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Obese patients show a depressed cytokine profile following severe blunt injury.

ABSTRACT: We hypothesized that severely injured obese patients would display increased concentrations of proinflammatory cytokines when compared with patients of normal body mass index (BMI) and that this would be associated with multiple organ failure (MOF). This was a retrospective review of prospectively collected data in the "Inflammation and the Host Response to Injury" trauma-related database. Data were collected prospectively from US level I trauma centers. The subjects were severely injured adult blunt trauma patients. Cytokine concentrations obtained within 12 h of injury and on days 1 and 4 were compared between subjects on the basis of BMI (normal, 18.5-24.9 kg/m, and obese, ?30 kg/m). Demographic measures, injury severity, cytokine concentrations, and outcome measures were compared between groups. Seventy-four adult blunt trauma victims were evaluated. Relative to patients of normal BMI (n = 34), obese patients (n = 40) demonstrated an overall depressed cytokine response to severe injury, with significantly lower concentrations of several cytokines. Obese patients showed greater incidences of nosocomial infection (60 vs. 45%, not statistically significant) and MOF (63% vs. 44%, not statistically significant) and a later onset of maximum MOF score (5 vs. 3 days, P < 0.04) when compared with those of normal BMI. Despite prior reports suggesting a proinflammatory cytokine profile in obese individuals, obese patients sustaining severe injury show a depressed early cytokine response when compared with patients of normal BMI. This may confer increased susceptibility to nosocomial infection and later MOF. Further study of immune dysfunction in the postinjury obese patient should assess the possibility of early immune suppression.

SUBMITTER: Winfield RD

PROVIDER: S-EPMC4001923 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Obese patients show a depressed cytokine profile following severe blunt injury.

Winfield Robert D RD Delano Matthew J MJ Cuenca Alex G AG Cendan Juan C JC Lottenberg Lawrence L Efron Philip A PA Maier Ronald V RV Remick Daniel G DG Moldawer Lyle L LL Cuschieri Joseph J

Shock (Augusta, Ga.) 20120301 3

We hypothesized that severely injured obese patients would display increased concentrations of proinflammatory cytokines when compared with patients of normal body mass index (BMI) and that this would be associated with multiple organ failure (MOF). This was a retrospective review of prospectively collected data in the "Inflammation and the Host Response to Injury" trauma-related database. Data were collected prospectively from US level I trauma centers. The subjects were severely injured adult ...[more]

PMID: 22266966

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Project description:ObjectivesObesity has been demonstrated to alter a number of acute and chronic medical conditions. The effect of obesity on severely injured patients, however, remains incompletely defined. We sought to unravel potential physiologic and genomic alterations induced by obesity in severely injured blunt trauma patients.DesignA retrospective review of clinical and genomic information contained in the Inflammation and the Host Response to Injury multicenter trauma-related database examining the relationship between body mass index and the early genomic response from peripheral blood leukocytes to patient outcome following severe blunt trauma was performed.SettingMulticenter collaboration between university-based academic trauma centers.PatientsSeverely injured blunt trauma patients enrolled in the database.InterventionsNone.Measurements and main resultsUnivariate analysis of 455 severely injured trauma patients using the National Institutes of Health/World Health Organization body mass index classification system revealed significant increases in morbidity, including longer intensive care unit stays and a greater number of ventilator days, cardiac arrests, episodes of acute renal failure, and patients developing multiple organ failure. Regression modeling identified body mass index class as being independently associated with adverse outcomes and increased morbidity but an inverse relationship with mortality in patients who suffered severe blunt traumatic injury. Initial leukocyte genomic expression patterns between 163 patients in the four different body mass index groupings did not differ; however, analysis of gene differences between body mass index classes occurring over time demonstrated significant changes in 513 probe sets with significant pathway differences being related to cellular metabolism.ConclusionsIncreasing body mass index is associated with increased morbidity following severe blunt trauma. The initial blood leukocyte inflammatory response to blunt trauma does not appear to differ significantly between patients despite increasing body mass index. Resolution of the inflammatory response may differ between patients on the basis of body mass index; however, additional work is needed to clarify the potential causality of this finding.

