Early Postinjury Period Research Articles

Distant neuroinflammation acutely induced by focal brain injury and its control by endocannabinoid system

IntroductionWe studied spatiotemporal features of acute transcriptional inflammatory response induced by a focal brain injury in distant uninjured neuronal tissue and a role of endocannabinoid (eCB) system in its control. Materials and methodsA focal excitotoxic lesion was induced by a unilateral injection of kainate in the dorsal hippocampus of awake Wistar rats. During acute post-injury period (3 h and 24 h post-injection), mRNA levels of genes associated with neuroinflammation (Il1b, Il6, Tnf, Ccl2; Cx3cl1, Zc3 h12a, Tgfb1) and eCB receptors of CB1 and CB2 types (Cnr1 and Cnr2) in intact regions of the hippocampus and neocortex were measured using qPCR. Occurrence of acute symptomatic seizures was controlled electrographically. To modulate eCB signaling during injury and acute post-injury period, antagonists (AM251, AM630) and agonist (WIN55–212-2) of eCB receptors were administered before the injury induction. ResultsLocal intrahippocampal injury triggered widespread time- and region-dependent neuroinflammation in undamaged brain regions remote from the lesion site. The distant areas of the hippocampus and hippocampal meninges exhibited early (3 h) transient upregulation of pro- and anti-inflammatory cytokines simultaneously with occurrence of acute symptomatic seizures. The neocortex and its meninges showed minor neuroinflammation early after injury (3 h) but later (24 h) significantly upregulated several genes, mainly with anti-inflammatory properties. Focal lesion also changed expression of eCB receptors in the distant extra-lesional regions – CB1 receptors at 3 h and both CB1 and CB2 receptors at 24 h. Within the hippocampus, significant regional differences in constitutive and post-injury expression CB1 receptors were found. Pharmacological blockade of eCB receptors during injury and early post-injury period lengthened hippocampal neuroinflammation and reversed upregulation of anti-inflammatory molecules in the neocortex. ConclusionThe findings show that focal brain injury rapidly triggers widespread parenchymal and extraparenchymal neuroinflammation. The early injury-induced response is likely to represent neurogenic neuroinflammation produced by network hyperexcitability (acute symptomatic seizures). Activation of eCB signaling during acute phase of the brain injury is important for initiation of adaptive anti-inflammatory processes and prevention of chronic pathologic neuroinflammation in distant uninjured structures. However, the beneficial role of injury-induced eCB activity appears to depend on many factors including time, brain region, eCB tone etc.

Chronic Adaptations in the Dorsal Horn Following a Cervical Spinal Cord Injury in Primates.

Spinal cord injury (SCI) is devastating, with limited treatment options and variable outcomes. Most in vivo SCI research has focused on the acute and early post-injury periods, and the promotion of axonal growth, so little is understood about the clinically stable chronic state, axonal growth over time, and what plasticity endures. Here, we followed animals into the chronic phase following SCI, to address this gap. Male macaques received targeted deafferentation, affecting three digits of one hand, and were divided into short (4-6 months) or long-term (11-12 months) groups, based on post-injury survival times. Monkeys were assessed behaviorally, where possible, and all exhibited an initial post-injury deficit in manual dexterity, with gradual functional recovery over 2 months. We previously reported extensive sprouting of somatosensory corticospinal (S1 CST) fibers in the dorsal horn in the first five post-injury months. Here, we show that by 1 year, the S1 CST sprouting is pruned, with the terminal territory resembling control animals. This was reflected in the number of putatively "functional" synapses observed, which increased over the first 4-5 months, and then returned to baseline by 1 year. Microglia density also increased in the affected dorsal horn at 4-6 months and then decreased, but did not return to baseline by 1 year, suggesting refinement continues beyond this time. Overall, there is a long period of reorganization and consolidation of adaptive circuitry in the dorsal horn, extending well beyond the initial behavioral recovery. This provides a potential window to target therapeutic opportunities during the chronic phase.

