Traumatic Hemorrhage Research Articles

Typical causes and clinical presentations of traumatic and nontraumatic soft tissue and organ haemorrhage in emergency departments

Acute bleeding often occurs in awide variety of forms in clinical emergency medicine. In traumatic bleeding, soft tissue injuries to the head or extremities are common, while severe bleeding is less common in chest injuries or pelvic trauma. In nontraumatic emergencies, gastrointestinal bleeding is the leading cause, but many other bleeding entities are possible. Structured management helps to detect the critically ill patient, identify the possible source of bleeding and provide appropriate radiological diagnostics and therapy. Clinical examination, blood gas analyses and emergency ultrasound are crucial in the initial phase of diagnosis. Initially, symptomatic therapy is usually indicated to stabilize the patient, and then interventional or surgical care is indicated in the course of the disease, depending on the location of the bleeding. Volume and catecholamine therapy, coagulation management and emergency transfusion are important components of interdisciplinary emergency care, in addition to primary bleeding control, especially in the case of open injuries.

Emergency neurosurgery for traumatic brain injury by general surgeons at local hospitals in Sweden: a viable option when time is brain.

Timing of surgical evacuation of mass lesions in traumatic brain injury (TBI) is crucial. However, due to geographical variations, transportation time to the nearest neurosurgical department may be long. To save time, general surgeons at a local hospital may perform the operation, despite more limited experience in neurosurgical techniques. This study aimed to determine whether patient outcomes differed between those who had undergone emergency neurosurgery at local hospitals by general surgeons vs. at university hospitals by neurosurgeons. A nationwide observational study was performed using data from the Swedish Trauma Registry (SweTrau) between 2018 and 2022. A total of 565 TBI patients (local hospitals, n = 21; university hospitals, n = 544) who underwent intracranial hematoma evacuation within 8h after arrival at the hospital were included. Data on demography, admission variables, traumatic injuries, and outcome (Glasgow Outcome Scale [GOS]) at discharge were evaluated. Favourable vs. unfavourable outcomes were defined as GOS scores of 4-5 vs. 1-3. Compared with those treated at university hospitals, patients treated with intracranial hematoma evacuation at local hospitals had lower median Glasgow Coma Scale (GCS) scores (8 vs. 12, p < 0.001), higher rate of acute subdural hematomas (86% vs. 77%, p < 0.001), and lower rate of contusions (14% vs. 53%, p = 0.01). Being operated on at a local hospital was independently associated with higher mortality (p = 0.03) but with a similar rate of favourable outcome (p = 0.74) in multiple logistic regressions after adjustment for demographic and injury-related variables. Although a slightly greater proportion of patients who underwent emergency neurosurgery at local hospitals died, there was no difference in the rate of favourable outcome. Thus, in patients with impending brain herniation, when time is of the essence, evacuation of traumatic intracranial bleeding by general surgeons at local hospitals remains a highly viable option.

Benefits of Different Balanced Resuscitation Ratios for Thoracic vs Abdominopelvic Traumatic Hemorrhage.

This comparative effectiveness research uses data from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized clinical trial to compare benefits with balanced resuscitation for thoracic vs abdominopelvic traumatic hemorrhage.

Early high-dose cryoprecipitate to reduce mortality in adult patients with traumatic haemorrhage: the CRYOSTAT-2 RCT with cost-effectiveness analysis.

