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Neurological Sciences : Official... Apr 2023Spectrin Breakdown Products (SBDPs) accumulate in the brain after traumatic brain injury (TBI) and are expected to become a potentially promising biomarker of TBI. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Spectrin Breakdown Products (SBDPs) accumulate in the brain after traumatic brain injury (TBI) and are expected to become a potentially promising biomarker of TBI.
OBJECTIVE
This systematic review and meta-analysis were undertaken to evaluate the role of SBDPs in the diagnosis and prognosis of TBI.
METHODS
We systematically searched the following databases up to 31 October 2022: Ovid MEDLINE, PubMed, EMBASE, Cochrane Library, and Web of Science Database, and studies were only included if they had sufficient data on SBDP concentrations in TBI patients. We calculated the standardized mean differences (SMDs) and 95% confidence intervals (CIs) for continuous outcomes and assessed the potential publication bias by using Egger's test and funnel plots. The statistical analysis was conducted by RevMan 5.4 and Stata 17.
RESULTS
Of 1429 identified studies, 10 studies involving 417 participants were included in our systematic review and meta-analysis. The results demonstrated that serum and cerebrospinal fluid (CSF) SBDP concentrations were significantly increased in TBI compared to controls (SBDP120: SMD = 1.42, 95% CI = 0.71 ~ 2.12, P < 0.00001; SBDP145: SMD = 1.32, 95% CI = 0.78 ~ 1.86, P < 0.00001; SBDP150: SMD = 1.39, 95% CI = 0.97 ~ 1.80, P < 0.00001), and CSF SBDPs were significantly associated with poor functional outcomes (PFO) (SBDP145: SMD = 1.75, 95% CI = 1.37 ~ 2.13, P < 0.00001; SBDP150: SMD = 1.14, 95% CI = 0.75 ~ 1.52, P < 0.00001). In addition, CSF and serum SBDP145 are valuable in diagnosing TBI (AUC = 0.89, 95% CI = 0.80 ~ 0.99, P < 0.00001), and CSF SBDP145 also has diagnostic value for PFO (AUC = 0.80, 95% CI = 0.76 ~ 0.84, P < 0.00001).
CONCLUSIONS
The limited evidence supports that the SBDPs can be employed as potential biomarkers for the diagnosis and prognosis of TBI.
Topics: Humans; Brain Injuries; Spectrin; Brain Injuries, Traumatic; Brain; Biomarkers
PubMed: 36547778
DOI: 10.1007/s10072-022-06558-y -
American Journal of Medical Genetics.... Oct 2020Rare loss of function variants in DSP, which codes for the desmosomal protein desmoplakin, have been implicated in dilated and arrhythmogenic right ventricular...
Rare loss of function variants in DSP, which codes for the desmosomal protein desmoplakin, have been implicated in dilated and arrhythmogenic right ventricular cardiomyopathies. We present a family with arrhythmogenic cardiomyopathy associated with a novel missense variant in DSP (NM_004415.4): c.877G>A, p.(Glu293Lys). The phenotype is characterized by predominant involvement of the left ventricle with systolic dysfunction, fibrosis, and life-threatening arrhythmias. We performed a systematic review of literature collecting all cardiomyopathy cases with rare missense variants in DSP. We demonstrate that the distribution of missense variants across the protein domains in cardiomyopathy cases differs from that in gnomAD (p = .04), with a case enrichment of rare missense variants in the spectrin repeat domain (36/78 [46%] in cases vs. 449/1495 [30%] in gnomAD; p = .004). Our findings highlight the predominance of cardiac arrhythmia and left ventricular involvement in desmoplakin cardiomyopathy and pinpoint to a potential mutation hotspot in DSP thereby facilitating missense variant interpretation in the diagnostic setting.