Structural and functional assessment of the condition of wound bed using microwave dielectrometry and laser doppler flowmetry

The aim of the work was to develop and test a combined method for assessing the structural and functional features of the burn wound and periwound area with the use of microwave dielectrometry and Dopplerometry. The study was performed on twenty Wistar rats, thermal injuries from contact were created on each rat, and ten healthy animals. The assessment of the wound condition was performed 24 and 72 hours after burn injury. The study of the dielectric properties of tissues was carried out using a hardware and software complex for near-field resonant microwave sensing. From the results of our studies, it can be concluded that in the early post-injury period (within the first days), a sharp coordinated decrease in the intensity of microcirculation and dielectric permittivity is observed in the wound tissues, gradually and partially restored by the end of the third day after burning. The increased microcirculatory blood flow to the periwound area, leading to an increase in the degree of tissue hydration was observed, and as a consequence, the values of these two indices became higher. In addition, it has been shown that during thermal trauma, a regulatory imbalance of factors providing capillary blood flow around a burn wound area and surrounding tissues is formed, which is compensatory in nature and, in the absence of adequate correction, contributes to the inhibition of regeneration processes. Thus, the combination of the methods used in this study may potentially provide more specific information for a description of the structural and functional features of the analyzed tissue and their dynamics. This is clearly shown by the example of an experimental burn wound.

KCC2 downregulation after sciatic nerve injury enhances motor function recovery

Injury to mature neurons induces downregulated KCC2 expression and activity, resulting in elevated intracellular [Cl−] and depolarized GABAergic signaling. This phenotype mirrors immature neurons wherein GABA-evoked depolarizations facilitate neuronal circuit maturation. Thus, injury-induced KCC2 downregulation is broadly speculated to similarly facilitate neuronal circuit repair. We test this hypothesis in spinal cord motoneurons injured by sciatic nerve crush, using transgenic (CaMKII-KCC2) mice wherein conditional CaMKIIα promoter-KCC2 expression coupling selectively prevents injury-induced KCC2 downregulation. We demonstrate, via an accelerating rotarod assay, impaired motor function recovery in CaMKII-KCC2 mice relative to wild-type mice. Across both cohorts, we observe similar motoneuron survival and re-innervation rates, but differing post-injury reorganization patterns of synaptic input to motoneuron somas—for wild-type, both VGLUT1-positive (excitatory) and GAD67-positive (inhibitory) terminal counts decrease; for CaMKII-KCC2, only VGLUT1-positive terminal counts decrease. Finally, we recapitulate the impaired motor function recovery of CaMKII-KCC2 mice in wild-type mice by administering local spinal cord injections of bicuculline (GABAA receptor blockade) or bumetanide (lowers intracellular [Cl−] by NKCC1 blockade) during the early post-injury period. Thus, our results provide direct evidence that injury-induced KCC2 downregulation enhances motor function recovery and suggest an underlying mechanism of depolarizing GABAergic signaling driving adaptive reconfiguration of presynaptic GABAergic input.

Immune system disorders in the early post-injury period in patients after severe brain injury from the perspective of the severity of the injury.

Brain injuries are the most common cause of death in productive age. Besides the extent of the injury, other systemic factors can also affect the outcome. Patients suffering from severe brain injury often experience extracranial inflammatory complications during the early period of treatment. Here, we investigate the changes in immunity in patients with brain injury. 121 patients and 92 healthy controls were included in the research. Blood samples were collected on admission and analyzed by flow cytometry and biochemical methods. Multiple clusters of differentiation (CD) and antibody levels were investigated. The results were compared between patients and controls. In addition, results of two classes of severity (Glasgow Coma Scale, GCS, of 3-5 vs. 6-8) were also compared. Parameters of humoral immunity in patients immediately after admission were significantly lower than those from healthy donors, with the exception of IgE elevated as much as to resemble allergic reaction (p < 0.01). Of cellular parameters, only natural killer (NK) cluster CD56 + was elevated (p < 0.01). Extracranial infectious complications were more common in patients with GCS 3-5. Strong immune system disorders were observed in patients after severe brain injury, which may contribute to the worse outcome in such patients.

Functional Neuroimaging as an Assessment Tool in Critically Ill Patients.

