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Pancreas Volume Declines During the First Year After Diagnosis of Type 1 Diabetes and Exhibits Altered Diffusion at Disease Onset.
Virostko J, Williams J, Hilmes M, Bowman C, Wright JJ, Du L, Kang H, Russell WE, Powers AC, Moore DJ
(2019) Diabetes Care 42: 248-257
MeSH Terms: Adolescent, Adult, Atrophy, Autoantibodies, Case-Control Studies, Child, Child, Preschool, Cohort Studies, Diabetes Mellitus, Type 1, Female, Glucose Tolerance Test, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Pancreas, Time Factors, Young Adult
Show Abstract · Added December 18, 2018
OBJECTIVE - This study investigated the temporal dynamics of pancreas volume and microstructure in children and adolescents with recent-onset type 1 diabetes (T1D) and individuals without diabetes, including a subset expressing autoantibodies associated with the early stages of T1D.
RESEARCH DESIGN AND METHODS - MRI was performed in individuals with recent-onset stage 3 T1D ( = 51; median age 13 years) within 100 days after diagnosis (mean 67 days), 6 months, and 1 year postdiagnosis. Longitudinal MRI measurements were also made in similarly aged control participants ( = 57) and in autoantibody-positive individuals without diabetes ( = 20). The MRI protocol consisted of anatomical imaging to determine pancreas volume and quantitative MRI protocols interrogating tissue microstructure and composition.
RESULTS - Within 100 days of diabetes onset, individuals with T1D had a smaller pancreas (median volume 28.6 mL) than control participants (median volume 48.4 mL; < 0.001), including when normalized by individual weight ( < 0.001). Longitudinal measurements of pancreas volume increased in control participants over the year, consistent with adolescent growth, but pancreas volume declined over the first year after T1D diagnosis ( < 0.001). In multiple autoantibody-positive individuals, the pancreas volume was significantly larger than that of the T1D cohort ( = 0.017) but smaller than that of the control cohort ( = 0.04). Diffusion-weighted MRI showed that individuals with recent-onset T1D had a higher apparent diffusion coefficient ( = 0.012), suggesting a loss of cellular structural integrity, with heterogeneous pancreatic distribution.
CONCLUSIONS - These results indicate that pancreas volume is decreased in stages 1, 2, and 3 of T1D and decreases during the first year after diabetes onset and that this loss of pancreatic volume is accompanied by microstructural changes.
© 2018 by the American Diabetes Association.
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19 MeSH Terms
Antimicrobial exposure and the risk of delirium in critically ill patients.
Grahl JJ, Stollings JL, Rakhit S, Person AK, Wang L, Thompson JL, Pandharipande PP, Ely EW, Patel MB
(2018) Crit Care 22: 337
MeSH Terms: Adult, Aged, Anti-Infective Agents, Cohort Studies, Critical Illness, Cross-Sectional Studies, Delirium, Female, Humans, Intensive Care Units, Length of Stay, Male, Middle Aged, Multivariate Analysis, Retrospective Studies
Show Abstract · Added December 16, 2018
BACKGROUND - Prior retrospective cross-sectional work has associated antimicrobials with a non-specific phrase: encephalopathy without seizures. The purpose of this study is to determine whether different classes of antimicrobials have differential associations with the daily risk of delirium after critical illness is adjusted for.
METHODS - Our study was a nested cohort that enrolled non-neurological critically ill adults from a medical or surgical intensive care unit (ICU) with daily follow-up to 30 days. Our independent variable was exposure to previous-day antimicrobial class: beta-lactams (subclasses: penicillins, first- to third-generation cephalosporins, fourth-generation cephalosporins, and carbapenems), macrolides, fluoroquinolones, and other. We adjusted for baseline covariates (age, comorbidities, cognition scores, sepsis, and mechanical ventilation), previous-day covariates (delirium, doses of analgesics/sedatives, and antipsychotic use), and same-day covariates (illness severity). Our primary outcome of delirium was measured by using the Confusion Assessment Method for the ICU. A daily delirium logistic regression model was used with an ICU time-restricted sensitivity analysis including daily adjustment for sepsis and mechanical ventilation.
RESULTS - Of 418 ICU patients, delirium occurred in 308 (74%) with a median of 3 days (interquartile range 2-6) among those affected and 318 (76%) were exposed to antimicrobials. When covariates and ICU type were adjusted for, only first- to third-generation cephalosporins were associated with delirium (logistic regression model odds ratio (OR) = 2.2, 95% confidence interval (CI) 1.28-3.79, P = 0.004; sensitivity analysis OR = 2.13, 95% CI 1.10-4.10, P = 0.024).
