with pelvic fractures on multivariable analysis.

Amyloid‐β and tau accumulation in traumatic brain injury: A study of Vietnam war veterans

AbstractBackgroundTraumatic brain injury (TBI) is widely viewed as a risk factor for dementia. Since amyloid‐β and tau pathology have been reported in up to a third of individuals with TBI – even after a single TBI event – their accumulation could be a potential mechanism underlying this association. The aim of this study was to examine the relationship between TBI and amyloid‐β and tau pathology more closely and to assess whether the association between amyloid‐β and tau is influenced by TBI status.MethodA total of 102 Vietnam war veterans (79% normal cognition, 21% mild cognitive impairment; 23% amyloid‐β positive) were included from the Alzheimer’s Disease Neuroimaging Initiative Department Of Defense study. Among these individuals, 65 had a history of TBI (42 mild and 23 moderate/severe TBI) whereas 37 did not. Amyloid‐PET ([18F]florbetapir) and tau‐PET ([18F]flortaucipir) SUVRs were assessed within regions from the Schaefer atlas. For both amyloid‐PET and tau‐PET ROI‐wise and global TBI group differences were determined by ANCOVAs. Moderating effects of TBI status on the association between ROI‐wise amyloid‐PET and tau‐PET SUVRs were tested using linear regression. Analyses were adjusted for age, sex, education, clinical diagnosis, and, where applicable, global amyloid‐PET and time lag between amyloid‐ and tau‐PET scans.ResultTBI groups did not show significant increases in amyloid‐ or tau‐PET uptake compared to no‐TBI groups, neither globally nor on the ROI‐level (i.e. all p&gt;0.05 after correcting for multiple comparisons, Fig. 1). However, we found that a history of (particularly moderate/severe) TBI was associated with a weaker relationship between amyloid‐PET and tau‐PET uptake in temporal and parietal brain regions compared to no history of TBI (Fig. 2). This effect seemed to be driven by the amyloid‐β positive group. TBI groups did not differ regarding age and APOE‐status.ConclusionWhile amyloid‐β is known to promote tau spreading in Alzheimer’s disease (AD), our results indicate that in TBI there might be a detachment of amyloid‐β and tau pathology in AD‐susceptible temporo‐parietal brain regions. This finding is supportive of the view that TBI could lead to distinct changes in the interplay of pathological proteins, potentially underlying the link between TBI and dementia.

Chronic kidney disease as a predictive factor for poor prognosis in traumatic brain injury among older adults: a case-control study

ObjectiveTraumatic brain injury (TBI) is a highly prevalent neurological disorder that affects a gradually increasing proportion of older adults. Chronic kidney disease (CKD) significantly contributes to global years of life lost, with an estimated one-tenth of the global population affected by CKD. However, it remains unclear whether CKD impacts TBI prognosis. We conducted a case-control study to investigate the clinical outcomes of TBI patients with or without CKD comorbidity and identified the risk factors associated with a poor prognosis.MethodsFrom January 2017 through April 2023, 11 patients with TBI and CKD were included, and 27 control TBI cases with normal kidney function were matched by age, gender, and admission Glasgow Coma Scale (GCS) score as the control group.ResultsThe CKD TBI group had a significantly lower GCS score upon discharge (7.1 ± 5.9) compared to the non-CKD TBI group (13.1 ± 2.6) (p &amp;lt; 0.01). ICU stay time and hospitalization expenses were higher in the CKD group than the non-CKD group, though there were no statistical differences. Additionally, patients in the CKD TBI group had a higher frequency of hospital-acquired infections (54.4%) compared with those in the non-CKD TBI group (7.4%) (p &amp;lt; 0.01). The two groups exhibited no differences in hemoglobin levels, albumin levels, or coagulation function. Logistic regression analysis showed that advanced age, low admission GCS score, elevated blood urea, and creatinine levels were associated with a poor neurological prognosis.ConclusionTBI patients comorbid with CKD have a poorer prognosis than those with normal kidney function.