Traumatic haemorrhage is common after severe injury, leading to disability and death. Cryoprecipitate, a source of fibrinogen, may improve outcomes for patients with traumatic haemorrhage. To investigate the effects of early fibrinogen supplementation in the form of 3 pools (15 units, approximately 6g of fibrinogen) of cryoprecipitate on 28-day mortality. A randomised, parallel-group, unblinded, multicentre, international trial and economic evaluation. Patients were randomised to either the intervention (early cryoprecipitate) or the comparator (standard major haemorrhage protocol) arm via opaque, sealed envelopes in the emergency department or the transfusion laboratory/blood bank. All analyses were performed on an intention-to-treat basis. A cost-effectiveness analysis was undertaken. Twenty-five major trauma centres in the UK and one level 1 trauma centre in the USA. Adults who had traumatic haemorrhage following severe injury requiring activation of the major haemorrhage protocol and had received a blood transfusion. Early cryoprecipitate - 3 pools (equivalent to 15 single units of cryoprecipitate or 6 g of fibrinogen supplementation), infused as rapidly as possible, within 90 minutes of arrival at hospital in addition to standard major haemorrhage protocol or standard major haemorrhage protocol only. The primary outcome was all-cause mortality at 28 days. The secondary outcomes were all-cause mortality at 6 hours, 24 hours, 6 months and 12 months from admission; death from bleeding at 6 hours and 24 hours; transfusion requirements at 24 hours from admission; destination of participant at discharge; quality-of-life measurements (EuroQol-5 Dimensions, five-level version and Glasgow Outcome Scale) at discharge/day 28 and 6 months after injury; and hospital resource use up to discharge or day 28 (including ventilator-days, hours spent in critical care and inpatient stays). Eight hundred and five patients were randomised to receive the standard major haemorrhage protocol (control arm). Seven hundred and ninety-nine patients were randomised to receive an additional three pools of cryoprecipitate in addition to standard care (intervention arm). Baseline characteristics appeared well matched. Patients had a median age of 39 (interquartile range 26-55) years, and the majority (79%) were male. All-cause 28-day mortality (n=1531 patients; intention to treat) was 25.3% in the intervention arm compared with 26.1% in the control arm (odds ratio 0.96; p=0.74). There was variability in the timing of cryoprecipitate administration, with overlap between the treatment arms, limiting the degree of intervention separation. There was no evidence that early empiric administration of high-dose cryoprecipitate reduced the risk of death in unselected patients with traumatic haemorrhage. There was also no difference in adverse events. The cost-effectiveness of the intervention was similar to that of standard care. Research to evaluate if fibrinogen replacement is more beneficial for selected patients, for example those with low fibrinogen blood levels, is needed, as is further exploration of whether there is a difference in outcome according to mechanism of injury. This trial is registered as ISRCTN14998314. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/57/02) and is published in full in Health Technology Assessment; Vol. 28, No. 76. See the NIHR Funding and Awards website for further award information.

Platelet to erythrocyte ratio and mortality in massively transfused trauma patients.

BackgroundThe optimal transfusion ratio of platelets (PLT), plasma and red blood cells (RBC) in trauma patients with massive haemorrhage is still a subject of discussion. The objective of this study is to assess the effect of platelet transfusion on mortality in trauma patients who received massive transfusion. MethodsData were collected from four Dutch level-1 trauma centres. All trauma patients aged ≥ 16 years who received ≥ 6 RBC / 6 hours from the time of injury were included. Patients were divided based on PLT:RBC ratio (no platelets, low (<1:5) and high (≥1:5)). Primary outcome measure was 6-hour mortality and secondary outcomes included mortality at other time points and transfusion characteristics. ResultsA total of 292 patients were included. Patients in the high PLT ratio group had lower mortality rates at six and 12 hours as compared to the low PLT ratio and no PLT group. In the high PLT group mortality as a result of exsanguination (12%) was significantly lower as compared to the low PLT group (23%). High PLT ratio had lower probability for 6-hour mortality multivariable analysis. Higher plasma:RBC ratios were associated with lower mortality at all time points. ConclusionsAlthough the optimal patient specific transfusion strategy in patients with traumatic haemorrhage is still not resolved, these results show that higher PLT to RBC ratios are associated with lower early mortality.

Divergent modulation of activated protein C pleiotropic functions by antibodies that differ by a single amino acid