Little is known about residual cognitive function in the earliest stages of serious brain injury. Functional neuroimaging has yielded valuable diagnostic and prognostic information in chronic disorders of consciousness, such as the vegetative state (also termed unresponsive wakefulness syndrome). The objective of the current study was to determine if functional neuroimaging could be efficacious in the assessment of cognitive function in acute disorders of consciousness, such as coma, where decisions about the withdrawal of life-sustaining therapies are often made. A hierarchical functional magnetic resonance imaging (fMRI) approach assessed sound perception, speech perception, language comprehension, and covert command following in 17 critically ill patients admitted to the intensive care unit (ICU). Preserved auditory function was observed in 15 patients (88%), whereas 5 (29%) also had preserved higher-order language comprehension. Notably, one patient could willfully modulate his brain activity when instructed to do so, suggesting a level of covert conscious awareness that was entirely inconsistent with his clinical diagnosis at the time of the scan. Across patients, a positive relationship was also observed between fMRI responsivity and the level of functional recovery, such that patients with the greatest functional recovery had neural responses most similar to those observed in healthy control participants. These results suggest that fMRI may provide important diagnostic and prognostic information beyond standard clinical assessment in acutely unresponsive patients, which may aid discussions surrounding the continuation or removal of life-sustaining therapies during the early post-injury period. ANN NEUROL 2023;93:131-141.

When in Doubt Give Blood Out: Transfusion of an Emergency Release Quick Pack does not Increase Late Mortality

Introduction: Differentiating patients with hemorrhage from those with other causes of hypotension in the early post-injury period can be challenging. It remains unclear what effect these small volume transfusions have on outcomes. We evaluated patient outcomes after early blood transfusion in the form of an emergency release quick pack (QP: up to 2U RBC + 2U FFP) for presumed hemorrhage. Methods: Retrospective review of trauma patients with initial shock index >0.9 admitted to our Level 1 trauma center from 2019-2021. Patients were categorized by blood products transfused in the first 24h: none or QP only. A Cox regression assuming equal time at risk was used to estimate risk ratios (RRs) for the association between blood product category and complication (including death). Models were adjusted for age, race, sex, blunt injury mechanism, thorax or abdominal AIS ≥3. Results: A total of 1176 patients were included. There was no significant difference in mortality after 72h between the QP and no product groups (RR 1.77, 95% CI 0.91-3.45). Compared with the no product group, QP patients were more likely to have a VTE (RR 2.08, 95% CI 1.11-3.88) but they had a similar risk of stroke and infectious complication. Conclusion: Compared with no transfusion, a small volume transfusion in the form of a quick pack while evaluating hemodynamic stability is not associated with increased late mortality. Given the high risk of mortality from massive hemorrhage, early empiric blood resuscitation should commence while attempts to determine the etiology of shock are ongoing.

Sciatic nerve stimulation alleviates acute neuropathic pain via modulation of neuroinflammation and descending pain inhibition in a rodent model

BackgroundNeuropathic pain (NP) is characterized by abnormal activation of pain conducting pathways and manifests as mechanical allodynia and thermal hypersensitivity. Peripheral nerve stimulation is used for treatment of medically refractory chronic NP and has been shown to reduce neuroinflammation. However, whether sciatic nerve stimulation (SNS) is of therapeutic benefit to NP remains unclear. Moreover, the optimal frequency for SNS is unknown. To address this research gap, we investigated the effect of SNS in an acute NP rodent model.MethodsRats with right L5 nerve root ligation (NRL) or Sham surgery were used. Ipsilateral SNS was performed at 2 Hz, 20 Hz, and 60 Hz frequencies. Behavioral tests were performed to assess pain and thermal hypersensitivity before and after NRL and SNS. Expression of inflammatory proteins in the L5 spinal cord and the immunohistochemical alterations of spinal cord astrocytes and microglia were examined on post-injury day 7 (PID7) following NRL and SNS. The involvement of the descending pain modulatory pathway was also investigated.ResultsFollowing NRL, the rats showed a decreased pain threshold and latency on the von Frey and Hargreaves tests. The immunofluorescence results indicated hyperactivation of superficial spinal cord dorsal horn (SCDH) neurons. Both 2-Hz and 20-Hz SNS alleviated pain behavior and hyperactivation of SCDH neurons. On PID7, NRL resulted in elevated expression of spinal cord inflammatory proteins including NF-κB, TNF-α, IL-1β, and IL-6, which was mitigated by 2-Hz and 20-Hz SNS. Furthermore, 2-Hz and 20-Hz SNS suppressed the activation of spinal cord astrocytes and microglia following NRL on PID7. Activity of the descending serotoninergic pain modulation pathway showed an increase early on PID1 following 2-Hz and 20-Hz SNS.ConclusionsOur results support that both 2-Hz and 20-Hz SNS can alleviate NP behaviors and hyperactivation of pain conducting pathways. We showed that SNS regulates neuroinflammation and reduces inflammatory protein expression, astrocytic gliosis, and microglia activation. During the early post-injury period, SNS also facilitates the descending pain modulatory pathway. Taken together, these findings support the therapeutic potential of SNS for acute NP.

