Temporal Acute Serum Estradiol and Tumor Necrosis Factor-α Associations and Risk of Death after Severe Traumatic Brain Injury.
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SUBMITTER: Kumar RG
PROVIDER: S-EPMC7580589 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AbstractEstradiol regulates spermatogenesis partly via estrogen receptor-alpha (ESRα). This study aimed to analyze the associations of serum estradiol level, serum ESRα level, and ESRα gene polymorphisms with sperm quality.This retrospective study included infertile men attending the Reproductive Center, Affiliated Hospital of Youjiang Medical University for Nationalities, and a control group without a history of fertility (October, 2016 to March, 2017). Data regarding sperm quality, serum levels of estradiol and ESRα, and rs2234693C/T genotype were extracted from the medical records. Pearson/Spearman correlations (as appropriate) between estradiol level, ESRα level, and sperm quality parameters were evaluated.The analysis included 215 men with infertility and 83 healthy controls. The infertile group had higher serum levels of estradiol (147.57 ± 35.3 vs 129.62 ± 49.11 pg/mL, P < .05) and ESRα (3.02 ± 2.62 vs 1.33 ± 0.56 pg/mL, P < .05) than the control group. For the infertile group, serum estradiol level was negatively correlated with sperm concentration, percentage of progressively motile sperm, and percentage of sperm with normal morphology (r = 0.309, 0.211, and 0.246, respectively; all P < .05). Serum estradiol and ESRα levels were lower in infertile men with normozoospermia than in those with azoospermia, oligozoospermia, mild azoospermia, or malformed spermatozoa (all P < .05). Sperm concentration, percentage of progressively motile sperm, serum ESRα level, and serum estradiol level did not differ significantly among the rs2234693 CC, CT, and TT genotypes.Elevated serum levels of estradiol and possibly ESRα might have a negative impact on sperm quality and fertility, whereas single nucleotide polymorphisms at rs2234693 of the ESRα gene had little or no effect.
| S-EPMC8294872 | biostudies-literature
Project description:Severe traumatic brain injury continues to present complex management and prediction challenges for the clinician. While there is some evidence that better systems of care can improve outcome, multiple multi-centre randomised controlled trials of specific therapies have consistently failed to show benefit. In addition, clinicians are challenged in attempting to accurately predict which children will recover well and which children will have severe and persisting neurocognitive deficits. Traumatic brain injury is vastly heterogeneous and so it is not surprising that one therapy or approach, when applied to a mixed cohort of children in a clinical trial setting, has yielded disappointing results. Children with severe traumatic brain injury have vastly different brain injury pathologies of widely varying severity, in any number of anatomical locations at what may be disparate stages of brain development. This heterogeneity may also explain why clinicians are unable to accurately predict outcome. Biomarkers are objective molecular signatures of injury that are released following traumatic brain injury and may represent a way of unifying the heterogeneity of traumatic brain injury into a single biosignature. Biomarkers hold promise to diagnose brain injury severity, guide intervention selection for clinical trials, or provide vital prognostic information so that early intervention and rehabilitation can be planned much earlier in the course of a child's recovery. Serum S100B and serum NSE levels show promise as a diagnostic tool with biomarker levels significantly higher in children with severe TBI including children with inflicted and non-inflicted head injury. Serum S100B and serum NSE also show promise as a predictor of neurodevelopmental outcome. The role of biomarkers in traumatic brain injury is an evolving field with the potential for clinical application within the next few years.
| S-EPMC8578762 | biostudies-literature
Project description:Early declines in gonadotropin production, despite elevated serum estradiol, among some individuals with severe traumatic brain injury (TBI) suggests amplified systemic aromatization occurs post-injury. Our previous work identifies estradiol (E2) as a potent mortality marker. Androstenedione (A), a metabolic precursor to E2, estrone (E1), and testosterone (T), is a steroid hormone substrate for aromatization that has not been explored previously as a biomarker in TBI. Here, we evaluated serum A, E1, T, and E2 values for 82 subjects with severe TBI. Daily hormone values were calculated, and E2:A and E1:T ratios were generated and then averaged for days 0-3 post-injury. After data inspection, mean E2:A values were categorized as above (high aromatization) and below (low aromatization) the 50th percentile for 30-day mortality assessment using Kaplan-Meier survival analysis and a multivariable Cox proportional hazard model adjusting for age, and Glasgow Coma Scale (GCS) to predict 30-day mortality status. Daily serum T, E1, and E2 were graphed by E2:A category. Serum E1 and E2 significantly differed over time (p?<?0.05); the high aromatization group had elevated levels and a significantly lower probability of survival within the first 30 days (p?=?0.0274). Multivariable Cox regression showed a significant E2:A*GCS interaction (p?=?0.0129), wherein GCS predicted mortality only among those in the low aromatization group. E2:A may be a useful mortality biomarker representing enhanced aromatization after TBI. E2:A ratios may represent non-neurological organ dysfunction after TBI and may be useful in defining injury subgroups in which GCS has variable capacity to serve as an accurate early prognostic marker.