AbstractActivated protein C (APC) is a pleiotropic plasma protease with diverse functions derived from its anticoagulant, anti-inflammatory, and cytoprotective activities. The selective uncoupling and/or modulation of these APC activities by antibodies may have therapeutic benefit in diseases such as traumatic bleeding, hemophilia, sepsis, and ischemia. TPP-26870 is an antibody that targets a nonactive site of APC for the selective modulation of APC activities. To optimize the potency of TPP-26870, variants with single amino acid mutation in the complementarity-determining regions (CDRs) were screened, and 21 variants with improved KD were identified. Interestingly, the affinity maturation of TPP-26870 did not merely generate a panel of variants with higher potency in functional assays. Functional data demonstrated that the pleiotropic functions of APC were very sensitive to epitope-CDR interactions. Single amino acid mutations within the CDRs of TPP-26870 were sufficient to elicit divergent antagonistic and agonistic effects on the various APC functional activities. These include prolonged in vitro APC plasma half-life, increased inhibition of anticoagulant activity, and agonistic enhancement of histone H3 cleavage, while having less impact on protease-activated receptor 1 cleavage, compared with TPP-26870. This study illustrates that APC is highly sensitive to non–active site targeting that can lead to unpredictable changes in its activity profile of this pleiotropic enzyme. Furthermore, this study demonstrates the ability to modify APC functions to advance the potential development of APC-targeted antibodies as therapeutics for the treatment of diseases including trauma bleeding, hemophilia, ischemia, and sepsis.

Concizumab prophylaxis in people with haemophilia A or haemophilia B without inhibitors (explorer8): a prospective, multicentre, open-label, randomised, phase 3a trial

Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody in development as a once-daily, subcutaneous prophylaxis for patients with haemophilia A or haemophilia B with or without inhibitors. We aimed to assess the efficacy and safety of concizumab in patients with haemophilia A or B without inhibitors. Here we report the results from the confirmatory analysis cutoff. This prospective, multicentre, open-label, randomised, phase 3a trial (explorer8) was conducted at 69 investigational sites in 31 countries. Eligible patients were male, aged 12 years or older, and had congenital severe haemophilia A or moderate or severe haemophilia B without inhibitors and with documented treatment with clotting factor concentrate in the 24 weeks before screening. The trial was paused because of non-fatal thromboembolic events in three patients (two from this trial [explorer8] and one from a related trial in haemophilia with inhibitors [explorer7; NCT04083781]) and restarted with mitigation measures, including a revised dosing regimen of subcutaneous concizumab at 1·0 mg/kg loading dose on day 1 and subsequent daily doses of 0·20 mg/kg from day 2, with options to decrease to 0·15 mg/kg, stay on 0·20 mg/kg, or increase to 0·25 mg/kg on the basis of concizumab plasma concentration measured after 4 weeks on concizumab. Patients recruited after treatment restart were randomly assigned 1:2 using an interactive web response system to receive no prophylaxis and continue on-demand clotting factor (group 1) or concizumab prophylaxis (group 2). The primary endpoints were the number of treated spontaneous and traumatic bleeding episodes for patients with haemophilia A and haemophilia B separately, assessed at the confirmatory analysis cutoff in randomly assigned patients. Analyses were by intention-to-treat. There were two additional groups containing non-randomly-assigned patients: group 3 contained patients who entered the trial before the trial pause and were receiving concizumab in the phase 2 trial (explorer5; NCT03196297), and group 4 contained patients who received previous clotting factor concentrate prophylaxis or on-demand treatment in the non-interventional trial (explorer6; NCT03741881), patients randomly assigned to groups 1 or 2 before the treatment pause, and patients from explorer5 enrolled after the treatment pause. The safety analysis set contained all patients who received concizumab. Superiority of concizumab over no prophylaxis was established if the two-sided 95% CI of the treatment ratio was less than 1 for haemophilia A and for haemophilia B. This trial is registered with ClinicalTrials.gov, NCT04082429, and its extension part is ongoing. Patients were recruited between Nov 13, 2019 and Nov 30, 2021; the cutoff date for the analyses presented was July 12, 2022. 173 patients were screened, of whom 148 (86%) were randomly assigned or allocated to the four groups in the study after trial restart on Sept 30, 2020 (nine with haemophilia A and 12 with haemophilia B in group 1; 18 with haemophilia A and 24 with haemophilia B in group 2; nine with haemophilia A in group 3; and 46 with haemophilia A and 30 with haemophilia B in group 4). The estimated mean annualised bleeding rate ratio for treated spontaneous and traumatic bleeding episodes during concizumab prophylaxis versus no prophylaxis was 0·14 (95% CI 0·07-0·29; p<0·0001) for patients with haemophilia A and 0·21 (0·10-0·45; p<0·0001) for patients with haemophilia B. The most frequent adverse events in patients who received concizumab were SARS-CoV-2 infection (19 [13%] of 151 patients), an increase in fibrin D-dimers (12 [8%] patients), and upper respiratory tract infection (ten [7%] patients). There was one fatal adverse event possibly related to treatment (intra-abdominal haemorrhage in a patient from group 4 with haemophilia A with a long-standing history of hypertension). No thromboembolic events were reported between the trial restart and confirmatory analysis cutoff. Concizumab was effective in reducing the bleeding rate compared with no prophylaxis and was considered safe in patients with haemophilia A or B without inhibitors. The results of this trial suggest that concizumab has the potential to be one of the first subcutaneous treatment options for patients with haemophilia B without inhibitors. Novo Nordisk.