Clinical presentation and gross appearance of diffuse axonal injury in the early post-injury period

The objective of the study was to investigate and characterize the clinical presentation, and establish macroscopic diagnostic signs of diffuse axonal injury (DAI) in the early (up to 3 days) post-injury period. In DAI, coma develops immediately after head injury and persists for 3 days post-injury until death. The coma is accompanied by dominant primary stem neurological symptoms, hemodynamic and respiratory disturbances and does not progress to a vegetative state. Lifetime computed tomography reveals cerebral hemorrhage in 40.5% of cases. We established the macroscopic signs of head injury in DAI. For the postmortem diagnosis of DAI, a detailed macroscopic appearance of pathognomonic cerebral hemorrhages is given, which are most frequently (67.5%) localized in the corpus callosum (CC), namely in the area from its genu to the middle of the trunk (97%). A rational, improved scheme of excision of CC trunk areas for the histological study is proposed.

Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injury

Background and PurposeDysfunction of the blood–brain-barrier (BBB) is a recognized pathological consequence of traumatic brain injury (TBI) which may play an important role in chronic TBI pathophysiology. We hypothesized that BBB disruption can be detected with dynamic contrast-enhanced (DCE) MRI not only in association with focal traumatic lesions but also in normal-appearing brain tissue of TBI patients, reflecting microscopic microvascular injury. We further hypothesized that BBB integrity would improve but not completely normalize months after TBI. Materials and MethodsDCE MRI was performed in 40 adult patients a median of 23 days after hospitalized TBI and in 21 healthy controls. DCE data was analyzed using Patlak and linear models, and derived metrics of BBB leakage including the volume transfer constant (Ktrans) and the normalized permeability index (NPI) were compared between groups. BBB metrics were compared with focal lesion distribution as well as with contemporaneous measures of symptomatology and cognitive function in TBI patients. Finally, BBB metrics were examined longitudinally among 18 TBI patients who returned for a second MRI a median of 204 days postinjury. ResultsTBI patients exhibited higher mean Ktrans (p = 0.0028) and proportion of suprathreshold NPI voxels (p = 0.001) relative to controls. Tissue-based analysis confirmed greatest TBI-related BBB disruption in association with focal lesions, however elevated Ktrans was also observed in perilesional (p = 0.011) and nonlesional (p = 0.044) regions. BBB disruption showed inverse correlation with quality of life (rho = −0.51, corrected p = 0.016). Among the subset of TBI patients who underwent a second MRI several months after the initial evaluation, metrics of BBB disruption did not differ significantly at the group level, though variable longitudinal changes were observed at the individual subject level. ConclusionsThis pilot investigation suggests that TBI-related BBB disruption is detectable in the early post-injury period in association with focal and diffuse brain injury.

Effect of precise partial scab removal on the repair of deep partial-thickness burn wounds in children: a retrospective study.

