Apolipoprotein E4 allele presence and functional outcome after severe traumatic brain injury

Presence of the apolipoprotein E (APOE) 4 allele has been associated with increased incidence and faster progression of neurodegenerative diseases, poorer recovery from neurologic insult, and decreased cognitive function in the well-elderly. The specific association between APOE genotype and recovery from severe traumatic brain injury (TBI) is conflicting with many groups finding the APOE 4 allele to be associated with poorer outcome while others have found no association. The purpose of this study was to investigate the association between APOE 4 allele presence and recovery during the two years after injury from severe TBI in light of other potential covariates, such as age, race, gender, hypotension or hypoxia before hospital admission and severity of injury. APOE genotype was determined for 123 subjects with severe TBI. Glasgow outcome score (GOS) and mortality were collected at 3, 6, 12, and 24 months after injury. Results showed individuals improved over the two year period following injury and those with the 4 allele had a slower recovery rate than those without the APOE 4 allele over the two year period. We did not however find significant differences in GOS at individual time points when controlling for other covariates. Our findings suggest that APOE 4 allele presence influences recovery rate from severe TBI independent of other covariates. The findings of this study are unique in that they address not only the relationship between APOE 4 allele presence and outcome from severe TBI, but also describe differences in trajectory of recovery by APOE 4 allele presence.     

The association between apolipoprotein E and traumatic brain injury severity and functional outcome in a rehabilitation sample

Traumatic brain injury (TBI) can result in significant disability, but outcome is variable. The impact of known predictors accounts for a limited proportion of the variance in outcomes. Apolipoprotein E (ApoE) genotype has been investigated as an additional source of variability in injury severity and outcome, with mixed findings reflecting variable methodology and generally limited sample sizes. This study aimed to examine whether possession of the ApoE ?4 allele was associated with greater acute injury severity and poorer long-term outcome in patients referred for rehabilitation following TBI. ApoE genotype was determined for 648 patients with TBI, who were prospectively followed up a mean of 1.9 years post-injury. Hypotheses that ?4 carriers would have lower Glasgow Coma Scale (GCS) scores and longer post-traumatic amnesia (PTA) duration were not supported. Prediction of worse Glasgow Outcome Scale-Extended (GOSE) scores for ?4 carriers was supported with greater susceptibility seen in females. These results indicate the ApoE ?4 allele may be associated with poorer long-term outcome, but not acute injury severity. Possible mechanisms include differential effects of the ?4 allele on inflammatory and cellular repair processes, and/or amyloid deposition.     

Correlation between APOE -491AA promoter in epsilon4 carriers and clinical deterioration in early stage of traumatic brain injury

The objective of this work was to investigate the relationship between apolipoprotein E (APOE) promoters (G-219T, C-427T, A-491T) polymorphisms and the clinical deterioration in early stage of traumatic brain injury (TBI) in a cohort of Chinese patients. In this study, we used the cohort of patients which has been reported previously. A total of 110 subjects with TBI (80 males and 30 females, with mean age of 43.87 years) were admitted from December 2003 to May 2004, and demographic and clinical data were collected. The clinical deterioration of patient's condition in acute stage (<7 days after TBI) was judged by either of the following criteria: decrease of Glasgow Coma Scale (GCS) score (compared with initial admission GCS), increase in hematoma volume or delayed hematoma both detected by repeated computed tomography (CT) scanning compared to that on admission. Venous blood was collected from patients with TBI on admission to determine the APOE promoter polymorphisms. The APOE genotyping was performed by means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). chi(2) test and logistic regression analyses were done by SPSS. In 110 Chinese patients, the distributions of APOE genotypes and alleles matched Hardy-Weinberg Law, and 19 subjects presented with deteriorated clinical condition in acute stage after hospitalization. chi(2) test showed insignificant differences in association of APOE promoter polymorphisms with clinical deterioration (p>0.05). But logistic regression analyses, after adjusting patients' age, injury severity and injury mechanism etc, showed that -491AA (OR=11.681, p=0.009, 95%, CI 1.824-74.790) and APOE epsilon4 were all risk factors, with injury severity and alcohol-drinking as other risk factors. In Chinese population, as a significant but not independent risk factor, only APOE -491AA promoter in epsilon4 carriers is apt to the clinical deterioration and may contribute to the poor outcome after TBI.     

