Vitamin D status is associated with hepcidin and hemoglobin concentrations in patients with severe traumatic injury.
Ontology highlight
ABSTRACT: Background
Severe traumatic injury leads to persistent injury-associated anemia that is associated with hypercatecholaminemia, systemic inflammation, increased hepcidin, and a functional iron deficiency. Vitamin D has been shown to reduce proinflammatory cytokines and hepcidin concentrations. This study aimed to investigate the association of vitamin D status with inflammation, iron biomarkers, and anemia following blunt trauma.Methods
A prospective observational cohort study comparing blunt trauma patients (n = 45) with elective hip replacement patients (n = 22) and healthy controls (n = 8) was performed. Bone marrow ferroportin, transferrin receptor, and erythroferrone expression was measured using quantitative polymerase chain reaction (qPCR). Plasma was assessed for systemic inflammation, erythropoietin (EPO), iron regulation, and vitamin D (25-OH) concentrations using enzyme-linked immunosorbent assay. Hemoglobin was measured on the day of discharge.Results
Compared with hip replacement, trauma patients had higher plasma interleukin-6 (90.1 vs. 3.8 pg/mL), C-reactive protein (6,223 vs. 2,612 ng/mL), and hepcidin (79.3 vs. 21.2 ng/mL) concentrations. Trauma patients had lower vitamin D (25-OH) (12.8 vs. 18.1 ng/mL) and iron (23.5 vs. 59.9 μg/mL) levels compared with hip replacement patients. Despite the higher hepcidin EPO levels, bone marrow erythroferrone expression was increased 69% following trauma.Conclusion
Following elective hip replacement, patients did have anemia and impaired iron homeostasis without a significant change in inflammatory biomarkers, EPO, and vitamin D status. Vitamin D status did correlate with systemic inflammation, iron dysfunction, and persistent injury-associated anemia following severe blunt trauma. Further research is needed to determine whether supplementation with vitamin D in the trauma population could improve the persistent injury-associated anemia.Level of evidence
Prospective study, prognostic, level III.
SUBMITTER: Apple CG
PROVIDER: S-EPMC7731614 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BACKGROUND:Anemia, iron deficiency, and hypovitaminosis D are well-known comorbidities in inflammatory bowel disease (IBD). Epidemiologic studies have linked vitamin D deficiency with increased risk of anemia, and in vitro studies suggest that vitamin D may improve iron recycling through downregulatory effects on hepcidin and proinflammatory cytokines. METHODS:We aimed to investigate the association of vitamin D status with inflammation, iron biomarkers, and anemia in pediatric IBD. Cross-sectional data were obtained from N = 69 patients with IBD aged 5 to <19 years. Iron biomarkers (ferritin, soluble transferrin receptor), and 25-hydroxyvitamin D (25(OH)D), inflammatory biomarkers (C-reactive protein and ?-1-acid glycoprotein), hepcidin, and hemoglobin were collected. Iron biomarkers were regression corrected for inflammation. Multivariable logistic/linear models were used to examine the associations of 25(OH)D with inflammation, iron status, hepcidin, and anemia. RESULTS:Approximately 50% of subjects were inflamed (C-reactive protein >5 mg/L or ?-1-acid glycoprotein >1 g/L). Iron deficiency prevalence (inflammation-corrected ferritin <15 ?g/L or soluble transferrin receptor >8.3 mg/L) was 67%; anemia was 36%, and vitamin D insufficiency (25(OH)D <30 ng/mL) was 77%. In linear regression models, vitamin D insufficiency was associated with increased hepcidin levels (? [SE] = 0.6 [0.2], P = 0.01) and reduced hemoglobin (? [SE] = -0.9 [0.5], P = 0.046), controlling for age, sex, race, insurance status, body mass index for age, inflammation, disease diagnosis (ulcerative colitis versus Crohn's disease), and disease duration, compared with 25(OH)D ?30 ng/mL. CONCLUSIONS:Our results suggest that concentrations of 25(OH)D ?30 ng/mL are associated with lower hepcidin and higher hemoglobin levels. Further research is needed to clarify the association of vitamin D with inflammation, iron status, and anemia in pediatric IBD.