BackgroundThe choice of treatment methods for children with deep partial-thickness burn wounds (DPBWs) is an issue that requires careful consideration from surgeons. The purpose of this study was to evaluate the efficacy of precise partial scab removal (PPSR) in the treatment of DPBWs in children.MethodsWe retrospectively analyzed the clinical data of 78 children with DPBWs. The children were divided into a PPSR group (n=37) and a routine dressing change (RDC) group (n=41). In the PPSR group, an electric dermatome was used to cut the scab in the early post-injury period. The thickness scale of the electric dermatome was set to 0.1 mm. The scab was removed to the base with scattered bleeding points. There was still a small amount of necrotic tissue in the base of the wound. For the acellular dermal matrix, the first dressing change was about 1 week after surgery. The RDC group was given conventional wound-dressing treatment. The wound dressing was changed with epidermal growth factor, silver-zinc antibacterial cream, and dressing change. The frequency of dressing change was adjusted once a day or once every other day depending on the condition of wound secretions. The hospitalization time, wound-healing time, fever duration, antibiotic use time, number of subsequent operations, and overall hospitalization expenses were compared between the two groups.ResultsThe wound-healing time of the PPSR group was 19.86±6.4 days, and the wound-healing time of the RDC group was 24.15±7.12 days (P=0.0068). The duration of fever in the PPSR group and RDC group was 2.62±1.99 and 4.44±3.10 days, respectively (P=0.0032). The antibiotic use time in the PPSR group and RDC group was 4.0±1.33 and 4.83±1.88 days, respectively (P=0.0292). The overall hospitalization cost of the PPSR group and RDC group was yuan renminbi ¥37,852.84±10,894.64 and ¥38,047.46±19,450.37, respectively (P=0.9573).ConclusionsPPSR can shorten wound-healing time, reduce the frequency of dressing changes, shorten the time of fever in children, lower the frequency of antibiotic use, and decrease number of dressing changes on the wound.

Compensatory functional connectome changes in a rat model of traumatic brain injury.

Penetrating cortical impact injuries alter neuronal communication beyond the injury epicentre, across regions involved in affective, sensorimotor and cognitive processing. Understanding how traumatic brain injury reorganizes local and brain wide nodal interactions may provide valuable quantitative parameters for monitoring pathological progression and recovery. To this end, we investigated spontaneous fluctuations in the functional MRI signal obtained at 11.1 T in rats sustaining controlled cortical impact and imaged at 2- and 30-days post-injury. Graph theory-based calculations were applied to weighted undirected matrices constructed from 12 879 pairwise correlations between functional MRI signals from 162 regions. Our data indicate that on Days 2 and 30 post-controlled cortical impact there is a significant increase in connectivity strength in nodes located in contralesional cortical, thalamic and basal forebrain areas. Rats imaged on Day 2 post-injury had significantly greater network modularity than controls, with influential nodes (with high eigenvector centrality) contained within the contralesional module and participating less in cross-modular interactions. By Day 30, modularity and cross-modular interactions recover, although a cluster of nodes with low strength and low eigenvector centrality remain in the ipsilateral cortex. Our results suggest that changes in node strength, modularity, eigenvector centrality and participation coefficient track early and late traumatic brain injury effects on brain functional connectivity. We propose that the observed compensatory functional connectivity reorganization in response to controlled cortical impact may be unfavourable to brain wide communication in the early post-injury period.

Arterial Spin Labeling Reveals Elevated Cerebral Blood Flow with Distinct Clusters of Hypo- and Hyperperfusion after Traumatic Brain Injury.