Apolipoprotein E polymorphism and outcome after closed traumatic brain injury: influence of ethnic and regional differences

OBJECT: The presence of the apolipoprotein E-epsilon4 (APOE-epsilon4) allele is reported to be associated with poor outcome after traumatic brain injury (TBI). This study was performed to determine if the presence of the APOE-epsilon4 allele influenced outcome in a cohort of black patients with TBI who had homogeneous neuropathological findings. METHODS: Venous blood was collected at the time of admission to determine the APOE genotype in black Zulu-speaking patients who presented with traumatic cerebral contusions. The frequency of the APOE-epsilon4 allele's appearance was correlated with outcome at a minimum of 6 months of follow up. Univariate and multivariate analyses were performed to determine independent risk factors and to control for confounding factors. In 110 black Zulu-speaking patients with traumatic cerebral contusions, genotypes for APOE were analyzed. Eleven of 45 (24.4%) with the APOE-epsilon4 allele experienced a poor outcome, compared with 10 (15.4%) of 65 without this allele (p = 0.34). Both patients with homozygous APOE-epsilon4 alleles experienced a good outcome (Glasgow Outcome Score 5). Univariate and multivariate analysis revealed no significant relationship in patients with the APOE-epsilon4 allele with regard to age, admission Glasgow Comas Scale score, contusion volume, type of neurosurgical management, and outcome. The risk of a poor outcome was, however, greater in patients with the APOE-epsilon4 allele (relative risk 1.59; 95% confidence interval 0.74-3.42). CONCLUSIONS: The authors recorded no relationship between APOE-epsilon4 allele status and outcome after TBI in black patients. Given the high regional susceptibility to the APOE gene, further studies, possibly even community-based investigations and studies conducted in other geographic areas, are probably warranted.     

Associations of APOE gene polymorphisms with bone mineral density and fracture risk: a meta-analysis

Summary  

To determine the association of the Apolipoprotein E (APOE) E4 gene polymorphism with bone mineral density (BMD) and fractures we conducted a meta-analysis of 17 reports. Despite lower trochanteric and lumbar BMD in APOE4 carriers, there is insufficient evidence to support a consistent association of APOE with bone health.     

The influence of apolipoprotein E genotype on outcome after spontaneous subarachnoid hemorrhage: a preliminary study

OBJECTIVE: Possession of an apolipoprotein E (APOE)epsilon4 allele has been shown to be associated with a poor outcome after closed head injury and spontaneous intracerebral hemorrhage but not after ischemic stroke. This study assessed the influence of the APOE genotype on outcome in patients admitted to a neurosurgical unit with spontaneous subarachnoid hemorrhage. METHODS: A total of 100 patients with spontaneous subarachnoid hemorrhage were studied. Four patients were excluded because the diagnosis of subarachnoid hemorrhage was not confirmed. The incidence of rehemorrhage and delayed ischemia and the outcome at 6 months were determined using the Glasgow Outcome Scale. APOE genotypes were determined by polymerase chain reaction and restriction enzyme digestion. RESULTS: Allele frequencies in this patient group were 0.04 for epsilon2, 0.86 for epsilon3, and 0.1 for epsilon4. Of 96 patients, 72 had an aneurysmal hemorrhage and 1 had a hemorrhage from an arteriovenous malformation. In 14 patients, the results of angiography were negative, and in 9, no angiogram was performed. Of the 96 patients, 20 had one or more epsilon4 allele. Outcome at 6 months was no worse in patients with one or more epsilon4 allele than in those with no epsilon4 allele (odds ratio, 0.98; 95% confidence interval, 0.35-2.74). None of the 12 patients who experienced delayed ischemic deterioration had an epsilon4 allele. Of the 20 patients with an epsilon4 allele, 3 had a rehemorrhage, as compared with 6 of 76 patients without an epsilon4 allele. CONCLUSION: There was underrepresentation of the epsilon4 allele in this group when compared with previously studied cases of subarachnoid hemorrhage with a fatal outcome and with the general population. This suggests that patients with the epsilon4 allele who have a subarachnoid hemorrhage are less likely to be admitted to a neurosurgical unit. This study does not support an association between possession of an epsilon4 allele and poor outcome in patients admitted to a neurosurgical unit with spontaneous subarachnoid hemorrhage, although the wide confidence interval does not preclude a clinically relevant association between APOE genotype and outcome. The findings indicate that an association between genotype and the development of delayed ischemic complications after subarachnoid hemorrhage may be possible.     

