| کلیدواژههای انگلیسی مقاله |
Serum, Brain injuries, Traumatic, Biomarker, What&,rsquo s Known After a traumatic brain injury (TBI), in addition to clinical indices, the serum level of neurological biomarkers may provide valuable diagnostic and prognostic information. Current studies on neurological biomarkers have mainly focused on severe TBI. Serum aldolase C (ALDOC) level is shown to increase in less than an hour after TBI in mice. What&,rsquo s New The diagnostic value of ALDOC for early detection of brain damage in patients with mild TBI (mTBI) is investigated. The median ALDOC serum level in the patients with positive CT scan findings was significantly higher than those with negative CT scan findings. IntroductionTraumatic brain injury (TBI) is caused by traumatic events that either damage the structure of the brain or disrupt its physiological function. 1, TBI occurs in 69 million (95% CI, 64-74 million) people worldwide annually. 2, Its severity is classified into mild, moderate, and severe categories based primarily on the patient&,rsquo s level of consciousness in the first 24 hours after head injury. 3, Mild TBI (mTBI) is the most common form of TBI that occurs in the age group 16-59 years with an overall incidence of 302 per 100,000 person-years (95% confidence interval 281-324). The incidence rate in the age group 16-20 years is 835 per 100,000 person-years in men and 726 in women. 4, TBI evaluation is made based on neurological imaging findings, such as a computed tomography scan (CT scan). CT scan has a low sensitivity for mTBI and exposes patients to significant radiation doses. 5, Given that a million people are admitted annually to the emergency department (ED) and discharged without hospitalization, using imaging studies to rule out brain pathologies in patients with TBI increases unnecessary procedures and medical care for both the patient and the medical center. 5, Currently, researchers are investigating mTBI at cellular and molecular levels, since brain imaging findings can be used for diagnosis and peripheral blood samples for predicting brain damage. Identifying a marker for early diagnosis of brain injury is of particular interest. 6, In contrast with cardiac events, patients admitted to ED with mTBI do not demonstrate any immediately appreciable clinical symptoms, and the clinical use of blood biomarkers is therefore not common to facilitate rapid diagnosis and treatment of mTBI. 7, In recent years, however, neuro-biomarker studies have mainly focused on severe TBI. Since more than 80% of TBIs are mTBI, it is essential to find a fast and reliable biomarker test that will allow ED physicians to diagnose this group of patients. 8, Among several recent studies on glial cells and neuronal biomarkers, the most widely studied biomarkers are S100B, glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCHL1). 9, However, these biomarkers were shown to have delayed appearance in serum after brain injury. Astrocytic biomarkers such as aldolase C (ALDOC), brain lipid-binding protein (BLBP), and phosphoprotein enriched in astrocytes 15 (PEA15) are new promising biomarkers that have been shown to appear in serum in less than one hour after brain injury. 10, ALDOC, unique in both astrocyte enrichment and abundance amongst proteins of the brain, is an astroglial injury-associated protein that can potentially be used to predict brain injury. 11, Brain injury causes astroglial protein depletion and disassembly in wounded and dying cell populations. According to several animal model studies, ALDOC is strongly associated with cell wounding and cell death. 11, The present study aimed to investigate ALDOC profiling in serum for the early diagnosis of brain damage in patients with mTBI presented to our ED. Materials and MethodsA single-center prospective cohort study was conducted in 2018-2019 at Imam Khomeini Hospital affiliated with Mazandaran University of Medical Sciences, Sari, Iran. The study was approved by the Clinical Research Development Unit of the hospital as well as the Ethics Committee of the University (code, IR.MAZUMS.IMAMHOSPITAL.REC.1397.002). Written informed consent was obtained from all the participants or their parents/legal guardians in case of an acute medical condition.A total of 89 patients with mTBI were enrolled in the study, and their data were analyzed. A brain CT scan is considered the gold standard for the diagnosis of mTBI. Inclusion criteria were TBI during the last 24 hours, a Glasgow coma scale (GSC) score of 13-15, and presentation of one or more of the following symptoms, post-traumatic loss of consciousness less than 30 minutes, amnesia immediately before and/or after trauma lasting less than 24 hours, temporary or permanent focal neurologic signs and symptoms, nausea, and vomiting. Exclusion criteria were age &,lt 18 years, pregnancy, spinal cord injury, and a history of psychosis, neurological