Imaging detection of brain perfusion alterations after traumatic brain injury (TBI) may provide prognostic insights. In this study, we used arterial spin labeling (ASL) to quantify cross-sectional and longitudinal changes in cerebral blood flow (CBF) after TBI and correlated changes with clinical outcome. We analyzed magnetic resonance imaging scans from adult participants with TBI requiring hospitalization in the acute (2 weeks post-injury, n = 33) and chronic (6 months post-injury, n = 16) phases, with 13 participants scanned longitudinally at both time points. We also analyzed 18 age- and sex-matched healthy controls. Whole-brain CBF maps were derived using a three-dimensional pseudo-continuous arterial spin label technique. Mean CBF across tissue-based regions (whole brain, gray matter, and white matter) was compared cross-sectionally and longitudinally. In addition, individual-level clusters of abnormal perfusion were identified using voxel-based z-score analysis of relative CBF maps, and number and volume of abnormally hypo- and hyperperfused clusters were assessed cross-sectionally and longitudinally. Finally, all CBF measures were correlated with clinical outcome measures. Mean global and gray matter CBF were significantly elevated in acute and chronic TBI participants compared to controls. Participants with better outcome at 6 months post-injury tended to have higher CBF in the acute phase compared to those with poorer outcome. Acute TBI participants had a significantly greater volume of hypo- and hyperperfused brain tissue compared to controls, with these regions partially normalizing by the chronic phase. Our findings demonstrate global elevation of CBF with focal hypo- and hyperperfusion in the early post-injury period and suggest a reparative role for acute elevation in CBF post-TBI.

Does the Location of Initial Management After Distal Radius Fracture Impact the Ultimate Need for Operative Intervention?

BACKGROUND: Fractures of the radius and/or ulna comprise the largest proportion (44%) of the estimated 1.5 million cases of hand and forearm fractures seen in Unites States emergency departments each year.1 Displaced distal radius fractures (DRFs) are often managed with closed reduction and splinting. After initial management of these injuries, patients are referred to tertiary care facilities or specialty groups for continuing care. Failure to obtain a stable, near-anatomic reduction may lead a specialist to recommend and/or perform surgery to re-establish appropriate radiographic relationships. Complication rates associated with nonoperative management have been studied though data on conversion to surgical management are not widely reported.2 Surgery incurs a significant financial and physical cost to the patient and healthcare system. The primary aim of this study was to assess how location and type of facility at which a DRF is initially managed impacts rates of surgical intervention. Specifically, we compared a tertiary care facility, staffed with hand specialists, to referring community institutions where no hand specialists were readily available. METHODS: We performed a retrospective chart review of all patients treated at University of Wisconsin—Hospital and Clinics (UW) for DRFs from January 1, 2018 to December 31, 2018. Patients were placed into one of 2 groups: (1) initial treatment performed at any location within the UW system and (2) initial treatment performed at any location outside of the UW system. We calculated the operative rate for each group. We also analyzed the effect of sex and type of injury on the conversion to surgical management. RESULTS: We identified 1,337 patient encounters associated with a DRF current procedural terminology (CPT) code. Eight hundred twenty-four patients were initially managed at UW Health, whereas 513 patients were initially managed at non-UW facilities. Patients initially managed at UW went on to surgical intervention at a significantly lower rate of 15.0% (n = 124) compared to those patients initially treated outside of UW Health who underwent surgery 26.3% of the time (n = 135) (P < 0.0001). Type of injury was not a predictor of conversion to surgery nor initial presentation to UW. Sex was not a predictor of surgical conversion. CONCLUSIONS: These data suggest that initial management of DRFs at UW Hospital and Clinics significantly decreases the rate of operative reduction and fixation. A decrease in operative intervention reduces both the physical and financial impact of DRFs. This indicates that there may be a need to educate community providers to either perform an acceptable bony reduction or refer patients to treating facilities capable of performing these techniques in the early postinjury period. REFERENCES: 1. Chung C, Spilson SV. The frequency and epidemiology of hand and forearm fractures in the United States. J Hand Surg Am. 2001;26:908–915. 2. Chung KC, Malay S, Shauver MJ, et al, for the WRIST Group. Assessment of distal radius fracture complications among adults 60 years or older: a secondary analysis of the WRIST Randomized Clinical Trial. JAMA Netw Open. 2019;2:e187053.

Novel Approach for Detecting the Neurological or Behavioral Impact of Physiological Episodes (PEs) in Military Aircraft Crews.