| S-EPMC5716347 | biostudies-literature
Project description:OBJECT There is limited literature available to guide transfusion practices for patients with severe traumatic brain injury (TBI). Recent studies have shown that maintaining a higher hemoglobin threshold after severe TBI offers no clinical benefit. The present study aimed to determine if a higher transfusion threshold was independently associated with an increased risk of progressive hemorrhagic injury (PHI), thereby contributing to higher rates of morbidity and mortality. METHODS The authors performed a secondary analysis of data obtained from a recently performed randomized clinical trial studying the effects of erythropoietin and blood transfusions on neurological recovery after severe TBI. Assigned hemoglobin thresholds (10 g/dl vs 7 g/dl) were maintained with packed red blood cell transfusions during the acute phase after injury. PHI was defined as the presence of new or enlarging intracranial hematomas on CT as long as 10 days after injury. A severe PHI was defined as an event that required an escalation of medical management or surgical intervention. Clinical and imaging parameters and transfusion thresholds were used in a multivariate Cox regression analysis to identify independent risk factors for PHI. RESULTS Among 200 patients enrolled in the trial, PHI was detected in 61 patients (30.5%). The majority of patients with PHI had a new, delayed contusion (n = 29) or an increase in contusion size (n = 15). The mean time interval between injury and identification of PHI was 17.2 ± 15.8 hours. The adjusted risk of severe PHI was 2.3 times higher for patients with a transfusion threshold of 10 g/dl (95% confidence interval 1.1-4.7; p = 0.02). Diffuse brain injury was associated with a lower risk of PHI events, whereas higher initial intracranial pressure increased the risk of PHI (p < 0.001). PHI was associated with a longer median length of stay in the intensive care unit (18.3 vs 14.4 days, respectively; p = 0.04) and poorer Glasgow Outcome Scale scores (42.9% vs 25.5%, respectively; p = 0.02) at 6 months. CONCLUSIONS A higher transfusion threshold of 10 g/dl after severe TBI increased the risk of severe PHI events. These results indicate the potential adverse effect of using a higher hemoglobin transfusion threshold after severe TBI.
| S-EPMC5065393 | biostudies-literature
Project description:The optimal management of severe traumatic brain injury (TBI) in the pediatric population has not been well studied. There are a limited number of research articles studying the management of TBI in children. Given the prevalence of severe TBI in the pediatric population, it is crucial to develop a reference TBI management plan for this vulnerable population. In this review, we seek to delineate the differences between severe TBI management in adults and children. Additionally, we also discuss the known molecular pathogenesis of TBI. A better understanding of the pathophysiology of TBI will inform clinical management and development of therapeutics. Finally, we propose a clinical algorithm for the management and treatment of severe TBI in children using published data.
| S-EPMC9263560 | biostudies-literature
Project description:BACKGROUND: Hypernatremia is common following traumatic brain injury (TBI) and occurs from a variety of mechanisms, including hyperosmotic fluids, limitation of free water, or diabetes insipidus. The purpose of this systematic review was to assess the relationship between hypernatremia and mortality in patients with TBI. METHODS: We searched the following databases up to November 2012: MEDLINE, EMBASE, and CENTRAL. Using a combination of MeSH and text terms, we developed search filters for the concepts of hypernatremia and TBI and included studies that met the following criteria: (1) compared hypernatremia to normonatremia, (2) adult patients with TBI, (3) presented adjusted outcomes for mortality or complications. RESULTS: Bibliographic and conference search yielded 1,152 citations and 11 abstracts, respectively. Sixty-five articles were selected for full-text review with 5 being included in our study. All were retrospective cohort studies totaling 5,594 (range 100-4,296) patients. There was marked between-study heterogeneity. The incidence of hypernatremia ranged between 16% and 40%. Use of hyperosmolar therapy was presented in three studies (range 14-85% of patients). Hypernatremia was associated with increased mortality across all four studies that presented this outcome. Only one study considered diabetes insipidus (DI) in their analysis where hypernatremia was associated with increased mortality in patients who did not receive DDAVP. CONCLUSIONS: Although hypernatremia was associated with increased mortality in the included studies, there was marked between-study heterogeneity. DI was a potential confounder in several studies. Considering these limitations, the clinical significance of hypernatremia in TBI is difficult to establish at this stage.