disorders, and cancer. A checklist was completed by the emergency medicine resident within the first three hours of a traumatic event. The list included information such as demographic characteristics of the patient, the cause of injury (vehicle crash, fall, heavy object), injury-associated symptoms (dizziness, nausea and vomiting, headache, tinnitus, pre-and/or post-traumatic amnesia), level of consciousness based on the GSC, and duration of the incident (in minutes). Upon admission, 10 cc venous blood samples were taken from the patients to examine biomarker levels. Bearing a trauma event in mind, a brain CT scan was immediately done. According to the clinical practice guidelines, a clinical neuro-radiologist blinded to the experiment performed all radiologic studies. The CT scan findings were also confirmed by an emergency medicine specialist and a neurosurgeon. Blood samples were transferred to the hospital laboratory in accordance with the blood cold chain system. After centrifugation and serum separation, ALDOC measurement was performed using an automated biochemistry analyzer (Stat Fax-2000, USA) and ALDOC ELISA kit (96T) (Zellbio, Germany). ALDOC assay was performed based on a double antibody sandwich method using the avidin-biotin system. The wells of the ELISA plate were percolated with an anti-ALDOC monoclonal antibody. The biotin-labeled ALDOC antibodies were mixed with streptavidin-HRP (assay range, 0.75-24 ng/mL, sensitivity, 0.02 ng/mL). The optical density (OD) values were used to plot the standard curve using point-to-point calculation mode. Statistical Analysis Data were analyzed using IBM SPSS software, version 25.0. Data distribution was examined using the Kolmogorov-Smirnov test. Quantitative and qualitative data were expressed as median (interquartile range [IQR]) and frequency (percentage), respectively. The Kruskal-Wallis, Mann-Whitney U, and Chi squared tests (or Fisher&,rsquo s exact test) were used for statistical analysis. The receiver-operating characteristic (ROC) curve plot was used to determine the optimal cutoff point for ALDOC and its predictive accuracy for positive CT scan findings. A 2&,times 2 table was drawn to calculate the sensitivity and specificity of the determined cutoff point. P values less than 0.05 were considered statistically significant. ResultsA total of 100 patients suffering from head trauma with the primary diagnosis of mTBI were enrolled in the study. Based on the exclusion criteria, nine patients were excluded from the study because of spinal cord injury (n=3), pregnancy (n=3), psychosis (n=1), and unavailability due to imprisonment (n=2). A further two patients refused to undergo the imaging study and were thus excluded. Of the remaining 89 patients, 30 (33.7%) had positive CT scan findings, and 59 (66.3%) had negative brain CT scan findings for TBI. Demographic characteristics of the patients and the cause of injury are shown in table 1,. GCS scores were significantly lower in the mTBI patients with positive than negative brain CT scan findings (P&,lt 0.001). A comparison between clinical features with CT scan findings is shown in table 2,. Nausea was the most common symptom of mTBI patients with positive CT scan findings (73.3%).VariablePositive CT scan (n=30)Negative CT scan (n=59)P valueAge (years)Median (IQR)35.5 (32.5)32 (15)0.430*,SexMale (n, %)26 (86.7)42 (71.2)0.080**,Female (n, %)4 (13.3)17 (28.8)The cause of injury Motor vehicle accident (n, %)25 (83.3)55 (93.2)0.050**,Fall (n, %)5 (16.7)2 (3.4)Struck by heavy object (n, %)0 (0)2 (3.4)Time to admission (minute)Median (IQR)30 (15)30 (10)0.830*,GCSMedian (IQR)14 (0)15 (0)&,lt 0.001*,*Mann-Whitney U test **Chi squared test P&,lt 0.05 is considered statistically significant GCS, Glasgow coma scale IQR, Interquartile range CT, Computed tomography |
| نویسندگان مقاله |
Kaveh Haddadi |
Department of Neurosurgery, School of Medicine, Orthopedic Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Siavash Moradi |
Education Development Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Leila Asadian |
Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
Seyed Hosein Montazer |
Department of Emergency Medicine, School of Medicine, Orthopedic Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Seyed Mohammad Hosseininejad |
Department of Emergency Medicine, School of Medicine, Diabetes Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Iraj Golikhatir |
Department of Emergency Medicine, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Saeid Abedian Kenari |
Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Abdulrassol Alaee |
Department of Radiology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Farzad Bozorgi |
Department of Emergency Medicine, School of Medicine, Orthopedic Research Center, Mazandaran University of Medical Sciences, Sari, Iran
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