Military and civil aviation have documented physiological episodes among aircrews. Therefore, continued efforts are being made to improve the internal environment. Studies have shown that exposures to many organic compounds present in emissions are known to cause a variety of physiological symptoms. We hypothesize that these compounds may reversibly inhibit acetylcholinesterase, which may disrupt synaptic signaling. As a result, neural proteins leak through the damaged blood-brain barrier into the blood and in some, elicit an autoimmune response. Neural-specific autoantibodies of immunoglobulin-G (IgG) class were estimated by the Western blotting technique in the sera of 26 aircrew members and compared with the sera of 19 normal healthy nonaircrew members, used as controls. We found significantly elevated levels of circulating IgG-class autoantibodies to neurofilament triplet proteins, tubulin, microtubule-associated tau proteins (Tau), microtubule-associated protein-2, myelin basic protein, and glial fibrillary acidic protein, but not S100 calcium-binding protein B compared to healthy controls. Repetitive physiological episodes may initiate cellular injury, leading to neuronal degeneration in selected individuals. Diagnosis and intervention should occur at early postinjury periods. Use of blood-based biomarkers to assess subclinical brain injury would help in both diagnosis and treatment.

Evaluation of Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in blunt chest trauma patients.

After blunt chest trauma, life-threatening arrhythmias may occur in the early post-injury period, as well as a few days after the injury. This study aimed to evaluate the risk of arrhythmias in blunt chest trauma patients using Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio. In this study, patients who applied to the emergency department due to blunt chest trauma were examined prospectively. The 12-lead ECG was performed to both blunt chest trauma and control group. ECG measurements of QT and Tp-e intervals were performed from both groups. A total of 81 participants; 41 blunt chest trauma patients and 40 healthy volunteers were included in this study. Tpe, Tpe/QT, Tpe/QTc values were statistically significant in the trauma group compared to the control group (p<0.001). Although Tpe/QTc, max QT and min QT were statistically significant (p<0.05) in patients with a rib fracture, no difference was detected concerning Tpe, Tpe/QT compared to no-rib fracture group (p>0.05). Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in ECG predict the arrhythmias that may occur in blunt cardiac trauma, especially in blunt chest trauma patients.

Oxygenation extremes after traumatic brain injury transiently affect coagulation

IntroductionTrauma patients may become hypoxic or iatrogenically hyperoxic in the early post-injury period. While both extremes of oxygenation may be harmful following injury, the mechanism has yet to be elucidated. We hypothesized that hypoxia or hyperoxia would induce changes in coagulation, creating a secondary insult exacerbating the primary injury. Materials and methodsMice underwent traumatic brain injury (TBI) or sham and were subsequently exposed to room air or brief hypoxia (15% FiO2) then sacrificed at intervals. Another cohort of uninjured mice underwent more prolonged hypoxia (10% FiO2) or hyperoxia (60% FiO2). Platelet function was evaluated by ADP- or ASPi-induced impedance aggregometry and viscoelastic coagulation parameters were assessed with rotational thromboelastometry. ResultsIn uninjured mice, ADP-induced platelet aggregation was acutely increased after prolonged hypoxia, but this difference did not persist at 6 h. Hypoxic and hyperoxic TBI mice had increased ADP induced platelet aggregation at 1 h compared to the normoxia group. TBI mice demonstrated an early increased platelet aggregation after hypoxia or hyperoxia. Viscoelastic coagulation parameters were similar between hypoxic, hyperoxic and room air groups at 1 h and 6 h. However, ROTEM clotting time and clot formation time were prolonged and maximal clot firmness were lower in sham TBI/hypoxia mice at 24 h. ConclusionPost-TBI hypoxia and hyperoxia resulted in transiently increased platelet aggregation in response to ADP, without lasting effecting on platelet function or coagulation. Hypoxia also induced delayed hypocoagulability after platelet aggregation normalized. Brief changes in oxygenation may temporally affect coagulation and platelet aggregation, which could contribute to physiologic secondary injury after trauma.

Evaluating the Utility of Follow-up Radiographs for Isolated Radial Head Fractures Undergoing Initial Nonoperative Treatment.