| S-EPMC3826846 | biostudies-other
Project description:Diagnostic and prognostic biomarkers of traumatic brain injury (TBI) are actively being pursued; potential candidates include glial fibrillary acid protein (GFAP), S100 calcium-binding protein B (S100B), and ubiquitin C-terminal hydrolase L1 (UCHL1), two of which the United States Food and Drug Administration (FDA) recently approved for marketing of blood tests for adult concussion. The relationship between biomarker-encoding genes and TBI outcomes remains unknown. This pilot study explores variation in 18 single nucleotide polymorphisms (SNPs) in biomarker-encoding genes as predictors of neurological outcome in a population of adults with severe TBI. Participants (n = 305) were assessed using the Glasgow Outcome Scale (GOS) at 3, 6, 12, and 24 months post-injury. Multivariate logistical regression was used to calculate the odds ratio (OR) and determine the odds of having a lower score on the GOS ( = 1-2 vs. 3-5) based on variant allele presence, while controlling for confounders. Possession of the variant allele of one S100B SNP (rs1051169) was associated with higher scores on the GOS at 3 months (OR = 0.39; p = 0.04), 6 months (OR = 0.34; p = 0.02), 12 months (OR = 0.32; p = 0.02), and 24 months (OR = 0.30; p = 0.02) post-severe TBI. The relationship among these polymorphisms, protein levels, and biomarker utility, merits examination. These findings represent a novel contribution to the evidence that can inform future studies aimed at enhancing interpretation of biomarker data, identifying novel biomarkers, and ultimately harnessing this information to improve clinical outcomes and personalize care.
| S-EPMC6238603 | biostudies-literature
Project description:BackgroundThe optimal hemoglobin (Hb) threshold at which to initiate red blood cell (RBC) transfusion in patients with acute brain injury is unknown. The aim of this survey was to investigate RBC transfusion practices used with these patients.MethodsWe conducted a web-based survey within various societies of critical care medicine for intensive care unit (ICU) physicians who currently manage patients with primary acute brain injury.ResultsA total of 868 responses were obtained from around the world, half of which (n = 485) were from European centers; 204 (24%) respondents had a specific certificate in neurocritical care, and most were specialists in anesthesiology or intensive care and had less than 15 years of practice experience. Four hundred sixty-six respondents (54%) said they used an Hb threshold of 7-8 g/dl to initiate RBC transfusion after acute brain injury, although half of these respondents used a different threshold (closer to 9 g/dl) in patients with traumatic brain injury, subarachnoid hemorrhage, or ischemic stroke. Systemic and cerebral factors were reported as influencing the need for higher Hb thresholds. Most respondents agreed that a randomized clinical trial was needed to compare two different Hb thresholds for RBC transfusion, particularly in patients with traumatic brain injury, subarachnoid hemorrhage, and ischemic stroke.ConclusionsThe Hb threshold used for RBC transfusion after acute brain injury was less than 8 g/dl in half of the ICU clinicians who responded to our survey. However, more than 50% of these physicians used higher Hb thresholds in certain conditions.
| S-EPMC5473997 | biostudies-literature
Project description:Traumatic brain injury (TBI) causes physical and cognitive-behavioral impairments that reduce participation in employment, leisure, and social relationships. Demographic and injury-related factors account for a small proportion of variance in participation post-injury. Personal factors such as resilience may also impact outcomes. This study aimed to examine the association of resilience alongside demographic, injury-related, cognitive, emotional, and family factors with participation following TBI. It was hypothesized that resilience would make an independent contribution to participation outcomes after TBI. Participants included 245 individuals with mild-severe TBI [Mage = 44.41, SDage = 16.09; post traumatic amnesia (PTA) duration M 24.95 days, SD 45.99] who completed the Participation Assessment with Recombined Tools-Objective (PART-O), TBI Quality of Life Resilience scale, Family Assessment Device General Functioning Scale, Rey Auditory Verbal Learning Test, National Adult Reading Test, and Hospital Anxiety and Depression Scale an average 4.63 years post-injury (SD 3.02, R 0.5-13). Multiple regression analyses were used to examine predictors of PART-O scores as the participation measure. Variables in the model accounted for a significant 38% of the variability in participation outcomes, F(13, 211) = 9.93, p < 0.05, R2 = 0.38, adjusted R2 = 0.34. Resilience was a significant predictor of higher participation, along with shorter PTA duration, more years since injury, higher education and IQ, and younger age. Mediation analyses revealed depression mediated the relationship between resilience and participation. As greater resilience may protect against depression and enhance participation this may be a focus of intervention.