CONCLUSIONS - First-, second-, and third-generation cephalosporins doubled the odds of delirium after baseline co-morbidities, ICU type, the course of critical care, and other competing antimicrobial and psychotropic medication risks were adjusted for. We did not find an association between delirium and cefepime, penicillins, carbapenems, fluoroquinolones, or macrolides.
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15 MeSH Terms
Relationship between very low low-density lipoprotein cholesterol concentrations not due to statin therapy and risk of type 2 diabetes: A US-based cross-sectional observational study using electronic health records.
Feng Q, Wei WQ, Chung CP, Levinson RT, Sundermann AC, Mosley JD, Bastarache L, Ferguson JF, Cox NJ, Roden DM, Denny JC, Linton MF, Edwards DRV, Stein CM
(2018) PLoS Med 15: e1002642
MeSH Terms: Adult, Case-Control Studies, Cholesterol, LDL, Cohort Studies, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Electronic Health Records, Female, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Risk Factors, United States, Young Adult
Show Abstract · Added April 2, 2019
BACKGROUND - Observations from statin clinical trials and from Mendelian randomization studies suggest that low low-density lipoprotein cholesterol (LDL-C) concentrations may be associated with increased risk of type 2 diabetes mellitus (T2DM). Despite the findings from statin clinical trials and genetic studies, there is little direct evidence implicating low LDL-C concentrations in increased risk of T2DM.
METHODS AND FINDINGS - We used de-identified electronic health records (EHRs) at Vanderbilt University Medical Center to compare the risk of T2DM in a cross-sectional study among individuals with very low (≤60 mg/dl, N = 8,943) and normal (90-130 mg/dl, N = 71,343) LDL-C levels calculated using the Friedewald formula. LDL-C levels associated with statin use, hospitalization, or a serum albumin level < 3 g/dl were excluded. We used a 2-phase approach: in 1/3 of the sample (discovery) we used T2DM phenome-wide association study codes (phecodes) to identify cases and controls, and in the remaining 2/3 (validation) we identified T2DM cases and controls using a validated algorithm. The analysis plan for the validation phase was constructed at the time of the design of that component of the study. The prevalence of T2DM in the very low and normal LDL-C groups was compared using logistic regression with adjustment for age, race, sex, body mass index (BMI), high-density lipoprotein cholesterol, triglycerides, and duration of care. Secondary analyses included prespecified stratification by sex, race, BMI, and LDL-C level. In the discovery cohort, phecodes related to T2DM were significantly more frequent in the very low LDL-C group. In the validation cohort (N = 33,039 after applying the T2DM algorithm to identify cases and controls), the risk of T2DM was increased in the very low compared to normal LDL-C group (odds ratio [OR] 2.06, 95% CI 1.80-2.37; P < 2 × 10-16). The findings remained significant in sensitivity analyses. The association between low LDL-C levels and T2DM was significant in males (OR 2.43, 95% CI 2.00-2.95; P < 2 × 10-16) and females (OR 1.74, 95% CI 1.42-2.12; P = 6.88 × 10-8); in normal weight (OR 2.18, 95% CI 1.59-2.98; P = 1.1× 10-6), overweight (OR 2.17, 95% CI 1.65-2.83; P = 1.73× 10-8), and obese (OR 2.00, 95% CI 1.65-2.41; P = 8 × 10-13) categories; and in individuals with LDL-C < 40 mg/dl (OR 2.31, 95% CI 1.71-3.10; P = 3.01× 10-8) and LDL-C 40-60 mg/dl (OR 1.99, 95% CI 1.71-2.32; P < 2.0× 10-16). The association was significant in individuals of European ancestry (OR 2.67, 95% CI 2.25-3.17; P < 2 × 10-16) but not in those of African ancestry (OR 1.09, 95% CI 0.81-1.46; P = 0.56). A limitation was that we only compared groups with very low and normal LDL-C levels; also, since this was not an inception cohort, we cannot exclude the possibility of reverse causation.
CONCLUSIONS - Very low LDL-C concentrations occurring in the absence of statin treatment were significantly associated with T2DM risk in a large EHR population; this increased risk was present in both sexes and all BMI categories, and in individuals of European ancestry but not of African ancestry. Longitudinal cohort studies to assess the relationship between very low LDL-C levels not associated with lipid-lowering therapy and risk of developing T2DM will be important.
