Cognitive dysfunction is a devastating consequence of traumatic brain injury that affects the majority of those who survive with moderate-to-severe injury, and many patients with mild head injury. ...Disruption of key monoaminergic neurotransmitter systems, such as the dopaminergic system, may play a key role in the widespread cognitive dysfunction seen after traumatic axonal injury. Manifestations of injury to this system may include impaired decision-making and impulsivity. We used the Cambridge Gambling Task to characterize decision-making and risk-taking behaviour, outside of a learning context, in a cohort of 44 patients at least six months post-traumatic brain injury. These patients were found to have broadly intact processing of risk adjustment and probability judgement, and to bet similar amounts to controls. However, a patient preference for consistently early bets indicated a higher level of impulsiveness. These behavioural measures were compared with imaging findings on diffusion tensor magnetic resonance imaging. Performance in specific domains of the Cambridge Gambling Task correlated inversely and specifically with the severity of diffusion tensor imaging abnormalities in regions that have been implicated in these cognitive processes. Thus, impulsivity was associated with increased apparent diffusion coefficient bilaterally in the orbitofrontal gyrus, insula and caudate; abnormal risk adjustment with increased apparent diffusion coefficient in the right thalamus and dorsal striatum and left caudate; and impaired performance on rational choice with increased apparent diffusion coefficient in the bilateral dorsolateral prefrontal cortices, and the superior frontal gyri, right ventrolateral prefrontal cortex, the dorsal and ventral striatum, and left hippocampus. Importantly, performance in specific cognitive domains of the task did not correlate with diffusion tensor imaging abnormalities in areas not implicated in their performance. The ability to dissociate the location and extent of damage with performance on the various task components using diffusion tensor imaging allows important insights into the neuroanatomical basis of impulsivity following traumatic brain injury. The ability to detect such damage in vivo may have important implications for patient management, patient selection for trials, and to help understand complex neurocognitive pathways.
Background:
Patients with traumatic brain injury (TBI) exhibit a variable and unpredictable outcome. The proteins interleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have shown ...predictive values for the presence of intracranial lesions.
Aim:
To evaluate the individual and combined outcome prediction ability of IL-10 and H-FABP, and to compare them to the more studied proteins S100β, glial fibrillary acidic protein (GFAP), and neurofilament light (NF-L), both with and without clinical predictors.
Methods:
Blood samples from patients with acute TBI (all severities) were collected <24 h post trauma. The outcome was measured >6 months post injury using the Glasgow Outcome Scale Extended (GOSE) score, dichotomizing patients into: (i) those with favorable (GOSE≥5)/unfavorable outcome (GOSE ≤ 4) and complete (GOSE = 8)/incomplete (GOSE ≤ 7) recovery, and (ii) patients with mild TBI (mTBI) and patients with TBIs of all severities.
Results:
When sensitivity was set at 95–100%, the proteins' individual specificities remained low. H-FABP showed the best specificity (%) and sensitivity (100%) in predicting complete recovery in patients with mTBI. IL-10 had the best specificity (50%) and sensitivity (96%) in identifying patients with favorable outcome in patients with TBIs of all severities. When individual proteins were combined with clinical parameters, a model including H-FABP, NF-L, and ISS yielded a specificity of 56% and a sensitivity of 96% in predicting complete recovery in patients with mTBI. In predicting favorable outcome, a model consisting IL-10, age, and TBI severity reached a specificity of 80% and a sensitivity of 96% in patients with TBIs of all severities.
Conclusion:
Combining novel TBI biomarkers H-FABP and IL-10 with GFAP, NF-L and S100β and clinical parameters improves outcome prediction models in TBI.
There is substantial interest in blood biomarkers as fast and objective diagnostic tools for traumatic brain injury (TBI) in the acute setting.
Adult patients (≥18) with TBI of any severity and ...indications for CT scanning and orthopaedic injury controls were prospectively recruited during 2011-2013 at Turku University Hospital, Finland. The severity of TBI was classified with GCS: GCS 13-15 was classified as mild (mTBI); GCS 9-12 as moderate (moTBI) and GCS 3-8 as severe (sTBI). Serum samples were collected within 24 hours of admission and biomarker levels analysed with high-performance kits. The ability of biomarkers to distinguish between severity of TBI and CT-positive and CT-negative patients was assessed.