| S-EPMC6354608 | biostudies-literature
Project description:BackgroundCognitive impairments commonly occur after traumatic brain injury (TBI) and affect daily functioning. Cortisol levels, which are elevated during acute hospitalization for most individuals after severe TBI, can influence cognition, but this association has not been studied previously in TBI.ObjectiveWe hypothesized that serum and cerebral spinal fluid (CSF) cortisol trajectories over days 0-5 post-injury are associated with cognition 6-month post-injury.MethodsWe examined 94 participants with severe TBI, collected acute serum and/or CSF samples over days 0-5 post-injury, and compared cortisol levels to those in 17 healthy controls. N = 88 participants had serum, and n = 84 had CSF samples available for cortisol measurement and had neuropsychological testing 6 months post-injury. Group based trajectory analysis (TRAJ) was used to generate temporal serum and CSF cortisol profiles which were examined for associations with neuropsychological performance. We used linear regression to examine relationships between cortisol TRAJ groups and both overall and domain-specific cognition.ResultsTRAJ analysis identified a high group and a decliner group for serum and a high group and low group for CSF cortisol. Multivariable analysis showed serum cortisol TRAJ group was associated with overall cognitive composites scores (P = .024) and with executive function (P = .039) and verbal fluency (P = .029) domain scores. CSF cortisol TRAJ group was associated with overall cognitive composite scores (P = .021) and domain scores for executive function (P = .041), verbal fluency (P = .031), and attention (P = .034).ConclusionsHigh acute cortisol trajectories are associated with poorer cognition 6 months post-TBI.
| S-EPMC8688285 | biostudies-literature
Project description:ObjectivesThe microbiome may be affected by trauma and critical illness. Many studies of the microbiome in critical illness are restricted to a single body site or time point and confounded by preexisting conditions. We report temporal and spatial alterations in the microbiome of previously healthy children with severe traumatic brain injury (TBI).DesignWe collected oral, rectal, and skin swabs within 72 hours of admission and then twice weekly until ICU discharge. Samples were analyzed by 16S rRNA gene amplicon sequencing. Children undergoing elective outpatient surgery served as controls. Alpha and beta diversity comparisons were performed with Phyloseq, and differentially abundant taxa were predicted using Analysis of Composition of Microbiomes.SettingFive quaternary-care PICUs.PatientsPatients less than 18 years with severe TBI requiring placement of an intracranial pressure monitor.InterventionsNone.Measurements and main resultsThree hundred twenty-seven samples were analyzed from 23 children with severe TBI and 35 controls. The community composition of initial oral (F = 3.2756, R2 = 0.0535, p = 0.012) and rectal (F = 3.0702, R2 = 0.0649, p = 0.007) samples differed between TBI and control patients. Rectal samples were depleted of commensal bacteria from Ruminococcaceae, Bacteroidaceae, and Lachnospiraceae families and enriched in Staphylococcaceae after TBI (p < 0.05). In exploratory analyses, antibiotic exposure, presence of an endotracheal tube, and occurrence of an infection were associated with greater differences of the rectal and oral microbiomes between TBI patients and healthy controls, whereas enteral nutrition was associated with smaller differences (p < 0.05).ConclusionsThe microbiome of children with severe TBI is characterized by early depletion of commensal bacteria, loss of site specificity, and an enrichment of potential pathogens. Additional studies are needed to determine the impact of these changes on clinical outcomes.