Isolated traumatic brain injury: age is an independent predictor of mortality and early outcome

BACKGROUND: Geriatric trauma patients have a worse outcome than the young with comparable injuries. The contribution of traumatic brain injury (TBI) to this increased mortality is unknown and has been confounded by the presence of other injuries. The purpose of this study was to investigate the role of age in the mortality and early outcome from isolated TBI. METHODS: This was a retrospective analysis of all adult patients with isolated TBI (Abbreviated Injury Scale score > or = 3) admitted during a 5-year period to two Level I trauma centers. Mortality, Glasgow Outcome Scale score at discharge, therapy, and complications were compared for elderly (age > or = 65 years) and younger patients. RESULTS: Of 694 patients, 22% were defined as elderly. The mortality for the elderly group was twice that of their younger counterparts (30% vs. 14%, p < 0.001), even for those with mild to moderate TBI (Glasgow Coma Scale score of 9-15). Thirteen percent of elderly survivors had a poor functional outcome (Glasgow Outcome Scale score of 2 or 3) at hospital discharge versus 5% in the young group (p < 0.01). Independent factors associated with a high mortality were age and Glasgow Coma Scale score. CONCLUSION: The mortality from TBI is higher in the geriatric population at all levels of head injury. In addition, functional outcome at hospital discharge is worse. Although some of this increased mortality may be explained by complications or type of head injury, age itself is an independent predictor for mortality in TBI.     

Severe traumatic brain injury: consequences of early adverse events

Background: Several factors associated with an unfavourable outcome after severe traumatic brain injury (TBI) have been described: prolonged pre‐hospital time, secondary referral to a level 1 trauma centre, the occurrence of secondary insults such as hypoxia, hypotension or low end‐tidal carbon dioxide (ETCO₂). To determine whether adverse events were linked to outcome, patients with severe TBI were studied before arrival at a level 1 trauma centre. Methods: Prospective, observational study design. Patients with severe TBI (n=48), admitted to Umeå University Hospital between January 2002 to December 2005 were included. All medical records from the site of the accident to arrival at the level 1 trauma centre were collected and evaluated. Results: A pre‐hospital time of >60 min, secondary referral to a level 1 trauma centre, documented hypoxia (oxygen saturation <95%), hypotension (systolic blood pressure <90 mmHg), hyperventilation (ETCO₂<4.5 kPa) or tachycardia (heart rate >100 beats/min) at any time before arrival at a level 1 trauma centre were not significantly related to an unfavourable outcome (Glasgow Outcome Scale 1–3). Conclusion: Early adverse events before arrival at a level 1 trauma centre were without significance for outcome after severe TBI in the trauma system studied.     

Young Age as a Risk Factor for Impaired Cerebral Autoregulation after Moderate to Severe Pediatric Traumatic Brain Injury

Background: Little is known about age and cerebral autoregulation in children with traumatic brain injury (TBI). The authors compared cerebral autoregulation between young (aged <4 yr) and older (aged >=4 yr) children with TBI.

