Progression Of Hemorrhage Research Articles

RADT-32. FREQUENT MULTIFOCAL INTRATUMORAL HEMORRHAGE IN MULTIPLE BRAIN METASTASES FROM HEPATOCELLULAR CARCINOMA

Abstract OBJECTIVE Brain metastasis (BM) rarely occurs in hepatocellular carcinoma (HCC); however, it frequently causes intratumoral hemorrhage (ITH). We investigated the clinical manifestations of ITH in patients with multiple BMs from HCC (HCC-BM). METHODS Patients who underwent treatment for multiple BMs with more than two metastatic sites were retrospectively reviewed and those diagnosed with HCC-BM were further analyzed. The multifocality of hemorrhage was classified into two groups, spatial and temporal multifocality, according to the radiological findings. The characteristics of multifocal hemorrhage in HCC were compared with those of BMs from other cancer types. RESULTS Fifteen out of 636 (2.36%) cases of multiple BMs were due to HCC metastasis. Out of 15 HCC-BM cases, 13 (86.7%) presented multifocal hemorrhage and 1 presented unifocal hemorrhage during the follow-up period. Spatial and temporal multifocality were observed in 9 and 5 cases, respectively, among 13 cases of multifocal hemorrhage. Among 636 cases of multiple BMs, HCC cases showed the highest frequency of multifocal hemorrhage, and HCC was significantly associated with multifocal hemorrhage compared with other primary-site cancer types (30/621 cases, 4.8%). Out of 15 patients with multiple HCC-BMs, 12 underwent whole-brain irradiation (WBI), and their median overall survival was 147 days. In one patient (8.3%), although treatment was stopped due to neurological deterioration by ITH, local BM control was favorable after the completion of WBI, and the only cause of death in six patients who completed WBI and were radiologically followed up until death was the progression of extracranial lesions. CONCLUSIONS Multiple HCC-BMs frequently present with multifocal ITH compared with BMs from other cancer types. Despite poor treatment outcome, WBI may show favorable local control considering the potential hemorrhagic event by tiny metastases that would not be detected radiologically. Immediate commencement of treatment before hemorrhage progression will be required for the treatment of multiple HCC-BMs.

Long-term administration of atorvastatin had no effect on the occurrence and progression of spontaneous hypertensive intracerebral hemorrhage in mice

Abstract Background Intracerebral hemorrhage (ICH) is a catastrophic disease with limited treatment options. Statins and low low-density lipoprotein cholesterol (LDL-C) levels have been reported to be associated with increased risk of ICH. Safety concerns of statins were raised as statins become the cornerstone of anti-atherosclerosis therapy. To date, the effect of statins on the incidence of ICH still remains a controversial topic. Purpose The aim of this study was to investigate the effect of atorvastatin on the occurrence and progression of hypertensive ICH in mice. Methods Male wild-type C57BL/6J mice, 13 months old, were randomly divided into atorvastatin (Ato, n=20) group and vehicle (Veh, n=20) group. The atorvastatin group and vehicle group were given atorvastatin (20 mg/kg) and same volume of 0.5% sodium carboxymethylcellulose by oral gavage for 8 weeks, separately. Angiotensin II (Ang II) and L-NAME were then used to induce hypertensive ICH. The time of stroke symptom onset was documented. Hemorrhage volumes were measured by spectrophotometric hemoglobin assay. Results After 8 weeks of atorvastatin or vehicle administration, serum LDL-C levels were significantly lower in the mice treated with atorvastatin than vehicle controls (0.705 vs. 1.008 mmol/L, P<0.001). The administration of atorvastatin did not show significant effects on the systolic blood pressure (SBP) levels when compared with the vehicle group (164 vs. 166 mmHg, P=0.497) after the induction of Ang II and L-NAME. Hemorrhage was observed in brain morphology, and was further verified by hematoxylin and eosin staining or MRI scans in mice that showed signs of stroke. During the 28-day experimental period, 75% (15/20) of mice in the atorvastatin group developed signs of ICH, and 70% (14/20) of mice in the vehicle group developed in the similar time window. The incidence of hypertensive ICH had no significant difference between atorvastatin and vehicle groups (Log-rank P=0.761). Hemorrhage volumes were also comparable between the two groups (1.462 vs. 1.392 uL, P=0.788). Conclusion Reducing serum LDL-C levels by long-term administration of atorvastatin had no effect on the occurrence and progression of spontaneous hypertensive ICH in middle-aged mice.