| S-EPMC9203870 | biostudies-literature
Project description:The pathophysiology of traumatic brain injury (TBI) requires further characterization to fully elucidate changes in molecular pathways. Cerebrospinal fluid (CSF) provides a rich repository of brain-associated proteins that may be affected by TBI. Here, we implemented high-resolution mass spectrometry to evaluate changes to the CSF proteome after severe TBI. 91 CSF samples were analyzed with mass spectrometry, collected from 16 patients with severe TBI (mean 32 yrs; 81% male) on day 0, 1, 2, 4, 7 and/or 10 post-injury (8-16 samples/timepoint) and compared to CSF obtained from 11 non-injured controls. We quantified 1152 proteins with mass spectrometry, of which approximately 80% were associated with CSF. 1083 proteins were differentially regulated after TBI compared to control samples. The most highly-upregulated proteins at each timepoint included neutrophil elastase, myeloperoxidase, cathepsin G, matrix metalloproteinase-8, and S100 calcium-binding proteins A8, A9 and A12—all proteins involved in neutrophil activation, recruitment, and degranulation. Pathway enrichment analysis confirmed the robust upregulation of proteins associated with innate immune responses. Conversely, downregulated pathways included those involved in nervous system development, and several proteins not previously identified after TBI such as testican-1 and latrophilin-1. We also identified 7 proteins (GM2A, Calsyntenin 1, FAT2, GANAB, Lumican, NPTX1, SFRP2) positively associated with an unfavorable outcome at 6 months post-injury. These findings highlight the robust innate immune response that occurs after severe TBI, supporting future studies to target neutrophil-related processes. In addition, the novel proteins we identified to be differentially regulated by severe TBI warrant further investigation as potential biomarkers or therapeutic targets.
2023-03-11 | PXD035289 | Pride
Project description:There has been little change in morbidity and mortality in traumatic brain injury (TBI) in the last 25 years. However, literature has emerged linking impaired cerebrovascular reactivity (a surrogate of cerebral autoregulation) with poor outcomes post-injury. Thus, cerebrovascular reactivity (derived through the pressure reactivity index; PRx) is emerging as an important continuous measure. Furthermore, recent literature indicates that autonomic dysfunction may drive impaired cerebrovascular reactivity in moderate/severe TBI. Thus, to improve our understanding of this association, we assessed the physiological relationship between PRx and the autonomic variables of heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) using time-series statistical methodologies. These methodologies include vector autoregressive integrative moving average (VARIMA) impulse response function analysis, Granger causality, and hierarchical clustering. Granger causality testing displayed inconclusive results, where PRx and the autonomic variables had varying bidirectional relationships. Evaluating the temporal profile of the impulse response function plots demonstrated that the autonomic variables of BRS, ratio of low/high frequency of HRV and very low frequency HRV all had a strong relation to PRx, indicating that the sympathetic autonomic response may be more closely linked to cerebrovascular reactivity, then other variables. Finally, BRS was consistently associated with PRx, possibly demonstrating a deeper relationship to PRx than other autonomic measures. Taken together, cerebrovascular reactivity and autonomic response are interlinked, with a bidirectional impact between cerebrovascular reactivity and circulatory autonomics. However, this work is exploratory and preliminary, with further study required to extract and confirm any underlying relationships.
| S-EPMC10013014 | biostudies-literature
Project description:Brain injury exosomal proteins are promising blood biomarker candidates in traumatic brain injury (TBI). A better understanding of their role in the diagnosis, characterization, and management of TBI is essential for upcoming clinical implementation. In the current investigation, we aimed to explore longitudinal trajectories of brain injury exosomal proteins in blood of patients with moderate-to-severe TBI, and to evaluate the relation with the free-circulating counterpart and patient imaging and clinical parameters. Exosomal levels of glial (glial fibrillary acidic protein (GFAP)) and neuronal/axonal (ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NFL), and total-tau (t-tau)) proteins were measured in serum of 21 patients for up 5 days after injury using single molecule array (Simoa) technology. Group-based trajectory analysis was used to generate distinct temporal exosomal biomarker profiles. We found altered profiles of serum brain injury exosomal proteins following injury. The dynamics and levels of exosomal and related free-circulating markers, although correlated, showed differences. Patients with diffuse injury displayed higher acute exosomal NFL and GFAP concentrations in serum than those with focal lesions. Exosomal UCH-L1 profile characterized by acutely elevated values and a secondary steep rise was associated with early mortality (n = 2) with a sensitivity and specificity of 100%. Serum brain injury exosomal proteins yielded important diagnostic and prognostic information and represent a novel means to unveil underlying pathophysiology in patients with moderate-to-severe TBI. Our findings support their utility as potential tools to improve patient phenotyping in clinical practice and therapeutic trials.