Methods: After University of Washington's institutional review board approval, a retrospective analysis of prospectively collected data (May 2002 and June 2007) was performed. Eligibility criteria included age 16 yr or younger, moderate to severe (admission Glasgow Coma Scale score <13) TBI, TBI on computed tomography scan, and tracheal intubation. Cerebral autoregulation testing was performed within 72 h after TBI, and autoregulation was quantified using the autoregulatory index. An autoregulatory index less than 0.4 represents impaired cerebral autoregulation. The 12-month Glasgow outcome score was measured. Data are presented as mean +/- SD or range.

Results: Thirty-seven children (8.9 +/- 5.1 yr; 0.8-16 yr) were enrolled. Children younger than 4 yr had a higher incidence of impaired cerebral autoregulation (8 of 10 vs. 7 of 27; P = 0.006) and worse 12-month outcome (Glasgow outcome score 3.0 +/- 1.0 vs. 4.0 +/- 1.0; P = 0.02) than older children. Age less than 4 yr (adjusted odds ratio, 12.2; 95% confidence interval, 1.5-98.5) and low Glasgow Coma Scale score (adjusted odds ratio for higher Glasgow Coma Scale, 0.53; 95% confidence interval, 0.30-0.96) were independently associated with impaired cerebral autoregulation.     

Subjective impact of traumatic brain injury on long-term outcome at a minimum of 10 years after trauma– first results of a survey on 368 patients from a single academic trauma center in Germany

Background

Traumatic Brain Injury (TBI) may lead to significant impairments in personal, social and professional life. However, knowledge of the influence on long-term outcome after TBI is sparse. We therefore aimed to investigate the subjective effects of TBI on long-term outcome at a minimum of 10 years after trauma in one of the largest study populations in Germany.

Methods

The current investigation represents a retrospective cohort study at a level I trauma center including physical examination or standardized questionnaires of patients with mild, moderate or severe isolated TBI with a minimum follow-up of 10 years. We investigated the subjective physical, psychological and social outcome evaluating the Glasgow Outcome Scale, short-form 12, and social as well as vocational living circumstances.

Results

368 patients aged 0 to 88 years were included. Patients with severe TBI were younger compared to patients with moderate or mild TBI (p?<?0.05). Patients with severe TBI lived more often as single after the trauma impact. A significantly worse outcome was associated with higher severity of TBI resulting in an increased incidence of mental disability. A professional decline was analyzed in case of severe TBI resulting in significant loss of salary.

Conclusions

The severity of TBI significantly influenced the subjective social and living conditions. Subjective mental and physical outcome as well as professional life depended on the severity of TBI 10 years after the injury.

     

Anterior tongue cancer: age is not a predictor of outcome and should not alter treatment

Background: Mucosal head and neck cancers usually occur in older males after years of smoking and alcohol abuse. Despite this, approximately 5% of cases occur in young adults. The aetiology remains unclear and the anterior tongue is a prevalent site. Prognosis has been reported as worse in young patients and some have proposed a more aggressive treatment approach. Methods: Patients diagnosed with previously untreated anterior tongue squamous cell carcinoma and treated with curative intent were identified. Retrospective and prospective data were collected. Univariate and multivariate analyses were undertaken using Cox regression analysis. The outcome of patients treated with anterior tongue cancer using a cut‐off age of 40 years was compared. Results: Between 1980 and 2000, 106 males and 58 females with anterior tongue squamous cell carcinoma were treated at Westmead Hospital. Median follow up was 47 months (6?210 months). Twenty‐two patients (13.4%) were aged ≤40 years. Other than age, patient demographics, TNM stage and treatment approach were similar between the two groups. Eighty‐one per cent had either a T1 or T2 primary. In total, 139 patients (84.8%) had surgery or surgery and radiotherapy. A total of 56 (34%) patients experienced a recurrent event, with nodal recurrence occurring most often as the first site (n = 33, 59%). Young patients had a higher recurrence rate (45.5% vs 32.4%; P = 0.23). Relapse‐free survival at 5 years was 62% versus 81% (P = 0.27). Overall survival at 5 years was 65% versus 67% (P = 0.74). Conclusions: In keeping with recently published evidence, young age at diagnosis with anterior tongue cancer did not portend worse outcome. There is therefore currently no strong evidence to support a different treatment approach in young patients.     