Antiplatelet Reversal Is Not Associated With Decreased Progression of Intracranial Hemorrhage in Near-Isolated Traumatic Brain Injury: A Retrospective Clustered Analysis From Two Trauma Centers

IntroductionAntiplatelet agents (AAs) may increase the risk of intracranial hemorrhage (ICH). It is unclear whether reversal of antiplatelet effects (REV = desmopressin acetate [DDAVP] + Platelets) decreases ICH progression. The goal of the study was to determine whether REV was associated with decreased progression of ICH on repeat brain computed tomography (CT) scan. MethodsThis is a clustered study (November 2019 to March 2022) at two regionally distinct trauma centers (TCs) with differing standards of practice in patients with ICH, one reversal with DDAVP + Platelets (REV+) and the other no reversal with DDAVP + Platelets (REV−). Using electronic and manual chart review, data were collected on inpatients aged ≥ 18 y on preinjury AAs with CT proven ICH (abbreviated injury scale head ≥ 2) and no other abbreviated injury scale > 2 injuries, who had at least one repeat CT scan within 120 h of admission. ICH progression on repeat brain CT scan, mortality, and resource utilization were compared via univariate analysis (α = 0.05). ResultsOne hundred fourteen patients were enrolled: 72 REV+ at the first TC and 42 REV− at the second TC. REV+ group had fewer White patients and a lower proportion on preinjury aspirin but were otherwise similar. ICH progression rate was 24/72 (33.3%) for REV+ and 11/42 (26.2%) for REV− (P = 0.43). Isolated subarachnoid hemorrhage was the most common lesion, followed by isolated subdural hemorrhage. No patients required cranial surgery. All-cause mortality (expired + hospice) was 5/72 (6.9%) and 1/42 (2.4%), respectively (P = 0.29). ConclusionsIn this study of patients on preinjury AAs, REV was not associated with decreased ICH progression, lower mortality, or less resource utilization. These findings should be confirmed in a larger, prospective study.

Intestinal flora influences the progression of subarachnoid hemorrhage by affecting peripheral and central inflammatory pathways

Subarachnoid hemorrhage (SAH) is a debilitating condition that leaves survivors with neurological disability for the rest of their lives. No effective treatment for early brain injury (EBI) has been developed. Gut microbiome (GM) impact the host immune system and can influence disease processes in several organs, including the brain. However, it remains unclear whether the GM has an impact on the outcome of SAH brain injury. Here, we wondered whether microbiota could relieve the injury. We changed the microbiota of 8-week-old male rats by administering antibiotic-containing water for 2 weeks. Composition of the GM was profiled by using 16S rRNA. We induced SAH by puncture the internal carotid artery of control rats and rats with altered GM. Additionally, we studied inflammatory cells using HE stains, Intestinal lymphocyte flow cytometry, and Neuroinflammatory factor WB. SAH was significantly averted by alterations in GM using antibiotics. The altered GM significantly increased the intestinal and intracranial inflammation after SAH. This was manifested by Mosin (MSN) inflammatory cytokines. Our findings demonstrated that the brain injury following SAH is associated with GM.

Machine learning models for predicting early hemorrhage progression in traumatic brain injury.

This study explores the progression of intracerebral hemorrhage (ICH) in patients with mild to moderate traumatic brain injury (TBI). It aims to predict the risk of ICH progression using initial CT scans and identify clinical factors associated with this progression. A retrospective analysis of TBI patients between January 2010 and December 2021 was performed, focusing on initial CT evaluations and demographic, comorbid, and medical history data. ICH was categorized into intraparenchymal hemorrhage (IPH), petechial hemorrhage (PH), and subarachnoid hemorrhage (SAH). Within our study cohort, we identified a 22.2% progression rate of ICH among 650 TBI patients. The Random Forest algorithm identified variables such as petechial hemorrhage (PH) and countercoup injury as significant predictors of ICH progression. The XGBoost algorithm, incorporating key variables identified through SHAP values, demonstrated robust performance, achieving an AUC of 0.9. Additionally, an individual risk assessment diagram, utilizing significant SHAP values, visually represented the impact of each variable on the risk of ICH progression, providing personalized risk profiles. This approach, highlighted by an AUC of 0.913, underscores the model's precision in predicting ICH progression, marking a significant step towards enhancing TBI patient management through early identification of ICH progression risks.