| S-EPMC7227241 | biostudies-literature
Project description:Summary Background Glycans play essential functional roles in the nervous system and their pathobiological relevance has become increasingly recognized in numerous brain disorders, but not fully explored in traumatic brain injury (TBI). We investigated longitudinal glycome patterns in patients with moderate to severe TBI (Glasgow Coma Scale [GCS] score ≤12) to characterize glyco-biomarker signatures and their relation to clinical features and long-term outcome. Methods This prospective single-center observational study included 51 adult patients with TBI (GCS ≤12) admitted to the neurosurgical unit of the University Hospital of Pecs, Pecs, Hungary, between June 2018 and April 2019. We used a high-throughput liquid chromatography–tandem mass spectrometry platform to assess serum levels of N-glycans up to 3 days after injury. Outcome was assessed using the Glasgow Outcome Scale-Extended (GOS-E) at 12 months post-injury. Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, were used to analyze glycomics data and define highly influential structures driving class distinction. Receiver operating characteristic analyses were used to determine prognostic accuracy. Findings We identified 94 N-glycans encompassing all typical structural types, including oligomannose, hybrid, and complex-type entities. Levels of high mannose, hybrid and sialylated structures were temporally altered (p<0·05). Four influential glycans were identified. Two brain-specific structures, HexNAc5Hex3DeoxyHex0NeuAc0 and HexNAc5Hex4DeoxyHex0NeuAc1, were substantially increased early after injury in patients with unfavorable outcome (GOS-E≤4) (area under the curve [AUC]=0·75 [95%CI 0·59-0·90] and AUC=0·71 [0·52-0·89], respectively). Serum levels of HexNAc7Hex7DeoxyHex1NeuAc2 and HexNAc8Hex6DeoxyHex0NeuAc0 were persistently increased in patients with favorable outcome, but undetectable in those with unfavorable outcome. Levels of HexNAc5Hex4DeoxyHex0NeuAc1 were acutely elevated in patients with mass lesions and in those requiring decompressive craniectomy. Interpretation In spite of the exploratory nature of the study and the relatively small number of patients, our results provide to the best of our knowledge initial evidence supporting the utility of glycomics approaches for biomarker discovery and patient phenotyping in TBI. Further larger multicenter studies will be required to validate our findings and to determine their pathobiological value and potential applications in practice. Funding This work was funded by the Italian Ministry of Health (grant number GR-2013-02354960), and also partially supported by a NIH grant (1R01GM112490-08).
| S-EPMC9218141 | biostudies-literature
Project description:BackgroundLactate is used to evaluate the prognosis of adult patients with trauma. However, the prognostic significance of admission serum lactate in the setting of pediatric traumatic brain injury (TBI) is still unclear. We aim to investigate the impact of admission lactate on the outcome in children with moderate to severe TBI.MethodsThis retrospective study was conducted in a tertiary pediatric hospital between May 2012 and Jun 2018 included children with an admission Glasgow Coma Scale (GCS) of ≤13. Two hundred and thirteen patients were included in the analysis and 45 patients died in hospital.ResultsAdmission lactate and glucose were significantly higher in non-survivors than those in survivors (P < 0.05). Admission lactate was positively correlated with admission glucose and negatively correlated with GCS in all patients (n = 213), subgroup of isolated TBI (n = 112) and subgroup of GCS ≤ 8 (n = 133), respectively. AUCs of lactate could significantly predict the mortality and were higher than those of glucose in all patients, subgroup of isolated TBI and subgroup of GCS ≤ 8, respectively. Multivariate logistic regression showed that admission lactate (Adjusted OR = 1.189; 95% CI: 1.002-1.410; P = 0.047) was independently associated with mortality, while admission glucose (Adjusted OR = 1.077; 95% CI: 0.978-1.186; P = 0.133) wasn't an independent risk factor of death. Elevated admission lactate (> 2 mmol/L) was associated with death, reduced 14-day ventilation-free days, 14-day ICU-free days and 28-day hospital-free days.ConclusionsAdmission serum lactate can effectively predict the mortality of children with moderate to severe TBI. Elevated admission lactate is associated with death, reduced ventilator-free, ICU-free, and hospital-free days. Admission serum lactate could be used as a prognostic biomarker of mortality in children with moderate to severe TBI.
| S-EPMC6752785 | biostudies-literature