Among 189 patients recruited, neurofilament light (NF-L) was obtained from 175 patients with TBI and 40 controls. S100 calcium-binding protein B (S100B), heart fatty-acid binding protein (H-FABP) and interleukin-10 (IL-10) were analysed for 184 patients with TBI and 39 controls. There were statistically significant differences between levels of all biomarkers between the severity classes, but none of the biomarkers distinguished patients with moTBI from patients with sTBI. Patients with mTBI discharged from the ED had lower levels of IL-10 (0.26, IQR=0.21, 0.39 pg/mL), H-FABP (4.15, IQR=2.72, 5.83 ng/mL) and NF-L (8.6, IQR=6.35, 15.98 pg/mL) compared with those admitted to the neurosurgical ward, IL-10 (0.55, IQR=0.31, 1.42 pg/mL), H-FABP (6.022, IQR=4.19, 20.72 ng/mL) and NF-L (13.95, IQR=8.33, 19.93 pg/mL). We observed higher levels of H-FABP and NF-L in older patients with mTBI. None of the biomarkers or their combinations was able to distinguish CT-positive (n=36) or CT-negative (n=58) patients with mTBI from controls.
S100B, H-FABP, NF-L and IL-10 levels in patients with mTBI were significantly lower than in patients with moTBI and sTBI but alone or in combination, were unable to distinguish patients with mTBI from orthopaedic controls. This suggests these biomarkers cannot be used alone to diagnose mTBI in trauma patients in the acute setting.
Traumatic axonal injury (TAI) contributes significantly to mortality and morbidity following traumatic brain injury (TBI), but is poorly characterized by conventional imaging techniques. Diffusion ...tensor imaging (DTI) may provide better detection as well as insights into the mechanisms of white matter injury. DTI data from 33 patients with moderate-to-severe TBI, acquired at a median of 32 h postinjury, were compared with data from 28 age-matched controls. The global burden of whole brain white matter injury (GBWMI) was quantified by measuring the proportion of voxels that lay below a critical fractional anisotropy (FA) threshold, identified from control data. Mechanisms of change in FA maps were explored using an Eigenvalue analysis of the diffusion tensor. When compared with controls, patients showed significantly reduced mean FA (p < 0.001) and increased apparent diffusion coefficient (ADC; p = 0.017). GBWMI was significantly greater in patients than in controls (p < 0.01), but did not distinguish patients with obvious white matter lesions seen on structural imaging. It predicted classification of DTI images as head injury with a high degree of accuracy. Eigenvalue analysis showed that reductions in FA were predominantly the result of increases in radial diffusivity (p < 0.001). DTI may help quantify the overall burden of white matter injury in TBI and provide insights into underlying pathophysiology. Eigenvalue analysis suggests that the early imaging changes seen in white matter are consistent with axonal swelling rather than axonal truncation. This technique holds promise for examining disease progression, and may help define therapeutic windows for the treatment of diffuse brain injury.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mineral-hosted melt inclusions have become an important source of information on magmatic processes. As the number of melt inclusion studies increases, so does the need to establish recommended ...practice guidelines for collecting and reporting melt inclusion data. These guidelines are intended to ensure certain quality criteria are met and to achieve consistency among published melt inclusion data in order to maximize their utility in the future. Indeed, with the improvement of analytical techniques, new processes affecting melt inclusions are identified. It is thus critical to be able to reprocess any previously published data, such that reporting the raw data is one of the first “recommended practices” for authors and a publication-criteria that reviewers should be sensitive to. Our guidelines start with melt inclusion selection, which is a critical first step, and then continue on to melt inclusion preparation and analysis, covering the entire field of methods applicable to melt inclusions.
In March of 2000, a melt inclusion workshop was held at the Chateau de Sassenage in Grenoble and a companion issue of Chemical Geology entitled “Melt Inclusions at the Millennium” was published. Erik Hauri was heavily involved with the meeting and contributed two landmark papers to the topical issue of Chemical Geology on the use of secondary ion mass spectrometry to analyze volatiles in melt inclusions. When the melt inclusion community re-convened at Woods Hole Oceanographic Institution (WHOI) in August of 2018, we were saddened that Erik was unable to join us due to his failing health. Less than a month later came the devastating news of his passing at only 52 years of age. In recognition of his incredible contributions to science in general and to the in situ analysis of melt inclusions in particular, the participants and organizers of the WHOI melt inclusion workshop dedicate this collegial paper to Erik Hauri, our colleague, mentor and friend. Thank you Erik.
Summary
Background
Allergic diseases cause a large and increasing burden in developed countries and in urban centres in middle‐income countries. The causes of this increase are unknown and, ...currently, there are no interventions to prevent the development of allergic diseases. The ‘hygiene hypothesis’ has tried to explain the increase through a reduction in the frequency of childhood infections causing a failure to program the immune system for adequate immune regulation. Intestinal helminth parasites are prevalent in childhood in developing countries and are associated with a lower prevalence of allergen skin test reactivity and asthma.