Spontaneous intracerebral hemorrhage: a review of the prevalence, trigger factors, therapeutic and surgical treatment

Spontaneous intracerebral hemorrhage is the second most common subtype of stroke and is a significant cause of mortality and morbidity worldwide. Trigger factors that “accelerate” disease onset may include hypertension, excessive alcohol consumption, constant smoking, hypocholesterolemia, medications, male sex, advanced age, living in an underdeveloped country, ethnicity, chronic kidney disease, cerebral amyloid angiopathy, and microhemorrhages. Therapeutic solutions for spontaneous intracerebral hemorrhage aimed at stopping the progression of hemorrhage, reducing the clot volume of intraventricular and parenchymal hematoma, combating perihematomal edema and inflammation, rapidly reducing blood pressure, and providing hemostatic therapy with transfusion of platelets and other coagulation complexes. Clinical trials on minimally invasive methods of surgical evacuation (endoscopic surgery, stereotactic aspiration, and invasive craniopuncture) are ongoing and may provide positive results because of the shorter operation time and use of local anesthesia. Minimally invasive surgery methods can theoretically improve the outcomes of open surgery by reducing damage to collateral tissues and reducing anesthesia time; however, they cannot be a full-fledged alternative.

Predicting Progression of Intracranial Hemorrhage in the Prehospital TXA for TBI Trial.

Progression of intracranial hemorrhage is a common, potentially devastating complication after moderate/severe traumatic brain injury (TBI). Clinicians have few tools to predict which patients with traumatic intracranial hemorrhage on their initial head computed tomography (hCT) scan will progress. The objective of this investigation was to identify clinical, imaging, and/or protein biomarkers associated with progression of intracranial hemorrhage (PICH) after moderate/severe TBI and to create an accurate predictive model of PICH based on clinical features available at presentation. We analyzed a subset of subjects from the phase II double-blind, multi-center, randomized "Prehospital Tranexamic Acid Use for TBI" trial. This subset was limited to the placebo arm of the parent trial with evidence of hemorrhage on the initial hCT and a follow-up hCT 6 h after. PICH was defined as an increase in hemorrhage size by 30% or more, or the development of new hemorrhage in the intra- and extra-axial intracranial vault between the initial and the follow-up hCT. Two independent radiologists evaluated each hCT, and conflicts were adjudicated by a third. Clinical and radiographic characteristics were collected, along with plasma protein biomarkers at admission. Principal component analysis (PCA) was performed, and each principal component (PC) was interrogated for its association with PICH. Finally, expert opinion and recursive feature extraction (RFE) were used to select input features for the construction of several supervised classification models. Their ability to predict PICH was quantified and compared. In this subset of subjects (n = 104), 46% (n = 48) demonstrated PICH. Univariate analyses showed no association between PICH and age, sex, admission Glasgow Coma Scale (GCS), GCS motor subscore, presence of midline shift, admission platelet count or admission INR. Radiographic severity scores (Marshall score [p = 0.007], Rotterdam score [p = 0.004]), and initial hematoma volume [p = 0.005] were associated with PICH. Higher levels of admission glial fibrillary acidic protein (p < 0.001) and MAP (p = 0.011) were also associated with PICH. Of the PCs, PC1 was significantly associated with PICH (p = 0.0125). Using multimodal data input, machine learning classifiers successfully discriminated patients with or without PICH. Models composed of machine-selected features performed better than models composed of expert-selected variables (reaching an average of 77% accuracy, AUC = 0.78 versus AUC = 0.68 for the expert-selected variables). Predictive models utilizing variables measured at admission can accurately predict PICH, confirmed by the 6-hour follow-up hCT. Our best-performing models must now be externally validated in a separate cohort of TBI patients with low GCS and initial hCT positive for hemorrhage.

The Impact of ADP Inhibition on Traumatic Brain Injury Outcomes.