To evaluate the utility of follow-up radiographs in patients with isolated partial articular radial head fractures (OTA/AO 2R1B1 or 2R1B3). Retrospective cohort study. Academic Level 1 Trauma Center. Adult patients (≥18 years) with isolated partial articular radial head fractures indicated for initial nonoperative treatment. Analysis of elbow radiographs at initial presentation and at postinjury follow-up of 3-8 weeks. Articular gap and step-off. Radiographic articular displacement between initial and follow-up radiographs. For 72 included patients, initial radiographs were obtained on average 2.6 days after injury and follow-up radiographs 33.7 days thereafter. Equivalence tests evaluating gap and step-off thresholds of <1 mm were both significant, indicating that the cohort displaced <1 mm for both parameters between initial and follow-up radiographs. No patients proceeded to surgical treatment following the repeat radiographs. These fractures do not displace in the early postinjury period, as defined as a <1 mm of change in both intra-articular gap and step-off, as compared to initial radiographs. Routine follow-up radiographs for these injuries is a source of cost, but with limited utility in detecting interval displacement or leading to a change in management. Selective use of radiographs to evaluate specific clinical concerns may lead to cost savings. Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Depletion of microglia immediately following traumatic brain injury in the pediatric rat: Implications for cellular and behavioral pathology

The inflammatory response is a significant component of the pathophysiology of pediatric traumatic brain injury. High levels of inflammatory mediators have been found in the cerebrospinal fluid of brain-injured children which have been linked to poor prognosis. Targeting aspects of the inflammatory response in the hopes of finding a viable post-injury therapeutic option has gained attention. Microglia are largely responsible for perpetuating the injury-induced inflammatory response but in the developing brain they play beneficial roles in both normal and disease states. Following closed head injury in the neonate rat, depletion of microglia with intracerebral injections of liposomes containing clodronate was associated with an increase in neurodegeneration in the early post-injury period (3 days) relative to those injected with empty liposomes suggestive of a decrease in clearance of dying cells. In sham-injured animals, microglia repopulated the clodrosome-mediated depleted brain regions over a period of 2–4 weeks and exhibited morphology typical of a resting phenotype. In brain-injured animals, the repopulated microglia in clodrosome-injected animals exhibited rod-like and amoeboid morphologies. However, fluoro-Jade B reactivity in these brain regions was more extensive than in empty liposome-injected animals suggesting that the active microglia may be unable to clear dying neurons. This was accompanied by an induction of hyperexcitability in the local cortical circuitry. Depletion of microglia within the white matter tracts and the thalamus did not affect the extent of injury-induced traumatic axonal injury. Increased neurodegeneration in the dorsal subiculum was not accompanied by any changes to injury-induced deficits in spatial learning and memory. These data suggest that activation of microglia may be important for removal of dying neurons in the traumatically-injured immature brain.

Pioglitazone Therapy and Fractures: Systematic Review and Meta- Analysis.

Background: Traumatic brain injury (TBI) constitutes the primary reason for mortality and morbidity in persons worldwide below 45 years of age. 1.7 million Traumatic events occur yearly in the United States alone, considering for 50,000 deaths. In severe traumatic brain injury sufferers, a considerable achievement attained in treating short-term conse-quences; but till date, huge failures are occurring in researcher’s capability to render severe traumatic brain injury sufferers to an elevated degree of performing.Methods: Initial damage force results in Primary brain injury, causing tissue destruction and distortion in the early post-injury period. These secondary injuries from TBI cause changes in cell performance and dissemination of trauma via activi-ties like free-radical generation, depolarization, and formation of edema, excitotoxicity, and disruption of blood brain barrier, calcium homeostasis, and intracranial hematoma. The expectation for developing effect in TBI sufferers is the best knowledge of these activities and enhancement of remedies that restrict secondary brain damage.Results: The focal point of this study is on knowing the complex outburst of secondary impairments and studying the path-ophysiology of TBI which provides alternative treatment benefits.Conclusion: While injured persons demonstrate dissimilar levels of harm and every case is novel with specific recovery pro-files, this article strengthens the recent pathophysiological sight of TBI mainly attention on oxidative stress, excitotoxicity, cerebral oxygenation and cerebral blood flow (CBF), development of edema, and inflammatory activities. For initial research acknowledgment of these recurring factors could permit clarification of possible beneficial targets.