Effect of Nrf2 on brain injury induced by hydraulic shock via regulation of mitophagy and apoptosis.

The specific protective mechanism of mitophagy and Nrf2 in brain injury has not been fully clarified. This study aimed to reveal the effect of Nrf2 on hydraulic shock brain injury in mice, and explore its possible mechanism. Twenty-four Nrf2 knockout (Nrf2-/-) and wild-type mice (WT) of C57BL/6J were randomly divided into two groups: control group (C) and brain injury group (TBI). Hematoxylin-eosin staining (HE) assay was used for the histomorphological observation. The apoptotic state of brain tissue was detected by TUNEL. Mechanical damage in vitro models of glial cells were prepared. The wild-type (WT) and Nrf2 knockout (KO) mice were constructed to investigate the changes of mitophagy and apoptosis-related indicators by Western blotting. The experimental results showed that 24 h after TBI, the tissue structure was highly porous, the cells were highly edema, the neuronal space increased significantly, the neuron degeneration, and the cell vacuolation was obvious. Meanwhile, the number of apoptotic cells and the apoptosis rate of glial cells increased significantly. After injury, the relative expression of Parkin, Pink, Beclin and LC-3II proteins were significantly decreased in all mice. The protein expressions of Caspase3 and Caspase12 were significantly increased. However, in the TBI group, KO mice were more impaired than WT mice. In conclusion, Nrf2 plays a protective role by promoting mitophagy to inhibit apoptosis in the process of brain injury caused by hydraulic shock in mice, which provides a new idea for the effective treatment of brain injury.

White Matter Organization and Cortical Thickness Differ Among Active Duty Service Members With Chronic Mild, Moderate, and Severe Traumatic Brain Injury.

Abstract This study compared findings from whole-brain diffusion tensor imaging (DTI) and volumetric magnetic resonance imaging (MRI) among 90 Active Duty Service Members with chronic mild traumatic brain injury (TBI; n = 52), chronic moderate-to-severe TBI (n = 17), and TBI-negative controls (n = 21). Data were collected on a Philips Ingenia 3T MRI with DTI in 32 directions. Results demonstrated that history of TBI was associated with differences in white matter microstructure, white matter volume, and cortical thickness in both mild TBI and moderate-to-severe TBI groups relative to controls. However, the presence, pattern, and distribution of these findings varied substantially depending on the injury severity. Spatially-defined forms of DTI fractional anisotropy (FA) analyses identified altered white matter organization within the chronic moderate-to-severe TBI group, but they did not provide clear evidence of abnormalities within the chronic mild TBI group. In contrast, DTI FA "pothole" analyses identified widely distributed areas of decreased FA throughout the white matter in both the chronic mild TBI and chronic moderate-to-severe TBI groups. Additionally, decreased white matter volume was found in several brain regions for the chronic moderate-to-severe TBI group compared with the other groups. Greater number of DTI FA potholes and reduced cortical thickness were also related to greater severity of self-reported symptoms. In sum, this study expands upon a growing body of literature using advanced imaging techniques to identify potential effects of brain injury in military Service Members. These findings may differ from work in other TBI populations due to varying mechanisms and frequency of injury, as well as a potentially higher level of functioning in the current sample related to the ability to maintain continued Active Duty status after injury. In conclusion, this study provides DTI and volumetric MRI findings across the spectrum of TBI severity. These results provide support for the use of DTI and volumetric MRI to identify differences in white matter microstructure and volume related to TBI. In particular, DTI FA pothole analysis may provide greater sensitivity for detecting subtle forms of white matter injury than conventional DTI FA analyses.

