Tjemme Beems

Bio: Tjemme Beems is an academic researcher from Radboud University Nijmegen Medical Centre. The author has contributed to research in topics: Traumatic brain injury & Prospective cohort study. The author has an hindex of 23, co-authored 43 publications receiving 2527 citations. Previous affiliations of Tjemme Beems include Radboud University Nijmegen.

Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury

Abstract: Objective: To study the ability of glial (glial fibrillary acidic protein [GFAP] and S100b) and neuronal (neuron specific enolase [NSE]) protein levels in peripheral blood to predict outcome after severe traumatic brain injury. Methods: Eighty-five patients with severe traumatic brain injury (admission Glasgow Coma Score [GCS] ≤ 8) were included. Blood samples taken at the time of hospital admission were analyzed for S100b, GFAP, and NSE. Data collected included demographic and clinical variables. Outcome was assessed using the Glasgow Outcome Scale (GOS) at 6 months post injury. Results: The median serum levels of S100b, GFAP, and NSE were raised 18.3 fold (S100b), 4.6 fold (GFAP), and twofold (NSE) compared to normal reference values. S100b, GFAP, and NSE serum levels correlated significantly with the injury severity score and CT findings but not with age, sex, or GCS. S100b, GFAP, and NSE levels were significantly higher in patients who died or had a poor outcome 6 months post injury than in those who were alive or had good outcome. S100b level >1.13 μg/L was the strongest predictor of death with 100% discrimination, but GFAP (>1.5 μg/L) and NSE (>21.7 μg/L) levels also strongly predicted death (adjusted odds ratios 5.82 [for GFAP] and 3.91 [for NSE]). S100b, GFAP, and NSE all strongly predicted poor outcome (adjusted odds ratios 5.12 [S100b], 8.82 [GFAP], and 3.95 [NSE]). Conclusions: These results suggest that determination of serum levels of glial and neuronal proteins may add to the clinical assessment of the primary damage and prediction of outcome after severe traumatic brain injury.

GFAP and S100B are biomarkers of traumatic brain injury: An observational cohort study

Abstract: Background: Biomarker levels in blood after traumatic brain injury (TBI) may offer diagnostic and prognostic tools in addition to clinical indices. This study aims to validate glial fibrillary acidic protein (GFAP) and S100B concentrations in blood as outcome predictors of TBI using cutoff levels of 1.5 μg/L for GFAP and 1.13 μg/L for S100B from a previous study. Methods: In 79 patients with TBI (Glasgow Coma Scale score [GCS] ≤12), serum, taken at hospital admission, was analyzed for GFAP and S100B. Data collected included injury mechanism, age, gender, mass lesion on CT, GCS, pupillary reactions, Injury Severity Score (ISS), presence of hypoxia, and hypotension. Outcome was assessed, using the Glasgow Outcome Scale Extended (dichotomized in death vs alive and unfavorable vs favorable), 6 months post injury. Results: In patients who died compared to alive patients, median serum levels were increased: GFAP 33.4-fold and S100B 2.1-fold. In unfavorable compared to favorable outcome, GFAP was increased 19.8-fold and S100B 2.1-fold. Univariate logistic regression analysis revealed that mass lesion, GFAP, absent pupils, age, and ISS, but not GCS, hypotension, or hypoxia, predicted death and unfavorable outcome. Multivariable analysis showed that models containing mass lesion, pupils, GFAP, and S100B were the strongest in predicting death and unfavorable outcome. S100B was the strongest single predictor of unfavorable outcome with 100% discrimination. Conclusion: This study confirms that GFAP and S100B levels in serum are adjuncts to the assessment of brain damage after TBI and may enhance prognostication when combined with clinical variables.

Outcome prediction in mild traumatic brain injury: age and clinical variables are stronger predictors than CT abnormalities.

Abstract: Mild traumatic brain injury (mTBI) is a common heterogeneous neurological disorder with a wide range of possible clinical outcomes. Accurate prediction of outcome is desirable for optimal treatment. This study aimed both to identify the demographic, clinical, and computed tomographic (CT) characteristics associated with unfavorable outcome at 6 months after mTBI, and to design a prediction model for application in daily practice. All consecutive mTBI patients (Glasgow Coma Scale [GCS] score: 13-15) admitted to our hospital who were age 16 or older were included during an 8-year period as part of the prospective Radboud University Brain Injury Cohort Study (RUBICS). Outcome was assessed at 6 months post-trauma using the Glasgow Outcome Scale-Extended (GOSE), dichotomized into unfavorable (GOSE score 1-6) and favorable (GOSE score 7-8) outcome groups. The predictive value of several variables was determined using multivariate binary logistic regression analysis. We included 2784 mTBI patients and found CT abnormalities in 20.7% of the 1999 patients that underwent a head CT. Age, extracranial injuries, and day-of-injury alcohol intoxication proved to be the strongest outcome predictors. The presence of facial fractures and the number of hemorrhagic contusions emerged as CT predictors. Furthermore, we showed that the predictive value of a scheme based on a modified Injury Severity Score (ISS), alcohol intoxication, and age equalled the value of one that also included CT characteristics. In fact, it exceeded one that was based on CT characteristics alone. We conclude that, although valuable for the identification of the individual mTBI patient at risk for deterioration and eventual neurosurgical intervention, CT characteristics are imperfect predictors of outcome after mTBI.