Topics: Arrhythmias, Cardiac; Arrhythmogenic Right Ventricular Dysplasia; Desmoplakins; Female; Genetic Predisposition to Disease; Genetic Variation; Heart Ventricles; Humans; Male; Mutation, Missense; Phenotype
PubMed: 32808748
DOI: 10.1002/ajmg.a.61799 -
International Journal of Clinical and... 2015Outcome prediction following traumatic brain injury (TBI) is a widely investigated field of research. Several outcome prediction models have been developed for prognosis... (Review)
Review
Outcome prediction following traumatic brain injury (TBI) is a widely investigated field of research. Several outcome prediction models have been developed for prognosis after TBI. There are two main prognostic models: International Mission for Prognosis and Clinical Trials in Traumatic Brain Injury (IMPACT) prognosis calculator and the Corticosteroid Randomization after Significant Head Injury (CRASH) prognosis calculator. The prognosis model has three or four levels: (1) model A included age, motor GCS, and pupil reactivity; (2) model B included predictors from model A with CT characteristics; and (3) model C included predictors from model B with laboratory parameters. In consideration of the fact that interventions after admission, such as ICP management also have prognostic value for outcome predictions and may improve the models' performance, Yuan F et al developed another prediction model (model D) which includes ICP. With the development of molecular biology, a handful of brain injury biomarkers were reported that may improve the predictive power of prognostic models, including neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), S-100β protein, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), myelin basic protein (MBP), cleaved tau protein (C-tau), spectrin breakdown products (SBDPs), and ubiquitin C-terminal hydrolase-L1 (UCH-L1), and sex hormones. A total of 40 manuscripts reporting 11 biomarkers were identified in the literature. Many substances have been implicated as potential biomarkers for TBI; however, no single biomarker has shown the necessary sensitivity and specificity for predicting outcome. The limited number of publications in this field underscores the need for further investigation. Through fluid biomarker analysis, the advent of multi-analyte profiling technology has enabled substantial advances in the diagnosis and treatment of a variety of conditions. Application of this technology to create a bio-signature for TBI using multiple biomarkers in combination will hopefully facilitate much-needed advances. We believe that further investigations about brain injury biomarkers may improve the predictive power of the contemporary outcome calculators and prognostic models, and eventually improve the care of patients with TBI.
PubMed: 26884899
DOI: No ID Found -
CNS Neuroscience & Therapeutics Aug 2013Rapid triage and decision-making in the treatment of traumatic brain injury (TBI) present challenging dilemma in "resource poor" environments such as the battlefield and... (Review)
Review
Rapid triage and decision-making in the treatment of traumatic brain injury (TBI) present challenging dilemma in "resource poor" environments such as the battlefield and developing areas of the world. There is an urgent need for additional tools to guide treatment of TBI. The aim of this review is to establish the possible use of diagnostic TBI biomarkers in (1) identifying diffuse and focal brain injury and (2) assess their potential for determining outcome, intracranial pressure (ICP), and responses to therapy. At present, there is insufficient literature to support a role for diagnostic biomarkers in distinguishing focal and diffuse injury or for accurate determination of raised ICP. Presently, neurofilament (NF), S100β, glial fibrillary acidic protein (GFAP), and ubiquitin carboxyl terminal hydrolase-L1 (UCH-L1) seemed to have the best potential as diagnostic biomarkers for distinguishing focal and diffuse injury, whereas C-tau, neuron-specific enolase (NSE), S100β, GFAP, and spectrin breakdown products (SBDPs) appear to be candidates for ICP reflective biomarkers. With the combinations of different pathophysiology related to each biomarker, a multibiomarker analysis seems to be effective and would likely increase diagnostic accuracy. There is limited research focusing on the differential diagnostic properties of biomarkers in TBI. This fact warrants the need for greater efforts to innovate sensitive and reliable biomarkers. We advocate awareness and inclusion of the differentiation of injury type and ICP elevation in further studies with brain injury biomarkers.
Topics: Animals; Biomarkers; Brain Injuries; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Humans; Phosphopyruvate Hydratase; S100 Calcium Binding Protein beta Subunit; Spectrin; Ubiquitin Thiolesterase; tau Proteins
PubMed: 23710877
DOI: 10.1111/cns.12127