Blast Clearance after High Dose-Melphalan Conditioning for Allogeneic Stem Cell Transplantation in Relapsed and Refractory Acute Myeloid Leukemia

Introduction: For patients (pts) with relapsed or refractory acute myeloid leukemia (r/r AML) allogeneic stem cell transplantation (ASCT) has become an established highly effective and potential curative treatment option. Even for pts with active disease, direct ASCT using sequential conditioning regimens has shown promising outcomes. In this retrospective study, we examined prognostic factors for long-term survival in r/r AML pts with active disease with special focus to the prognostic value of blast clearance during condition therapy. Patients and Methods: 186 r/r AML pts treated with sequential conditioning regimens at our center between 2014-2023 were included in our analysis. Patients underwent high-dose melphalan (100 - 140 mg/m 2, day -11 prior ASCT) followed by either fractionated total body irradiation with 8 Gy (TBI, n = 71) or non-TBI regimens (busulfan, n = 101, or treosulfan, n = 14) in combination with fludarabin (120 - 150 mg/m 2) from day -6 before ASCT. TBI-based conditioning was applied almost exclusively in patients aged &amp;lt; 60 years. Graft versus host-disease (GvHD) prophylaxis consisted of calcineurin inhibitors, mycophenolate and anti-T-lymphocyte globulin. In 180 out of 186 patients, blast clearance was assessed by cytologic and flow cytometric blast count via bone marrow (BM) aspirate in median 5 days after Melphalan and prior to continuation of the sequential conditioning therapy. Blast clearance was defined as cytologic BM blast count &amp;lt; 5% and &amp;lt; 0.1% BM cells with leukemia-associated immunophenotype in flow cytometry. Results: Median pts age was 67 years (range 45 - 76 years) in the non-TBI group and 51 years (range 19 - 71 years) in the TBI group, respectively. Median follow up of surviving patients was 46 months. As expected, comorbidities and disease-specific factors varied between these groups. HCTCI scores &amp;gt; 3 points were observed in 14% of TBI pts compared to 32% in non-TBI pts ( p .01) and 45% versus 54% harbored adverse risk genetics according to European Leukemia Net (ELN) 2017 classification ( p .41), respectively. In the non-TBI group, 38% of the pts had a secondary or therapy-related AML compared to 20% of pts in the TBI group ( p .03). HLA-mismatched (&amp;lt;10/10 matched) donor grafts were transplanted in 21% (TBI) vs. 20% (non-TBI) of the pts. 185 of 188 pts received GCS-F mobilized stem cell grafts; 3 pts received a bone marrow graft. Kaplan-Meier estimates for overall survival (OS) with and without blast clearance at 2 years were 69.6% (95% CI 60.1-80.6%) vs. 58% (95% CI 48.8-69.1%, p .33), for event free survival (EFS, event defined as death or overt relapse) 58.9% (95% CI 49-70.8%) vs. 46.1% (95% CI 36.7-58.1%, p .2), respectively. We included the re-occurrence / persistence of defined molecular and cytogenetic markers or decreasing CD34 + bone marrow chimerism (&amp;lt; 95%) after transplant as measures for impending relapse as a modified EFS. The EFS including impending relapse was 49.8% (95% CI 40-62%) vs. 36.4% (27.7-47.8%) after 2 years. A non-significant trend with reduced relapse risk for those patients who achieved blast clearance after Melphalan ( p .1, HR 0.73) was observed. Most patients with impending relapse showed similar survival as patients without evidence of relapse after ASCT. In multivariate cox regression, age, HCTCI scores &amp;gt; 3 points, adverse risk according to ELN 2017 definitions and donor mismatch &amp;lt; 10/10 resulted in adverse prognosis. Especially, patients with mismatched donors displayed highly significant inferior outcomes. Both leukemic burden prior to ASCT as well as blast clearance after melphalan showed no significant correlation with clinical outcome parameters. Conclusion: Sequential conditioning regimens followed by ASCT offer long-term survival for more than 50% of pts with active relapsed or refractory AML. Patients who did not achieve complete blast clearance during conditioning therapy showed a trend towards higher relapse risk after ASCT which did not result in inferior survival. This underscores the importance of close monitoring and early interventions such as accelerated immunosuppression tapering, preemptive donor lymphocyte infusions and targeted therapies in case of impending relapse after ASCT.