Overview of the clinical applications of vagus nerve stimulation.

Abstract: Vagus nerve stimulation (VNS) has become an established therapy for difficult-to-treat epilepsy during the past 20 years. The vagus nerve provides a unique entrance to the brain. Electrical stimulation of this structure in the cervical region allows direct modulative access to subcortical brain areas, requiring only minimally invasive surgery with low risks involved. VNS therapy has shown to reduce epileptic seizures both in number and severity in a group of patients not responding to antiepileptic drugs. The effects are accompanied by an atypical set of central side effects. After the success of the VNS therapy with epilepsy, the technique has been applied to a wide variety of disorders, ranging from major depressive disorder to Alzheimer's disease. The results of several of these are promising. In this review, the results as well as the rationale for the different applications of VNS are discussed.

Continued disability and pain after lumbar disc surgery: the role of cognitive-behavioral factors.

Abstract: Cognitive-behavioral factors are considered important in the development of chronic disability and pain in patients with low back pain. In a prospective cohort study of 277 patients undergoing surgery for lumbosacral radicular syndrome, the predictive value of preoperatively measured cognitive-behavioral factors (fear of movement/(re)injury, passive pain coping, and negative outcome expectancies) for disability and pain intensity at 6 weeks and 6 months after surgery was investigated, taking into account the effect of possible confounding variables. Higher levels of cognitive-behavioral factors were found to be associated with a worse outcome at both 6 weeks and 6 months. These associations remained significant after controlling for possible confounding variables (preoperative disability and pain intensity, age, gender, educational level, duration of complaints, neurological deficits, and intake of analgesics) and pain intensity 3 days postoperatively. In multiple regression analyses, the cognitive-behavioral factors independently predicted different outcomes. Fear of movement/(re)injury predicted more disability and more severe pain at 6 weeks and more severe pain at 6 months; passive pain-coping strategies predicted more disability at 6 months; and negative outcome expectancies predicted more disability and more severe pain at both 6 weeks and 6 months. The findings support the potential utility of preoperative screening measures that include cognitive-behavioral factors for predicting surgical outcome, as well as studies to examine the potential benefits of cognitive-behavioral treatment to improve surgical outcome.

Functions of S100 Proteins

Abstract: The S100 protein family consists of 24 members functionally distributed into three main subgroups: those that only exert intracellular regulatory effects, those with intracellular and extracellular functions and those which mainly exert extracellular regulatory effects. S100 proteins are only expressed in vertebrates and show cell-specific expression patterns. In some instances, a particular S100 protein can be induced in pathological circumstances in a cell type that does not express it in normal physiological conditions. Within cells, S100 proteins are involved in aspects of regulation of proliferation, differentiation, apoptosis, Ca2+ homeostasis, energy metabolism, inflammation and migration/invasion through interactions with a variety of target proteins including enzymes, cytoskeletal subunits, receptors, transcription factors and nucleic acids. Some S100 proteins are secreted or released and regulate cell functions in an autocrine and paracrine manner via activation of surface receptors (e.g. the receptor for advanced glycation end-products and toll-like receptor 4), G-protein-coupled receptors, scavenger receptors, or heparan sulfate proteoglycans and N-glycans. Extracellular S100A4 and S100B also interact with epidermal growth factor and basic fibroblast growth factor, respectively, thereby enhancing the activity of the corresponding receptors. Thus, extracellular S100 proteins exert regulatory activities on monocytes/macrophages/microglia, neutrophils, lymphocytes, mast cells, articular chondrocytes, endothelial and vascular smooth muscle cells, neurons, astrocytes, Schwann cells, epithelial cells, myoblasts and cardiomyocytes, thereby participating in innate and adaptive immune responses, cell migration and chemotaxis, tissue development and repair, and leukocyte and tumor cell invasion.

A Cross-Sectional Study

Abstract: In the study, skeletal status was evaluated in 2850 females aged 7 to 77 yr using quantitative ultrasound (QUS amplitude-dependent speed of sound [Ad-SoS]). Ad-SoS ranged from 1923 ± 30 to 1876 ± 81 m/s, and the peak value (2121 m/s) was achieved in 19-yr-old females. Ad-SoS increased significantly between subgroups aged 11 and 12 yr, 12 and 13 yr, 13 and 14 yr, 14 and 15 yr, and 15 and 16 yr. After the age of 19 yr the only significant drop was noted between age groups 47 and 48 yr. Ad-SoS was regressed on age, weight, and height for age ranges 7 to 11 yr. (before an increase in Ad-SoS), 12 to 19 yr (from the onset of the increase to the peak value), and older than 19 yr to menopause. In females after menopause, years since menopause (YSM) were taken into consideration. In the two youngest groups Ad-SoS was affected positively by age, and in the two next groups, age had a negative influence on Ad-SoS, whereas weight had a negative and height a positive influence in all groups. YSM did not influence the Ad-SoS value. It was concluded that QUS measurements at the hand phalanges are a useful tool in assessment of skeletal status in the female population.

Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and combinations of computed tomographic predictors.

Abstract: BACKGROUND AND OBJECTIVE: The Marshall computed tomographic (CT) classification identifies six groups of patients with traumatic brain injury (TBI), based on morphological abnormalities on the CT scan. This classification is increasingly used as a predictor of outcome. We aimed to examine the predictive value of the Marshall CT classification in comparison with alternative CT models. METHODS: The predictive value was investigated in the Tirilazad trials (n = 2269). Alternative models were developed with logistic regression analysis and recursive partitioning. Six month mortality was used as outcome measure. Internal validity was assessed with bootstrapping techniques and expressed as the area under the receiver operating curve (AUC). RESULTS: The Marshall CT classification indicated reasonable discrimination (AUC = 0.67), which could be improved by rearranging the underlying individual CT characteristics (AUC = 0.71). Performance could be further increased by adding intraventricular and traumatic subarachnoid hemorrhage and by a more detailed differentiation of mass lesions and basal cisterns (AUC = 0.77). Models developed with logistic regression analysis and recursive partitioning showed similar performance. For clinical application we propose a simple CT score, which permits a more clear differentiation of prognostic risk, particularly in patients with mass lesions. CONCLUSION: It is preferable to use combinations of individual CT predictors rather than the Marshall CT classification for prognostic purposes in TBI. Such models should include at least the following parameters: status of basal cisterns, shift, traumatic subarachnoid or intraventricular hemorrhage, and presence of different types of mass lesions. Copyright

Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis

Abstract: Rheumatoid arthritis (RA) is a heterogeneous, prevalent, chronic autoimmune disease characterized by painful swollen joints and significant disabilities. Symptomatic relief can be achieved in up to 50% of patients using biological agents that inhibit tumor necrosis factor (TNF) or other mechanisms of action, but there are no universally effective therapies. Recent advances in basic and preclinical science reveal that reflex neural circuits inhibit the production of cytokines and inflammation in animal models. One well-characterized cytokine-inhibiting mechanism, termed the "inflammatory reflex," is dependent upon vagus nerve signals that inhibit cytokine production and attenuate experimental arthritis severity in mice and rats. It previously was unknown whether directly stimulating the inflammatory reflex in humans inhibits TNF production. Here we show that an implantable vagus nerve-stimulating device in epilepsy patients inhibits peripheral blood production of TNF, IL-1β, and IL-6. Vagus nerve stimulation (up to four times daily) in RA patients significantly inhibited TNF production for up to 84 d. Moreover, RA disease severity, as measured by standardized clinical composite scores, improved significantly. Together, these results establish that vagus nerve stimulation targeting the inflammatory reflex modulates TNF production and reduces inflammation in humans. These findings suggest that it is possible to use mechanism-based neuromodulating devices in the experimental therapy of RA and possibly other autoimmune and autoinflammatory diseases.

Psychological considerations in the assessment and treatment of pain in neurorehabilitation and psychological factors predictive of therapeutic response: Evidence and recommendations from the Italian consensus conference on pain in neurorehabilitation

Abstract: Background In order to provide effective care to patients suffering from chronic pain secondary to neurological diseases, health professionals must appraise the role of the psychosocial factors in the genesis and maintenance of this condition whilst considering how emotions and cognitions influence the course of treatment. Furthermore, it is important not only to recognize the psychological reactions to pain that are common to the various conditions, but also to evaluate how these syndromes differ with regards to the psychological factors that may be involved. As an extensive evaluation of these factors is still lacking, the Italian Consensus Conference on Pain in Neurorehabilitation aimed to collate the evidence available across these topics. Objectives To determine the psychological factors which are associated with or predictive of pain secondary to neurological conditions and to assess the influence of these aspects on the outcome of neurorehabilitation. Methods Two reviews were performed. In the first, a PUBMED search of the studies assessing the association between psychological factors and pain or the predictive value of these aspects with respect to chronic pain was conducted. The included papers were then rated with regards to their methodological quality and recommendations were made accordingly. In the second study, the same methodology was used to collect the available evidence on the predictive role of psychological factors on the therapeutic response to pain treatments in the setting of neurorehabilitation. Results The first literature search identified 1170 results and the final database included 189 articles. Factors such as depression, anxiety, pain catastrophizing, coping strategies and cognitive functions were found to be associated with pain across the various conditions. However, there are differences between chronic musculoskeletal pain, migraine, neuropathy and conditions associated with complex disability with regards to the psychological aspects that are involved. The second PUBMED search yielded 252 studies, which were all evaluated. Anxiety, depression, pain catastrophizing, coping strategies and pain beliefs were found to be associated to different degrees with the outcomes of multidisciplinary programs, surgery, physical therapies and psychological interventions. Conclusions Several psychological factors are associated with pain secondary to neurological conditions and should be acknowledged and addressed.