Project description:Background: There is heterogeneity in neurosensory alterations following mild traumatic brain injury. Commonly assessed neurosensory symptoms following head injury include symptom reports and measures of oculomotor impairment, auditory changes, and vestibular impairment. Hypothesis/Purpose: Neurosensory alterations are prevalent acutely following mild traumatic brain injury secondary to blunt head trauma during collegiate varsity sports and may vary by sex and sport. Study Design: Retrospective study of a large collegiate athletic database. Methods: Analyses were performed using an established single University dataset of 177 male and female collegiate varsity athletes who were diagnosed with concussion/mild traumatic brain injury between September 2013 and October 2019. Descriptive and comparative analyses were performed on individual and grouped acute concussion assessments pertaining to neurosensory alterations obtained within 72 h of injury using components of the Sports Concussion Assessment Tool Version 5 and Vestibular/Ocular-Motor Screening. Results: Females had significantly more abnormal smooth pursuit (p-value: 0.045), convergence (p-value: 0.031), and visual motion sensitivity tests results (p-value: 0.023) than males. There were no differences in neurosensory alterations when grouped by overall auditory, vestibular, or oculomotor impairments. The majority of sports-related concussions occurred during football (50, 28.25%), wrestling (21, 11.86%), water polo (15, 8.47%), and basketball (14, 7.91%). Abnormal vestibular assessments were high in these top four sports categories, but statistically significant differences in overall auditory, vestibular, or oculomotor impairments were not reached by individual sport. However, water polo players had higher abnormal individual assessments related to balance reports on the sideline (60.00%, p-value: 0.045) and in the clinic setting (57.14%, p-value: 0.038) as compared to all other sports. Conclusion: While neurosensory alterations are prevalent in both male and female athletes acutely post-concussion, females have a higher incidence of abnormalities in smooth pursuit, convergence, and visual motion sensitivity and may benefit from early rehabilitation.

Project description:BackgroundAging is accompanied by alterations in immune functions. How these changes translate into levels of circulating inflammatory mediators and network expression after severe trauma is not well characterized. To address this, we compared time-dependent changes in the levels of an extensive biomarker panel in cohorts of severely injured young and aged adults.Study designCohorts of young (18 to 30 years old, n = 115) and aged (65 to 90 years old, n = 101) blunt trauma patients admitted to the ICU with plasma sampled 3 times within the first 24 hours and daily from day 1 to day 7 were assayed for 30 inflammatory biomarkers using Luminex analyzer. Stringently matched groups controlling for sex ratio and Injury Severity Score (n = 56 young vs n = 56 aged) were generated. Data were analyzed using 2-way ANOVA, area under the curve analysis, Dynamic Bayesian Network inference, and Dynamic Network Analysis.ResultsIn the overall cohorts, the young group had a significantly higher Injury Severity Score, which was associated with higher circulating levels of 18 inflammatory mediators from admission to day 7. The aged group had higher levels of C-X-C motif chemokine ligand 10/interferon gamma-induced protein 10 and C-X-C motif chemokine ligand 9/monokine induced by gamma interferon. In groups that were matched for Injury Severity Score, the significantly higher levels of interferon gamma-induced protein 10 and monokine induced by gamma interferon persisted in the aged. Dynamic Bayesian Network revealed interferon gamma-induced protein 10 and monokine induced by gamma interferon as key mediators in the aged, and Dynamic Network Analysis revealed higher network complexity in the aged.ConclusionsThese findings indicate that differences in the early inflammatory networks between young and aged trauma patients are not simply a suppression of pro-inflammatory responses in the aged, but are characterized by a major shift in the mediator profile patterns with high levels of CXC chemokines in the aged.

Project description:Animal studies suggest that the time of day is a determinant of the immunological response to both injury and infection. We hypothesized that due to this diurnal variation, time of injury could affect the systemic inflammatory response and outcomes post-trauma and tested this hypothesis by examining the dynamics of circulating inflammatory mediators in blunt trauma patients injured during daytime vs. nighttime. From a cohort of 472 blunt trauma survivors, two stringently matched sub-cohorts of moderately/severely injured patients [injury severity score (ISS) >20] were identified. Fifteen propensity-matched, daytime-inured ("mDay") patients (age 43.6 ± 5.2, M/F 11/4, ISS 22.9 ± 0.7) presented during the shortest local annual period (8:00 am-5:00 pm), and 15 propensity-matched "mNight" patients (age 43 ± 4.3, M/F 11/4, ISS 24.5 ± 2.5) presented during the shortest night period (10:00 pm-5:00 am). Serial blood samples were obtained (3 samples within the first 24 h and daily from days 1-7) from all patients. Thirty-two plasma inflammatory mediators were assayed. Two-way Analysis of Variance (ANOVA) was used to compare groups. Dynamic Network Analysis (DyNA) and Dynamic Bayesian Network (DyBN) inference were utilized to infer dynamic interrelationships among inflammatory mediators. Both total hospital and intensive care unit length of stay were significantly prolonged in the mNight group. Circulating IL-17A was elevated significantly in the mNight group from 24 h to 7 days post-injury. Circulating MIP-1?, IL-7, IL-15, GM-CSF, and sST2 were elevated in the mDay group. DyNA demonstrated elevated network complexity in the mNight vs. the mDay group. DyBN suggested that cortisol and sST2 were central nodes upstream of TGF-?1, chemokines, and Th17/protective mediators in both groups, with IL-6 being an additional downstream node in the mNight group only. Our results suggest that time of injury affects clinical outcomes in severely injured patients in a manner associated with an altered systemic inflammation program, possibly implying a role for diurnal or circadian variation in the response to traumatic injury.

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Obese patients show a depressed cytokine profile following severe blunt injury.

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Obese patients show a depressed cytokine profile following severe blunt injury.

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