Platelet inhibition correlates with severity of traumatic brain injury and may be associated with mortality. Adenosine diphosphate participates in platelet aggregation via the activation of the ADP receptors, P2Y1 and P2Y12. Prior work suggests this ADP pathway is significant in managing patients with head injuries. This study aimed to measure the influence of ADP inhibition on outcomes after a traumatic brain injury (TBI), as measured by thromboelastography with platelet mapping (TEG-PM). Outcomes were defined as (a) hospital length of stay; (b) ICU length of stay, (c) mortality, and (d) progression of hemorrhage on CT. The resulting cohort was split into quartiles to compare the effect of increasingly inhibited ADP values on the identified outcomes. Comparisons of 2 groups of patients were also conducted, one defined by ADP inhibition less than or equal to 60% and the other group by ADP inhibition of greater than 60%. 98 patients were included in final analysis, with 72.4% having ADP inhibition less than 60%. These patients were significantly older and had lower global injury severity scores (ISSs), although their head-specific ISS was equivalent. Compared to the group with ADP inhibition over 60%, there was no significant difference in mortality, hospital or ICU length of stay, or progression of lesion on CT. Patients with ADP less than 60% inhibited had smaller ISS and higher GCS, indicating they were less injured than those with greater ADP inhibition, consistent with prior literature. The equivalent ICU and hospital length of stay and mortality suggests that ADP inhibition plays a smaller role in outcomes. Additional study with a larger sample size and guideline-based assessments is necessary to further define the impact of ADP inhibition and to determine the role of platelet transfusion in this population.

Systemic immune inflammation index and system inflammation response index on the third postoperative day predict poor prognosis of aneurysmal subarachnoid hemorrhage patients.

The inflammatory response is involved in the progression of aneurysmal subarachnoid hemorrhage (aSAH). We sought to investigate the relationships of inflammatory indicators including blood cell counts and the ratios of different blood cells counts with the prognosis of aSAH patients. We performed a retrospective study including 140 patients with aSAH and aneurysm surgeries. The relationships of neutrophils, lymphocytes, monocytes, platelets, systemic immune inflammation index (SII), system inflammation response index (SIRI), neutrophil-lymphocyte ratio and platelet-lymphocyte ratio with prognosis were investigated by univariable analysis and multivariable logistic regression model. The patient with Modified Rankin Scale (mRS) score＜3 was defined as having a good prognosis, while with mRS score ≥3 was defined as having a poor prognosis. Among 140 patients included, there were 108 cases with good prognosis and 32 cases with poor prognosis after follow-up. On the 3rd postoperative day, the neutrophils counts, SIRI level and SII level in cases with poor prognosis were significantly higher than cases with good prognosis, P < .05. After adjusting for baseline differences in Hunt-Hess grade, Glasgow Coma Scale score, combination with intraventricular hemorrhage and maximum diameter of aneurysm, the levels of SIRI (odds ratio = 3.968, 95% CI: 1.432-10.992, P = .008) and SII (odds ratio = 3.313, 95% CI: 1.029-10.665, P = .045) on the 3rd postoperative day could predict poor prognosis. SII and SIRI on the 3rd postoperative day could independently predict the poor prognosis in aSAH. However, the cutoff values for predicting prognosis needs to be validated in larger-sample studies.

CSF1R blockade slows progression of cerebral hemorrhage by reducing microglial proliferation and increasing infiltration of CD8 + CD122+ T cells into the brain

Microglia play a pivotal role in the neuroinflammatory response after brain injury, and their proliferation is dependent on colony-stimulating factors. In the present study, we investigated the effect of inhibiting microglia proliferation on neurological damage post intracerebral hemorrhage (ICH) in a mouse model, an aspect that has never been studied before. Using a colony-stimulating factor-1 receptor antagonist (GW2580), we observed that inhibition of microglia proliferation significantly ameliorated neurobehavioral deficits, attenuated cerebral edema, and reduced hematoma volume after ICH. This intervention was associated with a decrease in pro-inflammatory factors in microglia and an increased infiltration of peripheral regulatory CD8 + CD122+ T cells into the injured brain tissue. The CXCR3/CXCL10 axis is the mechanism of brain homing of regulatory CD8 + CD122+ T cells, and the high expression of IL-10 is the hallmark of their synergistic anti-inflammatory effect with microglia. And activated astrocytes around the insult site are a prominent source of CXCL10. Thus, inhibition of microglial proliferation offers a new perspective for clinical translation. The cross-talk between multiple cells involved in the regulation of the inflammatory response highlights the comprehensive nature of neuroimmunomodulation.

