S100B levels are affected by older age but not by alcohol intoxication following mild traumatic brain injury

Introduction: Biomarkers of brain damage and head injury are potentially useful tools in the management of afflicted patients. Particularly S100B has received much attention and has been adapted into clinical guidelines. Alcohol intoxication and higher age (65 years and over) have been used as risk factors for serious complications following head injury. The effect of these factors on S100B levels has not been fully established in a relevant patient cohort. Methods: We prospectively included 621 adult patients with mild traumatic brain injury (TBI) and S100B sampling. Mild TBI was defined as Glasgow Come Scale 14-15 with loss of consciousness and/or amnesia, but without high-risk factors for intracranial complications. These patients would normally require CT scanning according to local and most international guidelines. S100B was sampled within 3 hours following trauma. Results: 280 patients (45%) were intoxicated by alcohol. Alcohol intoxication had no effect on S100B levels (p = 0.65) and the performance of S100B remained unchanged in these patients. 115 patients (22%) were 65 years or older with elevated S100B levels being more common in this group compared to patients under 65 (p = 0.029). Although the sensitivity of S100B was unchanged in older patients, the specificity was poorer. Conclusion: S100B can be used reliably in mild TBI patients with alcohol intoxication. The clinically utility of S100B in older patients may be limited by very poor specificity leading to only a small decrease in CT scanning

The addition of S100B to guidelines for management of mild head injury is potentially cost saving

Background: Mild traumatic brain injury (TBI) is associated with substantial costs due to over-triage of patients to computed tomography (CT) scanning, despite validated decision rules. Serum biomarker S100B has shown promise for safely omitting CT scans but the economic impact from clinical use has never been reported. In 2007, S100B was adapted into the existing Scandinavian management guidelines in Halmstad, Sweden, in an attempt to reduce CT scans and save costs. Methods: Consecutive adult patients with mild TBI (GCS 14-15, loss of consciousness and/or amnesia), managed with the aid of S100B, were prospectively included in this study. Patients were followed up after 3 months with a standardized questionnaire. Theoretical and actual cost differences were calculated. Results: Seven hundred twenty-six patients were included and 29 (4.7 %) showed traumatic abnormalities on CT. No further significant intracranial complications were discovered on follow-up. Two hundred twenty-nine patients (27 %) had normal S100B levels and 497 patients (73 %) showed elevated S100B levels. Over-triage occurred in 73 patients (32 %) and under-triage occurred in 39 patients (7 %). No significant intracranial complications were missed. The introduction of S100B could save 71 € per patient if guidelines were strictly followed. As compliance to the guidelines was not perfect, the actual cost saving was 39 € per patient. Conclusion: Adding S100B to existing guidelines for mild TBI seems to reduce CT usage and costs, especially if guideline compliance could be increased

Clinical validation of S100B use in management of mild head injury.

BACKGROUND: Despite validated guidelines, management of mild head injury (MHI) is still associated with excessive computed tomography (CT) scanning. Reports concerning serum levels of S100B have shown promise concerning safe reduction in CT scanning but clinical validation and actual impact on patient management is unclear. In 2007, S100B was introduced into emergency department (ED) clinical management routines in Halmstad, Sweden. MHI patients with low (<0.10 mikrogram/L) levels of S100B could be discharged without CT. Our aim was to examine the clinical impact and performance of S100B in clinical use for MHI patients. METHODS: Adult ([≥]18 years) patients with MHI (GCS 14–15, loss of consciousness and/or amnesia and no additional risk factors) and S100B sampling within 3 hours were prospectively included in this validation study. Patients were managed according to the adapted guidelines and management was documented. Outcome was determined with a questionnaire 3 months post-trauma and medical records to identify significant intracranial complications such as new neuroimaging, neurosurgery and/or death related to the trauma. RESULTS: 512 patients were included. 24 (4.7%) showed traumatic abnormalities on CT and 1 patient died (0.2%). 138 patients (27%) had normal S100B levels and 374 patients (73%) showed elevated S100B levels. No patients with a normal S100B level showed significant intracranial complication. 44 patients (32%) were managed with CT despite the guidelines recommending discharge (all these CT scans were normal) and 28 patients (7%) were discharged despite a CT recommendation (follow-up was normal in all these patients). S100B had a sensitivity of 100% (95% CI 83-100%) and a specificity of 28% (95% CI 24-33%) for significant intracranial complications. CONCLUSION: The clinical use of S100B within our existing guidelines for management of MHI is safe and effective. Adult MHI patients, without additional risk factors and with normal S100B levels within 3 hours of injury, can safely be discharged from the hospital