Cerebrospinal fluid apolipoprotein E concentration decreases after traumatic brain injury

The APOE epsilon4 allele has been associated with unfavorable outcome after several types of acute brain injury, yet the biological mechanisms underlying this observation are poorly understood. Postmortem and experimental brain injury studies suggest the presence of increased amounts of apolipoprotein E (apoE) within the neuropil after acute brain injury. We assayed the concentration of apolipoprotein E in the cerebrospinal fluid (CSF) of non-injured controls and patients with traumatic brain injury (TBI) to determine whether differences exist, and if these differences correlate with injury severity and clinical outcome. CSF apoE and S100B, a marker of injury severity, were measured by enzyme linked immunosorbant assay. CSF was sampled from 27 traumatic brain injury patients (mean age 32, median 25, range 16-65 years) within 3 days of injury, and 28 controls (mean age 40, median 37, range 19-73 years). The TBI patients all had a Glasgow Coma Score (GCS) of less than eight (i.e., severe head injury). Clinical outcome was determined using the Glasgow Outcome Score (GOS). The average concentration of apoE in the CSF of controls was 12.4 mg/L (95% CI: 10.5-14.3 mg/L) and in TBI patients was 3.7 mg/L (95% CI: 2.1-4.1 mg/L; Mann-Whitney: p < 0.0001). In contrast, the concentration of S100B in the CSF of TBI patients was significantly higher than that of controls (Mann-Whitney: p < 0.0001). We speculate that apoE is retained within the parenchyma of the central nervous system in response to injury where in view of previous data, it may have a protective role.     

Influence of aldosterone synthase gene C-344T polymorphism on focal segmental glomerulosclerosis

Aim: We evaluated the influence of C‐344T polymorphism of the aldosterone synthase gene, associated with aldosterone levels and the development of arterial hypertension, on focal segmental glomerulosclerosis (FSGS). Methods: We studied 81 patients with primary FSGS followed up for 8.0 ± 12 years. Patients were classified according to their slope of reciprocal serum creatinine into group A (slow progressors, n = 57) and B (fast progressors, n = 24). One hundred healthy volunteers were analysed as controls. The biopsies of n = 50 patients were reviewed and analysed by the same pathologist. C‐344T polymorphism was determined by polymerase chain reaction. Results: The allele frequencies differed significantly between patients (C‐allele: 0.55, T‐allele: 0.45) and controls (C‐allele: 0.45, T‐allele: 0.55; P < 0.05). Patients carrying the C‐allele tended to have a higher percentage of sclerosed glomeruli (41.8 ± 30% vs 31. 2 ± 19% in TT genotype, ns) and tubulointerstitial fibrosis (22.8 ± 18% vs 16.0 ± 5%, ns). The rate of deterioration of renal function was higher in the CC/CT genotypes (?0.216 ± 0.449 dL/mg per year) compared to the TT genotype (?0.030 ± 0.041 dL/mg per year, P = 0.002). Furthermore, 36.4% of the C‐allele carriers and none of the patients with the TT genotype belonged to group B (P = 0.005). C‐allele carriers also had a worse kidney survival in the Kaplan–Meier analysis (P = 0.027). Conclusion: Our results indicate that aldosterone synthase gene C‐344T polymorphism not only acts as a risk factor for the development of FSGS, but also may influence its pathologic appearance and could serve as a marker of disease progression.     