Head injuries in prehospital and Emergency Department settings: a prospective multicenter cross-sectional study in France

BackgroundHead injuries are the leading cause of trauma in Emergency Departments (EDs). Recent studies have shown epidemiological changes in patients consulting ED for head injuries. The main objective of this study was to describe the profile of head injury patients consulting in the EDs in France and assess i) head injury severity across age groups; ii) the delay between the occurrence of head injury and ED arrival; iii) factors associated with traumatic intracranial hemorrhage (ICH).MethodsThis cross-sectional study collected patient data over a three-day period in March 2023. All adult patients (≥ 18 years old) admitted to the ED with a head injury (defined as a trauma to the head) were included. TBI severity was classified according to patients’ initial Glasgow Coma Scale score in the ED: severe (3–8); moderate (9 -12); mild (13–15); and simple head trauma in the absence of transient or persistent neurological symptoms.ResultsAmong the 71 participating EDs, 26,008 patients visited EDs and a total of 1070 patients (4.1%, IC 95 3.9—4.4) presented a head injury were included in the study, with a median age of 68.5 [37–85] years old. Most of the patients (66.7%) were referred to ED after a call to the Emergency Medical Dispatcher (EMD). The median time from head injury to ED visit was 2 h [1.0 – 5.5]. Ground-level falls were the leading cause of head injury (60.3%). Most of patient presented a simple head trauma (n = 715, 66.8%) followed by mild TBI (n = 337, 31.5%). CT head scans were performed for 636 patients (59.6%), of which 58 were positive. Traumatic ICH prevalence was 5.4% (95% CI: 4.1–6.9) and three patients (0.3%) required an urgent neurosurgical intervention. Neither preinjury anticoagulant (p = 0.97) nor antiplatelet (p = 0.93) use was associated with an increased risk of traumatic ICH.ConclusionsOne head injury patient out of two presenting in the ED is aged over 65 years. Patients referred by EMD were more likely to visit ED promptly. The majority of older patients underwent a head CT scan and preinjury anticoagulant use was not associated with increased risk of traumatic ICH.

Angioembolization for hemostasis in craniofacial fractures had a higher probability of delayed traumatic intracerebral hemorrhage

IntroductionWhile angioembolization is occasionally required for craniofacial fracture patients who experience massive maxillofacial hemorrhage, complications such as headache, temporal-facial pain, soft tissue necrosis, and embolic material migration leading to stroke or blindness can arise. Few studies have explored delayed or progressive intracerebral hemorrhage (ICH) following angioembolization for craniofacial fractures. MethodsA retrospective review of craniofacial fracture patients from January 1, 2015, to December 31, 2022 at our institution was conducted. We applied univariate and multivariable logistic regression (MLR) analyses to assess whether angioembolization served as an independent factor for delayed or progressive ICH. Propensity score matching (PSM) was used to balance the groups of patients who underwent angioembolization with those who did not. Outcome measurements included delayed or progressive ICH occurring within 72 hours, the need for additional neurosurgical interventions, and the length of stay (LOS) in the intensive care unit (ICU) and hospital. ResultsOf the 2,519 craniofacial fracture patients studied over an 8-year period, 21 (0.8%) underwent angioembolization for maxillofacial hemorrhage. MLR analysis revealed that angioembolization was an independent factor for delayed or progressive ICH (odds ratio=5.71, p = 0.028). After 1:2 PSM, patients who underwent angioembolization had greater rates of delayed or progressive ICH (28.6% vs. 7.1%, p = 0.023), an extended hospital LOS (17.0 vs. 15.0 days, p = 0.009) and a longer ICU LOS (10.0 vs. 4.0 days, p = 0.004). ConclusionsA greater probability of delayed or progressive ICH was observed in craniofacial fracture patients who underwent angioembolization for maxillofacial hemostasis.