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16 MeSH Terms
Clustering of end-organ disease and earlier mortality in adults with sickle cell disease: A retrospective-prospective cohort study.
Chaturvedi S, Ghafuri DL, Jordan N, Kassim A, Rodeghier M, DeBaun MR
(2018) Am J Hematol 93: 1153-1160
MeSH Terms: Adolescent, Adult, Anemia, Sickle Cell, Cluster Analysis, Cohort Studies, Female, Humans, Male, Morbidity, Mortality, Multiple Organ Failure, Prognosis, Prospective Studies, Retrospective Studies, Young Adult
Show Abstract · Added November 9, 2018
Chronic end-organ complications result in morbidity and mortality in adults with sickle cell disease (SCD). In a retrospective-prospective cohort of 150 adults with SCD who received standard care screening for pulmonary function abnormalities, cardiac disease, and renal assessment from January 2003 to 2016, we tested the hypothesis that clustering of end-organ disease is common and multiple organ impairment predicts mortality. Any end-organ disease occurred in 59.3% of individuals, and 24.0% developed multiple organ (>1) end-organ disease. The number of end-organs affected was associated with mortality (P ≤ .001); 8.2% (5 of 61) of individuals with no affected end-organ, 9.4% (5 of 53) of those with 1 affected organ, 20.7% (6 of 29) of those with 2 affected end-organs, and 85.7% (6 of 7) with 3 affected end-organs died over a median follow up period of 8.7 (interquartile range 3.5-11.4) years. Of the 22 individuals who died, 77.3% had evidence of any SCD-related end-organ impairment, and this was the primary or secondary cause of death in 45.0%. SCD-related chronic impairment in multiple organs, and its association with mortality, highlights the need to understand the common mechanisms underlying chronic end-organ damage in SCD, and the urgent need to develop interventions to prevent irreversible end-organ complications in SCD.
© 2018 Wiley Periodicals, Inc.
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15 MeSH Terms
Serum metabolites are associated with all-cause mortality in chronic kidney disease.
Hu JR, Coresh J, Inker LA, Levey AS, Zheng Z, Rebholz CM, Tin A, Appel LJ, Chen J, Sarnak MJ, Grams ME
(2018) Kidney Int 94: 381-389
MeSH Terms: Adult, Aged, Allantoin, Biomarkers, Cause of Death, Cohort Studies, Female, Follow-Up Studies, Fumarates, Humans, Kidney, Male, Metabolomics, Middle Aged, Renal Insufficiency, Chronic
Show Abstract · Added April 6, 2019
Chronic kidney disease (CKD) involves significant metabolic abnormalities and has a high mortality rate. Because the levels of serum metabolites in patients with CKD might provide insight into subclinical disease states and risk for future mortality, we determined which serum metabolites reproducibly associate with mortality in CKD using a discovery and replication design. Metabolite levels were quantified via untargeted liquid chromatography and mass spectroscopy from serum samples of 299 patients with CKD in the Modification of Diet in Renal Disease (MDRD) study as a discovery cohort. Six among 622 metabolites were significantly associated with mortality over a median follow-up of 17 years after adjustment for demographic and clinical covariates, including urine protein and measured glomerular filtration rate. We then replicated associations with mortality in 963 patients with CKD from the African American Study of Kidney Disease and Hypertension (AASK) cohort over a median follow-up of ten years. Three of the six metabolites identified in the MDRD cohort replicated in the AASK cohort: fumarate, allantoin, and ribonate, belonging to energy, nucleotide, and carbohydrate pathways, respectively. Point estimates were similar in both studies and in meta-analysis (adjusted hazard ratios 1.63, 1.59, and 1.61, respectively, per doubling of the metabolite). Thus, selected serum metabolites were reproducibly associated with long-term mortality in CKD beyond markers of kidney function in two well characterized cohorts, providing targets for investigation.
Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
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1 Members
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15 MeSH Terms
Exploring the role of low-frequency and rare exonic variants in alcohol and tobacco use.