Association of plasminogen activator inhibitor-1 gene polymorphism and type 2 diabetic nephropathy

Background: We investigated the relationship between plasminogen activator inhibitor-1 (PAI-1) 4G/5G insertion/deletion polymorphism and prevalence of diabetic nephropathy (DN) in Chinese patients. Methods: A total of 107 patients with type 2 diabetes were randomly recruited in the study, and 102 healthy subjects were selected as Control. Patients were divided into three groups according to their urinary albumin–creatinine ratio (UACR). Group A (n?=?44), had patients without DN (serum creatinine <106?µmol/L and UACR <30?µg/mg); Group B (n?=?30), had patients with micro-albuminuria (UACR 30–299?µg/mg), and Group C (n?=?33), had patients with macro-albuminuria (UACR ≥300?µg/mg and creatinine <200?µmol/L). Plasma level of PAI-1 was measured by ELISA. PAI-1 polymorphism was determined by a polymerase chain reaction (PCR) method and DNA sequencing. Results: (1) The plasma PAI-1 levels of group A (60.39?±?17.01?ng/L), group B (68.76?±?17.81?ng/L) and group C and (68.63?±?18.30?ng/L) are higher than that of controls (46.26?±?26.04?ng/L); (2) Patients with genotype 4G/4G tended to exhibit higher PAI-1 level; (3) The distribution frequency of genotype 4G/4G in group C was significantly higher than in group A (42.4% vs. 28.7%, p?Conclusions: (1) Plasma PAI-1 level was elevated in Type 2 diabetic patients; (2) The level of plasma PAI-1 is closely related to PAI-1 gene 4G/5G polymorphism and (3) PAI-1 4G/5G polymorphism is associated with the development and progression of predominant proteinuria diabetes nephropathy.     

Influence of apolipoprotein E and its receptors on cerebral amyloid precursor protein metabolism following traumatic brain injury

Traumatic brain injury (TBI) is the leading cause of mortality and disability among young individuals in our society,and globally the incidence of TBI is rising sharply.Mounting evidence has indicated ...     

Apolipoprotein E epsilon4 and the risk of unfavorable outcome after aneurysmal subarachnoid hemorrhage

BACKGROUND: The APOE-E4 allele has been identified as a risk factor for Alzheimer's disease and unfavorable outcomes after brain injuries. The purpose of this study was to confirm that APOE allele polymorphism also represents a risk factor for unfavorable outcomes following aneurysmal subarachnoid hemorrhage (SAH). METHODS: A total of 104 patients with aneurysmal SAH were studied. Computed tomography (CT) scan findings of SAH were assessed by Fisher's grade and clinical neurologic assessment was performed using the Hunt and Hess (H&H)grading system. Serum lipids were also analyzed. Outcomes at 3 months after SAH were determined using the Glasgow Outcome Scale. RESULTS: The distributions of APOE genotypes and alleles of patients were matched with those of control subjects. That 5 of 18 patients with APOE-E4 allele (28%) had an unfavorable outcome was significantly different from those without APOE-E4 (8%, chi2, p = 0.032; OR = 4.34, 95% CI 1.20-15.75). However, the presence or absence of E2 or E3 alleles had no significant difference. The relative hazard of APOE-E4 for unfavorable outcome exited after adjustment for clinical assessment (OR = 6.95, 95% CI 1.21-39.75). Total serum cholesterol, low-density lipoprotein and apolipoprotein B were elevated in patients with unfavorable rather than favorable outcomes. CONCLUSION: Our findings confirmed that the patients with APOE-E4 allele were predisposed to unfavorable outcomes after aneurysmal SAH even though an association between APOE and incidence of the SAH may not exist. The effect of APOE on neurobiology and lipoprotein metabolism seems to partially explain the difference in outcomes and deserves further study.     