First experience of endovascular balloon occlusion of the aorta in the wounded with hemorrhagic shock during the war in Ukraine

Background. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used worldwide to stop bleeding in trauma and wounds in patients with hemorrhagic shock. REBOA allows for the hemodynamic stabilization, patient transportation and final bleeding control. The study aims to demonstrate the capabilities of REBOA as a method of bleeding control in the wounded with hemorrhagic shock in the context of war in Ukraine. Materials and methods. Five AFU servicemen who sustained mine-blast wounds in the Eastern Ukraine as a result of shelling by Russian troops were delivered with signs of internal bleeding and hemorrhagic shock to the primary and secondary levels of medical care (Role 1, 2). The REBOA balloon catheter was inserted and inflated by surgeons working in stabilization centers or advanced surgical teams. Upon admission, all patients underwent chest and abdominal ultrasound according to the FAST protocol. We used COBRA-OS 4 Fr and ER-REBOA 7 Fr balloon catheters. The positioning of the balloon in the aorta was performed according to external anatomical landmarks (3 cases) and ultrasound (2 cases). In all clinical cases, the balloon catheter was placed in zone I. In one case, the balloon was moved from zone I to zone III (control of the source of bleeding). The duration of aortic occlusion ranged from 15 to 50 minutes. Immediately after removal of the introducer, manual compression of the puncture site was used (3 cases) or suturing of the arteriotomy (2 cases). Results. The sources of bleeding in our clinical cases were injuries of the iliac vessels (2 cases), the renal artery (1 case), and injuries of the inferior vena cava and liver (2 cases). Four patients were evacuated to a higher level of medical care after the REBOA was installed. In one case, there were complications from vascular access (femoral artery thrombosis). We were unable to save one wounded soldier, most likely due to the delay in evacuation from the previous stage, the severity of injury, and massive blood loss. Conclusions. As our observations have shown, the use of REBOA in combat conditions allows not only to stabilize hemodynamics in the wounded with severe combined trauma and bleeding but also to conduct a successful evacuation to a higher level of medical care to stop bleeding ultimately. REBOA can be successfully used at the prehospital stage. This requires clearly defined indications for the technique’s use, training of medical personnel, and provision of balloon catheters to medical units of the Armed Forces of Ukraine.

Prognostic Factors of Outcome in Patients Undergoing Surgical Intervention following Traumatic Intracerebral Haemorrhage

Background: Intracerebral hemorrhage is a common complication after traumatic brain injury. While it is accepted practice to remove extra-axial (extradural and subdural) haematoma following traumatic brain injury, but surgical practice in the treatment of traumatic intracerebral hemorrhage (TICH) differs widely, and prognostic factors associated with outcome following surgery have not yet been well established. Aims: The study aimed to determine the prognostic factors of outcome in patients undergoing surgical intervention following traumatic intracerebral hemorrhage in a tertiary care hospital in southeastern part of Bangladesh. Materials and Methods: This prospective interventional study included 45 patients requiring craniotomies for decompression and evacuation of an intracranial hemorrhage following traumatic intracerebral hemorrhage in the Neurosurgery Department of Chittagong Medical College Hospital between December 2021 to June 2023. Demographic features, perioperative clinical and radiological characteristics of these patients were examined in relation to favorable/good outcome, defined as Glasgow Outcome Scale (GOS) score &gt;3 at 3months follow-up, and unfavorable/poor outcome, defined as 3months mortality or GOS score d”3 at 3months after surgery. Results: The median age was 45 (range 8-75) years, 82.2% were male, and road traffic accident was the commonest cause (73.3%). Initial loss of consciousness was found in 75.7% of patients and the median GCS on admission was 9 (Interquartile range 8-10). Craniotomy and evacuation was done in 23(51.1%) of the cases, followed by craniectomy and evacuation in 22 (48.9%)patients. In-hospital and 3 months mortality rate was 28.9%. At three months post surgery, all of the survived patients(32) had good outcomes; 29 (92.3%) had GOS scores of 5, while the remaining 3 had GOS scores of 4. In bivariate analysis, age, history of comorbidity and loss of consciousness, GCS on admission, hematoma volume, and injury to surgery interval was found to have significant association with poor outcome (p&lt;0.05). Age (OR: 1.211, 95% CI: 1.012-1.241, p=0.009) and GCS score on admission (OR: 0.301, 95% CI: 0.086-0.827, p=0.004) were independent predictors of 3-months poor outcome or mortality in multivariate logistic regression analysis. Conclusions: This study presented that older age(60 years) and lower GCS(7-10) on admission were the independent predictors of poor outcome after 3 months of surgery. Multicenter studies are needed to provide accurate data on traumatic intracerebral hemorrhage in Bangladesh. Bang. J Neurosurgery 2024; 13(2): 104-111