Imaging predictors of hemorrhagic progression of a contusion after traumatic brain injury: a systematic review and meta-analysis

The hemorrhagic progression of a contusion (HPC) after Traumatic brain injury (TBI) is one of the important causes of death in trauma patients. The purpose of this meta-analysis was to evaluate the predictive effect of imaging features of Computed tomography (CT) on HPC after TBI. A comprehensive systematic search was performed using PubMed, EMBASE, and WEB OF SCIENCE databases to identify all relevant literature. A total of 8 studies involving 2543 patients were included in this meta-analysis. Meta-analysis showed that subarachnoid hemorrhage (OR 3.28; 95% CI 2.57–4.20), subdural hemorrhage (OR 4.35; 95% CI 3.29–5.75), epidural hemorrhage (OR 1.47;95% CI 1.15–1.89), contrast extravasation (OR 11.81; 95% CI 4.86–28.71) had a predictive effect on the occurrence of HPC. Skull fracture (OR 1.64; 95% CI 0.84–3.19) showed no statistical significance, and midline displacement > 5 mm (OR 4.66; 95% CI 1.87–11.62) showed high heterogeneity. The results of this meta-analysis showed that some imaging features were effective predictors of HPC after TBI. Well-designed prospective studies are needed to more accurately assess the effective predictors of HPC after TBI.

Predicting Hematoma Expansion and Prognosis in Cerebral Contusions: A Radiomics-Clinical Approach.

Hemorrhagic progression of contusion (HPC) often occurs early in cerebral contusions (CC) patients, significantly impacting their prognosis. It is vital to promptly assess HPC and predict outcomes for effective tailored interventions, thereby enhancing prognosis in CC patients. We utilized the Attention-3DUNet neural network to semi-automatically segment hematomas from computed tomography (CT) images of 452 CC patients, incorporating 695 hematomas. Subsequently, 1502 radiomic features were extracted from 358 hematomas in 261 patients. After a selection process, these features were used to calculate the radiomic signature (Radscore). The Radscore, along with clinical features such as medical history, physical examinations, laboratory results, and radiological findings, was employed to develop predictive models. For prognosis (discharge Glasgow Outcome Scale score), radiomic features of each hematoma were augmented and fused for correlation. We employed various machine learning methodologies to create both a combined model, integrating radiomics and clinical features, and a clinical-only model. Nomograms based on logistic regression were constructed to visually represent the predictive procedure, and external validation was performed on 170 patients from three additional centers. The results showed that for HPC, the combined model, incorporating hemoglobin levels, Rotterdam CT score of 3, multi-hematoma fuzzy sign, concurrent subdural hemorrhage, international normalized ratio, and Radscore, achieved area under the receiver operating characteristic curve (AUC) values of 0.848 and 0.836 in the test and external validation cohorts, respectively. The clinical model predicting prognosis, utilizing age, Abbreviated Injury Scale for the head, Glasgow Coma Scale Motor component, Glasgow Coma Scale Verbal component, albumin, and Radscore, attained AUC values of 0.846 and 0.803 in the test and external validation cohorts, respectively. Selected radiomic features indicated that irregularly shaped and highly heterogeneous hematomas increased the likelihood of HPC, while larger weighted axial lengths and lower densities of hematomas were associated with a higher risk of poor prognosis. Predictive models that combine radiomic and clinical features exhibit robust performance in forecasting HPC and the risk of poor prognosis in CC patients. Radiomic features complement clinical features in predicting HPC, although their ability to enhance the predictive accuracy of the clinical model for adverse prognosis is limited.

Ubiquitin-like 4A alleviates the progression of intracerebral hemorrhage by regulating oxidative stress and mitochondrial damage.

Acupuncture has obvious therapeutic effect on intracerebral hemorrhage (ICH). miR-34a-5p regulated by acupuncture was found to attenuate neurological deficits in ICH. However, the underlying mechanisms are unclear. Ubiquitin-like 4A (UBL4A) has not been studied in ICH. SD rats were injected with autologous blood to induce ICH and treated with Baihui-penetrating-Qubin acupuncture. Acupuncture resulted in an increase in forelimb placing test scores, and a decrease in corner test scores and brain water content of ICH rats. Histopathological examination showed that acupuncture inhibited ICH-induced inflammation, decreased damaged neurons and increased UBL4A expression. UBL4A overexpression increased cell viability, inhibited apoptosis, reduced reactive oxygen species (ROS) level and increased manganese superoxide dismutase (MnSOD) activity, mitochondrial membrane potential and mtDNA level in rat embryonic primary cortical neurons. miR-34a-5p knockdown increased UBL4A expression, apoptosis rate and ROS level in hemin-treated neurons. Dual luciferase assays showed that miR-34a-5p bound to UBL4A. Apoptotic cells and ROS level were increased in hemin-treated neurons with UBL4A and miR-34a-5p knockdown. We firstly demonstrate the inhibitory effect of UBL4A on neuronal apoptosis, and the regulation relationship between UBL4A and miR-34a-5p. This study provides a new candidate target for ICH treatment and more basis for elucidating the molecular mechanism of acupuncture. In the future, we will conduct a deeper exploration of the effects of UBL4A on ICH.