| S-EPMC6054998 | biostudies-other
Project description:Importance:Advances in treatment of traumatic brain injury are hindered by the inability to monitor pathological mechanisms in individual patients for targeted neuroprotective treatment. Spreading depolarizations, a mechanism of lesion development in animal models, are a novel candidate for clinical monitoring in patients with brain trauma who need surgery. Objective:To test the null hypothesis that spreading depolarizations are not associated with worse neurologic outcomes. Design, Setting, and Participants:This prospective, observational, multicenter cohort study was conducted from February 2009 to August 2013 in 5 level 1 trauma centers. Consecutive patients who required neurological surgery for treatment of acute brain trauma and for whom research consent could be obtained were enrolled; participants were excluded because of technical problems in data quality, patient withdrawal, or loss to follow-up. Primary statistical analysis took place from April to December 2018. Evaluators of outcome assessments were blinded to other measures. Interventions:A 6-contact electrode strip was placed on the brain surface during surgery for continuous electrocorticography during intensive care. Main Outcomes and Measures:Electrocorticography was scored for depolarizations, following international consensus procedures. Six-month outcomes were assessed by the Glasgow Outcome Scale-Extended score. Results:A total of 157 patients were initially enrolled; 19 were subsequently excluded. The 138 remaining patients (104 men [75%]; median [interquartile range] age, 45 [29-64] years) underwent a median (interquartile range) of 75.5 (42.2-117.1) hours of electrocorticography. A total of 2837 spreading depolarizations occurred in 83 of 138 patients (60.1% incidence) who, compared with patients who did not have spreading depolarizations, had lower prehospital systolic blood pressure levels (mean [SD], 133 [31] mm Hg vs 146 [33] mm Hg; P?=?.03), more traumatic subarachnoid hemorrhage (depolarization incidences of 17 of 37 [46%], 18 of 32 [56%], 22 of 33 [67%], and 23 of 30 patients [77%] for Morris-Marshall Grades 0, 1, 2, and 3/4, respectively; P?=?.047), and worse radiographic pathology (in 38 of 73 patients [52%] and 42 of 60 patients [70%] for Rotterdam Scores 2-4 vs 5-6, respectively; P?=?.04). Of patients with depolarizations, 32 of 83 (39%) had only sporadic events that induced cortical spreading depression of spontaneous electrical activity, whereas 51 of 83 patients (61%) exhibited temporal clusters of depolarizations (?3 in a 2-hour span). Nearly half of those with clusters (23 of 51 [45%]) also had depolarizations in an electrically silent area of the cortex (isoelectric spreading depolarization). Patients with clusters did not improve in motor neurologic examinations from presurgery to postelectrocorticography, while other patients did improve. In multivariate ordinal regression adjusting for baseline prognostic variables, the occurrence of depolarization clusters had an odds ratio of 2.29 (95% CI, 1.13-4.65; P?=?.02) for worse outcomes. Conclusions and Relevance:In this cohort study of patients with acute brain trauma, spreading depolarizations were predominant but heterogeneous and independently associated with poor neurologic recovery. Monitoring the occurrence of spreading depolarizations may identify patients most likely to benefit from targeted management strategies.