Recovery at one year following isolated traumatic brain injury: a Western Trauma Association prospective multicenter trial

BACKGROUND: Age has been shown to be a primary determinant of survival following isolated traumatic brain injury (TBI). We have previously reported that patients > or =65 years who survived mild TBI have decreased functional outcome at 6 months compared with younger patients. The purpose of this study was to further investigate the effect of age on outcome at 1 year in all patients surviving isolated TBI. METHODS: The Western Trauma Association multicenter prospective study included all patients sustaining isolated TBI defined as Abbreviated Injury Scale score for Head > or = 3 with an Abbreviated Injury Scale score in any other body area < or = 1. Outcome data included discharge disposition, Glasgow Outcome Scale score (1 = dead to 5= full recovery) and modified Functional Independence Measure (FIM) score measuring feeding, expression, and locomotion (1 = total dependence to 4 = total independence) for each component at discharge and 1 year. RESULTS: In all, 295 patients were enrolled with a follow-up of 82%, resulting in 241 study patients. An additional five patients died from non-TBI causes and were excluded. The mean and median times for the last follow-up in the 236 remaining patients were 307 and 357 days, respectively. Patients were divided into four age ranges: 18 to 29 years (n = 66), 30 to 44 years (n = 54), 45 to 59 years (n = 50), and > or =60 years (n = 65). More severe TBIs, as measured by admitting Glasgow Coma Scale (GCS), were observed in the youngest group compared with all others but there were no differences in mean GCS between the remaining three groups. There were no differences in neurosurgical intervention between the groups. Age was a major determinant in the outcome at discharge and last follow-up. Patients over 60 years discharged with a GOS < or =4 were less likely to improve at 1 year than all other groups (37% versus 63 to 85%; p < or = 0.05). Patients between 18 and 29 years of age had the lowest mean Glasgow Outcome Scale and discharge FIM scores, which correlated with the low admission GCS. Despite the increased severity of TBI, this group had the best FIM score at 1 year. In contrast, patients older than 60 years had the least improvement and had a significantly lower final FIM score at 1 year compared with all other groups. CONCLUSION: Older patients following isolated TBI have poorer functional status at discharge and make less improvement at 1 year compared with all other patients. These worse outcomes occur despite what appears to be less severe TBI as measured by a higher GCS upon admission. Differences in outcome begin to appear even in patients between 45 and 59 years. Further investigations with more detailed outcome instruments are required to better understand the qualitative limitations of a patient's recovery and to devise strategies to maximize functional improvement following TBI. Age is an exceedingly important parameter affecting recovery from isolated TBI.     

Association between interleukin-1 beta (IL-1β) gene polymorphism and outcome after head injury: an early report

Summary Background. Recent studies focusing on the genetic influences on outcome after head injury (HI) have suggested that different alleles of certain genes are associated with different outcomes. Interleukin-1 beta (IL-1β) gene, especially β2 polymorphism, is frequently observed in Alzheimer’s disease, a remarkable degenerative state in which HI is among the known risk factors. Therefore, the aim of this paper was to search for the possible association between the outcome and IL-1β gene polymorphism in human HI.Methods. The study group was composed of the 69 patients admitted to the neurosurgery department after HI. The severity of the initial injury was evaluated by means of the Glasgow Coma Scale and outcome six months later was assessed by means of the Glasgow Outcome Scale. IL-1β genotypes were determined from blood samples by standard methods.Findings. Fourteen of 25 (56%) patients with IL-1β +3953 allele 2 had an unfavourable outcome (dead, vegetative state or severe disability) compared with eight of 44 (18.1%) patients without IL-1β +3953 (p = 0.0004). Similarly, 20 of 28 (71.4%) patients with IL-1β −511 allele 2 had an unfavourable outcome compared with two of 41 (4.8%) patients without IL-1β −511 (p = 0.005). Patients who had a composite of IL-1β 2/2 or 1/2 genotype from both −511 and +3953 region of the chromosome 2 were more prone to have bad prognosis.Conclusion. Results of our study demonstrated that there might be a significant association between IL-1β gene polymorphism and outcome after HI, supporting the hypothesis of a genetically determined influence.     