Objectives
To investigate whether children who had intestinal helminth infections during early childhood have a lower prevalence of allergen skin test reactivity later in childhood.
Methods
We re‐visited a population of 1055 children from whom stool samples had been collected for detection of intestinal helminth infections for another study, and collected new stool samples and performed allergen skin prick testing. Information on potential confounding variables was collected.
Results
Children with heavy infections with Trichuris trichiura in early childhood had a significantly reduced prevalence of allergen skin test reactivity in later childhood, even in the absence of T. trichiura infection at the time of skin testing in later childhood.
Conclusion
Early heavy infections with T. trichiura may protect against the development of allergen skin test reactivity in later childhood. Novel treatments to program immune‐regulation in early childhood in a way that mimics the effects of early infections with T. trichiura may offer new strategies for the prevention of allergic disease.
Pulmonary rehabilitation seems to be an effective intervention in patients with chronic obstructive pulmonary disease. We undertook a randomised controlled trial to assess the effect of outpatient ...pulmonary rehabilitation on use of health care and patients' wellbeing over 1 year.
200 patients with disabling chronic lung disease (the majority with chronic obstructive pulmonary disease) were randomly assigned a 6-week multidisciplinary rehabilitation programme (18 visits) or standard medical management. Use of health services was assessed from hospital and general-practice records. Analysis was by intention to treat.
There was no difference between the rehabilitation (n=99) and control (n=101) groups in the number of patients admitted to hospital (40
vs 41) but the number of days these patients spent in hospital differed significantly (mean 10·4 SD 9·7
vs 21·0 20·7, p=0·022). The rehabilitation group had more primary-care consultations at the general practitioner's premises than did the control group (8·6 6·8
vs 7·3 8·3, p=0·033) but fewer primary-care home visits (1·5 2·8
vs 2·8 4·6, p=0·037). Compared with control, the rehabilitation group also showed greater improvements in walking ability and in general and disease-specific health status.
For patients chronically disabled by obstructive pulmonary disease, an intensive, multidisciplinary, outpatient programme of rehabilitation is an effective intervention, in the short term and the long term, that decreases use of health services.
Most of the variation in outcome following severe traumatic brain injury (TBI) remains unexplained by currently recognized prognostic factors. Neuroinflammation may account for some of this ...difference. We hypothesized that TBI generated variable autoantibody responses between individuals that would contribute to outcome. We developed a custom protein microarray to detect autoantibodies to both CNS and systemic Ags in serum from the acute-phase (the first 7 d), late (6-12 mo), and long-term (6-13 y) intervals after TBI in human patients. We identified two distinct patterns of immune response to TBI. The first was a broad response to the majority of Ags tested, predominantly IgM mediated in the acute phase, then IgG dominant at late and long-term time points. The second was responses to specific Ags, most frequently myelin-associated glycopeptide (MAG), which persisted for several months post-TBI but then subsequently resolved. Exploratory analyses suggested that patients with a greater acute IgM response experienced worse outcomes than predicted from current known risk factors, suggesting a direct or indirect role in worsening outcome. Furthermore, late persistence of anti-MAG IgM autoantibodies correlated with raised serum neurofilament light concentrations at these time points, suggesting an association with ongoing neurodegeneration over the first year postinjury. Our results show that autoantibody production occurs in some individuals following TBI, can persist for many years, and is associated with worse patient outcome. The complexity of responses means that conventional approaches based on measuring responses to single antigenic targets may be misleading.
Lapatinib is associated with a low incidence of serious liver injury. Previous investigations have identified and confirmed the Class II allele HLA-DRB1*07:01 to be strongly associated with ...lapatinib-induced liver injury; however, the moderate positive predictive value limits its clinical utility. To assess whether additional genetic variants located within the major histocompatibility complex locus or elsewhere in the genome may influence lapatinib-induced liver injury risk, and potentially lead to a genetic association with improved predictive qualities, we have taken two approaches: a genome-wide association study and a whole-genome sequencing study. This evaluation did not reveal additional associations other than the previously identified association for HLA-DRB1*07:01. The present study represents the most comprehensive genetic evaluation of drug-induced liver injury (DILI) or hypersensitivity, and suggests that investigation of possible human leukocyte antigen associations with DILI and other hypersensitivities represents an important first step in understanding the mechanism of these events.
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