Antithrombotic and risk of hemorrhagic complications in over-60-year-olds after mild-minimal traumatic brain injury

ABSTRACT Primary objective to identify if antithombotics are risk factors for intracereral lesion in older adults with minimal-mild traumatic brain injury (m-mTBI) Research desing prospective cohort study Methods and Procedures We included 2,303 patients over 60 years arriving at our Emergency Department within 24 hours of an mTBI with a Glasgow Coma Scale (GSC) of 14–15. Data were gathered on clinical history, cranial CT scans, blood analyses. Outcomes and Results 91.1% had an admission GSC score of 15, and 23.6% developed intracranial complications. In bivariate analyses, statins were associated with a 1.28-fold lower risk of IC. Hemorrhagic progression was 29.76-fold higher in patients receiving anticoagulants, with no difference among anticoagulant types. Male sex, GSC of 14, alcohol consumption, and the presence of tumor were risk factors for IC. In multivariate analysis, GSC of 14, alcohol consumption, and malignancy emerged as risk factors for these complications, neurological disease and diabetes as protective factors. After exclusion of neurological disease and diabetes from the multivariate model, a GSC of 14 showed the highest predictive capacity. Conclusions Antithrombotics intake are not risks factor for intracranial injury in minimal-mild brain injury trauma. Further research is needed taking account of their fragility and comorbidities.

Skull Penetrating Stab Wound with Progression of Intraparenchymal Hemorrhage, A Case Report and Literature Review

Skull Penetrating Stab Wound with Progression of Intraparenchymal Hemorrhage, A Case Report and Literature Review

Systemic inflammation response index (SIRI) on the 3rd postoperative day are associated with severe pneumonia in cerebral hemorrhage patients: A single-center retrospective study.

Inflammatory response was involved in the progression of cerebral hemorrhage. We sought to explore the associations of easily obtained inflammatory indicators including blood cell counts and the ratios of different blood cells counts with pneumonia and severe pneumonia in cerebral hemorrhage patients. We carried 1 retrospective study including 200 patients with cerebral hemorrhage and surgeries. The associations of neutrophils, lymphocytes, monocytes, platelets, systemic immune inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) with pneumonia and severe pneumonia in cerebral hemorrhage patients were estimated by univariate analysis and multivariate logistic regression model. Among the 200 patients included, there were a total of 163 (81.5%) had pneumonia after surgeries. Among 163 cerebral hemorrhage patients with pneumonia, 60 (36.8%) cases were evaluated as severe pneumonia. The level of SIRI on the 1st postoperative day in patients with severe pneumonia was higher than non-severe pneumonia (10.89 ± 12.10 × 109/L vs 7.14 ± 9.76 × 109/L, P = .003). The level of SIRI on the 3rd postoperative day in patients with severe pneumonia was more significantly higher (7.98 ± 7.46 × 109/L vs 4.10 ± 3.74 × 109/L, P < .001). The results of multivariate analysis showed that SIRI level on the 3rd postoperative day (>6.5 × 109/L) was associated with severe pneumonia in cerebral hemorrhage patients (OR: 4.409, 95% CI: 1.799-10.806, P = .001). SIRI was possibly a superior predictor for severe pneumonia in cerebral hemorrhage patients compared with other inflammatory indicators. On the one hand, we intend to validate the cutoff value of SIRI for predicting severe pneumonia in larger samples and multicenter studies. On the other hand, we also intend to use this index to guide the choice of antibacterial drugs in order to better benefit patients.

Modified Brain Injury Guidelines for preinjury anticoagulation in traumatic brain injury: An opportunity to reduce health care resource utilization.