Blood pressure and outcome after severe pediatric traumatic brain injury

BACKGROUND: The relationship between systolic blood pressure and outcome in children after severe traumatic brain injury (TBI) is unclear. We examined the relationship between age-appropriate systolic blood pressure (AASBP) percentile and outcome after severe pediatric TBI. METHODS: We examined the association between AASBP percentiles and outcome in 172 children younger than 14 years of age with a Glasgow Coma Scale score < 9. Outcome was evaluated using discharge Glasgow Outcome Scale score. Poor outcome was defined as a Glasgow Outcome Scale score < 4. RESULTS: Poor outcome was associated with AASBP < 75th percentile (odds ratio, 4.2; 95% confidence interval, 2.1-8.3). Patients with systolic blood pressure (SBP) > or = 90 mm Hg and AASBP < 75th percentile had a higher odds for poor outcome compared with patients with SBP > or = 90 mm Hg and AASBP > or = 75th percentile (odds ratio, 3.5; 95% confidence interval, 1.7-7.3). CONCLUSION AASBP < 75th percentile was associated with poor outcome after severe pediatric TBI, even when SBP was > or = 90 mm Hg.     

Sex differences in bladder cancer outcomes among smokers with advanced bladder cancer

Study Type – Aetiology (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Smoking is well described among the most important risk factors for bladder cancer. It is also known that higher quantity of tobacco exposure is associated with higher bladder cancer risk and that smoking cessation is known to be associated with lower risk of bladder cancer. Furthermore, among patients with non‐muscle invasive bladder cancer, smoking cessation decreases the risk of tumour recurrence. On the other hand, the effect of smoking on tumour stages at presentation and especially on prognosis is not well studied. The current study describes the presentation and outcome of 564 patients (64% smokers, 36% non‐smokers) treated with radical cystectomy. Patients with smoking history have more advanced outcome at the time of radical surgery and significantly worse outcome after surgery when compared to non‐smokers, although the effect of smoking was not significant when survival was studied in multivariable analysis including classic prognostic parameters such as tumour grade, stage and adjuvant chemotherapy. Finally, there was a surprising finding that history of smoking affected outcome among male patients but such effect was not noted among female patients.

OBJECTIVE

? To study the effect of smoking on bladder cancer presentation and outcome in a large cystectomy population.

PATIENTS AND METHODS

? A database including 546 patients from the University Health Network (Toronto, Canada) and Turku University Hospital (Turku, Finland) was studied. ? In addition to the association of smoking with clinicopathological parameters, the effect of smoking on survival was analyzed. ? Categorical data were analyzed by the chi‐squared test and numerical data were analyzed by Student's t‐test. ? The Kaplan–Meier method, log‐rank test and a proportional hazards model were used to estimate the effect of smoking on survival.

RESULTS

? In total, 352 patients (64%) were smokers and 194 (36%) were non‐smokers. ? Smokers had more frequently advanced tumours and nodal metastasis. ? The 10‐year disease‐specific survival (DSS) was 52% vs 66% for smokers and non‐smokers, respectively (P= 0.039). ? Smokers also had significantly worse overall survival (10‐year overall survival 37% vs 62%; P= 0.015). ? Smoking affected significant DSS among men (P= 0.012), although no effect was observed among women. ? In a univariate model smoking was associated with a hazard ratio (HR) of 1.4 (95% confidence interval, CI, 1.0–1.9) for bladder cancer specific mortality and 1.4 (95% CI, 1.1–1.8) for overall mortality. ? In a multivariate model, smoking did not impact on DSS (HR, 1.1; 95% CI, 0.8–1.6; P= 0.41). ? In addition to advanced stage and nodal metastasis, female sex was an independent risk factor for DSS (HR, 1.6; 95% CI, 1.1–2.3; P= 0.007).

CONCLUSIONS

? Smokers appear to have worse outcomes after radical cystectomy for bladder cancer; however, it does not appear to be an independent prognostic factor for survival. ? Smoking affected survival only among men. ? Women had poorer survival but smoking was not a contributing factor to this.