Marees AT, Hammerschlag AR, Bastarache L, de Kluiver H, Vorspan F, van den Brink W, Smit DJ, Denys D, Gamazon ER, Li-Gao R, Breetvelt EJ, de Groot MCH, Galesloot TE, Vermeulen SH, Poppelaars JL, Souverein PC, Keeman R, de Mutsert R, Noordam R, Rosendaal FR, Stringa N, Mook-Kanamori DO, Vaartjes I, Kiemeney LA, den Heijer M, van Schoor NM, Klungel OH, Maitland-Van der Zee AH, Schmidt MK, Polderman TJC, van der Leij AR, Posthuma D, Derks EM
(2018) Drug Alcohol Depend 188: 94-101
MeSH Terms: Alcohol Drinking, Alcoholism, Cohort Studies, Exons, Female, Genetic Predisposition to Disease, Genetic Variation, Humans, Male, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Receptors, Nicotinic, Risk Factors, Tobacco Use, Tobacco Use Disorder
Show Abstract · Added May 26, 2018
BACKGROUND - Alcohol and tobacco use are heritable phenotypes. However, only a small number of common genetic variants have been identified, and common variants account for a modest proportion of the heritability. Therefore, this study aims to investigate the role of low-frequency and rare variants in alcohol and tobacco use.
METHODS - We meta-analyzed ExomeChip association results from eight discovery cohorts and included 12,466 subjects and 7432 smokers in the analysis of alcohol consumption and tobacco use, respectively. The ExomeChip interrogates low-frequency and rare exonic variants, and in addition a small pool of common variants. We investigated top variants in an independent sample in which ICD-9 diagnoses of "alcoholism" (N = 25,508) and "tobacco use disorder" (N = 27,068) had been assessed. In addition to the single variant analysis, we performed gene-based, polygenic risk score (PRS), and pathway analyses.
RESULTS - The meta-analysis did not yield exome-wide significant results. When we jointly analyzed our top results with the independent sample, no low-frequency or rare variants reached significance for alcohol consumption or tobacco use. However, two common variants that were present on the ExomeChip, rs16969968 (p = 2.39 × 10) and rs8034191 (p = 6.31 × 10) located in CHRNA5 and AGPHD1 at 15q25.1, showed evidence for association with tobacco use.
DISCUSSION - Low-frequency and rare exonic variants with large effects do not play a major role in alcohol and tobacco use, nor does the aggregate effect of ExomeChip variants. However, our results confirmed the role of the CHRNA5-CHRNA3-CHRNB4 cluster of nicotinic acetylcholine receptor subunit genes in tobacco use.
Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
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15 MeSH Terms
Race- and Sex-related Differences in Nephrolithiasis Risk Among Blacks and Whites in the Southern Community Cohort Study.
Hsi RS, Kabagambe EK, Shu X, Han X, Miller NL, Lipworth L
(2018) Urology 118: 36-42
MeSH Terms: Adult, African Americans, Aged, Cohort Studies, Continental Population Groups, European Continental Ancestry Group, Female, Humans, Incidence, Kidney Calculi, Male, Medicaid, Medicare, Middle Aged, Proportional Hazards Models, Risk Assessment, Risk Factors, Sex Factors, Socioeconomic Factors, United States
Show Abstract · Added July 18, 2018
OBJECTIVE - To investigate race-sex associations with risk among whites and blacks in the southeastern United States. The relationship between race, sex, and kidney stone risk is poorly understood.
METHODS - Participants were 42,136 black and white adults enrolled in the Southern Community Cohort Study between 2002 and 2009, with no history of kidney stones and receiving Medicare or Medicaid services. Incident kidney stone diagnoses through December 2014 were determined via linkage with Centers for Medicare and Medicaid Services research files. Hazard ratios (HRs) for associations with race and sex were computed from multivariable Cox proportional hazards models adjusting for baseline characteristics, comorbid diseases, and dietary intakes.
RESULTS - During 116,931 and 270,917 person-years of follow-up for whites and blacks, respectively, age-adjusted incidence rates (95% confidence interval [CI]) were 5.98 (4.73-7.23) and 4.50 (3.86-5.14) per 1000 person-years for white men and women, respectively, while corresponding rates among blacks were 2.19 (1.71-2.67) and 2.47 (2.19-2.75) per 1000 person-years. Risk was higher among whites compared to blacks (HR = 2.23, 95% CI 1.97-2.53). Male sex was significantly associated with risk among whites (HR = 1.45, 95% CI 1.20-1.75), but not among blacks (HR = 0.90, 95% CI 0.75-1.07). Formal tests of interaction by race and sex were statistically significant for all models (P = .01 for fully adjusted model).
CONCLUSION - The association of incident kidney stones with sex differs between whites and blacks. White men have the highest risk, while no difference in risk is observed between black men and women.