Damage Control Resuscitation in Traumatic Hemorrhage: Comment.

Damage Control Resuscitation in Traumatic Hemorrhage: Comment.

Damage Control Resuscitation in Traumatic Hemorrhage: Comment.

Damage Control Resuscitation in Traumatic Hemorrhage: Comment.

A Mouse Model of Temporal Lobe Contusion.

Trauma to the brain can induce a contusion characterized by a discrete intracerebral or diffuse interstitial hemorrhage. In humans, "computed tomography-positive," that is, hemorrhagic, temporal lobe contusions (tlCont) have unique sequelae. TlCont confers significantly increased odds for moderate or worse disability and the inability to return to baseline work capacity compared to intra-axial injuries in other locations. Patients with tlCont are at elevated risks of memory dysfunction, anxiety, and post-traumatic epilepsy due to involvement of neuroanatomical structures unique to the temporal lobe including the amygdala, hippocampus, and ento-/perirhinal cortex. Because of the relative inaccessibility of the temporal lobe in rodents, no preclinical model of tlCont has been described, impeding progress in elucidating the specific pathophysiology unique to tlCont. Here, we present a minimally invasive mouse model of tlCont with the contusion characterized by a traumatic interstitial hemorrhage. Mortality was low and sensorimotor deficits (beam walk, accelerating rotarod) resolved completely within 3-5 days. However, significant deficits in memory (novel object recognition, Morris water maze) and anxiety (elevated plus maze) persisted at 14-35 days and nonconvulsive electroencephalographic seizures and spiking were significantly increased in the hippocampus at 7-21 days. Immunohistochemistry showed widespread astrogliosis and microgliosis, bilateral hippocampal sclerosis, bilateral loss of hippocampal and cortical inhibitory parvalbumin neurons, and evidence of interhemispheric connectional diaschisis involving the fiber bundle in the ventral corpus callosum that connects temporal lobe structures. This model may be useful to advance our understanding of the unique features of tlCont in humans.

External evaluation of Brain Injury Guideline (BIG) low risk criteria for traumatic brain injury

BackgroundFewer than 20 % of traumatic brain injury (TBI) cases with traumatic intracranial hemorrhage (ICH) result in clinical deterioration. The Brain Injury Guideline (BIG) criteria were published in 2014 and categorize patients with TBI into three risk groups (BIG 1, 2, and 3) based on CT scan findings, neurological examination, anti-coagulant/platelet medications, and intoxication. Early data is promising, suggesting no instances of neurosurgical intervention or death in the low-risk BIG1 category within 30 days. We sought to externally validate the BIG criteria and identify patients with TBI at low risk of clinical deterioration. We hypothesized that patients meeting the BIG1 low risk criteria have less than a 1 % risk of death or neurosurgical intervention. MethodsWe performed a retrospective cohort study of a level 1 trauma center's trauma registry records from 2011 to 2022 to identify patients with head trauma. We abstracted demographics, injury characteristics, clinical course, CT imaging results, and outcomes, and we categorized patients according to the BIG criteria. The Clopper-Pearson Exact method was used to estimate outcome frequency with confidence intervals. The primary outcome was death or neurosurgical intervention within 30 days. Secondary outcomes included progression on repeat head CT (RHCT), ICU admission with neurocritical care intervention, and TBI-related hospital readmission within 30 days. ResultsA total of 1714 patients with TBI with ICH were identified from the trauma registry. 325 patients were excluded due to missing data, pregnancy, incarceration, polytrauma, or GCS < 13, leaving 1389 for analysis. 193 patients (13.9 %) were classified as BIG1. No patients classified as BIG1 experienced the primary outcome measures of death or neurosurgical intervention (95 % confidence interval [CI]: 0 %–1.9 %). The number of patients who experienced the secondary outcome measures of progression on RHCT, ICU admission with neurocritical care intervention, or TBI-related hospital readmission within 30 days were 9 (4.7 %, 95 % CI: 2.2 %–8.7 %), 1 (0.5 %, 95 % CI: 0 %–2.9 %), and 4 (2.1 %, 95 % CI: 0.6 %–5.2 %), respectively. ConclusionBIG1 criteria identified a low-risk subset of patients with TBI with ICH. However, an upper 95 % CI of 1.9 % does not exclude the risk of neurologic deterioration being <1 %. Validation of these criteria in larger cohorts is warranted.