Clinical validation of S100B use in management of mild head injury

Abstract Background Despite validated guidelines, management of mild head injury (MHI) is still associated with excessive computed tomography (CT) scanning. Reports concerning serum levels of S100B have shown promise concerning safe reduction in CT scanning but clinical validation and actual impact on patient management is unclear. In 2007, S100B was introduced into emergency department (ED) clinical management routines in Halmstad, Sweden. MHI patients with low ( Methods Adult ([≥]18 years) patients with MHI (GCS 14–15, loss of consciousness and/or amnesia and no additional risk factors) and S100B sampling within 3 hours were prospectively included in this validation study. Patients were managed according to the adapted guidelines and management was documented. Outcome was determined with a questionnaire 3 months post-trauma and medical records to identify significant intracranial complications such as new neuroimaging, neurosurgery and/or death related to the trauma. Results 512 patients were included. 24 (4.7%) showed traumatic abnormalities on CT and 1 patient died (0.2%). 138 patients (27%) had normal S100B levels and 374 patients (73%) showed elevated S100B levels. No patients with a normal S100B level showed significant intracranial complication. 44 patients (32%) were managed with CT despite the guidelines recommending discharge (all these CT scans were normal) and 28 patients (7%) were discharged despite a CT recommendation (follow-up was normal in all these patients). S100B had a sensitivity of 100% (95% CI 83-100%) and a specificity of 28% (95% CI 24-33%) for significant intracranial complications. Conclusion The clinical use of S100B within our existing guidelines for management of MHI is safe and effective. Adult MHI patients, without additional risk factors and with normal S100B levels within 3 hours of injury, can safely be discharged from the hospital.</p

Validation of the Scandinavian guidelines for initial management of minimal, mild and moderate traumatic brain injury in adults.

Acute management of traumatic brain injury (TBI), in particular mild TBI, focuses on the detection of the 5-7 % who may be harboring potentially life-threatening intracranial hemorrhage (IH) using CT scanning. Guidelines intending to reduce unnecessary head CT scans using available clinical variables to detect those at high IH risk have shown varying results. Recently, the Scandinavian Neurotrauma Committee (SNC) derived a new set of high-IH risk variables for adults with TBI using an evidence-based literature review. Unlike previous guidelines, the SNC guideline incorporates serum values of the brain protein S100B with clinical variables

Distinct mitotic segregation errors mediate chromosomal instability in aggressive urothelial cancers.

Purpose: Chromosomal instability (CIN) is believed to have an important role in the pathogenesis of urothelial cancer (UC). The aim of this study was to evaluate whether disturbances of mitotic segregation contribute to CIN in UC, if these processes have any effect on the course of disease, and how deregulation of these mechanisms affects tumor cell growth. Experimental Design: We developed molecular cytogenetic methods to classify mitotic segregation abnormalities in a panel of UC cell lines. Mitotic instabilities were then scored in biopsies from 52 UC patients and compared with the outcome of tumor disease. Finally, UC cells were exposed in vitro to a telomerase inhibitor to assess how this affects mitotic stability and cell proliferation. Results: Three distinct chromosome segregation abnormalities were identified: (a) telomere dysfunction, which triggers structural rearrangements and loss of chromosomes through anaphase bridging; (b) sister chromatid nondisjunction, which generates discrete chromosomal copy number variations; and (c) supernumerary centrosomes, which cause dramatic shifts in chromosome copy number through multipolar cell division. Chromosome segregation errors were already present in preinvasive tumors and a high rate mitotic instability was an independent predictor of poor survival. However, induction of even higher levels of the same segregation abnormalities in UC cells by telomerase inhibition in vitro led to reduced tumor cell proliferation and clonogenic survival. Conclusion: Several distinct chromosome segregation errors contribute to CIN in UC, and the rate of such mitotic errors has a significant effect on the clinical course. Efficient tumor cell proliferation may depend on the tight endogenous control of these processes