Copyright © 2018 Elsevier Inc. All rights reserved.
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20 MeSH Terms
Clinical Features Associated With Nascent Left Ventricular Diastolic Dysfunction in a Population Aged 40 to 55 Years.
Mosley JD, Levinson RT, Brittain EL, Gupta DK, Farber-Eger E, Shaffer CM, Denny JC, Roden DM, Wells QS
(2018) Am J Cardiol 121: 1552-1557
MeSH Terms: Adult, Age Distribution, Cohort Studies, Databases, Factual, Diabetes Mellitus, Type 2, Echocardiography, Female, Heart Failure, Diastolic, Humans, Hypertension, Incidence, Kaplan-Meier Estimate, Linear Models, Male, Middle Aged, Multivariate Analysis, Prognosis, Retrospective Studies, Risk Assessment, Severity of Illness Index, Sex Distribution, Stroke Volume, Survival Analysis, United States, Ventricular Dysfunction, Left
Show Abstract · Added June 7, 2018
Diastolic dysfunction (DD), an abnormality in cardiac left ventricular (LV) chamber compliance, is associated with increased morbidity and mortality. Although DD has been extensively studied in older populations, co-morbidity patterns are less well characterized in middle-aged subjects. We screened 156,434 subjects with transthoracic echocardiogram reports available through Vanderbilt's electronic heath record and identified 6,612 subjects 40 to 55 years old with an LV ejection fraction ≥50% and diastolic function staging. We tested 452 incident and prevalent clinical diagnoses for associations with early-stage DD (n = 1,676) versus normal function. There were 44 co-morbid diagnoses associated with grade 1 DD including hypertension (odds ratio [OR] = 2.02, 95% confidence interval [CI] 1.78 to 2.28, p <5.3 × 10-29), type 2 diabetes (OR 1.96, 95% CI 1.68 to 2.29, p = 2.1 × 10-17), tachycardia (OR 1.38, 95% CI 0.53 to 2.19, p = 2.9 × 10-6), obesity (OR 1.76, 95% CI 1.51 to 2.06, p = 1.7 × 10-12), and clinical end points, including end-stage renal disease (OR 3.29, 95% CI 2.19 to 4.96, p = 1.2 × 10-8) and stroke (OR 1.5, 95% CI 1.12 to 2.02, p = 6.9 × 10-3). Among the 60 incident diagnoses associated with DD, heart failure with preserved ejection fraction (OR 4.63, 95% CI 3.39 to 6.32, p = 6.3 × 10-22) had the most significant association. Among subjects with normal diastolic function and blood pressure at baseline, a blood pressure measurement in the hypertensive range at the time of the second echocardiogram was associated with progression to stage 1 DD (p = 0.04). In conclusion, DD was common among subjects 40 to 55 years old and was associated with a heavy burden of co-morbid disease.
Copyright © 2018 Elsevier Inc. All rights reserved.
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25 MeSH Terms
Overall and Central Obesity and Risk of Lung Cancer: A Pooled Analysis.
Yu D, Zheng W, Johansson M, Lan Q, Park Y, White E, Matthews CE, Sawada N, Gao YT, Robien K, Sinha R, Langhammer A, Kaaks R, Giovannucci EL, Liao LM, Xiang YB, Lazovich D, Peters U, Zhang X, Bueno-de-Mesquita B, Willett WC, Tsugane S, Takata Y, Smith-Warner SA, Blot W, Shu XO
(2018) J Natl Cancer Inst 110: 831-842
MeSH Terms: Adult, Aged, Body Mass Index, Cohort Studies, Female, Humans, Lung Neoplasms, Male, Middle Aged, Obesity, Obesity, Abdominal, Risk Factors, Waist Circumference, Waist-Hip Ratio
Show Abstract · Added March 26, 2018
Background - The obesity-lung cancer association remains controversial. Concerns over confounding by smoking and reverse causation persist. The influence of obesity type and effect modifications by race/ethnicity and tumor histology are largely unexplored.
Methods - We examined associations of body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) with lung cancer risk among 1.6 million Americans, Europeans, and Asians. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for potential confounders. Analyses for WC/WHR were further adjusted for BMI. The joint effect of BMI and WC/WHR was also evaluated.