| S-EPMC6990808 | biostudies-literature
Project description:See Schiff (doi:10.1093/awx209) for a scientific commentary on this article. Patients with acute severe traumatic brain injury may recover consciousness before self-expression. Without behavioural evidence of consciousness at the bedside, clinicians may render an inaccurate prognosis, increasing the likelihood of withholding life-sustaining therapies or denying rehabilitative services. Task-based functional magnetic resonance imaging and electroencephalography techniques have revealed covert consciousness in the chronic setting, but these techniques have not been tested in the intensive care unit. We prospectively enrolled 16 patients admitted to the intensive care unit for acute severe traumatic brain injury to test two hypotheses: (i) in patients who lack behavioural evidence of language expression and comprehension, functional magnetic resonance imaging and electroencephalography detect command-following during a motor imagery task (i.e. cognitive motor dissociation) and association cortex responses during language and music stimuli (i.e. higher-order cortex motor dissociation); and (ii) early responses to these paradigms are associated with better 6-month outcomes on the Glasgow Outcome Scale-Extended. Patients underwent functional magnetic resonance imaging on post-injury Day 9.2 ± 5.0 and electroencephalography on Day 9.8 ± 4.6. At the time of imaging, behavioural evaluation with the Coma Recovery Scale-Revised indicated coma (n = 2), vegetative state (n = 3), minimally conscious state without language (n = 3), minimally conscious state with language (n = 4) or post-traumatic confusional state (n = 4). Cognitive motor dissociation was identified in four patients, including three whose behavioural diagnosis suggested a vegetative state. Higher-order cortex motor dissociation was identified in two additional patients. Complete absence of responses to language, music and motor imagery was only observed in coma patients. In patients with behavioural evidence of language function, responses to language and music were more frequently observed than responses to motor imagery (62.5-80% versus 33.3-42.9%). Similarly, in 16 matched healthy subjects, responses to language and music were more frequently observed than responses to motor imagery (87.5-100% versus 68.8-75.0%). Except for one patient who died in the intensive care unit, all patients with cognitive motor dissociation and higher-order cortex motor dissociation recovered beyond a confusional state by 6 months. However, 6-month outcomes were not associated with early functional magnetic resonance imaging and electroencephalography responses for the entire cohort. These observations suggest that functional magnetic resonance imaging and electroencephalography can detect command-following and higher-order cortical function in patients with acute severe traumatic brain injury. Early detection of covert consciousness and cortical responses in the intensive care unit could alter time-sensitive decisions about withholding life-sustaining therapies.
| S-EPMC6059097 | biostudies-literature
Project description:Traumatic brain injury (TBI) is a leading cause of death with no pharmacological treatments that improve outcomes. Transporter proteins participate in TBI recovery by maintaining the central nervous system (CNS) biochemical milieu. Genetic variations in transporters that alter expression and/or function have been associated with TBI outcomes. The ATP-binding cassette transporter, ABCG2, is a uric acid (UA) transporter that effluxes UA from cells in the CNS and is responsible for systemic UA clearance. Uric acid is a CNS antioxidant and/or a biomarker that might support TBI recovery. Our objective was to investigate the impact of ABCG2 SNP: c.421C>A on TBI outcomes. Two cohorts (discovery [N?=?270] and replication [N?=?166]) were genotyped for ABCG2 c.421C>A. Glasgow Outcome Scale (GOS) scores were collected at 3, 6, 12, and 24 months post-injury and compared with mixed-effects multiple ordinal regression controlled for time post-injury, age, sex, time, post-injury imaging determined hemorrhage types, and Glasgow Coma Scale score. Variant alleles (genotype) were associated with better GOS scores (p?=?0.01 [discovery] and p?=?0.02 [replication]), whereas genotype*age interaction was associated with worse GOS scores (p?=?0.03 [discovery] and p?=?0.01 [replication]). Reversed coefficient directionality suggests variant allele(s) are protective up to approximately age 34 years. Overall, variant alleles at ABCG2 c.421C>A associate with better GOS scores post-injury in two independently sampled cohorts. This finding is mitigated by increasing subject age. This suggests that ABCG2 might have an age-dependent effect on TBI recovery and should be explored in future mechanistic studies.
| S-EPMC5757075 | biostudies-literature