The Brain Injury Guidelines (BIG) stratify patients by traumatic brain injury (TBI) severity to provide management recommendations to reduce health care resource burden but mandates that patients on anticoagulation (AC) are allocated to the most severe tertile (BIG 3). We sought to analyze TBI patients on AC therapy using a modified BIG model to determine if this population can offer further opportunity for safe reductions in health care resource utilization. Patients 55 years or older on AC with traumatic intracranial hemorrhage (ICH) from two centers were retrospectively stratified into BIG 1 to 3 risk groups using modified BIG criteria excluding AC as a criterion. Intracranial hemorrhage progression, neurosurgical intervention (NSI), death, and worsened discharge status were compared. A total of 221 patients were included, with 23%, 29%, and 48% classified as BIG 1, BIG 2, and BIG 3, respectively. The BIG 3 cohort had a higher rate of AC reversal agents administered (66%) compared with the BIG 1 (40%) and BIG 2 (54%) cohorts ( p < 0.01), as well as ICH progression discovered on repeat head computed tomography (56% vs. 38% vs. 26%, respectively; p < 0.001). No patients in the BIG 1 and 2 cohorts required NSI. No patients in BIG 1 and 3% of patients in BIG 2 died secondary to the ICH. In the BIG 3 cohort, 16% of patients required NSI and 26% died. Brain Injury Guidelines 3 patients had 15 times the odds of mortality compared with BIG 1 patients ( p < 0.01). The AC population had higher rates of ICH progression than the BIG literature, but this did not lead to more NSI or mortality in the lower tertiles of our modified BIG protocol. If the modified BIG used the original tertile management on our population, then NS consultation may have been reduced by up to 52%. These modified criteria may be a safe opportunity for further health care resource and cost savings in the TBI population. Prognostic and Epidemiological; Level IV.

Long non-coding RNA MIR17HG impedes FOSL2-mediated transcription activation of HIC1 to maintain a pro-inflammatory phenotype of microglia during intracerebral haemorrhage.

Activation and polarization of microglia play decisive roles in the progression of intracerebral haemorrhage (ICH), and lactate exposure correlates with microglia polarization. This study explores molecules influencing lactate production and microglia phenotype alteration following ICH. A murine model of ICH was induced by intracerebral injection of collagenase. The mice experienced autonomous neurological function recovery, haematoma resolution and rapid lactate production, along with a gradual increase in angiogenesis activity, neuronal recovery and an M1-to-M2 phenotype change of microglia. Galloflavin, a lactate dehydrogenase antagonist, suppressed this phenotype change and the functional recovery in mice. FOS like 2 (FOSL2) was significantly upregulated in the brain tissues from day 7 post-ICH. Overexpression of FOSL2 induced an M1-to-M2 phenotype shift in microglia and accelerated lactate production in vivo and in haemoglobin-treated microglia in vitro. Long non-coding RNA MIR17HG impeded FOSL2-mediated transcription activation of hypermethylated in cancer 1 (HIC1). MIR17HG overexpression induced pro-inflammatory activation of microglia in mice, which was blocked by further HIC1 overexpression. Overall, this study demonstrates that MIR17HG maintains a pro-inflammatory phenotype of microglia during ICH progression by negating FOSL2-mediated transcription activation of HIC1. Specific inhibition of MIR17HG or upregulation of FOSL2 or HIC1 may favour inflammation inhibition and haematoma resolution in ICH.

FRI240 Aspirin Induced Adrenal Hemorrhage: Rare Side Effect Of A Common Medication!