Results - During an average 12-year follow-up, 23 732 incident lung cancer cases were identified. While BMI was generally associated with a decreased risk, WC and WHR were associated with increased risk after controlling for BMI. These associations were seen 10 years before diagnosis in smokers and never smokers, were strongest among blacks, and varied by histological type. After excluding the first five years of follow-up, hazard ratios per 5 kg/m2 increase in BMI were 0.95 (95% CI = 0.90 to 1.00), 0.92 (95% CI = 0.89 to 0.95), and 0.89 (95% CI = 0.86 to 0.91) in never, former, and current smokers, and 0.86 (95% CI = 0.84 to 0.89), 0.94 (95% CI = 0.90 to 0.99), and 1.09 (95% CI = 1.03 to 1.15) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Hazard ratios per 10 cm increase in WC were 1.09 (95% CI = 1.00 to 1.18), 1.12 (95% CI = 1.07 to 1.17), and 1.11 (95% CI = 1.07 to 1.16) in never, former, and current smokers, and 1.06 (95% CI = 1.01 to 1.12), 1.20 (95% CI = 1.12 to 1.29), and 1.13 (95% CI = 1.04 to 1.23) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Participants with BMIs of less than 25 kg/m2 but high WC had a 40% higher risk (HR = 1.40, 95% CI = 1.26 to 1.56) than those with BMIs of 25 kg/m2 or greater but normal/moderate WC.
Conclusions - The inverse BMI-lung cancer association is not entirely due to smoking and reverse causation. Central obesity, particularly concurrent with low BMI, may help identify high-risk populations for lung cancer.
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14 MeSH Terms
Prognosis of diffuse axonal injury with traumatic brain injury.
Humble SS, Wilson LD, Wang L, Long DA, Smith MA, Siktberg JC, Mirhoseini MF, Bhatia A, Pruthi S, Day MA, Muehlschlegel S, Patel MB
(2018) J Trauma Acute Care Surg 85: 155-159
MeSH Terms: Adult, Brain Injuries, Traumatic, Cohort Studies, Diffuse Axonal Injury, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Middle Aged, Prognosis, Quality of Life, Retrospective Studies, Tomography, X-Ray Computed
Show Abstract · Added June 26, 2018
BACKGROUND - Determine the prognostic impact of magnetic resonance imaging (MRI)-defined diffuse axonal injury (DAI) after traumatic brain injury (TBI) on functional outcomes, quality of life, and 3-year mortality.
METHODS - This retrospective single center cohort included adult trauma patients (age > 17 years) admitted from 2006 to 2012 with TBI. Inclusion criteria were positive head computed tomography with brain MRI within 2 weeks of admission. Exclusion criteria included penetrating TBI or prior neurologic condition. Separate ordinal logistic models assessed DAI's prognostic value for the following scores: (1) hospital-discharge Functional Independence Measure, (2) long-term Glasgow Outcome Scale-Extended, and (3) long-term Quality of Life after Brain Injury-Overall Scale. Cox proportional hazards modeling assessed DAI's prognostic value for 3-year survival. Covariates included age, sex, race, insurance status, Injury Severity Score, admission Glasgow Coma Scale Score, Marshall Head computed tomography Class, clinical DAI on MRI (Y/N), research-level anatomic DAI Grades I-III (I, cortical; II, corpus callosum; III, brainstem), ventilator days, time to follow commands, and time to long-term follow-up (for logistic models).
RESULTS - Eligibility criteria was met by 311 patients, who had a median age of 40 years (interquartile range [IQR], 23-57 years), Injury Severity Score of 29 (IQR, 22-38), intensive care unit stay of 6 days (IQR, 2-11 days), and follow-up of 5 years (IQR, 3-6 years). Clinical DAI was present on 47% of MRIs. Among 300 readable MRIs, 56% of MRIs had anatomic DAI (25% Grade I, 18% Grade II, 13% Grade III). On regression, only clinical (not anatomic) DAI was predictive of a lower Functional Independence Measure score (odds ratio, 2.5; 95% confidence interval, 1.28-4.76], p = 0.007). Neither clinical nor anatomic DAI were related to survival, Glasgow Outcome Scale-Extended, or Quality of Life after Brain Injury-Overall Scale scores.
CONCLUSION - In this longitudinal cohort, clinical evidence of DAI on MRI may only be useful for predicting short-term in-hospital functional outcome. Given no association of DAI and long-term TBI outcomes, providers should be cautious in attributing DAI to future neurologic function, quality of life, and/or survival.
LEVEL OF EVIDENCE - Epidemiological, level III; Therapeutic, level IV.
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12 MeSH Terms