Traumatic Brain Injury Increasing Risk of Meningioma? From the Genetic Evidence

BackgroundNumerous studies have demonstrated a strong association between traumatic brain injury (TBI) and an increased risk of meningioma. However, this correlation remains controversial. This study utilized mendelian randomization to explore this relationship from perspective of genetic evidence. MethodsWe employed six traumatic brain injury genome-wide association study (GWAS) datasets from the IEU GWAS database. Summary statistics for meningioma were sourced from the FinnGen R10 database. We assessed heterogeneity and horizontal pleiotropy within the analyzed data. The primary method was inverse variance weighting (IVW) to investigate the causal relationship between TBI and meningioma, excluding cases with horizontal pleiotropy. Four supplementary analysis methods were also used, with abnormal results excluded based on leave-one-out sensitivity analysis. ResultsAll six Mendelian randomization analyses indicated no causal relationship between TBI and meningiomas (Focal brain injury IVW p-value = 0.98; Diffuse brain injury IVW p-value = 0.41; TBI without concussion IVW p-value = 0.45; Intracranial trauma IVW p-value = 0.34; Traumatic subdural hemorrhage IVW p-value = 0.80; Traumatic subarachnoid hemorrhage IVW p-value = 0.92). ConclusionsThe mendelian randomization study revealed that traumatic brain injury does not increase the risk of meningioma based on genetic evidence.

Combining Imaging and Electrophysiology to Visualize and Record Spreading Depolarizations in Mice.

Spreading Depolarizations (SDs) are massive events in the brain that often go undetected due to their slow propagation through gray matter. Because SD detection can be elusive, it is optimally confirmed using multiple methods. This protocol describes methods for combining imaging and electrophysiology to detect SDs in a manner that most laboratories can reliably and easily adopt. SDs occur following traumatic brain injuries, stroke, subarachnoid hemorrhages, ischemia, and migraine aura. Historically, SDs have been recorded using DC amplifiers, which can resolve the slow extracellular shift and the depression in high-frequency activity. However, DC amplifiers are nearly impossible to use for chronic in vivo recordings. This protocol employs a common AC amplifier for in vivo electrophysiology recordings to confirm high-frequency depression, along with non-invasive imaging necessary to detect the propagating wave of SD. These methods can be reliably adopted and/or modified for most experimental approaches to confirm the presence or absence of SDs following brain injury.

Ratios of calcium to citrate administration in blood transfusion for traumatic hemorrhage: A retrospective cohort study.

Massive transfusion with citrated blood products causes hypocalcemia, which is associated with mortality. Recognition of this problem has led to increased calcium administration; however, the optimal dosing is still unknown. This retrospective, single-center study included level 1 trauma patients in 2019 and 2020 who underwent an operation within 12 h of arrival and received a transfusion. Preoperative and intraoperative administrations were totaled to calculate the ratio of administered calcium to the number of blood transfusions for each patient. The citrate content of each blood component was estimated to calculate a second ratio, the ratio of administered calcium to administered citrate. Receiver Operating Characteristic (ROC) curves were performed on both ratios to determine the optimal cutoff values for predicting severe hypocalcemia (ionized calcium <0.9 mmol/L) and hypercalcemia (>1.35 mmol/L) at the end of the intraoperative period. A total of 506 trauma activations were included, receiving a mean of 17.4 citrated blood products and 16.3 mmol of calcium (equivalent to 2400 mg of calcium chloride). No ratio was statistically significant in differentiating severely hypocalcemic patients from the rest. A calcium to blood ratio of 0.903 mmol of administered calcium per citrated blood product differentiated hypercalcemic patients from the rest. Quantifying received calcium and citrated blood products was insufficient to predict severe hypocalcemia, suggesting other contributions to hypocalcemia. We demonstrated an upper-limit ratio for calcium administration in traumatic hemorrhage; however, further studies are required to determine what calcium dosing regimen results in the best outcomes.