Abstract Disclosure: H.A. Qadeer: None. R. Samkutty: None. V. Singh: None. Introduction: Adrenal hemorrhage is a heterogeneous disorder with various clinical presentations. Bilateral adrenal hemorrhage can result in acute adrenal insufficiency that can be fatal. With the increasing use of DOAC, cases of anticoagulation therapy induced adrenal hemorrhage have been reported. We present a rare case of unilateral adrenal hemorrhage in a patient with pre-existing adrenal myelolipoma after using Aspirin. Based on our literature search, previously only two cases of Aspirin Induced adrenal hemorrhage in a stable adrenal mass have been reported. Case Presentation: 55-year-old male with history of stable 6.2 cm right adrenal gland myelolipoma, fatty liver disease and hypertension, recent use of 2 doses 81 mg Aspirin after receiving right shoulder replacement surgery presented to emergency department with acute onset right sided flank pain, constant, radiating to the back and right upper quadrant associated with an episode of vomiting. He was hemodynamically stable. Blood work showed normal electrolytes, liver function and renal function at baseline. Hemoglobin was stable around 10g/dL. CT scan abdomen/pelvis with contrast showed increase in the size of a previously stable adrenal myelolipoma to 12.9 x 15.6 cm with mass effect upon the liver. Acute hemorrhage was suspected with the blood extending beyond the margins of the mass into the right retroperitoneal space, displacing the right kidney. On admission, aspirin was discontinued. With absence of hemodynamic instability, normal electrolytes, and normal AM cortisol level of 11.9 mcg/dL, adrenal insufficiency was ruled out. Hormonal work up for hyperfunctioning adrenal tumor was performed that ruled out pheochromocytoma, Cushing syndrome and Primary Aldosteronism. With symptomatic improvement, absence of progression of adrenal hemorrhage on repeat CT scan of the abdomen/pelvis, patient was discharged home. He received IR guided embolization of the right superior adrenal artery and middle adrenal artery in the outpatient setting. Discussion: Spontaneous adrenal gland hemorrhage is a rare event. Bilateral adrenal hemorrhage is associated with acute adrenal insufficiency that can be fatal. Major risk factors for adrenal hemorrhage include anticoagulant therapy, heparin Induced thrombocytopenia, hypercoagulable state, trauma and sever sepsis. Here we have reported a rare case of adrenal gland hemorrhage with therapeutic dose of aspirin used after orthopedic surgery. Aspirin is a very commonly used medication and high index of suspicion is required to avoid this side effect as Immediate discontinuation of the medication is necessary to prevent progression of the disease. Conclusion: Aspirin use can be associated with progression of stable benign adrenal tumors by causing spontaneous hemorrhage. A high index of clinical suspicion is required for timely recognition of this side effect. Presentation: Friday, June 16, 2023

A comprehensive approach to the prevention and treatment of massive obstetric hemorrhage

In the case of progression of obstetric haemorrhage (OH) and non-effective preventive and therapeutic measures during childbirth and after delivery, the volume of blood loss can increase and exceed &gt; 1.5% of body weight (25–30% of circulating blood volume – CBV). In such cases that we are talking about massive obstetric haemorrhage (MOH), which leads to an increase in the frequency of maternal morbidity and mortality.The objective: determine the effectiveness of various approaches to the restoration of blood loss in the cases of MOH development, which occurred to various etiological factors, with the introduction of the modern concept of damage control resuscitation (DCR) and innovative methods of surgical hemostasis.Materials and methods. During 2015–2023 years at five clinical bases of the Department of Obstetrics and Gynecology N1 of Shupyk National Healthcare University of Ukraine we analyzed 165 cases of MOH. In all MOH cases, an integrated approach was used to stop haemorrhage using both drug therapy and modern methods of surgical hemostasis in accordance with the regulatory documents of the Ukrainian Ministry of Healthcare.In main group of 59 women in labor with the MOH (2020–2023 years) an integrated approach to stop haemorrhage and restore the blood loss according to DCR concept with the priority of high-quality and rapid CBV restoration with blood products and minimization of infusion therapy was used. The comparison group consisted of 106 women in labor with MOH (2015–2019 years) and similar methods of haemorrhage termination to restore blood loss in accordance with the order N 205 of the Ukrainian Ministry of Healthcare «Obstetric haemorrhage» with the priority of rapid restoration of blood loss by crystalloids (during 2015–2019 years).Results. The mean blood loss, time till haemorrhage is stopped, and the duration of surgery in the main group were significantly lower than in the comparison group (p&lt;0.05). In the postpartum period the number of cases with severe anemia was significantly more often in the comparison group – 47.2% versus 11.9% in the main group (OR 6.6 CI 2.7–15.9; p&lt;0.01), as well as the frequency of hysterectomy – 50.9% versus 28.8% (OR 2.6 CI 1.3–5.1; p&lt;0.01).An early onset and a significantly higher rate of transfusions of fresh frozen plasma and erythrocyte mass were found in the main group – respectively 88.1% versus 38.7% in the comparison group (OR 11.7, CI: 4.8–28.4; p&lt;0.001). This resulted in a significantly lower volume of blood loss, duration of surgical intervention, and average time for haemorrhage stop in the main group compared to the comparison group (p&lt;0.05).Conclusions. The use of modern uterotonic agents (carbetocin), tranexamic acid preparations, innovative surgical technologies and early initiation of transfusion therapy with blood preparations with minimization of crystalloid infusion and according to the DCR concept for the development of MOH allows to reduce the volume of blood loss, the frequency of severe postpartum complications, and to prevent maternal morbidity and death.