Super-selective renal artery embolization (SRAE) for iatrogenic and traumatic renal hemorrhage

PurposeTo present the radiological and clinical outcomes of super-selective transcatheter renal artery embolization in patients with renal injury hemorrhage, and share our experience.Methods43 patients with renal injury hemorrhage who underwent 46 SRAEs were enrolled in this retrospective review study. Records, images, and outcomes were reviewed. The individual embolic method and its observed effects were investigated.ResultsAngiography showed free extravasation in 25 angiograms, pseudoaneurysm in 15 angiograms, and arteriovenous fistulas in 1 angiogram. Most patients achieved initial clinical success (38/43, 88.4%), and 41 patients achieved final clinical success (41/43, 95.3%). 9/11 patients who adopted empirical embolization achieved initial clinical success (81.8%). In our study, the combination of PVA particles and micro-coils has emerged as the most commonly utilized material combination (24/46, 52.2%). Significant differences in hemoglobin levels were observed before and after the embolization procedure (p = 0.026, 95%CI: 1.03–15.54). Post-embolization clinical follow-up showed no evidence of recurrent hematuria, progression of hematoma, hypertension, and no reflux of the embolic agent.ConclusionThough SRAE showed satisfactory results across a broad range of renal injury hemorrhage, there are still some aspects that need attention: (1) Surgical procedure should be understood, including the surgical site, access routes, and placement of implants, such as double-J stents. (2) In cases where identifying the bleeding point proves challenging, consider the possibility of an accessory renal artery.Trial registrationChinese Clinical Trial Registry ChiCTR2400085050, Registration Date: 30 May 2024, retrospectively, non-randomized.

Clinical and Humanistic Burden of Non-inhibitor HaemophiliaA in Five European Countries: Insights from the CHESSII Study.

HaemophiliaA (HA) is a congenital bleeding disorder caused by a deficiency/absence of factorVIII (FVIII) and characterised by frequent, acute and prolonged spontaneous or traumatic bleeding events, often leading to haemophilic arthropathy and progressive joint deterioration. HA severity is characterized by endogenous FVIII activity: mild (> 5-40%), moderate (1-5%), or severe (< 1%). HA poses a substantial clinical and socioeconomic burden on people with HA (PWHA), their caregivers, and society. This analysis evaluates clinical and patient-centric outcomes of a cohort of individuals with non-inhibitor HA sampled from France, Germany, Italy, Spain, and the UK in the 'Cost of Haemophilia in Europe: A Socioeconomic Survey II' (CHESSII) study. CHESSII was a cross-sectional burden-of-illness study collecting clinical and socioeconomic data on adult (≥ 18years) individuals with haemophiliaA or B of any severity with or without inhibitors from eight European countries. Descriptive analyses were conducted examining physician-reported demographics, clinical and health resource utilisation information. PWHA-reported health-related quality of life (HRQoL) using the EQ-5D-5L and Work Productivity and Activity Impairment (WPAI) were also examined. Outcomes were stratified by HA severity and reported at country level. Demographics and clinical characteristics of the cohort (N = 880) were generally consistent across countries. Individuals with severe HA experienced more frequent bleeding events and joint disease despite broad use of factor replacement therapy long-term prophylaxis. A minority of those with mild or moderate HA also experienced such challenges. HRQoL and workforce participation diminished, and chronic pain increased, with increasing HA severity. This analysis provides up-to-date insights on the impact of HA across five European countries. Increasing HA severity was generally associated with worse clinical outcomes, HRQoL and workforce participation. These findings suggest a place for continued evidence-based tailored treatment and clinical management approaches in addressing the residual burden of HA.